FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hoffmann, E Kline-Rogers, E Braverman, AG Voehringer, M Steg, PG Gourineni, V Montgomery, DG Isselbacher, EM Eagle, KA Nienaber, CA AF Hoffmann, E. Kline-Rogers, E. Braverman, A. G. Voehringer, M. Steg, P. G. Gourineni, V. Montgomery, D. G. Isselbacher, E. M. Eagle, K. A. Nienaber, C. A. CA Int Registry Acute Aortic Dissecti TI The use of chest x-ray as a diagnostic tool in acute aortic dissection: insights from the International Registry of Acute Aortic Dissection (IRAD) SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Hoffmann, E.; Nienaber, C. A.] Univ Hosp Rostock, Rostock, Germany. [Kline-Rogers, E.; Gourineni, V.; Montgomery, D. G.; Eagle, K. A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Braverman, A. G.] Washington Univ, St Louis, MO USA. [Voehringer, M.] Robert Bosch Krankenhaus, Stuttgart, Germany. [Steg, P. G.] Hosp Bichat Claude Bernard, AP HP, Paris, France. [Isselbacher, E. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 250 EP 250 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012402253 ER PT J AU Duerschmied, D Suidan, GL Herr, N Carbo, C Demers, M Brill, A Cifuni, SM Cicko, S Idzko, M Bode, C AF Duerschmied, D. Suidan, G. L. Herr, N. Carbo, C. Demers, M. Brill, A. Cifuni, S. M. Cicko, S. Idzko, M. Bode, C. TI Platelet serotonin promotes the efficient recruitment of neutrophils to sites of acute inflammation SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Duerschmied, D.; Herr, N.; Bode, C.] Univ Med Ctr Freiburg, Dept Cardiol Angiol, Freiburg, Germany. [Suidan, G. L.; Carbo, C.; Demers, M.; Brill, A.; Cifuni, S. M.] Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, Boston, MA USA. [Cicko, S.; Idzko, M.] Univ Med Ctr, Dept Pneumol, Freiburg, Germany. NR 0 TC 0 Z9 0 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 277 EP 277 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012402354 ER PT J AU Amabile, N Cheng, S Larson, MG Ghorbani, A Mc Cabe, E Griffin, G Cohen, KS Tedgui, A Boulanger, CM Wang, TJ AF Amabile, N. Cheng, S. Larson, M. G. Ghorbani, A. Mc Cabe, E. Griffin, G. Cohen, K. S. Tedgui, A. Boulanger, C. M. Wang, T. J. TI Association of circulating endothelial microparticles with cardiovascular risk factors in the Framingham Heart Study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Amabile, N.; Tedgui, A.; Boulanger, C. M.] Paris Cardiovasc Res Ctr PARCC, INSERM, U970, Paris, France. [Cheng, S.; Larson, M. G.; Wang, T. J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Ghorbani, A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Mc Cabe, E.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Griffin, G.] Duke Univ, Sch Med, Durham, NC USA. [Cohen, K. S.] Univ Chicago, Med Ctr, Sect Hematol Oncol, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 344 EP 344 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012403014 ER PT J AU Udell, J Scirica, BM Steg, PG Eagle, KA Goto, S Cho, JI Raz, I Bhatt, DL AF Udell, J. Scirica, B. M. Steg, P. G. Eagle, K. A. Goto, S. Cho, J. I. Raz, I. Bhatt, D. L. TI Hypoglycemia and cardiovascular risk in diabetic and non-diabetic outpatients at risk of or with atherothrombosis in the REACH registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Udell, J.; Scirica, B. M.; Cho, J. I.] Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Sch Med, Boston, MA 02115 USA. [Steg, P. G.] AP HP, INSERM, U698, Paris, France. [Steg, P. G.] Univ Paris 07, Paris, France. [Eagle, K. A.] Univ Michigan, Div Cardiol, Ann Arbor, MI 48109 USA. [Goto, S.] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Raz, I.] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Bhatt, D. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 359 EP 359 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012403070 ER PT J AU Kohli, P Chakrabarti, A Bansilal, S Dangas, G Nienaber, C Prats, J Gibson, CM AF Kohli, P. Chakrabarti, A. Bansilal, S. Dangas, G. Nienaber, C. Prats, J. Gibson, C. M. CA TIMI Study Grp TI Reduction in mortality from thrombin inhibition in CHF patients: results from the premier hospital database SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Kohli, P.; Bansilal, S.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Chakrabarti, A.; Gibson, C. M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Dangas, G.] Mt Sinai Hosp, New York, NY 10029 USA. [Nienaber, C.] Univ Hosp Rostock, Rostock, Germany. [Prats, J.] Med Co, Parsippany, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 393 EP 393 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012403199 ER PT J AU Ducrocq, G Labreuche, J Gao, R Panchenko, E Liau, CS Ikeda, Y Goto, S Amarenco, P Bhatt, DL Steg, PG AF Ducrocq, G. Labreuche, J. Gao, R. Panchenko, E. Liau, C. S. Ikeda, Y. Goto, S. Amarenco, P. Bhatt, D. L. Steg, P. G. CA REACH Registry Investigators TI International differences in outcomes in stable outpatients with atherothrombosis: Results from the REACH Registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Ducrocq, G.; Labreuche, J.; Amarenco, P.; Steg, P. G.] Hosp Bichat Claude Bernard, AP HP, Paris, France. [Gao, R.] Cardiovasc Inst, Beijing, Peoples R China. [Gao, R.] Fuwai Hosp, Beijing, Peoples R China. [Panchenko, E.] Cardiol Res Ctr, Moscow, Russia. [Liau, C. S.] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Ikeda, Y.] Kokura Mem Hosp, Fukuoka, Japan. [Goto, S.] Tokai Univ, Hiratsuka, Kanagawa 25912, Japan. [Bhatt, D. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 443 EP 443 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012403388 ER PT J AU Focks, JJ Brouwer, MA Van Oijen, MGH Lanas, A Bhatt, DL Verheugt, FWA AF Focks, J. Jaspers Brouwer, M. A. Van Oijen, M. G. H. Lanas, A. Bhatt, D. L. Verheugt, F. W. A. TI Recommendations on the combined use of clopidogrel and proton pump inhibitors: "Gut feeling" or "State of the heart"? SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Focks, J. Jaspers; Brouwer, M. A.; Verheugt, F. W. A.] Radboud Univ Nijmegen, Med Ctr, Dept Cardiol, NL-6525 ED Nijmegen, Netherlands. [Van Oijen, M. G. H.] Univ Calif Los Angeles, Los Angeles, CA USA. [Lanas, A.] Univ Hosp, CIBERehd, Zaragoza, Spain. [Bhatt, D. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RI Brouwer, Marc/B-1158-2014; Verheugt, F.W.A./H-8105-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 495 EP 495 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012404040 ER PT J AU Singh, JP Shen, J Chung, ES Martin, DO Abraham, WT Coles, JA AF Singh, J. P. Shen, J. Chung, E. S. Martin, D. O. Abraham, W. T. Coles, J. A., Jr. TI Clinical response with adaptive CRT algorithm compared with echo guided AV optimization: a propensity score analysis of multi-center trials SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Singh, J. P.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Shen, J.; Coles, J. A., Jr.] Medtronic Inc, Mounds View, NY USA. [Chung, E. S.] Christ Hosp, Heart & Vasc Ctr, Cincinnati, OH 45219 USA. [Martin, D. O.] Cleveland Clin, Cleveland, OH 44106 USA. [Abraham, W. T.] Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 538 EP 538 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012404197 ER PT J AU Ducrocq, G Amarenco, P Labreuche, J Alberts, M Mas, JL Ohman, M Goto, S Lavallee, P Bhatt, DL Steg, PG AF Ducrocq, G. Amarenco, P. Labreuche, J. Alberts, M. Mas, J. L. Ohman, M. Goto, S. Lavallee, P. Bhatt, D. L. Steg, P. G. CA REACH Registry Investigators TI History of stroke in patients with coronary artery disease in the REACH Registry: impact on cardiovascular and bleeding event rates SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Ducrocq, G.; Steg, P. G.] Hosp Bichat Claude Bernard, AP HP, Dept Cardiol, Paris, France. [Amarenco, P.; Labreuche, J.; Lavallee, P.] Hosp Bichat Claude Bernard, AP HP, Dept Neurol, Paris, France. [Amarenco, P.; Labreuche, J.; Lavallee, P.] Hosp Bichat Claude Bernard, AP HP, Stroke Ctr, Paris, France. [Alberts, M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Ohman, M.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Mas, J. L.] Hosp St Anne, AP HP, Paris, France. [Goto, S.] Tokai Univ, Hiratsuka, Kanagawa 25912, Japan. [Bhatt, D. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 673 EP 674 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012405062 ER PT J AU Kohli, P Steg, PG Crowley, K Murphy, SA Goto, S Bhatt, DL AF Kohli, P. Steg, P. G. Crowley, K. Murphy, S. A. Goto, S. Bhatt, D. L. CA TIMI Study Grp TI NSAID use is associated with an increase in adverse cardiac events: 4-year results from the REACH registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Kohli, P.; Crowley, K.; Murphy, S. A.] Brigham & Womens Hosp, Dept Med, Div Cardiol, TIMI Study Grp, Boston, MA USA. [Steg, P. G.] Hosp Bichat Claude Bernard, AP HP, Dept Cardiol, Paris, France. [Goto, S.] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Bhatt, D. L.] Vet Affairs Med Ctr, TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 673 EP 673 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012405061 ER PT J AU Berghausen, EM Vantler, M Janssen, W Ten Freyhaus, H Zhao, JJ Schermuly, RT Rosenkranz, S AF Berghausen, E. M. Vantler, M. Janssen, W. Ten Freyhaus, H. Zhao, J. J. Schermuly, R. T. Rosenkranz, S. TI The PI 3-kinase isoform p110alpha promotes vascular remodelling in pulmonary arterial hypertension SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Berghausen, E. M.; Vantler, M.; Ten Freyhaus, H.; Rosenkranz, S.] Univ Cologne, Dept Internal Med 3, D-50931 Cologne, Germany. [Janssen, W.] Max Planck Inst Heart & Lung Res, Bad Nauheim, Germany. [Zhao, J. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Schermuly, R. T.] Univ Giessen, Lung Ctr, Univ Hosp, Giessen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 753 EP 754 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012405372 ER PT J AU Turagam, M Velagapudi, P Hanumanthu, VS Kocheril, A Holley, J AF Turagam, M. Velagapudi, P. Hanumanthu, V. S. Kocheril, A. Holley, J. TI Continuous furosemide infusion versus furosemide mannitol infusion in acute congestive heart failure SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Turagam, M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Velagapudi, P.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Hanumanthu, V. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kocheril, A.; Holley, J.] Univ Illinois, Carle Fdn Hosp, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 807 EP 807 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012406046 ER PT J AU Kohli, P Murphy, SA Cannon, CP AF Kohli, P. Murphy, S. A. Cannon, C. P. CA TIMI Study Grp TI Who funds the evidence in the ESC guidelines: government or industry? Analysis of class I acute coronary syndrome recommendations from 2011 SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Kohli, P.; Murphy, S. A.; Cannon, C. P.; TIMI Study Grp] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 908 EP 909 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012406432 ER PT J AU Salomaa, V Havulinna, AS Kettunen, J Eriksson, J Jula, A Kontula, K Newton-Cheh, C AF Salomaa, V. Havulinna, A. S. Kettunen, J. Eriksson, J. Jula, A. Kontula, K. Newton-Cheh, C. TI A blood pressure genetic risk score predicts incident cardiovascular events in 36,950 Finnish individuals SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Salomaa, V.; Havulinna, A. S.; Kettunen, J.; Eriksson, J.] Natl Inst Hlth & Welf, Helsinki, Finland. [Jula, A.] Natl Inst Hlth & Welf, Turku, Finland. [Kontula, K.] Univ Helsinki, Dept Med, Helsinki, Finland. [Newton-Cheh, C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, C.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 943 EP 943 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012407001 ER PT J AU Duivenvoorden, R Mani, V Woodward, M Kallend, D Suchankova, G Fuster, V Rudd, JHF Tawakol, A Farkouh, ME Fayad, ZA AF Duivenvoorden, R. Mani, V. Woodward, M. Kallend, D. Suchankova, G. Fuster, V. Rudd, J. H. F. Tawakol, A. Farkouh, M. E. Fayad, Z. A. TI Serum inflammatory biomarkers and plaque inflammation assessed by [18F]-fluorodeoxyglucose positron emission tomography in the dal-PLAQUE study: a post-hoc analysis by baseline features SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Duivenvoorden, R.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY USA. [Woodward, M.] Univ Sydney, George Inst, Sydney, NSW 2006, Australia. [Kallend, D.; Suchankova, G.] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Fuster, V.] Mt Sinai Sch Med, Cardiovasc Inst, New York, NY USA. [Rudd, J. H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. [Tawakol, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tawakol, A.] Harvard Univ, Sch Med, Boston, MA USA. [Farkouh, M. E.] Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Farkouh, M. E.] Li Ka Shing Knowledge Inst, Toronto, ON, Canada. RI Mani, Venkatesh/B-8939-2011; Woodward, Mark/D-8492-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 945 EP 945 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012407011 ER PT J AU Piccini, JP Harrell, F Lokhnygina, Y Wang, J Oppenheimer, L Patel, MR Singer, DE Mahaffey, KW Fox, KAA Califf, RM AF Piccini, J. P. Harrell, F. Lokhnygina, Y. Wang, J. Oppenheimer, L. Patel, M. R. Singer, D. E. Mahaffey, K. W. Fox, K. A. A. Califf, R. M. CA ROCKET AF Investigators TI Relationship between center time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Piccini, J. P.; Lokhnygina, Y.; Patel, M. R.; Mahaffey, K. W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. [Harrell, F.] Vanderbilt Univ, Nashville, TN USA. [Wang, J.; Oppenheimer, L.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Singer, D. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fox, K. A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, K. A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Califf, R. M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 968 EP 969 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012407093 ER PT J AU Gaggin, H Szymonifka, J Bhardwaj, A Mohammed, A Rehman, S Truong, Q Januzzi, J AF Gaggin, H. Szymonifka, J. Bhardwaj, A. Mohammed, A. Rehman, S. Truong, Q. Januzzi, J. TI Serial measurement of soluble ST2, GDF-15, and highly sensitive troponin T in patients with chronic heart failure: results from the protect study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Gaggin, H.; Szymonifka, J.; Bhardwaj, A.; Mohammed, A.; Rehman, S.; Truong, Q.; Januzzi, J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 1093 EP 1094 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012407570 ER PT J AU Houbballah, R Raux, M LaMuraglia, G AF Houbballah, R. Raux, M. LaMuraglia, G. TI Part Two: Against the Motion. Endovascular Therapy is the Preferred Treatment for Patients < 65 Years Old with Symptomatic Infrainguinal Arterial Disease SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Editorial Material ID CRITICAL LIMB ISCHEMIA; LEG BASIL TRIAL; SUPERFICIAL FEMORAL-ARTERY; LOWER-EXTREMITY BYPASS; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; FEMOROPOPLITEAL OCCLUSIVE DISEASE; ISOLATED TIBIAL INTERVENTION; INTER-SOCIETY CONSENSUS; GRAFT FAILURE; REVASCULARIZATION STRATEGY C1 [LaMuraglia, G.] Massachusetts Gen Hosp, Gen Surg Serv, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP LaMuraglia, G (reprint author), Massachusetts Gen Hosp, Gen Surg Serv, Div Vasc & Endovasc Surg, ACC440,15 Pkman St, Boston, MA 02114 USA. EM glamuraglia@partners.org NR 49 TC 1 Z9 1 U1 0 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD AUG PY 2012 VL 44 IS 2 BP 116 EP 119 DI 10.1016/j.ejvs.2012.06.012 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 005TC UT WOS:000308772000003 PM 22878046 ER PT J AU Rolfson, O Strom, O Karrholm, J Malchau, H Garellick, G AF Rolfson, Ola Strom, Oskar Karrholm, Johan Malchau, Henrik Garellick, Goran TI Costs Related to Hip Disease in Patients Eligible for Total Hip Arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE cost of illness; hip disease; hip osteoarthritis; waiting time; total hip arthroplasty ID RHEUMATOID-ARTHRITIS; ECONOMIC BURDEN; OSTEOARTHRITIS; PROJECTIONS; SURGERY; HEALTH; CARE AB This study was designed to estimate direct and indirect costs incurred by hip disease in patients eligible for total hip arthroplasty (THA). Before THA, 2635 patients completed a questionnaire regarding the use of resources because of their hip disease. Costs were assigned using official statistical sources or market prices. Annual costs amounted to US$ 7666 per patient. In a regression analysis, higher annual costs were associated with working age, female gender, comorbidity, and operation waiting time more than 90 days (P < .005). The burden of disease for THA candidates is extensive, where loss of productivity is the principal cost. Long wait for surgery is associated with increased costs. This study provides baseline cost data, which will be useful for further health economic analyses and could provide guidance for health care decision makers. C1 [Rolfson, Ola; Karrholm, Johan; Garellick, Goran] Univ Gothenburg, Dept Orthoped, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden. [Strom, Oskar] Karolinska Inst, Med Management Ctr, Stockholm, Sweden. [Malchau, Henrik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped, Boston, MA USA. RP Rolfson, O (reprint author), Sahlgrenska Univ Hosp Molndal, SE-43182 Molndal, Sweden. OI Malchau, Henrik/0000-0002-4291-2441; Rolfson, Ola/0000-0001-6534-1242 NR 25 TC 8 Z9 8 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 2012 VL 27 IS 7 BP 1261 EP 1266 DI 10.1016/j.arth.2011.09.030 PG 6 WC Orthopedics SC Orthopedics GA 986CF UT WOS:000307317100001 PM 22209159 ER PT J AU Jones, DL Bhanegaonkar, AJ Billings, AA Kriska, AM Irrgang, JJ Crossett, LS Kwoh, CK AF Jones, Dina L. Bhanegaonkar, Abhijeet J. Billings, Anthony A. Kriska, Andrea M. Irrgang, James J. Crossett, Lawrence S. Kwoh, C. Kent TI Differences Between Actual and Expected Leisure Activities After Total Knee Arthroplasty for Osteoarthritis SO JOURNAL OF ARTHROPLASTY LA English DT Article DE leisure activities; total knee arthroplasty; osteoarthritis; physical activity; expectations ID TOTAL JOINT REPLACEMENT; HEALTH SURVEY SF-36; TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; SELF-EFFICACY; PATIENTS EXPECTATIONS; PATIENT EXPECTATIONS; OUTCOMES; QUESTIONNAIRE AB This prospective cohort study determined the type, frequency, intensity, and duration of actual vs expected leisure activity among a cohort undergoing total knee arthroplasty. Data on actual and expected participation in 36 leisure activities were collected preoperatively and at 12 months in 90 patients with knee osteoarthritis. Despite high expectations, there were statistically and clinically significant differences between actual and expected activity at 12 months suggesting that expectations may not have been fulfilled. The differences were equivalent to walking 14 less miles per week than expected, which is more than the amount of activity recommended in national physical activity guidelines. Perhaps an educational intervention could be implemented to help patients establish appropriate and realistic leisure activity expectations before surgery. C1 [Jones, Dina L.] W Virginia Univ, Sch Med, Dept Orthopaed, Hlth Sci Ctr S, Morgantown, WV 26506 USA. [Jones, Dina L.] W Virginia Univ, Div Phys Therapy, Sch Med, Hlth Sci Ctr S, Morgantown, WV 26506 USA. [Bhanegaonkar, Abhijeet J.] W Virginia Univ, Dept Pharmaceut Syst & Policy, Sch Pharm, Morgantown, WV 26506 USA. [Billings, Anthony A.] W Virginia Univ, Dept Stat, Eberly Coll Arts & Sci, Morgantown, WV 26506 USA. [Kriska, Andrea M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Irrgang, James J.; Crossett, Lawrence S.] Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA USA. [Kwoh, C. Kent] Univ Pittsburgh, Div Rheumatol & Clin Immunol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Jones, DL (reprint author), W Virginia Univ, Sch Med, Dept Orthopaed, Hlth Sci Ctr S, POB 9196,1 Med Ctr Dr,Room 3603A, Morgantown, WV 26506 USA. OI Kriska, Andrea/0000-0002-3522-0869 FU American College of Rheumatology Research and Education Foundation FX This study was funded by a grant from the American College of Rheumatology Research and Education Foundation. NR 49 TC 9 Z9 9 U1 2 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 2012 VL 27 IS 7 BP 1289 EP 1296 DI 10.1016/j.arth.2011.10.030 PG 8 WC Orthopedics SC Orthopedics GA 986CF UT WOS:000307317100006 PM 22480521 ER PT J AU Elias, PZ Spector, M AF Elias, Paul Z. Spector, Myron TI Viscoelastic characterization of rat cerebral cortex and type I collagen scaffolds for central nervous system tissue engineering SO JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS LA English DT Article DE Rat brain; Collagen; Scaffold; Viscoelastic; Mechanical properties ID BRAIN-INJURY; CROSS-LINKING; GAG SCAFFOLDS; CELL THERAPY; VIVO; MATRICES; MODEL; LEVEL; VITRO; BIOMECHANICS AB In the field of tissue engineering and regenerative medicine for the central nervous system, therapeutic strategies may involve implantation of biomaterial scaffolds into the brain. An understanding of the relationship between the brain and the scaffold mechanical properties can help in the selection of a safe and effective biomaterial. This research demonstrates the use of indentation testing along with viscoelastic modeling to characterize and compare mechanical properties of in situ rat cerebral cortex and collagen scaffolds of varying collagen concentration. The stress-relaxation solution for indentation of a viscoelastic material was derived based on a five-element Maxwell model and use of the correspondence principle. Applying the model to experimental stress-relaxation data, the brain was characterized by three shear moduli G(1) = 1.6 +/- 0.10 kPa, G(2) = 2.0 +/- 0.15 kPa, G(3) = 1.8 +/- 0.20 kPa, and two viscosities eta(2) = 11.0 +/- 0.44 kPa.s, eta(3) = 148.7 +/- 6.70 kPa.s, with corresponding relaxation time constants tau(1) = 5.7 +/- 0.3 s and tau(2) = 88.4 +/- 7.6 s. The brain showed average relaxation of 74% from its peak force during loading to an approximately asymptotic force over a 5 minute hold at constant displacement. Collagen scaffolds generally showed increasing trends in the shear moduli, viscosities, and percentage relaxation with increasing collagen concentration. While the brain had similar stiffness to the 1.0% collagen scaffold during the loading phase, the brain's relaxation behavior was distinct from all of the scaffolds. Similarities and differences between the mechanical behavior of the brain and collagen scaffolds of varying collagen concentration are discussed in relation to application of biomaterials for regenerative medicine. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Elias, Paul Z.; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Elias, Paul Z.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Elias, PZ (reprint author), VA Boston Healthcare Syst, Tissue Engn Labs, Mail Stop 151 Res,Room D1-151,150 S Huntington Av, Boston, MA 02130 USA. EM pzelias@alum.mit.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX The research reported here was supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. We thank Dr. Simona Socrate and Dr. Thibault Prevost (MIT Department of Mechanical Engineering) for assistance with the mechanical testing. NR 48 TC 14 Z9 14 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1751-6161 J9 J MECH BEHAV BIOMED JI J. Mech. Behav. Biomed. Mater. PD AUG PY 2012 VL 12 BP 63 EP 73 DI 10.1016/j.jmbbm.2012.03.014 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 003QL UT WOS:000308626300007 PM 22659367 ER PT J AU Loewenstein, G Volpp, KG Asch, DA AF Loewenstein, George Volpp, Kevin G. Asch, David A. TI Incentives in Health: Different Prescriptions for Physicians and Patients EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Financial incentives in health care are different for physicians and patients. For physicians, financial incentives involve methods of payment for their services. For patients, incentives involve the structuring of health insurance coverage, co-payments, and deductibles. It is often assumed that individuals act according to conventional economic principles and respond directly to changes in incentives in a rational manner. However, in many instances, neither physicians nor patients act rationally. This lack of rationality among patients can be related to the lack of information or to actions that are contrary to their own best interests such as overeating, failure to take medication, or not wearing seatbelts. Rationality is dependent on individual psychological or personality differences, as well as differences in education or income. Whether a medical decision is economically rational or irrational is influenced by differences among individuals in knowledge about alternatives, prior experience in similar decision making, availability of rapid feedback on the consequences of decisions, and the ability to make thoughtful dispassionate decisions or rapid decisions when emotionally stressed. Rationality is highly relevant to the discussion of the role of incentives in medicine for reducing widespread overuse of low-value services. Compared to physicians paid on a capitated basis, there is a tendency among physicians paid for specific procedures to recommend these procedures more frequently. Improvement in the value of health care spending in the US health care system will require moving away from payment systems that contribute to overuse of high-cost, low-value services, in large part, by exploiting the rationality of physicians. The primary focus of efforts to address overuse of low-value services should be physicians rather than patients. Insurance payments to physicians for services of low value should be reduced. Coupling lower payment to physicians for low-value services with higher payment for high-value services that are underused could offset the adverse financial effects of this approach. Broad-based physician incentive schemes, such as capitated payment or fee for service, can lead to unintended consequences-too much care with fee-for-service medicine and too little with capitation-that have little regard to value. Financial incentives for patients using health care services involve substantially different issues than for physicians. Patients receive relatively little useful feedback about the quality of their medical decisions. The behavior of ill and emotionally vulnerable patients can be less than perfectly rational, and it is difficult for them to balance the costs and benefits of alternative tests or treatments in a rational, dispassionate fashion. Patients play a significant role in cost sharing programs. The role of patient cost sharing is different for acute and chronic illnesses. Acutely ill patients are poor targets of cost-sharing incentive programs. Unlike the acutely ill, patients with chronic conditions, who have prior experience in making similar decisions, can make a dispassionate evaluation of costs and benefits and are more appropriate targets of higher cost sharing for low-value services. It is hoped that financial incentives can change patient behavior (ie, lifestyle changes), thereby improving health care outcomes. There are only limited data on how much measured indicators of health outcomes resulting from changes in patient behaviors can be modified through use of premium-based health incentives. With financial incentives, the intended goals of improved health care at lower cost, while minimizing unintended consequences, can only be achieved through the design and implementation of programs that consider the individual response of patients and physicians to incentives and how they respond in different circumstances. C1 [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. Univ Penn, Wharton Sch, Penn CMU Roybal P30 Ctr Behav Econ & Hlth, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Leonard Davis Inst Ctr Hlth Incent & Behav Econom, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Loewenstein, G (reprint author), Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD AUG PY 2012 VL 67 IS 8 BP 464 EP 465 DI 10.1097/01.ogx.0000419560.63610.67 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 005LG UT WOS:000308751300006 ER PT J AU van Ravesteyn, NT Miglioretti, DL Stout, NK Lee, SJ Schechter, CB Buist, DSM Huang, H Heijnsdijk, EAM Trentham-Dietz, A Alagoz, O Near, AM Kerlikowske, K Nelson, HD Mandelblatt, JS de Koning, HJ AF van Ravesteyn, Nicolien T. Miglioretti, Diana L. Stout, Natasha K. Lee, Sandra J. Schechter, Clyde B. Buist, Diana S. M. Huang, Hui Heijnsdijk, Eveline A. M. Trentham-Dietz, Amy Alagoz, Oguzhan Near, Aimee M. Kerlikowske, Karla Nelson, Heidi D. Mandelblatt, Jeanne S. de Koning, Harry J. TI Tipping the Balance of Benefits and Harms to Favor Screening Mammography Starting at Age 40 Years: A Comparative Modeling Study of Risk SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB The US Preventive Services Task Force recommends biennial breast cancer mammography screening for women aged 50 to 74 years. A large body of evidence has shown a favorable balance of benefits and harms for screening in this age group. All current guidelines support this recommendation. However, the US Preventive Services Task Force did not recommend routine screening before age 50 based on the high false-positive rate in younger women. A strategy focused on screening only the younger women at greatest risk of breast cancer would address concerns over the high ratio of harm to benefit. The aim of this comparative modeling study was to determine the threshold relative risk (RR) at which the harm-benefit ratio of starting screening women aged 40 to 49 years equals that of biennial screening for average-risk women aged 50 to 74 years. The effect of screening method (film, digital) and screening interval (annual, biennial) on the threshold RR was also evaluated. Data from the Surveillance, Epidemiology, and End Results program, the Breast Cancer Surveillance Consortium, and the medical literature were used to generate simulation models estimating risk/benefits of screening before and after the age of 50 years. A cohort of women eligible for routine screening who were born in 1960 was simulated and observed throughout their lifetime. Outcome measures evaluated included the following: benefits (life-years gained, breast cancer deaths averted, harms (false-positive mammography findings), and harm-benefit ratios (false-positive findings/life-years gained, false-positive findings/deaths averted). Screening of women at increased risk for breast cancer results in a more favorable harm-benefit ratio in all models. Starting biennial screening with digital mammography at the age of 40 years in high-risk women (those with a 2-fold increased risk above average) yields the same false-positive findings/life-years gained as biennial screening of average-risk women aged 50 to 74 years [ threshold RR, 1.9 (range across models, 1.5-4.4)]. The model predicts that threshold RRs for annual screening with digital mammography for women aged 40 to 49 years would be 4-fold higher to achieve the same false-positive findings/life-years gained as biennial screening of average-risk women aged 50 to 74 years [ median threshold RR, 4.3 (range, 3.3-10)]. A more favorable harm-benefit ratio was found with the use of film mammography than digital mammography because of the lower false-positive rate for film. There were only small differences between film and digital mammography with respect to benefits of screening. Use of a more comprehensive measure of harm led to a slight change in predicted median threshold RRs. One limitation of the study was the assumption that that the higher risk influenced only the onset of disease and not the screening performance (sensitivity, specificity). These findings show that harm-benefit ratios for biennial screening mammography in women aged 40 to 49 years with a 2-fold increased risk for breast cancer are comparable to those of average-risk women aged 50 to 74 years. Variations in screening method, interval, and outcome measures influence the threshold RRs required for a favorable harm-benefit ratio. C1 [van Ravesteyn, Nicolien T.] Erasmus MC, Rotterdam, Netherlands. Univ Washington, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Wisconsin, Madison, WI USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, Washington, DC USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Providence Hlth & Serv, Providence Canc Ctr, Portland, OR USA. RP van Ravesteyn, NT (reprint author), Erasmus MC, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD AUG PY 2012 VL 67 IS 8 BP 481 EP 482 DI 10.1097/01.ogx.0000418532.21029.ea PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 005LG UT WOS:000308751300015 ER PT J AU McMahon, PM Hazelton, WD Kimmel, M Clarke, LD AF McMahon, Pamela M. Hazelton, William D. Kimmel, Marek Clarke, Lauren D. TI CISNET Lung Models: Comparison of Model Assumptions and Model Structures SO RISK ANALYSIS LA English DT Article DE Lung cancer; modeling; population trends; tobacco control ID CLONAL EXPANSION MODEL; CPS-I DATA; CANCER MORTALITY; MULTISTAGE CARCINOGENESIS; 2-STAGE MODEL; TEMPORAL VARIATION; SMOKING-CESSATION; CIGARETTE-SMOKING; 2-MUTATION MODEL; TOBACCO CONTROL AB Sophisticated modeling techniques can be powerful tools to help us understand the effects of cancer control interventions on population trends in cancer incidence and mortality. Readers of journal articles are, however, rarely supplied with modeling details. Six modeling groups collaborated as part of the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET) to investigate the contribution of U.S. tobacco-control efforts toward reducing lung cancer deaths over the period 1975-2000. The six models included in this monograph were developed independently and use distinct, complementary approaches toward modeling the natural history of lung cancer. The models used the same data for inputs, and agreed on the design of the analysis and the outcome measures. This article highlights aspects of the models that are most relevant to similarities of or differences between the results. Structured comparisons can increase the transparency of these complex models. C1 [McMahon, Pamela M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [McMahon, Pamela M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hazelton, William D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Kimmel, Marek] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Clarke, Lauren D.] Cornerstone Syst NW, Lynden, WA USA. RP McMahon, PM (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pamela@mgh-ita.org FU CISNET Lung investigators, the National Cancer Institute [R01 CA97337, R00 CA126147, U01 CA152956] FX CISNET Lung investigators, the National Cancer Institute (R01 CA97337, R00 CA126147, U01 CA152956). NR 63 TC 10 Z9 10 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 EI 1539-6924 J9 RISK ANAL JI Risk Anal. PD AUG PY 2012 VL 32 SU 1 SI SI BP S166 EP S178 DI 10.1111/j.1539-6924.2011.01714.x PG 13 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 986KA UT WOS:000307339300014 PM 22882887 ER PT J AU McMahon, PM Kong, CY Johnson, BE Weinstein, MC Weeks, JC Tramontano, AC Cipriano, LE Bouzan, C Gazelle, GS AF McMahon, Pamela M. Kong, Chung Yin Johnson, Bruce E. Weinstein, Milton C. Weeks, Jane C. Tramontano, Angela C. Cipriano, Lauren E. Bouzan, Colleen Gazelle, G. Scott TI The MGH-HMS Lung Cancer Policy Model: Tobacco Control Versus Screening SO RISK ANALYSIS LA English DT Article DE Lung cancer; mass screening; microsimulation modeling; tobacco control ID MULTISTAGE CARCINOGENESIS; MORTALITY; SMOKING; PERIOD; HEALTH; DEATH AB The natural history model underlying the MGH Lung Cancer Policy Model (LCPM) does not include the two-stage clonal expansion model employed in other CISNET lung models. We used the LCPM to predict numbers of U. S. lung cancer deaths for ages 30-84 between 1975 and 2000 under four scenarios as part of the comparative modeling analysis described in this issue. The LCPM is a comprehensive microsimulation model of lung cancer development, progression, detection, treatment, and survival. Individual-level patient histories are aggregated to estimate cohort or population-level outcomes. Lung cancer states are defined according to underlying disease variables, test results, and clinical events. By simulating detailed clinical procedures, the LCPM can predict benefits and harms attributable to a variety of patient management practices, including annual screening programs. Under the scenario of observed smoking patterns, predicted numbers of deaths from the calibrated LCPM were within 2% of observed over all years (1975-2000). The LCPM estimated that historical tobacco control policies achieved 28.6% (25.2% in men, 30.5% in women) of the potential reduction in U. S. lung cancer deaths had smoking had been eliminated entirely. The hypothetical adoption in 1975 of annual helical CT screening of all persons aged 55-74 with at least 30 pack-years of cigarette exposure to historical tobacco control would have yielded a proportion realized of 39.0% (42.0% in men, 33.3% in women). The adoption of annual screening would have prevented less than half as many lung cancer deaths as the elimination of cigarette smoking. C1 [McMahon, Pamela M.; Kong, Chung Yin; Tramontano, Angela C.; Cipriano, Lauren E.; Bouzan, Colleen; Gazelle, G. Scott] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McMahon, Pamela M.; Kong, Chung Yin; Johnson, Bruce E.; Weinstein, Milton C.; Weeks, Jane C.; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Weinstein, Milton C.; Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Johnson, Bruce E.; Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP McMahon, PM (reprint author), Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pamela@mgh-ita.org RI Cipriano, Lauren/C-3521-2017 OI Cipriano, Lauren/0000-0001-5568-4516 FU CISNET Lung Investigators; National Cancer Institute [R01 CA97337, R00 CA126147, U01CA152956]; American Cancer Society [RSG 2008A060554] FX Karen M. Kuntz, Sc.D., David C. Christiani, M.D., M.P.H., CISNET Lung Investigators, the National Cancer Institute (R01 CA97337, R00 CA126147, U01CA152956), and the American Cancer Society (RSG 2008A060554). NR 18 TC 17 Z9 17 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 EI 1539-6924 J9 RISK ANAL JI Risk Anal. PD AUG PY 2012 VL 32 SU 1 SI SI BP S117 EP S124 DI 10.1111/j.1539-6924.2011.01652.x PG 8 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 986KA UT WOS:000307339300010 PM 22882882 ER PT J AU Rosenberg, MA Feuer, EJ Yu, BB Sun, JF Henley, SJ Shanks, TG Anderson, CM McMahon, PM Thun, MJ Burns, DM AF Rosenberg, Marjorie A. Feuer, Eric J. Yu, Binbing Sun, Jiafeng Henley, S. Jane Shanks, Thomas G. Anderson, Christy M. McMahon, Pamela M. Thun, Michael J. Burns, David M. TI Cohort Life Tables by Smoking Status, Removing Lung Cancer as a Cause of Death SO RISK ANALYSIS LA English DT Article DE Competing risks; life tables; lung cancer and smoking ID MORTALITY; DISEASE AB The purpose of this study was to develop life tables by smoking status removing lung cancer as a cause of death. These life tables are inputs to studies that compare the effectiveness of lung cancer treatments or interventions, and provide a way to quantify time until death from causes other than lung cancer. The study combined actuarial and statistical smoothing methods, as well as data from multiple sources, to develop separate life tables by smoking status, birth cohort, by single year of age, and by sex. For current smokers, separate life tables by smoking quintiles were developed based on the average number of cigarettes smoked per day by birth cohort. The end product is the creation of six non-lung-cancer life tables for males and six tables for females: five current smoker quintiles and one for never smokers. Tables for former smokers are linear combinations of the appropriate table based on the current smoker quintile before quitting smoking and the never smoker probabilities, plus added covariates for the smoking quit age and time since quitting. C1 [Rosenberg, Marjorie A.; Sun, Jiafeng] Univ Wisconsin, Madison, WI 53706 USA. [Feuer, Eric J.] NCI, Bethesda, MD 20892 USA. [Yu, Binbing] NIA, Baltimore, MD 21224 USA. [Henley, S. Jane; Thun, Michael J.] Amer Canc Soc, Atlanta, GA 30329 USA. [Shanks, Thomas G.; Anderson, Christy M.; Burns, David M.] Univ Calif San Diego, San Diego, CA 92103 USA. [McMahon, Pamela M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McMahon, Pamela M.] Harvard Univ, Sch Med, Boston, MA USA. RP Rosenberg, MA (reprint author), Univ Wisconsin, 975 Univ Ave, Madison, WI 53706 USA. EM mrosenberg@bus.wisc.edu FU NCI [263-MQ-319824, 263-MQ-416726-1]; Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health [1UL1RR025011]; Intramural Research Program of the National Institute on Aging FX Partially supported by NCI contract numbers 263-MQ-319824 and 263-MQ-416726-1, by Grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health, and by the Intramural Research Program of the National Institute on Aging. We acknowledge Jerry Vaughn of the University of California San Diego for his contribution on this article. NR 15 TC 20 Z9 20 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD AUG PY 2012 VL 32 SU 1 SI SI BP S25 EP S38 DI 10.1111/j.1539-6924.2011.01662.x PG 14 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 986KA UT WOS:000307339300004 PM 22882890 ER PT J AU Helenius, J Arsava, EM Goldstein, JN Cestari, DM Buonanno, FS Rosen, BR Ay, H AF Helenius, Johanna Arsava, E. Murat Goldstein, Joshua N. Cestari, Dean M. Buonanno, Ferdinando S. Rosen, Bruce R. Ay, Hakan TI Concurrent acute brain infarcts in patients with monocular visual loss SO ANNALS OF NEUROLOGY LA English DT Article ID CENTRAL RETINAL ARTERY; ISCHEMIC-STROKE; TRANSIENT; HEMORRHAGE; MANAGEMENT; EMBOLISM; DISEASE AB Objective: Embolism from a proximal source to the retinal circulation could be a sign of embolism from the same source to the hemispheric circulation. We sought to determine the frequency of acute brain infarcts on diffusion-weighted imaging (DWI) in patients with monocular visual loss of presumed ischemic origin (MVL). Methods: We retrospectively studied 129 consecutive patients with MVL secondary to retinal ischemia. All patients underwent DWI, comprehensive ophthalmologic and neurologic examination, and diagnostic evaluations for the underlying etiology. Statistical analyses explored univariate and multivariate predictors of DWI evidence of acute brain infarcts. Results: DWI revealed concurrent acute brain infarct(s) in 31 of the 129 patients (24%). The probability of positive DWI was higher in embolic versus nonembolic MVL (28 vs 8%, p = 0.04), in MVL characterized by permanent visual loss versus transient symptoms (33 vs 18%, p = 0.04), and in MVL associated with concurrent hemispheric symptoms versus isolated MVL (53 vs 20%, p < 0.01). Patients with positive DWI were more likely to harbor a major underlying etiology as compared to those with normal DWI (odds ratio, 3.7; 95% confidence interval, 1.59.4). Interpretation: This study demonstrates that MVL does not always represent an isolated disease of the retina; approximately 1 of every 4 patients with MVL demonstrates acute brain infarcts on DWI. Because patients with concurrent brain infarcts are more likely to exhibit a cardiac or vascular source of embolism, imaging evidence of brain injury in patients with MVL may be a useful marker to guide the timing and extent of diagnostic examinations. ANN NEUROL 2012;72:286293. C1 [Helenius, Johanna; Arsava, E. Murat; Rosen, Bruce R.; Ay, Hakan] Harvard Univ, Sch Med, Dept Radiol, AA Martinos Ctr Biomed Imaging,Massachusetts Gen, Boston, MA 02115 USA. [Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Cestari, Dean M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Buonanno, Ferdinando S.; Ay, Hakan] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ay, H (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 13th St,Bldg 149-2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013; Goldstein, Joshua/H-8953-2016 OI Arsava, Ethem Murat/0000-0002-6527-4139; FU NIH National Institute of Neurological Disorders and Stroke [R01-NS059710]; Finnish Cultural Foundation; Paulo Foundation; Orion-Farmos Foundation; Paavo Nurmi Foundation; Emil Aaltonen Foundation; Finnish Foundation for Cardiovascular Research; National Institute of Neurological Disorders and Stroke [K23-NS059774]; Finnish Medical Foundation; Finnish Brain Research Foundation; Maire Taponen Foundation; Swedish Cultural Foundation in Finland FX H.A. was funded by NIH National Institute of Neurological Disorders and Stroke grant R01-NS059710. J.H. was partly supported by the Finnish Cultural Foundation, Paulo Foundation, Orion-Farmos Foundation, Paavo Nurmi Foundation, Emil Aaltonen Foundation, and Finnish Foundation for Cardiovascular Research. J.N.G. was supported by National Institute of Neurological Disorders and Stroke grant K23-NS059774.; J.H.: grants/grants pending, Finnish Medical Foundation, Finnish Brain Research Foundation, Maire Taponen Foundation, and Swedish Cultural Foundation in Finland. NR 24 TC 19 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2012 VL 72 IS 2 BP 286 EP 293 DI 10.1002/ana.23597 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 994QK UT WOS:000307946000018 PM 22926859 ER PT J AU Wheeler, JM Guthrie, CR Kraemer, BC AF Wheeler, Jeanna M. Guthrie, Chris R. Kraemer, Brian C. TI Potential neuroprotective strategies against tauopathy SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE autophagy; mammalian suppressor of tau pathology 2 (MSUT2); neurodegeneration; neuroprotection; tau; tauopathy ID TAU-INDUCED NEUROTOXICITY; CAENORHABDITIS-ELEGANS; NEUROFIBRILLARY TANGLES; FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; FTDP-17 MUTATIONS; IN-VITRO; EXON 10; PROTEIN; AGGREGATION AB Tauopathies are neurodegenerative diseases, including AD (Alzheimer's disease) and FTLD-T (tau-positive frontotemporal lobar degeneration), with shared pathology presenting as accumulation of detergent-insoluble hyperphosphorylated tau deposits in the central nervous system. The currently available treatments for AD address only some of the symptoms, and do not significantly alter the progression of the disease, namely the development of protein aggregates and loss of functional neurons. The development of effective treatments for various tauopathies will require the identification of common mechanisms of tau neurotoxicity, and pathways that can be modulated to protect against neurodegeneration. Model organisms, such as Caenorhabditis elegans, provide methods for identifying novel genes and pathways that are involved in tau pathology and may be exploited for treatment of various tauopathies. In the present paper, we summarize data regarding characterization of MSUT2 (mammalian suppressor of tau pathology 2), a protein identified in a C. elegans tauopathy model and subsequently shown to modify tau toxicity in mammalian cell culture via the effects on autophagy pathways. MSUT2 represents a potential drug target for prevention of tau-related neurodegeneration. C1 [Wheeler, Jeanna M.; Guthrie, Chris R.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Wheeler, Jeanna M.; Guthrie, Chris R.; Kraemer, Brian C.] Univ Washington, Dept Med, Div Gerontol, Seattle, WA 98195 USA. [Wheeler, Jeanna M.; Guthrie, Chris R.; Kraemer, Brian C.] Univ Washington, Dept Med, Div Geriatr Med, Seattle, WA 98195 USA. RP Kraemer, BC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way, Seattle, WA 98108 USA. EM kraemerb@u.washington.edu FU Department of Veterans Affairs Merit Review Grant; National Institute of Neurological Disorders and Stroke [R01NS064131] FX This work was supported by a Department of Veterans Affairs Merit Review Grant and by the National Institute of Neurological Disorders and Stroke [grant number R01NS064131] (to B.C.K.). NR 47 TC 1 Z9 1 U1 0 U2 9 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 2012 VL 40 BP 656 EP 660 DI 10.1042/BST20120017 PN 4 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 987QH UT WOS:000307431700011 PM 22817711 ER PT J AU Schroy, PC Coe, AM Mylvaganam, SR Ahn, LB Lydotes, MA Robinson, PA Davis, JT Chen, CA Ashba, J Atkinson, ML Colditz, GA Heeren, TC AF Schroy, Paul C., III Coe, Alison M. Mylvaganam, Shamini R. Ahn, Lynne B. Lydotes, Maria A. Robinson, Patricia A. Davis, Julie T. Chen, Clara A. Ashba, Jacqueline Atkinson, Michael L. Colditz, Graham A. Heeren, Timothy C. TI The Your Disease Risk Index for Colorectal Cancer Is an Inaccurate Risk Stratification Tool for Advanced Colorectal Neoplasia at Screening Colonoscopy SO CANCER PREVENTION RESEARCH LA English DT Article ID SERVICES-TASK-FORCE; UNITED-STATES; AVERAGE-RISK; ADENOMATOUS POLYPS; PRIMARY PREVENTION; PREDICTION TOOL; WHITE PATIENTS; METAANALYSIS; VALIDATION; CAPACITY AB Tailoring the use of screening colonoscopy based on the risk of advanced colorectal neoplasia (ACN) could optimize the cost-effectiveness of colorectal cancer (CRC) screening. Our goal was to assess the accuracy of the Your Disease Risk (YDR) CRC risk index for stratifying average risk patients into low-versus intermediate/high-risk categories for ACN. The YDR risk assessment tool was administered to 3,317 asymptomatic average risk patients 50 to 79 years of age just before their screening colonoscopy. Associations between YDR-derived relative risk (RR) scores and ACN prevalence were examined using logistic regression and chi(2) analyses. ACN was defined as a tubular adenoma >= 1 cm, tubulovillous or villous adenoma of any size, and the presence of high-grade dysplasia or cancer. The overall prevalence of ACN was 5.6%. Although YDR-derived RR scores were linearly associated with ACN after adjusting for age and gender (P = 0.033), the index was unable to discriminate "below average" from "above/average" risk patients [OR, 1.01; 95% confidence interval (CI), 0.75-1.37]. Considerable overlap in rates of ACN was also observed between the different YDR risk categories in our age-and gender-stratified analyses. The YDR index lacks accuracy for stratifying average risk patients into low-versus intermediate/high-risk categories for ACN. Cancer Prev Res; 5(8); 1044-52. (C) 2012 AACR. C1 [Schroy, Paul C., III; Coe, Alison M.; Mylvaganam, Shamini R.; Ahn, Lynne B.; Lydotes, Maria A.; Robinson, Patricia A.; Davis, Julie T.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Heeren, Timothy C.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Chen, Clara A.; Ashba, Jacqueline] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Atkinson, Michael L.] Dana Farber Canc Inst, Channing Lab, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Prevent & Control Siteman Canc Ctr, St Louis, MO USA. RP Schroy, PC (reprint author), Boston Med Ctr, 85 E Concord St,Suite 7715, Boston, MA 02118 USA. EM paul.schroy@bmc.org RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Heeren, Timothy/0000-0001-5643-3559 FU National Cancer Institute [R01 CA131197] FX The study was supported by the National Cancer Institute Award R01 CA131197 (to P. C. Schroy III) NR 42 TC 13 Z9 13 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD AUG PY 2012 VL 5 IS 8 BP 1044 EP 1052 DI 10.1158/1940-6207.CAPR-12-0014 PG 9 WC Oncology SC Oncology GA 998FS UT WOS:000308223500007 PM 22689913 ER PT J AU Casement, MD Swanson, LM AF Casement, Melynda D. Swanson, Leslie M. TI A meta-analysis of imagery rehearsal for post-trauma nightmares: Effects on nightmare frequency, sleep quality, and posttraumatic stress SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article DE Imagery rehearsal therapy; Rescripting therapy; Nightmares; Sleep; Post-traumatic stress ID SEXUAL ASSAULT SURVIVORS; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; DISORDER; PTSD; VETERANS; DISTURBANCE; INSOMNIA; IMPAIRMENT; INSTRUMENT AB This meta-analysis evaluates the efficacy of imagery rehearsal as a treatment for nightmares, general sleep disturbance, and symptoms of post-traumatic stress. Bibliographic databases and cited references were searched to identify clinical trials of imagery rehearsal in individuals with post-trauma nightmares. Thirteen studies met inclusion criteria and reported sleep and post-traumatic stress outcomes in sufficient detail to calculate effect sizes. Results indicate that imagery rehearsal had large effects on nightmare frequency, sleep quality, and PTSD symptoms from the initial to post-treatment assessments. These effects were sustained through 6 to 12 months follow-up. Furthermore, interventions that included both imagery rehearsal and cognitive behavioral therapy for insomnia resulted in greater treatment-related improvement in sleep quality than imagery rehearsal alone. Combined treatment did not improve outcomes for PTSD or nightmares. Notably, effect sizes were small in the single study that included an active-treatment control condition. Future research should identify necessary and sufficient components of interventions for trauma-related sleep disturbance and post-traumatic stress (e.g., exposure, cognitive reappraisal, sleep and circadian regulation). Published by Elsevier Ltd. C1 [Casement, Melynda D.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Casement, Melynda D.] Boston Univ, Med Ctr, Boston, MA USA. [Swanson, Leslie M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Casement, MD (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, 3811 OHara St,Keystone 310, Pittsburgh, PA 15213 USA. EM casementmd@upmc.edu OI Casement, Melynda/0000-0002-5906-0994 FU NIMH NIH HHS [T32 MH019836, T32MH019836] NR 53 TC 33 Z9 33 U1 4 U2 29 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD AUG PY 2012 VL 32 IS 6 BP 566 EP 574 DI 10.1016/j.cpr.2012.06.002 PG 9 WC Psychology, Clinical SC Psychology GA 995XW UT WOS:000308049600012 PM 22819998 ER PT J AU Koshkareva, YA Cohen, M Gaughan, JP Callanan, V Szeremeta, W AF Koshkareva, Yekaterina A. Cohen, Michael Gaughan, John P. Callanan, Vincent Szeremeta, Wasyl TI Utility of preoperative hematologic screening for pediatric adenotonsillectomy SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Article ID LUPUS ANTICOAGULANT SYNDROME; POST-TONSILLECTOMY; HEMOSTATIC ASSESSMENT; COAGULATION; HEMORRHAGE; CHILDREN; ADENOIDECTOMY; PREDICTOR; HISTORY AB We conducted a 3-year retrospective study to examine the results of preoperative hematologic screening, the incidence of postoperative bleeding, and the possible relationship between the two factors in patients who had undergone tonsillectomy with or without adenoidectomy. Our study population was made up of 875 patients-441 boys and 434 girls, aged 2 to 18 years (mean: 7.52 +/- 4.25)-who had been treated at our institution from January 2004 through December 2006. In addition to demographic data, we compiled information on each patient's medical and surgical history, personal and family history of abnormal bleeding, indication for tonsillectomy, and preoperative hematologic screening results. The latter included determinations of the prothrombin time, activated partial thromboplastin time, international normalized ratio (INR), and platelet count. A total of 748 patients (85.5%) had normal findings on preoperative hematologic screening, and 127(14.5%) had at least one abnormality. Postoperatively, hemorrhagic complications occurred in 31 children (3.5%)-in 22 of the 748 patients with normal screening results (2.9%) and in 9 of the 127 with a screening abnormality (7.1%); the difference between the two groups was statistically significant (p = 0.041). The abnormalities in the latter group consisted of an elevated INR but no otherwise identifiable coagulopathy. Another 14 patients with an abnormal screening result (11.0%) were found to have at least one coagulopathy that was newly diagnosed during our preoperative evaluation; they were treated perioperatively, and none bled postoperatively. Of 21 patients who had a personal or family history of abnormal bleeding, 5 (23.8%) were found to have a coagulopathy, but none bled following surgery. In conclusion, we found that preoperative hematologic screening identified patients with undiagnosed coagulopathies, and with appropriate treatment our surgeons were able to prevent some bleeding events in these patients. Our finding that patients with a mildly elevated INR had a higher incidence of postoperative hemorrhage warrants further study. C1 [Koshkareva, Yekaterina A.] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Cohen, Michael] Massachusetts Eye & Ear Infirm, ENT Serv, Boston, MA 02114 USA. [Gaughan, John P.] Temple Univ, Sch Med, Biostat Consulting Ctr, Philadelphia, PA 19122 USA. [Callanan, Vincent] Women & Childrens Hosp Buffalo, Dept Pediat Otolaryngol Head & Neck Surg, Buffalo, NY USA. [Szeremeta, Wasyl] SUNY Stony Brook, Dept Surg, Div Otolaryngol Head & Neck Surg, Med Ctr, Stony Brook, NY 11794 USA. Temple Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19122 USA. RP Koshkareva, YA (reprint author), Univ Pittsburgh, Med Ctr, Dept Otolaryngol, 200 Lothrop St,EI 500, Pittsburgh, PA 15213 USA. EM koshkarevaye@ph.upmc.edu NR 23 TC 1 Z9 1 U1 0 U2 1 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0145-5613 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD AUG PY 2012 VL 91 IS 8 BP 346 EP + PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 994HG UT WOS:000307920900010 PM 22930084 ER PT J AU Tanaka, M Bailey, JN Bai, DS Ishikawa-Brush, Y Delgado-Escueta, AV Olsen, RW AF Tanaka, Miyabi Bailey, Julia N. Bai, Dongsheng Ishikawa-Brush, Yumiko Delgado-Escueta, Antonio V. Olsen, Richard W. TI Effects on promoter activity of common SNPs in 5 ' region of GABRB3 exon 1A SO EPILEPSIA LA English DT Article DE Luciferase activity; rs20317; rs4906902; Epigenetic modulator REST; Childhood absence epilepsy ID CHILDHOOD ABSENCE EPILEPSY; GABA(A) RECEPTOR; TARGET GENES; REST; SUBUNIT; GENOME; IDENTIFICATION; DISORDERS; REPRESSOR; ELEMENT AB Purpose: The beta 3 subunit of the c-aminobutyric acid type A receptors (GABA(A)-Rs) is an essential component of GABA(A)-Rs in fetal, perinatal, and adult mammalian brain. Various transcripts of the beta 3 subunit gene (GABRB3) produce various proteins with different N-termini. Rare variants in this N-terminus (exon 1A and exon 2) of GABRB3 protein segregate in affected family members of two multigeneration-multiplex families with remitting childhood absence epilepsy (rCAE), suggesting GABRB3 is a major Mendelian epilepsy gene for rare families with CAE. Therefore, the N-terminus of GABRB3 could be important for GABRB3 regulation in development, and its alteration could produce rCAE. Herein we determine if single nucleotide polymorphisms (SNPs) within the 1,148-bp region upstream from exon 1A influence the expression of GABRB3. Methods: We studied luciferase reporter expression for promoter activity, 1,148-bp upstream from exon 1A, using human embryonic kidney 293 cells. We generated constructs of the promoter region and compared different SNP haplotypes in 48 patients with rCAE. Next, we compared frequencies of rs20317, located in the core promoter region, and rs4906902, located in the enhancer region between 48 patients with rCAE and >500 healthy controls matched for ethnicity and ancestral origin. Key Findings: Highest luciferase expression occurred 230-bp upstream of exon 1A. The construct that excluded this region lost luciferase activity. Therefore, this region contains the core promoter of exon 1A. Allele C but not allele G (rs20317) significantly increased luciferase expression activity. Allele C creates binding motifs for cMYB and EGR-3. Longer constructs overlapping this region have a binding motif for REST (RE1-silencing transcription factor), a critical epigenetic modulator for neuronal genes. REST represses expression of neuronal genes in nonneuronal tissues, resulting in reduced luciferase expression activity. Even in the suppressed condition, the longer construct enhanced luciferase expression activity of the shorter construct, which excluded the distal end containing rs4906902. However, allele frequencies of rs20317 and rs4906902 were not significantly associated with 48 rCAE patients in comparison to >500 controls matched for ethnicity and ancestral origin. Significance: Common SNPs in the promoter region increase luciferase expression activity. An epigenetic modulator, REST, specifically alters expression of GABRB3 exon 1A transcripts, suggesting epigenetic regulation by REST dominantly controls the expression of GABRB3 variant 2 transcript in early life GABA(A) signaling. Abnormal epigenetic regulation could be involved in absence seizures. C1 [Tanaka, Miyabi; Olsen, Richard W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Tanaka, Miyabi; Bailey, Julia N.; Bai, Dongsheng; Delgado-Escueta, Antonio V.] Vet Affairs Greater Los Angeles Healthcare Syst, Genom Lab, Neurol & Res Serv, Los Angeles, CA USA. [Bailey, Julia N.] Univ Calif Los Angeles, Dept Epidemiol, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Bai, Dongsheng; Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ishikawa-Brush, Yumiko] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94143 USA. RP Olsen, RW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. EM escueta@ucla.edu; rolsen@mednet.ucla.edu OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU National Institutes of Health [NS35985]; National Institutes of Health NINDS [NS055057]; Veterans Administration Merit Review Grant FX We thank all CAE patients and their families for their cooperation, GENESS site neurologists and staff for their help, Ziwei Chen for helpful advice, the J Huang laboratory, and Computational Sciences Group, UCLA Pharmacology Dept, for their cooperation. This work was supported by National Institutes of Health Grant NS35985 to RWO; by National Institutes of Health NINDS Grant NS055057 to AVDE, and a Veterans Administration Merit Review Grant to AVDE. NR 21 TC 7 Z9 8 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2012 VL 53 IS 8 BP 1450 EP 1456 DI 10.1111/j.1528-1167.2012.03572.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 001EI UT WOS:000308442800026 PM 22765836 ER PT J AU Jiwani, AZ Rhee, DJ Brauner, SC Gardiner, MF Chen, TC Shen, LQ Chen, SH Grosskreutz, CL Chang, KK Kloek, CE Greenstein, SH Borboli-Gerogiannis, S Pasquale, DL Chaudhry, S Loomis, S Wiggs, JL Pasquale, LR Turalba, AV AF Jiwani, A. Z. Rhee, D. J. Brauner, S. C. Gardiner, M. F. Chen, T. C. Shen, L. Q. Chen, S. H. Grosskreutz, C. L. Chang, K. K. Kloek, C. E. Greenstein, S. H. Borboli-Gerogiannis, S. Pasquale, D. L. Chaudhry, S. Loomis, S. Wiggs, J. L. Pasquale, L. R. Turalba, A. V. TI Effects of caffeinated coffee consumption on intraocular pressure, ocular perfusion pressure, and ocular pulse amplitude: a randomized controlled trial SO EYE LA English DT Article DE caffeine; coffee; intraocular pressure; ocular perfusion pressure; ocular pulse amplitude; primary open-angle glaucoma ID OPEN-ANGLE GLAUCOMA; BLOOD-PRESSURE; RISK-FACTORS; NORMAL-TENSION; BARBADOS EYE; LONG-TERM; HYPERTENSION; POPULATION; ADENOSINE; DISEASE AB Purpose To examine the effects of caffeinated coffee consumption on intraocular pressure (IOP), ocular perfusion pressure (OPP), and ocular pulse amplitude (OPA) in those with or at risk for primary open-angle glaucoma (POAG). Methods We conducted a prospective, double-masked, crossover, randomized controlled trial with 106 subjects: 22 with high tension POAG, 18 with normal tension POAG, 20 with ocular hypertension, 21 POAG suspects, and 25 healthy participants. Subjects ingested either 237 ml of caffeinated (182mg caffeine) or decaffeinated (4mg caffeine) coffee for the first visit and the alternate beverage for the second visit. Blood pressure (BP) and pascal dynamic contour tonometer measurements of IOP, OPA, and heart rate were measured before and at 60 and 90 min after coffee ingestion per visit. OPP was calculated from BP and IOP measurements. Results were analysed using paired t-tests. Multivariable models assessed determinants of IOP, OPP, and OPA changes. Results There were no significant differences in baseline IOP, OPP, and OPA between the caffeinated and decaffeinated visits. After caffeinated as compared with decaffeinated coffee ingestion, mean mmHg changes (+/- SD) in IOP, OPP, and OPA were as follows: 0.99 (+/- 1.52, P<0.0001), 1.57 (+/- 6.40, P = 0.0129), and 0.23 (+/- 0.52, P<0.0001) at 60 min, respectively; and 1.06 (+/- 1.67, P<0.0001), 1.26 (+/- 6.23, P = 0.0398), and 0.18 (+/- 0.52, P = 0.0006) at 90 min, respectively. Regression analyses revealed sporadic and inconsistent associations with IOP, OPP, and OPA changes. Conclusion Consuming one cup of caffeinated coffee (182mg caffeine) statistically increases, but likely does not clinically impact, IOP and OPP in those with or at risk for POAG. Eye (2012) 26, 1122-1130; doi:10.1038/eye.2012.113; published online 8 June 2012 C1 [Jiwani, A. Z.; Rhee, D. J.; Brauner, S. C.; Gardiner, M. F.; Chen, T. C.; Shen, L. Q.; Chen, S. H.; Grosskreutz, C. L.; Chang, K. K.; Kloek, C. E.; Greenstein, S. H.; Borboli-Gerogiannis, S.; Pasquale, D. L.; Loomis, S.; Wiggs, J. L.; Pasquale, L. R.; Turalba, A. V.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Jiwani, A. Z.] Yale Univ, Sch Med, New Haven, CT USA. [Chaudhry, S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Pasquale, LR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM louis_pasquale@meei.harvard.edu OI Gardiner, Matthew/0000-0002-8864-2379 FU Fight for Sight Postdoctoral Grant; Doris Duke Charitable Foundation; Yale School of Medicine Summer Fellowship; Research to Prevent Blindness Physician Scientist Award; Harvard Medical School Ophthalmology Scholar Award; Allergan Horizon Award FX This work was supported by a Fight for Sight Postdoctoral Grant (Angela V Turalba). Aliya Z Jiwani is funded by a Doris Duke Charitable Foundation One-Year Clinical Research Fellowship and a Yale School of Medicine Summer Fellowship. Louis R Pasquale is supported by a Research to Prevent Blindness Physician Scientist Award, Harvard Medical School Ophthalmology Scholar Award, and an Allergan Horizon Award. NR 55 TC 7 Z9 8 U1 0 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD AUG PY 2012 VL 26 IS 8 BP 1122 EP 1130 DI 10.1038/eye.2012.113 PG 9 WC Ophthalmology SC Ophthalmology GA 991TW UT WOS:000307726000017 PM 22678051 ER PT J AU Ogino, S Giovannucci, E AF Ogino, Shuji Giovannucci, Edward TI Commentary: Lifestyle factors and colorectal cancer microsatellite instability-molecular pathological epidemiology science, based on unique tumour principle SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID ISLAND METHYLATOR PHENOTYPE; ACID SYNTHASE EXPRESSION; BODY-MASS INDEX; COLON-CANCER; RISK; ASSOCIATIONS; SURVIVAL; FIELD; DIET C1 [Ogino, Shuji] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Pathol, Boston, MA 02215 USA. [Ogino, Shuji; Giovannucci, Edward] Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. [Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Pathol, 450 Brookline Ave,Room JF-215C, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [R01 CA151993, P01 CA55075, P01 CA87969] NR 22 TC 20 Z9 22 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2012 VL 41 IS 4 BP 1072 EP 1074 DI 10.1093/ije/dys076 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 998IV UT WOS:000308232200025 PM 22596930 ER PT J AU Kitahara, CM Wang, SS Melin, BS Wang, ZM Braganza, M Inskip, PD Albanes, D Andersson, U Freeman, LEB Buring, JE Carreon, T Feychting, M Gapstur, SM Gaziano, JM Giles, GG Hallmans, G Hankinson, SE Henriksson, R Hsing, AW Johansen, C Linet, MS McKean-Cowdin, R Michaud, DS Peters, U Purdue, MP Rothman, N Ruder, AM Sesso, HD Severi, G Shu, XO Stevens, VL Visvanathan, K Waters, MA White, E Wolk, A Zeleniuch-Jacquotte, A Zheng, W Hoover, R Fraumeni, JF Chatterjee, N Yeager, M Chanock, SJ Hartge, P Rajaraman, P AF Kitahara, Cari M. Wang, Sophia S. Melin, Beatrice S. Wang, Zhaoming Braganza, Melissa Inskip, Peter D. Albanes, Demetrius Andersson, Ulrika Freeman, Laura E. Beane Buring, Julie E. Carreon, Tania Feychting, Maria Gapstur, Susan M. Gaziano, J. Michael Giles, Graham G. Hallmans, Goran Hankinson, Susan E. Henriksson, Roger Hsing, Ann W. Johansen, Christoffer Linet, Martha S. McKean-Cowdin, Roberta Michaud, Dominique S. Peters, Ulrike Purdue, Mark P. Rothman, Nathaniel Ruder, Avima M. Sesso, Howard D. Severi, Gianluca Shu, Xiao-Ou Stevens, Victoria L. Visvanathan, Kala Waters, Martha A. White, Emily Wolk, Alicja Zeleniuch-Jacquotte, Anne Zheng, Wei Hoover, Robert Fraumeni, Joseph F., Jr. Chatterjee, Nilanjan Yeager, Meredith Chanock, Stephen J. Hartge, Patricia Rajaraman, Preetha TI Association between adult height, genetic susceptibility and risk of glioma SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Height; brain cancer; glioma; cancer; epidemiology ID BASE-LINE CHARACTERISTICS; BODY-MASS INDEX; GENOME-WIDE ASSOCIATION; CANCER-RISK; PROSPECTIVE COHORT; WOMENS HEALTH; LEG LENGTH; GROWTH; MORTALITY; DESIGN AB Background Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub- types, and investigated effect modification by genetic susceptibility to the disease. Methods We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants. Results Among men, we found a positive association between height and glioma risk (epsilon 190 vs 170-174 cm, pooled OR = 1.70, 95% CI: 1.11-2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17-3.38; P-trend = 0.02). Among women, these associations were less clear (epsilon 175 vs 160-164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70-1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77-2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk. Conclusion An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease. C1 [Kitahara, Cari M.; Wang, Zhaoming; Braganza, Melissa; Inskip, Peter D.; Albanes, Demetrius; Freeman, Laura E. Beane; Hsing, Ann W.; Linet, Martha S.; Purdue, Mark P.; Rothman, Nathaniel; Hoover, Robert; Fraumeni, Joseph F., Jr.; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J.; Hartge, Patricia; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Melin, Beatrice S.; Andersson, Ulrika; Henriksson, Roger] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Wang, Zhaoming; Yeager, Meredith; Chanock, Stephen J.] NCI, Core Genotyping Facil, SAIC Frederick Inc, Gaithersburg, MD USA. [Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Carreon, Tania; Ruder, Avima M.; Waters, Martha A.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Feychting, Maria; Wolk, Alicja] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden. [Hankinson, Susan E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Henriksson, Roger] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Johansen, Christoffer] Danish Canc Soc, Unit Survivorship, Copenhagen, Denmark. [McKean-Cowdin, Roberta] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Michaud, Dominique S.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Peters, Ulrike; White, Emily] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Peters, Ulrike; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN USA. [Visvanathan, Kala] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, Div Epidemiol, New York, NY 10016 USA. RP Kitahara, CM (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 7053,6120 Execut Blvd, Rockville, MD 20852 USA. EM kitaharac@mail.nih.gov RI Ruder, Avima/I-4155-2012; Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016; Beane Freeman, Laura/C-4468-2015; Kitahara, Cari/R-8267-2016; OI Ruder, Avima/0000-0003-0419-6664; Purdue, Mark/0000-0003-1177-3108; Beane Freeman, Laura/0000-0003-1294-4124; Giles, Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI, National Institutes of Health; American Cancer Society; Centers for Disease Control and Prevention's National Program of Cancer Registries and cancer registries; National Cancer Institute's Surveillance Epidemiology and End Results Program; National Cancer Institute [R01 CA098661, P30 CA016087]; National Institute of Environmental Health Sciences [ES000260]; National Institutes of Health [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; State of Maryland; Maryland Cigarette Restitution Fund; National Program of Cancer Registries of the Centers for Disease Control and Prevention; Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, NCI, National Institutes of Health (NIH); Department of Health and Human Services (DHHS); VicHealth; Australian National Health and Medical Research Council [209057, 251533, 396414]; NCI [K05CA154337]; NIH Office of Dietary Supplements (ODS) FX This work was supported in part by the Intramural Research Program of the NCI, National Institutes of Health.; For CPS-II Nutrition Cohort: The Cancer Prevention Studies are supported by the American Cancer Society. Efforts of the ACS the study management group to maintain and follow the cohort are acknowledged. ACS investigators also acknowledge the contributions from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries and cancer registries supported by the National Cancer Institute's Surveillance Epidemiology and End Results Program.; For NYUWHS: The NYUWHS is supported by National Cancer Institute grants R01 CA098661 and P30 CA016087 and by Center grant ES000260 from the National Institute of Environmental Health Sciences.; For PHS: The PHS is supported by grants CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health.; For CLUE: Cancer incidence data were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene, 201 W. Preston Street, Room 400, Baltimore, MD 21201, USA; www.fha.state.md.us/cancer/registry/, 410-767-4055. The authors acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data. The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Maryland Cancer Registry.; For PLCO: This research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, NCI, National Institutes of Health (NIH) and Department of Health and Human Services (DHHS). The authors thank Drs Christine Berg and Philip Prorok, Division of Cancer Prevention, NCI, the Screening Center investigators and staff of the PLCO cancer screening trial, Mr Tom Riley and staff, Information Management Services, Inc., Ms Barbara O'Brien and staff, Westat, Inc., Mr Tim Sheehy and staff, DNA Extraction and Staging Laboratory, SAIC-Frederick, Inc. and Ms Jackie King and staff, BioReliance, Inc.; For MCCS: Infrastructure support for the MCCS recruitment and follow-up is provided by the Cancer Council Victoria, and cohort recruitment was partly funded by VicHealth. This work using the MCCS was supported by the Australian National Health and Medical Research Council (grant numbers 209057, 251533 and 396414).; For VITAL: Grant K05CA154337 is funded by the NCI and the NIH Office of Dietary Supplements (ODS). NR 47 TC 7 Z9 7 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2012 VL 41 IS 4 BP 1075 EP 1085 DI 10.1093/ije/dys114 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 998IV UT WOS:000308232200026 PM 22933650 ER PT J AU Elmariah, S Delaney, JAC Bluemke, DA Budoff, MJ O'Brien, KD Fuster, V Kronmal, RA Halperin, JL AF Elmariah, Sammy Delaney, Joseph A. C. Bluemke, David A. Budoff, Matthew J. O'Brien, Kevin D. Fuster, Valentin Kronmal, Richard A. Halperin, Jonathan L. TI Associations of LV Hypertrophy With Prevalent and Incident Valve Calcification Multi-Ethnic Study of Atherosclerosis SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE aortic valve; calcification; left ventricular mass; mitral valve annulus ID MITRAL ANNULAR CALCIFICATION; LEFT-VENTRICULAR HYPERTROPHY; COMPUTED-TOMOGRAPHY; DISEASE; SCLEROSIS; CALCIUM; RISK; MESA; HYPERTENSION; MORBIDITY AB OBJECTIVES The aim of this study was to evaluate the relationship between percentage of predicted left ventricular mass (%PredLVM) and valve calcification in the MESA (Multi-Ethnic Study of Atherosclerosis) study. BACKGROUND Cardiac valve calcification has been associated with left ventricular hypertrophy (LVH), which portends cardiovascular events. However, this relationship and its mediators are poorly understood. METHODS The MESA study is a longitudinal cohort study of men and women 45 to 84 years of age without clinical cardiovascular disease in whom serial cardiac magnetic resonance and computed tomography imaging were performed. The relationships between baseline %PredLVM and the prevalence, severity, and incidence of aortic valve (AVC) and mitral annulus calcification (MAC) were determined by regression modeling. RESULTS Prevalent AVC was observed in 630, and MAC was observed in 442 of 5,042 subjects (median 55.9 and 71.1 Agatston units, respectively). After adjustment for age, sex, body mass index (BMI), ethnicity, socioeconomic status, physical activity, diabetes, cholesterol levels, blood pressure, smoking, kidney function, serum lipids, and antihypertensive and statin medications, %PredLVM was associated with prevalent AVC (odds ratio [OR]: 1.18/SD increase in %PredLVM [95% confidence interval (CI): 1.08 to 1.30]; p = 0.0004) and MAC (OR: 1.18 [95% CI: 1.06 to 1.32]; p = 0.002). Similarly, %PredLVM was associated with increased severity of prevalent AVC (risk difference = 0.26 [95% CI: 0.15 to 0.38]; p < 0.0001) and MAC (risk difference = 0.20 [95% CI: 0.03 to 0.37]; p = 0.02). During follow-up (mean 2.4 +/- 0.9 years), 153 subjects (4%) developed AVC, and 198 (5%) developed MAC. The %PredLVM was associated with incident AVC (OR: 1.24 [95% CI: 1.04 to 1.47]; p = 0.02) and MAC (OR: 1.18 [95% CI: 1.01 to 1.40]; p = 0.04). Further adjustment for inflammatory markers and coronary artery calcification did not attenuate these associations. Specifically, concentric LVH most strongly predicted incident valve calcification. CONCLUSIONS Within the MESA cohort, LVH was associated with prevalence, severity, and incidence of valve calcification independent of hypertension and other identified confounders. (J Am Coll Cardiol Img 2012; 5: 781-8) (C) 2012 by the American College of Cardiology Foundation C1 [Elmariah, Sammy] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. [Elmariah, Sammy; Fuster, Valentin; Halperin, Jonathan L.] Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA. [Delaney, Joseph A. C.] Univ Florida, Dept Pharmaceut Outcomes & Policy, Gainesville, FL USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA. [Budoff, Matthew J.] Harbor UCLA, Div Cardiol, Los Angeles Biomed Res Inst, Torrance, CA USA. [O'Brien, Kevin D.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Fuster, Valentin] CNIC, Madrid, Spain. [Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Elmariah, S (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med,Dept Med, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM selmariah@partners.org RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute at the National Institutes of Health [R01 HL071739, T32 HL007824, N01-HC-95159, N01-HC-95165, N01-HC-95169]; GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease International Competitive Grants Award Program for Young Investigators; BG Medicine; Astellas Pharma; Bayer AG Healthcare; Bristol-Myers Squibb/Sanofi Partnership; Boehringer-Ingelheim; Daiichi Sankyo; Johnson Johnson; Sanofi-Aventis; Biotronik FX This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health (Grants R01 HL071739 [to Dr. Budoff] and T32 HL007824 [to Dr. Elmariah] and by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169) and the GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease International Competitive Grants Award Program for Young Investigators (to Dr. Elmariah). Dr. Budoff has a modest consulting agreement with the General Electric Company. Dr. O'Brien receives speaker honoraria from AstraZeneca and Merck. Dr. Fuster chairs the HRP study, which is funded by BG Medicine. Dr. Halperin receives consulting fees from Astellas Pharma, Bayer AG Healthcare, the Bristol-Myers Squibb/Sanofi Partnership, Boehringer-Ingelheim, Daiichi Sankyo, Johnson & Johnson, and Sanofi-Aventis; honoraria from Genzyme and Portola Pharmaceuticals; and is co-chairman of the IMPACT trial, which is sponsored by Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. H. William Strauss, MD, served as Guest Editor for this paper. NR 27 TC 7 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD AUG PY 2012 VL 5 IS 8 BP 781 EP 788 DI 10.1016/j.jcmg.2011.12.025 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 003DN UT WOS:000308588500003 PM 22897991 ER PT J AU Bruijnzeel, H Neuhaus, V Fostvedt, S Jupiter, JB Mudgal, CS Ring, DC AF Bruijnzeel, Hanneke Neuhaus, Valentin Fostvedt, Sigrid Jupiter, Jesse B. Mudgal, Chaitanya S. Ring, David C. TI Adverse Events of Open A1 Pulley Release for Idiopathic Trigger Finger SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE A1 pulley; classification; complications; open release; trigger finger ID MANAGEMENT; SURGERY AB Purpose To classify and report adverse events of trigger finger release in a large cohort of patients. Methods We retrospectively reviewed 1,598 trigger finger releases performed by 12 surgeons in 984 patients between 2001 and 2011. Adverse events were classified based on a system derived from the Centers for Disease Control and Prevention criteria and clinical experience. Risk factors for various adverse events were sought in bivariate and multivariable statistical analysis. Results At the latest follow-up, 66 patients (7%), or 84 operated trigger digits (5%), experienced a documented adverse event. The most common adverse events were recovery issues in 46 patients (3%) (such as postoperative symptoms treated with steroid injection or slow recovery of motion treated with hand therapy), wound problems in 30 patients (2%) (consisting of suture abscess, superficial infection, or wound separation), persistent postoperative triggering in 10 patients (0.6%), and recurrent triggering in 4 patients (0.3%). Diabetes mellitus was associated with wound problems, slow recovery of motion, and recurrence. Concomitant carpal tunnel release on the same side was associated with slow recovery. Conclusions Fourteen patients, less than 1%, in this cohort experienced an adverse event, such as persistent or recurrent triggering, requiring secondary surgery. No nerve injury or deep infection occurred in our cohort. One in 15 patients experienced a minor transient or treatable adverse event, and patients with diabetes were at greater risk. (J Hand Surg 2012;37A: 1650-1656. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Therapeutic IV. C1 [Ring, David C.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 15 TC 15 Z9 15 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD AUG PY 2012 VL 37A IS 8 BP 1650 EP 1656 DI 10.1016/j.jhsa.2012.05.014 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 985JK UT WOS:000307260200020 PM 22763058 ER PT J AU Pace-Schott, EF Verga, PW Bennett, TS Spencer, RMC AF Pace-Schott, Edward F. Verga, Patrick W. Bennett, Tobias S. Spencer, Rebecca M. C. TI Sleep promotes consolidation and generalization of extinction learning in simulated exposure therapy for spider fear SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Sleep; Extinction; Spider phobia; Fear conditioning; Exposure therapy ID POSTTRAUMATIC-STRESS-DISORDER; ANXIETY DISORDERS; CONDITIONED FEAR; POTENTIATED STARTLE; HUMANS; PHOBIA; ACQUISITION; ETIOLOGY; AMYGDALA; QUESTIONNAIRES AB Simulated exposure therapy for spider phobia served as a clinically naturalistic model to study effects of sleep on extinction. Spider-fearing, young adult women (N = 66), instrumented for skin conductance response (SCR), heart rate acceleration (HRA) and corrugator electromyography (EMG), viewed 14 identical 1-min videos of a behaving spider before a 12-hr delay containing a normal night's Sleep (N = 20) or continuous daytime Wake (N = 23), or a 2-hr delay of continuous wake in the Morning (N = 11) or Evening (N = 12). Following the delay, all groups viewed this same video 6 times followed by six 1-min videos of a novel spider. After each video, participants rated disgust, fearfulness and unpleasantness. In all 4 groups, all measures except corrugator EMG diminished across Session 1 (extinction learning) and, excepting SCR to a sudden noise, increased from the old to novel spider in Session 2. In Wake only, summed subjective ratings and SCR to the old spider significantly increased across the delay (extinction loss) and were greater for the novel vs. the old spider when it was equally novel at the beginning of Session 1 (sensitization). In Sleep only, SCR to a sudden noise decreased across the inter-session delay (extinction augmentation) and, along with HRA, was lower to the novel spider than initially to the old spider in Session 1 (extinction generalization). None of the above differentiated Morning and Evening groups suggesting that intervening sleep, rather than time-of-testing, produced differences between Sleep and Wake. Thus, sleep following exposure therapy may promote retention and generalization of extinction learning. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Pace-Schott, Edward F.; Verga, Patrick W.; Bennett, Tobias S.; Spencer, Rebecca M. C.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pace-Schott, Edward F.; Spencer, Rebecca M. C.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Pace-Schott, Edward F.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pace-Schott, EF (reprint author), Univ Massachusetts, Dept Psychol, Tobin Hall,Rm 522,135 Hicks Way, Amherst, MA 01003 USA. EM epacesch@psych.umass.edu OI Spencer, Rebecca/0000-0002-8674-2384 FU NIA [R00AG029710]; NIMH [R21MH090357] FX NIA R00AG029710 provided salary support for Edward F. Pace-Schott and Rebecca M.C. Spencer, Ph.D. as well as equipment and materials support for the study. NIMH R21MH090357 provided salary support for Edward F. Pace-Schott. NR 52 TC 34 Z9 34 U1 4 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD AUG PY 2012 VL 46 IS 8 BP 1036 EP 1044 DI 10.1016/j.jpsychires.2012.04.015 PG 9 WC Psychiatry SC Psychiatry GA 980AF UT WOS:000306865300010 PM 22578824 ER PT J AU Xiu, MH Chen, DC Wang, D Zhang, K Dong, AL Tang, W Zhang, FX Liu, LJ Liu, JH Liu, HB Yang, FD Kosten, TR Zhang, XY AF Xiu, Mei Hong Chen, Da Chun Wang, Dong Zhang, Kui Dong, AiLing Tang, Wei Zhang, Feixue Liu, Lian Jing Liu, Jia Hong Liu, Hai Bo Yang, Fu De Kosten, Thomas R. Zhang, Xiang Yang TI Elevated interleukin-18 serum levels in chronic schizophrenia: Association with psychopathology SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Interleukin; Cytokines; Immune ID CYTOTOXIC T-LYMPHOCYTES; CYTOKINE ALTERATIONS; IL-18; AUTOIMMUNITY; PATHOGENESIS; RISPERIDONE; INDUCTION; INFECTION; DISEASES; PLASMA AB Background: Schizophrenia is associated with various abnormalities in the immune system including elevated levels of Interleukin-18 (IL-18), a potent inflammatory cytokine in T-helper 1 (Th1) responses. The aim of this study was to assess the clinical significance of serum IL-18 levels in various stages of schizophrenia. Methods: We measured serum IL-18 levels using a sandwich enzyme-linked immunosorbent assay (ELISA) from 78 never-medicated first-episode schizophrenia, 79 medicated chronic schizophrenia and 78 healthy control subjects. The symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS). Results: The chronic patients had significantly greater serum IL-18 levels than both first-episode patients and controls. Serum IL-18 was also positively correlated with the PANSS general psychopathology subscore in chronic schizophrenic patients. Conclusions: Our results showed elevated IL-18 pathway activity may be involved in the psychopathology of schizophrenia. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Xiu, Mei Hong; Chen, Da Chun; Liu, Hai Bo; Yang, Fu De; Kosten, Thomas R.; Zhang, Xiang Yang] Peking Univ, Beijing HuiLongGuan Hosp, Psychiat Res Ctr, Beijing 100871, Peoples R China. [Wang, Dong; Zhang, Kui; Dong, AiLing] JingQu Hosp, Dept Psychiat, Weihai, Shandong, Peoples R China. [Tang, Wei; Zhang, Feixue; Liu, Lian Jing; Liu, Jia Hong] Kangning Hosp, Dept Psychiat, Wenzhou, Zhejiang, Peoples R China. [Kosten, Thomas R.; Zhang, Xiang Yang] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Kosten, TR (reprint author), VA Med Ctr, Res Bldg 110,Room 229,2002 Holcombe Blvd, Houston, TX 77030 USA. EM kosten@bcm.edu; xyzhang@bcm.edu FU National Natural Science Foundation of China [81000509]; Beijing Municipal Excellent Talents Foundation [2010D003034000032]; Stanley Medical Research Institute [03T-459, 05T-726]; United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was funded by National Natural Science Foundation of China (81000509), and Beijing Municipal Excellent Talents Foundation (2010D003034000032), and the Stanley Medical Research Institute (03T-459 and 05T-726), and the United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. These sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 44 TC 20 Z9 20 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD AUG PY 2012 VL 46 IS 8 BP 1093 EP 1098 DI 10.1016/j.jpsychires.2012.04.026 PG 6 WC Psychiatry SC Psychiatry GA 980AF UT WOS:000306865300018 PM 22647522 ER PT J AU Adelmant, G Calkins, AS Garg, BK Card, JD Askenazi, M Miron, A Sobhian, B Zhang, Y Nakatani, Y Silver, PA Iglehart, JD Marto, JA Lazaro, JB AF Adelmant, Guillaume Calkins, Anne S. Garg, Brijesh K. Card, Joseph D. Askenazi, Manor Miron, Alex Sobhian, Bijan Zhang, Yi Nakatani, Yoshihiro Silver, Pamela A. Iglehart, J. Dirk Marto, Jarrod A. Lazaro, Jean-Bernard TI DNA Ends Alter the Molecular Composition and Localization of Ku Multicomponent Complexes SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID DEPENDENT PROTEIN-KINASE; RNA-POLYMERASE-II; INDUCED REPLICATION STRESS; TRANSCRIPTION INITIATION; CATALYTIC SUBUNIT; HUMAN TELOMERASE; GENE-EXPRESSION; WERNER PROTEIN; IN-VITRO; PHOSPHORYLATION AB The Ku heterodimer plays an essential role in non-homologous end-joining and other cellular processes including transcription, telomere maintenance and apoptosis. While the function of Ku is regulated through its association with other proteins and nucleic acids, the specific composition of these macromolecular complexes and their dynamic response to endogenous and exogenous cellular stimuli are not well understood. Here we use quantitative proteomics to define the composition of Ku multicomponent complexes and demonstrate that they are dramatically altered in response to UV radiation. Subsequent biochemical assays revealed that the presence of DNA ends leads to the substitution of RNA-binding proteins with DNA and chromatin associated factors to create a macromolecular complex poised for DNA repair. We observed that dynamic remodeling of the Ku complex coincided with exit of Ku and other DNA repair proteins from the nucleolus. Microinjection of sheared DNA into live cells as a mimetic for double strand breaks confirmed these findings in vivo. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.013581, 411-421, 2012. C1 [Adelmant, Guillaume; Garg, Brijesh K.; Card, Joseph D.; Askenazi, Manor; Miron, Alex; Sobhian, Bijan; Zhang, Yi; Nakatani, Yoshihiro; Iglehart, J. Dirk; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Adelmant, Guillaume; Garg, Brijesh K.; Card, Joseph D.; Askenazi, Manor; Zhang, Yi; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Adelmant, Guillaume; Askenazi, Manor; Nakatani, Yoshihiro; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Silver, Pamela A.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Calkins, Anne S.; Miron, Alex; Iglehart, J. Dirk; Lazaro, Jean-Bernard] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM Jarrod_Marto@dfci.harvard.edu FU National Institutes of Health (NIH) [P50HG004233, P01NS047572]; Susan Smith Center for Women's Cancers; Strategic Research Initiative at the Dana-Farber Cancer Institute; NIH [R37GM36373-24]; Marsha Rivkin Foundation; Catt Family Foundation; James and Kimberly Pallotta Fund for Ovarian Cancer Research FX This work was supported by the National Institutes of Health (NIH) (P50HG004233 and P01NS047572), the Susan Smith Center for Women's Cancers, and the Strategic Research Initiative at the Dana-Farber Cancer Institute (to J. A. M.), in addition to NIH (R37GM36373-24) to P. A. S., along with support from the Marsha Rivkin Foundation, The Catt Family Foundation, and The James and Kimberly Pallotta Fund for Ovarian Cancer Research (to J. D. I.). NR 50 TC 15 Z9 15 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2012 VL 11 IS 8 BP 411 EP 421 DI 10.1074/mcp.M111.013581 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 995PW UT WOS:000308024200015 PM 22535209 ER PT J AU Xu, CJ Miranda-Nieves, D Ankrum, JA Matthiesen, ME Phillips, JA Roes, I Wojtkiewicz, GR Juneja, V Kultima, JR Zhao, WA Vemula, PK Lin, CP Nahrendorf, M Karp, JM AF Xu, Chenjie Miranda-Nieves, David Ankrum, James A. Matthiesen, Mads Emil Phillips, Joseph A. Roes, Isaac Wojtkiewicz, Gregory R. Juneja, Vikram Kultima, Jens Roat Zhao, Weian Vemula, Praveen Kumar Lin, Charles P. Nahrendorf, Matthias Karp, Jeffrey M. TI Tracking Mesenchymal Stem Cells with Iron Oxide Nanoparticle Loaded Poly(lactide-co-glycolide) Microparticles SO NANO LETTERS LA English DT Article DE Stem cell tracking; MRI contrast agents; iron oxide nanoparticles; cell therapy; mesenchymal stem cell; cell homing ID VERSUS-HOST-DISEASE; BONE-MARROW; CONTRAST AGENTS; MRI; PARTICLES; THERAPIES AB Monitoring the location, distribution and long-term engraftment of administered cells is critical for demonstrating the success of a cell therapy. Among available imaging-based cell tracking tools, magnetic resonance imaging (MRI) is advantageous due to its noninvasiveness, deep penetration, and high spatial resolution. While tracking cells in preclinical models via internalized MRI contrast agents (iron oxide nanoparticles, IO-NPs) is a widely used method, IO-NPs suffer from low iron content per particle, low uptake in nonphagocytotic cell types (e.g., mesenchymal stem cells, MSCs), weak negative contrast, and decreased MRI signal due to cell proliferation and cellular exocytosis. Herein, we demonstrate that internalization of IO-NP (10 nm) loaded biodegradable poly(lactide-co-glycolide) microparticles (IO/PLGA-MPs, 0.4-3 mu m) in MSCs enhances MR parameters such as the r(2) relaxivity (5-fold), residence time inside the cells (3-fold) and R-2 signal (2-fold) compared to IO-NPs alone. Intriguingly, in vitro and in vivo experiments demonstrate that internalization of IO/PLGA-MPs in MSCs does not compromise inherent cell properties such as viability, proliferation, migration and their ability to home to sites of inflammation. C1 [Xu, Chenjie; Miranda-Nieves, David; Ankrum, James A.; Matthiesen, Mads Emil; Phillips, Joseph A.; Roes, Isaac; Juneja, Vikram; Kultima, Jens Roat; Zhao, Weian; Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Univ, Brigham & Womens Hosp,Div Hlth Sci & Technol, Sch Med,Harvard Stem Cell Inst,Harvard MIT, Div Biomed Engn,Dept Med,Ctr Regenerat Therapeut, Cambridge, MA 02139 USA. [Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adv Microscopy Program,Ctr Syst Biol, Boston, MA 02114 USA. [Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kultima, Jens Roat] EMBL, D-69117 Heidelberg, Germany. [Xu, Chenjie] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China. RP Karp, JM (reprint author), Harvard Univ, Brigham & Womens Hosp,Div Hlth Sci & Technol, Sch Med,Harvard Stem Cell Inst,Harvard MIT, Div Biomed Engn,Dept Med,Ctr Regenerat Therapeut, 65 Landsdowne St, Cambridge, MA 02139 USA. EM jkarp@rics.bwh.harvard.edu RI Ankrum, James/N-4175-2014; xu, chenjie/E-4075-2012; OI Ankrum, James/0000-0003-3959-6158; Xu, Chenjie/0000-0002-8278-3912 FU Harvard Stem Cell Institute; National Institute of Health [HL095722, HL097172]; MIT-UROP program; John Reed Fund; Hugh Hampton Young Memorial Fund; National Science Foundation; National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN268201000044C] FX This work was supported by the Harvard Stem Cell Institute, and the National Institute of Health Grants HL095722 and HL097172 to J.M.K. D.M.N is supported by MIT-UROP program and the John Reed Fund. J.A.A. is supported by the Hugh Hampton Young Memorial Fund and the National Science Foundation. M.N. was supported by funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN268201000044C. We thank Dr. Nikolay Sergeyev (MGH) in "Center for Systems Biology Mouse Imaging Program" for helping us perform the relaxivity measurement with the benchtop relaxometer. NR 30 TC 62 Z9 64 U1 7 U2 71 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD AUG PY 2012 VL 12 IS 8 BP 4131 EP 4139 DI 10.1021/nl301658q PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 984SD UT WOS:000307211000042 PM 22769232 ER PT J AU Howitt, MR Garrett, WS AF Howitt, Michael R. Garrett, Wendy S. TI A complex microworld in the gut Gut microbiota and cardiovascular disease connectivity SO NATURE MEDICINE LA English DT Editorial Material ID OBESITY; MICE AB Millions of healthy bacteria colonize our guts from the moment we are born. Changes in the composition and abundance of these commensals affect the entire immune system and can predispose us to a variety of diseases, including intestinal infections, inflammatory and metabolic diseases, and cancer. The gut microbiome interacts not only with the host mucosa but also with potential pathogens; understanding what interactions and pathways are crucial for maintaining homeostasis and protecting the host from harmful bacteria and diseases can open new avenues to developing gut microbiota-based therapeutic approaches. In 'Bench to Bedside', Michael R. Howitt and Wendy S. Garrett examine the importance of metabolic crosstalk between the microbiota and the host in human metabolism and the development of cardiovascular disease. This adds one more layer of complexity to understanding what contributes to this pathology and how to harness the microbiota and their metabolic pathways to prevent it. In 'Bedside to Bench', Nobuhiko Kamada, Grace Chen and Gabriel Nunez discuss how targeting interactions between commensals and bacteria causing intestinal disease can lead to effective therapies to control these infections, which currently seem to lack an adequate treatment. Unraveling how commensals help the host prevent or block colonization of these pathogens can suggest new ways to increase our armamentarium to deal with these sometimes deadly intestinal infections. C1 [Howitt, Michael R.; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. [Howitt, Michael R.; Garrett, Wendy S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Howitt, MR (reprint author), Harvard Univ, Sch Publ Hlth, Sch Med, 665 Huntington Ave, Boston, MA 02115 USA. EM wgarrett@hsph.harvard.edu FU NCI NIH HHS [R01 CA154426]; NIAID NIH HHS [K08 AI078942] NR 16 TC 24 Z9 28 U1 4 U2 38 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2012 VL 18 IS 8 BP 1188 EP 1189 DI 10.1038/nm.2895 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 988DU UT WOS:000307469300022 PM 22869188 ER PT J AU Deng, XY Li, QL Hoff, J Novak, M Yang, HL Jin, HY Erfani, SF Sharma, C Zhou, PC Rabinovitz, I Sonnenberg, A Yi, YJ Zhou, P Stipp, CS Kaetzel, DM Hemler, ME Yang, XWH AF Deng, Xinyu Li, Qinglin Hoff, John Novak, Marian Yang, Helen Jin, Hongyan Erfani, Sonia F. Sharma, Chandan Zhou, Pengcheng Rabinovitz, Isaac Sonnenberg, Arnoud Yi, Yajun Zhou, Peter Stipp, Christopher S. Kaetzel, David M. Hemler, Martin E. Yang, Xiuwei H. TI Integrin-Associated CD151 Drives ErbB2-Evoked Mammary Tumor Onset and Metastasis SO NEOPLASIA LA English DT Article ID GENE-EXPRESSION SIGNATURE; LAMININ-BINDING INTEGRINS; BREAST-CANCER; TETRASPANIN CD151; IN-VIVO; EPITHELIAL-CELLS; BETA-4 INTEGRIN; MICE LACKING; MOUSE MODEL; STEM-CELLS AB ErbB2(+) human breast cancer is a major clinical problem. Prior results have suggested that tetraspanin CD151 might contribute to ErbB2-driven breast cancer growth, survival, and metastasis. In other cancer types, CD151 sometimes supports tumor growth and metastasis. However, a definitive test of CD151 effects on de novo breast cancer initiation, growth, and metastasis has not previously been done. We used CD151 gene-deleted mice expressing the MMTV-ErbB2 transgene to show that CD151 strongly supports ErbB2(+) mammary tumor initiation and metastasis. Delayed tumor onset (by 70-100 days) in the absence of CD151 was accompanied by reduced survival of mammary epithelial cells and impaired activation of FAK- and MAPK-dependent pathways. Both primary tumors and metastatic nodules showed smooth, regular borders, consistent with a less invasive phenotype. Furthermore, consistent with impaired oncogenesis and decreased metastasis, CD151-targeted MCF-10A/ErbB2 cells showed substantial decreases in three-dimensional colony formation, EGF-stimulated tumor cell motility, invasion, and transendothelial migration. These CD151-dependent functions were largely mediated through alpha(6)beta(4) integrin. Moreover, CD151 ablation substantially prevented PKC- and EGFR/ERK-dependent alpha(6)beta(4) integrin phosphorylation, consistent with retention of epithelial cell polarity and intermediate filament cytoskeletal connections, which helps to explain diminished metastasis. Finally, clinical data analyses revealed a strong correlation between CD151 and ErbB2 expression and metastasis-free survival of breast cancer patients. In conclusion, we provide strong evidence that CD151 collaborates with LB integrins (particularly alpha(6)beta(4)) and ErbB2 (and EGFR) receptors to regulate multiple signaling pathways, thereby driving mammary tumor onset, survival, and metastasis. Consequently, CD151 is a useful therapeutic target in malignant ErbB2(+) breast cancer. C1 [Deng, Xinyu; Hoff, John; Novak, Marian; Jin, Hongyan; Erfani, Sonia F.; Zhou, Peter; Kaetzel, David M.; Yang, Xiuwei H.] Univ Kentucky, Dept Mol & Biomed Pharmacol, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA. [Deng, Xinyu; Hoff, John; Novak, Marian; Jin, Hongyan; Erfani, Sonia F.; Zhou, Peter; Kaetzel, David M.; Yang, Xiuwei H.] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA. [Li, Qinglin; Sharma, Chandan; Zhou, Pengcheng; Hemler, Martin E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Qinglin; Sharma, Chandan; Zhou, Pengcheng; Rabinovitz, Isaac; Hemler, Martin E.] Harvard Univ, Sch Med, Boston, MA USA. [Yang, Helen] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Rabinovitz, Isaac] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, Boston, MA 02215 USA. [Sonnenberg, Arnoud] Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands. [Yi, Yajun] Vanderbilt Univ, Div Med Genet, Nashville, TN USA. [Stipp, Christopher S.] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA. RP Yang, XWH (reprint author), Univ Kentucky, Dept Mol & Biomed Pharmacol, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA. EM xiuwei-yang@uky.edu RI Deng, Xinyu/J-5732-2015; Li, Qinglin/K-2570-2015 OI Li, Qinglin/0000-0002-4125-1944 FU Susan G. Komen Career Catalyst Award; Department of Defense Concept award [W81XWH-06-BCRP-CA]; National Institutes of Health [2P20 RR020171/Pilot, RO1 CA42368]; Dana-Farber Cancer Institute/Claudia Adams Barr Grant FX This work was supported by the Susan G. Komen Career Catalyst Award, a Department of Defense Concept award (W81XWH-06-BCRP-CA), National Institutes of Health grant 2P20 RR020171/Pilot Project, and Dana-Farber Cancer Institute/Claudia Adams Barr Grant (to X.H.Y.), and National Institutes of Health grant RO1 CA42368 (to M.E.H.). The authors declare that they have no competing interests. NR 61 TC 35 Z9 39 U1 2 U2 9 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD AUG PY 2012 VL 14 IS 8 BP 678 EP + DI 10.1593/neo.12922 PG 14 WC Oncology SC Oncology GA 001WJ UT WOS:000308490500002 PM 22952421 ER PT J AU Raj, A Ko, N Battaglia, TA Chabner, BA Moy, B AF Raj, Aparna Ko, Naomi Battaglia, Tracy A. Chabner, Bruce A. Moy, Beverly TI Patient Navigation for Underserved Patients Diagnosed with Breast Cancer SO ONCOLOGIST LA English DT Article DE Patient navigation; Cancer disparities; Breast cancer; Outcomes ID AFFORDABLE CARE ACT; LOW-INCOME WOMEN; MAMMOGRAPHY; DISPARITIES; PROTECTION; PROGRAMS; IMPACT AB The elimination of cancer disparities is critically important for lessening the burden of breast cancer (BC). Patient navigator programs (PNPs) have been shown to improve rates of BC screening in underserved communities, but there is a dearth of evidence regarding their benefits after the actual diagnosis of BC. We retrospectively examined sociodemographic characteristics, disease characteristics, and concordance to quality measures (QMs) of BC care among women participating in a PNP that services disadvantaged minority communities in the greater Boston area. Of the 186 PNP patients diagnosed with BC in 2001-2011 in three neighborhood community health centers, treatment data was available for 158 (85%) and race and disease stage information was available for 149 (80%). Regarding stage, 25% were diagnosed with in situ cancer, 32% had stage 1, 25% had stage 2, 13% had stage 3, and 5% had stage 4 BC. Guideline-indicated care was received by 70 of 74 patients (95%) for the hormonal therapy QM, 15 of 17 (88%) patients for the chemotherapy QM, and 65 of 71 (92%) patients for the radiation QM, all similar to published concordance rates at elite National Comprehensive Cancer Network institutions. These findings suggest that PNPs may facilitate evidence-based quality care for vulnerable populations. Future research should prospectively analyze quality metrics to assess measures to improve the process and outcomes of patient navigation in diverse underserved settings, compared with control non-navigated populations. The Oncologist 2012;17:1027-1031 C1 [Raj, Aparna; Chabner, Bruce A.; Moy, Beverly] Harvard Univ, Sch Med, Gillette Ctr Womens Cancers, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ko, Naomi; Battaglia, Tracy A.] Boston Med Ctr, Boston, MA USA. RP Moy, B (reprint author), Harvard Univ, Sch Med, Gillette Ctr Womens Cancers, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9A, Boston, MA 02114 USA. EM bmoy@partners.org OI Battaglia, Tracy/0000-0001-8475-1212 FU Avon Foundation; Novartis; Roche; AstraZeneca; Pfizer; Abraxis; Boehringer-Ingelheim; GlaxoSmithKline FX Disclosures: Bruce A. Chabner: BOD - PharmaMar (Spain) BOD - CTNET SAB- Epizyme (E); Merrimack, Sanofi, Peregrine, Allergan, Redwood (C/A); Beverly Moy: Avon Foundation (RF). The other authors indicated no financial relationships.; Section Editors: Gabriel Hortobagyi: Amgen, Antigen Express, Galena Biopharma, Genentech, Novartis, Rockpointe (C/A); Novartis (RF); Taivex (O); Citizen's Oncology Foundation (founder and member of the board of directors); Kathleen Pritchard: Novartis, Roche, AstraZeneca, Pfizer, Abraxis, Boehringer-Ingelheim, GlaxoSmithKline (C/A, RF) NR 24 TC 6 Z9 6 U1 1 U2 10 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 AUG PY 2012 VL 17 IS 8 BP 1027 EP 1031 DI 10.1634/theoncologist.2012-0191 PG 5 WC Oncology SC Oncology GA 996WS UT WOS:000308126100005 PM 22752069 ER PT J AU Cannon, JW Chung, KK King, DR AF Cannon, Jeremy W. Chung, Kevin K. King, David R. TI Advanced Technologies in Trauma Critical Care Management SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Innovation; Trauma critical care; Ultrasound; Hemodynamic monitoring; Extracorporeal therapy; Wound management ID PULMONARY-ARTERY CATHETERS; HEART-RATE-VARIABILITY; EXTRACORPOREAL MEMBRANE-OXYGENATION; HYPOTHERMIC CARDIOPULMONARY BYPASS; RESPIRATORY-DISTRESS-SYNDROME; SURGEON-PERFORMED ULTRASOUND; PENETRATING CARDIAC WOUNDS; VACUUM-ASSISTED CLOSURE; CENTRAL VENOUS CATHETER; ACUTE LUNG INJURY AB Care of critically injured patients has evolved over the 50 years since Shoemaker established one of the first trauma units at Cook County Hospital in 1962. Modern trauma intensive care units offer a high nurse-to-patient ratio, physicians and midlevel providers who manage the patients, and technologically advanced monitors and therapeutic devices designed to optimize the care of patients. This article describes advances that have transformed trauma critical care, including bedside ultrasonography, novel patient monitoring techniques, extracorporeal support, and negative pressure dressings. It also discusses how to evaluate the safety and efficacy of future advances in trauma critical care. C1 [Cannon, Jeremy W.] San Antonio Mil Med Ctr, Div Trauma & Acute Care Surg, Ft Sam Houston, TX 78234 USA. [Cannon, Jeremy W.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Chung, Kevin K.] USA, Clin Div, Inst Surg Res, Ft Sam Houston, TX 78234 USA. [King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [King, David R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cannon, JW (reprint author), San Antonio Mil Med Ctr, Div Trauma & Acute Care Surg, 3551 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA. EM jcannon@massmed.org OI King, David/0000-0003-1028-1478 NR 113 TC 2 Z9 2 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD AUG PY 2012 VL 92 IS 4 BP 903 EP + DI 10.1016/j.suc.2012.04.001 PG 22 WC Surgery SC Surgery GA 000IE UT WOS:000308379100009 PM 22850154 ER PT J AU Matar, AJ Pathiraja, V Wang, ZR Duran-Struuck, R Gusha, A Crepeau, R Tasaki, M Sachs, DH Huang, CA AF Matar, Abraham J. Pathiraja, Vimukthi Wang, Zhirui Duran-Struuck, Raimon Gusha, Ashley Crepeau, Rebecca Tasaki, Masayuki Sachs, David H. Huang, Christene A. TI Effect of pre-existing anti-diphtheria toxin antibodies on T cell depletion levels following diphtheria toxin-based recombinant anti-monkey CD3 immunotoxin treatment SO TRANSPLANT IMMUNOLOGY LA English DT Article DE Immunotoxin; T cell depletion; Antibody; Diphtheria toxin ID SINGLE-CHAIN IMMUNOTOXIN; LYMPHOMA AB Diphtheria toxin (DT)-based anti-CD3 immunotoxins have clinical relevance in numerous applications including autoimmune disease therapies and organ transplantation tolerance protocols. Pre-existing anti-DT antibodies acquired either by vaccination against diphtheria toxin or infections with C diphtheriae may interfere or inhibit the function of these anti-CD3 immunotoxins. Previously, a full-length anti-rhesus monkey CD3 immunotoxin, FN18-CRM9, was shown to be less effective at depleting circulating T cells in animals with pre-existing anti-DT antibody titers than in animals without antibodies, and subsequent doses were ineffective. In this study, the T cell depletion function of a truncated DT based recombinant anti-monkey CD3 immunotoxin, A-dmDT390-scfbDb (C207), as part of a reduced intensity conditioning regimen prior to hematopoietic cell transplantation, was compared between two groups of monkeys: those with and without pre-existing anti-diphtheria titers. T cell depletion was comparable in both groups of monkeys, and therefore appeared to be unaffected by the presence of moderate levels of pre-existing anti-diphtheria antibodies. (C) 2012 Elsevier B.V. All rights reserved. C1 [Matar, Abraham J.; Pathiraja, Vimukthi; Wang, Zhirui; Duran-Struuck, Raimon; Gusha, Ashley; Crepeau, Rebecca; Tasaki, Masayuki; Sachs, David H.; Huang, Christene A.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Huang, CA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM huangc@helix.mgh.harvard.edu FU NIH [U01DK080653, U19AI051731] FX This work was supported by NIH grants U01DK080653 and U19AI051731. The authors would like to acknowledge Ms. Jaclyn Peraino and Dr. Isabel Hanekamp for the critical review of this manuscript. NR 12 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD AUG PY 2012 VL 27 IS 1 BP 52 EP 54 DI 10.1016/j.trim.2012.05.003 PG 3 WC Immunology; Transplantation SC Immunology; Transplantation GA 002HB UT WOS:000308521600009 PM 22676970 ER PT J AU Guzman-Suarez, BB Buckley, MW Gilmore, ET Vocca, E Moss, R Marty, FM Sanders, R Baden, LR Wurtman, D Issa, NC Fang, F Koo, S AF Guzman-Suarez, B. B. Buckley, M. W. Gilmore, E. T. Vocca, E. Moss, R. Marty, F. M. Sanders, R. Baden, L. R. Wurtman, D. Issa, N. C. Fang, F. Koo, S. TI Clinical potential of DAS181 for treatment of parainfluenza-3 infections in transplant recipients SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE parainfluenza-3 infection; respiratory viruses; sialic acid; DAS181 ID RESPIRATORY VIRUS-INFECTIONS; SIALIDASE FUSION PROTEIN; STEM-CELL TRANSPLANTATION; SYNCYTIAL VIRUS; IN-VITRO; INFLUENZA; OUTBREAK; SAFETY; UNIT AB Parainfluenza virus (PIV) infections can cause serious respiratory infections and death in immunocompromised patients. No antiviral agents have proven efficacy against PIV, and therapy generally consists of supportive care. DAS181, a novel sialidase fusion protein that temporarily disables airway epithelial PIV receptors by enzymatic removal of sialic acid moieties, has been shown to inhibit infection with PIV strains in vitro and in an animal model. We describe here the clinical course of 2 immunocompromised patients with PIV-3 infection, one with a history of lung transplantation and the other neutropenic after autologous hematopoietic stem cell transplantation for multiple myeloma. Both patients had substantial clinical improvement in respiratory and systemic symptoms after a 5-day DAS181 treatment course, although the clinical improvement in the autologous stem cell transplantation patient also paralleled neutrophil engraftment. C1 [Guzman-Suarez, B. B.; Buckley, M. W.; Gilmore, E. T.; Vocca, E.; Marty, F. M.; Baden, L. R.; Issa, N. C.; Koo, S.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Guzman-Suarez, B. B.; Buckley, M. W.; Gilmore, E. T.; Vocca, E.; Marty, F. M.; Baden, L. R.; Issa, N. C.; Koo, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Guzman-Suarez, B. B.; Marty, F. M.; Baden, L. R.; Issa, N. C.; Koo, S.] Harvard Univ, Sch Med, Boston, MA USA. [Moss, R.; Sanders, R.; Wurtman, D.; Fang, F.] NexBio Inc, San Diego, CA USA. RP Koo, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4 Boston, Boston, MA 02115 USA. EM skoo@partners.org OI Koo, Sophia/0000-0002-4973-7439 NR 20 TC 23 Z9 23 U1 0 U2 4 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 AUG PY 2012 VL 14 IS 4 BP 427 EP 433 DI 10.1111/j.1399-3062.2012.00718.x PG 7 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 991VT UT WOS:000307731800024 PM 22340538 ER PT J AU Brizendine, KD Baddley, JW Pappas, PG Leon, KJ Rodriguez, JM AF Brizendine, K. D. Baddley, J. W. Pappas, P. G. Leon, K. J. Rodriguez, J. M. TI Fatal Burkholderia gladioli infection misidentified as Empedobacter brevis in a lung transplant recipient with cystic fibrosis SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE Burkholderia gladioli; Burkholderia; Empedobacter brevis; cystic fibrosis; lung transplantation ID PSEUDOMONAS-CEPACIA; SURVIVAL; PATIENT; COMPLEX AB Data describing the risk of lung transplantation (LT), clinical features, and outcomes of patients with cystic fibrosis (CF) infected with Burkholderia gladioli are limited. Herein, we report a case of disseminated B. gladioli infection characterized by bacteremia, necrotizing pneumonia, lung abscess, and empyema in a lung transplant recipient with CF, highlight the importance of accurate microbiological identification, and review published outcomes of LT in CF patients infected with B. gladioli, which include cases of pneumonia, tracheobronchitis, bacteremia, and abscesses, and demonstrate an all-cause 1-year mortality of approximately 23%, often after combined medical and surgical treatment. C1 [Brizendine, K. D.; Baddley, J. W.; Pappas, P. G.; Rodriguez, J. M.] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA. [Baddley, J. W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Leon, K. J.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Dept Med, Birmingham, AL 35294 USA. RP Rodriguez, JM (reprint author), Univ Alabama Birmingham, Div Infect Dis, Dept Med, Tinsley Harrison Tower 229,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mrodri2@uab.edu NR 20 TC 1 Z9 2 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 AUG PY 2012 VL 14 IS 4 BP E13 EP E18 DI 10.1111/j.1399-3062.2012.00726.x PG 6 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 991VT UT WOS:000307731800003 PM 22429703 ER PT J AU Berg, LJ Delgado, MK Ginde, AA Montoy, JC Bendavid, E Camargo, CA AF Berg, Laura J. Delgado, M. Kit Ginde, Adit A. Montoy, Juan Carlos Bendavid, Eran Camargo, Carlos A., Jr. TI Characteristics of US Emergency Departments That Offer Routine Human Immunodeficiency Virus Screening SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID HEALTH-CARE SETTINGS; FOR-DISEASE-CONTROL; RECOMMENDATIONS; COHORT; RISK AB ACADEMIC EMERGENCY MEDICINE 2012; 19:894900 (c) 2012 by the Society for Academic Emergency Medicine Abstract Objectives: The association between emergency department (ED) characteristics, ED directors perceptions of preventive services, and the availability of human immunodeficiency virus (HIV) screening are unknown. The authors hypothesized that, after adjusting for ED operational and demographic characteristics, teaching hospital status would be associated with increased availability, and ED crowding and ED director agreement with barriers to screening would be associated with decreased availability. Methods: This was a secondary, cross-sectional analysis on previously collected data from 2008 to 2009 regarding availability of ED preventive services. Data were obtained from a random sample of 277 EDs in which ED directors provided information on ED characteristics and availability of HIV screening and rated five barriers to providing preventive services. The association between the availability of HIV screening and teaching hospital and crowding status, ED volume, urbanrural location, ownership, geographic region, patient demographics, state HIV testing consent laws, and ED director opinions on barriers to providing preventive services were determined in univariate analyses and a multivariate logistic regression model. Results: Nineteen percent of the sampled EDs offer HIV screening. Teaching hospitals offer HIV screening more frequently than nonteaching hospitals (38% vs. 18%; p = 0.03), but after adjusting for other characteristics in a multivariate model, this association was not significant (relative risk ratio [RR] = 2.07, 95% confidence interval [CI] = 0.91 to 3.59). ED crowding also was not significantly associated with screening availability (RR = 0.66, 95% CI = 0.34 to 1.21). However, public ownership (RR = 2.13, 95% CI = 1.28 to 3.14), 24-hour social work (RR = 1.87, 95% CI = 1.02 to 2.99), uninsured population =35% (RR = 2.48, 95% CI = 1.39 to 3.69), increased local nonwhite minority population percentage (RR = 1.14 per 10%, 95% CI = 1.02 to 1.26), and state laws allowing opt-out consent for testing (RR = 1.76, 95% CI = 1.01 to 2.74) were associated with increased availability of screening in multivariable analysis. EDs whose directors were concerned about added costs were associated with decreased availability of screening (RR = 0.45, 95% CI = 0.23 to 0.85). Conclusions: After adjusting for other ED operational and demographic characteristics, ED crowding and teaching hospital affiliation were not independently associated with the availability of HIV screening. EDs whose directors were concerned about the cost of preventive services were less likely to provide routine HIV screening. Addressing ED directors concerns about the added costs of ED preventive services, increasing social work availability, and implementing testing laws consistent with Centers for Disease Control and Prevention (CDC) recommendations may facilitate increased adoption of ED HIV screening. C1 [Delgado, M. Kit; Bendavid, Eran] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Berg, Laura J.] Stanford Kaiser Emergency Med Residency, Stanford, CA USA. [Delgado, M. Kit] Stanford Univ, Sch Med, Div Emergency Med, Stanford, CA 94305 USA. [Bendavid, Eran] Stanford Univ, Sch Med, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Ginde, Adit A.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Montoy, Juan Carlos] Univ Calif San Francisco, San Francisco Gen Hosp, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Delgado, MK (reprint author), Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. EM kdelgado@stanford.edu RI bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017 FU Agency for Health Care Research and Quality [T32HS00028]; NIH FX Dr. Delgado was supported by the Agency for Health Care Research and Quality training grant T32HS00028 to the Center for Primary Care and Outcomes Research, Stanford University. Dr. Bendavid was supported in part by an NIH Career Development award. NR 17 TC 7 Z9 7 U1 0 U2 2 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 AUG PY 2012 VL 19 IS 8 BP 894 EP 900 DI 10.1111/j.1553-2712.2012.01401.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 992JR UT WOS:000307772300001 PM 22849642 ER PT J AU Ferencik, M Schlett, CL Bamberg, F Truong, QA Nichols, JH Pena, AJ Shapiro, MD Rogers, IS Seneviratne, S Parry, BA Cury, RC Brady, TJ Brown, DF Nagurney, JT Hoffmann, U AF Ferencik, Maros Schlett, Christopher L. Bamberg, Fabian Truong, Quynh A. Nichols, John H. Pena, Antonio J. Shapiro, Michael D. Rogers, Ian S. Seneviratne, Sujith Parry, Blair Alden Cury, Ricardo C. Brady, Thomas J. Brown, David F. Nagurney, John T. Hoffmann, Udo TI Comparison of Traditional Cardiovascular Risk Models and Coronary Atherosclerotic Plaque as Detected by Computed Tomography for Prediction of Acute Coronary Syndrome in Patients With Acute Chest Pain SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT PATIENTS; INTERNATIONAL MULTICENTER REGISTRY; ELEVATION MYOCARDIAL-INFARCTION; ASSOCIATION TASK-FORCE; ACUTE CARDIAC ISCHEMIA; PROGNOSTIC VALUE; UNSTABLE ANGINA; ARTERY-DISEASE; CT ANGIOGRAPHY; INTRAVASCULAR ULTRASOUND AB ACADEMIC EMERGENCY MEDICINE 2012; 19:934942 (c) 2012 by the Society for Academic Emergency Medicine Abstract Objectives: The objective was to determine the association of four clinical risk scores and coronary plaque burden as detected by computed tomography (CT) with the outcome of acute coronary syndrome (ACS) in patients with acute chest pain. The hypothesis was that the combination of risk scores and plaque burden improved the discriminatory capacity for the diagnosis of ACS. Methods: The study was a subanalysis of the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) triala prospective observational cohort study. The authors enrolled patients presenting to the emergency department (ED) with a chief complaint of acute chest pain, inconclusive initial evaluation (negative biomarkers, nondiagnostic electrocardiogram [ECG]), and no history of coronary artery disease (CAD). Patients underwent contrast-enhanced 64-multidetector-row cardiac CT and received standard clinical care (serial ECG, cardiac biomarkers, and subsequent diagnostic testing, such as exercise treadmill testing, nuclear stress perfusion imaging, and/or invasive coronary angiography), as deemed clinically appropriate. The clinical providers were blinded to CT results. The chest pain score was calculated and the results were dichotomized to =10 (high-risk) and <10 (low-risk). Three risk scores were calculated, Goldman, Sanchis, and Thrombolysis in Myocardial Infarction (TIMI), and each patient was assigned to a low-, intermediate-, or high-risk category. Because of the low number of subjects in the high-risk group, the intermediate- and high-risk groups were combined into one. CT images were evaluated for the presence of plaque in 17 coronary segments. Plaque burden was stratified into none, intermediate, and high (zero, one to four, and more than four segments with plaque). An outcome panel of two physicians (blinded to CT findings) established the primary outcome of ACS (defined as either an acute myocardial infarction or unstable angina) during the index hospitalization (from the presentation to the ED to the discharge from the hospital). Logistic regression modeling was performed to examine the association of risk scores and coronary plaque burden to the outcome of ACS. Unadjusted models were individually fitted for the coronary plaque burden and for Goldman, Sanchis, TIMI, and chest pain scores. In adjusted analyses, the authors tested whether the association between risk scores and ACS persisted after controlling for the coronary plaque burden. The prognostic discriminatory capacity of the risk scores and plaque burden for ACS was assessed using c-statistics. The differences in area under the receiver-operating characteristic curve (AUC) and c-statistics were tested by performing the -2 log likelihood ratio test of nested models. A p value <0.05 was considered statistically significant. Results: Among 368 subjects, 31 (8%) subjects were diagnosed with ACS. Goldman (AUC = 0.61), Sanchis (AUC = 0.71), and TIMI (AUC = 0.63) had modest discriminatory capacity for the diagnosis of ACS. Plaque burden was the strongest predictor of ACS (AUC = 0.86; p < 0.05 for all comparisons with individual risk scores). The combination of plaque burden and risk scores improved prediction of ACS (plaque + Goldman AUC = 0.88, plaque + Sanchis AUC = 0.90, plaque + TIMI AUC = 0.88; p < 0.01 for all comparisons with coronary plaque burden alone). Conclusions: Risk scores (Goldman, Sanchis, TIMI) have modest discriminatory capacity and coronary plaque burden has good discriminatory capacity for the diagnosis of ACS in patients with acute chest pain. The combined information of risk scores and plaque burden significantly improves the discriminatory capacity for the diagnosis of ACS. C1 [Ferencik, Maros; Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Schlett, Christopher L.; Bamberg, Fabian; Truong, Quynh A.; Nichols, John H.; Pena, Antonio J.; Shapiro, Michael D.; Rogers, Ian S.; Seneviratne, Sujith; Cury, Ricardo C.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Parry, Blair Alden; Brown, David F.; Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Ferencik, Maros; Schlett, Christopher L.; Bamberg, Fabian; Truong, Quynh A.; Nichols, John H.; Pena, Antonio J.; Shapiro, Michael D.; Rogers, Ian S.; Seneviratne, Sujith; Cury, Ricardo C.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM maros_ferencik@hms.harvard.edu FU National Institutes of Health [RO1 HL080053, T32 HL076136]; Siemens Medical Solutions; General Electrics Healthcare; Biosite FX This work was supported by the National Institutes of Health (RO1 HL080053) and in part supported by Siemens Medical Solutions and General Electrics Healthcare.; Drs. Ferencik, Rogers, Truong, and Shapiro were supported by the National Institutes of Health grant (T32 HL076136). Dr. Hoffmann has received research grants from Siemens Medical Solutions and General Electric Healthcare. Dr. Nagurney is funded by Biosite for a biomarker research study. The rest of the authors have no disclosures or potential conflicts of interest to report. NR 49 TC 11 Z9 11 U1 0 U2 8 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 AUG PY 2012 VL 19 IS 8 BP 934 EP 942 DI 10.1111/j.1553-2712.2012.01417.x PG 9 WC Emergency Medicine SC Emergency Medicine GA 992JR UT WOS:000307772300006 PM 22849339 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Peptic ulcer disease and heart disease are associated with periprosthetic fractures after total hip replacement SO ACTA ORTHOPAEDICA LA English DT Article ID TOTAL KNEE ARTHROPLASTY; PROTON PUMP INHIBITORS; FEMORAL FRACTURES; RISK; REVISION; REGISTER; COMORBIDITY; MORBIDITY; MORTALITY; PREDICT AB Background and purpose There have been no published studies assessing the possible association of medical comorbidities with periprosthetic fracture risk. We therefore assessed whether medical comorbidity is associated with risk of periprosthetic fractures after total hip replacement (THR). Material and methods We used prospectively collected data from 1989-2008 in the Mayo Clinic Total Joint Registry for 2 cohorts: primary THR and revision THR. The main variables of interest were Deyo-Charlson comorbidities at the time of surgery. Outcome of interest was p ostoperative periprosthetic fracture at postoperative day 1 onwards. Multivariable Cox regression models were additionally adjusted for age, sex, body mass index, American Society of Anesthesiology (ASA) class, and operative diagnosis. Results We identified 14,065 primary THRs and 6,281 revision THRs with mean follow-up times of 6.3 and 5.6 years, respectively. There were 305 postoperative periprosthetic fractures in the primary THR cohort and 330 in the revision THR cohort. In patients who underwent primary THR, 2 comorbidities were associated with higher risk of periprosthetic fracture: peptic ulcer disease with adjusted hazard ratio of 1.5 (95% CI: 1.1-2.2) and heart disease with adjusted hazard ratio of 1.7 (CI: 1.2-2.4). In patients with revision THR, peptic ulcer disease was associated with a higher adjusted risk of periprosthetic fracture, 1.6 (CI: 1.1-2.3). Interpretation Peptic ulcer disease and heart disease in primary THR patients and peptic ulcer disease in revision THR patients were associated with higher postoperative periprosthetic fracture risk. Further studies are needed to understand whether disease severity or specific medications used for treatment, or both, are responsible for this association. This may allow identification of modifiable factors. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Mayo Clinic Orthopedic Surgery research funds; Birmingham VA Medical Center, Alabama; NIH (Mayo Clinic Center for Clinical and Translational Research) [1 KL2 RR024151-01]; URL Pharmaceuticals; Savient; Takeda; Novartis; Zimmer; DePuy; Stryker FX We thank Scott Harmsen and Matthew Jensen at the Mayo Clinic for assistance in data programming and data analysis. This work was supported through an NIH Clinical Translational Science Award (1 KL2 RR024151-01; Mayo Clinic Center for Clinical and Translational Research), by Mayo Clinic Orthopedic Surgery research funds, and by the Birmingham VA Medical Center, Alabama (resources and use of facilities).; There are no financial conflicts relating directly to this study. JA has received speaker honoraria from Abbott; research and travel grants from Takeda, Savient, Wyeth and Amgen; and consultant fees from URL Pharmaceuticals, Savient, Takeda, and Novartis. DGL has received royalties/speaker fees from Zimmer, has been a paid consultant to Zimmer, and has received institutional research funds from DePuy, Stryker, and Zimmer. None of the sources of funding (NIH, Mayo Clinic, Birmingham VA) had any role in the design or conduct of the study, data analysis, interpretation of the results, or preparation of the manuscript for publication. NR 37 TC 3 Z9 4 U1 0 U2 3 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 AUG PY 2012 VL 83 IS 4 BP 353 EP 359 DI 10.3109/17453674.2012.717844 PG 7 WC Orthopedics SC Orthopedics GA 993HO UT WOS:000307848600007 PM 22900908 ER PT J AU Armstrong, EJ Kulkarni, AR Hoffmayer, KS Bhave, PD MacGregor, JS Hsue, P Stein, JC Kinlay, S Ganz, P McCabe, JM AF Armstrong, Ehrin J. Kulkarni, Ameya R. Hoffmayer, Kurt S. Bhave, Prashant D. MacGregor, John S. Hsue, Priscilla Stein, John C. Kinlay, Scott Ganz, Peter McCabe, James M. TI Delaying Primary Percutaneous Coronary Intervention for Computed Tomographic Scans in the Emergency Department SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; MASSIVE PULMONARY-EMBOLISM; ST-SEGMENT ELEVATION; ISCHEMIC-STROKE; SYSTEM DELAY; CHEST-PAIN; DISEASE; GUIDELINES; MANAGEMENT; REGISTRY AB Patients presenting with suspected ST-segment elevation myocardial infarction (STEMI) may have important alternative diagnoses (e.g., aortic dissection, pulmonary emboli) or safety concerns for STEMI management (e.g., head trauma). Computed tomographic (CT) scanning may help in identifying these alternative diagnoses but may also needlessly delay primary percutaneous coronary intervention (PCI). We analyzed the ACTIVATE-SF Registry, which consists of consecutive patients with a clinical diagnosis of STEMI admitted to the emergency departments of 2 urban hospitals. Of 410 patients with a suspected diagnosis of STEMI, 45 (11%) underwent CT scanning before primary PCI. Presenting electrocardiograms, baseline risk factors, and presence of an angiographic culprit vessel were similar in those with and without CT scanning before PCI. Only 2 (4%) of these CT scans changed clinical management by identifying a stroke. Patients who underwent CT scanning had far longer door-to-balloon times (median 166 vs 75 minutes, p <0.001) and higher in-hospital mortality (20% vs 7.8%, p = 0.006). After multivariate adjustment, CT scanning in the emergency department before primary PCI remained independently associated with longer door-to-balloon times (100% longer, 95% confidence interval 60 to 160, p <0.001) but was no longer associated with mortality (odds ratio 1.4, p = 0.5). In conclusion, CT scanning before primary PCI rarely changed management and was associated with significant delays in door-to-balloon times. More judicious use of CT scanning should ne considered. (c) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:345-349) C1 [Kinlay, Scott; McCabe, James M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Kinlay, Scott; McCabe, James M.] Harvard Univ, Sch Med, Boston, MA USA. [Armstrong, Ehrin J.] Univ Calif Davis, Div Cardiovasc Med, Davis, CA 95616 USA. [Kulkarni, Ameya R.; Hoffmayer, Kurt S.; MacGregor, John S.; Hsue, Priscilla; Ganz, Peter] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Bhave, Prashant D.] Northwestern Univ, Div Electrophysiol, Evanston, IL USA. [MacGregor, John S.; Hsue, Priscilla; Ganz, Peter] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Stein, John C.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, Boston, MA USA. RP McCabe, JM (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM mccabe@aya.yale.edu NR 16 TC 5 Z9 5 U1 1 U2 4 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 AUG 1 PY 2012 VL 110 IS 3 BP 345 EP 349 DI 10.1016/j.amjcard.2012.03.032 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 986DL UT WOS:000307321000005 PM 22534052 ER PT J AU Thorpe, JM Thorpe, CT Kennelty, KA Gellad, WF Schulz, R AF Thorpe, Joshua M. Thorpe, Carolyn T. Kennelty, Korey A. Gellad, Walid F. Schulz, Richard TI The Impact of Family Caregivers on Potentially Inappropriate Medication Use in Noninstitutionalized Older Adults With Dementia SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Article DE care quality; dementia; inappropriate medications; informal caregivers ID RANDOMIZED CONTROLLED-TRIAL; BEERS CRITERIA; COMMUNITY; HOME; PRESCRIPTION; CARE; HOSPITALIZATION; POLYPHARMACY; DISORDERS; FRAMEWORK AB Background: The risk of potentially inappropriate medication (PIM), both prescription and over-the-counter, use in dementia patients is high. Informal caregivers often facilitate patients' use of medications, but the effect of caregiver factors on PIM use has not been a focus of previous research. Objective: The aim of this study was to examine PIM use in dementia patients and caregivers and identify caregiver risk factors for PIM use in dementia patients. Methods: We conducted a secondary data analysis of the baseline wave of the Resources for Enhancing Alzheimer's Caregiver's Health study. The sample comprised 566 persons with dementia aged 65 and older and their coresiding family caregiver. PIM was defined using the 2003 Beers criteria and was examined in both dementia patients and their caregivers. Caregiver and patient risk factors included a range of sociodemographic and health variables. Results: In dementia patients, 33% were taking at least 1 PIM, and 39% of their caregivers were also taking a PIM. In fully adjusted models, the following caregiver factors were associated with an increased risk of dementia patient PIM use: caregiver's own PIM use, spouse caregivers, Hispanic caregivers, and greater number of years that the caregiver has lived in the United States. Increased caregiver age was associated with a decreased risk of PIM use in patients. Conclusions: PIM use may be higher in dementia patients and their informal caregivers compared with the general older adult population. Further, patterns of medication use in 1 member of the dyad may influence PIM risk in the other dyad member. These results suggest that interventions to increase appropriate medication use in dementia patients and their caregivers should target both members of the dyad and target over-the-counter agents along with prescription medications. (Am J Geriatr Pharmacother. 2012;10:230-241) Published by Elsevier HS Journals, Inc. C1 [Thorpe, Joshua M.; Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Thorpe, Joshua M.; Thorpe, Carolyn T.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kennelty, Korey A.] Univ Wisconsin, Madison Sch Pharm, Div Social & Adm Sci, Madison, WI USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Dept Med Gen Med, Pittsburgh, PA USA. [Gellad, Walid F.] RAND Corp, Pittsburgh, PA USA. [Schulz, Richard] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Schulz, Richard] Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA 15260 USA. RP Thorpe, JM (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, 916 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM jmthorpe@pitt.edu; ctthorpe@pitt.edu RI Thorpe, Joshua/C-1188-2013 FU National Institute on Aging, National Institutes of Health; Veterans Affairs Career Development Award [CDA 09-207]; Health Innovation Program; Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR); Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health [1UL1 RR025011] FX This study was supported by grant R03AG029995 from the National Institute on Aging, National Institutes of Health, and a Veterans Affairs Career Development Award (CDA 09-207). Additional support was provided by the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR), grant 1UL1 RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health. 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. No funding source had a role in the design, methods, subject recruitment, data collection, analysis, or preparation of the manuscript. The authors have indicated that they have no other conflicts of interest regarding the content of this article. NR 53 TC 14 Z9 14 U1 7 U2 14 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1543-5946 J9 AM J GERIATR PHARMAC JI Am. J. Geriatr. Pharmacother. PD AUG PY 2012 VL 10 IS 4 BP 230 EP 241 DI 10.1016/j.amjopharm.2012.05.001 PG 12 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 992QV UT WOS:000307795700002 PM 22683399 ER PT J AU Woltmann, E Grogan-Kaylor, A Perron, B Georges, H Kilbourne, AM Bauer, MS AF Woltmann, Emily Grogan-Kaylor, Andrew Perron, Brian Georges, Hebert Kilbourne, Amy M. Bauer, Mark S. TI Comparative Effectiveness of Collaborative Chronic Care Models for Mental Health Conditions Across Primary, Specialty, and Behavioral Health Care Settings: Systematic Review and Meta-Analysis SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the VA-Health-Services-Research-and-Development CY FEB 16, 2011 CL Baltimore, MD SP VA Hlth Serv Res & Dev ID RANDOMIZED-CONTROLLED-TRIAL; MEDICATION ALGORITHM PROJECT; IMPROVING PRIMARY-CARE; LATE-LIFE DEPRESSION; DISSEMINATING QUALITY IMPROVEMENT; STARTING ANTIDEPRESSANT TREATMENT; DISEASE MANAGEMENT PROGRAMS; REDUCING SUICIDAL IDEATION; LONG-TERM EFFECTIVENESS; LOW-INCOME WOMEN AB Objective: Collaborative chronic care models (CCMs) improve outcome in chronic medical illnesses and depression treated in primary care settings. The effect of such models across other treatment settings and mental health conditions has not been comprehensively assessed. The authors performed a systematic review and meta-analysis to assess the comparative effectiveness of CCMs for mental health conditions across disorders and treatment settings. Method: Randomized controlled trials comparing CCMs with other care conditions, published or in press by August 15, 2011, were identified in a literature search and through contact with investigators. CCMs were defined a priori as interventions with at least three of the six components of the Improving Chronic Illness Care initiative (patient self-management support, clinical information systems, delivery system redesign, decision support, organizational support, and community,resource linkages). Articles were included if the CCM effect on mental health symptoms or mental quality of life was reported. Data extraction included analyses of these outcomes plus social role function, physical and overall quality of life, and costs. Meta-analyses included comparisons using unadjusted continuous measures. Results: Seventy-eight articles yielded 161 analyses from 57 trials (depression, N=40; bipolar disorder, N=4; anxiety disorders, N=3; multiple/other disorders, N=10). The meta-analysis indicated significant effects across disorders and care settings for depression as well as for mental and physical quality of life and social role function (Cohen's d values, 0.20-0.33). Total health care costs did not differ between CCMs and comparison models. A systematic review largely confirmed and extended these findings across conditions and outcome domains. Conclusions: CCMs can improve mental and physical outcomes for individuals with mental disorders across a wide variety of care settings, and they provide a robust clinical and policy framework for care integration. C1 [Bauer, Mark S.] Washington Univ, Brown Sch, St Louis, MO 63130 USA. Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Harvard S Shore Psychiat Residency Training Progr, Brockton, MA 02401 USA. Ann Arbor VA Med Ctr, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Dept Psychiat, Ann Arbor, MI USA. VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. RP Bauer, MS (reprint author), Washington Univ, Brown Sch, St Louis, MO 63130 USA. EM mark.bauer@va.gov OI Grogan-Kaylor, Andrew/0000-0003-0065-9991 FU NIMH NIH HHS [R-01-MH-079994] NR 139 TC 133 Z9 135 U1 7 U2 42 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 AUG PY 2012 VL 169 IS 8 BP 790 EP 804 DI 10.1176/appi.ajp.2012.11111616 PG 15 WC Psychiatry SC Psychiatry GA 980JH UT WOS:000306888900007 PM 22772364 ER PT J AU Gray, KM Carpenter, MJ Baker, NL DeSantis, SM Kryway, E Hartwell, KJ McRae-Clark, AL Brady, KT AF Gray, Kevin M. Carpenter, Matthew J. Baker, Nathaniel L. DeSantis, Stacia M. Kryway, Elisabeth Hartwell, Karen J. McRae-Clark, Aimee L. Brady, Kathleen T. TI A Double-Blind Randomized Controlled Trial of N-Acetylcysteine in Cannabis-Dependent Adolescents SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PLACEBO-CONTROLLED TRIAL; YOUTH TREATMENT CYT; CONTINGENCY MANAGEMENT; MAIN FINDINGS; DRUG; RELIABILITY; MEDICATIONS; ADDICTIONS; CESSATION AB Objective: Preclinical findings suggest that the over-the-counter supplement N-acetylcysteine (NAC), via glutamate modulation in the nucleus accumbens, holds promise as a pharmacotherapy for substance dependence. The authors investigated NAC as a novel cannabis cessation treatment in adolescents, a vulnerable group for whom existing treatments have shown limited efficacy. Method: In an 8-week double-blind randomized placebo-controlled trial, treatment-seeking cannabis-dependent adolescents (ages 15-21 years; N=116) received NAC (1200 mg) or placebo twice daily as well as a contingency management intervention and brief (< 10 minutes) weekly cessation counseling. The primary efficacy measure was the odds of negative weekly urine cannabinoid test results during treatment among participants receiving NAC compared with those receiving placebo, in an intent-to-treat analysis. The primary tolerability measure was frequency of adverse events, compared by treatment group. Results: Participants receiving NAC had more than twice the odds, compared with those receiving placebo, of having negative urine cannabinoid test results during treatment (odds ratio=2.4, 95% CI=1.1-5.2). Exploratory secondary abstinence outcomes favored NAC but were not statistically significant. NAC was well tolerated, with minimal adverse events. Conclusions: This is the first randomized controlled trial of pharmacotherapy for cannabis dependence in any age group to yield a positive primary cessation outcome in an intent-to-treat analysis. Findings support NAC as a pharmacotherapy to complement psychosocial treatment for cannabis dependence in adolescents. C1 [Gray, Kevin M.] Med Univ S Carolina, Hollings Canc Ctr, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Gray, KM (reprint author), Med Univ S Carolina, Hollings Canc Ctr, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. EM graykm@musc.edu RI McRae-Clark, Aimee/I-3341-2013 OI McRae-Clark, Aimee/0000-0002-9774-318X FU Merck; Supernus Pharmaceuticals; Pfizer; Shire Pharmaceuticals; GlaxoSmithKline; National Institute on Drug Abuse (NIDA) [R01DA026777]; National Center for Research Resources [UL1RR029882]; NIDA [K23DA020482] FX Dr. Gray has received research funding from Merck and Supernus Pharmaceuticals. Dr. Hartwell has received research funding from Pfizer. Dr. McRae-Clark has received research funding from Shire Pharmaceuticals. Dr. Brady has received research funding from GlaxoSmithKline. The other authors report no financial relationships with commercial interests.; Supported by National Institute on Drug Abuse (NIDA) grant R01DA026777, via the American Recovery and Reinvestment Act of 2009. Administrative and technical support was provided by National Center for Research Resources grant UL1RR029882. Dr. Carpenter's effort was supported by NIDA grant K23DA020482. NR 40 TC 64 Z9 67 U1 7 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 AUG PY 2012 VL 169 IS 8 BP 805 EP 812 DI 10.1176/appi.ajp.2012.12010055 PG 8 WC Psychiatry SC Psychiatry GA 980JH UT WOS:000306888900008 PM 22706327 ER PT J AU Vizueta, N Rudie, JD Townsend, JD Torrisi, S Moody, TD Bookheimer, SY Altshuler, LL AF Vizueta, Nathalie Rudie, Jeffrey D. Townsend, Jennifer D. Torrisi, Salvatore Moody, Teena D. Bookheimer, Susan Y. Altshuler, Lori L. TI Regional fMRI Hypoactivation and Altered Functional Connectivity During Emotion Processing in Nonmedicated Depressed Patients With Bipolar II Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID VOXEL-BASED METAANALYSIS; FACIAL EXPRESSIONS; AMYGDALA ACTIVATION; RATING-SCALE; RESPONSES; MANIA; FACES; STATE; RECOGNITION; TRAIT AB Objective: Although the amygdala and ventrolateral prefrontal cortex have been implicated in the pathophysiology of bipolar I disorder, the neural mechanisms underlying bipolar II disorder remain unknown. The authors examined neural activity in response to negative emotional faces during an emotion perception task that reliably activates emotion regulatory regions. Method: Twenty-one nonmedicated depressed bipolar II patients and 21 healthy comparison subjects underwent functional MRI (fMRI) while performing an emotional face-matching task. Within- and between-group whole-brain fMRI activation and seed-based connectivity analyses were conducted. Results: In depressed bipolar II patients, random-effects between-group fMRI analyses revealed a significant reduction in activation in several regions, including the left and right ventrolateral prefrontal cortices (Brodmann's area [BA] 47) and the right amygdala, a priori regions of interest. Additionally, bipolar patients exhibited significantly reduced negative functional connectivity between the right amygdala and the right orbitofrontal cortex (BA 10) as well as the right dorsolateral prefrontal cortex (BA 46) relative to healthy comparison subjects. Conclusions: These findings suggest that bipolar II depression is characterized by reduced regional orbitofrontal and limbic activation and altered connectivity in a fronto-temporal circuit implicated in working memory and emotional learning. While the amygdala hypoactivation observed in bipolar II depression is opposite to the direction seen in bipolar I mania and may therefore be state dependent, the observed orbitofrontal cortex hypoactivation is consistent with findings in bipolar I depression, mania, and euthymia, suggesting a physiologic trait marker of the disorder. C1 [Vizueta, Nathalie] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Neurosci Interdept Program, Los Angeles, CA 90095 USA. W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Vizueta, N (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. EM vizuetan@gmail.com FU NIMH [K24 MH-01848, T32 MH-17140]; University of California, Los Angeles, Integrative Study Center in Mood Disorders; National Center for Research Resources [RR12169, RR13642, RR00865]; Ahmanson Foundation; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Capital Group Companies Charitable Foundation; Jennifer Jones-Simon Foundation; Northstar Fund; Pierson-Lovelace Foundation; Robson Family; Tamkin Foundation; Northern Piedmont Community Foundation FX Supported by NIMH grants (K24 MH-01848, T32 MH-17140) and a fellowship from the University of California, Los Angeles, Integrative Study Center in Mood Disorders to Dr. Vizueta; by grants from the National Center for Research Resources (RR12169, RR13642, and RR00865); and by the Ahmanson Foundation, the Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Capital Group Companies Charitable Foundation, the Jennifer Jones-Simon Foundation, the Northstar Fund, the Pierson-Lovelace Foundation, the Robson Family, the Tamkin Foundation, and the William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation. NR 46 TC 43 Z9 44 U1 1 U2 13 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 AUG PY 2012 VL 169 IS 8 BP 831 EP 840 DI 10.1176/appi.ajp.2012.11030349 PG 10 WC Psychiatry SC Psychiatry GA 980JH UT WOS:000306888900011 PM 22773540 ER PT J AU Matsunaga, J Coutinho, ML AF Matsunaga, James Coutinho, Mariana L. TI Positive Regulation of Leptospira interrogans kdp Expression by KdpE as Demonstrated with a Novel beta-Galactosidase Reporter in Leptospira biflexa SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; GENE-EXPRESSION; OUTER-MEMBRANE; SPIROCHETE; INACTIVATION; MUTAGENESIS; CONSTRUCTION; PATHOGENESIS; VIRULENCE AB Leptospirosis is a potentially deadly zoonotic disease that afflicts humans and animals. Leptospira interrogans, the predominant agent of leptospirosis, encounters diverse conditions as it proceeds through its life cycle, which includes stages inside and outside the host. Unfortunately, the number of genetic tools available for examining the regulation of gene expression in L. interrogans is limited. Consequently, little is known about the genetic circuits that control gene expression in Leptospira. To better understand the regulation of leptospiral gene expression, the L. interrogans kdp locus, encoding homologs of the P-type ATPase KdpABC potassium transporter with their KdpD sensors and KdpE response regulators, was selected for analysis. We showed that a kdpE mutation in L. interrogans prevented the increase in kdpABC mRNA levels observed in the wild-type L interrogans strain when external potassium levels were low. To confirm that KdpE was a positive regulator of kdpABC transcription, we developed a novel approach for constructing chromosomal genetic fusions to the endogenous bgaL (beta-galactosidase) gene of the nonpathogen Leptospira biflexa. We demonstrated positive regulation of a kdpA'-bgaL fusion in L. biflexa by the L. interrogans KdpE response regulator. A control lipL32'-bgaL fusion was not regulated by KdpE. These results demonstrate the utility of genetic fusions to the bgaL gene of L. biflexa for examining leptospiral gene regulation. C1 [Matsunaga, James; Coutinho, Mariana L.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Matsunaga, James; Coutinho, Mariana L.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Coutinho, Mariana L.] Univ Fed Pelotas, Ctr Biotecnol, Pelotas, Brazil. RP Matsunaga, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. EM jamesm@ucla.edu RI Coutinho, Mariana/J-9024-2012 FU VA Medical Research Funds FX This study was supported by VA Medical Research Funds (to J.M.). NR 44 TC 8 Z9 8 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 2012 VL 78 IS 16 BP 5699 EP 5707 DI 10.1128/AEM.00713-12 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 983SR UT WOS:000307139500028 PM 22685146 ER PT J AU Ginat, DT Sedaghat, AR Robson, CD Whittemore, KR AF Ginat, Daniel T. Sedaghat, Ahmad R. Robson, Caroline D. Whittemore, Kenneth R., Jr. TI Radiology Quiz Case 3 Malleus fixation SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material C1 [Ginat, Daniel T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sedaghat, Ahmad R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Sedaghat, Ahmad R.; Whittemore, Kenneth R., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Robson, Caroline D.; Whittemore, Kenneth R., Jr.] Childrens Hosp, Boston, MA 02115 USA. RP Ginat, DT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2012 VL 138 IS 8 BP 775 EP 776 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 991YW UT WOS:000307741400014 PM 22911306 ER PT J AU Naunheim, MR Abbott, MM Lin, HW Faquin, WC Deschler, DG AF Naunheim, Matthew R. Abbott, Megan M. Lin, Harrison W. Faquin, William C. Deschler, Daniel G. TI Pathology Quiz Case 3 Carcinoma ex pleomorphic adenoma (CXPA), salivary duct carcinoma type, noninvasive SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID POSTOPERATIVE RADIATION-THERAPY; PAROTID-GLAND C1 [Naunheim, Matthew R.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Abbott, Megan M.; Lin, Harrison W.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Naunheim, MR (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2012 VL 138 IS 8 BP 781 EP 783 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 991YW UT WOS:000307741400017 PM 22911312 ER PT J AU Malandraki, GA Kaufman, A Hind, J Ennis, S Gangnon, R Waclawik, A Robbins, J AF Malandraki, Georgia A. Kaufman, Andrew Hind, Jacqueline Ennis, Stephanie Gangnon, Ronald Waclawik, Andrew Robbins, JoAnne TI The Effects of Lingual Intervention in a Patient With Inclusion Body Myositis and Sjogren's Syndrome: A Longitudinal Case Study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Inclusion body myositis; Longitudinal studies; Neuromuscular diseases; Rehabilitation; Swallowing ID IDIOPATHIC INFLAMMATORY MYOPATHIES; PENETRATION-ASPIRATION SCALE; ORAL MANIFESTATIONS; OLDER-ADULTS; DYSPHAGIA; EXERCISE; STRENGTH; MUSCLE AB Objective: To report the 5-year course of a patient's swallowing disorder in the context of progressive neuromuscular disease and the effectiveness of a lingual strengthening treatment program. Design: This is a case report that describes a lingual treatment protocol that was repeated 3 times over a 5-year period with and without maintenance periods. Setting: The study was completed in 2 settings an outpatient swallowing clinic at an acute care hospital and the patient's home. Participant: The subject was a 77-year-old woman who was diagnosed with inclusion body myositis and Sjogren's syndrome. Intervention: The patient participated in an intensive 8-week lingual strengthening protocol 3 times (at years 1, 4, and 5) and a subsequent maintenance program twice (at years 4 and 5). Main Outcome Measures: Three outcome measures were collected during the study: (I) lingual manometric pressures at the anterior and posterior tongue, measured by using a lingual manometric device, (2) airway invasion measured by using an 8-point Penetration-Aspiration Scale, and (3) clearance of the bolus measured by using a 3-point residue scale. Result: Isometric lingual strengthening was effective in maintaining posterior tongue lingual pressure and Penetration-Aspiration Scale scores during the treatment periods. Residue scale scores did not significantly change during treatment. Conclusions: We conclude that, in this patient, lingual strengthening slowed the progression of disease-related lingual strength loss and extended functional swallowing performance. Thus, this type of intervention may hold promise as an effective swallowing treatment option for patients with neurodegenerative inflammatory diseases such as inclusion body myositis and Sjogren's syndrome. C1 [Malandraki, Georgia A.] Columbia Univ, Dept Biobehav Sci, Teachers Coll, Program Speech & Language Pathol, New York, NY 10027 USA. [Malandraki, Georgia A.; Hind, Jacqueline; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Malandraki, Georgia A.; Hind, Jacqueline; Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI USA. [Gangnon, Ronald] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Gangnon, Ronald] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. [Waclawik, Andrew] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. [Kaufman, Andrew] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD USA. [Ennis, Stephanie] Univ Washington, Seattle, WA 98195 USA. RP Malandraki, GA (reprint author), Columbia Univ, Dept Biobehav Sci, Teachers Coll, Program Speech & Language Pathol, 1052A Thorndike Hall,525 W 120th St, New York, NY 10027 USA. EM malandraki@tc.columbia.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service FX Supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service. NR 37 TC 6 Z9 6 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 2012 VL 93 IS 8 BP 1469 EP 1475 DI 10.1016/j.apmr.2012.02.010 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 983XJ UT WOS:000307151700028 PM 22480545 ER PT J AU Flower, C Hennis, AJM Hambleton, IR Nicholson, GD Liang, MH AF Flower, Cindy Hennis, Anselm J. M. Hambleton, Ian R. Nicholson, George D. Liang, Matthew H. CA Barbados Natl Lupus Registry Grp TI Systemic Lupus Erythematosus in an African Caribbean Population: Incidence, Clinical Manifestations, and Survival in the Barbados National Lupus Registry SO ARTHRITIS CARE & RESEARCH LA English DT Article ID REVISED CRITERIA; WEST-AFRICA; MORTALITY; COHORT; CLASSIFICATION; RACE; EPIDEMIOLOGY; PREVALENCE; RATES; BALTIMORE AB Objective. To assess the epidemiology, clinical features, and outcomes of systemic lupus erythematosus (SLE) in the predominantly African Caribbean population of Barbados. Methods. A national registry of all patients diagnosed with SLE was established in 2007. Complete case ascertainment was facilitated by collaboration with the island's sole rheumatology service, medical practitioners, and the lupus advocacy group. Informed consent was required for inclusion. Results. Between January 1, 2000 and December 31, 2009, there were 183 new cases of SLE (98% African Caribbean) affecting 172 women and 11 men for unadjusted annual incidence rates of 12.21 (95% confidence interval [95% CI] 10.46-14.18) and 0.84 (95% CI 0.42-1.51) per 100,000 person-years, respectively. Excluding pediatric cases (ages <18 years), the unadjusted incidence rate among women was 15.14 per 100,000 person-years. The principal presenting manifestations were arthritis (84%), nephritis (47%), pleuritis (41.5%), malar rash (36.4%), and discoid lesions (33.1%). Antinuclear antibody positivity was 95%. The overall 5-year survival rate was 79.9% (95% CI 69.6-87.1), decreasing to 68% in patients with nephritis. A total of 226 persons with SLE were alive at the end of the study for point prevalences of 152.6 (95% CI 132.8-174.5) and 10.1 (95% CI 5.4-17.2) per 100,000 among women and men, respectively. Conclusion. Rates of SLE in Barbadian women are among the highest reported to date, with clinical manifestations similar to African American women and high mortality. Further study of this population and similar populations of West African descent might assist our understanding of environmental, genetic, and health care issues underpinning disparities in SLE. C1 [Flower, Cindy] Univ W Indies, Fac Med Sci, Bridgetown, Barbados. [Liang, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Liang, Matthew H.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Flower, C (reprint author), Univ W Indies, Fac Med Sci, Cave Hill Campus, Bridgetown, Barbados. EM cindy.flower@cavehill.uwi.edu FU Alliance for Lupus Research [55506] FX Supported by the Alliance for Lupus Research (award 55506). NR 51 TC 16 Z9 16 U1 2 U2 3 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 AUG PY 2012 VL 64 IS 8 BP 1151 EP 1158 DI 10.1002/acr.21656 PG 8 WC Rheumatology SC Rheumatology GA 995SM UT WOS:000308032900007 PM 22392730 ER PT J AU Larkin, ME Lorenzi, GM Bayless, M Cleary, PA Barnie, A Golden, E Hitt, S Genuth, S AF Larkin, Mary E. Lorenzi, Gayle M. Bayless, Meg Cleary, Patricia A. Barnie, Annette Golden, Ellen Hitt, Susan Genuth, Saul TI Evolution of the study coordinator role: The 28-year experience in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) SO CLINICAL TRIALS LA English DT Article ID CLINICAL-TRIALS; NEUROPATHY; COHORT; NURSE AB Background The role of the study coordinator (SC) in multicenter studies of long duration has received limited attention. Purpose To describe the evolution of the SC's role during the 28-year Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Methods The evolution of the SC's position from the traditional role of protocol implementation to that of research collaborator and co-investigator, based on personal experience and observation, is described in detail. Findings from a survey regarding professional demographics and job satisfaction, completed by all 28 SCs in 2010, provided additional information. We used dimensions of the SC's role specific to DCCT/EDIC to construct a classification schema of functions and responsibilities that describe the SC's role. Results Among the 28 SCs, 24 were nurses, 12 held bachelor's degrees, 11 had a master's degree, 19 were certified diabetes educators (CDEs), 12 had worked with DCCT/ EDIC for more than 20 years, and 5 had been with the study since its inception (>26 years). Responses confirmed a high degree of functional consistency across sites with data acquisition, performing study procedures, recruitment and consent for additional ancillary studies, regulatory management, scheduling, clinical consultation, and ongoing contact with study participants frequently reported. Study-wide leadership activities, a category not generally included in the usual SC role, were reported by approximately 30% of the SCs. The level of professional satisfaction was high with two-thirds being very satisfied, one-third moderately to quite satisfied, and none dissatisfied. Limitations The limitations include a relatively small sample size, self-reported data, and a single long-term multicenter trial and observational follow-up study on which we based our findings and conclusions. Conclusions By optimizing their organizational and scientific contributions to the overall research endeavor, SCs in DCCT/EDIC have made major contributions to the unprecedented success of the study and report high job satisfaction. The efforts of the SCs have been integral to the remarkably high participant retention and data completion rates. The DCCT/EDIC experience may serve as a model for the role of the SC in future diabetes and other multicenter clinical trials. Clinical Trials 2012; 9 : 418-425. http://ctj.sagepub.com C1 [Larkin, Mary E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Diabet, Sch Med, Boston, MA 02114 USA. [Lorenzi, Gayle M.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Bayless, Meg] Univ Iowa, Iowa City, IA USA. [Cleary, Patricia A.] George Washington Univ, Rockville, MD USA. [Barnie, Annette] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Golden, Ellen] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hitt, Susan] Univ Missouri, Columbia, MO USA. [Genuth, Saul] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Larkin, ME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Diabet, Sch Med, 50 Staniford St, Boston, MA 02114 USA. EM mlarkin1@partners.org FU Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases; National Eye Institute; National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical and Translational Science Awards Program; National Center for Research Resources; Genentech through a Cooperative Research and Development Agreement; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; US Department of Health and Human Services FX The DCCT/EDIC project is supported by contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases; National Eye Institute; National Institute of Neurological Disorders and Stroke; the General Clinical Research Centers Program and the Clinical and Translational Science Awards Program; National Center for Research Resources; and Genentech through a Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and US Department of Health and Human Services. NR 23 TC 2 Z9 2 U1 1 U2 6 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 AUG PY 2012 VL 9 IS 4 BP 418 EP 425 DI 10.1177/1740774512449532 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 995BV UT WOS:000307982600005 PM 22729476 ER PT J AU Blum, MA Ibrahim, SA AF Blum, Marissa A. Ibrahim, Said A. TI Race/Ethnicity and Use of Elective Joint Replacement in the Management of End-Stage Knee/Hip Osteoarthritis A Review of the Literature SO CLINICS IN GERIATRIC MEDICINE LA English DT Review DE Disparity; Joint arthroplasty; Osteoarthritis; Race/ethnicity ID TOTAL HIP-ARTHROPLASTY; STATES MEDICARE POPULATION; UNITED-STATES; RACIAL DISPARITIES; AFRICAN-AMERICANS; DECISION-MAKING; HEALTH-SERVICES; ETHNIC-DIFFERENCES; NATIONAL-HEALTH; OLDER PATIENTS AB Osteoarthritis is the most prevalent form of arthritis for which elective knee and hip joint replacement are effective treatment options in the management of end-stage disease. There are marked racial disparities in the utilization of joint arthroplasty. This article reviews the rationale for understanding this disparity, the evidence base that supports the disparity, and some known potential explanations, as well as additional data on racial disparities emerging in research on postarthroplasty outcomes and quality of care. The article concludes with a call for more research examining patient, provider and system-level factors that underlie these disparities. C1 [Blum, Marissa A.] Temple Univ, Sch Med, Div Rheumatol, Philadelphia, PA 19140 USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Blum, MA (reprint author), Temple Univ, Sch Med, Div Rheumatol, 3322 N Broad St,Suite 205, Philadelphia, PA 19140 USA. EM Marissa.blum@tuhs.temple.edu NR 71 TC 8 Z9 8 U1 3 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2012 VL 28 IS 3 BP 521 EP + DI 10.1016/j.cger.2012.05.002 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 998VG UT WOS:000308267900011 PM 22840312 ER PT J AU Wilson, BZ Anzueto, A Restrepo, MI Pugh, MJV Mortensen, EM AF Wilson, Bryan Z. Anzueto, Antonio Restrepo, Marcos I. Pugh, Mary Jo V. Mortensen, Eric M. TI Comparison of two guideline-concordant antimicrobial combinations in elderly patients hospitalized with severe community-acquired pneumonia SO CRITICAL CARE MEDICINE LA English DT Article DE antimicrobial therapy; length of stay; mortality; pneumonia ID BACTEREMIC PNEUMOCOCCAL PNEUMONIA; INITIAL EMPIRIC THERAPY; MACROLIDE ANTIBIOTICS; CLINICAL-OUTCOMES; COMORBIDITY INDEX; MEDICAL OUTCOMES; BETA-LACTAM; MORTALITY; IMPACT; VALIDATION AB Objective: Two of the guideline-concordant therapies for severe community-acquired pneumonia are either a beta-lactam and fluoroquinolone or beta-lactam and macrolide. However it is unclear if there is a benefit for one vs. the other for elderly patients with severe community-acquired pneumonia. Design: A retrospective population-based cohort study of patients with community-acquired pneumonia. Setting: Patients admitted to an intensive care unit of any Department of Veterans Affairs hospital during 5-yr period. Patients: We included only those patients >65 yrs of age admitted to the intensive care unit with community-acquired pneumonia who received either beta-lactam +fluoroquinolone or beta-lactam + macrolide antibiotic therapy for pneumonia. Intervention: Not applicable. Measurements: We used multilevel regression models to examine the effect of beta-lactam + fluoroquinolone vs. beta-lactam + macrolide on each of the outcomes after adjusting for potential confounders using propensity scores. Main Results: The cohort consisted of 1,989 patients: 98.5% male and a mean age of 74 yrs. For treatment, 44% of subjects received beta-lactam + fluoroquinolone and 56% received beta-lactam + macrolide. Unadjusted 30-day mortality was 27% for beta-lactam + fluoroquinolone and 24% for beta-lactam + macrolide (p = .11). In the multilevel models, the use of beta-lactam + fluoroquinolone was not significantly associated with 30-day mortality (odds ratio 1.05, 95% confidence interval 0.85-1.30). However, the use of beta-lactam + fluoroquinolone was significantly associated with increased mean length of stay (incidence rate ratio 1.30, 95% confidence interval 1.27-1.33). Conclusions: We found no significant difference for 30-day mortality but did demonstrate an association with increase in length of stay associated with the use of beta-lactam + fluoroquinolone. Randomized controlled trials are needed to determine the most effective antibiotics regimes for patients with severe pneumonia. (Crit Care Med 2012; 40:2310-2314) C1 [Anzueto, Antonio; Restrepo, Marcos I.; Pugh, Mary Jo V.; Mortensen, Eric M.] VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Div Hosp Med, San Antonio, TX 78229 USA. [Anzueto, Antonio; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Wilson, Bryan Z.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Mortensen, EM (reprint author), VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX USA. EM Eric.Mortensen@UTSouthwestern.edu RI Restrepo, Marcos/H-4442-2014; OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research [R01NR010828]; National Heart, Lung, and Blood Institute [K23HL096054]; National Institute of Health [K23HL096054] FX The project described was supported by Grant Number R01NR010828 from the National Institute of Nursing Research. Dr. Restrepo is supported by grant K23HL096054 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. Dr. Marcos I. Restrepo participated in advisory boards for Theravan, Forest Laboratories, Johnson and Johnson, and Novartis and was a consultant for Trius, Theravan and Pfizer (Wyeth). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs and National Institutes of Health. This material is the result of work supported with resources and the use of facilities at the South Texas Veterans Health Care System. The funding agencies had no role in conducting the study, or role in the preparation, review, or approval of the manuscript.; Drs. Restrepo and Mortensen received funding from the National Institute of Health K23HL096054. The remaining authors have not disclosed any potential conflicts of interest. NR 37 TC 15 Z9 16 U1 1 U2 2 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 AUG PY 2012 VL 40 IS 8 BP 2310 EP 2314 DI 10.1097/CCM.0b013e31825151a8 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 976SM UT WOS:000306604900006 PM 22622401 ER PT J AU Laghi, F AF Laghi, Franco TI Proteasome inhibition and ventilator-induced diaphragmatic dysfunction: Is the glass half full or half empty? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE diaphragm weakness; diaphragmatic function; mechanical ventilation; oxidative stress; proteasome; proteolysis; respiratory muscles; weaning failure ID MECHANICAL VENTILATION; ATROPHY; RATS; PROTEOLYSIS C1 [Laghi, Franco] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Laghi, Franco] Loyola Univ, Maywood, IL 60153 USA. RP Laghi, F (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 18 TC 1 Z9 1 U1 0 U2 1 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 AUG PY 2012 VL 40 IS 8 BP 2525 EP 2526 DI 10.1097/CCM.0b013e318258ebc5 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 976SM UT WOS:000306604900050 PM 22809936 ER PT J AU Seo, JH Guo, SZ Lok, J Navaratna, D Whalen, MJ Kim, KW Lo, EH AF Seo, Ji Hae Guo, Shuzhen Lok, Josephine Navaratna, Deepti Whalen, Michael J. Kim, Kyu-Won Lo, Eng H. TI Neurovascular Matrix Metalloproteinases and the Blood-Brain Barrier SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Brain edema; neuroprotection; neurodegeneration; neurovascular unit; stroke recovery ID FOCAL CEREBRAL-ISCHEMIA; OLIGODENDROCYTE PRECURSOR CELLS; SPINAL-CORD-INJURY; GENE KNOCK-OUT; HEMORRHAGIC TRANSFORMATION; SUBARACHNOID HEMORRHAGE; ENDOTHELIAL-CELLS; CARDIOEMBOLIC STROKE; MATRIX-METALLOPROTEINASE-9; EXPRESSION AB Blood-brain barrier (BBB) leakage and brain edema is a critical part of stroke pathophysiology. In this mini-review, we briefly survey the potential role of matrix metalloproteinases (MMPs) in BBB dysfunction. A large body of data in both experimental models as well as clinical patient populations suggests that MMPs may disrupt BBB permeability and interfere with cell-cell signaling in the neurovascular unit. Hence, ongoing efforts are underway to validate MMPs as potential biomarkers in stroke as well as pursue MMP blockers as therapeutic opportunities. Because BBB perturbations may also occur in neurodegeneration, MMPs and associated neurovascular unit mechanisms may also be potential targets in a broader range of CNS disorders. C1 [Seo, Ji Hae; Guo, Shuzhen; Lok, Josephine; Navaratna, Deepti; Whalen, Michael J.; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol Radiol & Pediat, Boston, MA 02115 USA. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, NeuroVasc Coordinat Res Ctr, Seoul, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul 151742, South Korea. [Kim, Kyu-Won] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Kim, Kyu-Won] Seoul Natl Univ Hosp, Innovat Res Inst Cell Therapy, Seoul 110744, South Korea. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol Radiol & Pediat, Boston, MA 02115 USA. EM Lo@helix.mgh.harvard.edu FU NIH [R01-NS56458, R37-NS37074, P01-NS55104, K08-NS57339]; National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology (MEST) through the Creative Research Initiative Program [R16-2004-001-01001-0]; World Class University Program [R31-2008-000-10103-0]; Global Research Laboratory Program [2011-0021874] FX Supported in part by NIH grants R01-NS56458, R37-NS37074, P01-NS55104 and K08-NS57339. Kyu-Won Kim is supported by National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) through the Creative Research Initiative Program (R16-2004-001-01001-0), the World Class University Program (R31-2008-000-10103-0) and the Global Research Laboratory Program (2011-0021874). NR 71 TC 24 Z9 27 U1 0 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD AUG PY 2012 VL 18 IS 25 BP 3645 EP 3648 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993OR UT WOS:000307869600004 PM 22574977 ER PT J AU Hu, XM Zhang, MJ Leak, RK Gan, Y Li, PY Gao, YQ Chen, J AF Hu, Xiaoming Zhang, Meijuan Leak, Rehana K. Gan, Yu Li, Peiying Gao, Yanqin Chen, Jun TI Delivery of Neurotherapeutics Across the Blood Brain Barrier in Stroke SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Cell penetrating peptide; TAT protein transduction domains; blood brain barrier; stroke; neuroprotection ID CELL-PENETRATING PEPTIDE; FOCAL CEREBRAL-ISCHEMIA; VECTOR-MEDIATED STRATEGY; ARGININE-RICH PEPTIDES; TAT-FUSION PROTEINS; KINASE-C-DELTA; POLY(BUTYL CYANOACRYLATE) NANOPARTICLES; HUMAN IMMUNODEFICIENCY VIRUS; MEMBRANE-PERMEABLE PEPTIDES; NEURONAL PRECURSOR CELLS AB Stroke is a devastating disease with few therapeutic options. Despite our growing understanding of the critical mechanistic events in post-stroke brain injury, the clinical translation of these findings has been less effective. A monumental hurdle to the field has been the inability of many systemically applied therapies to efficiently cross the blood brain barrier (BBB) and enter brain cells. Over the last two decades, however, significant technological achievements have overcome this obstacle to facilitate central nervous system (CNS) drug delivery. Noninvasive drug carriers, especially cell penetrating peptide (CPP) show great potential to deliver neurotherapeutics across the BBB for the treatment of ischemic brain injury. This review begins with a brief introduction to the BBB in relation to drug delivery and then provides an overview of the development of drug carriers for neurotherapeutics, with a focus on CPP-mediated transduction. We discuss recent advances and limitations in this field, as well as mechanisms underlying CPP-mediated brain targeting. We also summarize the application of CPPs in stroke research. Continuing modifications and improvements of CPPs are expected to enhance both their feasibility in clinical stroke management and their specificity towards particular cell types. C1 [Hu, Xiaoming; Zhang, Meijuan; Gan, Yu; Li, Peiying; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Hu, Xiaoming; Zhang, Meijuan; Gan, Yu; Li, Peiying; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Hu, Xiaoming; Gan, Yu; Li, Peiying; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Hu, Xiaoming; Gan, Yu; Li, Peiying; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM yqgao@shmu.edu.cn; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417 FU American Heart Association [10POST4150028]; National Institutes of Health/NINDS Grants [NS36736, NS43802, NS56118, NS45048]; Chinese Natural Science Foundation grants [30670642, 30870794, 81020108021] FX XIAOMING HU is supported by a grant (10POST4150028) from the American Heart Association. JUN CHEN is supported by National Institutes of Health/NINDS Grants NS36736, NS43802, NS56118, and NS45048. YANQIN GAO is supported by Chinese Natural Science Foundation grants 30670642, 30870794, and 81020108021. We thank Pat Strickler for excellent secretarial support. NR 188 TC 4 Z9 4 U1 1 U2 37 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD AUG PY 2012 VL 18 IS 25 BP 3704 EP 3720 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993OR UT WOS:000307869600012 PM 22574984 ER PT J AU Wolf, EJ Lunney, CA Miller, MW Resick, PA Friedman, MJ Schnurr, PP AF Wolf, Erika J. Lunney, Carole A. Miller, Mark W. Resick, Patricia A. Friedman, Matthew J. Schnurr, Paula P. TI THE DISSOCIATIVE SUBTYPE OF PTSD: A REPLICATION AND EXTENSION SO DEPRESSION AND ANXIETY LA English DT Article DE dissociation; PTSD; multivariate analysis; taxonomy; Veterans ID BORDERLINE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD ABUSE; TRAUMA; SCALE; VETERANS; VALIDITY; THERAPY; MIXTURE; NUMBER AB Background: The nature of the relationship between dissociation and posttraumatic stress disorder (PTSD) has clinical and nosological importance. The aim of this study was to evaluate the evidence for a dissociative subtype of PTSD in two independent samples and to examine the pattern of personality disorder (PD) comorbidity associated with the dissociative subtype of PTSD. Methods: Latent profile analyses were conducted on PTSD and dissociation items reflecting derealization and depersonalization in two samples of archived data: Study 1 included 360 male Vietnam War Veterans with combat-related PTSD; Study 2 included 284 female Veterans and active duty service personnel with PTSD and a high base rate of exposure to sexual trauma. Results: The latent profile analysis yielded evidence for a three-class solution in both samples: the model was defined by moderate and high PTSD classes and a class marked by high PTSD severity coupled with high levels of dissociation. Approximately 15% of the male sample and 30% of the female sample were classified into the dissociative class. Women (but not men) in the dissociative group exhibited higher levels of comorbid avoidant and borderline PD diagnoses. Conclusions: Results provide support for a dissociative subtype of PTSD and also suggest that dissociation may play a role in the frequent co-occurrence of PTSD and borderline PD among women. These results are pertinent to the on-going revisions to the DSM and suggest that consideration should be given to incorporating a dissociative subtype into the revised PTSD criteria. Depression and Anxiety 29: 679-688, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Wolf, Erika J.; Miller, Mark W.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, Erika J.; Miller, Mark W.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Lunney, Carole A.; Friedman, Matthew J.; Schnurr, Paula P.] Natl Ctr PTSD, White River Jct, VT USA. [Friedman, Matthew J.; Schnurr, Paula P.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. RP Schnurr, PP (reprint author), VA Med Ctr, Natl Ctr PTSD 116D, White River Jct, VT 05009 USA. EM paula.schnurr@dartmouth.edu RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435; Lunney, Carole A./0000-0002-0077-1281 FU VA Cooperative Studies Program [420, 494]; Department of Defense [494]; VA Career Development Award FX The data reported in this article were drawn from grants CSP #420 and #494 from the VA Cooperative Studies Program and support from the Department of Defense for CSP #494. However, the views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the Department of Defense, or any US government agency. Trial registration information for CSP #494: clinicaltrials.gov Identifier NCT00032617. This work was also supported by a VA Career Development Award to Erika J. Wolf. NR 42 TC 54 Z9 54 U1 3 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD AUG PY 2012 VL 29 IS 8 BP 679 EP 688 DI 10.1002/da.21946 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 981ZR UT WOS:000307012000003 PM 22639402 ER PT J AU Resick, PA Suvak, MK Johnides, BD Mitchell, KS Iverson, KM AF Resick, Patricia A. Suvak, Michael K. Johnides, Benjamin D. Mitchell, Karen S. Iverson, Katherine M. TI THE IMPACT OF DISSOCIATION ON PTSD TREATMENT WITH COGNITIVE PROCESSING THERAPY SO DEPRESSION AND ANXIETY LA English DT Article DE posttraumatic stress disorder; dissociation; cognitive processing therapy; randomized controlled trial ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; EXPOSURE; RESPONSES; VICTIMS; IMAGERY; TRIAL AB Background This secondary analysis of data from a randomized controlled trial of cognitive processing therapy (CPT) and its constituent components investigated whether dissociation decreased over the course of treatment primarily targeting symptoms of posttraumatic stress disorder (PTSD) and explored whether levels of dissociation predicted treatment outcome differentially by treatment condition. Methods An intention to treat sample of 150 women were randomized to CPT, cognitive therapy only (CPT-C) or written trauma accounts only (WA). Dissociation was measured by the dissociation subscale of the Traumatic Stress Inventory and the Multiscale Dissociation Inventory. Results Multilevel regression analyses revealed significant decreases in dissociation that did not vary as a function of treatment condition. Growth curve modeling revealed significant treatment condition by dissociation interactions such that the impact of pretreatment levels of dissociation impacted the treatment conditions differently. Conclusions Women who endorsed low pretreatment levels of dissociation responded most efficiently to CPT-C, whereas women with the highest levels of dissociation, in particular high levels of depersonalization, responded better to CPT. C1 [Resick, Patricia A.] VA Boston Healthcare Syst, WHSD 116B 3, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. [Resick, Patricia A.; Mitchell, Karen S.; Iverson, Katherine M.] Boston Univ, Boston, MA 02215 USA. [Suvak, Michael K.] Suffolk Univ, Boston, MA 02114 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, WHSD 116B 3, Natl Ctr Posttraumat Stress Disorder, 150 S Huntington St, Boston, MA 02130 USA. EM Patricia.Resick@va.gov FU NIMH [2-R01-MH51509] FX Contract grant sponsor: NIMH; Contract grant number: 2-R01-MH51509 to PAS. NR 38 TC 35 Z9 35 U1 7 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD AUG PY 2012 VL 29 IS 8 BP 718 EP 730 DI 10.1002/da.21938 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 981ZR UT WOS:000307012000007 PM 22473922 ER PT J AU Levine, M Brown, DFM AF Levine, Michael Brown, David F. M. TI SUCCINYLCHOLINE-INDUCED HYPERKALEMIA IN A PATENT WITH MULTIPLE SCLEROSIS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE succinylcholine; multiple sclerosis; hyperkalemia; intubation; RSI ID ACETYLCHOLINE-RECEPTORS; CARDIAC-ARREST; BLOCKERS AB Background: Succinylcholine administration is associated with hyperkalemia in patients with a variety of medical conditions, including many neuromuscular disorders. Nonetheless, there is a paucity of literature describing hyperkalemia after the administration of succinylcholine to patients with multiple sclerosis. Case Report: This case report describes a 38-year-old woman with multiple sclerosis who developed life-threatening hyperkalemia after the administration of succinylcholine during rapid sequence intubation. Conclusion: This case highlights the potential for iatrogenic hyperkalemia after succinylcholine in patients with neurologic diseases, including multiple sclerosis. (C) 2012 Elsevier Inc. C1 [Levine, Michael] Univ So Calif, Sect Med Toxicol, Dept Emergency Med, Los Angeles, CA 90033 USA. [Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Levine, M (reprint author), Univ So Calif, Sect Med Toxicol, Dept Emergency Med, 1200 N State St,Room 1011, Los Angeles, CA 90033 USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2012 VL 43 IS 2 BP 279 EP 282 DI 10.1016/j.jemermed.2011.06.062 PG 4 WC Emergency Medicine SC Emergency Medicine GA 994HC UT WOS:000307920500013 PM 22142672 ER PT J AU Martindale, JL Hwang, JQ Nadel, ES Brown, DFM AF Martindale, Jennifer L. Hwang, James Q. Nadel, Eric S. Brown, David F. M. TI ACUTE ATRAUMATIC QUADRIPLEGIA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID SPINAL EPIDURAL HEMATOMA; PROTHROMBIN COMPLEX CONCENTRATE; ORAL ANTICOAGULANT REVERSAL; INTRACEREBRAL HEMORRHAGE; AORTIC DISSECTION; WARFARIN REVERSAL; MANAGEMENT; EFFICACY; THERAPY C1 [Nadel, Eric S.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Martindale, Jennifer L.; Nadel, Eric S.; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Hwang, James Q.; Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 114,55 Fruit St, Boston, MA 02114 USA. NR 27 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2012 VL 43 IS 2 BP 335 EP 338 PG 4 WC Emergency Medicine SC Emergency Medicine GA 994HC UT WOS:000307920500023 PM 22494603 ER PT J AU Wajnberg, A Hwang, U Torres, L Yang, S AF Wajnberg, Ania Hwang, Ula Torres, Lucille Yang, Samuel TI CHARACTERISTICS OF FREQUENT GERIATRIC USERS OF AN URBAN EMERGENCY DEPARTMENT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 13-17, 2009 CL New Orleans, LA SP Soc Acad Emergency Med DE geriatrics; ED overcrowding; access to care; primary care ID PRIMARY-CARE; ELDERLY-PATIENTS; BARRIERS; VISITS; ACCESS AB Background: As the population ages, it is projected that older adults will increase emergency department (ED) utilization and contribute to ED crowding. Older patients are at risk of decreased health-related quality of life after an ED visit. Characteristics of older adults that frequently use the ED have not been well studied, and prior studies have shown that lack of access to primary care may influence ED utilization. Objective: Determine factors associated with frequent Emergency Department (ED) utilization by older adults. Methods: Retrospective chart review of all patients >= 65 years of age seen in an urban ED between December 2007 and September 2008. A prospective telephone survey was done of "frequent" (>= 4 ED visits over a 6-month period) geriatric users. "Frequent" and "infrequent" geriatric ED users were compared using chi-squared and t-test. Survey results are univariate descriptive statistics. Results: There were 8520 ED visits of adults >= 65 years of age analyzed, of which 5718 were unique patients. Of these, 268 (5%) were frequent ED users. Frequent geriatric ED users were more likely to be Black or Hispanic and were considered less urgent at triage. Of the 59 surveyed frequent users of the ED, 95% reported having a usual source of care, though only 36% contacted their outpatient provider before a visit to the ED. Conclusion: Frequent geriatric users of the ED were considered less urgent at triage, and although most identified themselves as having a primary care provider in the community, many did not contact them before going to the ED. (C) 2012 Elsevier Inc. C1 [Wajnberg, Ania; Torres, Lucille; Yang, Samuel] Mt Sinai Sch Med, Dept Gen Internal Med, Mt Sinai Visiting Doctors Program, New York, NY 10029 USA. [Hwang, Ula; Torres, Lucille; Yang, Samuel] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Hwang, Ula] Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. [Hwang, Ula] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Wajnberg, A (reprint author), Mt Sinai Sch Med, Dept Gen Internal Med, Mt Sinai Visiting Doctors Program, 1 Gustave L Levy Pl,Box 1216, New York, NY 10029 USA. FU NIA NIH HHS [K24 AG022345] NR 20 TC 9 Z9 9 U1 1 U2 6 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 AUG PY 2012 VL 43 IS 2 BP 376 EP 381 DI 10.1016/j.jemermed.2011.06.056 PG 6 WC Emergency Medicine SC Emergency Medicine GA 994HC UT WOS:000307920500034 PM 22040771 ER PT J AU Hu, YY Kwok, AC Jiang, W Taback, N Loggers, ET Ting, GV Lipsitz, SR Weeks, JC Greenberg, CC AF Hu, Yue-Yung Kwok, Alvin C. Jiang, Wei Taback, Nathan Loggers, Elizabeth T. Ting, Gladys V. Lipsitz, Stuart R. Weeks, Jane C. Greenberg, Caprice C. TI High-Cost Imaging in Elderly Patients with Stage IV Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; AMERICAN-SOCIETY; BREAST-CANCER; MEDICARE BENEFICIARIES; COLORECTAL-CANCER; UNITED-STATES; TRENDS; LIFE; CARE; END AB Background Medicare expenditures for high-cost diagnostic imaging have risen faster than those for total cancer care and have been targeted for potential cost reduction. We sought to determine recent and long-term patterns in high-cost diagnostic imaging use among elderly (aged >= 65 years) patients with stage IV cancer. Methods We identified claims within the Surveillance, Epidemiology, and End Results (SEER)-Medicare database with computed tomography, magnetic resonance imaging, positron emission tomography, and nuclear medicine scans between January 1994 and December 2009 for patients diagnosed with stage IV breast, colorectal, lung, or prostate cancer between January 1995 and December 2006 (N = 100 594 patients). The proportion of these patients imaged and rate of imaging per-patient per-month of survival were calculated for each phase of care in patients diagnosed between January 2002 and December 2006 (N = 55 253 patients). Logistic regression was used to estimate trends in imaging use in stage IV patients diagnosed between January 1995 and December 2006, which were compared with trends in imaging use in early-stage (stages I and II) patients with the same tumor types during the same period (N = 192 429 patients). Results Among the stage IV patients diagnosed between January 2002 and December 2006, 95.9% underwent a high-cost diagnostic imaging procedure, with a mean number of 9.79 (SD = 9.77) scans per patient and 1.38 (SD = 1.24) scans per-patient per-month of survival. After the diagnostic phase, 75.3% were scanned again; 34.3% of patients were scanned in the last month of life. Between January 1995 and December 2006, the proportion of stage IV cancer patients imaged increased (relative increase = 4.6%, 95% confidence interval [CI] = 3.7% to 5.6%), and the proportion of early-stage cancer patients imaged decreased (relative decrease = -2.5%, 95% CI = -3.2% to -1.9%). Conclusions Diagnostic imaging is used frequently in patients with stage IV disease, and its use increased more rapidly over the decade of study than that in patients with early-stage disease. C1 [Greenberg, Caprice C.] Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program, Madison, WI USA. [Greenberg, Caprice C.] Univ Wisconsin, Dept Surg, Hlth Innovat Program, Madison, WI USA. [Hu, Yue-Yung; Kwok, Alvin C.; Jiang, Wei; Lipsitz, Stuart R.; Greenberg, Caprice C.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Hu, Yue-Yung] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Taback, Nathan; Ting, Gladys V.; Weeks, Jane C.; Greenberg, Caprice C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Loggers, Elizabeth T.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Loggers, Elizabeth T.] Grp Hlth Res Inst, Seattle, WA USA. RP Greenberg, CC (reprint author), Univ Wisconsin Hosp & Clin, Dept Surg, 600 Highland Ave,H4-730, Madison, WI 53792 USA. EM greenberg@surgery.wisc.edu RI JIANG, WEI /F-3930-2015 FU National Institutes of Health [RC2CA148185-01, 2T32DK00754-12] FX National Institutes of Health (RC2CA148185-01 to JCW and 2T32DK00754-12 to Richard Hodin, Department of Surgery, Massachusetts General Hospital, Boston, MA. NR 33 TC 11 Z9 11 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG PY 2012 VL 104 IS 15 BP 1164 EP 1172 DI 10.1093/jnci/djs286 PG 9 WC Oncology SC Oncology GA 992VW UT WOS:000307809300009 PM 22851271 ER PT J AU Gierach, GL Ichikawa, L Kerlikowske, K Brinton, LA Farhat, GN Vacek, PM Weaver, DL Schairer, C Taplin, SH Sherman, ME AF Gierach, Gretchen L. Ichikawa, Laura Kerlikowske, Karla Brinton, Louise A. Farhat, Ghada N. Vacek, Pamela M. Weaver, Donald L. Schairer, Catherine Taplin, Stephen H. Sherman, Mark E. TI Relationship Between Mammographic Density and Breast Cancer Death in the Breast Cancer Surveillance Consortium SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PARENCHYMAL PATTERNS; TUMOR CHARACTERISTICS; POSTMENOPAUSAL WOMEN; SUBSEQUENT RISK; ASSOCIATION; FEATURES; MENOPAUSE; ACCURACY; SURVIVAL; MARKERS AB Women with elevated mammographic density have an increased risk of developing breast cancer. However, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent of other factors. We evaluated relationships between mammographic density and risk of death from breast cancer and all causes within the US Breast Cancer Surveillance Consortium. We studied 9232 women diagnosed with primary invasive breast carcinoma during 19962005, with a mean follow-up of 6.6 years. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; women with scattered fibroglandular densities (BI-RADS 2) were the referent group. All statistical tests were two-sided. A total of 1795 women died, of whom 889 died of breast cancer. In multivariable analyses (adjusted for site, age at and year of diagnosis, American Joint Committee on Cancer stage, body mass index, mode of detection, treatment, and income), high density (BI-RADS 4) was not related to risk of death from breast cancer (HR = 0.92, 95% CI = 0.71 to 1.19) or death from all causes (HR = 0.83, 95% CI = 0.68 to 1.02). Analyses stratified by stage and other prognostic factors yielded similar results, except for an increased risk of breast cancer death among women with low density (BI-RADS 1) who were either obese (HR = 2.02, 95% CI = 1.37 to 2.97) or had tumors of at least 2.0cm (HR = 1.55, 95% CI = 1.14 to 2.09). High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics. Thus, risk factors for the development of breast cancer may not necessarily be the same as factors influencing the risk of death after breast cancer has developed. C1 [Gierach, Gretchen L.; Brinton, Louise A.; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Rockville, MD USA. [Schairer, Catherine] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Taplin, Stephen H.] NCI, Proc Care Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. [Ichikawa, Laura] Grp Hlth Res Inst, Seattle, WA USA. [Kerlikowske, Karla] Univ Calif San Francisco, Gen Internal Med Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Farhat, Ghada N.] Univ Balamand, Beirut, Lebanon. [Vacek, Pamela M.] Univ Vermont, Coll Med, Dept Med Biostat, Burlington, VT USA. [Weaver, Donald L.] Vermont Canc Ctr, Burlington, VT USA. [Weaver, Donald L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. RP Gierach, GL (reprint author), 6120 Execut Blvd,Ste 550,Rm 5016, Rockville, MD 20852 USA. EM gierachg@mail.nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 FU National Institutes of Health, National Cancer Institute (NCI); NCI [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040, HHSN261201100031C] FX This work was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), and the NCI-funded Breast Cancer Surveillance Consortium (U01CA63740 to KK, U01CA86076 to DM, U01CA86082 to TO, U01CA63736 to GC, U01CA70013 to BG, U01CA69976 to RR, U01CA63731 to DB, U01CA70040 to BY, and HHSN261201100031C to DM). NR 32 TC 54 Z9 54 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG PY 2012 VL 104 IS 16 BP 1218 EP 1227 DI 10.1093/jnci/djs327 PG 10 WC Oncology SC Oncology GA 998JO UT WOS:000308234100006 PM 22911616 ER PT J AU Regan, MM Bouzyk, M Rae, JM Viale, G Leyland-Jones, B AF Regan, Meredith M. Bouzyk, Mark Rae, James M. Viale, Giuseppe Leyland-Jones, Brian TI Re: CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women With Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID ASSOCIATION; VARIANTS; OUTCOMES; SULT1A1 C1 [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, IBCSG Stat Ctr,Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Bouzyk, Mark] AKESOgen Inc, Norcross, GA USA. [Rae, James M.] Univ Michigan, Med Ctr, Dept Internal Med, Breast Oncol Program, Ann Arbor, MI 48109 USA. [Leyland-Jones, Brian] Edith Sanford Breast Canc Res, Sioux Falls, SD USA. [Viale, Giuseppe] European Inst Oncol, Div Pathol & Lab Med, IBCSG Cent Pathol Off, Milan, Italy. RP Regan, MM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, IBCSG Stat Ctr,Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM mregan@jimmy.harvard.edu; mbouzyk@akesogen.com; jimmyrae@med.umich.edu; brian.leyland-jones@sanfordhealth.org NR 7 TC 1 Z9 1 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG PY 2012 VL 104 IS 16 BP 1266 EP 1267 DI 10.1093/jnci/djs313 PG 2 WC Oncology SC Oncology GA 998JO UT WOS:000308234100014 ER PT J AU Ryan, ML Thorson, CM King, DR Van Haren, RM Manning, RJ Andrews, DM Livingstone, AS Proctor, KG AF Ryan, Mark L. Thorson, Chad M. King, David R. Van Haren, Robert M. Manning, Ronald J. Andrews, David M. Livingstone, Alan S. Proctor, Kenneth G. TI Insertion of central venous catheters induces a hypercoagulable state SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Venous thromboembolism; deep venous thrombosis; thromboelastography ID PULMONARY-ARTERY CATHETERS; RAPID THROMBELASTOGRAPHY; RISK-FACTORS; HEPARIN; THROMBOEMBOLISM; THROMBOGENICITY; ANTICOAGULATION; COAGULOPATHY; THROMBOSIS; BLOOD AB BACKGROUND: Central venous catheters (CVCs) increase the risk of venous thromboembolism. We have previously demonstrated that pulmonary artery catheters are associated with a hypercoagulable state in an animal model and in patients. The purpose of this study is to determine whether the insertion of a CVC is associated with a similar response. METHODS: Animal: 7F femoral artery catheters were placed in healthy anesthetized swine (N = 16). Serial arterial blood samples were drawn immediately before and after an 8.5F jugular vein CVC and then for 3 hours after CVC removal. Samples were analyzed using kaolin-activated thromboelastography (TEG) at precisely 2 minutes. Human: An institutional review board-approved prospective observational trial was conducted, with informed consent, in patients with critical illness (N = 8) at a Level I trauma center. Blood was drawn from indwelling arterial catheters immediately before and 60 minutes after CVC insertion. Samples were stored in sodium citrate for 15 minutes before TEG. Routine and special coagulation tests were performed on stored samples in the hospital pathology laboratory. RESULTS: Insertion of a CVC decreased TEG clotting time (R) by 55% in swine and by 29% in humans (p < 0.001 and 0.019, respectively). Initial clot formation time (K) was reduced by 41% in swine and by 36% in humans (p = 0.003 and 0.019). Fibrin cross-linking (alpha) was accelerated by 28% in swine and by 17% in humans (p = 0.007 and 0.896), but overall clot strength (maximum amplitude) was not affected. There was no change in routine or special coagulation factors, including von Willebrand factor, antithrombin III, prothrombin time, international normalized ratio, or activated partial thromboplastin time. In animals, the hypercoagulable TEG response was persistent for 3 hours after CVC removal and was prevented by pretreatment with enoxaparin (n = 4) but not heparin (n = 2). CONCLUSION: In healthy swine and patients with critical illness, a systemic hypercoagulable state occurred after CVC insertion, and this may partially account for an increased risk of venous thromboembolism. However, because the sample size was small and not powered to detect changes in coagulation proteins, no inferences can be made about the mechanism for the hypercoagulable response. (J Trauma Acute Care Surg. 2012; 73: 385-390. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Ryan, Mark L.; Thorson, Chad M.; Van Haren, Robert M.; Manning, Ronald J.; Livingstone, Alan S.; Proctor, Kenneth G.] Univ Miami, Sch Med, Div Trauma & Surg Crit Care, Daughtry Family Dept Surg,Ryder Trauma Ctr, Miami, FL 33136 USA. [Andrews, David M.] Univ Miami, Sch Med, Dept Pathol, Ryder Trauma Ctr, Miami, FL 33136 USA. [King, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA. RP Proctor, KG (reprint author), Univ Miami, Sch Med, Div Trauma & Surg Crit Care, Daughtry Family Dept Surg,Ryder Trauma Ctr, 1800 NW 10th Ave, Miami, FL 33136 USA. EM kproctor@miami.edu OI King, David/0000-0003-1028-1478 FU Office of Naval Research [N140610670]; US Army Medical Research & Materiel Command [W81XWH-11-2-0098] FX This work was supported in part by Grant No. N140610670 from the Office of Naval Research and by Grant No. W81XWH-11-2-0098 from the US Army Medical Research & Materiel Command. The authors thank the nurses and support staff of the trauma ICU for their cooperation. This study would have been impossible otherwise. The authors also thank Christian Otero, MD, and Thai Vu, MD, for helping in the consent of patients and Sarita Paulino in the Department of Pathology for assaying the coagulation factors. NR 27 TC 10 Z9 10 U1 1 U2 3 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 AUG PY 2012 VL 73 IS 2 BP 385 EP 390 DI 10.1097/TA.0b013e31825a0519 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 992VG UT WOS:000307807400023 PM 22846944 ER PT J AU Brasky, TM Baik, CS Slatore, CG Potter, JD White, E AF Brasky, Theodore M. Baik, Christina S. Slatore, Christopher G. Potter, John D. White, Emily TI Non-steroidal anti-inflammatory drugs and small cell lung cancer risk in the VITAL study SO LUNG CANCER LA English DT Article DE Aspirin; Ibuprofen; NSAID; Small cell lung cancer ID SEX-DIFFERENCES; WOMENS HEALTH; ASPIRIN USE; EXPRESSION; COHORT; METAANALYSIS; ASSOCIATION; SMOKING; USERS; MEN AB Few studies have examined the association between non-steroidal anti-inflammatory drug (NSAID) use and risk of small cell lung cancer (SCLC); among them, findings are mixed. Recently, we found that use of NSAIDs was differentially associated with lung cancer risk by histology. Here, we examine, more comprehensively, the association between individual NSAIDs and SCLC risk. 75,546 residents of western Washington State, ages 50-76, completed a baseline questionnaire in 2000-2002 and reported on their use of individual NSAIDs over the past 10 years. NSAID use was categorized as non-users, low (<4 days/week or <4 years), and high (>= 4 days/week and >= 4 years). 111 SCLC were identified through linkage to a population-based cancer registry. Multivariable-adjusted Cox proportional hazards models including strong adjustment for smoking were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Compared to non-use, high use of regular-strength aspirin was associated with an elevated risk of SCLC (HR 1.78,95% CI: 1.05-3.02; P-trend = 0.03). Findings for low-dose aspirin were elevated but did not reach statistical significance. Use of non-aspirin NSAIDs was not associated with SCLC risk. Our findings provide further indication of heterogeneity in the association between aspirin and lung cancer morphologies. Large, prospective studies with comprehensive assessments of NSAID use and smoking history and data on both men and women, are needed in order to better understand the association between use of aspirin and SCLC. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Brasky, Theodore M.; Baik, Christina S.; Potter, John D.; White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. [Brasky, Theodore M.] Ohio State Univ, James Comprehens Canc Ctr, Dept Canc Prevent & Control, Columbus, OH 43210 USA. [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. RP Brasky, TM (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM tbrasky@fhcrc.org OI Potter, John/0000-0001-5439-1500; Slatore, Christopher/0000-0003-0958-8122 FU National Institutes of Health [R25-CA094880, K05-CA154337]; VA HSRD Career Development Awards FX This work is supported by National Institutes of Health grants R25-CA094880 (National Cancer Institute) and K05-CA154337 (National Cancer Institute and Office of Dietary Supplements). Dr. Slatore is a recipient of a VA HSRD Career Development Awards and is supported by resources from the Portland VA Medical Center. The Department of Veterans Affairs did not have a role in the conduct of the study, in the collection, management, analysis, or interpretation of data, or in the preparation of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the US Government. NR 26 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD AUG PY 2012 VL 77 IS 2 BP 260 EP 264 DI 10.1016/j.lungcan.2012.04.015 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 982IM UT WOS:000307036500004 PM 22608142 ER PT J AU Milford, CE Ferris, TG AF Milford, Creagh E. Ferris, Timothy G. TI A Modified "Golden Rule" for Health Care Organizations SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Milford, Creagh E.; Ferris, Timothy G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ferris, Timothy G.] Partners Healthcare, Boston, MA USA. RP Milford, CE (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,BUL 205, Boston, MA 02114 USA. EM Cmilford1@partners.org NR 7 TC 7 Z9 7 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 2012 VL 87 IS 8 BP 717 EP 720 DI 10.1016/j.mayocp.2012.05.009 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 994NL UT WOS:000307937400008 PM 22862860 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Catherine Verfaillie-Stem Cell Researcher 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 1 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 2012 VL 87 IS 8 BP E59 EP E59 DI 10.1016/j.mayocp.2012.05.013 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 994NL UT WOS:000307937400002 PM 22862876 ER PT J AU Karam, C Quinn, CC Paganoni, S David, WS AF Karam, Chafic Quinn, Colin C. Paganoni, Sabrina David, William S. TI Teaching NeuroImages: Ganglion cyst causing pure sensory ulnar neuropathy at the wrist SO NEUROLOGY LA English DT Editorial Material C1 [Karam, Chafic; Quinn, Colin C.; Paganoni, Sabrina; David, William S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuromuscular Diagnost Ctr, Boston, MA 02115 USA. RP Karam, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuromuscular Diagnost Ctr, Boston, MA 02115 USA. EM chafickaram@gmail.com NR 1 TC 1 Z9 1 U1 2 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 AUG PY 2012 VL 79 IS 8 BP E76 EP E76 DI 10.1212/WNL.0b013e318266200c PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 996JD UT WOS:000308080100003 PM 22915183 ER PT J AU Lee, JJ Drakaki, A Iliopoulos, D Struhl, K AF Lee, J-J Drakaki, A. Iliopoulos, D. Struhl, K. TI MiR-27b targets PPAR gamma to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells SO ONCOGENE LA English DT Article DE miR-27b; PPAR gamma; NHE1; NF-kappa beta; inflammation; neuroblastomas ID ACTIVATED-RECEPTOR-GAMMA; FACTOR-KAPPA-B; BREAST-CANCER; TERMINAL DIFFERENTIATION; INTRACELLULAR PH; EXPRESSION; ROSIGLITAZONE; MICRORNAS; AGONISTS; TRANSFORMATION AB The peroxisome proliferators-activated receptor (PPAR)gamma pathway is involved in cancer, but it appears to have both tumor suppressor and oncogenic functions. In neuroblastoma cells, miR-27b targets the 30 untranslated region of PPAR gamma and inhibits its mRNA and protein expression. miR-27b overexpression or PPAR gamma inhibition blocks cell growth in vitro and tumor growth in mouse xenografts. PPAR gamma activates expression of the pH regulator NHE1, which is associated with tumor progression. Lastly, miR-27b through PPAR gamma regulates nuclear factor-kappa B activity and transcription of inflammatory target genes. Thus, in neuroblastoma, miR-27b functions as a tumor suppressor by inhibiting the tumor-promoting function of PPAR gamma, which triggers an increased inflammatory response. In contrast, in breast cancer cells, PPAR gamma inhibits NHE1 expression and the inflammatory response, and it functions as a tumor suppressor. We suggest that the ability of PPAR gamma to promote or suppress tumor formation is linked to cell type-specific differences in regulation of NHE1 and other target genes. Oncogene (2012) 31, 3818-3825; doi: 10.1038/onc.2011.543; published online 28 November 2011 C1 [Lee, J-J; Iliopoulos, D.; Struhl, K.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Drakaki, A.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Iliopoulos, D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Struhl, K (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM kevin@hms.harvard.edu FU Dana Farber Cancer Institute; National Institutes of Health [CA 107486] FX This work was supported by start-up funds to DI from the Dana Farber Cancer Institute and by a research grant to KS from the National Institutes of Health (CA 107486). NR 44 TC 49 Z9 52 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 2012 VL 31 IS 33 BP 3818 EP 3825 DI 10.1038/onc.2011.543 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 994IU UT WOS:000307924900008 PM 22120719 ER PT J AU Chen, LM Aktas, BH Wang, YB He, XY Sahoo, R Zhang, NC Denoyelle, S Kabha, E Yang, HW Freedman, RY Supko, JG Chorev, M Wagner, G Halperin, JA AF Chen, Limo Aktas, Bertal H. Wang, Yibo He, Xiaoying Sahoo, Rupam Zhang, Nancy Denoyelle, Severine Kabha, Eihab Yang, Hongwei Freedman, Revital Yefidoff Supko, Jeffrey G. Chorev, Michael Wagner, Gerhard Halperin, Jose A. TI Tumor suppression by small molecule inhibitorss of translation initiation SO ONCOTARGET LA English DT Article DE Translation; eIF4F; eIF4E; ternary complex; eIF2 ID MAMMARY EPITHELIAL-CELLS; 4E PROTEIN ELEVATION; MESSENGER-RNA; EIF4E EXPRESSION; MAMMALIAN TARGET; CANCER; PROGRESSION; PHOSPHORYLATION; TRANSFORMATION; MALIGNANCIES AB Translation initiation factors are over-expressed and/or activated in many human cancers and may contribute to their genesis and/or progression. Removal of physiologic restraints on translation initiation causes malignant transformation. Conversely, restoration of physiological restrains on translation initiation reverts malignant phenotypes. Here, we extensively characterize the anti-cancer activity of two small molecule inhibitors of translation initiation: #1181, which targets the eIF2-GTP-Met-tRNA(i) ternary complex, and 4EGI-1, which targets the eIF4F complex. In vitro, both molecules inhibit translation initiation, abrogate preferentially translation of mRNAs coding for oncogenic proteins, and inhibit proliferation of human cancer cells. In vivo, both #1181 and 4EGI-1 strongly inhibit growth of human breast and melanoma cancer xenografts without any apparent macroscopic-or microscopictoxicity. Mechanistically, #1181 phosphorylates eIF2 alpha while 4EGI-1 disrupts eIF4G/eIF4E interaction in the tumors excised from mice treated with these agents. These data indicate that inhibition of translation initiation is a new paradigm in cancer therapy. C1 [Chen, Limo; Aktas, Bertal H.; Wang, Yibo; He, Xiaoying; Sahoo, Rupam; Zhang, Nancy; Denoyelle, Severine; Kabha, Eihab; Yang, Hongwei; Freedman, Revital Yefidoff; Supko, Jeffrey G.; Chorev, Michael; Wagner, Gerhard; Halperin, Jose A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Aktas, Bertal H.; Chorev, Michael; Halperin, Jose A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [He, Xiaoying; Supko, Jeffrey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Halperin, JA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM jose_halperin@hms.harvard.edu RI wang, yibo/A-6484-2013; SAHOO, RUPAM/B-3935-2016 FU NCI NIH HHS [5R01CA121357, 1R01CA152312, R01 CA068262, R01 CA121357, R01 CA152312] NR 50 TC 38 Z9 39 U1 0 U2 13 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG PY 2012 VL 3 IS 8 BP 869 EP U3 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 997ZD UT WOS:000308206100015 PM 22935625 ER PT J AU Zhang, C Ruvkun, G AF Zhang, Chi Ruvkun, Gary TI New insights into siRNA amplification and RNAi SO RNA BIOLOGY LA English DT Editorial Material DE rde-10; rde-11; RNAi; small interfering RNAs; C. elegans ID GERM-LINE DEVELOPMENT; CAENORHABDITIS-ELEGANS; C-ELEGANS; INTERFERENCE; GENES; SID-1; REVEALS AB In the nematode Caenorhabditis elegans (C. elegans), gene inactivation by RNA interference can achieve remarkable potency due to the amplification of initial silencing triggers by RNA-dependent RNA polymerases (RdRPs). RdRPs catalyze the biogenesis of an abundant species of secondary small interfering RNAs (siRNAs) using the target mRNA as template. The interaction between primary siRNAs derived from the exogenous double-stranded RNA (dsRNA) trigger and the target mRNA is required for the recruitment of RdRPs. Other genetic requirements for RdRP activities have not been characterized. Recent studies have identified the RDE-10/RDE-11 complex which interacts with the primary siRNA bound target mRNA and acts upstream of the RdRPs. rde-10 and rde-11 mutants show an RNAi defective phenotype because the biogenesis of secondary siRNAs is completely abolished. In addition, the RDE-10/RDE-11 complex plays a similar role in the endogenous RNAi pathway for the biogenesis of a subset of siRNAs targeting recently acquired, duplicated genes. C1 [Zhang, Chi; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Zhang, Chi; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM044619] NR 33 TC 6 Z9 9 U1 0 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1547-6286 J9 RNA BIOL JI RNA Biol. PD AUG PY 2012 VL 9 IS 8 BP 1045 EP 1049 DI 10.4161/rna.21246 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 003EG UT WOS:000308590400003 PM 22858672 ER PT J AU Voils, CI Coffman, CJ Edelman, D Maciejewski, ML Grubber, JM Sadeghpour, A Cho, A McKenzie, J Blanpain, F Scheuner, M Sandelowski, M Gallagher, MP Ginsburg, GS Yancy, WS AF Voils, Corrine I. Coffman, Cynthia J. Edelman, David Maciejewski, Matthew L. Grubber, Janet M. Sadeghpour, Azita Cho, Alex McKenzie, Jamiyla Blanpain, Francoise Scheuner, Maren Sandelowski, Margarete Gallagher, M. Patrick Ginsburg, Geoffrey S. Yancy, William S., Jr. TI Examining the impact of genetic testing for type 2 diabetes on health behaviors: study protocol for a randomized controlled trial SO TRIALS LA English DT Article DE Genetic testing; Type II diabetes; Weight loss ID LOW-CARBOHYDRATE DIET; WEIGHT-LOSS; SELF-EFFICACY; RISK; PREVENTION; QUESTIONNAIRE; INTERVENTION; RELIABILITY; PROGRESSION; NUMERACY AB Background: We describe the study design, procedures, and development of the risk counseling protocol used in a randomized controlled trial to evaluate the impact of genetic testing for diabetes mellitus (DM) on psychological, health behavior, and clinical outcomes. Methods/Design: Eligible patients are aged 21 to 65 years with body mass index (BMI) >= 27 kg/m(2) and no prior diagnosis of DM. At baseline, conventional DM risk factors are assessed, and blood is drawn for possible genetic testing. Participants are randomized to receive conventional risk counseling for DM with eye disease counseling or with genetic test results. The counseling protocol was pilot tested to identify an acceptable graphical format for conveying risk estimates and match the length of the eye disease to genetic counseling. Risk estimates are presented with a vertical bar graph denoting risk level with colors and descriptors. After receiving either genetic counseling regarding risk for DM or control counseling on eye disease, brief lifestyle counseling for prevention of DM is provided to all participants. Discussion: A standardized risk counseling protocol is being used in a randomized trial of 600 participants. Results of this trial will inform policy about whether risk counseling should include genetic counseling. C1 [Voils, Corrine I.; Coffman, Cynthia J.; Edelman, David; Maciejewski, Matthew L.; Grubber, Janet M.; Sadeghpour, Azita; McKenzie, Jamiyla; Gallagher, M. Patrick; Yancy, William S., Jr.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Voils, Corrine I.; Edelman, David; Maciejewski, Matthew L.; Yancy, William S., Jr.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Coffman, Cynthia J.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Cho, Alex; Ginsburg, Geoffrey S.] Duke Univ, Med Ctr, Inst Genom Sci & Policy, Durham, NC USA. [Blanpain, Francoise] Duke Univ, Med Ctr, Clin Mol Diagnost Lab, Durham, NC USA. [Scheuner, Maren] VA Greater Los Angeles Healthcare Syst, Div Med Genet, Los Angeles, CA USA. [Scheuner, Maren] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Sandelowski, Margarete] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA. [Voils, Corrine I.] Vet Affairs Med Ctr 152, Durham, NC 27705 USA. RP Voils, CI (reprint author), Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. EM corrine.voils@dm.duke.edu OI Voils, Corrine/0000-0003-1913-663X; Edelman, David/0000-0001-7112-6151 FU Department of Veterans Affairs (DVA) Health Services Research and Development (HSRD) service [IIR 09-039]; Career Scientist Award from DVA HSRD [RCS 10-391] FX This research was supported by a grant from the Department of Veterans Affairs (DVA) Health Services Research and Development (HSR&D) service (IIR 09-039). Dr. Maciejewski was supported by a Career Scientist Award from DVA HSR&D (RCS 10-391). The views expressed in this article are those of the authors and do not necessarily represent the views of the DVA. We express our deepest gratitude to Tamika Brown and Cherisa Williams for their assistance with data collection, to Jennifer Hoff for development of the study database, and to Karen Nicely, MS for delivery of genetic counseling. Dr. Sadeghpour is now at Duke University Medical Center. Ms. Blanpain is now at Pathgroup in Nashville, TN. Dr. Gallagher is now at Altisource Solutions in Winston-Salem, NC. NR 35 TC 6 Z9 6 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD AUG 1 PY 2012 VL 13 AR 121 DI 10.1186/1745-6215-13-121 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 992YN UT WOS:000307817600001 PM 22852560 ER PT J AU Choi, HG Zhang, JW Deng, XM Hatcher, JM Patricelli, MP Zhao, Z Alessi, DR Gray, NS AF Choi, Hwan Geun Zhang, Jinwei Deng, Xianming Hatcher, John M. Patricelli, Matthew P. Zhao, Zheng Alessi, Dario R. Gray, Nathanael S. TI Brain Penetrant LRRK2 Inhibitor SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE LRRK2; blood-brain barrier; brain penetrant inhibitor; 2,4-diaminopyrimidine ID KINASE 2 LRRK2; PARKINSONS-DISEASE; POTENT; NEURODEGENERATION; SELECTIVITY; TOXICITY; MODELS AB Activating mutations in leucine-rich repeat kinase 2 (LARK2) are present in a subset of Parkinson's disease (PD) patients and may represent an attractive therapeutic target. Here, we report that a 2-anilino-4-methylamino-5-chloropyrimidine, HG-10-102-01 (4), is a potent and selective inhibitor of wild-type LRRK2 and the G2019S mutant. Compound 4 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3 mu M in cells and is the first compound reported to be capable of inhibiting Ser910 and Ser935 phosphorylation in mouse brain following intraperitoneal delivery of doses as low as 50 mg/kg. C1 [Zhang, Jinwei; Alessi, Dario R.] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. [Choi, Hwan Geun; Deng, Xianming; Hatcher, John M.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Choi, Hwan Geun; Deng, Xianming; Hatcher, John M.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, SGM 628, Boston, MA 02115 USA. [Patricelli, Matthew P.] ActivX Biosci, La Jolla, CA 92037 USA. [Zhao, Zheng] Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Anhui, Peoples R China. RP Alessi, DR (reprint author), Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dow St, Dundee DD1 5EH, Scotland. EM d.r.alessi@dundee.ac.uk; Nathanael_Gray@dfci.harvard.edu OI Alessi, Dario/0000-0002-2140-9185; Zhang, Jinwei/0000-0001-8683-509X FU NIH [P41 GM079575-03]; Medical Research Council; Michael J. Fox foundation for Parkinson's disease research; AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Merck KgaA; Pfizer FX This work was supported by NIH Grant P41 GM079575-03 (N.S.G.), the Medical Research Council (D.R.A.), the Michael J. Fox foundation for Parkinson's disease research (N.S.G. and D.R.A.), and the pharmaceutical companies supporting the DSTT (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA, and Pfizer) (D.R.A.). NR 23 TC 60 Z9 60 U1 1 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD AUG PY 2012 VL 3 IS 8 BP 658 EP 662 DI 10.1021/ml300123a PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 988GX UT WOS:000307478600015 PM 23066449 ER PT J AU Shaw, LJ Weintraub, WS Maron, DJ Hartigan, PM Hachamovitch, R Min, JK Dada, M Mancini, GBJ Hayes, SW O'Rourke, RA Spertus, JA Kostuk, W Gosselin, G Chaitman, BR Knudtson, M Friedman, J Slomka, P Germano, G Bates, ER Teo, KK Boden, WE Berman, DS AF Shaw, Leslee J. Weintraub, William S. Maron, David J. Hartigan, Pamela M. Hachamovitch, Rory Min, James K. Dada, Marcin Mancini, G. B. John Hayes, Sean W. O'Rourke, Robert A. Spertus, John A. Kostuk, William Gosselin, Gilbert Chaitman, Bernard R. Knudtson, Merill Friedman, John Slomka, Piotr Germano, Guido Bates, Eric R. Teo, Koon K. Boden, William E. Berman, Daniel S. TI Baseline stress myocardial perfusion imaging results and outcomes in patients with stable ischemic heart disease randomized to optimal medical therapy with or without percutaneous coronary intervention SO AMERICAN HEART JOURNAL LA English DT Article ID EMISSION COMPUTED-TOMOGRAPHY; EVALUATION COURAGE TRIAL; UTILIZING REVASCULARIZATION; ARTERY-DISEASE; HIGH-RISK; STRATEGIES; PCI; MANAGEMENT; INFARCTION; BENEFIT AB Background The COURAGE trial reported similar clinical outcomes for patients with stable ischemic heart disease (SIHD) receiving optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). The current post hoc substudy analysis examined the relationship between baseline stress myocardial ischemia and clinical outcomes based on randomized treatment assignment. Methods A total of 1,381 randomized patients (OMT n = 699, PCI + OMT n = 682) underwent baseline stress myocardial perfusion single-photon emission computed tomographic imaging. Site investigators interpreted the extent of ischemia by the number of ischemic segments using a 6-segment myocardial model. Patients were divided into those with no to mild (<3 ischemic segments) and moderate to severe ischemia (>= 3 ischemic segments). Cox proportional hazards models were calculated to assess time to the primary end point of death or myocardial infarction. Results At baseline, moderate to severe ischemia occurred in more than one-quarter of patients (n = 468), and the incidence was comparable in both treatment groups (P = .36). The primary end point, death or myocardial infarction, was similar in the OMT and PCI + OMT treatment groups for no to mild (18% and 19%, P = .92) and moderate to severe ischemia (19% and 22%, P = .53, interaction P value = .65). There was no gradient increase in events for the overall cohort with the extent of ischemia. Conclusions From the COURAGE trial post hoc substudy, the extent of site-defined ischemia did not predict adverse events and did not alter treatment effectiveness. Currently, evidence supports equipoise as to whether the extent and severity of ischemia impact on therapeutic effectiveness. (Am Heart J 2012; 164: 243-50.) C1 [Shaw, Leslee J.] Emory Univ, Emory Clin Cardiovasc Res Inst, Sch Med, Atlanta, GA 30306 USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Maron, David J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Hartigan, Pamela M.] VA Connecticut Healthcare Syst, VA Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA. [Hachamovitch, Rory] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Min, James K.; Hayes, Sean W.; Friedman, John; Slomka, Piotr; Germano, Guido] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA. [Mancini, G. B. John] Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. [O'Rourke, Robert A.] S Texas Vet HCS, San Antonio, TX USA. [Spertus, John A.] Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64110 USA. [Kostuk, William] London Hlth Sci Ctr, London, ON, Canada. [Gosselin, Gilbert] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Chaitman, Bernard R.] St Louis Univ, St Louis, MO 63103 USA. [Knudtson, Merill] Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. [Bates, Eric R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Teo, Koon K.] McMaster Univ, Hamilton, ON, Canada. [Boden, William E.] SUNY Buffalo, Buffalo Gen Hosp, Western New York VA Healthcare Network, Buffalo, NY 14260 USA. RP Shaw, LJ (reprint author), Emory Univ, Emory Clin Cardiovasc Res Inst, Sch Med, Room 529,1462 Clifton Rd NE, Atlanta, GA 30306 USA. EM leslee.shaw@emory.edu FU Astellas Healthcare; Lantheus Medical Imaging; Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; Canadian Institute of Health Research-Institute for Circulatory and Respiratory Health FX Partial funding for this substudy was provided by Astellas Healthcare and Lantheus Medical Imaging. Drs Shaw and Berman have declared a conflict for substudy 0 with grant support to the Department of Veterans' Affairs, Astellas Healthcare, and Lantheus Medical Imaging. No other authors have any conflicts to disclose.; Supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development and Canadian Institute of Health Research-Institute for Circulatory and Respiratory Health. Additional support for this nuclear substudy was provided by Astellas Healthcare and Lantheus Imaging in the form of unrestricted research grants to the Department of Veterans Affairs. NR 29 TC 70 Z9 74 U1 1 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 AUG PY 2012 VL 164 IS 2 BP 243 EP 250 DI 10.1016/j.ahj.2012.05.018 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991AR UT WOS:000307673700018 PM 22877811 ER PT J AU Kimmel, SE Troxel, AB Loewenstein, G Brensinger, CM Jaskowiak, J Doshi, JA Laskin, M Volpp, K AF Kimmel, Stephen E. Troxel, Andrea B. Loewenstein, George Brensinger, Colleen M. Jaskowiak, Jane Doshi, Jalpa A. Laskin, Mitchell Volpp, Kevin TI Randomized trial of lottery-based incentives to improve warfarin adherence SO AMERICAN HEART JOURNAL LA English DT Article ID PAY-FOR-PERFORMANCE; IN-RANGE; PATIENT ADHERENCE; RISK-FACTORS; CARE; ANTICOAGULATION; MEDICATION; QUALITY AB Background Poor adherence to medications is a major cause of morbidity and inadequate drug effectiveness. Efforts to improve adherence have typically been either ineffective or too complex to implement in clinical practice. Lottery-based incentive interventions could be a scalable approach to improving adherence. Methods This was a randomized, controlled clinical trial of a daily lottery-based incentive in patients on warfarin stratified by baseline international normalized ratio (INR). The trial randomized 100 patients to either a lottery-based incentive or no lottery intervention. Main outcome was out-of-range INRs. Results Over 6 months, the overall percentage of out-of-range INRs did not differ between the 2 arms (mean 23.0% in lottery arm and 25.9% in control arm, adjusted odds ratio [OR] 0.93, 95% CI 0.62-1.41). However, among the a priori subgroup with a baseline INR below therapeutic range, there was a significant reduction in out-of-range INR in the lottery arm versus the control arm (adjusted OR 0.39, 95% CI 0.25-0.62), whereas there was no such effect among those with therapeutic INRs at baseline (adjusted OR 1.26, 95% CI, 0.76-2.09, P value for interaction = .0016). Among those with low INR at baseline, there was a nonsignificant 49% reduction in the odds of nonadherence with the intervention (OR 0.51, 95% CI 0.23-1.14 ). Conclusions Although a lottery-based intervention was not associated with a significant improvement in anticoagulation control among all study participants, it improved control among an a priori group of patients at higher risk for poor adherence. (Am Heart J 2012; 164: 268-74.) C1 [Kimmel, Stephen E.; Troxel, Andrea B.; Brensinger, Colleen M.; Jaskowiak, Jane] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kimmel, Stephen E.; Doshi, Jalpa A.; Volpp, Kevin] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Kimmel, Stephen E.; Troxel, Andrea B.; Loewenstein, George; Doshi, Jalpa A.; Volpp, Kevin] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. [Laskin, Mitchell] Hosp Univ Penn, Dept Pharm Serv, Philadelphia, PA 19104 USA. [Volpp, Kevin] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Volpp, Kevin] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. RP Kimmel, SE (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 717 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM stevek@mail.med.upenn.edu OI Troxel, Andrea/0000-0002-1393-3075 FU Aetna Foundation FX The study was funded by the Aetna Foundation who had no role in the design of the study; execution of the study; analysis, interpretation, and writing of the manuscript; or decision to submit the manuscript for publication. Aetna also did not have access to the data. All authors had access to the data. NR 19 TC 28 Z9 28 U1 0 U2 8 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 AUG PY 2012 VL 164 IS 2 BP 268 EP 274 DI 10.1016/j.ahj.2012.05.005 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991AR UT WOS:000307673700021 PM 22877814 ER PT J AU Hiramoto, JS Katz, R Peralta, CA Ix, JH Fried, L Cushman, M Siscovick, D Palmas, W Sarnak, M Shlipak, MG AF Hiramoto, Jade S. Katz, Ronit Peralta, Carmen A. Ix, Joachim H. Fried, Linda Cushman, Mary Siscovick, David Palmas, Walter Sarnak, Mark Shlipak, Michael G. TI Inflammation and Coagulation Markers and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Kidney function; inflammation; coagulation markers ID C-REACTIVE PROTEIN; SERUM CYSTATIN-C; RENAL-FUNCTION; FACTOR-VIII; VENOUS THROMBOEMBOLISM; PLASMA-CONCENTRATION; OLDER-ADULTS; RISK-FACTOR; DISEASE; INTERLEUKIN-6 AB Background: The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remain unclear, especially in a population-based setting. Study Design: Prospective observational study. Setting & Participants: 4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C-based estimate of glomerular filtration rate (eGFR(cys)) >60 mL/min/1.73 m(2) and at least one follow-up measurement of kidney function. All participants were free of cardiovascular disease at entry. Predictor: We evaluated the associations of C-reactive protein (CRP), interleukin 6 (IL-6), fibrinogen, factor VIII, and D-dimer levels with kidney function decrease. Outcomes & Measurements: Kidney function decrease was assessed primarily by repeated measurements of eGFR(cys) over 5 years. Rapid decrease in kidney function was defined as eGFR decrease >3 mL/min/1.73 m(2) per year. Incident low eGFR was defined as the onset of eGFR(cys) <60 mL/min/1.73 m(2) at any follow-up examination and eGFR(cys) decrease >= 1 mL/min/1.73 m(2) per year. Results: Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFR(cys) was 96 mL/min/1.73 m(2) and 7% had albuminuria. Median follow-up was 4.77 years. Higher factor VIII levels (per 1 standard deviation [SD] of biomarker) had the strongest association with kidney function decrease (beta = -0.25; 95% CI, -0.38 to -0.12; P < 0.001), followed by IL-6 (beta = -0.16; 95% CI, -0.29 to -0.03; P = 0.01), CRP (beta = -0.09; 95% CI, -0.22 to 0.03; P = 0.1), and fibrinogen levels (beta = -0.09; 95% CI, -0.22 to 0.04; P = 0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07-1.23), factor VIII (OR, 1.11; 95% CI, 1.03-1.18), and CRP (OR, 1.09; 95% CI, 1.02-1.16) at baseline was associated significantly with rapid kidney function decrease. Only IL-6 level was associated significantly with incident low eGFR (OR, 1.09; 95% CI, 1.00-1.19). Limitations: Observational study design and absence of measured GFR. Conclusions: Inflammation and coagulation biomarkers are associated with decreasing kidney function in ambulatory adults without established cardiovascular disease or chronic kidney disease. Am J Kidney Dis. 60(2):225-232. (C) 2012 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Hiramoto, Jade S.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Fried, Linda] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Fried, Linda] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. [Fried, Linda] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Cushman, Mary] Univ Vermont, Dept Med, Thrombosis & Hemostasis Program, Burlington, VT USA. [Siscovick, David] Univ Washington, Dept Epidemiol & Biostat, Seattle, WA 98195 USA. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. [Sarnak, Mark] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. RP Hiramoto, JS (reprint author), UCSF Vasc Surg, 400 Parnassus Ave,A-581,Box 0222, San Francisco, CA 94143 USA. EM jade.hiramoto@ucsfmedctr.org FU National Institutes of Health (NIH)/National Center for Research Resources/OD UCSF-CTSI [KL2 RR024130]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK066488-01]; American Heart Association (AHA) [0640012N] FX This publication was supported by National Institutes of Health (NIH)/National Center for Research Resources/OD UCSF-CTSI grant KL2 RR024130 (Dr Hiramoto), NIH/National Institute of Diabetes and Digestive and Kidney Diseases/R01 DK066488-01 (Dr Shlipak), and American Heart Association (AHA) Established Investigator Award 0640012N (Dr Shlipak). Its contents are the responsibility of the authors and do not necessarily represent the official views of the NIH or AHA. NR 45 TC 28 Z9 28 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2012 VL 60 IS 2 BP 225 EP 232 DI 10.1053/j.ajkd.2012.02.335 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 974ZW UT WOS:000306477200010 PM 22560844 ER PT J AU Vijayan, A Palevsky, PM AF Vijayan, Anitha Palevsky, Paul M. TI In Reply to 'Renal Replacement Therapy Dosing in Acute Kidney Injury' SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Letter ID CRITICALLY-ILL PATIENTS C1 [Vijayan, Anitha] Washington Univ, St Louis, MO 63130 USA. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Pittsburgh, PA USA. RP Vijayan, A (reprint author), Washington Univ, St Louis, MO 63130 USA. OI Palevsky, Paul/0000-0002-7334-5400 NR 4 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2012 VL 60 IS 2 BP 328 EP 329 DI 10.1053/j.ajkd.2012.05.015 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 974ZW UT WOS:000306477200026 ER PT J AU Souza, LCS Yoo, AJ Chaudhry, ZA Payabvash, S Kemmling, A Schaefer, PW Hirsch, JA Furie, KL Gonzalez, RG Nogueira, RG Lev, MH AF Souza, L. C. S. Yoo, A. J. Chaudhry, Z. A. Payabvash, S. Kemmling, A. Schaefer, P. W. Hirsch, J. A. Furie, K. L. Gonzalez, R. G. Nogueira, R. G. Lev, M. H. TI Malignant CTA Collateral Profile Is Highly Specific for Large Admission DWI Infarct Core and Poor Outcome in Acute Stroke SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; CLINICAL-RESPONSE; LESION VOLUMES; SYMPTOM ONSET; PERFUSION-CT; THROMBOLYSIS; DIFFUSION; ANGIOGRAPHY; RECANALIZATION; PREDICTION AB BACKGROUND AND PURPOSE: Large admission DWI lesion volumes are associated with poor outcomes despite acute stroke treatment. The primary aims of our study were to determine whether CTA collaterals correlate with admission DWI lesion volumes in patients with AIS with proximal occlusions, and whether a CTA collateral profile could identify large DWI volumes with high specificity. MATERIALS AND METHODS: We studied 197 patients with AIS with M1 and/or intracranial ICA occlusions. We segmented admission and follow-up DWI lesion volumes, and categorized CTA collaterals by using a 5-point CS system. ROC analysis was used to determine CS accuracy in predicting DWI lesion volumes >100 mL. Patients were dichotomized into 2 categories: CS = 0 (malignant profile) or CS>0. Univariate and multivariate analyses were performed to compare imaging and clinical variables between these 2 groups. RESULTS: There was a negative correlation between CS and admission DWI lesion volume (rho = -0.54, P < .0001). ROC analysis revealed that CTA CS was a good discriminator of DWI lesion volume >100 mL (AUC = 0.84, P < .001). CS = 0 had 97.6% specificity and 54.5% sensitivity for DWI volume >100 mL. CS = 0 patients had larger mean admission DWI volumes (165.8 mL versus 32.7 mL, P < .001), higher median NIHSS scores (21 versus 15, P < .001), and were more likely to become functionally dependent at 3 months (95.5% versus 64.0%, P = .003). Admission NIHSS score was the only independent predictor of a malignant CS (P = .007). CONCLUSIONS: In patients with AIS with PAOs, CTA collaterals correlate with admission DWI infarct size. A malignant collateral profile is highly specific for large admission DWI lesion size and poor functional outcome. C1 [Souza, L. C. S.; Yoo, A. J.; Chaudhry, Z. A.; Payabvash, S.; Kemmling, A.; Schaefer, P. W.; Hirsch, J. A.; Gonzalez, R. G.; Lev, M. H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Furie, K. L.; Nogueira, R. G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yoo, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB241, Boston, MA 02114 USA. EM ajyoo@partners.org FU NIH SPOTRIAS Network [P50 NS051343]; Agency for Healthcare Research and Quality [R01 HS11392]; MGH Clinical Research Center [1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center (National Center for Research Resources); Penumbra, Inc.; GE Healthcare; Care Fusion; PHS; NINDS SPOTRIAS; DOD; NBIB FX This work was supported by an NIH SPOTRIAS Network grant (P50 NS051343), an Agency for Healthcare Research and Quality grant (R01 HS11392), and the MGH Clinical Research Center (No. 1 UL1 RR025758-01) Harvard Clinical and Translational Science Center (National Center for Research Resources). A.J.Y. and R.G.G. receive research support from Penumbra, Inc. M.H.L. receives research support from GE Healthcare and is Consultant to Co-Axis, GE Healthcare, and Millennium Pharmaceuticals.; Disclosures: Albert Yoo-UNRELATED. Grants/Grants Pending: Penumbra, Inc.* Joshua Hirsch-UNRELATED: Consultancy: CareFusion, Phillips, Comments: Vertebral Augmentatwo (Phillips Participated in focus group of NI specialists for NI suites of the future; CareFusion-participated on NextGen team for product development); Royalties: Care Fusion, Comments: as above; Stock/Stock Options: Intratech, NFocus, Nevro, Comments: Development stage companies that are working on NI products (IntraTech and N-Focus) and nerve imaging (Nevro). Karen Furie-RELATED: Grants: PHS.* Raul G. Nogueira-UNRELATED: Board Membership: Concentric Medical, eV3 Neurovascular, Coaxia; Consultancy: Concentric Medical, eV3 Neurovascular, Coaxia. Michael Lev-RELATED: Grant: NINDS SPOTRIAS,* GE Healthcare,* Comments: Research support; UNRELATED: Consultancy: Millennium Pharmaceuticals, GE Healthcare, Comments: < $10K; Grants/Grants Pending: DOD,* NBIB;* Royalties: Q&A color review of neuroimaging, Comments: < $1K, Stock/Stock Options: GE, Comments: Own common stock < $10K. (*Money paid to institution.) NR 20 TC 67 Z9 69 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 2012 VL 33 IS 7 BP 1331 EP 1336 DI 10.3174/ajnr.A2985 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 990KA UT WOS:000307628200024 PM 22383238 ER PT J AU Valente, AJ Yoshida, T Murthy, SN Sakamuri, SSVP Katsuyama, M Clark, RA Delafontaine, P Chandrasekar, B AF Valente, Anthony J. Yoshida, Tadashi Murthy, Subramanyam N. Sakamuri, Siva S. V. P. Katsuyama, Masato Clark, Robert A. Delafontaine, Patrice Chandrasekar, Bysani TI Angiotensin II enhances AT(1)-Nox1 binding and stimulates arterial smooth muscle cell migration and proliferation through AT(1), Nox1, and interleukin-18 SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE renin-angiotensin-aldosterone system; mitogenesis; migration; atherosclerosis; restenosis; angiotensin II type 1 receptor ID NF-KAPPA-B; NADPH OXIDASE; MATRIX METALLOPROTEINASES; NEOINTIMAL FORMATION; INDUCED HYPERTENSION; SIGNALING PATHWAYS; OXIDATIVE STRESS; TYPE-1 RECEPTOR; GENE-EXPRESSION; CROSS-TALK AB Valente AJ, Yoshida T, Murthy SN, Sakamuri SS, Katsuyama M, Clark RA, Delafontaine P, Chandrasekar B. Angiotensin II enhances AT(1)-Nox1 binding and stimulates arterial smooth muscle cell migration and proliferation through AT(1), Nox1, and interleukin18. Am J Physiol Heart Circ Physiol 303: H282-H296, 2012. First published May 25, 2012; doi:10.1152/ajpheart.00231.2012.-The redox- sensitive transcription factors NF-kappa B and activator protein-1 (AP-1) are critical mediators of ANG II signaling. The promitogenic and promigratory factor interleukin (IL)-18 is an NF-kappa B- and AP-1-responsive gene. Therefore, we investigated whether ANG II-mediated smooth muscle cell (SMC) migration and proliferation involve IL-18. ANG II induced rat carotid artery SMC migration and proliferation and IL-18 and metalloproteinase (MMP)-9 expression via ANG II type 1 (AT1) receptor. ANG II-induced superoxide generation, NF-kappa B and AP-1 activation, and IL-18 and MMP-9 induction were all markedly attenuated by losartan, diphenyleneiodonium chloride (DPI), and Nox1 knockdown. Similar to ANG II, addition of IL-18 also induced superoxide generation, activated NF-kappa B and AP-1, and stimulated SMC migration and proliferation, in part via Nox1, and both ANG II and IL-18 induced NOX1 transcription in an AP-1-dependent manner. AT1 physically associates with Nox1 in SMC, and ANG II enhanced this binding. Interestingly, exogenous IL-18 neither induced AT1 binding to Nox1 nor enhanced the ANG II-induced increase in AT(1)/Nox1 binding. Importantly, IL-18 knockdown, or pretreatment with IL-18 neutralizing antibodies, or IL-18 binding protein, all attenuated the migratory and mitogenic effects of ANG II. Continuous infusion of ANG II for 7 days induced carotid artery hyperplasia in rats via AT1 and was associated with increased AT(1)/Nox1 binding (despite lower AT1 levels); increased DPI-inhibitable superoxide production; increased phospho-IKK beta, JNK, p65, and c-Jun; and induction of IL-18 and MMP-9 in endothelium-denuded carotid arteries. These results indicate that IL-18 amplifies the ANG II-induced, redox-dependent inflammatory cascades by activating similar promitogenic and promigratory signal transduction pathways. The ANG II/Nox1/IL-18 pathway may be critical in hyperplastic vascular diseases, including atherosclerosis and restenosis. C1 [Yoshida, Tadashi; Sakamuri, Siva S. V. P.; Delafontaine, Patrice; Chandrasekar, Bysani] Tulane Univ, Inst Heart & Vasc, Sch Med, New Orleans, LA 70112 USA. [Valente, Anthony J.; Clark, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Valente, Anthony J.; Clark, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Katsuyama, Masato] Kyoto Prefectural Univ Med, Radioisotope Ctr, Kamigyo Ku, Kyoto, Japan. [Chandrasekar, Bysani] SE Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA USA. RP Chandrasekar, B (reprint author), Tulane Univ, Inst Heart & Vasc, Sch Med, 1430 Tulane Ave,SL 48, New Orleans, LA 70112 USA. OI Delafontaine, Patrice/0000-0003-3744-3617; Yoshida, Tadashi/0000-0002-4544-1497 FU Veterans Affairs Office of Research; Development-Biomedical Laboratory Research; Development Service Award [1IO1BX000246]; National Heart, Lung, and Blood Institute [HL-86787, HL-70241, HL-80682] FX This work was supported by the Veterans Affairs Office of Research and Development-Biomedical Laboratory Research and Development Service Award 1IO1BX000246 and National Heart, Lung, and Blood Institute Grant HL-86787 to BC. P. Delafontaine is supported by National Heart, Lung, and Blood Institute Grants HL-70241 and HL-80682. NR 52 TC 35 Z9 37 U1 1 U2 7 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 AUG PY 2012 VL 303 IS 3 BP H282 EP H296 DI 10.1152/ajpheart.00231.2012 PG 15 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 984ZG UT WOS:000307231900004 PM 22636674 ER PT J AU Vaporidi, K Vergadi, E Kaniaris, E Hatziapostolou, M Lagoudaki, E Georgopoulos, D Zapol, WM Bloch, KD Iliopoulos, D AF Vaporidi, Katerina Vergadi, Eleni Kaniaris, Evangelos Hatziapostolou, Maria Lagoudaki, Eleni Georgopoulos, Dimitrios Zapol, Warren M. Bloch, Kenneth D. Iliopoulos, Dimitris TI Pulmonary microRNA profiling in a mouse model of ventilator-induced lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE inflammation; miR-21; TGF-beta; miRNA-gene network ID RESPIRATORY-DISTRESS-SYNDROME; MECHANICAL VENTILATION; INFLAMMATORY RESPONSE; EXPRESSION; ACTIVATION; FIBROSIS; MIR-21; PTEN; LIPOPOLYSACCHARIDE; DIFFERENTIATION AB Vaporidi K, Vergadi E, Kaniaris E, Hatziapostolou M, Lagoudaki E, Georgopoulos D, Zapol WM, Bloch KD, Iliopoulos D. Pulmonary microRNA profiling in a mouse model of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 303: L199-L207, 2012. First published June 1, 2012; doi:10.1152/ajplung.00370.2011.-The aim of this study was to investigate the changes induced by high tidal volume ventilation (HVTV) in pulmonary expression of micro-RNAs (miRNAs) and identify potential target genes and corresponding miRNA-gene networks. Using a real-time RT-PCR-based array in RNA samples from lungs of mice subjected to HVTV for 1 or 4 h and control mice, we identified 65 miRNAs whose expression changed more than twofold upon HVTV. An inflammatory and a TGF-beta-signaling miRNA-gene network were identified by in silico pathway analysis being at highest statistical significance (P = 10(-43) and P = 10(-28), respectively). In the inflammatory network, IL-6 and SOCS-1, regulated by miRNAs let-7 and miR-155, respectively, appeared as central nodes. In TGF-beta-signaling network, SMAD-4, regulated by miR-146, appeared as a central node. The contribution of miRNAs to the development of lung injury was evaluated in mice subjected to HVTV treated with a precursor or antagonist of miR-21, a miRNA highly upregulated by HVTV. Lung compliance was preserved only in mice treated with anti-miR-21 but not in mice treated with pre-miR-21 or negative-control miRNA. Both alveolar-arterial oxygen difference and protein levels in bronchoalveolar lavage were lower in mice treated with anti-miR-21 than in mice treated with pre-miR-21 or negative-control miRNA (DA-a: 66 +/- 27 vs. 131 +/- 22, 144 +/- 10 mmHg, respectively, P < 0.001; protein concentration: 1.1 +/- 0.2 vs. 2.3 +/- 1, 2.1 +/- 0.4 mg/ml, respectively, P < 0.01). Our results show that HVTV induces changes in miRNA expression in mouse lungs. Modulation of miRNA expression can affect the development of HVTV-induced lung injury. C1 [Vaporidi, Katerina; Vergadi, Eleni; Kaniaris, Evangelos; Georgopoulos, Dimitrios] Univ Crete, Fac Med, Dept Intens Care Med, Iraklion, Crete, Greece. [Lagoudaki, Eleni] Univ Crete, Fac Med, Dept Med, Iraklion, Crete, Greece. [Vaporidi, Katerina; Zapol, Warren M.; Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, Boston, MA USA. [Hatziapostolou, Maria; Iliopoulos, Dimitris] Harvard Univ, Sch Med, Dept Microbiol Immunol, Boston, MA USA. [Iliopoulos, Dimitris] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Vaporidi, K (reprint author), Univ Crete, Fac Med, Dept Intens Care Med, Iraklion, Crete, Greece. EM vaporidi@med.uoc.gr RI Hatziapostolou, Maria/N-1820-2015 OI Hatziapostolou, Maria/0000-0003-2493-7028 FU US Public Health Service [HL-42397, HL74352]; LeDucq Foundation; European Society of Intensive Care Medicine research grant; University of Crete Research Committee [KA 2869, 3500] FX This work has been supported by US Public Health Service grant HL-42397 to W. M. Zapol, by the LeDucq Foundation and US Public Health Service grant HL74352 to K.D. Bloch, by European Society of Intensive Care Medicine research grant to K. Vaporidi, and by University of Crete Research Committee grants to D. Georgopoulos and K. Vaporidi (KA 2869, 3500). NR 48 TC 30 Z9 33 U1 1 U2 19 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2012 VL 303 IS 3 BP L199 EP L207 DI 10.1152/ajplung.00370.2011 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 984VH UT WOS:000307220000004 PM 22659882 ER PT J AU Goldstein, JE Massof, RW Deremeik, JT Braudway, S Jackson, ML Kehler, KB Primo, SA Sunness, JS AF Goldstein, Judith E. Massof, Robert W. Deremeik, James T. Braudway, Sonya Jackson, Mary Lou Kehler, K. Bradley Primo, Susan A. Sunness, Janet S. CA Low Vision Res Network Study Grp TI Baseline Traits of Low Vision Patients Served by Private Outpatient Clinical Centers in the United States SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BLUE-MOUNTAINS-EYE; AGE-RELATED MACULOPATHY; QUALITY-OF-LIFE; BEAVER DAM EYE; VISUAL IMPAIRMENT; OLDER-ADULTS; MACULAR DEGENERATION; HEARING-LOSS; REHABILITATION SERVICES; COGNITIVE IMPAIRMENT AB Objective: To characterize the traits of low vision patients who seek outpatient low vision rehabilitation (LVR) services in the United States. Methods: In a prospective observational study, we enrolled 764 new low vision patients seeking outpatient LVR services from 28 clinical centers in the United States. Before their initial appointment, multiple questionnaires assessing daily living and vision, physical, psychological, and cognitive health states were administered by telephone. Baseline clinical visual impairment measures and disorder diagnoses were recorded. Results: Patients had a median age of 77 years, were primarily female (66%), and had macular disease (55%), most of which was nonneovascular age-related macular degeneration. More than one-third of the patients (37%) had mild vision impairment with habitual visual acuity (VA) of 20/60 or greater. The VA correlated well with contrast sensitivity (r=-0.52) but poorly with self-reported vision quality. The intake survey revealed self-reported physical health limitations, including decreased endurance (68%) and mobility problems (52%). Many patients reported increased levels of frustration (42%) and depressed mood (22%); memory and cognitive impairment (11%) were less frequently endorsed. Patients relied on others for daily living support (87%), but many (31%) still drove. Conclusions: Most patients seeking LVR are geriatric and have macular disease with relatively preserved VA. The disparity between VA and subjective quality of vision suggests that LVR referrals are based on symptoms rather than on VA alone. Patients seen for LVR services have significant physical, psychological, and cognitive disorders that can amplify vision disabilities and decrease rehabilitation potential. C1 [Goldstein, Judith E.; Massof, Robert W.; Deremeik, James T.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Lions Vis Res & Rehabil Ctr, Baltimore, MD 21205 USA. [Braudway, Sonya] Ctr Retina & Macular Dis, Winter Haven, FL USA. [Jackson, Mary Lou] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Kehler, K. Bradley] Vanderbilt Eye Inst, Nashville, TN USA. [Primo, Susan A.] Emory Eye Ctr, Atlanta, GA USA. [Sunness, Janet S.] Greater Baltimore Med Ctr, Hoover Low Vis Rehabil Serv, Baltimore, MD USA. RP Goldstein, JE (reprint author), Lions Vis Ctr, 6th Floor,550 N Broadway, Baltimore, MD 21205 USA. EM jgolds28@jhmi.edu FU National Eye Institute, National Institutes of Health [EY012045, EY018696]; Reader's Digest Partners for Sight Foundation; Research to Prevent Blindness; National Eye Institute [P30EY006360] FX This study was supported by grants EY012045 and EY018696 from the National Eye Institute, National Institutes of Health, and by a grant from Reader's Digest Partners for Sight Foundation. Dr Kehler was supported by an unrestricted grant from Research to Prevent Blindness. Dr Primo was supported in part by an unrestricted departmental grant from Research to Prevent Blindness and National Eye Institute Core Grant for Vision Research P30EY006360. NR 71 TC 21 Z9 21 U1 4 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2012 VL 130 IS 8 BP 1028 EP 1037 PG 10 WC Ophthalmology SC Ophthalmology GA 987YU UT WOS:000307455800011 PM 22893074 ER PT J AU Bandopadhayay, P Dagi, L Robison, N Goumnerova, L Ullrich, NJ AF Bandopadhayay, Pratiti Dagi, Linda Robison, Nathan Goumnerova, Liliana Ullrich, Nicole J. TI Morning Glory Disc Anomaly in Association With Ipsilateral Optic Nerve Glioma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID DEFECTS C1 [Ullrich, Nicole J.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Bandopadhayay, Pratiti; Robison, Nathan] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Dagi, Linda] Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. [Goumnerova, Liliana] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Ullrich, NJ (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM nicole.ullrich@childrens.harvard.edu NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2012 VL 130 IS 8 BP 1082 EP 1083 PG 3 WC Ophthalmology SC Ophthalmology GA 987YU UT WOS:000307455800029 PM 22893090 ER PT J AU Morikawa, T Tanaka, N Kuchiba, A Nosho, K Yamauchi, M Hornick, JL Swanson, RS Chan, AT Meyerhardt, JA Huttenhower, C Schrag, D Fuchs, CS Ogino, S AF Morikawa, Teppei Tanaka, Noriko Kuchiba, Aya Nosho, Katsuhiko Yamauchi, Mai Hornick, Jason L. Swanson, Richard S. Chan, Andrew T. Meyerhardt, Jeffrey A. Huttenhower, Curtis Schrag, Deborah Fuchs, Charles S. Ogino, Shuji TI Predictors of Lymph Node Count in Colorectal Cancer Resections Data From US Nationwide Prospective Cohort Studies SO ARCHIVES OF SURGERY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; COLON-CANCER; MICROSATELLITE INSTABILITY; BRAF MUTATION; TUMOR FACTORS; SURVIVAL; RETRIEVAL; SPECIMENS; NUMBER AB Objective: To identify factors that influence the total and negative lymph node counts in colorectal cancer resection specimens independent of pathologists and surgeons. Design: We used multivariate negative binomial regression. Covariates included age, sex, body mass index, family history of colorectal carcinoma, year of diagnosis, hospital setting, tumor location, resected colorectal length (specimen length), tumor size, circumferential growth, TNM stage, lymphocytic reactions and other pathological features, and tumor molecular features (microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element 1 [LINE-1] methylation, and BRAF, KRAS, and PIK3CA mutations). Setting: Two US nationwide prospective cohort studies. Patients: Patients with rectal and colon cancer (N = 918). Main Outcome Measures: The negative and total node counts (continuous). Results: Specimen length, tumor size, ascending colon location, T3N0M0 stage, and year of diagnosis were positively associated with the negative node count (all P <= .002). Mutation of KRAS might also be positively associated with the negative node count (P = . 03; borderline significance considering multiple hypothesis testing). Among node-negative (stages I and II) cases, specimen length, tumor size, and ascending colon location remained significantly associated with the node count (all P <= .002), and PIK3CA and KRAS mutations might also be positively associated (P = . 03 and P = . 049, respectively, with borderline significance). Conclusions: This molecular pathological epidemiology study shows that specimen length, tumor size, tumor location, TNM stage, and year of diagnosis are operator-independent predictors of the lymph node count. These crucial variables should be examined in any future evaluation of the adequacy of lymph node harvest and nodal staging when devising individualized treatment plans for patients with colorectal cancer. C1 [Ogino, Shuji] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Morikawa, Teppei; Kuchiba, Aya; Yamauchi, Mai; Meyerhardt, Jeffrey A.; Schrag, Deborah; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Hornick, Jason L.; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Swanson, Richard S.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02215 USA. [Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tanaka, Noriko] Natl Surg Adjuvant Breast & Bowel Project Operat, Pittsburgh, PA USA. [Nosho, Katsuhiko] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, 450 Brookline Ave,Room JF 215C, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu FU National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA151993, R01 CA137178]; Bennett Family Fund for Targeted Therapies Research; Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance FX This work was supported by grants P01 CA87969, P01 CA55075, P50 CA127003 (Dr Fuchs), R01 CA151993 (Dr Ogino), and R01 CA137178 (Dr Chan) from the National Institutes of Health; the Bennett Family Fund for Targeted Therapies Research; and the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance. NR 55 TC 20 Z9 20 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD AUG PY 2012 VL 147 IS 8 BP 715 EP 723 DI 10.1001/archsurg.2012.353 PG 9 WC Surgery SC Surgery GA 991VV UT WOS:000307732100006 PM 22508672 ER PT J AU Nasr, S AF Nasr, S. TI Sensitivity of event-related brain potentials to task rules SO ATTENTION PERCEPTION & PSYCHOPHYSICS LA English DT Article DE Decision-making; Object Recognition; Perceptual categorization and identification; Sensory perception; Visual matching ID PERCEPTUAL DECISION-MAKING; FACE REPRESENTATIONS; NAME RECOGNITION; REPETITION; ERP; MECHANISMS; OBJECT; CORTEX; MEMORY; SCALP AB Previous studies have suggested that brain potentials evoked around 300 ms after stimulus onset index the processes underlying perceptual decision-making. However, the sensitivity of these evoked potentials to the task rules, which link sensory perception to the proper action, has not been studied previously. In this study, event-related potentials (ERPs) of the human brain were examined when subjects randomly performed delayed-matching-to-identity (DMI) and delayed-matching-to-category (DMC) tasks. The results showed that the amplitudes of the brain potentials evoked 228-328 ms after test-stimulus onset varied according to the task rules and indexed the processes responsible for decision-making. In contrast to these potentials, the preceding evoked activity (< 228 ms) did not show any sensitivity to the changes in the subjects' responses and indexed the processes responsible for stimulus perception. These findings support the idea that the potentials evoked after 228 ms from stimulus onset are influenced by the task rules and do not index simple sensory perception. C1 [Nasr, S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Nasr, S.] Inst Res Fundamental Sci IPM, Sch Cognit Sci, Tehran, Iran. [Nasr, S.] Shahid Beheshti Univ, Res Ctr Brain & Cognit Sci, Sch Med, Tehran, Iran. RP Nasr, S (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM shahin@nmr.mgh.harvard.edu NR 47 TC 1 Z9 1 U1 0 U2 2 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 AUG PY 2012 VL 74 IS 6 BP 1343 EP 1354 DI 10.3758/s13414-012-0309-9 PG 12 WC Psychology; Psychology, Experimental SC Psychology GA 981EQ UT WOS:000306950100022 PM 22585340 ER PT J AU Steensma, DP AF Steensma, David P. TI Tuning the Rigging before Sailing off into the Stormy Sea of Stem Cell Transplants for Patients with Myelodysplastic Syndromes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; MDS; AML; FEASIBILITY; AZACITIDINE; REGIMENS; THERAPY; ADULTS; OLDER C1 [Steensma, David P.] Dana Farber Canc Inst, Div Hematol Malignancies, Dept Med Oncol, Boston, MA 02215 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 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 NR 22 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2012 VL 18 IS 8 BP 1145 EP 1147 DI 10.1016/j.bbmt.2012.05.004 PG 3 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 982KB UT WOS:000307040800001 PM 22609039 ER PT J AU Martin, PJ Rizzo, JD Wingard, JR Ballen, K Curtin, PT Cutler, C Litzow, MR Nieto, Y Savani, BN Schriber, JR Shaughnessy, PJ Wall, DA Carpenter, PA AF Martin, Paul J. Rizzo, J. Douglas Wingard, John R. Ballen, Karen Curtin, Peter T. Cutler, Corey Litzow, Mark R. Nieto, Yago Savani, Bipin N. Schriber, Jeffrey R. Shaughnessy, Paul J. Wall, Donna A. Carpenter, Paul A. TI First- and Second-Line Systemic Treatment of Acute Graft-versus-Host Disease: Recommendations of the American Society of Blood and Marrow Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Acute graft-versus-host disease; Hematopoietic cell transplantation; Treatment ID STEROID-REFRACTORY ACUTE; STEM-CELL TRANSPLANTATION; RECEPTOR MONOCLONAL-ANTIBODY; MYCOPHENOLATE-MOFETIL; ACUTE GVHD; RANDOMIZED-TRIAL; ANTITHYMOCYTE GLOBULIN; DENILEUKIN DIFTITOX; THYMOCYTE GLOBULIN; IMPROVED SURVIVAL AB Despite prophylaxis with innmunosuppressive agents or a variety of other approaches, many patients suffer from acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation. Although consensus has emerged supporting the use of high-dose methylprednisolone or prednisone for initial treatment of aGVHD, practices differ among centers with respect to the initial glucocorticoid dose, the use of additional immunosuppressive agents, and the approach to withdrawal of treatment after initial improvement. Despite many studies, practices vary considerably with respect to the selection of agents for treatment of glucocorticoid-resistant or refractory GVHD. Investigators and clinicians have recognized the lack of progress and lamented the absence of an accepted standard of care for secondary treatment of aGVHD. The American Society of Blood and Marrow Transplantation has developed recommendations for treatment of aGVHD to be considered by care providers, based on a comprehensive and critical review of published reports. Because the literature provides little basis for a definitive guideline, this review also provides a framework for the interpretation of previous results and the design of future studies. Biol Blood Marrow Transplant 18: 1150-1163 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Martin, Paul J.; Carpenter, Paul A.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Wingard, John R.] Univ Florida, Coll Med, Gainesville, FL USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Curtin, Peter T.] Moores Univ Calif San Diego Canc Ctr, San Diego, CA USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Nieto, Yago] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Schriber, Jeffrey R.] Virginia G Piper Canc Ctr, Scottsdale, AZ USA. [Shaughnessy, Paul J.] Texas Transplant Inst, San Antonio, TX USA. [Wall, Donna A.] Univ Manitoba Canc Care Manitoba, Winnipeg, MB, Canada. RP Martin, PJ (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, POB 19024, Seattle, WA 98109 USA. EM pmartin@fhcrc.org FU Department of Health and Human Services [CA18029]; Soligenix, Inc.; Roche Laboratories FX Funding for this work was provided in part by CA18029 (P.J.M.) from the Department of Health and Human Services.; P.J.M. has received research support from Soligenix, Inc. and Roche Laboratories, administered through the Fred Hutchinson Cancer Research Center. P.J.S. has received honoraria from Millenium, Otsuka, and Sanofi/Genzyme. The other authors declared no conflict of interest. NR 50 TC 111 Z9 114 U1 2 U2 14 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 AUG PY 2012 VL 18 IS 8 BP 1150 EP 1163 DI 10.1016/j.bbmt.2012.04.005 PG 14 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 982KB UT WOS:000307040800003 PM 22510384 ER PT J AU Freytes, CO Zhang, MJ Carreras, J Burns, LJ Gale, RP Isola, L Perales, MA Seftel, M Vose, JM Miller, AM Gibson, J Gross, TG Rowlings, PA Inwards, DJ Pavlovsky, S Martino, R Marks, DI Hale, GA Smith, SM Schouten, HC Slavin, S Klumpp, TR Lazarus, HM van Besien, K Hari, PN AF Freytes, Cesar O. Zhang, Mei-Jie Carreras, Jeanette Burns, Linda J. Gale, Robert Peter Isola, Luis Perales, Miguel-Angel Seftel, Matthew Vose, Julie M. Miller, Alan M. Gibson, John Gross, Thomas G. Rowlings, Philip A. Inwards, David J. Pavlovsky, Santiago Martino, Rodrigo Marks, David I. Hale, Gregory A. Smith, Sonali M. Schouten, Harry C. Slavin, Simon Klumpp, Thomas R. Lazarus, Hillard M. van Besien, Koen Hari, Parameswaran N. TI Outcome of Lower-Intensity Allogeneic Transplantation in Non-Hodgkin Lymphoma after Autologous Transplantation Failure SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic; Relapse; Reduced-intensity ID STEM-CELL TRANSPLANTATION; PROGRESSIVE DISEASE; REGISTRY; BLOOD; MALIGNANCIES; RELAPSE; THERAPY; EXPERIENCE; REMISSION AB We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006. The median follow-up of survivors was 68 months (range, 3-111 months). Three-year nonrelapse mortality was 44% (95% confidence interval [CI], 37%-50%). Lymphoma progression/relapse at 3 years was 35% (95% CI, 29%-41%). Three-year probabilities of PFS and overall survival were 21% (95% CI, 16%-27%) and 32% (95% CI, 27%-38%), respectively. Superior Karnofsky Performance Score, longer interval between transplantations, total body irradiation-based conditioning regimen, and lymphoma remission at transplantation were correlated with improved PFS. Allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning is associated with significant nonrelapse mortality but can result in long-term PFS. We describe a quantitative risk model based on pretransplantation risk factors to identify those patients likely to benefit from this approach. Biol Blood Marrow Transplant 18: 1255-1264 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Zhang, Mei-Jie; Carreras, Jeanette; Hari, Parameswaran N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Burns, Linda J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Isola, Luis] Mt Sinai Hosp, New York, NY 10029 USA. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Seftel, Matthew] Univ Manitoba, Winnipeg, MB, Canada. [Vose, Julie M.] Univ Nebraska Med Ctr, Omaha, NE USA. [Miller, Alan M.] Baylor Univ, Med Ctr, Dallas, TX USA. [Gibson, John] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Gross, Thomas G.] Ohio State Univ, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Rowlings, Philip A.] Calvary Mater Hosp, Waratah, Australia. [Inwards, David J.] Mayo Clin, Rochester, MN USA. [Pavlovsky, Santiago] Fundaleu, Buenos Aires, DF, Argentina. [Martino, Rodrigo] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Smith, Sonali M.; van Besien, Koen] Univ Chicago Hosp, Chicago, IL 60637 USA. [Schouten, Harry C.] Univ Hosp Maastricht, Maastricht, Netherlands. [Slavin, Simon] Hadassah Med Ctr, Tel Aviv, Israel. [Klumpp, Thomas R.] Temple Univ, BMT Program, Philadelphia, PA 19122 USA. [Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, POB 26509, Milwaukee, WI 53226 USA. EM phari@mcw.edu RI van Besien, Koen/G-4221-2012; OI van Besien, Koen/0000-0002-8164-6211; PERALES, MIGUEL-ANGEL/0000-0002-5910-4571; Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute, Public Health Service [U24-CA76518]; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Cancer Institute [5U01HL069294]; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos; Amgen; Angioblast; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene; CellGenix; Children's Leukemia Research Association; Fresenius-Biotech North America, Gamida Cell Teva Joint Venture; Genentech; Genzyme; GlaxoSmithKline; Kiadis Pharma; Leukemia and Lymphoma Society; Medical College of Wisconsin; Millennium Pharmaceuticals; Milliman USA; Miltenyi Biotec, National Marrow Donor Program; Optum Healthcare Solutions; Otsuka America Pharmaceutical; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix; Swedish Orphan Biovitrum; THERAKOS; Well-point FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, National Heart, Lung and Blood Institute, and National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U01HL069294 from the National Cancer Institute and National Heart, Lung and Blood Institute; Contract HHSH234200637015C with the Health Resources and Services Administration; Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Amgen, Angioblast, anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, Blue Cross and Blue Shield Association, Buchanan Family Foundation, CaridianBCT, Celgene, CellGenix, Children's Leukemia Research Association, Fresenius-Biotech North America, Gamida Cell Teva Joint Venture, Genentech, Genzyme, GlaxoSmithKline, Kiadis Pharma, Leukemia and Lymphoma Society, Medical College of Wisconsin, Millennium Pharmaceuticals, Milliman USA, Miltenyi Biotec, National Marrow Donor Program, Optum Healthcare Solutions, Otsuka America Pharmaceutical, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, Swedish Orphan Biovitrum, THERAKOS, and Well-point. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, Department of the Navy, Department of Defense, or any other agency of the US Government. The authors have no conflicts of interest to disclose. NR 29 TC 15 Z9 15 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2012 VL 18 IS 8 BP 1255 EP 1264 DI 10.1016/j.bbmt.2011.12.581 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 982KB UT WOS:000307040800015 PM 22198543 ER PT J AU Battiwalla, M Ellis, K Li, PG Pavletic, SZ Akpek, G Hematti, P Klumpp, TR Maziarz, RT Savani, BN Aljurf, MD Cairo, MS Drobyski, WR George, B Hahn, T Khera, N Litzow, MR Loren, AW Saber, W Arora, M Urbano-Ispizua, A Cutler, C Flowers, MED Spellman, SR AF Battiwalla, Minoo Ellis, Kristin Li, Peigang Pavletic, Steven Z. Akpek, Gorgun Hematti, Peiman Klumpp, Thomas R. Maziarz, Richard T. Savani, Bipin N. Aljurf, Mahmoud D. Cairo, Mitchell S. Drobyski, William R. George, Biju Hahn, Theresa Khera, Nandita Litzow, Mark R. Loren, Alison W. Saber, Wael Arora, Mukta Urbano-Ispizua, Alvaro Cutler, Corey Flowers, Mary E. D. Spellman, Stephen R. TI HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE DR15; Hematopoietic stem cell transplantation (HSCT); GVHD; Survival; graft-versus-lymphoma ID APLASTIC-ANEMIA PATIENTS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; STEM-CELL TRANSPLANTATION; REDUCED RELAPSE RATE; IMMUNOSUPPRESSIVE THERAPY; MYELODYSPLASTIC SYNDROME; INCREASED FREQUENCY; POPULATION; HLA-DR15; DR2 AB The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from MLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning. T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRBI*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS. Biol Blood Marrow Transplant 18: 1302-1308 (2012) Published by Elsevier Inc on behalf of American Society for Blood and Mal-row Transplantation C1 [Battiwalla, Minoo] NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. [Ellis, Kristin; Li, Peigang; Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Pavletic, Steven Z.] NCI, NIH, Bethesda, MD 20892 USA. [Akpek, Gorgun] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Hematti, Peiman] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Klumpp, Thomas R.] Temple Bone Marrow Transplant Program, Philadelphia, PA USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Brentwood, TN USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [George, Biju] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Hahn, Theresa] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Khera, Nandita; Flowers, Mary E. D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Loren, Alison W.] Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Urbano-Ispizua, Alvaro] Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain. [Cutler, Corey] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. RP Battiwalla, M (reprint author), NHLBI, NIH, Hematol Branch, 10-CRC,Rm 5-3581,9000 Rockville Pike, Bethesda, MD 20892 USA. EM minoo.battiwalla@nih.gov FU National Institute of Health (NIH) intramural research programs of the NHLBI; NCI; Public Health Service from the National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID); Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-10-1-0204, N00014-1-1-0339]; Altos, Inc.; Amgen, Inc.; Angioblast; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; OptumHealth Care Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; Wellpoint, Inc. FX This work was supported by the National Institute of Health (NIH) intramural research programs of the NHLBI and NCI. CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-10-1-0204 and N00014-1-1-0339 from the Office of Naval Research; and grants from Altos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; OptumHealth Care Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc. NR 25 TC 3 Z9 3 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 AUG PY 2012 VL 18 IS 8 BP 1302 EP 1308 DI 10.1016/j.bbmt.2012.02.011 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 982KB UT WOS:000307040800021 PM 22414493 ER PT J AU Goh, EJ Kim, KS Kim, YR Jung, HS Beack, S Kong, WH Scarcelli, G Yun, SH Hahn, SK AF Goh, Eun Ji Kim, Ki Su Kim, Yi Rang Jung, Ho Sang Beack, Songeun Kong, Won Ho Scarcelli, Giuliano Yun, Seok Hyun Hahn, Sei Kwang TI Bioimaging of Hyaluronic Acid Derivatives Using Nanosized Carbon Dots SO BIOMACROMOLECULES LA English DT Article ID SEMICONDUCTOR QUANTUM DOTS; NEAR-INFRARED FLUORESCENCE; NANOTUBES; MICE; NANOPARTICLES; DELIVERY; BRIGHT; CELLS; OXIDE AB Fluorescent nanosized carbon dots (Cdots) are an emerging bioimaging agent with excellent chemical inertness and marginal cytotoxicity in comparison to widely used semiconductor quantum dots. In this work, we report the application of Cdots for real time bioimaging of target specific delivery of hyaluronic acid (HA) derivatives. Polyethylene glycol (PEG) diamine-capped Cdots were synthesized by the pyrolysis of citric acid in a hot solvent The synthesized Cdots showed strong fluorescence under UV excitation with emission properties dependending on the excitation wavelength. HA-Cdot conjugates were synthesized by amide bond formation between amine groups of Cdot and carboxylic groups of HA. After confirmation of the negligible cytotoxicity of Cdots and HA Cdot conjugates, in vitro bioimaging was carried out for target specific intracellular delivery of the HA-Cdot conjugates by HA receptor mediated endocytosis. Furthermore, in vivo real-time bioimaging of Cdots and HA-Cdot conjugates exhibited the target specific delivery of HA-Cdot conjugates to the liver with abundant HA receptors. Taken together, we could confirm the feasibility of HA derivatives as a target specific drug delivery carrier for the treatment of liver diseases and Cdots as a promising bioimaging agent. C1 [Goh, Eun Ji; Kim, Ki Su; Jung, Ho Sang; Beack, Songeun; Kong, Won Ho; Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea. [Kim, Yi Rang; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, Taejon 305701, South Korea. [Scarcelli, Giuliano; Yun, Seok Hyun; Hahn, Sei Kwang] Harvard Univ, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Scarcelli, Giuliano; Yun, Seok Hyun; Hahn, Sei Kwang] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. RP Hahn, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, San 31, Pohang 790784, Kyungbuk, South Korea. EM skhanb@postech.ac.kr OI scarcelli, giuliano/0000-0002-1736-077X FU LG Yeonam Foundation Scholarship; Convergence Research Center Program through the National Research Foundation (NRF) of Korea; Ministry of Education, Science and Technology [2009-0081871] FX This research was financially supported by the LG Yeonam Foundation Scholarship. This work was also financially supported by the Convergence Research Center Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (2009-0081871). NR 36 TC 69 Z9 73 U1 20 U2 161 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD AUG PY 2012 VL 13 IS 8 BP 2554 EP 2561 DI 10.1021/bm300796q PG 8 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 987MV UT WOS:000307422300039 PM 22804331 ER PT J AU Holmes, LB Hernandez-Diaz, S AF Holmes, Lewis B. Hernandez-Diaz, Sonia TI Newer anticonvulsants: Lamotrigine, topiramate and gabapentin SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID NEWER ANTIEPILEPTIC DRUGS; ISOLATED CLEFT-PALATE; EXPOSED IN-UTERO; INCREASED FREQUENCY; PREGNANCY-REGISTER; SODIUM VALPROATE; UK-EPILEPSY; CHILDREN; MALFORMATIONS; INFANTS AB BACKGROUND The second generation antiepileptic drugs (AEDs), which include lamotrigine, topiramate, and gabapentin, have been introduced during the past 20 years. Because the newer AEDs differ in their pharmacokinetics from the first generation AEDs, it is hoped that the second generation AEDs will be less teratogenic. METHODS The findings in pregnancy cohorts and case-control studies concerning lamotrigine, topiramate and gabapentin-exposed pregnancies have been analyzed. RESULTS The rate of all malformations in lamotrigine monotherapy-exposed pregnancies has been between 2.0 and 5.6%, in comparison to baseline rates of 1.1 to 3.6% in two unexposed comparison groups. Compared to reference populations, a higher risk (0.4%) of isolated oral clefts has been observed in one cohort of 1562 lamotrigine-exposed pregnancies, but the risk was lower (0.1%) in other studies. In topiramate-exposed pregnancies, the rate of all malformations has been 4.2 to 4.9%, with an increase in oral clefts with and without other anomalies. The limited information available now for gabapentin has shown no evidence of teratogenicity. Concerning other developmental effects of these drugs, young children exposed to lamotrigine in utero have shown no deficits in cognitive function. Prenatal exposure to topiramate has been associated with an elevated frequency of small size for gestational age newborns. CONCLUSIONS The information available suggests an increased risk of oral clefts in infants exposed to topiramate, and perhaps lamotrigine, early in pregnancy, and of growth retardation for topiramate-exposed infants. Larger sample sizes are needed to clarify the questions that have been raised. Birth Defects Research (Part A) 94:599606, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Holmes, Lewis B.] Harvard Univ, Dept Pediat, Genet Unit, MassGen Hosp Children,Med Sch, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [Holmes, Lewis B.; Hernandez-Diaz, Sonia] Massachusetts Gen Hosp, N Amer Antiepilept Drug Pregnancy Registry, Somerville, MA USA. RP Holmes, LB (reprint author), Harvard Univ, Dept Pediat, Genet Unit, MassGen Hosp Children,Med Sch, 175 Cambridge St,504, Boston, MA 02114 USA. EM holmes.lewis@mgh.harvard.edu NR 51 TC 27 Z9 28 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD AUG PY 2012 VL 94 IS 8 SI SI BP 599 EP 606 DI 10.1002/bdra.23028 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 986YF UT WOS:000307382900004 PM 22730257 ER PT J AU De Zwart, AD Beeres, FJP Ring, D Kingma, LM Coerkamp, EG Meylaerts, SAG Rhemrev, SJ AF De Zwart, A. D. Beeres, F. J. P. Ring, D. Kingma, L. M. Coerkamp, E. G. Meylaerts, S. A. G. Rhemrev, S. J. TI MRI as a reference standard for suspected scaphoid fractures SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID BONE-SCINTIGRAPHY AB Objectives: Some have suggested that MRI might be the best reference standard for a true fracture among patients with suspected scaphoid fractures. The primary aim of this study was to determine the rate of false-positive diagnosis of an acute scaphoid fracture in a cohort of healthy volunteers. Methods: In a prospective study, 33 healthy volunteers were recruited and both wrists of each were scanned, except for 2 volunteers for whom only one wrist was scanned. To simulate the usual clinical context the 64 scans of healthy volunteers were mixed with 60 MRI scans of clinically suspected scaphoid fractures but normal scaphoid radiographs. These 124 MRI scans were blinded and randomly ordered. Five radiologists evaluated the MRI scans independently for the presence or absence of a scaphoid fracture and other injuries according to a standard protocol. Results: To answer the primary question, only the diagnoses from the 64 scans of healthy volunteers were used. The radiologists diagnosed a total of 13 scaphoid fractures; therefore, specificity for diagnosis of scaphoid fracture was 96% (95% confidence interval: range 94-98%). The 5 observers had a moderate interobserver agreement regarding diagnosis of scaphoid fracture in healthy volunteers (multirater kappa=0.44; p<0.001). Conclusions: The specificity of MRI for scaphoid fractures is high (96%), but false-positives do occur. Radiologists have only moderate agreement when interpreting MRI scans from healthy volunteers. MRI is not an adequate reference standard for true fractures among patients with suspected scaphoid fractures. C1 [De Zwart, A. D.; Beeres, F. J. P.; Meylaerts, S. A. G.; Rhemrev, S. J.] Med Ctr Haaglanden, Dept Surg, NL-2501 CK The Hague, Netherlands. [Coerkamp, E. G.] Med Ctr Haaglanden, Dept Radiol, NL-2501 CK The Hague, Netherlands. [Ring, D.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Beeres, F. J. P.] Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands. [Kingma, L. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, NL-9713 AV Groningen, Netherlands. RP De Zwart, AD (reprint author), Med Ctr Haaglanden, Dept Surg, Postbus 432, NL-2501 CK The Hague, Netherlands. EM andeledezwart@gmail.com OI Beeres, Frank/0000-0002-7277-3438 NR 12 TC 6 Z9 6 U1 1 U2 6 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD AUG PY 2012 VL 85 IS 1016 BP 1098 EP 1101 DI 10.1259/bjr/73145885 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 988OK UT WOS:000307500200040 PM 22815412 ER PT J AU Cheng, G AF Cheng, G. TI The diagnostic value of FDG-PET cannot be judged by iliac bone marrow biopsy SO BRITISH JOURNAL OF RADIOLOGY LA English DT Letter ID POSITRON-EMISSION-TOMOGRAPHY; NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMA; INVOLVEMENT; UTILITY C1 Philadelphia VA Med Ctr, 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 NR 17 TC 2 Z9 2 U1 0 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD AUG PY 2012 VL 85 IS 1016 BP 1204 EP 1205 DI 10.1259/bjr/61638269 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 988OK UT WOS:000307500200057 PM 22815418 ER PT J AU Mullen, JT Kobayashi, W Wang, JJ Harmon, DC Choy, E Hornicek, FJ Rosenberg, AE Chen, YL Spiro, IJ DeLaney, TF AF Mullen, John T. Kobayashi, Wendy Wang, Jing Jing Harmon, David C. Choy, Edwin Hornicek, Francis J. Rosenberg, Andrew E. Chen, Yen-Lin Spiro, Ira J. DeLaney, Thomas F. TI Long-term follow-up of patients treated with neoadjuvant chemotherapy and radiotherapy for large, extremity soft tissue sarcomas SO CANCER LA English DT Article DE soft tissue sarcoma; neoadjuvant chemotherapy; radiotherapy; follow-up; extremity sarcoma; mesna; Adriamycin (doxorubicin); ifosfamide; and dacarbazine (MAID) ID ADJUVANT CHEMOTHERAPY; HIGH-GRADE; HIGH-RISK; RADIATION-THERAPY; LOCAL-CONTROL; BODY-WALL; PHASE-II; SURGERY; TRIAL; METAANALYSIS AB BACKGROUND: Patients with large, high-grade, extremity soft tissue sarcomas (STS) are at significant risk for distant recurrence and death. A regimen of preoperative chemotherapy consisting of mesna, Adriamycin (doxorubicin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT) and followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. We report the long-term follow-up data on 48 patients treated with this regimen compared to an historical matched-control patient population. METHODS: Adult patients with high-grade extremity STS = 8 cm were treated with 3 cycles of preoperative chemotherapy combined with 44 Gy of RT followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy of RT was delivered postoperatively. RESULTS: Patients received the MAID/RT regimen from 1989 through 1999. After a median follow-up of 9.3 years in surviving patients in the MAID group and 13.2 years in surviving patients in the control group, the 7-year disease-specific and overall survival rates were 81% and 50% (P = .004) and 79% and 45% (P = .003) for the MAID and control patients, respectively. Five of 11 patients in the MAID group and 7 of 25 control patients died of sarcoma =5 years after treatment. One patient in the MAID group developed a fatal myelodysplasia at 53 months. CONCLUSIONS: For patients with high-risk, extremity STS, the significant survival benefits conferred by an intense regimen of neoadjuvant chemoradiotherapy and surgery are sustained even with long-term follow-up. Cancer 2012. (C) 2011 American Cancer Society. C1 [Mullen, John T.] Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. [Kobayashi, Wendy; Wang, Jing Jing; Chen, Yen-Lin; Spiro, Ira J.; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Harmon, David C.; Choy, Edwin] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Hornicek, Francis J.] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jmullen@partners.org OI Choy, Edwin/0000-0001-9896-8084 NR 18 TC 22 Z9 24 U1 1 U2 4 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 AUG 1 PY 2012 VL 118 IS 15 BP 3758 EP 3765 DI 10.1002/cncr.26696 PG 8 WC Oncology SC Oncology GA 977NU UT WOS:000306671300014 PM 22180344 ER PT J AU Demark-Wahnefried, W Platz, EA Ligibel, JA Blair, CK Courneya, KS Meyerhardt, JA Ganz, PA Rock, CL Schmitz, KH Wadden, T Philip, EJ Wolfe, B Gapstur, SM Ballard-Barbash, R McTiernan, A Minasian, L Nebeling, L Goodwin, PJ AF Demark-Wahnefried, Wendy Platz, Elizabeth A. Ligibel, Jennifer A. Blair, Cindy K. Courneya, Kerry S. Meyerhardt, Jeffrey A. Ganz, Patricia A. Rock, Cheryl L. Schmitz, Kathryn H. Wadden, Thomas Philip, Errol J. Wolfe, Bruce Gapstur, Susan M. Ballard-Barbash, Rachel McTiernan, Anne Minasian, Lori Nebeling, Linda Goodwin, Pamela J. TI The Role of Obesity in Cancer Survival and Recurrence SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID BODY-MASS INDEX; STAGE BREAST-CANCER; III COLON-CANCER; GROWTH-FACTOR-I; RANDOMIZED CONTROLLED-TRIAL; TREATMENT-RELATED TOXICITY; LIFE-STYLE INTERVENTION; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; PROSTATE-CANCER AB Obesity and components of energy imbalance, that is, excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, "The Role of Obesity in Cancer Survival and Recurrence"; discussions included (i) mechanisms associated with obesity and energy balance that influence cancer progression; (ii) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; (iii) associations between obesity and cancer risk, recurrence, and mortality; (iv) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and (v) future directions. Cancer Epidermal Biomarkers Prev; 21(8); 1244-59. (c) 2012 AACR. C1 [Demark-Wahnefried, Wendy; Blair, Cindy K.] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Ligibel, Jennifer A.; Meyerhardt, Jeffrey A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Courneya, Kerry S.] Univ Alberta, Fac Phys Educ & Recreat, Edmonton, AB, Canada. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Rock, Cheryl L.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Schmitz, Kathryn H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Wadden, Thomas] Univ Penn, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA. [Philip, Errol J.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Wolfe, Bruce] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Ballard-Barbash, Rachel] NCI, Appl Res Program, Bethesda, MD 20892 USA. [Minasian, Lori] NCI, Community Oncol & Prevent Trials Res Grp, Bethesda, MD 20892 USA. [Nebeling, Linda] NCI, Behav Res Program, Bethesda, MD 20892 USA. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Goodwin, Pamela J.] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. RP Demark-Wahnefried, W (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 1675 Univ Blvd,Room 346, Birmingham, AL 35294 USA. EM demark@uab.edu RI Goodwin, Pamela/K-1477-2013 FU Nutrisystem; [CA13148]; [CA148791]; [CA047888] FX T. Wadden is a recipient of commercial research grant from Nutrisystem and is also a consultant and an advisory board member of Novo Nordisk and Orexigen. E.J. Philip is a consultant and an advisory board member of Kantar Health. A. McTiernan has ownership interest (including patents) in Merck and is a consultant and an advisory board member of Metagenics.; The work was supported by the following grants: CA13148 (W. Demark-Wahnefried), CA148791 (C.L. Rock, W. Demark-Wahnefried), and CA047888 (C.K. Blair) NR 144 TC 79 Z9 81 U1 3 U2 25 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 AUG PY 2012 VL 21 IS 8 BP 1244 EP 1259 DI 10.1158/1055-9965.EPI-12-0485 PG 16 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 987RC UT WOS:000307433800003 PM 22695735 ER PT J AU Caan, BJ Kwan, ML Shu, XO Pierce, JP Patterson, RE Nechuta, SJ Poole, EM Kroenke, CH Weltzien, EK Flatt, SW Quesenberry, CP Holmes, MD Chen, WY AF Caan, Bette J. Kwan, Marilyn L. Shu, Xiao Ou Pierce, John P. Patterson, Ruth E. Nechuta, Sarah J. Poole, Elizabeth M. Kroenke, Candyce H. Weltzien, Erin K. Flatt, Shirley W. Quesenberry, Charles P., Jr. Holmes, Michelle D. Chen, Wendy Y. TI Weight Change and Survival after Breast Cancer in the After Breast Cancer Pooling Project SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; CARDIOVASCULAR-DISEASE MORTALITY; CORONARY-ARTERY-DISEASE; ALL-CAUSE MORTALITY; OBESITY PARADOX; ADJUVANT CHEMOTHERAPY; POSTMENOPAUSAL WOMEN; RISK-FACTORS; OLDER WOMEN; LIVING WHEL AB Background: Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of postchagnostic weight variation on survival, we examined the relationship by comorbid status and initial body mass index (BMI). Methods: The current analysis included 12,915 patients with breast cancer diagnosed between 1990 and 2006 with stage I-III tumors from four prospective cohorts in the United States and China. HRs and 95% confidence intervals (CI) representing the associations of five weight change categories [within <5% (reference); 5%-<10% and >= 10% loss and gain] with mortality were estimated using Cox proportional hazards models. Results: Mean weight change was 1.6 kg. About 14.7% women lost and 34.7% gained weight. Weight stability in the early years postdiagnosis was associated with the lowest overall mortality risk. Weight loss >= 10% was related to a 40% increased risk of death (HR, 1.41; 95% CI, 1.14-1.75) in the United States and over three times the risk of death (HR, 3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by prediagnosis BMI, and in the United States, lower survival was seen for women who lost weight and had comorbid conditions. Weight gain >= 10% was associated with a nonsignificant increased risk of death. Conclusions: Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. Impact: Weight control strategies for breast cancer survivors should be personalized to the individual's medical history. Cancer Epidemiol Biomarkers Prey; 21(8); 1260-71. (c) 2012 AACR. C1 [Caan, Bette J.; Kwan, Marilyn L.; Kroenke, Candyce H.; Weltzien, Erin K.; Quesenberry, Charles P., Jr.] Kasier Permanente, Div Res, Oakland, CA 94612 USA. [Shu, Xiao Ou; Nechuta, Sarah J.] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA. [Pierce, John P.; Patterson, Ruth E.; Flatt, Shirley W.] Univ Calif San Diego, Moores UCSD Canc Ctr, Canc Prevent & Control Program, San Diego, CA 92103 USA. [Poole, Elizabeth M.; Holmes, Michelle D.; Chen, Wendy Y.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Poole, Elizabeth M.; Holmes, Michelle D.; Chen, Wendy Y.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Caan, BJ (reprint author), Kasier Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM bette.caan@kp.org FU NIH grants [3R01CA118229-03S1, R01 CA118229, R01 CA 129059, P01 CA87969]; Susan G. Komen Foundation [KG100988]; Department of Defense [DAMD 17-02-1-0607] FX This work was supported by the NIH grants (3R01CA118229-03S1, R01 CA118229, R01 CA 129059, P01 CA87969); Susan G. Komen Foundation (KG100988); and the Department of Defense (DAMD 17-02-1-0607). NR 66 TC 33 Z9 33 U1 0 U2 12 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 AUG PY 2012 VL 21 IS 8 BP 1260 EP 1271 DI 10.1158/1055-9965.EPI-12-0306 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 987RC UT WOS:000307433800004 PM 22695738 ER PT J AU Ding, YC McGuffog, L Healey, S Friedman, E Laitman, Y Shani-Paluch-Shimon Kaufman, B Liljegren, A Lindblom, A Olsson, H Kristoffersson, U Stenmark-Askmalm, M Melin, B Domchek, SM Nathanson, KL Rebbeck, TR Jakubowska, A Lubinski, J Jaworska, K Durda, K Gronwald, J Huzarski, T Cybulski, C Byrski, T Osorio, A Cajal, TR Stavropoulou, AV Benitez, J Hamann, U Rookus, M Aalfs, CM de Lange, JL Meijers-Heijboer, HEJ Oosterwijk, JC van Asperen, CJ Garcia, EBG Hoogerbrugge, N Jager, A van der Luijt, RB Easton, DF Peock, S Frost, D Ellis, SD Platte, R Fineberg, E Evans, DG Lalloo, F Izatt, L Eeles, R Adlard, J Davidson, R Eccles, D Cole, T Cook, J Brewer, C Tischkowitz, M Godwin, AK Pathak, H Stoppa-Lyonnet, D Sinilnikova, OM Mazoyer, S Barjhoux, L Leone, M Gauthier-Villars, M Caux-Moncoutier, V de Pauw, A Hardouin, A Berthet, P Dreyfus, H Ferrer, SF Collonge-Rame, MA Sokolowska, J Buys, S Daly, M Miron, A Terry, MB Chung, W John, EM Southey, M Goldgar, D Singer, CF Tea, MKM Gschwantler-Kaulich, D Fink-Retter, A Hansen, TVO Ejlertsen, B Johannsson, OT Offit, K Sarrel, K Gaudet, MM Vijai, J Robson, M Piedmonte, MR Andrews, L Cohn, D DeMars, LR DiSilvestro, P Rodriguez, G Toland, AE Montagna, M Agata, S Imyanitov, E Isaacs, C Janavicius, R Lazaro, C Blanco, I Ramus, SJ Sucheston, L Karlan, BY Gross, J Ganz, PA Beattie, MS Schmutzler, RK Wappenschmidt, B Meindl, A Arnold, N Niederacher, D Preisler-Adams, S Gadzicki, D Varon-Mateeva, R Deissler, H Gehrig, A Sutter, C Kast, K Nevanlinna, H Aittomaki, K Simard, J Spurdle, AB Beesley, J Chen, XQ Tomlinson, GE Weitzel, J Garber, JE Olopade, OI Rubinstein, WS Tung, N Blum, JL Narod, SA Brummel, S Gillen, DL Lindor, N Fredericksen, Z Pankratz, VS Couch, FJ Radice, P Peterlongo, P Greene, MH Loud, JT Mai, PL Andrulis, IL Glendon, G Ozcelik, H Gerdes, AM Thomassen, M Jensen, UB Skytte, AB Caligo, MA Lee, A Chenevix-Trench, G Antoniou, AC Neuhausen, SL AF Ding, Yuan C. McGuffog, Lesley Healey, Sue Friedman, Eitan Laitman, Yael Shani-Paluch-Shimon Kaufman, Bella Liljegren, Annelie Lindblom, Annika Olsson, Hakan Kristoffersson, Ulf Stenmark-Askmalm, Marie Melin, Beatrice Domchek, Susan M. Nathanson, Katherine L. Rebbeck, Timothy R. Jakubowska, Anna Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Gronwald, Jacek Huzarski, Tomasz Cybulski, Cezary Byrski, Tomasz Osorio, Ana Ramony Cajal, Teresa Stavropoulou, Alexandra V. Benitez, Javier Hamann, Ute Rookus, Matti Aalfs, Cora M. de Lange, Judith L. Meijers-Heijboer, Hanne E. J. Oosterwijk, Jan C. van Asperen, Christi J. Garcia, Encarna B. Gomez Hoogerbrugge, Nicoline Jager, Agnes van der Luijt, Rob B. Easton, Douglas F. Peock, Susan Frost, Debra Ellis, Steve D. Platte, Radka Fineberg, Elena Evans, D. Gareth Lalloo, Fiona Izatt, Louise Eeles, Ros Adlard, Julian Davidson, Rosemarie Eccles, Diana Cole, Trevor Cook, Jackie Brewer, Carole Tischkowitz, Marc Godwin, Andrew K. Pathak, Harsh Stoppa-Lyonnet, Dominique Sinilnikova, Olga M. Mazoyer, Sylvie Barjhoux, Laure Leone, Melanie Gauthier-Villars, Marion Caux-Moncoutier, Virginie de Pauw, Antoine Hardouin, Agnes Berthet, Pascaline Dreyfus, Helene Ferrer, Sandra Fert Collonge-Rame, Marie-Agnes Sokolowska, Johanna Buys, Saundra Daly, Mary Miron, Alex Terry, Mary Beth Chung, Wendy John, Esther M. Southey, Melissa Goldgar, David Singer, Christian F. Tea, Muy-Kheng Maria Gschwantler-Kaulich, Daphne Fink-Retter, Anneliese Hansen, Thomas V. O. Ejlertsen, Bent Johannsson, Oskar T. Offit, Kenneth Sarrel, Kara Gaudet, Mia M. Vijai, Joseph Robson, Mark Piedmonte, Marion R. Andrews, Lesley Cohn, David DeMars, Leslie R. DiSilvestro, Paul Rodriguez, Gustavo Toland, Amanda Ewart Montagna, Marco Agata, Simona Imyanitov, Evgeny Isaacs, Claudine Janavicius, Ramunas Lazaro, Conxi Blanco, Ignacio Ramus, Susan J. Sucheston, Lara Karlan, Beth Y. Gross, Jenny Ganz, Patricia A. Beattie, Mary S. Schmutzler, Rita K. Wappenschmidt, Barbara Meindl, Alfons Arnold, Norbert Niederacher, Dieter Preisler-Adams, Sabine Gadzicki, Dorotehea Varon-Mateeva, Raymonda Deissler, Helmut Gehrig, Andrea Sutter, Christian Kast, Karin Nevanlinna, Heli Aittomaki, Kristiina Simard, Jacques Spurdle, Amanda B. Beesley, Jonathan Chen, Xiaoqing Tomlinson, Gail E. Weitzel, Jeffrey Garber, Judy E. Olopade, Olufunmilayo I. Rubinstein, Wendy S. Tung, Nadine Blum, Joanne L. Narod, Steven A. Brummel, Sean Gillen, Daniel L. Lindor, Noralane Fredericksen, Zachary Pankratz, Vernon S. Couch, Fergus J. Radice, Paolo Peterlongo, Paolo Greene, Mark H. Loud, Jennifer T. Mai, Phuong L. Andrulis, Irene L. Glendon, Gord Ozcelik, Hilmi Gerdes, Anne-Marie Thomassen, Mads Jensen, Uffe Birk Skytte, Anne-Bine Caligo, Maria A. Lee, Andrew Chenevix-Trench, Georgia Antoniou, Antonis C. Neuhausen, Susan L. CA SWE-BRCA HEBON EMBRACE GEMO Study Collaborators KConFab Investigators OCGN Consortium Investigators Modifiers TI A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AMINO-ACID POLYMORPHISM; GROWTH-FACTOR-I; GENETIC-VARIATION; INSULIN; RECEPTOR; EXPRESSION; IGF; NEOPLASIA; PROTEINS; FAMILY AB Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P-difference, 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03). Conclusion: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers. Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(8); 1362-70. (C)2012 AACR. C1 [McGuffog, Lesley; Lee, Andrew; Antoniou, Antonis C.] Univ Cambridge Worts Causeway, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England. [Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Tischkowitz, Marc] Univ Cambridge, Dept Med Genet, Cambridge, England. [Healey, Sue; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Royal Brisbane Hosp, Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4029, Australia. [Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon; Kaufman, Bella] Chaim Sheba Med Ctr, Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon; Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon; Kaufman, Bella] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Liljegren, Annelie] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Lindblom, Annika] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Olsson, Hakan] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Kristoffersson, Ulf] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. [Stenmark-Askmalm, Marie] Linkoping Univ, Dept Clin & Expt Med, Div Clin Genet, Linkoping, Sweden. [Melin, Beatrice] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Daly, Mary] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Spanish Network Rare Dis CIBERER, Barcelona, Spain. [Ramony Cajal, Teresa] Hosp Santa Creu & Sant Pau, Oncol Serv, Barcelona, Spain. [Lazaro, Conxi] Inst Catala Oncol, Lab Recerca Translac, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain. [Blanco, Ignacio] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain. [Stavropoulou, Alexandra V.] Natl Ctr Sci Res Demokritos, IRRP, Mol Diagnost Lab, Athens, Greece. [Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. [Rookus, Matti; de Lange, Judith L.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, London SW3 6JB, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, London, England. [Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Eccles, Diana] Univ Hosp Southampton NHS Fdn Trust, Wessex Clin Genet Serv, Southampton, Hants, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England. [Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Godwin, Andrew K.; Pathak, Harsh] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Stoppa-Lyonnet, Dominique; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine] Inst Curie, Dept Tumour Biol, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, Unite INSERM U830, Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Paris, France. [Dreyfus, Helene] CHU Grenoble, Dept Genet, F-38043 Grenoble, France. [Dreyfus, Helene] Univ Grenoble, Inst Albert Bonniot, Grenoble, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure] Univ Lyon 1, CNRS, UMR5286, Ctr Rech Cancerol Lyon,INSERM,U1052, F-69365 Lyon, France. [Sinilnikova, Olga M.; Leone, Melanie] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Collonge-Rame, Marie-Agnes] CHU Besancon, Serv Genet Biol Histol Biol Dev & Reprod, F-25030 Besancon, France. [Sokolowska, Johanna] Nancy Univ, Ctr Hosp Reg & Univ, Med Genet Lab, Vandoeuvre Les Nancy, France. [Hardouin, Agnes; Berthet, Pascaline] Ctr Francois Baclesse, F-14021 Caen, France. [Buys, Saundra] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA. [Goldgar, David] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [Miron, Alex] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Garber, Judy E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Brummel, Sean] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Terry, Mary Beth; Chung, Wendy] Columbia Univ, Dept Epidemiol, New York, NY USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [John, Esther M.] Stanford Canc Inst, Palo Alto, CA USA. [Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia. [Singer, Christian F.; Tea, Muy-Kheng Maria; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese] Med Univ Vienna, Dept OB GYN, Vienna, Austria. [Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark. [Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark. [Johannsson, Oskar T.] Landspitali Univ Hosp, Dept Oncol, Reykjavik, Iceland. [Johannsson, Oskar T.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Offit, Kenneth; Sarrel, Kara; Vijai, Joseph] Clin Canc Genet Lab, Buffalo, NY USA. [Robson, Mark] Mem Sloan Kettering Canc Ctr, Buffalo, NY USA. [Piedmonte, Marion R.] Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Ding, Yuan C.; Weitzel, Jeffrey; Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Ferrer, Sandra Fert] Hotel Dieu Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Andrews, Lesley] Australia New Zealand Gynaecol Oncol Grp, Camperdown, NSW, Australia. [Cohn, David] Ohio State Univ, Columbus Canc Council, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Dept Internal Med, OSU Comprehens Canc Ctr, Div Human Canc Genet, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, OSU Comprehens Canc Ctr, Dept Mol Virol Immunol & Med Genet, Div Human Canc Genet, Columbus, OH 43210 USA. [DeMars, Leslie R.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [DiSilvestro, Paul] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Rodriguez, Gustavo] NorthShore Univ Hlth Syst, Evanston, IL USA. [Montagna, Marco; Agata, Simona] Ist Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny] NN Petrov Oncol Res Inst, St Petersburg, Russia. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Janavicius, Ramunas] Vilnius Univ Hosp, Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Vilnius, Lithuania. [Ramus, Susan J.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Karlan, Beth Y.; Gross, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, CIO, Cologne, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Obstet & Gynaecol, D-8000 Munich, Germany. [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Obstet & Gynaecol, D-40225 Dusseldorf, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany. [Gadzicki, Dorotehea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany. [Varon-Mateeva, Raymonda] Charite, Campus Virchov Klinikum, Inst Human Genet, Berlin, Germany. [Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Gehrig, Andrea] Univ Wurzburg, Inst Human Genet, Dept Med Genet, Ctr Familial Breast & Ovarian Canc, D-8700 Wurzburg, Germany. [Sutter, Christian] Univ Heidelberg Hosp, Dept Human Genet, Inst Human Genet, Heidelberg, Germany. [Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Obstet & Gynaecol, D-01062 Dresden, Germany. [Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Nevanlinna, Heli] Univ Helsinki, Dept Clin Genet, Helsinki, Finland. Univ Helsinki, Cent Hosp, Helsinki, Finland. [Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Canada Res Chair Oncogenet, Quebec City, PQ, Canada. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [KConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Melbourne, Vic, Australia. [Tomlinson, Gail E.] Univ Texas Hlth Sci Ctr San Antonio, Div Pediat Hematol Oncol, San Antonio, TX 78229 USA. [Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Olopade, Olufunmilayo I.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Rubinstein, Wendy S.] NorthShore Univ HealthSyst, Evanston, IL USA. [Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Narod, Steven A.] Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. [OCGN] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Gillen, Daniel L.] Univ Calif Irvine, Dept Stat, Irvine, CA USA. [Gillen, Daniel L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Lindor, Noralane] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Fredericksen, Zachary; Pankratz, Vernon S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Expt Oncol & Mol Med, Unit Genet Susceptibil Canc, Milan, Italy. [Radice, Paolo; Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Jensen, Uffe Birk] Skejby Hosp, Dept Clin Genet, Aarhus, Denmark. [Skytte, Anne-Bine] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Caligo, Maria A.] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy. [Caligo, Maria A.] Univ Hosp Pisa, Pisa, Italy. [Oosterwijk, Jan C.] Univ Groningen, Univ Med Ctr, Dept Genet, Groningen, Netherlands. [van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands. [Garcia, Encarna B. Gomez] MUMC, Sch Oncol & Dev Biol, Dept Clin Genet, Maastricht, Netherlands. [Garcia, Encarna B. Gomez] MUMC, Sch Oncol & Dev Biol, GROW, Maastricht, Netherlands. [Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, Hereditary Canc Clin, NL-6525 ED Nijmegen, Netherlands. [Jager, Agnes] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [van der Luijt, Rob B.; HEBON] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. RP Neuhausen, SL (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM sneuhausen@coh.org RI Arnold, Norbert/E-3012-2010; Gronwald, Jacek/A-4576-2017; montagna, marco/E-2225-2012; Andrulis, Irene/E-7267-2013; Toland, Amanda/E-4202-2011; Joseph, Vijai/J-9158-2013; Hoogerbrugge, Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013; Oosterwijk, Jan C./G-5770-2011; Osorio, Ana/I-4324-2014; Jakubowska, Anna/O-8050-2014; Spurdle, Amanda/A-4978-2011; OI Arnold, Norbert/0000-0003-4523-8808; Gronwald, Jacek/0000-0002-3643-2871; Janavicius, Ramunas/0000-0002-3773-8485; montagna, marco/0000-0002-4929-2150; Joseph, Vijai/0000-0002-7933-151X; Blanco, Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984; Robson, Mark/0000-0002-3109-1692; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Ramus, Susan/0000-0003-0005-7798; Spurdle, Amanda/0000-0003-1337-7897; Nevanlinna, Heli/0000-0002-0916-2976; Evans, Gareth/0000-0002-8482-5784 FU NIH [R01CA74415, P30CA033752]; Israel cancer association; Mutua Madrilena Foundation; Red de Investigacion en Cancer [RD06/0020/1160]; Spanish Ministry of Science and Innovation [FIS P1081120, SAF2010-20493]; Cancer Research UK [C1287/A10118, C1287/A11990, C5047/A8385]; NIHR; NEYE Foundation; Clinical Genetics Branch, DCEG National Cancer Institute (NCI); Community Oncology and Prevention Trials Program-COPTRG National Cancer Institute (NCI); Russian Foundation for Basic Research [10-04-92110, 10-04-92601, 11-04-00227]; Federal Agency for Science and Innovations [02.740.11.0780]; Royal Society [JP090615]; Research Council of Lithuania [LIG-19/2010]; Institut Catala d'Oncologia (ICO); Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute; Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, 2009SGR290]; American Cancer Society [120950-SIOP-06-258-06-COUN]; German Cancer Aid [DKH 109076]; Helsinki University Central Hospital; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Canadian Institutes of Health Research; Canadian Breast Cancer Research Alliance [019511]; NCI, under RFA [CA-06-503]; Cancer Care Ontario [U01 CA69467]; Cancer Prevention Institute of California [U01 CA69417]; Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer Institute [U01 CA69446]; University of Melbourne [U01 CA69638]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; NITA [P01 CA16094, R01 CA22435]; National Institutes of Health [P30 CA13696, P30 ES009089, UL1 RR025764, R01278978]; National Center for Research Resources; National Center for Advancing Translational Sciences; NCI [P30 CA042014]; NHMRC [145684, 288704, 454508]; US NCI at the NIH [NO2-CP-11019-50, N02-CP-65504]; Westat, Inc.; Breast cancer Research Foundation; Komen Foundation for the Cure; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; ZonMW [91109024]; OSU Comprehensive Cancer Center; [R01-CA083855]; [R01-CA102776]; [R01CA140323]; [U01CA69631]; [5U01CA113916] FX Beckman Research Institute of the City of Hope (BRICOH) study was supported by NIH R01CA74415 (S.L. Neuhausen) and P30CA033752. S.L. Neuhausen is the Morris and Horowitz Families Endowed Professor. Sheba Medical Center Study (SMC) was in part sponsored by a grant from the Israel cancer association to E. Friedman on behalf of the Israeli consortium of inherited breast cancer. University of Pennsylvania (UPENN) study was supported by R01-CA083855 and R01-CA102776 (T. R. Rebbeck). Spanish National Cancer Center (CNIO) study has been partially funded by Mutua Madrilena Foundation, "Red de Investigacion en Cancer RD06/0020/1160", and Spanish Ministry of Science and Innovation (FIS P1081120 and SAF2010-20493). Epidemiologic study of BRCA1 and BRCA2 mutation carriers (EMBRACE) is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D.G. Evans and F. Lalloo are supported by an NIHR grant to the Biomedical Research Centre (Manchester, UK). The Investigators at The Institute of Cancer Research and The Royal Marsden NMS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R. Eeles and E. B. Gomez Garcia are supported by Cancer Research UK Grant C5047/A8385. Fox Chase Cancer Center (FCCC) study was supported by R01CA140323, U01CA69631, and 5U01CA113916 (to A.K. Godwin). Copenhagen Breast Cancer Study (CBCS) was supported by the NEYE Foundation. Gynecologic Oncology Group (COG) was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program-COPTRG) National Cancer Institute (NCI) programs, and was based in GOG's Cancer Prevention and Control Committee. N.N. Petrov Institute of Oncology (NNPIO) study is supported by the Russian Foundation for Basic Research (grants 10-04-92110, 10-04-92601, and 11-04-00227), the Federal Agency for Science and Innovations (contract 02.740.11.0780), and through a Royal Society International Joint Grant (JP090615). The Baltic Familial Breast and Ovarian Cancer Consortium (BFBOCC, Latvia and Lithuania) study is supported by the Research Council of Lithuania grant LIG-19/2010 to R.J. Institut Catala d'Oncologia (ICO); Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute, and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. UK and Gilds Radner Familial Ovarian Cancer Registries (UKGRFOCR) study was supported by a project grant from CRUK (to P. Peterlongo). Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute (WCP) is supported by American Cancer Society (120950-SIOP-06-258-06-COUN). The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) was supported by a grant of the German Cancer Aid (DKH 109076). Helsinki Breast Cancer Study (HEBCS) was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. Interdisciplinary Health Research International Team Breast Cancer Susceptibility (INHERIT BRCAs) was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511.; The Breast Cancer Family Registry (BCFR) was supported by the NCI, under RFA # CA-06-503, and through cooperative agreements with members of the BCFR and principal investigators, including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute of California (U01 CA69417), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), and University of Melbourne (U01 CA69638). The Australian BCFR was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia), and the Victorian Breast Cancer Research Consortium. M.C. Southey is an NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. J.L. Hopper is an Australia Fellow of the NHMRC and a Victorian Breast Cancer Research Consortium Group Leader. Carriers at FCCC were also identified with support from the NITA grants P01 CA16094 and R01 CA22435. The New York BCFR was also supported by National Institutes of Health grants P30 CA13696 and P30 ES009089. The Utah BCFR was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Grant UL1 RR025764, and by Award Number P30 CA042014 from the NCI. Kathleen Cuningham Consortium for Research into Familial Breast Cancer (KCONFAB) is funded by NHMRC grants 145684, 288704, and 454508. A.B. Spurdle is supported by an NHMRC Senior Research Fellowship, and G-CT by an NHMRC Senior Principal Research Fellowship. National Cancer Institute (NCI): P.L. Mai, J.T. Loud, and M.H. Greene were funded by the Intramural Research Program of the US NCI at the NIH with infrastructure support from contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. Mayo Clinic Study (MAYO) was supported by NIH R01278978 and grants from the Breast cancer Research Foundation and the Komen Foundation for the Cure. The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, and the ZonMW grant 91109024. OSU CCG: This work was funded by the OSU Comprehensive Cancer Center. NR 31 TC 9 Z9 9 U1 2 U2 14 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 AUG PY 2012 VL 21 IS 8 BP 1362 EP 1370 DI 10.1158/1055-9965.EPI-12-0229 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 987RC UT WOS:000307433800016 PM 22729394 ER PT J AU Hess, DR Branson, RD AF Hess, Dean R. Branson, Richard D. TI Know Your Ventilator to Beat the Leak SO CHEST LA English DT Editorial Material ID NONINVASIVE VENTILATION; ICU VENTILATORS; HOSPITALS; MODEL C1 [Hess, Dean R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Branson, Richard D.] Univ Cincinnati, Cincinnati, OH 45221 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 14 TC 6 Z9 6 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2012 VL 142 IS 2 BP 274 EP 275 DI 10.1378/chest.12-0489 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 987LJ UT WOS:000307418200002 PM 22871746 ER PT J AU Harbst, K Staaf, J Lauss, M Karlsson, A Masback, A Johansson, I Bendahl, PO Vallon-Christersson, J Torngren, T Ekedahl, H Geisler, J Hoglund, M Ringner, M Lundgren, L Jirstrom, K Olsson, H Ingvar, C Borg, A Tsao, H Jonsson, G AF Harbst, Katja Staaf, Johan Lauss, Martin Karlsson, Anna Masback, Anna Johansson, Iva Bendahl, Par-Ola Vallon-Christersson, Johan Torngren, Therese Ekedahl, Henrik Geisler, Jurgen Hoglund, Markus Ringner, Mattias Lundgren, Lotta Jirstrom, Karin Olsson, Hakan Ingvar, Christian Borg, Ake Tsao, Hensin Jonsson, Goran TI Molecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; PRIMARY CUTANEOUS MELANOMA; GENE-EXPRESSION; PROGNOSTIC-SIGNIFICANCE; MALIGNANT-MELANOMA; SURVIVAL; FEATURES; MITF AB Purpose: For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome. Experimental Design: We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data. Results: Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets. Conclusions: We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease. Clin Cancer Res; 18(15); 4026-36. (C)2012 AACR. C1 [Harbst, Katja; Staaf, Johan; Lauss, Martin; Karlsson, Anna; Bendahl, Par-Ola; Vallon-Christersson, Johan; Torngren, Therese; Ekedahl, Henrik; Hoglund, Markus; Ringner, Mattias; Lundgren, Lotta; Olsson, Hakan; Borg, Ake; Jonsson, Goran] Lund Univ, Dept Oncol, S-22185 Lund, Sweden. [Harbst, Katja; Staaf, Johan; Lauss, Martin; Vallon-Christersson, Johan; Hoglund, Markus; Ringner, Mattias; Borg, Ake; Jonsson, Goran] Lund Univ, CRE ATE Hlth Strateg Ctr Clin Canc Res, S-22185 Lund, Sweden. [Masback, Anna; Johansson, Iva; Jirstrom, Karin] Lund Univ, Dept Pathol, S-22185 Lund, Sweden. [Ingvar, Christian] Lund Univ, Dept Surg, S-22185 Lund, Sweden. [Geisler, Jurgen] Univ Oslo, Akershus Univ Hosp, Dept Oncol, N-0316 Oslo, Norway. [Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Jonsson, G (reprint author), Lund Univ, Dept Oncol, S-22185 Lund, Sweden. EM htsao@partners.org; goran_b.jonsson@med.lu.se RI Ringner, Markus/G-3641-2011; Jonsson, Goran/D-1212-2014 OI Vallon-Christersson, Johan/0000-0002-2195-0385; Hoglund, Mattias/0000-0001-9283-4421; Ringner, Markus/0000-0001-5469-8940; FU Swedish Cancer Society; Crafoord Foundation; Mrs. Berta Kamprad Foundation; Gunnar Nilsson Cancer Foundation; Lund University Hospital Research Funds; Lund University Medical Faculty/ALF, BioCare; Gustav Vth Jubilee Foundation; U.S. NIH [K24 CA149202, P50 CA93683] FX This work was supported by the Swedish Cancer Society, the Crafoord Foundation, the Mrs. Berta Kamprad Foundation, the Gunnar Nilsson Cancer Foundation, the Lund University Hospital Research Funds, Lund University Medical Faculty/ALF, BioCare, and the Gustav Vth Jubilee Foundation. This activity was also supported in part by the U.S. NIH (K24 CA149202 and P50 CA93683) and by the generous donors to the MGH Millennium Melanoma Fund. NR 22 TC 37 Z9 37 U1 0 U2 2 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 AUG 1 PY 2012 VL 18 IS 15 BP 4026 EP 4036 DI 10.1158/1078-0432.CCR-12-0343 PG 11 WC Oncology SC Oncology GA 988PS UT WOS:000307503600005 PM 22675174 ER PT J AU Smits, M van Rijn, S Hulleman, E Biesmans, D van Vuurden, DG Kool, M Haberler, C Aronica, E Vandertop, WP Noske, DP Wurdinger, T AF Smits, Michiel van Rijn, Sjoerd Hulleman, Esther Biesmans, Dennis van Vuurden, Dannis G. Kool, Marcel Haberler, Christine Aronica, Eleonora Vandertop, W. Peter Noske, David P. Wuerdinger, Thomas TI EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival SO CLINICAL CANCER RESEARCH LA English DT Article ID ABERRANT PROMOTER METHYLATION; PROTEIN HDAB2IP GENE; GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; MOUSE MODEL; SPORADIC MEDULLOBLASTOMAS; DOWN-REGULATION; CELL-LINES; DE-NOVO; EXPRESSION AB Purpose: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches. Experimental Design: Here, we conducted a meta-analysis of mouse and human medulloblastoma gene expression data sets, to identify potential medulloblastoma tumor suppressor genes. Results: We identified DAB2IP, a member of the RAS-GTPase-activating protein family (RAS GAP), and showed that DAB2IP expression is repressed in medulloblastoma by EZH2-induced trimethylation. Moreover, we observed that reduced DAB2IP expression correlates significantly with a poor overall survival of patients with medulloblastoma, independent of metastatic stage. Finally, we showed that ectopic DAB2IP expression enhances stress-induced apoptosis in medulloblastoma cells and that reduced expression of DAB2IP in medulloblastoma cells conveys resistance to irradiation-induced cell death. Conclusion: These results suggest that repression of DAB2IP may at least partly protect medulloblastoma cells from apoptotic cell death. Moreover, DAB2IP may represent a molecular marker to distinguish patients with medulloblastoma at high risk from those with a longer survival prognosis. Clin Cancer Res; 18(15); 4048-58. (C)2012 AACR. C1 [Smits, Michiel; van Rijn, Sjoerd; Hulleman, Esther; Biesmans, Dennis; van Vuurden, Dannis G.; Vandertop, W. Peter; Noske, David P.; Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp,Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands. [Smits, Michiel; van Rijn, Sjoerd; Hulleman, Esther; Biesmans, Dennis; van Vuurden, Dannis G.; Vandertop, W. Peter; Noske, David P.; Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Dept Pediat Oncol Hematol, NL-1081 HV Amsterdam, Netherlands. [Aronica, Eleonora] Univ Amsterdam, Acad Med Ctr, Dept Neuropathol, NL-1105 AZ Amsterdam, Netherlands. [Vandertop, W. Peter] Univ Amsterdam, Acad Med Ctr, Neurosurg Ctr Amsterdam, NL-1105 AZ Amsterdam, Netherlands. [Kool, Marcel] German Canc Res Ctr, Dept Mol Genet, Heidelberg, Germany. [Haberler, Christine] Inst Curie, Lab Genet & Biol Canc, Paris, France. [Wuerdinger, Thomas] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Mol Neurogenet Unit, Boston, MA 02115 USA. [Wuerdinger, Thomas] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wuerdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp,Dept Neurosurg, CCA Room 3-60,De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM t.wurdinger@vumc.nl RI Kool, Marcel/H-2541-2013; OI Van Vuurden, Dannis/0000-0002-1364-9007 NR 57 TC 22 Z9 24 U1 0 U2 2 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 AUG 1 PY 2012 VL 18 IS 15 BP 4048 EP 4058 DI 10.1158/1078-0432.CCR-12-0399 PG 11 WC Oncology SC Oncology GA 988PS UT WOS:000307503600007 PM 22696229 ER PT J AU Cantu-Brito, C Chiquete, E Ruiz-Sandoval, JL Gaxiola, E Albuquerque, DC Corbalan, R Ramos, A Bhatt, DL Steg, PG AF Cantu-Brito, Carlos Chiquete, Erwin Ruiz-Sandoval, Jose L. Gaxiola, Efrain Albuquerque, Denilson C. Corbalan, Ramon Ramos, Alma Bhatt, Deepak L. Steg, P. Gabriel CA REACH Latin Amer Collaborative Grp TI Atherothrombotic Disease, Traditional Risk Factors, and 4-Year Mortality in a Latin American Population: The REACH Registry SO CLINICAL CARDIOLOGY LA English DT Article ID CARDIOVASCULAR EVENT RATES; PERIPHERAL ARTERY-DISEASE; ACUTE ISCHEMIC-STROKE; BODY-MASS INDEX; OBESITY PARADOX; MYOCARDIAL-INFARCTION; VASCULAR-DISEASE; HEART-FAILURE; FOLLOW-UP; OUTPATIENTS AB Background: Atherothrombosis is becoming the leading cause of chronic morbidity in developing countries. This epidemiological transition will represent an unbearable socioeconomic burden in the near future. We investigated factors associated with 4-year all-cause mortality in a Latin American population at high risk. Hypothesis: Largely modifiable risk factors as well as polyvascular disease are the main predictors of 4-year all-cause and cardiovascular mortality in this Latin American cohort. Methods: We analyzed 1816 Latin American stable outpatients (62.3% men, mean age 67 years) with symptomatic atherothrombosis (87.1%) or with multiple risk factors only (12.9%), in the Reduction of Atherothrombosis for Continued Health registry. Results: Of patients with symptomatic atherothrombosis, 57.3% had coronary artery disease, 32% cerebrovascular disease, and 11.7% peripheral artery disease at baseline (9.1% polyvascular). The main risk factors were hypertension (76%), hypercholesterolemia (60%), and smoking (52.3%) in patients with established atherothrombosis; and hypertension (89.7%), diabetes (80.8%), and hypercholesterolemia (73.9%) in those with risk factors only. Four-year all-cause mortality steeply increased with none (6.8%), 1 (9.2%), 2 (15.5%), and 3 (29.2%) symptomatic arterial disease locations. In patients with only 1 location, cardiovascular mortality was significantly higher with peripheral artery disease (11.3%) than with cerebrovascular disease (6%) or coronary artery disease (5.1%). Significant baseline predictors of 4-year all-cause mortality were congestive heart failure (hazard ratio [HR]: 3.81), body mass index <20 (HR: 2.32), hypertension (HR: 1.84), polyvascular disease (HR: 1.69), and age =65 years (HR: 1.47), whereas statin use (HR: 0.49) and body mass index =30 (HR: 0.58) were associated with a reduced risk. Conclusions: Hypertension was the main modifiable risk factor for atherothrombosis and all-cause mortality in this Latin American cohort. Nearly one-third of the population with 3 symptomatic vascular-disease locations died at 4-year follow-up. The REACH registry is sponsored by sanofi, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH registry is endorsed by the World Heart Federation. The REACH registry enforces a no-ghostwriting policy. This manuscript was written and edited by the authors, who take full responsibility for its content. Dr. Cantu-Brito and Dr. Chiquete wrote the first draft of this manuscript. Dr. Cantu-Brito has received research grants from sanofi, Ferrer Grupo and Bayer, as well as speaker honoraria from sanofi. Dr. Chiquete has received research grants from sanofi and Ferrer Grupo, as well as speaker honoraria from Novartis. Dr. Ruiz-Sandoval has received research grants from sanofi, Boehringer Ingelheim, and Ferrer Grupo. Dr. Gaxiola has received research grants from sanofi and Eli Lilly, as well as consultancy and speaker honoraria from Sanofi, Eli Lilly, Pfizer, AstraZeneca, and Abbott. Dr. Albuquerque has received research grants from sanofi, AstraZeneca, Servier, Roche, and BMS/Pfizer, as well as consultancy and speaker honoraria from sanofi and AstraZeneca. Dr. Corbalan has no relevant disclosures. Mrs. Ramos is an employee at sanofi, in the Clinical Research Department. Dr. Deepak L. Bhatt discloses the following relationships - 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); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: PLx Pharma, Takeda. Dr. Steg has received research grants from Servier; consultancy fees/honoraria from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo/Eli Lilly alliance, Eisai, GlaxoSmithKline, Medtronic, Merck Sharpe and Dohme, Pfizer, Roche, sanofi, Servier, and The Medicines Company; and has equity ownership in Aterovax. The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Cantu-Brito, Carlos] Salvador Zubiran Natl Inst Med Sci & Nutr, Dept Neurol & Psychiat, Mexico City, DF, Mexico. [Ruiz-Sandoval, Jose L.] Fray Antonio Alcalde Publ Hosp, Dept Neurol, Guadalajara, Jalisco, Mexico. [Gaxiola, Efrain] Jardines Specialty Hosp, Dept Cardiol, Zapopan, Jalisco, Mexico. [Albuquerque, Denilson C.] Univ Estado Rio De Janeiro, Hosp Pedro Ernesto, Dept Cardiol, Rio De Janeiro, Brazil. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Dept Cardiovasc Dis, Santiago, Chile. [Ramos, Alma] Dept Sci, Dept Clin Res, Sanofi, Mexico. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Cardiol, Boston, MA 02115 USA. [Steg, P. Gabriel] Univ Hosp N Paris Val Seine, Hop Bichat Claude Bernard, Paris, France. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Steg, P. Gabriel] Paris Diderot Univ, Paris, France. RP Cantu-Brito, C (reprint author), Salvador Zubiran Natl Inst Med Sci & Nutr, Dept Neurol & Psychiat, Mexico City, DF, Mexico. RI Pazin Filho, Antonio/E-9495-2010 OI Pazin Filho, Antonio/0000-0001-5242-329X FU sanofi; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Ferrer Grupo; Bayer; Boehringer Ingelheim; Eli Lilly; AstraZeneca; Servier; Roche; BMS/ Pfizer; Amarin; Eisai; Ethicon; Medtronic; Sanofi Aventis; Amgen; Astellas; GlaxoSmithKline; Merck Sharpe and Dohme; Daiichi Sankyo/ Eli Lilly alliance FX The REACH registry is sponsored by sanofi, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH registry is endorsed by the World Heart Federation. The REACH registry enforces a no-ghostwriting policy. This manuscript was written and edited by the authors, who take full responsibility for its content. Dr. Cantu-Brito and Dr. Chiquete wrote the first draft of this manuscript.; Dr. Cantu-Brito has received research grants from sanofi, Ferrer Grupo and Bayer, as well as speaker honoraria from sanofi. Dr. Chiquete has received research grants from sanofi and Ferrer Grupo, as well as speaker honoraria from Novartis. Dr. Ruiz-Sandoval has received research grants from sanofi, Boehringer Ingelheim, and Ferrer Grupo. Dr. Gaxiola has received research grants from sanofi and Eli Lilly, as well as consultancy and speaker honoraria from Sanofi, Eli Lilly, Pfizer, AstraZeneca, and Abbott. Dr. Albuquerque has received research grants from sanofi, AstraZeneca, Servier, Roche, and BMS/Pfizer, as well as consultancy and speaker honoraria from sanofi and AstraZeneca. Dr. Corbalan has no relevant disclosures. Mrs. Ramos is an employee at sanofi, in the Clinical Research Department. Dr. Deepak L. Bhatt discloses the following relationships-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); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: PLx Pharma, Takeda. Dr. Steg has received research grants from Servier; consultancy fees/honoraria from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo/Eli Lilly alliance, Eisai, GlaxoSmithKline, Medtronic, Merck Sharpe and Dohme, Pfizer, Roche, sanofi, Servier, and The Medicines Company; and has equity ownership in Aterovax. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 38 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD AUG PY 2012 VL 35 IS 8 BP 451 EP 457 DI 10.1002/clc.22005 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 983JV UT WOS:000307116500001 PM 22653654 ER PT J AU Hails, K Brill, CD Chang, T Yeung, A Fava, M Trinh, NH AF Hails, Katherine Brill, Charlotte D. Chang, Trina Yeung, Albert Fava, Maurizio Trinh, Nhi-Ha TI Cross-Cultural Aspects of Depression Management in Primary Care SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Major depressive disorder; Cross-cultural psychiatry; Primary care; Collaborative care; Interventions; Minority patients ID SENSITIVE COLLABORATIVE TREATMENT; RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; CHINESE-AMERICANS; UNITED-STATES; HEALTH; DISORDER; OUTCOMES; DISPARITIES; ADAPTATION AB Major depressive disorder (MDD) is a prevalent illness in minority populations. Minority patients with MDD are often unrecognized and untreated. This review examines promising interventions to address MDD in primary care settings, where minority groups are more likely to seek care. Since 2010, eleven interventions have been developed to address patient-specific and provider-specific barriers, many of which are adaptations of the collaborative care model. Other promising interventions include cultural tailoring of the collaborative care model, as well as the addition of telepsychiatry, motivational interviewing, cultural consultation, and innovations in interpreting. Overall, collaborative care was found feasible and improved satisfaction and treatment engagement of depressed minority patients in primary care. It remains inconclusive whether these newer intervention models improve MDD treatment outcomes. Future research will be needed to establish the effectiveness of these intervention models in improving the treatment outcomes of minority populations with MDD. C1 [Hails, Katherine; Brill, Charlotte D.; Chang, Trina; Yeung, Albert; Fava, Maurizio; Trinh, Nhi-Ha] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Yeung, Albert] S Cove Community Hlth Ctr, Boston, MA 02111 USA. RP Hails, K (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM khails@partners.org FU AstraZeneca; CeNeRx BioPharma; Euthymics Bioscience; Forest Pharmaceuticals; GlaxoSmithKline; Johnson Johnson; Pfizer; Lippincott Williams Wilkins; Wolters Kluwer; World Scientific Publishing; MGH Cognitive and Physical Functioning Questionnaire (CPFQ); Sexual Functioning Inventory (SFI); Antidepressant Treatment Response Questionnaire (ATRQ); Discontinuation-Emergent Signs & Symptoms (DESS); SAFER; National Institute of Mental Health (NIMH); National Center for Complementary and Alternative Medicine (NCCAM); National Institutes of Health (NIH); NIDA; Bristol-Myers Squibb; Ganeden Biotech; Pamlab; Clinical Trials Solutions; Pfizer Forest; i3Research; Covance; Novartis; Roche; Sanofi-Aventis FX Dr. Chang has served as a consultant for OptumInsight; has received research support from AstraZeneca, CeNeRx BioPharma, Euthymics Bioscience, Forest Pharmaceuticals, GlaxoSmithKline, Johnson & Johnson, and Pfizer; and has received honoraria from and had travel/accommodations expenses covered/reimbursed by Bristol-Myers Squibb.; Dr. Fava has received equity holdings from Compellis; has received royalties from Lippincott Williams & Wilkins, Wolters Kluwer, and World Scientific Publishing; has received compensation for editing from Belvoir Media Group, Massachusetts General Hospital Psychiatry Academy, CME Institute/Physicians Postgraduate Press, and Association for Health Research & Development (ACINDES); has received honoraria from Eisai, Johnson & Johnson Pharmaceutical Research & Development, Lundbeck, Pfizer, and Servier Laboratories; has served as a board member of BrainCells, Bristol-Myers Squibb, Eisai, EnVivo Pharmaceuticals, Ganeden Biotech, Genomind, Johnson & Johnson, Lundbeck/Takeda, National Institute on Drug Abuse (NIDA), Neuronetics, PsychoGenics, Psylin Neurosciences, Schering-Plough, Transcept Pharmaceuticals; has received patents for Sequential Parallel Comparison Design (SPCD), a patent for research and licensing of SPCD with RCT Logic, a patent application for a combination of azapirones and bupropion in major depressive disorder (MDD), and copyright royalties for the MGH Cognitive and Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), and SAFER; has received research support from National Institute of Mental Health (NIMH), National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health (NIH), NIDA, Bristol-Myers Squibb, Ganeden Biotech, Johnson & Johnson, Pamlab, Clinical Trials Solutions, Pfizer Forest, CeNeRx BioPharma, i3Research, Euthymics Bioscience, Covance, GlaxoSmithKline, AstraZeneca, Novartis, Roche, and Sanofi-Aventis; and has served as a consultant for Abbott Laboratories, Affectis Pharmaceuticals, Alkermes, Amarin Pharma, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer, Best Practice Project Management, BioMarin Pharmaceutical, Biovail Corporation, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, CNS Response, Compellis Pharmaceuticals, Cypress Pharmaceutical, DiagnoSearch Life Sciences, Dainippon Sumitomo Pharma, DOV Pharmaceutical, Edgemont Pharmaceuticals, Eisai, Eli Lilly and Company, EnVivo Pharmaceuticals, ePharmaSolutions, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, Genomind, GlaxoSmithKline, Grunenthal, i3 Innovus/Ingenis, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Johnson & Johnson Pharmaceutical Research & Development, Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck & Co., MSI Methylation Sciences, Naurex; Neuronetics, NextWave Pharmaceuticals, Novartis, Nutrition 21, Orexigen Therapeutics, Organon Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Puretech Ventures, PsychoGenics, Psylin Neurosciences, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche, RCT Logic, Sanofi-Aventis, Sepracor, Servier Laboratories; Schering-Plough, Solvay Pharmaceuticals, Somaxon Pharmaceuticals, Somerset Pharmaceuticals, Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Synthelabo, Takeda, Tal Medical, Tetragenex Pharmaceuticals, TransForm Pharmaceuticals, Transcept Pharmaceuticals, Vanda Pharmaceuticals. NR 38 TC 5 Z9 5 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD AUG PY 2012 VL 14 IS 4 BP 336 EP 344 DI 10.1007/s11920-012-0276-9 PG 9 WC Psychiatry SC Psychiatry GA 985NR UT WOS:000307273900009 PM 22580834 ER PT J AU Izikson, L Helm, T Sroa, N Zeitouni, NC AF Izikson, Leonid Helm, Thomas Sroa, Novie Zeitouni, Nathalie C. TI Clinical Stage of Merkel Cell Carcinoma and Survival Are Not Associated with Breslow Thickness of Biopsied Tumor SO DERMATOLOGIC SURGERY LA English DT Article ID SINGLE INSTITUTION; SPECIMENS; SKIN AB Background Merkel cell carcinoma (MCC) is an aggressive malignancy that often presents on the skin with concurrent metastatic disease. Objective To determine whether Breslow thickness of biopsied MCC correlates with clinical disease stage. Materials and Methods We performed a retrospective review of clinical data and histopathology specimens from 34 individuals with MCC treated at the Roswell Park Cancer Institute for whom complete clinical information and histopathology specimens were available. Results There was no correlation between Breslow thickness of biopsied MCC on the head and neck or body and clinical stage of disease, progression-free survival, or overall survival. Hence, thin MCCs should not be taken to represent lesions with less-aggressive clinical behavior. Conclusion Our findings validate the current practice of staging all newly diagnosed MCC, irrespective of size or Breslow thickness. C1 [Sroa, Novie; Zeitouni, Nathalie C.] Roswell Pk Canc Inst, Dept Dermatol, Buffalo, NY 14263 USA. [Izikson, Leonid] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Helm, Thomas] SUNY Buffalo, Dept Dermatol, Buffalo, NY 14260 USA. RP Zeitouni, NC (reprint author), Roswell Pk Canc Inst, Dept Dermatol, Elm & Carlton St, Buffalo, NY 14263 USA. EM nathalie.zeitouni@roswellpark.org NR 12 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD AUG PY 2012 VL 38 IS 8 BP 1351 EP 1356 DI 10.1111/j.1524-4725.2012.02398.x PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 983KX UT WOS:000307119300014 PM 22455371 ER PT J AU Dalamaga, M Diakopoulos, KN Mantzoros, CS AF Dalamaga, Maria Diakopoulos, Kalliope N. Mantzoros, Christos S. TI The Role of Adiponectin in Cancer: A Review of Current Evidence SO ENDOCRINE REVIEWS LA English DT Review ID ACTIVATED PROTEIN-KINASE; HIGH-MOLECULAR-WEIGHT; RENAL-CELL CARCINOMA; CHRONIC HEPATITIS-C; NF-KAPPA-B; RANDOMIZED CONTROLLED-TRIAL; COMPLEMENT-RELATED PROTEIN; INDUCED INSULIN-RESISTANCE; CHRONIC MYELOID-LEUKEMIA; NECROSIS-FACTOR-ALPHA AB Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies. (Endocrine Reviews 33: 547-594, 2012) C1 [Diakopoulos, Kalliope N.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. [Mantzoros, Christos S.] VA Boston Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. [Dalamaga, Maria] Univ Athens, Sch Med, Lab Clin Biochem, Attikon Gen Univ Hosp, Athens 12462, Greece. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Internal Med, 330 Brookline Ave,FD-876, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu OI Diakopoulos, Kalliope/0000-0002-9236-0489; Dalamaga, Maria/0000-0002-7008-388X FU Beth Israel Deaconess Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases [DK058785, DK079929, DK081913]; National Institute on Aging [AG032030]; VA Merit Award; California Walnut Commission FX This work was supported by a discretionary grant from Beth Israel Deaconess Medical Center (to C. S. M.). The Mantzoros laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (Grants DK058785, DK079929, and DK081913), the National Institute on Aging (Grant AG032030), a VA Merit Award, and the California Walnut Commission. NR 434 TC 151 Z9 159 U1 3 U2 40 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD AUG PY 2012 VL 33 IS 4 BP 547 EP 594 DI 10.1210/er.2011-1015 PG 48 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987IA UT WOS:000307409200004 PM 22547160 ER PT J AU Xu, YH Cai, WL Nappi, J Yoshida, H AF Xu, Yonghua Cai, Wenli Nappi, Janne Yoshida, Hiro TI Fecal-tagging CT colonography with structure-analysis electronic cleansing for detection of colorectal flat lesions SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Colonography; Computed tomographic; Diagnosis; Electronic cleansing; Flat polyps ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; POLYPS; COLON AB Purpose: To evaluate the feasibility and sensitivity of the 3D-reading of fecal-tagging CT colonography (CTC) with a novel structure-analysis electronic cleansing (SAEC) in detecting colorectal flat lesions in comparison with a cleansed 3D reading with Viatronix V3D Colon system (V3D) and primary uncleansed 2D reading (2D). Materials and methods: Forty CTC cases with flat lesions were retrospectively observed. The Subjects from a multicenter clinical trial underwent cathartic bowel preparation with orally administrated barium-based fecal-tagging. Sixty-nine flat lesions were confirmed using colonoscopy and histopathology as a reference standard. The results from SAEC reading were compared with those of prospective V3D and 2D readings. Results: Overall detection sensitivity with SAEC was 52% (36/69), which was statistically higher than that of 32% (22/69) and 29% (20/69) with V3D and 2D readings, respectively (p < 0.05). The sensitivities in detecting not-on-fold flat lesions were 63% (24/38), 45% (17/38), and 42% (16/38) with SAEC, V3D, and 2D readings, respectively; whereas those of on-fold flat lesions were 39% (12/31), 16% (5/31), and 13% (4/31), respectively. None of the eight flat lesions (2-9 mm) at cecum was detected by any of the three reading methods. Excluding the flat lesions at cecum, the sensitivity with SAEC for detecting flat lesion >= 4 mm increased to 84% (31/37). Conclusions: The fecal-tagging CTC with structure-analysis electronic cleansing could yield a high sensitivity for detecting flat lesions >= 4 mm. The not-on-fold flat lesions were detected with higher sensitivity than on-fold flat lesions. (c) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Xu, Yonghua] Xuhui Cent Hosp Shanghai, Dept Radiol, Shanghai 200031, Peoples R China. [Xu, Yonghua] Chinese Acad Sci, Shanghai Med Ctr, Shanghai 200031, Peoples R China. [Xu, Yonghua] Chongqing Med Univ, Dept Biomed Engn, Chongqing 400016, Peoples R China. [Cai, Wenli; Nappi, Janne; Yoshida, Hiro] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli; Nappi, Janne; Yoshida, Hiro] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Xu, YH (reprint author), Xuhui Cent Hosp Shanghai, Dept Radiol, 966 Huai Hai Cent Rd, Shanghai 200031, Peoples R China. EM howardyonghua@gmail.com NR 15 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD AUG PY 2012 VL 81 IS 8 BP 1712 EP 1716 DI 10.1016/j.ejrad.2011.04.051 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 983NO UT WOS:000307126200026 PM 21596500 ER PT J AU Li, G De La Garza, B Shih, YYI Muir, ER Duong, TQ AF Li, Guang De La Garza, Bryan Shih, Yen-Yu I. Muir, Eric R. Duong, Timothy Q. TI Layer-specific blood-flow MRI of retinitis pigmentosa in RCS rats SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retinal degeneration; retinitis pigmentosa; arterial spin labeling; blood flow; retina; choroid ID OPTICAL COHERENCE TOMOGRAPHY; MANGANESE-ENHANCED MRI; HEREDITARY RETINAL DEGENERATION; OXYGEN-METABOLISM; ABYSSINIAN CATS; OCULAR FUNDUS; MOUSE RETINA; MUTATIONS; PERFUSION; GENE AB The Royal College of Surgeons (RCS) rat is an established animal model of retinitis pigmentosa, a family of inherited retinal diseases which starts with loss of peripheral vision and progresses to eventual blindness. Blood flow (BF), an important physiological parameter, is intricately coupled to metabolic function under normal physiological conditions and is perturbed in many neurological and retinal diseases. This study reports non-invasive high-resolution MRI (44 x 44 x 600 pm) to image quantitative retinal and choroidal BF and layer-specific retinal thicknesses in RCS rat retinas at different stages of retinal degeneration compared with age-matched controls. The unique ability to separate retinal and choroidal BF was made possible by the depth-resolved MRI technique. RBF decreased with progressive retinal degeneration, but ChBF did not change in RCS rats up to post-natal day 90. We concluded that choroidal and retinal circulations have different susceptibility to progressive retinal degeneration in RCS rats. Layer-specific retinal thickness became progressively thinner and was corroborated by histological analysis in the same animals. MRI can detect progressive anatomical and BF changes during retinal degeneration with laminar resolution. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Li, Guang; De La Garza, Bryan; Shih, Yen-Yu I.; Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Li, Guang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Li, Guang/C-9539-2011; Muir, Eric/H-8830-2013; OI Li, Guang/0000-0002-7648-0464; Shih, Yen-Yu Ian/0000-0001-6529-911X FU NIH/NEI [R01 EY014211, EY018855]; MERIT Award from the Department of Veterans Affairs; Clinical Translational Science Award Supplement (parent grant) [UL1RR025767] FX Grant support: This work was supported in part by the NIH/NEI (R01 EY014211 and EY018855), and a MERIT Award from the Department of Veterans Affairs, and a Clinical Translational Science Award Supplement (parent grant UL1RR025767). NR 58 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 2012 VL 101 BP 90 EP 96 DI 10.1016/j.exer.2012.06.006 PG 7 WC Ophthalmology SC Ophthalmology GA 984QE UT WOS:000307205300012 PM 22721720 ER PT J AU Prosser, LA Grosse, SD Kemper, AR Tarini, BA Perrin, JM AF Prosser, Lisa A. Grosse, Scott D. Kemper, Alex R. Tarini, Beth A. Perrin, James M. TI Decision analysis, economic evaluation, and newborn screening: challenges and opportunities SO GENETICS IN MEDICINE LA English DT Review DE cost-effectiveness; decision analysis; economic evaluation; health policy; newborn screening ID COA DEHYDROGENASE-DEFICIENCY; CONGENITAL ADRENAL-HYPERPLASIA; SEVERE COMBINED IMMUNODEFICIENCY; TANDEM MASS-SPECTROMETRY; COST-UTILITY; PRIMER; DISORDERS; AUSTRALIA; MORTALITY; DIAGNOSIS AB The number of conditions included in newborn screening panels has increased rapidly in the United States during the past decade, and many more conditions are under consideration for addition to state panels. The rare nature of candidate conditions for newborn screening makes their evaluation challenging. The scarcity of data on the costs of screening, follow-up, treatment, and long-term disability must be addressed to improve the evaluation process for nominated conditions. Decision analyses and economic evaluations can help inform policy decisions for newborn screening programs by providing a systematic approach to synthesizing available evidence and providing projected estimates of long-term clinical and economic outcomes when long-term data are not available. In this review, we outline the types of data required for the development of decision analysis and cost-effectiveness models for newborn screening programs and discuss the challenges faced when applying these methods in the arena of newborn screening to help inform policy decisions. Genet Med 2012:14(8):703-712 C1 [Prosser, Lisa A.; Tarini, Beth A.] Univ Michigan, Div Gen Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI 48109 USA. [Grosse, Scott D.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Kemper, Alex R.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Perrin, James M.] Harvard Univ, Sch Med, MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. RP Prosser, LA (reprint author), Univ Michigan, Div Gen Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI 48109 USA. EM lisapros@med.umich.edu FU University of Michigan; Duke University; MassGeneral Hospital for Children [HHSP23320045014XI]; Department of Health and Human Services; Health Resources and Services Administration; Maternal and Child Health Bureau FX This work was supported by subcontracts to the University of Michigan, Duke University, and MassGeneral Hospital for Children under prime contract (HHSP23320045014XI) to the Altarum Institute from the Department of Health and Human Services, the Health Resources and Services Administration, and the Maternal and Child Health Bureau. We also appreciate the expert research assistance of Kara Lamarand. NR 54 TC 8 Z9 9 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD AUG PY 2012 VL 14 IS 8 BP 703 EP 712 DI 10.1038/gim.2012.24 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 985SC UT WOS:000307288900001 ER PT J AU Aronson, SJ Clark, EH Varugheese, M Baxter, S Babb, LJ Rehm, HL AF Aronson, Samuel J. Clark, Eugene H. Varugheese, Matthew Baxter, Samantha Babb, Lawrence J. Rehm, Heidi L. TI Communicating new knowledge on previously reported genetic variants SO GENETICS IN MEDICINE LA English DT Article DE clinical decision support; electronic health record; GeneInsight; genetic reports; knowledge base; report updating; variant classification AB Genetic tests often identify variants whose significance cannot be determined at the time they are reported. In many situations, it is critical that clinicians be informed when new information emerges on these variants. It is already extremely challenging for laboratories to provide these updates. These challenges will grow rapidly as an increasing number of clinical genetic tests are ordered and as the amount of patient DNA assayed per test expands; the challenges will need to be addressed before whole-genome sequencing is used on a widespread basis. Information technology infrastructure can be useful in this context. We have deployed an infrastructure enabling clinicians to receive knowledge updates when a laboratory changes the classification of a variant. We have gathered statistics from this deployment regarding the frequency of both variant classification changes and the effects of these classification changes on patients. We report on the system's functionality as well as the statistics derived from its use. Genet Med 2012:14(8):713-719 C1 [Aronson, Samuel J.; Clark, Eugene H.; Varugheese, Matthew; Babb, Lawrence J.] Partners HealthCare Ctr Personalized Genet Med, Informat Syst Dept, Cambridge, MA USA. [Aronson, Samuel J.; Clark, Eugene H.; Varugheese, Matthew; Babb, Lawrence J.] Partners HealthCare, Informat Syst Dept, Cambridge, MA USA. [Baxter, Samantha; Rehm, Heidi L.] Partners HealthCare Ctr Personalized Genet Med, Lab Mol Med, Cambridge, MA USA. [Rehm, Heidi L.] Massachusetts Gen Hosp, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02114 USA. [Rehm, Heidi L.] Harvard Univ, Sch Med, Boston, MA USA. RP Aronson, SJ (reprint author), Partners HealthCare Ctr Personalized Genet Med, Informat Syst Dept, Cambridge, MA USA. EM saronson@partners.org FU Partners HealthCare and National Institutes of Health (NIH) Challenge Grant through the National Library of Medicine [RC1LM010526]; GeneInsight Lab FX We acknowledge all of our colleagues at the Partners HealthCare Center for Personalized Genetic Medicine who contributed to developing, testing, and rolling out the GeneInsight Suite, the GeneInsight Suite user community, which provided constant feedback, and the Refining IT Support for Genetics in Medicine team for its guidance. This work was supported in part by Partners HealthCare and National Institutes of Health (NIH) Challenge Grant RC1LM010526 administered through the National Library of Medicine. GeneInsight Lab licensing fees also supported this effort. NR 7 TC 28 Z9 28 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD AUG PY 2012 VL 14 IS 8 BP 713 EP 719 DI 10.1038/gim.2012.19 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 985SC UT WOS:000307288900002 ER PT J AU Leshchiner, I Alexa, K Kelsey, P Adzhubei, I Austin-Tse, CA Cooney, JD Anderson, H King, MJ Stottmann, RW Garnaas, MK Ha, SS Drummond, IA Paw, BH North, TE Beier, DR Goessling, W Sunyaev, SR AF Leshchiner, Ignaty Alexa, Kristen Kelsey, Peter Adzhubei, Ivan Austin-Tse, Christina A. Cooney, Jeffrey D. Anderson, Heidi King, Matthew J. Stottmann, Rolf W. Garnaas, Maija K. Ha, Seungshin Drummond, Iain A. Paw, Barry H. North, Trista E. Beier, David R. Goessling, Wolfram Sunyaev, Shamil R. TI Mutation mapping and identification by whole-genome sequencing SO GENOME RESEARCH LA English DT Article ID ZEBRAFISH; GENERATION; LINEAGES; GENE; MICE AB Genetic mapping of mutations in model systems has facilitated the identification of genes contributing to fundamental biological processes including human diseases. However, this approach has historically required the prior characterization of informative markers. Here we report a fast and cost-effective method for genetic mapping using next-generation sequencing that combines single nucleotide polymorphism discovery, mutation localization, and potential identification of causal sequence variants. In contrast to prior approaches, we have developed a hidden Markov model to narrowly define the mutation area by inferring recombination breakpoints of chromosomes in the mutant pool. In addition, we created an interactive online software resource to facilitate automated analysis of sequencing data and demonstrate its utility in the zebrafish and mouse models. Our novel methodology and online tools will make next-generation sequencing an easily applicable resource for mutation mapping in all model systems. C1 [Leshchiner, Ignaty; Alexa, Kristen; Kelsey, Peter; Adzhubei, Ivan; Stottmann, Rolf W.; Garnaas, Maija K.; Ha, Seungshin; Beier, David R.; Goessling, Wolfram; Sunyaev, Shamil R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Austin-Tse, Christina A.; Drummond, Iain A.] Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. [Cooney, Jeffrey D.; Anderson, Heidi; King, Matthew J.; Paw, Barry H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02114 USA. [North, Trista E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Goessling, Wolfram] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Goessling, Wolfram] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. RP Goessling, W (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. EM wgoessling@partners.org; ssunyaev@rics.bwh.harvard.edu OI Austin-Tse, Christina/0000-0001-6492-6716; Goessling, Wolfram/0000-0001-9972-1569 FU Harvard Stem Cell Institute; American Heart Association; Sigrid Juselius Foundation; March of Dimes grant; NIH [1R01DK090311, 5R01MH084676, R01HD036404, R01MH081187, R01DK070838, P01HL032262] FX This work was supported by a Junior Faculty Grant from the Harvard Stem Cell Institute and institutional start-up funds to W.G., American Heart Association grants to J.D.C. and M.J.K., Sigrid Juselius Foundation grant to H.A., March of Dimes grant to B.H.P., and NIH grants 1R01DK090311 to W.G., 5R01MH084676 to S.S., R01HD036404 and R01MH081187 to D.R.B, R01DK070838 and P01HL032262 to B.H.P. NR 25 TC 52 Z9 53 U1 3 U2 24 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 AUG PY 2012 VL 22 IS 8 BP 1541 EP 1548 DI 10.1101/gr.135541.111 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 983BD UT WOS:000307090300016 PM 22555591 ER PT J AU Brastianos, PK Batchelor, TT AF Brastianos, Priscilla K. Batchelor, Tracy T. TI Primary Central Nervous System Lymphoma Overview of Current Treatment Strategies SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Primary central nervous system lymphoma; Treatment; Chemotherapy; Radiation ID PRIMARY CNS LYMPHOMA; HIGH-DOSE METHOTREXATE; NON-HODGKINS-LYMPHOMA; WHOLE-BRAIN RADIOTHERAPY; STEM-CELL TRANSPLANTATION; RECURRENT PRIMARY CNS; MULTICENTER PHASE-II; IMMUNOCOMPETENT PATIENTS; RADIATION-THERAPY; INTRAOCULAR LYMPHOMA AB Primary central nervous system lymphoma (PCNSL) is an uncommon and aggressive variant of non-Hodgkin lymphoma that involves the brain, eyes, leptomeninges, or spinal cord. Therapeutic progress has been modest, and our understanding of the molecular mechanisms that drive this disease is limited. Clinicians treating PCNSL face a challenge to balance the need to administer aggressive regimens to achieve a cure with the risks of delayed neurotoxicity after treatment. The standard treatment is a methotrexate-containing chemotherapy regimen. The timing and dose of whole-brain radiation therapy is controversial, given the significant risks of late neurotoxic effects, particularly in elderly patients. C1 [Brastianos, Priscilla K.; Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp Canc Ctr, Stephen E & Catherine Pappas Ctr Neurooncol, Div Hematol & Oncol,Dept Neurol,Med Sch, Boston, MA 02114 USA. [Brastianos, Priscilla K.] Harvard Univ, Dept Med Oncol, Dana Farber Brigham & Womens Canc Ctr, Sch Med, Boston, MA 02115 USA. [Batchelor, Tracy T.] Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Brastianos, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp Canc Ctr, Stephen E & Catherine Pappas Ctr Neurooncol, Div Hematol & Oncol,Dept Neurol,Med Sch, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM pbrastianos@partners.org OI Brastianos, Priscilla/0000-0003-4470-8425 NR 93 TC 10 Z9 13 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2012 VL 26 IS 4 BP 897 EP + DI 10.1016/j.hoc.2012.05.003 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA 989ZW UT WOS:000307601800011 PM 22794289 ER PT J AU Delmonico, FL AF Delmonico, Francis L. TI Organ transplantation in China-the 21st century SO HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. EM francis_delmonico@neob.org NR 2 TC 1 Z9 1 U1 1 U2 5 PU ZHEJIANG UNIV SCH MEDICINE PI HANGZHOU PA FIRST AFFILIATED HOSPITAL, 79 QINGCHUN ROAD, HANGZHOU, 310003, PEOPLES R CHINA SN 1499-3872 J9 HEPATOB PANCREAT DIS JI Hepatob. Pancreatic. Dis. Int. PD AUG PY 2012 VL 11 IS 4 BP 346 EP 348 DI 10.1016/S1499-3872(12)60191-X PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 984RX UT WOS:000307210300001 PM 22893460 ER PT J AU Wen, HY Schumacher, HR Li, XF Gu, JR Ma, L Wei, H Yokogawa, N Shiroto, K Baker, JF Dinnella, J Ogdie, A AF Wen, Hongyan Schumacher, H. Ralph Li, Xiaofeng Gu, Jieruo Ma, Li Wei, Hua Yokogawa, Naoto Shiroto, Katsuaki Baker, Joshua F. Dinnella, Janet Ogdie, Alexis TI Comparison of expectations of physicians and patients with rheumatoid arthritis for rheumatology clinic visits: a pilot, multicenter, international study SO INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES LA English DT Article DE clinical aspects; drug treatment; education; rehabilitation; rheumatoid arthritis ID DISEASE-ACTIVITY; DEPRESSION; COMMUNICATION; OUTCOMES; PARTICIPATION; PREVALENCE; DISORDERS; SYMPTOM AB Aim To describe and compare expectations of patients with rheumatoid arthritis (RA) and their physicians with regard to what is most important to achieve during a rheumatology clinic visit. Methods Subjects were RA patients enrolled in four centers from China, one from Japan and one from the USA, and rheumatologists at those centers. The questionnaires were provided at clinics and patients were asked to list their three top priorities for the rheumatology clinic visit. Physicians were contacted separately and asked to give three general expectations, not for specific visits. We classified clinical expectations into a series of 24 terms for patients and 17 for physicians. We compared physicians' to patients' responses, compared expectations among centers in China, Japan and the USA, and evaluated relationships between patients' responses and age, gender, nationality, disease duration and DAS-28 (Disease Activity Score-28). Results Patients' clinical expectations for visits focused primarily on control of pain (63.7%), improvement of function (49.3%) and discussion of effects of medication (38.1%). Physicians also included control of pain (59.5%), but also emphasized inquiry about drug side-effects (47.8%) and objective assessment of disease activity (41.4%). We found no differences related to patients' gender, disease duration and DAS-28, but there were some differences related to age and nationality. Conclusion We found some agreement and some discordance of clinical expectations between RA patients and physicians. There appear to be some different expectations in different countries. Findings from this pilot survey may help physicians consider patients' expectations in planning rheumatology clinic visits and may lead to further hypothesis-driven studies. C1 [Schumacher, H. Ralph] Philadelphia Vet Affairs Med Ctr, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Wen, Hongyan; Schumacher, H. Ralph; Baker, Joshua F.; Dinnella, Janet; Ogdie, Alexis] Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Wen, Hongyan; Li, Xiaofeng] Shanxi Med Univ, Hosp 2, Taiyuan, Shanxi Province, Peoples R China. [Gu, Jieruo] Sun Yat Sen Univ, Affiliated Hosp 3, Guangzhou 510275, Guangdong, Peoples R China. [Ma, Li] China Japan Friendship Hosp, Beijing, Peoples R China. [Wei, Hua] No Jiangsu Peoples Hosp, Yangzhou, Jiangsu, Peoples R China. [Yokogawa, Naoto; Shiroto, Katsuaki] Tokyo Metropolitan Tama Med Ctr, Sect Rheumatol 2 8 29, Tokyo, Japan. RP Schumacher, HR (reprint author), Philadelphia Vet Affairs Med Ctr, Dept Med, Div Rheumatol, 151K Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu OI Ogdie, Alexis/0000-0002-4639-0775 NR 29 TC 9 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1756-1841 J9 INT J RHEUM DIS JI Int. J. Rheum. Dis. PD AUG PY 2012 VL 15 IS 4 BP 380 EP 389 DI 10.1111/j.1756-185X.2012.01752.x PG 10 WC Rheumatology SC Rheumatology GA 989OK UT WOS:000307569600014 PM 22898218 ER PT J AU Gaggin, HK Mohammed, AA Bhardwaj, A Rehman, SU Gregory, SA Weiner, RB Baggish, AL Moore, SA Semigran, MJ Januzzi, JL AF Gaggin, Hanna K. Mohammed, Asim A. Bhardwaj, Anju Rehman, Shafiq U. Gregory, Shawn A. Weiner, Rory B. Baggish, Aaron L. Moore, Stephanie A. Semigran, Marc J. Januzzi, James L., Jr. TI Heart Failure Outcomes and Benefits of NT-proBNP-Guided Management in the Elderly: Results From the Prospective, Randomized ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Natriuretic peptides; age; outcomes; biomarker ID BRAIN NATRIURETIC PEPTIDE; CLINICAL EPIDEMIOLOGY; EMERGENCY-DEPARTMENT; MEDICAL THERAPY; BETA-BLOCKER; VAL-HEFT; TRIAL; DYSFUNCTION; PREDICTION; VALSARTAN AB Background: Elderly patients with heart failure (HF) have a worse prognosis than younger patients. We wished to study whether elders benefit from natriuretic peptide-guided HF care in this single-center study. Methods and Results: A total of 151 patients with HF resulting from left ventricular systolic dysfunction (LVSD) were treated with HF treatment by standard-of-care (SOC) management or guided by N-terminal pro-B type natriuretic peptide (NT-proBNP) values (with a goal to lower NT-proBNP <= 1000 pg/mL) over 10 months. The primary end point for this post-hoc analysis was total cardiovascular events in 2 age categories (<75 and >= 75 years). In those >= 75 years of age (n = 38), NT-proBNP values increased in the SOC arm (2570 to 3523 pg/mL, P = .01), but decreased in the NT-proBNP guided arm (2664 to 1418 pg/mL, P = .001). Elderly patients treated with SOC management had the highest rate of cardiovascular events, whereas the elderly with NT-proBNP management had the lowest rate of cardiovascular events (1.76 events per patient versus 0.71 events per patient, P = .03); the adjusted logistic odds for cardiovascular events related to NT-proBNP guided care for elders was 0.24 (P = .008), whereas in those <75 years (n = 113), the adjusted logistic odds for events following NT-proBNP guided care was 0.61 (P = .10). Conclusions: Natriuretic peptide guided HF care was well tolerated and resulted in substantial improvement in cardiovascular event rates in elders (Clinical Trials.Gov #00351390). (J Cardiac Fail 2012;18:626-634) C1 [Gaggin, Hanna K.; Mohammed, Asim A.; Bhardwaj, Anju; Rehman, Shafiq U.; Gregory, Shawn A.; Weiner, Rory B.; Baggish, Aaron L.; Moore, Stephanie A.; Semigran, Marc J.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Roche Diagnostics, Inc.; Dennis and Marilyn Barry Cardiology Fellowship; Balson Cardiac Scholar Fund; Siemens Diagnostics; Critical Diagnostics; Thermo-Fisher Diagnostics FX Dr Januzzi reports the following disclosures: Roche Diagnostics, research grants, consultancy; Siemens Diagnostics, research grants; Critical Diagnostics, research grants, consultancy; and Thermo-Fisher Diagnostics, research grants. None of the other authors have disclosures. This work was supported in part by Roche Diagnostics, Inc. S.U.R., Drs Mohammed, Bhardwaj, and Gaggin are supported by the Dennis and Marilyn Barry Cardiology Fellowship. Dr Januzzi is supported in part by the Balson Cardiac Scholar Fund. NR 30 TC 32 Z9 37 U1 1 U2 9 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2012 VL 18 IS 8 BP 626 EP 634 DI 10.1016/j.cardfail.2012.05.005 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991CP UT WOS:000307679400006 PM 22858078 ER PT J AU Groessl, EJ Liu, L Ho, SB Kanwal, F Gifford, AL Asch, SM AF Groessl, Erik J. Liu, Lin Ho, Samuel B. Kanwal, Fasiha Gifford, Allen L. Asch, Steven M. TI National patterns and predictors of liver biopsy use for management of hepatitis C SO JOURNAL OF HEPATOLOGY LA English DT Article DE Hepatitis C; Liver biopsy; Guidelines ID GENOTYPE 1 INFECTION; VIRUS-INFECTION; AMINOTRANSFERASE LEVELS; PLUS RIBAVIRIN; UNITED-STATES; HEALTH-CARE; VETERANS; HCV; CARRIERS; PEGINTERFERON AB Background & Aims: Liver biopsy remains the standard, recommended method for assessing liver damage associated with chronic hepatitis C (HCV) infection. However, there is considerable debate about how liver biopsy should best be used, especially with the advent of more efficacious antiviral therapies. To identify the factors that influence the use of liver biopsy for HCV patients, we describe variations in liver biopsy use at the delivery system and patient level in a national VA sample. Methods: We analyzed VA HCV registry data for 171,893 VA patients with confirmed chronic HCV. Delivery system characteristics included geographic region and specialist time. Patient characteristics included antiviral treatment indicators, contraindications, volume of healthcare visits, and demographic variables. Logistic regression was used to explore correlates of biopsy use. Results: Liver biopsy use in the VA system increased from 1997 to 2003 but began declining in 2004. Rates of liver biopsy from 2004 to 2006 varied by VA region, ranging from 5% to 18%. Treatment contraindications and laboratory tests were significantly associated with more biopsies. Demographic variables (higher age, lower BMI, race/ethnicity, and less% service connected disability) were associated with fewer biopsies. Regional variability remained significant independent of volume of care and specialist time. Conclusions: Liver biopsy rates in the VA system have variability that seems unrelated to clinical need. New antiviral therapies and non-invasive assessment techniques may create additional uncertainty for the role of liver biopsy, perhaps explaining its decline in recent years. The availability of more effective antiviral therapies may also affect biopsy rates in the future. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Groessl, Erik J.; Ho, Samuel B.] VA San Diego Healthcare Syst, La Jolla, CA 92161 USA. [Groessl, Erik J.; Liu, Lin; Ho, Samuel B.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Gifford, Allen L.] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Gifford, Allen L.] Boston Univ, Boston, MA 02215 USA. [Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Kanwal, Fasiha] VA St Louis, St Louis, MO USA. [Kanwal, Fasiha] Washington Univ, St Louis, MO 63130 USA. RP Groessl, EJ (reprint author), VA San Diego Healthcare Syst, 3550 La Jolla Village Dr,Mail Code 111 N-1, La Jolla, CA 92161 USA. EM egroessl@ucsd.edu FU VA HSRD [SHP - 08-203] FX VA HSR&D, Project SHP - 08-203. NR 36 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD AUG PY 2012 VL 57 IS 2 BP 252 EP 259 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 991EW UT WOS:000307685300008 PM 22521358 ER PT J AU Lucas, K Karamichos, D Mathew, R Zieske, JD Stein-Streilein, J AF Lucas, Kenyatta Karamichos, Dimitris Mathew, Rose Zieske, James D. Stein-Streilein, Joan TI Retinal Laser Burn-Induced Neuropathy Leads to Substance P-Dependent Loss of Ocular Immune Privilege SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEUROKININ-1 RECEPTOR EXPRESSION; T-CELL-ACTIVATION; INFLAMMATORY CONDITIONS; PIGMENT-EPITHELIUM; ANTERIOR-CHAMBER; NERVOUS-SYSTEM; AQUEOUS-HUMOR; NEUROPEPTIDES; EYE; INDUCTION AB Inflammation in the eye is tightly regulated by multiple mechanisms that together contribute to ocular immune privilege. Many studies have shown that it is very difficult to abrogate the immune privileged mechanism called anterior chamber-associated immune deviation (ACAID). Previously, we showed that retinal laser burn (RLB) to one eye abrogated immune privilege (ACAID) bilaterally for an extended period of time. In an effort to explain the inflammation in the nonburned eye, we postulated that neuronal signals initiated inflammation in the contralateral eye. In this study, we test the role of substance P, a neuroinflamatory peptide, in RLB-induced loss of ACAID. Histological examination of the retina with and without RLB revealed an increase of the substance P-inducible neurokinin 1 receptor (NK1-R) in the retina of first, the burned eye, and then the contralateral eye. Specific antagonists for NK1-R, given locally with Ag within 24 h, but not 3, 5, or 7 d post-RLB treatment, prevented the bilateral loss of ACAID. Substance P knockout (KO) mice retained their ability to develop ACAID post-RLB. These data support the postulate that substance P transmits early inflammatory signals from the RLB eye to the contralateral eye to induce changes to ocular immune privilege and has a central role in the bilateral loss of ACAID. The possibility is raised that blocking of the substance P pathway with NK1-R antagonists postocular trauma may prevent unwanted and perhaps extended consequences of trauma-induced inflammation in the eye. The Journal of Immunology, 2012, 189: 1237-1242. C1 [Lucas, Kenyatta; Karamichos, Dimitris; Mathew, Rose; Zieske, James D.; Stein-Streilein, Joan] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Schepens Eye Res I, Boston, MA 02114 USA. RP Stein-Streilein, J (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Schepens Eye Res I, 20 Staniford St, Boston, MA 02114 USA. EM joan.stein@schepens.harvard.edu RI karamichos, dimitrios/D-9651-2015 FU National Institutes of Health [EY11983, EY016476, EY020614, F32 EY018983]; Department of Defense [W81XWH] FX This work was supported in part by National Institutes of Health Grants EY11983 (to J.S.-S.), EY016476 (to J.S.-S.), EY020614 (to J.S.-S.), and F32 EY018983 (to K. L.) and Department of Defense Grant W81XWH (to J.S.-S.). NR 42 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2012 VL 189 IS 3 BP 1237 EP 1242 DI 10.4049/jimmunol.1103264 PG 6 WC Immunology SC Immunology GA 976QJ UT WOS:000306599100020 PM 22745377 ER PT J AU Su, CW Cao, Y Zhang, M Kaplan, J Su, LB Fu, Y Walker, WA Xavier, R Cherayil, BJ Shi, HN AF Su, Chien-wen Cao, Yue Zhang, Mei Kaplan, Jess Su, Libo Fu, Ying Walker, W. Allan Xavier, Ramnik Cherayil, Bobby J. Shi, Hai Ning TI Helminth Infection Impairs Autophagy-Mediated Killing of Bacterial Enteropathogens by Macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALTERNATIVELY ACTIVATED MACROPHAGES; MYCOBACTERIUM-TUBERCULOSIS; MONITORING AUTOPHAGY; TOXOPLASMA-GONDII; TRICHURIS-SUIS; GENE ATG16L1; DISEASE; CELLS; SUPPRESSES; PATHOLOGY AB Autophagy is an important mechanism used by macrophages to kill intracellular pathogens. The results reported in this study demonstrate that autophagy is also involved in the macrophage killing of the extracellular enteropathogen Citrobacter rodentium after phagocytosis. The process was significantly impaired in macrophages isolated from mice chronically infected with the helminth parasite Heligmosomoides polygyrus. The H. polygyrus-mediated inhibition of autophagy was Th2 dependent because it was not observed in macrophages isolated from helminth-infected STAT6-deficient mice. Moreover, autophagy of Citrobacter was inhibited by treating macrophages with IL-4 and IL-13. The effect of H. polygyrus on autophagy was associated with decreased expression and processing of L chain protein 3 (LC3), a key component of the autophagic machinery. The helminth-induced inhibition of LC3 expression and processing was STAT6 dependent and could be recapitulated by treatment of macrophages with IL-4 and IL-13. Knockdown of LC3 significantly inhibited autophagic killing of Citrobacter, attesting to the functional importance of the H. polygyrus-mediated downregulation of this process. These observations reveal a new aspect of the immunosuppressive effects of helminth infection and provide mechanistic insights into our earlier finding that H. polygyrus significantly worsens the in vivo course of Citrobacter infection. The Journal of Immunology, 2012, 189: 1459-1466. C1 [Su, Chien-wen; Cao, Yue; Zhang, Mei; Kaplan, Jess; Su, Libo; Fu, Ying; Walker, W. Allan; Cherayil, Bobby J.; Shi, Hai Ning] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Su, Chien-wen; Cao, Yue; Zhang, Mei; Kaplan, Jess; Su, Libo; Fu, Ying; Walker, W. Allan; Cherayil, Bobby J.; Shi, Hai Ning] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Shi, HN (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Bldg 114,16th St,Room 3504, Charlestown, MA 02129 USA. EM shiha@helix.mgh.harvard.edu RI Fu, Ying/G-2899-2015 FU National Institutes of Health [DK074727, DK082427, AI089700]; Clinical Nutrition Research Center at Harvard [P30 DK040561]; Inflammatory Bowel Disease [DK43351]; Boston Area Diabetes and Endocrinology Research Center [DK57521] FX This work was supported by the National Institutes of Health (Grants DK074727 and DK082427 to H.N.S.; Grant AI089700 to B.J.C.) and the Clinical Nutrition Research Center at Harvard (Grant P30 DK040561 to W. A. W.). Electron microscopy was supported by Inflammatory Bowel Disease Grant DK43351 and Boston Area Diabetes and Endocrinology Research Center Award DK57521. NR 37 TC 16 Z9 16 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2012 VL 189 IS 3 BP 1459 EP 1466 DI 10.4049/jimmunol.1200484 PG 8 WC Immunology SC Immunology GA 976QJ UT WOS:000306599100043 PM 22732589 ER PT J AU Hancock, KE Chung, Y Delgutte, B AF Hancock, Kenneth E. Chung, Yoojin Delgutte, Bertrand TI Neural ITD coding with bilateral cochlear implants: effect of binaurally coherent jitter SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE binaural hearing; temporal coding; congenital deafness; inferior colliculus; interaural time difference ID INTERAURAL TIME DIFFERENCES; INFERIOR COLLICULUS NEURONS; SPIRAL GANGLION NEURONS; DEAF WHITE CATS; ELECTRICAL-STIMULATION; AUDITORY-NERVE; POTASSIUM CURRENTS; TEMPORAL RESOLUTION; RESPONSE PROPERTIES; PULSE TRAINS AB Hancock KE, Chung Y, Delgutte B. Neural ITD coding with bilateral cochlear implants: effect of binaurally coherent jitter. J Neurophysiol 108: 714-728, 2012. First published May 16, 2012; doi:10.1152/jn.00269.2012.-Poor sensitivity to the interaural time difference (ITD) constrains the ability of human bilateral cochlear implant users to listen in everyday noisy acoustic environments. ITD sensitivity to periodic pulse trains degrades sharply with increasing pulse rate but can be restored at high pulse rates by jittering the interpulse intervals in a binaurally coherent manner (Laback and Majdak. Binaural jitter improves interaural time-difference sensitivity of cochlear implantees at high pulse rates. Proc Natl Acad Sci USA 105: 814-817, 2008). We investigated the neural basis of the jitter effect by recording from single inferior colliculus (IC) neurons in bilaterally implanted, anesthetized cats. Neural responses to trains of biphasic pulses were measured as a function of pulse rate, jitter, and ITD. An effect of jitter on neural responses was most prominent for pulse rates above 300 pulses/s. High-rate periodic trains evoked only an onset response in most IC neurons, but introducing jitter increased ongoing firing rates in about half of these neurons. Neurons that had sustained responses to jittered high-rate pulse trains showed ITD tuning comparable with that produced by low-rate periodic pulse trains. Thus, jitter appears to improve neural ITD sensitivity by restoring sustained firing in many IC neurons. The effect of jitter on IC responses is qualitatively consistent with human psychophysics. Action potentials tended to occur reproducibly at sparse, preferred times across repeated presentations of high-rate jittered pulse trains. Spike triggered averaging of responses to jittered pulse trains revealed that firing was triggered by very short interpulse intervals. This suggests it may be possible to restore ITD sensitivity to periodic carriers by simply inserting short interpulse intervals at select times. C1 [Hancock, Kenneth E.; Chung, Yoojin; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Hancock, Kenneth E.; Chung, Yoojin; Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Hancock, KE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. EM Ken_Hancock@meei.harvard.edu OI , /0000-0003-1349-9608 FU National Institute on Deafness and Other Communication Disorders [R01-DC-005775, P30-DC-005209] FX This work was supported by National Institute on Deafness and Other Communication Disorders Grants R01-DC-005775 and P30-DC-005209. NR 59 TC 19 Z9 19 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2012 VL 108 IS 3 BP 714 EP 728 DI 10.1152/jn.00269.2012 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 985BK UT WOS:000307238100003 PM 22592306 ER PT J AU Sepulcre, J Sabuncu, MR Yeo, TB Liu, HS Johnson, KA AF Sepulcre, Jorge Sabuncu, Mert R. Yeo, Thomas B. Liu, Hesheng Johnson, Keith A. TI Stepwise Connectivity of the Modal Cortex Reveals the Multimodal Organization of the Human Brain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INTRINSIC FUNCTIONAL CONNECTIVITY; HUMAN PARIETAL OPERCULUM; PRIMATE CEREBRAL-CORTEX; CORTICAL NETWORK; MULTISENSORY INTEGRATION; SPATIAL ATTENTION; BINDING PROBLEM; SOMATOTOPIC ORGANIZATION; NEUROCOGNITIVE NETWORKS; SUPERIOR COLLICULUS AB How human beings integrate information from external sources and internal cognition to produce a coherent experience is still not well understood. During the past decades, anatomical, neurophysiological and neuroimaging research in multimodal integration have stood out in the effort to understand the perceptual binding properties of the brain. Areas in the human lateral occipitotemporal, prefrontal, and posterior parietal cortices have been associated with sensory multimodal processing. Even though this, rather patchy, organization of brain regions gives us a glimpse of the perceptual convergence, the articulation of the flow of information from modality-related to the more parallel cognitive processing systems remains elusive. Using a method called stepwise functional connectivity analysis, the present study analyzes the functional connectome and transitions from primary sensory cortices to higher-order brain systems. We identify the large-scale multimodal integration network and essential connectivity axes for perceptual integration in the human brain. C1 [Sepulcre, Jorge; Johnson, Keith A.] Harvard Univ, Sch Med, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sepulcre, Jorge; Sabuncu, Mert R.; Yeo, Thomas B.; Liu, Hesheng] Athinioula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Yeo, Thomas B.] Duke Natl Univ Singapore, Grad Sch Med, Dept Neurosci & Behav Disorders, Singapore 169857, Singapore. [Johnson, Keith A.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Cambridge, MA 02139 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. RP Sepulcre, J (reprint author), Harvard Univ, 52 Oxford St,NW Bldg 280-02, Cambridge, MA 02138 USA. EM sepulcre@nmr.mgh.harvard.edu OI Liu, Hesheng/0000-0002-7233-1509; Yeo, B.T. Thomas/0000-0002-0119-3276 FU Alzheimer's Association Grants [NIRG-11-205690, ZEN-10-174210]; NIH Grants [K25NS069805, K25EB013649-01, R01AG037497, R01AG036694] FX This work was supported by the Alzheimer's Association Grants NIRG-11-205690 (J.S.) and ZEN-10-174210 (K.A.J.) and NIH Grants K25NS069805 (H. L.), K25EB013649-01 (M.R.S.), and R01AG037497 and R01AG036694 (K.A.J.). We thank Randy L. Buckner for generously providing the data and also for his valuable comments on this study. We thank Tom Brady for his valuable comments on this study. We also recognize the influence of Prof. Jon Driver's legacy in the study. NR 73 TC 53 Z9 54 U1 0 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 2012 VL 32 IS 31 BP 10649 EP 10661 DI 10.1523/JNEUROSCI.0759-12.2012 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 983NL UT WOS:000307125900022 PM 22855814 ER PT J AU Liu, B Yu, ZT Chen, C Kling, DE Newburg, DS AF Liu, Bo Yu, Zhuoteng Chen, Ceng Kling, David E. Newburg, David S. TI Human Milk Mucin 1 and Mucin 4 Inhibit Salmonella enterica Serovar Typhimurium Invasion of Human Intestinal Epithelial Cells In Vitro SO JOURNAL OF NUTRITION LA English DT Article ID ESCHERICHIA-COLI; CACO-2 CELLS; HOST-CELLS; ADHERENCE; INFANTS; SURFACE; OLIGOSACCHARIDES; COMPONENTS; INFECTION; BINDING AB Many human milk glycans inhibit pathogen binding to host receptors and their consumption by infants is associated with reduced risk of disease. Salmonella infection is more frequent among infants than among the general population, but the incidence is lower in breast-fed babies, suggesting that human milk could contain components that inhibit Salmonella. This study aimed to test whether human milk per se inhibits Salmonella invasion of human intestinal epithelial cells in vitro and, if so, to identify the milk components responsible for inhibition. Salmonella enterica serovar Typhimurium SL1344 (SL1344) invasion of FHs 74 Int and Caco-2 cells were the models of human intestinal epithelium infection. Internalization of fluorescein-5-isothiocyanate labeled SL1344 into intestinal cells was measured by flow cytometry to quantify infection. Human milk and its fractions inhibited infection; the inhibitory activity localized to the high molecular weight glycans. Mucin 1 and mucin 4 were isolated to homogeneity. At 150 mu g/L, a typical concentration in milk, human milk mucin 1 and mucin 4 inhibited SL1344 invasion of both target cell types. These mucins inhibited SL1344 invasion of epithelial cells in a dose-dependent manner. Thus, mucins may prove useful as a basis for developing novel oral prophylactic and therapeutic agents that inhibit infant diseases caused by Salmonella and related pathogens. J. Nutr. 142: 1504-1509, 2012. C1 [Liu, Bo; Yu, Zhuoteng; Chen, Ceng; Newburg, David S.] Harvard Univ, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. [Liu, Bo; Yu, Zhuoteng; Chen, Ceng; Newburg, David S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liu, Bo; Yu, Zhuoteng; Chen, Ceng; Kling, David E.; Newburg, David S.] Boston Coll, Program Glycobiol, Dept Biol, Chestnut Hill, MA 02167 USA. RP Newburg, DS (reprint author), Harvard Univ, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. EM david.newburg@bc.edu FU NIH [HD013021, AI075563]; Abbott Nutrition FX Supported by NIH grants HD013021 and AI075563 and by Abbott Nutrition. NR 35 TC 10 Z9 12 U1 1 U2 11 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2012 VL 142 IS 8 BP 1504 EP 1509 DI 10.3945/jn.111.155614 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 980AE UT WOS:000306865200013 PM 22718031 ER PT J AU van Leeuwen, DH Guitton, TG Lambers, K Ring, D AF van Leeuwen, Diederik H. Guitton, Thierry G. Lambers, Kaj Ring, David TI Quantitative measurement of radial head fracture location SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Computed tomography; fractures; location; quantitative; radial head ID DISTAL BICEPS TENDON; BONE AB Background: The most common location of a displaced fracture of part of the radial head is often described as the anterior lateral aspect of the radial head with the forearm in neutral position, based on observation rather than precise measurements. The purpose of our study was to measure the exact location of fractures involving part of the radial head using quantitative 3-dimensional computed tomography (CT). Materials and methods: We measured the fracture lines with respect to the biceps tuberosity in 24 patients with a displaced articular fracture of part of the radial head (Mason type 2). Two observers preformed each measurement twice. Reliability was measured using the concordance correlation coefficient according to Lin. Results: The average start of the fracture was 97 degrees (standard deviation [SD]) 48.3 degrees; range 31 degrees-254 degrees) clockwise from the biceps tuberosity, the average end of the fracture was 241.6 degrees (SD, 61.0; range 19 degrees-330 degrees), and the average fracture subtends was 170 degrees (SD, 32.8 degrees; range 99 degrees-252 degrees). The fracture was through the anterolateral quadrant of the radial head in 22 of the 24 patients and through the posteromedial quadrant in 2 patients. Conclusion: This quantitative analysis of CT scans of displaced articular fractures of part of the radial head (Mason type 2) confirms that the most common location is the anterolateral quadrant with the forearm in neutral rotation. Given the important role of the radial head in elbow stability, more accurate characterization of incomplete radial head fractures may improve our understanding of treatment and outcome of these fractures. Level of evidence: Basic Science Study, Anatomic Study, Imaging. (C) 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [van Leeuwen, Diederik H.; Guitton, Thierry G.; Lambers, Kaj; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985 NR 13 TC 17 Z9 17 U1 0 U2 1 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 AUG PY 2012 VL 21 IS 8 BP 1013 EP 1017 DI 10.1016/j.jse.2011.08.056 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 992UP UT WOS:000307805600009 PM 22071412 ER PT J AU Hodin, R Angelos, P Carty, S Chen, H Clark, O Doherty, G Duh, QY Evans, DB Heller, K Inabnet, W Kebebew, E Pasieka, J Perrier, N Sturgeon, C AF Hodin, Richard Angelos, Peter Carty, Sally Chen, Herb Clark, Orlo Doherty, Gerard Duh, Quan-Yang Evans, Douglas B. Heller, Keith Inabnet, William Kebebew, Electron Pasieka, Janice Perrier, Nancy Sturgeon, Cord TI No Need to Abandon Unilateral Parathyroid Surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Letter C1 [Hodin, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Angelos, Peter] Univ Chicago, Chicago, IL 60637 USA. [Carty, Sally] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Chen, Herb] Univ Wisconsin, Madison, WI 53706 USA. [Clark, Orlo; Duh, Quan-Yang] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Doherty, Gerard] Boston Univ, Boston, MA 02215 USA. [Evans, Douglas B.] Med Coll Wisconsin, Milwaukee, WI USA. [Heller, Keith] NYU, Langone Med Ctr, New York, NY 10003 USA. [Inabnet, William] Mt Sinai Sch Med, New York, NY USA. [Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA. [Pasieka, Janice] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Sturgeon, Cord] Northwestern Univ, Evanston, IL 60208 USA. [Perrier, Nancy] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. RP Hodin, R (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Doherty, Gerard/0000-0002-1685-9552; Heller, Keith/0000-0003-2836-3359 NR 2 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2012 VL 215 IS 2 BP 297 EP 297 DI 10.1016/j.jamcollsurg.2012.04.024 PG 1 WC Surgery SC Surgery GA 988PL UT WOS:000307502900020 PM 22818100 ER PT J AU von Mehren, M Benjamin, RS Bui, MM Casper, ES Conrad, EU DeLaney, TF Ganjoo, KN George, S Gonzalez, R Heslin, MJ Kane, JM Mayerson, J McGarry, SV Meyer, C O'Donnell, RJ Paz, IB Pfeifer, JD Pollock, RE Randall, RL Riedel, RF Schuetze, S Schupak, KD Schwartz, HS Shankar, S Van Tine, BA Wayne, J Sundar, H McMillian, NR AF von Mehren, Margaret Benjamin, Robert S. Bui, Marilyn M. Casper, Ephraim S. Conrad, Ernest U., III DeLaney, Thomas F. Ganjoo, Kristen N. George, Suzanne Gonzalez, Ricardo Heslin, Martin J. Kane, John M., III Mayerson, Joel McGarry, Sean V. Meyer, Christian O'Donnell, Richard J. Paz, I. Benjamin Pfeifer, John D. Pollock, Raphael E. Randall, R. Lor Riedel, Richard F. Schuetze, Scott Schupak, Karen D. Schwartz, Herbert S. Shankar, Sridhar Van Tine, Brian A. Wayne, Jeffrey Sundar, Hema McMillian, Nicole R. TI Soft Tissue Sarcoma, Version 2.2012 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; OF-FUNCTION MUTATIONS; PHASE-II TRIAL; IMATINIB MESYLATE; PROGNOSTIC-FACTORS; ADJUVANT IMATINIB; DESMOID TUMOR; GIST; KIT; FIBROMATOSIS AB The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors. (JNCCN 2012;10:951-960) C1 [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Benjamin, Robert S.; Pollock, Raphael E.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Bui, Marilyn M.; Gonzalez, Ricardo] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Casper, Ephraim S.; Schupak, Karen D.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Conrad, Ernest U., III] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [DeLaney, Thomas F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ganjoo, Kristen N.] Stanford Canc Inst, Stanford, CA USA. [Heslin, Martin J.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Kane, John M., III] Roswell Pk Canc Inst, Buffalo, NY USA. [Mayerson, Joel] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [McGarry, Sean V.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Meyer, Christian] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [O'Donnell, Richard J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Paz, I. Benjamin] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Pfeifer, John D.; Van Tine, Brian A.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Pfeifer, John D.; Van Tine, Brian A.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Randall, R. Lor] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Schuetze, Scott] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Schwartz, Herbert S.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Shankar, Sridhar] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Wayne, Jeffrey] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RP von Mehren, M (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RI Mayerson, Joel/E-3616-2011 NR 30 TC 61 Z9 65 U1 0 U2 1 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 AUG PY 2012 VL 10 IS 8 BP 951 EP 960 PG 10 WC Oncology SC Oncology GA 988MB UT WOS:000307494000006 PM 22878820 ER PT J AU O'Donnell, MR Abboud, CN Altman, J Appelbaum, FR Arber, DA Attar, E Borate, U Coutre, SE Damon, LE Goorha, S Lancet, J Maness, LJ Marcucci, G Millenson, MM Moore, JO Ravandi, F Shami, PJ Smith, BD Stone, RM Strickland, SA Tallman, MS Wang, ES Naganuma, M Gregory, KM AF O'Donnell, Margaret R. Abboud, Camille N. Altman, Jessica Appelbaum, Frederick R. Arber, Daniel A. Attar, Eyal Borate, Uma Coutre, Steven E. Damon, Lloyd E. Goorha, Salil Lancet, Jeffrey Maness, Lori J. Marcucci, Guido Millenson, Michael M. Moore, Joseph O. Ravandi, Farhad Shami, Paul J. Smith, B. Douglas Stone, Richard M. Strickland, Stephen A. Tallman, Martin S. Wang, Eunice S. Naganuma, Maoko Gregory, Kristina M. TI Acute Myeloid Leukemia Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID ACUTE MYELOGENOUS LEUKEMIA; INTERNAL TANDEM DUPLICATION; STEM-CELL TRANSPLANTATION; HIGH-DOSE CYTARABINE; CORE-BINDING-FACTOR; RISK MYELODYSPLASTIC SYNDROME; 1ST COMPLETE REMISSION; FAVORABLE PROGNOSTIC-SIGNIFICANCE; ACUTE PROMYELOCYTIC LEUKEMIA; CONVENTIONAL CARE REGIMENS AB Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML provide recommendations on the diagnostic evaluation and workup for AML, risk assessment based on cytogenetic and molecular features, treatment options for induction and consolidation therapies for younger and older (age 65 years) adult patients, and key supportive care considerations. (JNCCN 2012;10:984-1021) C1 [O'Donnell, Margaret R.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Abboud, Camille N.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Abboud, Camille N.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Altman, Jessica] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Appelbaum, Frederick R.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Arber, Daniel A.; Coutre, Steven E.] Stanford Canc Inst, Stanford, CA USA. [Attar, Eyal] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Borate, Uma] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Damon, Lloyd E.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Goorha, Salil] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Lancet, Jeffrey] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Maness, Lori J.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Marcucci, Guido] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Moore, Joseph O.] Duke Canc Inst, Durham, NC USA. [Ravandi, Farhad] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Shami, Paul J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Smith, B. Douglas] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Stone, Richard M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Strickland, Stephen A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Wang, Eunice S.] Roswell Pk Canc Inst, Buffalo, NY USA. RP O'Donnell, MR (reprint author), City Hope Comprehens Canc Ctr, Duarte, CA USA. FU NCI NIH HHS [P30 CA016672] NR 113 TC 98 Z9 111 U1 1 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 AUG PY 2012 VL 10 IS 8 BP 984 EP 1021 PG 38 WC Oncology SC Oncology GA 988MB UT WOS:000307494000010 PM 22878824 ER PT J AU Brill, A AF Brill, A. TI Stroke-associated inflammation: is von Willebrand factor a 'bad guy'? SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article ID MIDDLE CEREBRAL-ARTERY; NITRIC-OXIDE SYNTHASE; ISCHEMIC-STROKE; FOCAL ISCHEMIA; REPERFUSION INJURY; BRAIN-DAMAGE; NEUTROPHILS; MICE; ACCUMULATION; PATHOGENESIS C1 [Brill, A.] Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02115 USA. [Brill, A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Brill, A (reprint author), Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM brill@idi.harvard.edu NR 33 TC 1 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD AUG PY 2012 VL 10 IS 8 BP 1662 EP 1664 DI 10.1111/j.1538-7836.2012.04820.x PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 989HW UT WOS:000307551900026 PM 22712638 ER PT J AU Ishaque, B Zayed, MA Miller, J Nguyen, D Kaji, AH Lee, JT O'Connell, J de Virgilio, C AF Ishaque, Brandon Zayed, Mohamed A. Miller, Jessica Nguyen, David Kaji, Amy H. Lee, Jason T. O'Connell, Jessica de Virgilio, Christian TI Ethnic differences in arm vein diameter and arteriovenous fistula creation rates in men undergoing hemodialysis access SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Western-Vascular-Surgical-Society CY SEP 17-20, 2011 CL Lihue, HI SP Western Vasc Surg Soc ID PREOPERATIVE NONINVASIVE EVALUATION; 1ST-TIME DIALYSIS ACCESS; VASCULAR ACCESS; AUTOLOGOUS FISTULAS; NATURAL-HISTORY; INCREASING USE; KDOQI ERA; MATURATION; FAILURE; IMPACT AB Objective: The National Kidney Foundation recommends that arteriovenous fistulas (AVFs) be placed in at least 65% of hemodialysis patients. Some studies suggest that African American patients are less likely to receive a first-time AVF than patients of other ethnicities, although the reason for this disparity is unclear. The purpose of our study is to determine (1) whether there are ethnic differences in AVF creation, (2) whether this may be related to differences in vein diameters, and (3) whether AVF patency rates are similar between African American and non-African American male patients. Methods: Consecutive male patients undergoing first-time hemodialysis access from 2006 to 2010 at two institutions were retrospectively reviewed. Data collected included age, ethnicity, weight, height, body mass index, diabetes, hypertension, congestive heart failure, smoking history, intravenous drug abuse, need for temporary access placement, and preoperative venous ultrasound measurements. Categoric variables were compared using chi(2) analysis, and the Wilcoxon rank-sum test was used to compare continuous variables. Results: Of 249 male patients identified, 95 were African American. Median age in African American and non-African American patients was 63 years. Hypertension and hyperlipidemia were statistically significantly greater in African American patients. The need for temporary access before hemoaccess was similar between the cohorts. African American patients demonstrated significantly smaller median basilic and cephalic vein diameters at most measured sites. Overall, 221 of 249 (88.8%) underwent AVF first. An AV graft was created in 17.9% of African American patients vs in only 7.1% of non-African Americans (odds ratio, 2.8; 95% confidence interval, 1.3-6.4; P = .009). The difference between median vein diameters used for autologous fistula creation in African American and non-African American patients was not significant. There was no significant difference in the primary patency (80.8% vs 76.2%; P = .4), primary functional patency (73.1% vs 69.2%; P = .5), or secondary functional patency rates (91.0% vs 96.5%; P = .1). Average primary fistula survival time was 257 days in African American and 256 in non-African American patients (P = .2). Conclusions: African American patients are less likely than non-African American patients to undergo AVF during first-time hemodialysis access surgery. This ethnic discrepancy appears to be due to smaller arm vein diameters in African American patients. In African American patients with appropriate vein diameters who do undergo AVF, primary and functional patencies are equivalent to non-African American patients. (J Vasc Surg 2012;56:424-32.) C1 [de Virgilio, Christian] Harbor UCLA Med Ctr, Dept Surg, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Ishaque, Brandon; Miller, Jessica; Nguyen, David; O'Connell, Jessica; de Virgilio, Christian] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Zayed, Mohamed A.; Lee, Jason T.] Stanford Univ, Med Ctr, Dept Vasc Surg, Stanford, CA 94305 USA. [Kaji, Amy H.] Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA. [O'Connell, Jessica; de Virgilio, Christian] W Los Angeles Vet Affairs Hosp, Div Vasc Surg, Los Angeles, CA USA. RP de Virgilio, C (reprint author), Harbor UCLA Med Ctr, Dept Surg, Los Angeles Biomed Res Inst, 1000 W Carson St, Torrance, CA 90509 USA. EM cdevirgilio@labiomed.org NR 27 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 2012 VL 56 IS 2 BP 424 EP 432 DI 10.1016/j.jvs.2012.01.029 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 984AS UT WOS:000307160400020 PM 22551911 ER PT J AU Lepantalo, MJA Houbballah, R Raux, M LaMuraglia, G AF Lepantalo, Mauri J. A. Houbballah, Rabih Raux, Maxime LaMuraglia, Glenn TI Lower extremity bypass vs endovascular therapy for young patients with symptomatic peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CRITICAL LIMB ISCHEMIA; SUPERFICIAL FEMORAL-ARTERY; RANDOMIZED CONTROLLED-TRIAL; LEG BASIL TRIAL; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; FEMOROPOPLITEAL OCCLUSIVE DISEASE; ISOLATED TIBIAL INTERVENTION; INTER-SOCIETY CONSENSUS; INFRAINGUINAL BYPASS; VASCULAR-SURGERY AB The uncertainty continues over the best approach to patients with symptomatic peripheral arterial disease. Medical therapy and risk factor modification is part of any treatment regimen; with this there is little disagreement. However, with the introduction of lesser invasive percutaneous technologies, the discussion regarding surgical and endovascular therapies has become more and more complicated. Unfortunately, there is a relative shortage of robust outcomes data to support many of our specific treatment recommendations. Younger patients are an especially troublesome patient cohort. They have consistently shown poorer outcomes after any intervention compared with older patients and may represent a subset of more aggressive atherosclerotic disease. Our debaters will discuss their preferred approaches to these difficult patients in the context of the currently available supporting literature. (J Vasc Surg 2012;56:545-55.) C1 [Lepantalo, Mauri J. A.] Univ Helsinki, Cent Hosp, Dept Vasc Surg, Helsinki, Finland. [Houbballah, Rabih; Raux, Maxime; LaMuraglia, Glenn] Massachusetts Gen Hosp, Gen Surg Serv, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Houbballah, Rabih; Raux, Maxime; LaMuraglia, Glenn] Harvard Univ, Sch Med, Boston, MA USA. RP Lepantalo, MJA (reprint author), Univ Helsinki, Cent Hosp, Dept Vasc Surg, POB 40, Helsinki 00029, Finland. EM mauri.lepantalo@hus.fi; glamuraglia@partners.org FU Monte and Rita Goldman Fund; John F. Murphy and the Bay State Federal Savings Foundation FX Dr LaMuraglia was supported, in part, by grants from the Monte and Rita Goldman Fund and John F. Murphy and the Bay State Federal Savings Foundation. NR 82 TC 3 Z9 3 U1 1 U2 5 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 AUG PY 2012 VL 56 IS 2 BP 545 EP 555 DI 10.1016/j.jvs.2012.06.053 PG 12 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 984AS UT WOS:000307160400043 PM 22840905 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Balance disorders in the elderly: Epidemiology and functional impact SO LARYNGOSCOPE LA English DT Article DE Elderly; geriatric; balance disorder; dizziness; vertigo ID PRIMARY-CARE; DIZZINESS; POPULATION; PREVALENCE; COMMUNITY AB Objectives/Hypothesis: To quantify the prevalence and determine the impact of dizziness and balance disorders in the elderly. Study Design: Cross-sectional analysis of a national database. Methods: The balance problems survey module of the 2008 National Health Interview Survey was examined, and cases of reported dizziness or balance problems in persons =65 years old were identified. The prevalence of balance disorders and associated symptoms and their impacts on self-reported functional limitations were determined. The related impact on daily activities for elderly persons with balance problems was quantified. Sex-based differences in balance problems were determined. Results: Among 37.3 +/- 0.9 million elderly persons (mean age, 74.4 +/- 0.1 years; 56.9% +/- 0.9% female), 7.0 +/- 0.2 million persons (19.6% +/- 0.7%) reported a problem with dizziness or balance in the preceding 12 months. Balance problems included difficulty with unsteadiness (68.0%), walking on uneven surfaces (54.8%), vertigo (30.1%), and faintness (29.6%). Prescription medication triggered the balance problem in 18.7%. Among the 50.0% of elderly persons with balance problems who sought care, 85.6%, 30.3%, 23.9%, and 16.8% saw a general practitioner, internist, neurologist, or otolaryngologist, respectively. Of this group, 27.4% reported that balance problems specifically prevented them from participating in activities including exercise (61.2%), social events (45.8%), and driving (47.1%). Females were more likely to experience balance problems than males (21.0% vs. 17.7%, P = .025). Conclusions: Approximately one in five elderly persons experiences annual problems with dizziness or balance. Given the significant prevalence and negative effect of balance problems on daily activities in the elderly, balance disorders merit special attention, particularly in the face of an aging population. C1 [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 12 TC 30 Z9 35 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 2012 VL 122 IS 8 BP 1858 EP 1861 DI 10.1002/lary.23376 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 980LK UT WOS:000306894500035 PM 22645067 ER PT J AU Mar, BG Bullinger, L Basu, E Schlis, K Silverman, LB Dohner, K Armstrong, SA AF Mar, B. G. Bullinger, L. Basu, E. Schlis, K. Silverman, L. B. Doehner, K. Armstrong, S. A. TI Sequencing histone-modifying enzymes identifies UTX mutations in acute lymphoblastic leukemia SO LEUKEMIA LA English DT Letter ID ACUTE MYELOID-LEUKEMIA; SOMATIC MUTATIONS; CANCER; INACTIVATION; INSIGHTS; EZH2 C1 [Mar, B. G.; Schlis, K.; Silverman, L. B.; Armstrong, S. A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mar, B. G.; Schlis, K.; Silverman, L. B.; Armstrong, S. A.] Childrens Hosp Boston, Dept Hematol Oncol, Boston, MA USA. [Bullinger, L.; Doehner, K.] Univ Ulm, Dept Internal Med 3, D-7900 Ulm, Germany. [Basu, E.] Mem Sloan Kettering, Dept Pediat, New York, NY USA. RP Mar, BG (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM Scott.Armstrong@childrens.harvard.edu OI Mar, Brenton/0000-0002-3857-9324 FU NCI NIH HHS [P01 CA068484, P01CA684841] NR 15 TC 30 Z9 33 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2012 VL 26 IS 8 BP 1881 EP 1883 DI 10.1038/leu.2012.56 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 990RW UT WOS:000307650000017 PM 22377896 ER PT J AU Ali, M Ananthakrishnan, AN Ahmad, S Kumar, N Kumar, G Saeian, K AF Ali, Muhammad Ananthakrishnan, Ashwin N. Ahmad, Shahryar Kumar, Nilay Kumar, Gagan Saeian, Kia TI Clostridium difficile infection in hospitalized liver transplant patients: A nationwide analysis SO LIVER TRANSPLANTATION LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; DIARRHEA; OUTCOMES; COLITIS; MULTICENTER; INPATIENT; DIAGNOSIS; CIRRHOSIS; SURGERY; IMPACT AB The incidence of Clostridium difficile infection (CDI) is increasing among hospitalized patients. Liver transplantation (LT) patients are at higher risk for acquiring CDI. Small, single-center studies (but no nationwide analyses) have assessed this association. We used the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project (2004-2008) for this retrospective, cross-sectional study. Patients with any discharge diagnosis of LT composed the study population, and they were identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes. Those with a discharge diagnosis of CDI were considered cases. Our primary outcomes were the prevalence of CDI and the effects of CDI on inpatient mortality. Our secondary outcomes included the length of stay and hospitalization charges. A regression analysis was used to derive odds ratios (ORs) adjusted for potential confounders. There were 193,174 discharges with a diagnosis of LT from 2004 to 2008. The prevalence of CDI was 2.7% in the LT population and 0.9% in the non-LT population (P < 0.001). Most of the LT patients were 50 to 64 years old. LT patients had higher odds of developing CDI [OR = 2.88, 95% confidence interval (CI) = 2.68-3.10]. Increasing age and increasing comorbidity (including inflammatory bowel disease and nasogastric tube placement) were also independent CDI risk factors. CDI was associated with a higher mortality rate: 5.5% for LT patients with CDI versus 3.2% for LT-only patients (adjusted OR = 1.70, 95% CI = 1.29-2.25). In conclusion, the prevalence of CDI is higher for LT patients versus non-LT patients (2.7% versus 0.9%). CDI is an independent risk factor for mortality in the LT population. Liver Transpl, 2012. (c) 2012 AASLD. C1 [Ali, Muhammad; Ahmad, Shahryar; Kumar, Gagan] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Kumar, Nilay; Saeian, Kia] Med Coll Wisconsin, Dept Gastroenterol & Hepatol, Milwaukee, WI 53226 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Ali, M (reprint author), Med Coll Wisconsin, Dept Med, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM muali@mcw.edu FU Clinical and Translational Science Institute of Southeast Wisconsin (National Institutes of Health) [UL1RR031973] FX This study was supported in part by the Clinical and Translational Science Institute of Southeast Wisconsin (National Institutes of Health grant UL1RR031973). NR 34 TC 27 Z9 27 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD AUG PY 2012 VL 18 IS 8 BP 972 EP 978 DI 10.1002/lt.23449 PG 7 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 979XU UT WOS:000306858200014 PM 22505356 ER PT J AU Ensrud, KE Joffe, H Guthrie, KA Larson, JC Reed, SD Newton, KM Sternfeld, B LaCroix, AZ Landis, CA Woods, NF Freeman, EW AF Ensrud, Kristine E. Joffe, Hadine Guthrie, Katherine A. Larson, Joseph C. Reed, Susan D. Newton, Katherine M. Sternfeld, Barbara LaCroix, Andrea Z. Landis, Carol A. Woods, Nancy F. Freeman, Ellen W. TI Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes: a randomized controlled trial SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Randomized trial; Escitalopram; Sleep; Hot flashes; Menopause ID MENOPAUSAL TRANSITION; HORMONE-THERAPY; CLINICAL-TRIAL; ANTIDEPRESSANTS; INDEX; DISTURBANCE; POPULATION; MEDICATION; DEPRESSION; CITALOPRAM AB Objective: The aim of this study was to determine the effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes. Methods: A randomized, blinded, multicenter, placebo-controlled parallel-group 8-week trial with 205 women (95 African American, 102 white, 8 other) was conducted between July 2009 and June 2010. The participants received escitalopram (10-20 mg/d) or placebo. Insomnia symptoms (Insomnia Severity Index [ISI]) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at weeks 4 and 8 were the prespecified secondary outcomes. A total of 199 women (97%) provided ISI data, and 194 (95%) women provided PSQI data at follow-up. Results: At baseline, mean hot flash frequency was 9.78 per day (SD, 5.60), mean ISI was 11.4 (SD, 6.3), and mean PSQI was 8.0 (SD, 3.7). Treatment with escitalopram reduced ISI at week 8 (mean difference, -2.00; 95% CI, -3.43 to -0.57; P < 0.001 overall treatment effect), with mean differences of -4.73 (95% CI, -5.72 to -3.75) in the escitalopram group and -2.73 (95% CI, -3.78 to -1.69) in the placebo group. The reduction in PSQI was greater in the escitalopram than in the placebo group at week 8 (mean difference, -1.31; 95% CI, -2.14 to -0.49; P < 0.001 overall treatment effect). Clinical improvement in insomnia symptoms and subjective sleep quality (>= 50% decreases in ISI and PSQI from baseline) was observed more frequently in the escitalopram group than in the placebo group (ISI, 50.0% vs 35.4%, P = 0.04; PSQI, 29.6% vs 19.2%, P = 0.09). Conclusions: Among healthy perimenopausal and postmenopausal women with hot flashes, escitalopram at 10 to 20 mg/day compared with placebo reduced insomnia symptoms and improved subjective sleep quality at 8 weeks of follow-up. C1 [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ensrud, Kristine E.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Joffe, Hadine] Massachusetts Gen Hosp, Dept Psychiat, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Guthrie, Katherine A.; Larson, Joseph C.; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Reed, Susan D.] Univ Washington, Dept Med, Seattle, WA USA. [Newton, Katherine M.] Grp Hlth Res Inst, Oakland, CA USA. [Sternfeld, Barbara] Kaiser Permanente, Div Res, Oakland, CA USA. [Landis, Carol A.; Woods, Nancy F.] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Freeman, Ellen W.] Univ Penn, Dept Obstet & Gynecol & Psychiat, Philadelphia, PA 19104 USA. RP Ensrud, KE (reprint author), 1 Vet Dr,Gen Internal Med 111-0, Minneapolis, MN 55417 USA. EM ensru001@umn.edu FU National Institute on Aging (NIA); Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Center for Complementary and Alternative Medicine; Office of Research on Women's Health [U01 AG032656, U01AG032659, U01AG032669, U01AG032699, U01AG032700]; Indiana Clinical and Translational Sciences Institute; National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award [UL1 RR025761] FX This study was supported by a cooperative agreement issued by the National Institute on Aging (NIA), in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Center for Complementary and Alternative Medicine, and the Office of Research on Women's Health (U01 AG032656, U01AG032659, U01AG032669, U01AG032699, U01AG032700). At the University of Indiana site, the project was funded, in part, with support from the Indiana Clinical and Translational Sciences Institute, by Grant UL1 RR025761 from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award. Escitalopram and matching placebo pills were provided by Forest Research Institute. NR 36 TC 27 Z9 28 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD AUG PY 2012 VL 19 IS 8 BP 848 EP 855 DI 10.1097/gme.0b013e3182476099 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 979TZ UT WOS:000306844000005 PM 22433978 ER PT J AU Vajaranant, TS Pasquale, LR AF Vajaranant, Thasarat S. Pasquale, Louis R. TI Estrogen deficiency accelerates aging of the optic nerve SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Review DE Aging; Glaucoma; Sex difference; Estrogen; Blindness ID OPEN-ANGLE GLAUCOMA; HORMONE REPLACEMENT THERAPY; FEMALE REPRODUCTIVE FACTORS; OXIDE SYNTHASE GENE; BLUE MOUNTAINS EYE; RETINAL BLOOD-FLOW; ANGELES LATINO EYE; INTRAOCULAR-PRESSURE; FIBER LAYER; OCULAR HYPERTENSION AB The aim of this study was to provide a comprehensive review on hormone-based pathophysiology of aging of the optic nerve and glaucoma, including a literature review and expert opinions. Glaucoma, a group of intraocular pressure-related optic neuropathies, is characterized by the slow progressive neurodegeneration of retinal ganglion cells and their axons, resulting in irreversible visual sensitivity loss and blindness. Increasing evidence suggests that glaucoma represents the accelerated aging of the optic nerve and is a neurodegenerative disease of the central nervous system. This review highlights the high burden of glaucoma in older women and the importance of understanding the hormone-related pathophysiology of optic nerve aging and glaucoma in women. Strong epidemiological, clinical, and experimental evidence supports the proposed hypothesis that early loss of estrogen leads to premature aging and increased susceptibility of the optic nerve to glaucomatous damage. Future investigations into the hormone-related mechanisms of aging and glaucoma will support the development of novel sex-specific preventive and therapeutic strategies in glaucoma. C1 [Vajaranant, Thasarat S.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA. [Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Vajaranant, TS (reprint author), 1855 W Taylor St, Chicago, IL USA. EM thasarat@uic.edu FU National Institute of Child Health and Human Development (NICHD) [K12HD055892]; Office of Research on Women's Health; National Eye Institute (NEI) [EY015473]; Research to Prevent Blindness Physician Scientist award; Harvard Glaucoma Center of Excellence; Distinguished Ophthalmology Scholar from the Department of Ophthalmology, Harvard Medical School FX This study was supported by grant K12HD055892 (T.S.V.) from the National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health and EY015473 (L.R.P.) from the National Eye Institute (NEI). Dr. Pasquale is also supported by a Research to Prevent Blindness Physician Scientist award, the Harvard Glaucoma Center of Excellence, and a Distinguished Ophthalmology Scholar from the Department of Ophthalmology, Harvard Medical School. NR 78 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD AUG PY 2012 VL 19 IS 8 BP 942 EP 947 DI 10.1097/gme.0b013e3182443137 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 979TZ UT WOS:000306844000017 PM 22415565 ER PT J AU Louissaint, A Ferry, JA Soupir, CP Hasserjian, RP Harris, NL Zukerberg, LR AF Louissaint, Abner, Jr. Ferry, Judith A. Soupir, Chad P. Hasserjian, Robert P. Harris, Nancy L. Zukerberg, Lawrence R. TI Infectious mononucleosis mimicking lymphoma: distinguishing morphological and immunophenotypic features SO MODERN PATHOLOGY LA English DT Article DE Epstein-Barr virus; infectious mononucleosis; lymphoma ID EPSTEIN-BARR-VIRUS; B-CELL LYMPHOMA; REED-STERNBERG CELLS; ATYPICAL LYMPHOPROLIFERATIVE DISORDERS; HODGKINS-DISEASE; WALDEYERS-RING; MALIGNANT-LYMPHOMA; ANTIGEN EXPRESSION; T-CELLS; LYMPHADENOPATHY AB The diagnosis of infectious mononucleosis (acute Epstein-Barr virus (EBV) infection) is usually made on the basis of clinical and laboratory findings. However, an atypical clinical presentation occasionally results in a lymph node or tonsillar biopsy. The morphological features of EBV-infected lymphoid tissue can easily mimic lymphoma. Furthermore, the immunophenotype of the immunoblasts has not been well characterized. To assess the morphological spectrum of acute EBV infection and the utility of immunohistochemistry in diagnosing difficult cases that resemble lymphoma, we reviewed 18 cases of acute EBV infection submitted in consultation to our institution with an initial diagnosis of/or suspicion for lymphoma. Patients included nine male and nine female individuals with a median age of 18 years (range 9-69). Biopsies were obtained from lymph nodes (3/18) or Waldeyer's ring (15/18). Infectious mononucleosis was confirmed by monospot or serological assays in 72% of cases (13/18). All cases featured architectural distortion by a polymorphous infiltrate with an immunoblastic proliferation, sometimes forming sheets. Reed-Sternberg-like cells were present in 8/18 (44%) of the cases. Infiltrates were often accompanied by necrosis (10/18) and mucosal ulceration (6/15). The majority of immunoblasts in all cases were CD20+ B cells with a post-germinal center immunophenotype (strongly positive for MUM1/IRF4 (18/18), CD10- (18/18 negative) and BCL-6- (16/18 negative; 2/18 faint BCL-6 expression in <10% of immunoblasts)). Immunoblasts showed variable weak expression of BCL-2 and polyclonal expression of kappa and lambda immunoglobulin light chains in 81% cases. Reed-Sternberg-like cells in 8/8 cases were CD30+, CD15-, BOB.1+ and OCT-2+. In conclusion, an atypical lymphoid infiltrate with numerous MUM1+, CD10-, BCL-6- immunoblasts should raise the suspicion of a reactive process, such as infectious mononucleosis, and warrants additional consideration before a diagnosis of lymphoma is made. Modern Pathology (2012) 25, 1149-1159; doi:10.1038/modpathol.2012.70; published online 25 May 2012 C1 [Louissaint, Abner, Jr.; Ferry, Judith A.; Soupir, Chad P.; Hasserjian, Robert P.; Harris, Nancy L.; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Louissaint, A (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM alouissaint@partners.org NR 45 TC 16 Z9 17 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD AUG PY 2012 VL 25 IS 8 BP 1149 EP 1159 DI 10.1038/modpathol.2012.70 PG 11 WC Pathology SC Pathology GA 984WD UT WOS:000307222200010 PM 22627742 ER PT J AU Heinrich, MC Marino-Enriquez, A Presnell, A Donsky, RS Griffith, DJ McKinley, A Patterson, J Taguchi, T Liang, CW Fletcher, JA AF Heinrich, Michael C. Marino-Enriquez, Adrian Presnell, Ajia Donsky, Rachel S. Griffith, Diana J. McKinley, Arin Patterson, Janice Taguchi, Takahiro Liang, Cher-Wei Fletcher, Jonathan A. TI Sorafenib Inhibits Many Kinase Mutations Associated with Drug-Resistant Gastrointestinal Stromal Tumors SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; DIAGNOSED CHRONIC-PHASE; FACTOR-RECEPTOR-BETA; IMATINIB MESYLATE; IN-VITRO; KIT; MUTANTS; MECHANISMS; SUNITINIB; FREQUENCY AB Sorafenib has substantial clinical activity as third-or fourth-line treatment of imatinib-and sunitinib-resistant gastrointestinal stromal tumors (GIST). Because sorafenib targets both angiogenesis-related kinases (VEGFR) and the pathogenetic kinases found in GIST (KIT or PDGFRA), the molecular basis for sorafenib efficacy in this setting remains unknown. We sought to determine the spectrum of activity of sorafenib against different mutant kinases associated with drug-sensitive and drug-resistant GIST. We compared the activity of imatinib and sorafenib against transiently expressed mutant forms of KIT and PDGFRA, including various secondary mutations that have been identified in imatinib-resistant or sunitinib-resistant GISTs. We also examined these drugs against four GIST cell lines, three of which are imatinib resistant. In our in vitro studies, we determined that sorafenib inhibited imatinib-resistant mutations in exons encoding the ATP/drug-binding pocket and in exons encoding the activation loop, with the exception of substitutions at KIT codon D816 and PDGFRA codon 842. Notably our data indicate that sorafenib is more effective than imatinib or sunitinib for inhibiting the kinase activity of drug-resistant KIT mutants (as assessed by biochemical IC50). We hypothesize that a major determinant of the efficacy of sorafenib for treatment of advanced GIST is the activity of this agent against KIT or PDGFRA-mutant kinases. These results have implications for the further development of treatments for drug-resistant GIST. Mol Cancer Ther; 11(8); 1770-80. (C) 2012 AACR. C1 [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Med, Div Hematol Oncol, Portland, OR 97239 USA. [Heinrich, Michael C.; Presnell, Ajia; Griffith, Diana J.; McKinley, Arin; Patterson, Janice] Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Portland, OR 97239 USA. [Marino-Enriquez, Adrian; Donsky, Rachel S.; Liang, Cher-Wei; Fletcher, Jonathan A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Marino-Enriquez, Adrian; Donsky, Rachel S.; Liang, Cher-Wei; Fletcher, Jonathan A.] Harvard Univ, Sch Med, Boston, MA USA. [Taguchi, Takahiro] Kochi Univ, Kochi 780, Japan. RP Heinrich, MC (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Med, Div Hematol Oncol, R&D-19 3710,US Vet Hosp Rd, Portland, OR 97239 USA. EM Heinrich@ohsu.edu OI Patterson, Janice/0000-0002-8969-2933; LIANG, CHER-WEI/0000-0001-8903-6082 FU Veterans Affairs Merit Review Grant; Life Raft Group; GIST Cancer Research Fund; GI SPORE [1P50CA127003]; BP Lester Foundation; Virginia and Daniel K. Ludwig Trust for Cancer Research; Fundacion Alfonso Martin Escudero; Cathay General Hospital Research Fund; Novartis; AROG; Imclone; Ariad FX M.C. Heinrich is a recipient of commercial research grant from Novartis, AROG, Imclone, and Ariad; has received honoraria from Speakers Bureau of Novartis and has ownership interest (including patents) from MolecularMD. He is also a consultant and advisory board member of Novartis.; This work was supported in part from funding from a Veterans Affairs Merit Review Grant (M. C. Heinrich), the Life Raft Group (M. C. Heinrich, J. A. Fletcher), the GIST Cancer Research Fund (M. C. Heinrich, J. A. Fletcher), GI SPORE 1P50CA127003 (J. A. Fletcher), BP Lester Foundation (M. C. Heinrich), the Virginia and Daniel K. Ludwig Trust for Cancer Research (J. A. Fletcher), Fundacion Alfonso Martin Escudero (A. Marino-Enriquez), and Cathay General Hospital Research Fund (C.-W. Liang). NR 34 TC 23 Z9 23 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2012 VL 11 IS 8 BP 1770 EP 1780 DI 10.1158/1535-7163.MCT-12-0223 PG 11 WC Oncology SC Oncology GA 995PG UT WOS:000308022100016 PM 22665524 ER PT J AU Shapiro, KA Bove, RM Volpicelli, ER Mallery, RM Stone, JH AF Shapiro, Kevin A. Bove, Riley M. Volpicelli, Elgida R. Mallery, Robert M. Stone, John H. TI RELAPSING COURSE OF IMMUNOGLOBULIN G4-RELATED PACHYMENINGITIS SO NEUROLOGY LA English DT Editorial Material ID IGG4-RELATED SYSTEMIC-DISEASE C1 [Stone, John H.] Massachusetts Gen Hosp, Dept Med, Rheumatol Unit, Boston, MA 02114 USA. [Shapiro, Kevin A.; Bove, Riley M.; Mallery, Robert M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Shapiro, Kevin A.; Bove, Riley M.; Mallery, Robert M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Volpicelli, Elgida R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Dept Med, Rheumatol Unit, Boston, MA 02114 USA. EM jhstone@partners.org NR 7 TC 17 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 2012 VL 79 IS 6 BP 604 EP 605 DI 10.1212/WNL.0b013e31826356fc PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 987ZW UT WOS:000307458800024 PM 22843267 ER PT J AU Schwarzschild, MA AF Schwarzschild, Michael A. TI Caffeine in Parkinson disease Better for cruise control than snooze patrol? SO NEUROLOGY LA English DT Editorial Material ID ADENOSINE A(2A) RECEPTORS; MOTOR; BRAIN C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Schwarzschild, MA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM MichaelS@helix.mgh.harvard.edu NR 10 TC 4 Z9 5 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 2012 VL 79 IS 7 BP 616 EP 618 DI 10.1212/WNL.0b013e318263580e PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 988FT UT WOS:000307475200005 PM 22855870 ER PT J AU Wang, CY Tian, R Zhao, Q Xu, H Meyer, CA Li, C Zhang, Y Liu, XS AF Wang, Chengyang Tian, Rui Zhao, Qian Xu, Han Meyer, Clifford A. Li, Cheng Zhang, Yong Liu, X. Shirley TI Computational inference of mRNA stability from histone modification and transcriptome profiles SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; MICRORNA TARGET SITES; GENE-EXPRESSION; HUMAN GENOME; POLYMERASE-II; INTERACTION MAPS; CHROMATIN STATE; CANCER-CELLS; SEQ DATA; DECAY AB Histone modifications play important roles in regulating eukaryotic gene expression and have been used to model expression levels. Here, we present a regression model to systematically infer mRNA stability by comparing transcriptome profiles with ChIP-seq of H3K4me3, H3K27me3 and H3K36me3. The results from multiple human and mouse cell lines show that the inferred unstable mRNAs have significantly longer 3'Untranslated Regions (UTRs) and more microRNA binding sites within 3'UTR than the inferred stable mRNAs. Regression residuals derived from RNA-seq, but not from GRO-seq, are highly correlated with the half-lives measured by pulse-labeling experiments, supporting the rationale of our inference. Whereas, the functions enriched in the inferred stable and unstable mRNAs are consistent with those from pulse-labeling experiments, we found the unstable mRNAs have higher cell-type specificity under functional constraint. We conclude that the systematical use of histone modifications can differentiate non-expressed mRNAs from unstable mRNAs, and distinguish stable mRNAs from highly expressed ones. In summary, we represent the first computational model of mRNA stability inference that compares transcriptome and epigenome profiles, and provides an alternative strategy for directing experimental measurements. C1 [Xu, Han; Meyer, Clifford A.; Li, Cheng; Liu, X. Shirley] Harvard Univ, Dana Farber Canc Inst, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Wang, Chengyang; Tian, Rui; Zhao, Qian; Zhang, Yong] Tongji Univ, Dept Bioinformat, Sch Life Sci & Technol, Shanghai 20092, Peoples R China. RP Liu, XS (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Publ Hlth, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM xsliu@jimmy.harvard.edu RI Zhang, Yong/B-4838-2011 OI Zhang, Yong/0000-0001-6316-2734 FU National Basic Research [973] Program of China [2010CB944904]; National Natural Science Foundation of China [31028011]; NIH [HG4069] FX National Basic Research [973] Program of China No. [2010CB944904], National Natural Science Foundation of China NO. [31028011] and NIH grant [HG4069]. Funding for open access charge: National Basic Research [973] Program of China No. [2010CB944904], National Natural Science Foundation of China No. [31028011] and NIH grant [HG4069]. NR 66 TC 8 Z9 9 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG PY 2012 VL 40 IS 14 BP 6414 EP 6423 DI 10.1093/nar/gks304 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 988QD UT WOS:000307504700012 PM 22495509 ER PT J AU Reynolds, JJ Walker, AK Gilmore, EC Walsh, CA Caldecott, KW AF Reynolds, John J. Walker, Alexandra K. Gilmore, Edward C. Walsh, Christopher A. Caldecott, Keith W. TI Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN POLYNUCLEOTIDE KINASE; LIGASE-IV; SPINOCEREBELLAR ATAXIA; TOPOISOMERASE-I; IMMUNODEFICIENCY; SUPERFAMILY; PHOSPHATASE; MECHANISMS; XRCC1; RATES AB Microcephaly with early-onset, intractable seizures and developmental delay (MCSZ) is a hereditary disease caused by mutations in polynucleotide kinase/phosphatase (PNKP), a DNA strand break repair protein with DNA 5'-kinase and DNA 3'-phosphatase activity. To investigate the molecular basis of this disease, we examined the impact of MCSZ mutations on PNKP activity in vitro and in cells. Three of the four mutations currently associated with MCSZ greatly reduce or ablate DNA kinase activity of recombinant PNKP at 30 degrees C (L176F, T424Gfs48X and exon15 delta fs4X), but only one of these mutations reduces DNA phosphatase activity under the same conditions (L176F). The fourth mutation (E326K) has little impact on either DNA kinase or DNA phosphatase activity at 30 degrees C, but is less stable than the wild-type enzyme at physiological temperature. Critically, all of the MCSZ mutations identified to date result in similar to 10-fold reduced cellular levels of PNKP protein, and reduced rates of chromosomal DNA strand break repair. Together, these data suggest that all four known MCSZ mutations reduce the cellular stability and level of PNKP protein, with three mutations likely ablating cellular DNA 5'-kinase activity and all of the mutations greatly reducing cellular DNA 3'-phosphatase activity. C1 [Reynolds, John J.; Walker, Alexandra K.; Caldecott, Keith W.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. [Gilmore, Edward C.; Walsh, Christopher A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Genet,Manton Ctr Orphan Dis,Childrens Hosp, Boston, MA 02115 USA. [Gilmore, Edward C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Child Neurol,Dept Neurol, Boston, MA 02114 USA. [Walsh, Christopher A.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. RP Caldecott, KW (reprint author), Univ Sussex, Genome Damage & Stabil Ctr, Sci Pk Rd, Brighton BN1 9RQ, E Sussex, England. EM k.w.caldecott@sussex.ac.uk FU Medical Research Council [G0600776]; Cancer Research UK [C6563/A10192]; Medical Research Council FX Medical Research Council [G0600776] and Cancer Research UK [C6563/A10192] (to K. W. C.). Funding for open access charge: Medical Research Council. NR 37 TC 22 Z9 25 U1 0 U2 4 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 AUG PY 2012 VL 40 IS 14 BP 6608 EP 6619 DI 10.1093/nar/gks318 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 988QD UT WOS:000307504700027 PM 22508754 ER PT J AU Schiffman, ED McCarthy, JC Kwon, JY AF Schiffman, Eric D. McCarthy, Joseph C. Kwon, John Y. TI Ankle Fracture Following Hip Arthroscopy SO ORTHOPEDICS LA English DT Article ID COMPLICATIONS AB This article describes a case of an ankle fracture following hip arthroscopy. A 58-year-old woman underwent hip arthroscopy for a labral tear. She was placed in a lateral decubitus position with her foot in a padded boot. Traction was maintained for approximately 30 minutes. She was instructed to bear weight as tolerated with crutches postoperatively. At 2-week follow-up, she reported ipsilateral ankle pain. Radiographs revealed a minimally displaced medial malleolus fracture. She was treated with a cast followed by a cam walker boot and successfully went on to complete union and resolution of her symptoms. The following risk factors exist for ankle fracture after hip arthroscopy: history of ankle sprains, ligamentous laxity (more common in women), and small feet with large calves (more likely to become plantarflexed during traction). Distraction performed with the ankle rotated is also likely to place added stress on the medial or lateral ligamentous structures. It is important to counsel patients preoperatively about the risk of ankle pain after hip arthroscopy, to be aware of the possibility of ankle pathology postoperatively, and to have a low threshold for ordering radiographs. Radiographs are warranted if patients continue to have ankle pain after 72 hours postoperatively. C1 [Schiffman, Eric D.; McCarthy, Joseph C.; Kwon, John Y.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Schiffman, ED (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM ees24@partners.org NR 23 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD AUG PY 2012 VL 35 IS 8 BP E1290 EP E1292 DI 10.3928/01477447-20120725-38 PG 3 WC Orthopedics SC Orthopedics GA 988UI UT WOS:000307515800028 PM 22868624 ER PT J AU Maserejian, NN Trachtenberg, FL Hauser, R McKinlay, S Shrader, P Tavares, M Bellinger, DC AF Maserejian, Nancy N. Trachtenberg, Felicia L. Hauser, Russ McKinlay, Sonja Shrader, Peter Tavares, Mary Bellinger, David C. TI Dental Composite Restorations and Psychosocial Function in Children SO PEDIATRICS LA English DT Article DE composite dental resin; composite resins; bisphenol A-glycidyl methacrylate; compomers; child behavior; behavioral symptoms; affective symptoms ID RANDOMIZED CLINICAL-TRIAL; BISPHENOL-A EXPOSURE; AMALGAM TRIAL; BEHAVIOR; MERCURY; RELEASE; RESIN; MICE; COMPONENTS; REMOVAL AB BACKGROUND AND OBJECTIVE: Resin-based dental materials may intraorally release their chemical components and bisphenol A. The New England Children's Amalgam Trial found that children randomized to amalgam had better psychosocial outcomes than those assigned to composites for posterior tooth restorations. The objective of this study was to examine whether greater exposure to dental composites is associated with psychosocial problems in children. METHODS: Analysis of treatment-level data from the New England Children's Amalgam Trial, a 2-group randomized safety trial comparing amalgam with the treatment plan of bisphenol A-glycidyl methacrylate (bisGMA)-based composite and urethane dimethacrylate-based polyacid-modified composite (compomer), among 534 children aged 6 to 10 years at baseline. Psychosocial function at follow-up (n = 434) was measured by using the self-reported Behavior Assessment System for Children (BASC-SR) and parent-reported Child Behavior Checklist (CBCL). RESULTS: Children with higher cumulative exposure to bisGMA-based composite had poorer follow-up scores on 3 of 4 BASC-SR global scales: Emotional Symptoms (beta = 0.8, SE = 0.3, P = .003), Clinical Maladjustment (beta = 0.7, SE = 0.3, P = .02), and Personal Adjustment (beta = -0.8, SE = 0.2, P = .002). Associations were stronger with posterior-occlusal (chewing) surfaces, where degradation of composite wasmore likely. For CBCL change, associations were not statistically significant. At-risk or clinically significant scores were more common among children with greater exposure for CBCL Total Problem Behaviors (16.3% vs 11.2%, P-trend = .01) and numerous BASC-SR syndromes (eg, >= 13 vs 0 surface-years, Interpersonal Relations 13.7% vs 4.8%, P-trend = .01). No associations were found with compomer, nor with amalgam exposure levels among children randomized to amalgam. CONCLUSIONS: Greater exposure to bisGMA-based dental composite restorations was associated with impaired psychosocial function in children, whereas no adverse psychosocial outcomes were observed with greater urethane dimethacrylate-based compomer or amalgam treatment levels. Pediatrics 2012;130:e328-e338 C1 [Maserejian, Nancy N.; Trachtenberg, Felicia L.; McKinlay, Sonja; Shrader, Peter] New England Res Inst, Dept Epidemiol, Watertown, MA 02172 USA. [Hauser, Russ; Bellinger, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hauser, Russ; Bellinger, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Hauser, Russ] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tavares, Mary] Forsyth Inst, Cambridge, MA USA. [Bellinger, David C.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Maserejian, NN (reprint author), New England Res Inst Inc, 9 Galen St, Watertown, MA 02472 USA. EM nmaserejian@neriscience.com FU National Institute of Environmental Health Sciences [R01ES019155]; New England Research Institutes [U01 DE11886]; National Institute of Dental and Craniofacial Research [U01 DE11886]; National Institutes of Health (NIH) FX The analyses presented in this article were funded by award number R01ES019155 from the National Institute of Environmental Health Sciences. The data collection was supported by a cooperative agreement (U01 DE11886) between the New England Research Institutes and the National Institute of Dental and Craniofacial Research, both of which participated in the design and conduct of the New England Children's Amalgam Trial, including collection and management of data. Funded by the National Institutes of Health (NIH). NR 42 TC 24 Z9 26 U1 1 U2 11 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 AUG PY 2012 VL 130 IS 2 BP E328 EP E338 DI 10.1542/peds.2011-3374 PG 11 WC Pediatrics SC Pediatrics GA 983MI UT WOS:000307123000011 PM 22802599 ER PT J AU Min, C Ohta, K Kajiya, M Zhu, T Sharma, K Shin, J Mawardi, H Howait, M Hirschfeld, J Bahammam, L Ichimonji, I Ganta, S Amiji, M Kawai, T AF Min, Christine Ohta, Kouji Kajiya, Mikihito Zhu, Tongbo Sharma, Kanika Shin, Jane Mawardi, Hani Howait, Mohammed Hirschfeld, Josefine Bahammam, Laila Ichimonji, Isao Ganta, Srinivas Amiji, Mansoor Kawai, Toshihisa TI The antimicrobial activity of the appetite peptide hormone ghrelin SO PEPTIDES LA English DT Article DE Ghrelin; Peptide; Escherichia coli; Pseudomonas aeruginosa; LL37; Antimicrobial activity ID PROINFLAMMATORY CYTOKINE EXPRESSION; BETA-DEFENSINS; CARIOGENIC BACTERIA; SUSCEPTIBILITY; CELLS; IDENTIFICATION; EPITHELIA; LEPTIN; PLASMA; LL-37 AB The present study examined the antimicrobial activity of the peptide ghrelin. Both major forms of ghrelin, acylated ghrelin (AG) and desacylated ghrelin (DAG), demonstrated the same degree of bactericidal activity against Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), while bactericidal effects against Gram-positive Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis) were minimal or absent, respectively. To elucidate the bactericidal mechanism of AG and DAG against bacteria, we monitored the effect of the cationic peptides on the zeta potential of E. coli. Our results show that AG and DAG similarly quenched the negative surface charge of E. coli, suggesting that ghrelin-mediated bactericidal effects are influenced by charge-dependent binding and not by acyl modification. Like most cationic antimicrobial peptides (CAMPs), we also found that the antibacterial activity of AG was attenuated in physiological NaCl concentration (150 mM). Nonetheless, these findings indicate that both AG and DAG can act as CAMPs against Gram-negative bacteria. (C) 2012 Elsevier Inc. All rights reserved. C1 [Min, Christine; Ohta, Kouji; Kajiya, Mikihito; Zhu, Tongbo; Mawardi, Hani; Howait, Mohammed; Hirschfeld, Josefine; Bahammam, Laila; Ichimonji, Isao; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Cambridge, MA 02142 USA. [Ohta, Kouji; Kajiya, Mikihito; Zhu, Tongbo; Sharma, Kanika; Shin, Jane; Mawardi, Hani; Howait, Mohammed; Kawai, Toshihisa] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Mawardi, Hani] King Abdulaziz Univ, Fac Dent, Oral Basic & Clin Sci Dept, Ora Med & Oral Diag Div, Jeddah 21589, Saudi Arabia. [Howait, Mohammed; Bahammam, Laila] King Abdulaziz Univ, Fac Dent, Dept Conservat Dent Sci, Endodont Div, Jeddah 21589, Saudi Arabia. [Ganta, Srinivas; Amiji, Mansoor] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 245 1st St, Cambridge, MA 02142 USA. EM tkawai@forsyth.org RI Amiji, Mansoor/A-4365-2014; howait, mohammed/K-4478-2016 OI Amiji, Mansoor/0000-0001-6170-881X; howait, mohammed/0000-0002-6268-4941 FU NIH from National Institute of Dental and Craniofacial Research [DE-018310]; Harvard Catalyst FX This study was supported by NIH grant DE-018310 from the National Institute of Dental and Craniofacial Research and Pilot Grant from Harvard Catalyst. We acknowledge Max Goodson at the Forsyth Institute for his critical comments on this manuscript. NR 28 TC 5 Z9 5 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD AUG PY 2012 VL 36 IS 2 BP 151 EP 156 DI 10.1016/j.peptides.2012.05.006 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 983YR UT WOS:000307155100001 PM 22634233 ER PT J AU Pekary, AE Sattin, A AF Pekary, A. Eugene Sattin, Albert TI Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by ghrelin and 3-TRP-ghrelin SO PEPTIDES LA English DT Article DE Ghrelin; TRH-like peptides; Rat; Limbic system ID HORMONE TRH; MESSENGER-RNA; FOOD-INTAKE; SECRETION; RECEPTOR; STIMULATION; MECHANISM; BEHAVIOR; SYSTEM; LEPTIN AB Ghrelin is not only a modulator of feeding and energy expenditure but also regulates reproductive functions, CNS development and mood. Obesity and major depression are growing public health concerns which may derive, in part, from dysregulation of ghrelin feedback at brain regions regulating feeding and mood. We and others have previously reported that thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2) and TRH-like peptides (pGIu-X-Pro-NH2, where "X" can be any amino acid residue) have neuroprotective, antidepressant, anti-epileptic, analeptic, anti-ataxic, and anorectic properties. For this reason male Sprague-Dawley rats were injected ip with 0.1 mg/kg rat ghrelin or 0.9 mg/kg 3-Trp-rat ghrelin. Twelve brain regions: cerebellum, medulla oblongata, anterior cingulate, posterior cingulate, frontal cortex, nucleus accumbens, hypothalamus, entorhinal cortex, hippocampus, striatum, amygdala, piriform cortex and 5 peripheral tissues (adrenals, testes, epididymis, pancreas and prostate) were analyzed. Rapid and profound decreases in TRH and TRH-like peptide levels (increased release) occurred throughout brain and peripheral tissues following ip ghrelin. Because ghrelin is rapidly deacylated in vivo we also studied 3-Trp-ghrelin which cannot be deacylated. Significant increases in TRH and TRH-like peptide levels following 3-Trp-ghrelin, relative to those after ghrelin were observed in all brain regions except posterior cingulate and all peripheral tissues except prostate and testis. The rapid stimulation of TRH and TRH-like peptide release by ghrelin in contrast with the inhibition of such release by 3-Trp-TRH is consistent with TRH and TRH-like peptides modulating the downstream effects of both ghrelin and unacylated ghrelin. Published by Elsevier Inc. C1 [Pekary, A. Eugene; Sattin, Albert] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Sattin, Albert] VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. [Pekary, A. Eugene] VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Pekary, A. Eugene] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Pekary, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, Bldg 114,Rm 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Eugene.Pekary@va.gov FU Department of Veterans Affairs Medical Research funds; Pekary Trust FX This work was supported by the Department of Veterans Affairs Medical Research funds (AEP and AS) and the Pekary Trust. NR 74 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD AUG PY 2012 VL 36 IS 2 BP 157 EP 167 DI 10.1016/j.peptides.2012.04.021 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 983YR UT WOS:000307155100002 PM 22634385 ER PT J AU Cohen, JM Fagin, AP Hariton, E Niska, JR Pierce, MW Kuriyama, A Whelan, JS Jackson, JL Dimitrakoff, JD AF Cohen, Jeffrey M. Fagin, Adam P. Hariton, Eduardo Niska, Joshua R. Pierce, Michael W. Kuriyama, Akira Whelan, Julia S. Jackson, Jeffrey L. Dimitrakoff, Jordan D. TI Therapeutic Intervention for Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS): A Systematic Review and Meta-Analysis SO PLOS ONE LA English DT Review ID CHRONIC NONBACTERIAL PROSTATITIS; PLACEBO-CONTROLLED TRIAL; SYNDROME CATEGORY IIIA; DOUBLE-BLIND TRIAL; CLINICAL-TRIALS; CONTROLLED MULTICENTER; TERAZOSIN THERAPY; SYMPTOM INDEX; MEN; TAMSULOSIN AB Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has been treated with several different interventions with limited success. This meta-analysis aims to review all trials reporting on therapeutic intervention for CP/CPPS using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). Methods: We searched Medline, PubMed, the Cochrane Pain, Palliative & Supportive Care Trials, the Cochrane Register of Controlled Trials, CINAHL, ClinicalTrials.gov, and the NIDDK website between 1947 and December 31, 2011 without language or study type restrictions. All RCTs for CP/CPPS lasting at least 6 weeks, with a minimum of 10 participants per arm, and using the NIH-CPSI score, the criterion standard for CP/CPPS, as an outcome measure were included. Data was extracted from each study by two independent reviewers. Gillbraith and I-squared plots were used for heterogeneity testing and Eggers and Peters methods for publication bias. Quality was assessed using a component approach and meta-regression was used to analyze sources of heterogeneity. Results: Mepartricin, percutaneous tibial nerve stimulation (PTNS), and triple therapy comprised of doxazosin + ibuprofen + thiocolchicoside (DIT) resulted in clinically and statistically significant reduction in NIH-CPSI total score. The same agents and aerobic exercise resulted in clinically and statistically significant NIH-CPSI pain domain score reduction. Acupuncture, DIT, and PTNS were found to produce statistically and clinically significant reductions in the NIH-CPSI voiding domain. A statistically significant placebo effect was found for all outcomes and time analysis showed that efficacy of all treatments increased over time. Alpha-blockers, antibiotics, and combinations of the two failed to show statistically or clinically significant NIH-CPSI reductions. Conclusion: Results from this meta-analysis reflect our current inability to effectively manage CP/CPPS. Clinicians and researchers must consider placebo effect and treatment efficacy over time and design studies creatively so we can more fully elucidate the etiology and role of therapeutic intervention in CP/CPPS. C1 [Cohen, Jeffrey M.; Hariton, Eduardo; Niska, Joshua R.; Pierce, Michael W.; Whelan, Julia S.; Dimitrakoff, Jordan D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Dimitrakoff, Jordan D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fagin, Adam P.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Jackson, Jeffrey L.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Kuriyama, Akira] Kurashiki Cent Hosp, Okayama, Japan. RP Cohen, JM (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM jordan.dimitrakoff@gmail.com OI Dimitrakoff, Jordan/0000-0001-6827-1382 NR 62 TC 21 Z9 26 U1 0 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 1 PY 2012 VL 7 IS 8 AR e41941 DI 10.1371/journal.pone.0041941 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984SU UT WOS:000307212800045 PM 22870266 ER PT J AU Greaney, ML Puleo, E Sprunck-Harrild, K Bennett, GG Cunningham, MA Gillman, MW Coeling, M Emmons, KM AF Greaney, Mary L. Puleo, Elaine Sprunck-Harrild, Kim Bennett, Gary G. Cunningham, Moira A. Gillman, Matthew W. Coeling, Molly Emmons, Karen M. TI Electronic reminders for cancer prevention: Factors associated with preference for automated voice reminders or text messages SO PREVENTIVE MEDICINE LA English DT Article DE SMS text messages; Automated voice recordings; Prompting; Electronic reminders ID PHYSICAL-ACTIVITY; INTERVENTIONS; PROMOTION; FRAMEWORK; CARE AB Objective. Prompting may promote engagement with behavior change interventions. Prompts can be delivered inexpensively via automated voice response (AVR) reminders or short message service (SMS) text messages. We examined the association between participants' characteristics and preferred reminder modality. Methods. Healthy Directions 2 is a cluster randomized controlled trial implemented in Boston, Massachusetts to promote change in multiple behavioral cancer risk factors. At baseline (2009), participants completed a survey assessing socio-demographics, health status, height/weight, and factors associated with technology. One-third of participants randomized to receive the intervention (n =598) were randomized to receive automated reminders, with participants selecting modality. Results. 28% (167/598) of participants selected SMS reminders. Controlling for clustering by primary care provider, younger participants (OR = 0.97,95% CI = (0.95, 0.99), p<0.01), those most comfortable with computers (very uncomfortable OR = 0.54, 95% CI = (0.29, 1.01), p <= 0.05: referent group = very comfortable), and those who frequently sent/received text messages (never OR = 0.09 CI = (0.04, 0.16) p<0.01; 1-3 times/month OR = 038, 95% CI = (0.15, 0.93) p = 0.04: referent group = 1-5 times/week) were more likely to choose SMS. Conclusions. Interventions should make both modalities available to ensure that more participants can benefit from prompting. Studies examining the effect of automated reminders may have reduced effectiveness or generalizability if they employ only one modality. (C) 2012 Elsevier Inc. All rights reserved. C1 [Greaney, Mary L.; Sprunck-Harrild, Kim; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Puleo, Elaine] Univ Massachusetts, Dept Publ Hlth, Amherst, MA 01003 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Bennett, Gary G.] Duke Univ, Duke Obes Prevent Program, Durham, NC USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Cunningham, Moira A.] Harvard Vanguard Med Associates, Boston, MA USA. [Gillman, Matthew W.] Harvard Univ, Sch Med, Dept Populat Med,Harvard Pilgrim Hth Care Inst, Obes Prevent Program, Boston, MA 02115 USA. [Coeling, Molly] Univ Chicago, Chicago, IL 60637 USA. RP Greaney, ML (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave St, Boston, MA 02215 USA. EM Mary_Greaney@dfci.harvard.edu FU NIH [R01 CA123228, 1K05 CA124415] FX This work was supported by NIH grants R01 CA123228 and 1K05 CA124415. We thank Harvard Vanguard Medical Associates for the opportunity to conduct our research in their clinical sites, and all of the health care providers who participated in this study. We would like acknowledge Jess Haines, PhD, RD, an HD2 co-investigator, as well as the HD2 staff: Louisa Bloomstein, Joanne Chin, Lindsay ElShazly, Emma Issenberg, Fatima Shahzad, Kim Skeete, Kristie Usher, and Val Varner. We also would like to thank Martha Zorn for her statistical support. NR 13 TC 8 Z9 8 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD AUG PY 2012 VL 55 IS 2 BP 151 EP 154 DI 10.1016/j.ypmed.2012.05.014 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 983AO UT WOS:000307088800014 PM 22659227 ER PT J AU Zivin, K Ilgen, MA Pfeiffer, PN Welsh, DE McCarthy, J Valenstein, M Miller, EM Islam, K Kales, HC AF Zivin, Kara Ilgen, Mark A. Pfeiffer, Paul Nelson Welsh, Deborah E. McCarthy, John Valenstein, Marcia Miller, Erin M. Islam, Khairul Kales, Helen C. TI Early Mortality and Years of Potential Life Lost Among Veterans Affairs Patients With Depression SO PSYCHIATRIC SERVICES LA English DT Article ID SUICIDE MORTALITY; RISK-FACTOR; ILLNESS; CARE AB Objective: Substantial literature documents excess and early mortality among individuals with serious mental illness, but there are relatively few data about mortality and depression. Methods: During fiscal year 2007, data from the U.S. Department of Veterans Affairs and the National Death Index were used to calculate mean age of death and years of potential life lost (YPLL) associated with 13 causes of death among veterans with (N=701,659) or without (N=4,245,193) depression. Results: Compared with nondepressed patients, depressed patients died younger (71.1 versus 75.9) and had more YPLL (13.4 versus 10.2) as a result of both natural and unnatural causes. Depending on the cause of death, depressed patients died between 2.5 and 8.7 years earlier and had 1.5 to 6.1 YPLL compared with nondepressed patients. Conclusions: These findings have important implications for clinical practice, given that improved quality of care may be needed to reduce early mortality among depressed VA patients. (Psychiatric Services 63:823-826, 2012; doi: 10.1176/appi.ps.201100317) C1 [Zivin, Kara; Ilgen, Mark A.; Pfeiffer, Paul Nelson; Welsh, Deborah E.; McCarthy, John; Valenstein, Marcia; Miller, Erin M.; Kales, Helen C.] US Dept Vet Affairs, Natl Serious Mental Illness Treatment Res & Evalu, Ann Arbor, MI 48109 USA. [Zivin, Kara; Ilgen, Mark A.; Pfeiffer, Paul Nelson; Welsh, Deborah E.; McCarthy, John; Valenstein, Marcia; Miller, Erin M.; Kales, Helen C.] US Dept Vet Affairs, Hlth Serv Res & Dev Ctr Clin Management Res, Ann Arbor, MI 48109 USA. [Zivin, Kara; Ilgen, Mark A.; Pfeiffer, Paul Nelson; McCarthy, John; Valenstein, Marcia; Miller, Erin M.; Islam, Khairul; Kales, Helen C.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Zivin, K (reprint author), US Dept Vet Affairs, Natl Serious Mental Illness Treatment Res & Evalu, N Campus Res Complex,2800 Plymouth Rd,Bldg 14, Ann Arbor, MI 48109 USA. EM kzivin@umich.edu FU U.S. Department of Veterans Affairs Health Services Research and Development Service [IIR 10-176-3, CD2 07-206-1, CDA 10-036-1] FX This study was funded by grants IIR 10-176-3, CD2 07-206-1, and CDA 10-036-1 from the U.S. Department of Veterans Affairs Health Services Research and Development Service. NR 14 TC 10 Z9 10 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD AUG PY 2012 VL 63 IS 8 BP 823 EP 826 DI 10.1176/appi.ps.201100317 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 984PX UT WOS:000307204600015 PM 22854727 ER PT J AU Martin-Ibanez, R Crespo, E Esgleas, M Urban, N Wang, B Waclaw, R Georgopoulos, K Martinez, S Campbell, K Vicario-Abejon, C Alberch, J Chan, S Kastner, P Rubenstein, JL Canals, JM AF Martin-Ibanez, Raquel Crespo, Empar Esgleas, Miriam Urban, Noelia Wang, Bei Waclaw, Ronald Georgopoulos, Katia Martinez, Salvador Campbell, Kenneth Vicario-Abejon, Carlos Alberch, Jordi Chan, Susan Kastner, Philippe Rubenstein, John L. Canals, Josep M. TI Helios Transcription Factor Expression Depends on Gsx2 and Dlx1&2 Function in Developing Striatal Matrix Neurons SO STEM CELLS AND DEVELOPMENT LA English DT Article ID CELL FATE SPECIFICATION; NEURAL STEM-CELLS; OLFACTORY-BULB; MAMMALIAN TELENCEPHALON; CEREBRAL-CORTEX; MOUSE TELENCEPHALON; PROGENITOR DOMAINS; BASAL FOREBRAIN; NERVOUS-SYSTEM; HOMEOBOX GENES AB Development of the nervous system is finely regulated by consecutive expression of cell-specific transcription factors. Here we show that Helios, a member of the Ikaros transcription factor family, is expressed in ectodermal and neuroectodermal-derived tissues. During embryonic development, Helios is expressed by several brain structures including the lateral ganglionic eminence (LGE, the striatal anlage); the cingulated, insular and retrosplenial cortex; the hippocampus; and the accessory olfactory bulb. Moreover, Helios is also expressed by Purkinje neurons during postnatal cerebellar development. Within the LGE, Helios expression follows a dynamic spatio-temporal pattern starting at embryonic stages (E14.5), peaking at E18.5, and completely disappearing during postnatal development. Helios is expressed by a small population of nestin-positive neural progenitor cells located in the subventricular zone as well as by a larger population of immature neurons distributed throughout the mantle zone. In the later, Helios is preferentially expressed in the matrix compartment, where it colocalizes with Bcl11b and Foxp1, well-known markers of striatal projection neurons. In addition, we observed that Helios expression is not detected in Dlx1/2 and Gsx2 null mutants, while its expression is maintained in Ascl1 mutants. These findings allow us to introduce a new transcription factor in the cascade of events that take part of striatal development postulating the existence of at least 4 different neural progenitors in the LGE. An Ascl1-independent but Gsx2- & Dlx1/2-dependent precursor will express Helios defining a new lineage for a subset of matrix striatal neurons. C1 [Martin-Ibanez, Raquel; Crespo, Empar; Esgleas, Miriam; Urban, Noelia; Alberch, Jordi; Canals, Josep M.] Univ Barcelona, Fac Med, Dept Cell Biol Immunol & Neurosci, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain. [Martin-Ibanez, Raquel; Crespo, Empar; Esgleas, Miriam; Urban, Noelia; Alberch, Jordi; Canals, Josep M.] Univ Barcelona, Fac Med, Cell Therapy Program, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain. [Wang, Bei; Rubenstein, John L.] Univ Calif San Francisco, Dept Psychiat, Nina Ireland Lab Dev Neurobiol, San Francisco, CA USA. [Waclaw, Ronald; Campbell, Kenneth] Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH 45229 USA. [Georgopoulos, Katia] Harvard Univ, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Martinez, Salvador] Miguel Hernandez Univ, Alicante Neurosci Inst, Consejo Super Invest Cient CSIC, Alacant, Spain. [Vicario-Abejon, Carlos] CSIC, Dept Neurobiol Mol Celular & Desarrollo, Inst Cajal, Madrid, Spain. [Chan, Susan; Kastner, Philippe] CNRS, Dept Canc Biol, Inst Genet & Biol Mol & Cellulaire, INSERM, Illkirch Graffenstaden, France. RP Canals, JM (reprint author), Univ Barcelona, Fac Med, Dept Cell Biol Immunol & Neurosci, Inst Invest Biomed August Pi & Sunyer IDIBAPS, C Casanova 143, Barcelona 08036, Spain. EM jmcanals@ub.edu RI Canals, Josep/M-3846-2014; OI Canals, Josep/0000-0001-6829-7670; Martinez, Salvador/0000-0002-9320-4103; Martinez, Salvador/0000-0002-2910-8926; Urban Avellaneda, Noelia/0000-0003-4813-9274; Alberch, Jordi/0000-0002-8684-2721 FU Ministerio de Ciencia e Innovacion, Spain [BFU2007-61230/BFI, SAF2008-04360, SAF2009-07774, PLE2009-0089]; Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion [CI-BERNED]; RETICS (Red de Terapia Celular), Spain [RD06/0010/0006, RD06/0010/0023]; Generalitat de Catalunya, Spain [2009SGR-00326]; Centre of Regenerative Medicine in Barcelona (CMRB) [Promt-0901]; Generalitat de Catalunya, Spain FX We would like to thank Cristina Herranz and Ana Lopez for technical assistance and Dr. Maria Calvo from the confocal microscopy unit of the Serveis Cientifico-Tecnics (Universitat de Barcelona) for their support and advice on confocal techniques. We are also grateful to Dr. Rudolf Grosschedl for Ebf-1-/- mice. We also thank Dr. Stephen T. Smale (Howard Hughes Medical Institute, Molecular Biology Institute, and Department of Microbiology and Immunology, University of California, Los Angeles School of Medicine) for anti-Helios antibody and Dr. Christopher A. Klug (Department of Microbiology, Division of Developmental, and Clinical Immunology, University of Alabama at Birmingham) for the MSCV plasmid encoding Helios. This study was supported by grants from the Ministerio de Ciencia e Innovacion (BFU2007-61230/BFI to C. V.-A; SAF2008-04360, to J. A.; and SAF2009-07774 and PLE2009-0089, to J. M. C.), Spain; Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion [CI-BERNED, to C. V.-A. and to J. A.; and RETICS (Red de Terapia Celular, RD06/0010/0006 to J. M. C. and RD06/0010/0023 to S. M.], Spain; and Generalitat de Catalunya (2009SGR-00326 to J. A.), Spain. The Cell Therapy Program is supported by the Centre of Regenerative Medicine in Barcelona (CMRB; Promt-0901 to J. M. C.); Generalitat de Catalunya, Spain. E. C. was a fellow of the Ministerio de Investigacion y Ciencia, Spain. NR 70 TC 9 Z9 9 U1 1 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD AUG PY 2012 VL 21 IS 12 BP 2239 EP 2251 DI 10.1089/scd.2011.0607 PG 13 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 985UH UT WOS:000307295500015 PM 22142223 ER PT J AU Eaddy, AC Cummings, BS Mchowat, J Schnellmann, RG AF Eaddy, Andre C. Cummings, Brian S. Mchowat, Jane Schnellmann, Rick G. TI The Role of Endoplasmic Reticulum Ca2+-Independent Phospholipase A(2)gamma in Oxidant-Induced Lipid Peroxidation, Ca2+ Release, and Renal Cell Death SO TOXICOLOGICAL SCIENCES LA English DT Article DE lipid peroxidation; phospholipase A(2); Ca2+ release; necrotic cell death ID ELECTROSPRAY MASS-SPECTROMETRY; OXIDATIVE STRESS; A(2) ENZYMES; FATTY-ACIDS; IDENTIFICATION; INJURY; PERMEABILITY; IPLA(2)GAMMA; SUPERFAMILY; METABOLISM AB Oxidant-induced lipid peroxidation and cell death are major components of ischemia/reperfusion and toxicant injury. Our previous studies showed that renal proximal tubular cells (RPTCs) express Ca2+-independent phospholipase A(2)gamma (iPLA(2)gamma) in endoplasmic reticulum (ER) and mitochondria and that iPLA(2)gamma is cyto-protective. Our present studies reveal the role of ER-iPLA(2)gamma in oxidant-induced ER lipid peroxidation, Ca2+ release, and cell death. Oxidant tert-butyl hydroperoxide (TBHP) caused ER lipid peroxidation and Ca2+ release in isolated rabbit kidney cortex microsomes. ER-iPLA(2)gamma inhibition, using bromoenol lactone (BEL), potentiated both oxidant-induced ER lipid peroxidation and Ca2+ release. Assessment of fatty acids using electrospray ionization-mass spectrometry revealed that ER-iPLA(2)gamma mediates the TBHP-induced release of arachidonic acid (20:4), linoleic acid (18:2), and their oxidized forms (18:2-OH, 18:2-OOH, 20:4-OH, 20:4-OOH, 20:4-(OH)(3). iPLA(2)gamma inhibition also accelerated oxidant-induced ER Ca2+ release in RPTC. Depletion of ER Ca2+ stores in RPTC with thapsigargin, an ER Ca2+ pump inhibitor, prior to TBHP exposure reduced necrotic cell death and blocked the potentiation of TBHP-induced necrotic cell death by BEL. Together, these data provide strong evidence that ER-iPLA(2)gamma protects renal cells from oxidant-induced necrotic cell death by releasing unsaturated and/or oxidized fatty acids from ER membranes, thereby preserving ER membrane integrity and preventing ER Ca2+ release. C1 [Eaddy, Andre C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Cummings, Brian S.] Univ Georgia, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA. [Mchowat, Jane] St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63104 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health (NIH) [DK-62028]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; Southern Regional Educational Board Predoctoral Scholarship; National Institute of Environmental Health Sciences (NIEHS), NIH [T32 ESO12878, F30 ES015964]; NIH [C06 RR-015455] FX This research was supported by National Institutes of Health (NIH) Grant DK-62028 and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs to R.G.S. A.C.E. was supported by a Southern Regional Educational Board Predoctoral Scholarship, a training grant from the National Institute of Environmental Health Sciences (NIEHS), NIH (T32 ESO12878), and an Individual National Research Service Award Fellowship (F30 ES015964) from NIEHS, NIH. The Medical University of South Carolina animal facilities were funded by NIH Grant C06 RR-015455. NR 32 TC 4 Z9 5 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2012 VL 128 IS 2 BP 544 EP 552 DI 10.1093/toxsci/kfs175 PG 9 WC Toxicology SC Toxicology GA 991JY UT WOS:000307698500023 PM 22584685 ER PT J AU Braquehais, MD Picouto, MD Casas, M Sher, L AF Dolores Braquehais, Maria Dolores Picouto, Maria Casas, Miquel Sher, Leo TI Hypothalamic-pituitary-adrenal axis dysfunction as a neurobiological correlate of emotion dysregulation in adolescent suicide SO WORLD JOURNAL OF PEDIATRICS LA English DT Review DE adolescence; hypothalamic-pituitary-adrenal axis; suicide ID DEXAMETHASONE-SUPPRESSION TEST; POSTTRAUMATIC-STRESS-DISORDER; SALIVARY CORTISOL; PSYCHIATRIC-SYMPTOMS; ANXIETY DISORDER; HEALTHY CONTROLS; YOUNG-ADULTS; CHILDHOOD; CHILDREN; DEPRESSION AB Biological markers of vulnerability for current or future risk of suicide in adolescents could be important adjuncts to the treatment and prevention of this phenomenon. We conducted a PubMed search of all English-language articles published between January 1990 and June 2011 using the following search terms: ("hypothalamic-pituitary-adrenal" OR "HPA") AND ("adolescence" OR "adolescent" OR "teenager") AND ("depression" OR "major depressive disorder" OR "suicidal behavior" OR "suicidal ideation" OR "suicidal thoughts" OR "deliberate self-harm" OR "suicidal attempt" OR "suicide"). HPA axis activity can be examined using different methods that do not have the same biological interpretation. An abnormal HPA axis functioning together with an anomalous interaction between HPA mechanisms and other systems such as the serotonergic system may be one of the neurobiological correlates of emotion dysregulation (ED). ED may play an important role in adolescent suicidal behavior. Some psychopathological conditions such as depression or childhood psychological trauma that increase suicidal risk in adolescents are also associated with HPA axis dysregulation. ED, a personality trait, can also be viewed as a predisposing factor that augments the vulnerability to suffer from psychiatric conditions. Correlating HPA axis dysfunction with psychological factors such as ED could lead to a better understanding of the role of HPA abnormalities in adolescent suicide and may enhance preventive and treatment strategies. C1 [Dolores Braquehais, Maria; Casas, Miquel] Univ Autonoma Barcelona, Vall Hebron Univ Hosp, Dept Psychiat & Legal Med, Barcelona 08035, Spain. [Dolores Picouto, Maria] Univ Barcelona, St Joan de Deu Hosp, Dept Child & Adolescent Psychiat & Psychol, Barcelona, Spain. [Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, James J Peters Vet Adm Med Ctr, New York, NY USA. RP Braquehais, MD (reprint author), Univ Autonoma Barcelona, Vall Hebron Univ Hosp, Dept Psychiat & Legal Med, Pg Vall Hebron 119-129, Barcelona 08035, Spain. EM mdbraquehais@vhebron.net FU Department of Health of the Government of Catalonia (Generalitat de Catalonia), Spain; Department of Health of the Generalitat of Catalonia FX The work of Dr. Maria Dolores Braquehais and Prof. Miquel Casas was partly supported by a grant from the Department of Health of the Government of Catalonia (Generalitat de Catalonia), Spain.; The work of Dr. Braquehais and Dr. Casas was partly supported by a grant of the Department of Health of the Generalitat of Catalonia. NR 90 TC 7 Z9 7 U1 2 U2 13 PU ZHEJIANG UNIV SCH MEDICINE PI HANGZHOU PA CHILDRENS HOSPITAL, 57 ZHUGAN XIANG, HANGZHOU, 310003, PEOPLES R CHINA SN 1708-8569 J9 WORLD J PEDIATR JI World Journal of Pediatrics PD AUG PY 2012 VL 8 IS 3 BP 197 EP 206 DI 10.1007/s12519-012-0358-0 PG 10 WC Pediatrics SC Pediatrics GA 988RE UT WOS:000307507400001 PM 22886191 ER PT J AU Siedner, MJ Tsai, AC Dworkin, S Mukiibi, NFB Emenyonu, NI Hunt, PW Haberer, JE Martin, JN Bangsberg, DR Weiser, SD AF Siedner, Mark J. Tsai, Alexander C. Dworkin, Shari Mukiibi, Nozmo F. B. Emenyonu, Nneka I. Hunt, Peter W. Haberer, Jessica E. Martin, Jeffrey N. Bangsberg, David R. Weiser, Sheri D. TI Sexual Relationship Power and Malnutrition Among HIV-Positive Women in Rural Uganda SO AIDS AND BEHAVIOR LA English DT Article DE Gender Equality; Malnutrition; HIV/AIDS; Sub-Saharan Africa ID INTIMATE-PARTNER VIOLENCE; SOUTH-AFRICA; SOCIAL INEQUALITIES; DISEASE PROGRESSION; NUTRITIONAL-STATUS; FOOD INSECURITY; WEIGHT-LOSS; INFECTION; RISK; INTERVENTION AB Inequality within partner relationships is associated with HIV acquisition and gender violence, but little is known about more pervasive effects on women's health. We performed a cross-sectional analysis of associations between sexual relationship power and nutritional status among women in Uganda. Participants completed questionnaires and anthropometric measurements. We assessed sexual relationship power using the Sexual Relationship Power Scale (SRPS). We performed logistic regression to test for associations between sexual relationship power and poor nutritional status including body mass index, body fat percentage, and mid-upper arm circumference. Women with higher sexual relationship power scores had decreased odds of low body mass index (OR 0.29, p = 0.01), low body fat percentage (OR 0.54, p = 0.04), and low mid-upper arm circumference (OR 0.22, p = 0.01). These relationships persisted in multivariable models adjusted for potential confounders. Targeted interventions to improve intimate partner relationship equality should be explored to improve health status among women living with HIV in rural Africa. C1 [Siedner, Mark J.; Haberer, Jessica E.; Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Infect Dis, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Boston, MA 02114 USA. [Dworkin, Shari; Hunt, Peter W.; Martin, Jeffrey N.; Weiser, Sheri D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mukiibi, Nozmo F. B.; Emenyonu, Nneka I.; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] MIT, Ragon Inst Massachusetts Gen Hosp, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Siedner, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Infect Dis, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. EM msiedner@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIAID NIH HHS [P30 AI027763, P30 AI027793, P30 AI060354]; NIMH NIH HHS [K23 MH079713, K23 MH079713-03S1, K24 MH087227, R01 MH054907] NR 48 TC 3 Z9 3 U1 3 U2 148 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD AUG PY 2012 VL 16 IS 6 BP 1542 EP 1548 DI 10.1007/s10461-012-0162-9 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 977WI UT WOS:000306695100019 PM 22382629 ER PT J AU Kreitchmann, R Harris, DR Kakehasi, F Haberer, JE Cahn, P Losso, M Teles, E Pilotto, JH Hofer, CB Read, JS AF Kreitchmann, Regis Harris, D. Robert Kakehasi, Fabiana Haberer, Jessica E. Cahn, Pedro Losso, Marcelo Teles, Elizabete Pilotto, Jose H. Hofer, Cristina B. Read, Jennifer S. CA NISDI LILAC Study Team TI Antiretroviral Adherence During Pregnancy and Postpartum in Latin America SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SELF-REPORTED ADHERENCE; WOMENS INTERAGENCY HIV; MEDICATION ADHERENCE; THERAPY ADHERENCE; INFECTED WOMEN; DRUG-USE; ASSOCIATION; HAART; NONADHERENCE AB Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p < 0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR] = 2.9, 95% confidence interval [CI]: 1.46-6.14; p = 0.0029). At 6-12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR = 1.06, 95% CI: 1.00-1.12, p = 0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR = 3.04, 95% CI: 1.34-6.90; p = 0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users. C1 [Kreitchmann, Regis] Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, Brazil. [Harris, D. Robert] WESTAT Corp, Rockville, MD 20850 USA. [Kakehasi, Fabiana] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Haberer, Jessica E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cahn, Pedro] Hosp Gen Agudos Juan A Fernandez, Buenos Aires, DF, Argentina. [Losso, Marcelo] Hosp Gen Agudos Jose Maria Ramos Mejia, Buenos Aires, DF, Argentina. [Teles, Elizabete] Hosp Femina Grp Hosp Conceicao, Porto Alegre, RS, Brazil. [Pilotto, Jose H.] Hosp Geral Nova Iguacu HIV Family Care Clin, Rio De Janeiro, Brazil. [Pilotto, Jose H.] Lab AIDS & Imunol Mol IOC Fiocruz, Rio De Janeiro, Brazil. [Hofer, Cristina B.] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, Rio De Janeiro, Brazil. [Hofer, Cristina B.] Univ Fed Rio de Janeiro, Dept Prevent Med, Rio De Janeiro, Brazil. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. RP Kreitchmann, R (reprint author), STD AIDS Municipal Ctr, Hlth Secretary, Manoel Lobato 151, Porto Alegre, RS, Brazil. EM regis.kr@terra.com.br RI Mussi-Pinhata, Marisa/G-6568-2012; Inca, Inct/K-2204-2013 FU NICHD NIH HHS [N01-HD-3-3345, N01-HD-8-0001]; PHS HHS [HHSN267200800001C] NR 34 TC 20 Z9 20 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD AUG PY 2012 VL 26 IS 8 BP 486 EP 495 DI 10.1089/apc.2012.0013 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 983KS UT WOS:000307118800007 PM 22663185 ER PT J AU Lemaitre, RN Sitlani, C Song, XL King, IB McKnight, B Spiegelman, D Sacks, FM Djousse, L Rimm, EB Siscovick, DS Mozaffarian, D AF Lemaitre, Rozenn N. Sitlani, Colleen Song, Xiaoling King, Irena B. McKnight, Barbara Spiegelman, Donna Sacks, Frank M. Djousse, Luc Rimm, Eric B. Siscovick, David S. Mozaffarian, Dariush TI Circulating and dietary alpha-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID N-3 FATTY-ACIDS; NATIONAL-HEART; FISH-OIL; ERYTHROCYTE-MEMBRANES; MYOCARDIAL-INFARCTION; RISK; DISEASE; OMEGA-3-FATTY-ACIDS; LUNG; MEN AB Background: Few studies have evaluated the association between the n-3 fatty acid alpha-linolenic acid (ALA) and the incidence of congestive heart failure (CHF). Objective: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF. Design: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged >= 65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression. Results: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535). Conclusion: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133. Am J Clin Nutr 2012;96:269-74. C1 [Lemaitre, Rozenn N.; Sitlani, Colleen; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98101 USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Song, Xiaoling] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [King, Irena B.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Spiegelman, Donna; Rimm, Eric B.; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Sacks, Frank M.; Rimm, Eric B.; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Djousse, Luc] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Sacks, Frank M.; Mozaffarian, Dariush] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Sacks, Frank M.; Siscovick, David S.; Mozaffarian, Dariush] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. RP Lemaitre, RN (reprint author), Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM rozenl@u.washington.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C]; NHLBI grants [HL080295, HL087652, HL105756, HL085710]; National Institute of Neurological Disorders and Stroke; National Institute on Aging grants [AG-023629, AG-15928, AG-20098, AG-027058] FX The research reported in this article was supported by the National Heart, Lung, and Blood Institute (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 HHSN268201200036C; NHLBI grants HL080295, HL087652, HL105756, and HL085710; the National Institute of Neurological Disorders and Stroke; and National Institute on Aging grants AG-023629, AG-15928, AG-20098, and AG-027058. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 39 TC 11 Z9 11 U1 1 U2 11 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 AUG PY 2012 VL 96 IS 2 BP 269 EP 274 DI 10.3945/ajcn.112.037960 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 978TW UT WOS:000306769700008 PM 22743310 ER PT J AU Garrett-Mayer, E Wagner, CL Hollis, BW Kindy, MS Gattoni-Celli, S AF Garrett-Mayer, Elizabeth Wagner, Carol L. Hollis, Bruce W. Kindy, Mark S. Gattoni-Celli, Sebastiano TI Vitamin D-3 supplementation (4000 IU/d for 1 y) eliminates differences in circulating 25-hydroxyvitamin D between African American and white Men SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; CARDIOVASCULAR HEALTH; US POPULATION; DISPARITIES; SAFETY AB Background: African Americans suffer disproportionately from diabetes and cardiovascular disease and are significantly more likely to have suboptimal concentrations of circulating 25-hydroxyvitamin D [25(OH)D]. The results of epidemiologic and observational studies suggest that there is a link between vitamin D deficiency and the risk of cardiometabolic disorders, which underscores the importance of maintaining healthy concentrations of 25(OH)D. Objective: The objective was to investigate whether daily supplementation with 4000 IU vitamin D-3 for 1 y would eliminate any disparities in circulating concentrations of 25(OH)D between African American and white men. Design: Serum concentrations of 25(OH)D were measured every 2 mo in 47 subjects who received a daily oral dose of 4000 IU vitamin D3 for I y. Results: More than 90% of African Americans had serum concentrations of 25(OH)D <32 ng/mL, and approximately two-thirds had serum concentrations <20 ng/mL. Furthermore, there were significant disparities in serum concentrations of 25(OH)D between African American and white men. Supplementation with 4000 IU/d for 1 y eliminated any significant differences in circulating concentrations of 25(OH)D between African American and white men. Conclusion: The results of this clinical study show the feasibility and efficacy of this approach in the elimination of hypovitaminosis D, which is a widespread health disparity among African Americans. This trial was registered at clinicaltrials.gov as NCT01045109. Am J Clin Num 2012:96:332-6. C1 [Garrett-Mayer, Elizabeth] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Wagner, Carol L.; Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Kindy, Mark S.; Gattoni-Celli, Sebastiano] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Gattoni-Celli, S (reprint author), Strom Thurmond Biomed Res Bldg,Room 338C,114 Doug, Charleston, SC 29403 USA. EM gattonis@musc.edu FU Gateway for Cancer Research; Health Services Research and Development Program of the Department of Veterans Affairs; South Carolina Clinical and Translational Research Institute; Biostatistics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina FX Supported in part by grants from the Gateway for Cancer Research, the Health Services Research and Development Program of the Department of Veterans Affairs, the South Carolina Clinical and Translational Research Institute, and the Biostatistics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina. NR 32 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2012 VL 96 IS 2 BP 332 EP 336 DI 10.3945/ajcn.112.034256 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 978TW UT WOS:000306769700016 PM 22760568 ER PT J AU Williams, BA Stern, MF Mellow, J Safer, M Greifinger, RB AF Williams, Brie A. Stern, Marc F. Mellow, Jeff Safer, Meredith Greifinger, Robert B. TI Aging in Correctional Custody: Setting a Policy Agenda for Older Prisoner Health Care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PALLIATIVE CARE; ALZHEIMERS-DISEASE; ELDERLY PERSONS; INMATES; COMMUNITY; DEMENTIA; RELEASE; STATE; RISK; COMORBIDITIES AB An exponential rise in the number of older prisoners is creating new and costly challenges for the criminal justice system, state economies, and communities to which older former prisoners return. We convened a meeting of 29 national experts in correctional health care, academic medicine, nursing, and civil rights to identify knowledge gaps and to propose a policy agenda to improve the care of older prisoners. The group identified 9 priority areas to be addressed: definition of the older prisoner, correctional staff training, definition of functional impairment in prison, recognition and assessment of dementia, recognition of the special needs of older women prisoners, geriatric housing units, issues for older adults upon release, medical early release, and prison-based palliative medicine programs. (Am J Public Health. 2012;102:1475-1481. doi:10.2105/AJPH.2012.300704) C1 [Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94117 USA. [Williams, Brie A.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Stern, Marc F.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Mellow, Jeff] CUNY John Jay Coll Criminal Justice, Dept Criminal Justice, New York, NY USA. [Greifinger, Robert B.] CUNY John Jay Coll Criminal Justice, Ctr Evaluat & Res, New York, NY USA. [Safer, Meredith] Liberian Minist Hlth & Social Welf, US Agcy Int Dev, Monrovia, Liberia. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, 3333 Calif St,Suite 380, San Francisco, CA 94117 USA. EM brie.williams@ucsf.edu FU National Institute of Aging [K23AG033102]; Jacob and Valeria Langeloth Foundation; University of California, San Francisco Hartford Center of Excellence; Langeloth Foundation Leadership Symposia in Correctional Health Care FX B. A. Williams is supported by the National Institute of Aging (grant K23AG033102), the Jacob and Valeria Langeloth Foundation, and the University of California, San Francisco Hartford Center of Excellence. This study and J. Mellow and R. B. Greifinger were also supported by a grant from the Langeloth Foundation Leadership Symposia in Correctional Health Care. NR 60 TC 30 Z9 30 U1 3 U2 28 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2012 VL 102 IS 8 BP 1475 EP 1481 DI 10.2105/AJPH.2012.300704 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 981AO UT WOS:000306937900009 PM 22698042 ER PT J AU Kapuku, GK Davis, HC Thomas, P Januzzi, J Harshfield, GA AF Kapuku, Gaston K. Davis, Harry C. Thomas, Patrick Januzzi, James Harshfield, Gregory A. TI Does the Relationship Between Natriuretic Hormones and Diastolic Function Differ by Race? SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Natriuretic hormones; Mental stress; Diastolic function; Race ID LEFT-VENTRICULAR HYPERTROPHY; CARDIOVASCULAR-DISEASE; HEART-FAILURE; HYPERTENSIVE PATIENTS; AFRICAN-AMERICANS; PEPTIDE INFUSION; BRAIN; PREVALENCE; PRESSURE; IMPACT AB Introduction: Heart failure develops earlier and is more prevalent in blacks than whites because of their higher incidence of hypertension and diabetes and likely subsequent diastolic dysfunction. Natriuretic peptides (NP) prevent cardiac malfunction through pressure, natriuresis action. However, whether race affects the relationships of NP action with cardiac function is unknown. Methods: To assess this, 55 (21 whites and 27 males) normotensive adults underwent a 2-hour protocol of 40 minutes rest, video game stressor and recovery. Mitral inflow and myocardial velocities (tissue Doppler) were recorded every 20 minutes. Blood pressure and heart rate were obtained at 10-minute intervals. Blood samples for proatrial NP and pro-brain NP (pro-BNP) were collected every 40 minutes. Results: There were differences in the association between (1) the changes from rest to stress for E/A ratio and double product (whites, r = -0.42; blacks, r = 0. 10; P = 0.034 for difference between correlations); (2) stress E-m and pro-atrial NP (whites, r = 0.59; blacks, r = -0.25; P = 0.025); (3) rest E-m and BNP (whites, r = 0.83; blacks r = -0.17; P = 000); (4) rest E-m/A(m) and pro-BNP (whites, r = 0.70; blacks, r = -0.42; P = 0.003); (5) rest E/E-m and pro-BNP (whites, r = -0.61; blacks, r = 0.31; P = 0.015) and (6) stress E and pro-BNP (whites, r = 0.56; blacks, r = -0.18; P = 0.043). Conclusion: The higher correlations between levels of NP and diastolic function indices both at rest and stress suggest that NP protective action is more pronounced in whites than in blacks. C1 [Kapuku, Gaston K.; Davis, Harry C.; Harshfield, Gregory A.] Georgia Hlth Sci Univ, Med Coll Georgia, Georgia Prevent Inst, Dept Pediat, Augusta, GA 30912 USA. [Kapuku, Gaston K.] Georgia Hlth Sci Univ, Dept Med, Med Coll Georgia, Augusta, GA USA. [Thomas, Patrick; Januzzi, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kapuku, GK (reprint author), Georgia Hlth Sci Univ, Med Coll Georgia, Georgia Prevent Inst, Dept Pediat, MCG Annex HS 1640, Augusta, GA 30912 USA. EM gkapuku@georgiahealth.edu FU NIH [HL076696]; AHA [0530046N] FX This study was supported by grants from NIH (HL076696) and AHA (0530046N). NR 28 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD AUG PY 2012 VL 344 IS 2 BP 96 EP 99 DI 10.1097/MAJ.0b013e31823673fd PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 981KJ UT WOS:000306966300003 PM 22314104 ER PT J AU Rosow, CE AF Rosow, Carl E. TI Making Sedation Safer Is Simulation the Answer? SO ANESTHESIOLOGY LA English DT Editorial Material ID MIDAZOLAM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Rosow, CE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. EM crosow@partners.org NR 4 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 AUG PY 2012 VL 117 IS 2 BP 232 EP 233 DI 10.1097/ALN.0b013e31825fb1e9 PG 2 WC Anesthesiology SC Anesthesiology GA 981RG UT WOS:000306986600004 PM 22692383 ER PT J AU Buvanendran, A Rathmell, JP AF Buvanendran, Asokumar Rathmell, James P. TI Ultrasound versus Fluoroscopy in Image-guided Pain Treatment Use Caution SO ANESTHESIOLOGY LA English DT Editorial Material ID STELLATE GANGLION BLOCK; MEDIAL BRANCH-BLOCK; NERVE; ACCURACY C1 [Buvanendran, Asokumar] Rush Univ, Coll Med, Dept Anesthesiol, Chicago, IL 60612 USA. [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Rathmell, James P.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Buvanendran, A (reprint author), Rush Univ, Coll Med, Dept Anesthesiol, Chicago, IL 60612 USA. EM asokumar@aol.com NR 9 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 2012 VL 117 IS 2 BP 236 EP 237 DI 10.1097/ALN.0b013e3182605e2a PG 2 WC Anesthesiology SC Anesthesiology GA 981RG UT WOS:000306986600006 PM 22705570 ER PT J AU Wilhelm, S Peterson, AL Piacentini, J Woods, DW Deckersbach, T Sukhodolsky, DG Chang, S Liu, HB Dziura, J Walkup, JT Scahill, L AF Wilhelm, Sabine Peterson, Alan L. Piacentini, John Woods, Douglas W. Deckersbach, Thilo Sukhodolsky, Denis G. Chang, Susanna Liu, Haibei Dziura, James Walkup, John T. Scahill, Lawrence TI Randomized Trial of Behavior Therapy for Adults With Tourette Syndrome SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; HABIT REVERSAL; TIC DISORDERS; SUPPORTIVE PSYCHOTHERAPY; CHILDREN; SUPPRESSION; RISPERIDONE; ADOLESCENTS; SEVERITY AB Context: Tics in Tourette syndrome begin in childhood, peak in early adolescence, and often decrease by early adulthood. However, some adult patients continue to have impairing tics. Medications for tics are often effective but can cause adverse effects. Behavior therapy may offer an alternative but has not been examined in a large-scale controlled trial in adults. Objective: To test the efficacy of a comprehensive behavioral intervention for tics in adults with Tourette syndrome of at least moderate severity. Design: A randomized controlled trial with posttreatment evaluations at 3 and 6 months for positive responders. Setting: Three outpatient research clinics. Patients: Patients (N=122; 78 males; age range, 16-69 years) with Tourette syndrome or chronic tic disorder were recruited between December 27, 2005, and May 21, 2009. Interventions: Patients received 8 sessions of comprehensive behavioral intervention for tics or 8 sessions of supportive treatment for 10 weeks. Patients with a positive response were given 3 monthly booster sessions. Main Outcome Measures: Total tic score on the Yale Global Tic Severity Scale and the Clinical Global Impression-Improvement scale rated by a clinician masked to treatment assignment. Results: Behavior therapy was associated with a significantly greater mean (SD) decrease on the Yale Global Tic Severity Scale (24.0[6.47] to 17.8[7.32]) from baseline to end point compared with the control treatment (21.8[6.59] to 19.3[7.40]) (P < .001; effect size=0.57). Twenty-four of 63 patients (38.1%) were rated as much improved or very much improved on the Clinical Global Impression-Improvement scale compared with 4 of 63 (6.4%) in the control group (P < .001). Attrition was 13.9%, with no difference across groups. Patients receiving behavior therapy who were available for assessment at 6 months after treatment showed continued benefit. Conclusion: Comprehensive behavior therapy is a safe and effective intervention for adults with Tourette syndrome. C1 [Wilhelm, Sabine; Deckersbach, Thilo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sukhodolsky, Denis G.; Scahill, Lawrence] Yale Univ, Sch Nursing, Yale Child Study Ctr, New Haven, CT 06536 USA. [Liu, Haibei; Dziura, James] Yale Univ, Sch Med, New Haven, CT USA. [Piacentini, John; Chang, Susanna] Univ Calif Los Angeles, Los Angeles, CA USA. [Woods, Douglas W.] Univ Wisconsin, Milwaukee, WI 53201 USA. [Walkup, John T.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Wilhelm, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Ste 2282, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu OI Sukhodolsky, Denis/0000-0002-5401-792X; Scahill, Lawrence/0000-0001-5073-1707 FU Oxford University Press; National Institutes of Health; Guilford Publications; New Harbinger Publications; American Psychological Association; National Institute of Mental Health; New Harbinger and Springer Publications; American Psychiatric Press; Eli Lilly; JAZZ Pharmaceuticals; CMP Media; Medical Education Reviews; McMahon Group; DiMedix; Tourette Disorder Association; National Institute of Mental Health [5R01MH069877, R01MH069874, RO1MH069875]; Yale University Clinical and Translational Sciences Award [UL1 RR024139]; National Center for Research Resources, National Institutes of Health; Tourette Syndrome Association FX Drs Wilhelm, Peterson, Piacentini, Woods, Deckersbach, Chang, Walkup, and Scahill report receiving royalties from Oxford University Press for a treatment manual on tic disorders. Drs Wilhelm, Peterson, Piacentini, Woods, Chang, Sukhodolsky, Walkup, and Scahill report receiving honoraria for continuing education presentations from the Tourette Syndrome Association. Drs Piacentini, Woods, and Walkup receive royalties from Guilford Press for a book on Tourette disorder. Dr Wilhelm reports receiving support in the form of free medication and matching placebo from Forest Laboratories for clinical trials funded by the National Institutes of Health and receiving book royalties from Guilford Publications, New Harbinger Publications, and Oxford University Press and speaking honoraria from PRIMEDIA Healthcare, a publicly traded company working as a logistics collaborator for the Massachusetts General Hospital Psychiatry Academy (the education programs conducted by the Massachusetts General Hospital Psychiatry Academy were supported through independent medical education grants from pharmaceutical companies cosupporting the overall program, along with participant tuition). Dr Piacentini reports receiving royalties from Oxford University Press for treatment manuals on child obsessive-compulsive disorder and American Psychological Association Books for other books on child mental health, speaking honoraria from Janssen-Cilag, and support in the form of free medication and matching placebo from Pfizer for clinical trials funded by the National Institute of Mental Health. Dr Woods reports receiving book royalties from New Harbinger and Springer Publications. Dr Scahill has received royalties from Oxford University Press and American Psychiatric Press; has served as a consultant for Boehringer-Ingelheim, Biomarin, Hoffman NeuroSearch, and Pfizer; and has had research support from Shire Pharmaceutical and Seaside Therapeutics. He also reports receiving support in the form of free medication and matching placebo from Shire Pharmaceuticals for a clinical trial funded by the National Institute of Mental Health. Dr Deckersbach reports receiving consulting fees from the Constella Group for serving as a reviewer for the Department of Defense's Congressionally Directed Medical Research Program. He also reports receiving honoraria, consulting fees, and/or royalties from Medacorp, Massachusetts General Hospital Psychiatry Academy, BrainCells Inc, Systems Research and Applications Corp, Boston University, the Catalan Agency for Health Technology Assessment and Research, and the National Association of Social Workers-Massachusetts. He reports participating in research funded by Janssen, Forest Research Institute, Shire Development Inc, Medtronic, Cyberonics, and Northstar. Dr Walkup reports receiving consulting fees from Eli Lilly and JAZZ Pharmaceuticals and lecture fees from CMP Media, Medical Education Reviews, McMahon Group, DiMedix, and the Tourette Disorder Association. He reports receiving free drug and matching placebo from Pfizer and Lilly and free drugs from Abbott for National Institute of Mental Health-funded clinical trials. He reports receiving fees for consultation with defense counsel and submission of written reports in litigation involving GlaxoSmithKline. This work was supported by grants 5R01MH069877 (Dr Wilhelm), R01MH069874 (Dr Scahill), and RO1MH069875 (Dr Petersen) from the National Institute of Mental Health with subcontracts to Drs Piacentini and Woods. Dr Walkup consulted on this grant.; Drs Scahill and Dziura receive support from the Yale University Clinical and Translational Sciences Award grant UL1 RR024139 from the National Center for Research Resources, National Institutes of Health. This study was also supported by Tourette Syndrome Association funding to Dr Scahill. NR 47 TC 72 Z9 72 U1 1 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2012 VL 69 IS 8 BP 795 EP 803 DI 10.1001/archgenpsychiatry.2011.1528 PG 9 WC Psychiatry SC Psychiatry GA 984JD UT WOS:000307185000005 PM 22868933 ER PT J AU Mansbach, JM Piedra, PA Teach, SJ Sullivan, AF Forgey, T Clark, S Espinola, JA Camargo, CA AF Mansbach, Jonathan M. Piedra, Pedro A. Teach, Stephen J. Sullivan, Ashley F. Forgey, Tate Clark, Sunday Espinola, Janice A. Camargo, Carlos A., Jr. CA MARC-30 Investigators TI Prospective Multicenter Study of Viral Etiology and Hospital Length of Stay in Children With Severe Bronchiolitis SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; REAL-TIME PCR; RHINOVIRUS INFECTION; HUMAN METAPNEUMOVIRUS; ASTHMA DEVELOPMENT; CLINICAL SYMPTOMS; DISEASE SEVERITY; RISK-FACTORS; INFANTS; EXPRESSION AB Objective: To determine whether hospital length of stay (LOS) for acute bronchiolitis is influenced by the infecting pathogen. Design: A prospective observational cohort study was performed during 3 consecutive years. Setting: Sixteen US hospitals participated in the study. Participants: Children younger than 2 years hospitalized with bronchiolitis were included. Main Exposure: The results of nasopharyngeal aspirate polymerase chain reaction pathogen testing served as the main exposure. Main Outcome Measure: Hospital LOS was determined. Results: Of 2207 participants, 72.0% had respiratory syncytial virus (RSV) and 25.6% had human rhinovirus (HRV); the incidence of each of the other viruses and bacteria was 7.8% or less. Multiple pathogen infections were present in 29.8% of the children. There were 1866 children (84.5%) with RSV and/or HRV. Among these 1866 children, the median age was 4 months and 59.5% were male. The median LOS was 2 days (interquartile range, 1-4 days). Compared with children who had only RSV, an LOS of 3 or more days was less likely among children with HRV alone (adjusted odds ratio [AOR], 0.36; 95% CI, 0.20-0.63; P < .001) and those with HRV plus non-RSV pathogens (AOR, 0.39; 95% CI, 0.23-0.66; P < .001) but more likely among children with RSV plus HRV(AOR, 1.33; 95% CI, 1.02-1.73; P =. 04), controlling for 15 demographic and clinical factors. Conclusions: In this multicenter study of children hospitalized with bronchiolitis, RSV was the most common virus detected, but HRV was detected in one-quarter of the children. Since 1 in 3 children had multiple virus infections and HRV was associated with LOS, these data challenge the effectiveness of current RSV-based cohorting practices, the sporadic testing for HRV in bronchiolitis research, and current thinking that the infectious etiology of severe bronchiolitis does not affect short-term outcomes. C1 [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Sullivan, Ashley F.; Forgey, Tate; Espinola, Janice A.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Teach, Stephen J.] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. [Clark, Sunday] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Mansbach, JM (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, 300 Longwood Ave,Main Clin Bldg 9 S,Ste 9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu FU National Institutes of Health [U01 AI-67693, K23 AI-77801, UL1 RR-031988] FX This study was supported by grants U01 AI-67693, K23 AI-77801, and UL1 RR-031988 from the National Institutes of Health. NR 45 TC 95 Z9 102 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 2012 VL 166 IS 8 BP 700 EP 706 DI 10.1001/archpediatrics.2011.1669 PG 7 WC Pediatrics SC Pediatrics GA 984KU UT WOS:000307189300003 PM 22473882 ER PT J AU Morell, E Wolfe, J Scheurer, M Thiagarajan, R Morin, C Beke, DM Smoot, L Cheng, H Gauvreau, K Blume, ED AF Morell, Emily Wolfe, Joanne Scheurer, Mark Thiagarajan, Ravi Morin, Caroline Beke, Dorothy M. Smoot, Leslie Cheng, Henry Gauvreau, Kimberlee Blume, Elizabeth D. TI Patterns of Care at End of Life in Children With Advanced Heart Disease SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID UNITED-STATES; CANCER; TRANSPLANTATION AB Objective: To describe patterns of care for pediatric patients with advanced heart disease who experience in-hospital death. Design: Retrospective single-institution medical record review. Setting: A tertiary care pediatric hospital. Participants: All patients younger than 21 years who died in the inpatient setting between January 1, 2007, and December 31, 2009, with primary cardiac diagnoses or who had ever received a cardiology consult (N = 468). After excluding patients with significant noncardiac primary diagnoses, 111 children formed the analytic sample. Main Outcome Measure: In-hospital deaths of children with heart disease during a 3-year period. Results: Median age at death was 4.8 months (age range, 1 day to 20.5 years), with 84 deaths (75.7%) occurring before age 1 year. Median length of terminal hospital stay was 22 days (range, 1-199 days). Diagnoses included 84 patients (75.7%) with congenital heart disease, 10 (9.0%) with cardiomyopathy/ myocarditis, 9 (8.1%) with pulmonary hypertension, and 8 (7.2%) with heart transplants. Sixty-two patients (55.9%) had received cardiopulmonary resuscitation during their last hospital admission. At the end of life, 21 children (18.9%) had gastrostomy tubes and 26 (23.4%) had peritoneal drains. Most patients (91.9%) received ventilation, with half also receiving mechanical circulatory support. Eighty-three patients (74.8%) experienced additional end-organ failure. Classified by mode of death, 76 patients (68.5%) had disease-directed support withdrawn, 28 (25.2%) died during resuscitation, and 7 (6.3%) died while receiving comfort care after birth. Eighty-three percent of parents were present at the time of death. Conclusion: Infants and children who die of advanced heart disease frequently succumb in the intensive care setting with multisystem organ failure and exposure to highly technical care. C1 [Scheurer, Mark; Thiagarajan, Ravi; Morin, Caroline; Beke, Dorothy M.; Smoot, Leslie; Cheng, Henry; Gauvreau, Kimberlee; Blume, Elizabeth D.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Morell, Emily] Harvard Univ, Sch Med, Boston, MA USA. [Wolfe, Joanne] Dana Farber Canc Inst, Div Palliat Care Med, Boston, MA 02115 USA. [Scheurer, Mark] Med Univ S Carolina, Dept Pediat, Div Cardiol, Charleston, SC USA. RP Blume, ED (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM Betsy.Blume@CARDIO.CHBOSTON.ORG FU Heart Failure and Transplant Educational Fund; Kara Duclos Fund; Ghiso Fellowship for Compassionate Medical Care, Harvard Medical School FX This study was supported by the Heart Failure and Transplant Educational Fund (Dr Blume), the Kara Duclos Fund, and the Ghiso Fellowship for Compassionate Medical Care, Harvard Medical School (Ms Morell). NR 9 TC 13 Z9 13 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 2012 VL 166 IS 8 BP 745 EP 748 DI 10.1001/archpediatrics.2011.1829 PG 4 WC Pediatrics SC Pediatrics GA 984KU UT WOS:000307189300010 PM 22473887 ER PT J AU Wong, S Smith, M Oudard, S Karsh, L Egerdie, B Van Veldhuizen, P Gomez-Veiga, F Dearnaley, D Dogliotti, L Fisher, H Wirth, M Charu, V Kueppers, F de Oca, LM Rendon, R Pavlik, I Julka, PK Ye, Z Dansey, R Goessl, C AF Wong, S. Smith, M. Oudard, S. Karsh, L. Egerdie, B. Van Veldhuizen, P. Gomez-Veiga, F. Dearnaley, D. Dogliotti, L. Fisher, H. Wirth, M. Charu, V. Kueppers, F. Montes de Oca, L. Rendon, R. Pavlik, I. Julka, P. K. Ye, Z. Dansey, R. Goessl, C. TI BONE METASTASIS-FREE SURVIVAL IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER TREATED WITH DENOSUMAB: SUB-GROUP ANALYSES FROM A PHASE III RANDOMISED, DOUBLE-BLIND TRIAL SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Wong, S.] Western Hosp, Melbourne, Vic, Australia. [Smith, M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Oudard, S.] Georges Pompidou Hosp, Paris, France. [Karsh, L.] Urol Ctr Colorado, Denver, CO USA. [Egerdie, B.] Urol Associates Urol Med Res, Kitchener, ON, Canada. [Van Veldhuizen, P.] Kansas City VA Med Ctr, Kansas City, MO USA. [Gomez-Veiga, F.] Hosp Univ Juan Canalejo, La Coruna, Spain. [Dearnaley, D.] Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. [Dogliotti, L.] Osped San Luigi Gonzaga, Orbassano, Italy. [Fisher, H.] Urol Inst NE New York, Albany, NY USA. [Wirth, M.] Univ Klinikum Carl Gustav Carus, Dresden, Germany. [Charu, V.] Pacific Canc Med Ctr Inc, Anaheim, CA USA. [Kueppers, F.] Canterbury Urol Res Trust, Christchurch, New Zealand. [Montes de Oca, L.] Ctr Diagnost Urol, Buenos Aires, DF, Argentina. [Rendon, R.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Pavlik, I.] Gen Teaching Hosp, Prague, Czech Republic. [Pavlik, I.] Fac Med 1, Prague, Czech Republic. [Julka, P. K.] All India Inst Med Sci, New Delhi, India. [Ye, Z.; Dansey, R.; Goessl, C.] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD AUG PY 2012 VL 8 SU 2 SI SI BP 41 EP 42 PG 2 WC Oncology SC Oncology GA 981IK UT WOS:000306960100013 ER PT J AU Marx, GM Smith, MR Saad, F Shore, ND Oudard, S Miller, K Tombal, B Sieber, P Fizazi, K Van Veldhuizen, PJ Damiao, R Morote, J Feng, A Dansey, R Goessl, C AF Marx, G. M. Smith, M. R. Saad, F. Shore, N. D. Oudard, S. Miller, K. Tombal, B. Sieber, P. Fizazi, K. Van Veldhuizen, P. J. Damiao, R. Morote, J. Feng, A. Dansey, R. Goessl, C. TI DENOSUMAB PROLONGS BONE-METASTASIS-FREE SURVIVAL IN MEN WITH NON-METASTATIC CASTRATE-RESISTANT PROSTATE CANCER PRESENTING WITH AGGRESSIVE PROSTATE-SPECIFIC ANTIGEN KINETICS: A POST HOC SUBSET ANALYSIS SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Marx, G. M.] Sydney Haematol Oncol Clin, Sydney, NSW, Australia. [Marx, G. M.] Univ Sydney, Sydney, NSW 2006, Australia. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Saad, F.] Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. [Shore, N. D.] Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Oudard, S.] Georges Pompidou European Hosp, Paris, France. [Miller, K.] Charite, D-13353 Berlin, Germany. [Tombal, B.] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. [Sieber, P.] Urol Associates Lancaster Ltd, Lancaster, PA USA. [Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Paris, France. [Van Veldhuizen, P. J.] Kansas City VA Med Ctr, Kansas City, MO USA. [Damiao, R.] Hosp Univ Pedro Ernesto, Rio De Janeiro, Brazil. [Morote, J.] Vall dHebron Univ Hosp, Barcelona, Spain. [Feng, A.; Dansey, R.; Goessl, C.] Amgen Inc, Thousand Oaks, CA 91320 USA. EM khutton@amgen.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD AUG PY 2012 VL 8 SU 2 SI SI BP 45 EP 45 PG 1 WC Oncology SC Oncology GA 981IK UT WOS:000306960100016 ER PT J AU Park, EY Kazlauskas, A AF Park, Eun Young Kazlauskas, Andrius TI Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA) SO BIOSCIENCE REPORTS LA English DT Article DE conditioned medium; endothelial cell; intracellular signalling; lysophosphatidic acid; vascular endothelial growth factor A ID PHOSPHOLIPASE C-GAMMA; CELLULAR-RESPONSES; GROWTH-FACTOR; PHOSPHORYLATION; RECEPTORS; AUTOTAXIN; BLOOD; DESENSITIZATION; GELSOLIN; DISEASE AB The plasma level of LPA (lysophosphatidic acid) (200-600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA. C1 [Park, Eun Young; Kazlauskas, Andrius] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. EM andrius_kazlauskas@meei.harvard.edu FU National Institutes of Health [EY018344] FX This work was supported by the National Institutes of Health [grant number EY018344 (to A.K.)]. NR 29 TC 5 Z9 5 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PD AUG PY 2012 VL 32 IS 4 BP 393 EP 400 DI 10.1042/BSR20120033 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 983TG UT WOS:000307141000005 PM 22639801 ER PT J AU Yuen, HF Abramczyk, O Montgomery, G Chan, KK Huang, YH Sasazuki, T Shirasawa, S Gopesh, S Chan, KW Fennell, D Janne, P El-Tanani, M Murray, JT AF Yuen, Hiu-Fung Abramczyk, Olga Montgomery, Grant Chan, Ka-Kui Huang, Yu-Han Sasazuki, Takehiko Shirasawa, Senji Gopesh, Srivastava Chan, Kwok-Wah Fennell, Dean Janne, Pasi El-Tanani, Mohamed Murray, James T. TI Impact of oncogenic driver mutations on feedback between the PI3K and MEK pathways in cancer cells SO BIOSCIENCE REPORTS LA English DT Article DE Akt; cancer cell; c-Met; K-Ras; mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase (MEK); phosphoinositide 3-kinase (PI3K) ID KINASE INHIBITOR CI-1040; PYRIDINYLFURANOPYRIMIDINE INHIBITOR; PANCREATIC-CANCER; BREAST-CANCER; TUMOR-GROWTH; IN-VIVO; SURVIVAL; PI-103; ACTIVATION; COLON AB Inhibition of the PI3K (phosphoinositide 3-kinase)/Akt/mTORC1 (mammalian target of rapamycin complex 1) and Ras/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK pathways for cancer therapy has been pursued for over a decade with limited success. Emerging data have indicated that only discrete subsets of cancer patients have favourable responses to these inhibitors. This is due to genetic mutations that confer drug insensitivity and compensatory mechanisms. Therefore understanding of the feedback mechanisms that occur with respect to specific genetic mutations may aid identification of novel biomarkers that predict patient response. In the present paper, we show that feedback between the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways is cell-line-specific and highly dependent on the activating mutation of K-Ras or overexpression c-Met. We found that cell lines exhibited differential signalling and apoptotic responses to PD184352, a specific MEK inhibitor, and PI103, a second-generation class I PI3K inhibitor. We reveal that feedback from the PI3K/Akt/mTORC1 to the Ras/MEK/ERK pathway is present in cancer cells harbouring either K-Ras activating mutations or amplification of c-Met but not the wild-type counterparts. Moreover, we demonstrate that inhibition of protein phosphatase activity by OA (okadaic acid) restored PI103-mediated feedback in wild-type cells. Together, our results demonstrate a novel mechanism for feedback between the PI3K/Akt/mTORC1 and the Ras/MEK/ERK pathways that only occurs in K-Ras mutant and c-Met amplified cells but not the isogenic wild-type cells through a mechanism that may involve inhibition of a specific endogenous phosphatase(s) activity. We conclude that monitoring K-Ras and c-Met status are important biomarkers for determining the efficacy of PI103 and other PI3K/Akt inhibitors in cancer therapy. C1 [Yuen, Hiu-Fung; Montgomery, Grant; Chan, Ka-Kui; El-Tanani, Mohamed; Murray, James T.] Queens Univ Belfast, CCRCB, Belfast, Antrim, North Ireland. [Yuen, Hiu-Fung; Huang, Yu-Han] ASTAR, Inst Mol & Cell Biol, Singapore, Singapore. [Abramczyk, Olga] M Nencki Inst Expt Biol, PL-02093 Warsaw, Poland. [Sasazuki, Takehiko; Shirasawa, Senji] Fukuoka Univ, Fac Med, Dept Cell Biol, Fukuoka, Japan. [Gopesh, Srivastava; Chan, Kwok-Wah] Univ Hong Kong, Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Fennell, Dean] Univ Leicester, MRC Toxicol Unit, Leicester, Leics, England. [Janne, Pasi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP El-Tanani, M (reprint author), Queens Univ Belfast, CCRCB, Belfast, Antrim, North Ireland. EM m.el-tanani@qub.ac.uk; j.t.murray@qub.ac.uk RI ASTAR, IMCB/E-2320-2012; OI Murray, James/0000-0002-6928-2347 FU Cancer Research, U.K. (China Fellowship); Almac Discovery, U.K. FX This study was supported by Cancer Research, U.K. (China Fellowship to H.-F.Y.) and Almac Discovery, U.K. (an exploratory grant to O.A.) NR 40 TC 11 Z9 11 U1 0 U2 6 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PD AUG PY 2012 VL 32 IS 4 BP 413 EP 422 DI 10.1042/BSR20120050 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 983TG UT WOS:000307141000007 PM 22668349 ER PT J AU Ancukiewicz, M Miller, CL Skolny, MN O'Toole, J Warren, LE Jammallo, LS Specht, MC Taghian, AG AF Ancukiewicz, Marek Miller, Cynthia L. Skolny, Melissa N. O'Toole, Jean Warren, Laura E. Jammallo, Lauren S. Specht, Michelle C. Taghian, Alphonse G. TI Comparison of relative versus absolute arm size change as criteria for quantifying breast cancer-related lymphedema: the flaws in current studies and need for universal methodology SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer-related lymphedema; Quantification of lymphedema; Arm swelling; Quality of life ID RANDOMIZED CONTROLLED-TRIAL; SENTINEL NODE BIOPSY; LIMB VOLUME CHANGE; QUALITY-OF-LIFE; POSTMASTECTOMY LYMPHEDEMA; AXILLARY DISSECTION; LASER THERAPY; RISK-FACTORS; SURGERY; SURVIVORS AB The purpose of this article is to evaluate arm measurements of breast cancer patients to critically assess absolute change in arm size compared to relative arm volume change as criteria for quantifying breast cancer-related lymphedema (BCRL). We used pre-operative measurements of 677 patients screened for BCRL before and following treatment of unilateral breast cancer at Massachusetts General Hospital between 2005 and 2008 to model the effect of an absolute change in arm size of 200 mL or 2 cm compared to relative arm volume change. We also used sequential measurements to analyze temporal variation in unaffected arm volume. Pre-operative arm volumes ranged from 1,270 to 6,873 mL and correlated strongly (Kendall's tau = 0.55) with body mass index (BMI). An absolute arm volume change of 200 mL corresponded to relative arm volume changes ranging from 2.9 to 15.7 %. In a subset of 45 patients, modeling of a 2-cm change in arm circumference predicted relative arm volume changes ranging from 6.0 to 9.8 %. Sequential measurements of 124 patients with > 6 measurements demonstrated remarkable temporal variation in unaffected arm volume (median within-patient change 10.5 %). The magnitude of such fluctuations correlated (tau = 0.36, P < 0.0001) with pre-operative arm volume, patient weight, and BMI when quantified as absolute volume change, but was independent of these variables when quantified as relative arm volume change (P > .05). Absolute changes in arm size used as criteria for BCRL are correlated with pre-operative and temporal changes in body size. Therefore, utilization of absolute volume or circumference change in clinical trials is flawed because specificity depends strongly on patient body size. Relative arm volume change is independent of body size and should thus be used as the standard criterion for diagnosis of BCRL. C1 [Ancukiewicz, Marek; Miller, Cynthia L.; Skolny, Melissa N.; Warren, Laura E.; Jammallo, Lauren S.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [O'Toole, Jean] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. [Specht, Michelle C.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ataghian@partners.org FU National Cancer Institute [R01CA139118, P50CA089393] FX The project described was supported by Award no. R01CA139118 (AGT) and Award no. P50CA089393 (AGT) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 61 TC 29 Z9 29 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2012 VL 135 IS 1 BP 145 EP 152 DI 10.1007/s10549-012-2111-8 PG 8 WC Oncology SC Oncology GA 986HW UT WOS:000307333700014 PM 22710706 ER PT J AU Jakubowiak, AJ Richardson, PG Zimmerman, T Alsina, M Kaufman, JL Kandarpa, M Kraftson, S Ross, CW Harvey, C Hideshima, T Sportelli, P Poradosu, E Gardner, L Giusti, K Anderson, KC AF Jakubowiak, Andrzej J. Richardson, Paul G. Zimmerman, Todd Alsina, Melissa Kaufman, Jonathan L. Kandarpa, Malathi Kraftson, Stephanie Ross, Charles W. Harvey, Colleen Hideshima, Teru Sportelli, Peter Poradosu, Enrique Gardner, Lesa Giusti, Kathy Anderson, Kenneth C. TI Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE perifosine; lenalidomide; dexamethasone; relapsed multiple myeloma; Akt ID DOSE DEXAMETHASONE; BORTEZOMIB; COMBINATION; AKT; DOXORUBICIN; RAPAMYCIN; CELLS AB The combination of lenalidomidedexamethasone is active in multiple myeloma (MM). Preclinical data showed that the Akt inhibitor, perifosine, sensitized MM cells to lenalidomide and dexamethasone, providing the rationale for this Phase I, multicentre, single-arm study to assess the safety and determine the maximum-tolerated dose (MTD) of perifosinelenalidomidedexamethasone in relapsed and relapsed/refractory MM. Patients received escalating doses of perifosine 50100mg daily and lenalidomide 1525mg once daily on days 121 of each 28-d cycle, plus dexamethasone 2040mg weekly thereafter, as indicated. Thirty-two patients were enrolled across four dose cohorts. MTD was not reached, with 31 patients evaluable for safety/tolerability. The most common all-causality grade 1-2 adverse events were fatigue (48%) and diarrhoea (45%), and grade 34 neutropenia (26%), hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%). Among 30 evaluable patients, 73% (95% confidence interval, 57.589.2%) achieved a minimal response or better, including 50% with a partial response or better. Median progression-free survival was 10.8months and median overall survival 30.6months. Response was associated with phospho-Akt in pharmacodynamic studies. Perifosinelenalidomidedexamethasone was well tolerated and demonstrated encouraging clinical activity in relapsed and relapsed/refractory MM. C1 [Jakubowiak, Andrzej J.; Kandarpa, Malathi; Kraftson, Stephanie; Harvey, Colleen] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. [Richardson, Paul G.; Hideshima, Teru; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zimmerman, Todd] Univ Chicago, Ctr Canc, Chicago, IL 60637 USA. [Alsina, Melissa] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Kaufman, Jonathan L.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Ross, Charles W.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Sportelli, Peter; Poradosu, Enrique; Gardner, Lesa] Keryx Biopharmaceut Inc, New York, NY USA. [Giusti, Kathy] Multiple Myeloma Res Consortium, Norwalk, CT USA. RP Jakubowiak, AJ (reprint author), Univ Chicago, Med Ctr, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM ajakubowiak@medicine.bsd.uchicago.edu FU Keryx Biopharmaceuticals, Inc.; MMRC; Celgene; Millennium; Ortho-Biotech; Merck FX This trial was supported by Keryx Biopharmaceuticals, Inc. and the MMRC. Writing support was funded by Keryx Biopharmaceuticals, Inc.; Research funding: MA (Celgene, Millennium, Ortho-Biotech), JLK (Merck, Celgene), KG No conflicts of interest declared NR 30 TC 29 Z9 29 U1 1 U2 3 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 AUG PY 2012 VL 158 IS 4 BP 472 EP 480 DI 10.1111/j.1365-2141.2012.09173.x PG 9 WC Hematology SC Hematology GA 978QO UT WOS:000306760500006 PM 22640031 ER PT J AU Yotsumoto, Y Seitz, AR Shimojo, S Sakagami, M Watanabe, T Sasaki, Y AF Yotsumoto, Yuko Seitz, Aaron R. Shimojo, Shinsuke Sakagami, Masamichi Watanabe, Takeo Sasaki, Yuka TI Performance Dip in Motor Response Induced by Task-Irrelevant Weaker Coherent Visual Motion Signals SO CEREBRAL CORTEX LA English DT Article DE fMRI; performance dip; pre-SMA/SMA; task-irrelevant stimulus; visual motion stimulus ID SURFACE-BASED ANALYSIS; MEDIAL FRONTAL-CORTEX; EVENT-RELATED FMRI; PREFRONTAL CORTEX; FUNCTIONAL MRI; PRE-SMA; MOVING STIMULI; MACAQUE MT; AREA; INHIBITION AB The Performance Dip is a newly characterized behavioral phenomenon, where, paradoxically, a weaker task-irrelevant visual stimulus causes larger disturbances on the accuracy of a main letter identification task than a stronger stimulus does. Understanding mechanisms of the Performance Dip may provide insight into unconsciousness behavior. Here, we investigated the generalization of the Performance Dip. Specifically, we tested whether the Performance Dip occurs in a motion-related Simon task, and if so, whether the Performance Dip involves the same brain region, that is, the dorsolateral prefrontal cortex (DLPFC), previously implicated in the Performance Dip, or the supplementary motor area (SMA) and pre-SMA, implicated in a motion-related Simon Task. Subjects made manual directional responses according to the color of stochastic moving dots while ignoring the global direction of moving dots, which could be either congruent or incongruent to the response appropriate to the main task. We found that weak incongruent task-irrelevant stimuli caused a Performance Dip, in which the SMA and pre-SMA, rather than DLPFC, played critical roles. Our results suggest a possible common brain mechanism across different neural circuits, in which weak, but not strong, task-irrelevant information is free from inhibition and intrudes into neural circuits relevant to the main task. C1 [Yotsumoto, Yuko; Sasaki, Yuka] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Yotsumoto, Yuko; Seitz, Aaron R.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Yotsumoto, Yuko; Watanabe, Takeo] Keio Univ, Global Ctr Excellence Program, Ctr Adv Res Log & Sensibil, Minato Ku, Tokyo 1080073, Japan. [Seitz, Aaron R.] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. [Shimojo, Shinsuke] CALTECH, Div Biol Computat & Neural Syst, Pasadena, CA 91125 USA. [Sakagami, Masamichi] Tamagawa Univ, Brain Sci Res Ctr, Machida, Tokyo 1948610, Japan. [Sasaki, Yuka] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Sasaki, Y (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM yuka@nmr.mgh.harvard.edu FU National Institutes of Health (NIH) [R01EY015980, EY019466, AG031941, MH091801]; National Science Foundation [BCS-0345746, BCS-0549036, BSC-0946776]; Human Frontier Foundation [RGP 18/2004]; NIH National Center for Research Resources [P41RR14075, S10RR021110]; Mental Illness and Neuroscience Discovery Institute; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts General Hospital; ministry of education, culture, sports, science and technology, Japan (MEXT); Japan Science and Technology Agency (CREST); ERATO Shimojo Implicit Brain Function Project; [KAKENHI-22830081]; [23680028] FX National Institutes of Health (NIH, R01EY015980, EY019466, AG031941, MH091801); the National Science Foundation (BCS-0345746, BCS-0549036, BSC-0946776); the Human Frontier Foundation (RGP 18/2004); the NIH National Center for Research Resources (P41RR14075, S10RR021110); grants-in-aid for Scientific Research (KAKENHI-22830081, 23680028); the Mental Illness and Neuroscience Discovery Institute; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts General Hospital; The ministry of education, culture, sports, science and technology, Japan (MEXT) (Tamagawa global COE program, Grant-in-aid for Scientific Research (A), Grant-in-aid for Scientific Research On Innovative Areas); Japan Science and Technology Agency (CREST); and the ERATO Shimojo Implicit Brain Function Project for their support on this project. NR 42 TC 2 Z9 2 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2012 VL 22 IS 8 BP 1887 EP 1893 DI 10.1093/cercor/bhr270 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 988JI UT WOS:000307486100015 PM 21940704 ER PT J AU Stevens, WD Kahn, I Wig, GS Schacter, DL AF Stevens, W. Dale Kahn, Itamar Wig, Gagan S. Schacter, Daniel L. TI Hemispheric Asymmetry of Visual Scene Processing in the Human Brain: Evidence from Repetition Priming and Intrinsic Activity SO CEREBRAL CORTEX LA English DT Article DE conceptual; laterality; parahippocampal place area; repetition suppression; resting-state functional connectivity ID STATE FUNCTIONAL CONNECTIVITY; EVENT-RELATED FMRI; HUMAN PARAHIPPOCAMPAL CORTEX; LATERAL OCCIPITAL COMPLEX; RIGHT CEREBRAL HEMISPHERE; DEFAULT MODE NETWORK; RESTING HUMAN BRAIN; EXPLICIT MEMORY; STRUCTURAL CONNECTIVITY; ATTENTIONAL MODULATION AB Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes. C1 [Stevens, W. Dale; Wig, Gagan S.; Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Stevens, W. Dale; Kahn, Itamar; Wig, Gagan S.; Schacter, Daniel L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kahn, Itamar] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Wig, Gagan S.] Washington Univ, Dept Neurol, Sch Med, St Louis, MO 63104 USA. RP Stevens, WD (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Rm 4C-101, Bethesda, MD 20892 USA. EM william.stevens@nih.gov OI Schacter, Daniel/0000-0002-2460-6061 FU National Institutes of Health [MH060941] FX National Institutes of Health grant (MH060941 to D.L.S.). NR 120 TC 19 Z9 19 U1 10 U2 30 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2012 VL 22 IS 8 BP 1935 EP 1949 DI 10.1093/cercor/bhr273 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 988JI UT WOS:000307486100020 PM 21968568 ER PT J AU Arifuzzaman, M Rashu, R Leung, DT Hosen, MI Bhuiyan, TR Bhuiyan, MS Rahman, MA Khanam, F Saha, A Charles, RC LaRocque, RC Weil, AA Clements, JD Holmes, RK Calderwood, SB Harris, JB Ryan, ET Qadri, F AF Arifuzzaman, Mohammad Rashu, Rasheduzzaman Leung, Daniel T. Hosen, M. Ismail Bhuiyan, Taufiqur Rahman Bhuiyan, M. Saruar Rahman, Mohammad Arif Khanam, Farhana Saha, Amit Charles, Richelle C. LaRocque, Regina C. Weil, Ana A. Clements, John D. Holmes, Randall K. Calderwood, Stephen B. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi TI Antigen-Specific Memory T Cell Responses after Vaccination with an Oral Killed Cholera Vaccine in Bangladeshi Children and Comparison to Responses in Patients with Naturally Acquired Cholera SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HELICOBACTER-PYLORI; IMMUNE-RESPONSE; HELPER-CELLS; O1 INFECTION; WHOLE-BLOOD; FOLLOW-UP; CD4(+); TOXIN; TRIAL; IMMUNOGENICITY AB Young children, older children, and adults develop comparable levels and durations of immunity following cholera. In comparison, young children receiving oral killed cholera vaccines (OCV) develop a lower level and shorter duration of protection than those of older children and adults. The reasons for this are unclear. We investigated OCV-induced memory T cell responses in younger and older children and compared responses to those in children with cholera. We found that patients with cholera developed significant levels of toxin-specific effector memory T cells (T-EM) with follicular helper and gut-homing characteristics. Older children (6 to 14 years of age) receiving two doses of OCV containing recombinant cholera toxin B subunit (rCTB) had more modest T-EM responses with follicular helper and gut-homing characteristics, but younger vaccinees (24 to 71 months of age) did not develop T-EM responses. The T-EM response correlated positively with subsequent IgG memory B cell responses specific to rCTB in older vaccinees. Cytokine analyses indicated that cholera patients developed significant Th1, Th17, and Th2 responses, while older children receiving vaccine developed more modest increases in Th1 and Th17 cells. Younger vaccinees had no increase in Th1 cells, a decrease in Th17 cells, and an increase in regulatory T (Treg) cells. Our findings suggest that T cell memory responses are markedly diminished in children receiving OCV, especially young children, compared to responses following naturally acquired cholera, and that these differences affect subsequent development of memory B cell responses. These findings may explain the lower efficacy and shorter duration of protection afforded by OCV in young children. C1 [Arifuzzaman, Mohammad; Leung, Daniel T.; Charles, Richelle C.; LaRocque, Regina C.; Weil, Ana A.; Calderwood, Stephen B.; Harris, Jason B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Arifuzzaman, Mohammad; Rashu, Rasheduzzaman; Leung, Daniel T.; Hosen, M. Ismail; Bhuiyan, Taufiqur Rahman; Bhuiyan, M. Saruar; Rahman, Mohammad Arif; Khanam, Farhana; Saha, Amit; Qadri, Firdausi] Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh. [Leung, Daniel T.; Charles, Richelle C.; LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Clements, John D.] Tulane Univ, Med Ctr, Dept Microbiol & Immunol, New Orleans, LA USA. [Holmes, Randall K.] Univ Colorado, Sch Med, Dept Microbiol, Aurora, CO USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Qadri, F (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM fqadri@icddrb.org OI leung, daniel/0000-0001-8401-0801 FU icddr,b; National Institutes of Health; National Institute of Allergy and Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883, R01 AI31940]; Training Grant in Vaccine Development and Public Health [TW005572]; American Recovery and Reinvestment Act (ARRA) Post-doctoral Fellowship in Global Infectious Diseases [TW05572]; Career Development Awards [K01 TW07409, TW07144, K08 AI089721]; Fogarty International Center [R24 TW007988]; Howard Hughes Medical Institute; Burroughs Welcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases; Swedish Agency for International Development and Cooperation FX This work was supported by the icddr,b and grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [to S.B.C. and E.T.R.], R03 AI063079 [to F.Q.], U01 AI077883 [to E.T.R.], R01 AI31940 [to R.K.H.]), a Training Grant in Vaccine Development and Public Health (TW005572 [to M.A., F.K., T.R.B., M.S.B., and F.Q.]), an American Recovery and Reinvestment Act (ARRA) Post-doctoral Fellowship in Global Infectious Diseases (TW05572 [to D.T.L.]), Career Development Awards (K01 TW07409 [to J.B.H.], TW07144 [to R.C.L.], K08 AI089721 [to R.C.C.]), a Clinical Research Scholars Award (R24 TW007988 [to S.B.C.]) from the Fogarty International Center, a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (to R.C.L.), the Burroughs Welcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases (to D.T.L.), and the Swedish Agency for International Development and Cooperation (to F.Q.). NR 48 TC 19 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2012 VL 19 IS 8 BP 1304 EP 1311 DI 10.1128/CVI.00196-12 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 983HR UT WOS:000307110900026 PM 22739692 ER PT J AU Leung, DT Rahman, MA Mohasin, M Patel, SM Aktar, A Khanam, F Uddin, T Riyadh, MA Saha, A Alam, MM Chowdhury, F Khan, AI Charles, R LaRocque, R Harris, JB Calderwood, SB Qadri, F Ryan, ET AF Leung, Daniel T. Rahman, Mohammad Arif Mohasin, M. Patel, Sweta M. Aktar, Amena Khanam, Farhana Uddin, Taher Riyadh, M. Asrafuzzaman Saha, Amit Alam, Mohammad Murshid Chowdhury, Fahima Khan, Ashraful Islam Charles, Richelle LaRocque, Regina Harris, Jason B. Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. TI Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh (vol 19, pg 690, 2012) SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Correction C1 [Leung, Daniel T.] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Leung, DT (reprint author), Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. NR 1 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2012 VL 19 IS 8 BP 1337 EP 1337 DI 10.1128/CVI.00299-12 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 983HR UT WOS:000307110900033 ER PT J AU Harrington, KM Miller, MW Wolf, EJ Reardon, AF Ryabchenko, KA Ofrat, S AF Harrington, Kelly M. Miller, Mark W. Wolf, Erika J. Reardon, Annemarie F. Ryabchenko, Karen A. Ofrat, Shani TI Attention-deficit/hyperactivity disorder comorbidity in a sample of veterans with posttraumatic stress disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ADMINISTERED PTSD SCALE; CONFIRMATORY FACTOR-ANALYSIS; SEXUALLY ABUSED-CHILDREN; PSYCHIATRIC-DISORDERS; SURVEY REPLICATION; COLLEGE-STUDENTS; TRAUMA EXPOSURE; PARENT DATA; CHILDHOOD AB This study examined attention-deficit/hyperactivity disorder (ADHD) comorbidity in military veterans with a high prevalence of posttraumatic stress disorder (PTSD) and evaluated the relationships between the 2 disorders and exposure to traumatic events. The sample included 222 male and female military veterans who were administered structured clinical interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Results show that 54.5% met the criteria for current PTSD, 11.5% of whom also met the criteria for current adult ADHD. Level of trauma exposure and ADHD severity were significant predictors of current PTSD severity. Evaluation of the underlying structure of symptoms of PTSD and ADHD using confirmatory factor analysis yielded a best-fitting measurement model that comprised 4 PTSD factors and 3 ADHD factors. Standardized estimates of the correlations among PTSD and ADHD factors suggested that the largest proportion of shared variance underlying PTSD-ADHD comorbidity is related to problems with modulating arousal levels that are common to both disorders (ie, hyperarousal and hypoarousal). Published by Elsevier Inc. C1 [Harrington, Kelly M.] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02130 USA. [Harrington, Kelly M.; Miller, Mark W.; Wolf, Erika J.; Reardon, Annemarie F.; Ofrat, Shani] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Harrington, Kelly M.; Miller, Mark W.; Wolf, Erika J.; Ofrat, Shani] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Harrington, KM (reprint author), VA Boston Healthcare Syst, MAVERIC, 150 S Huntington Ave,151-MAV, Boston, MA 02130 USA. EM kelly.harrington@va.gov; mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU VA Merit Review Award; National Institute of MentalHealth [T32MH019836] FX Funding for this study was provided by a VA Merit Review Award to Mark W. Miller. Kelly M. Harrington was supported by National Institute of MentalHealth Training Grant T32MH019836. NR 82 TC 16 Z9 16 U1 5 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD AUG PY 2012 VL 53 IS 6 BP 679 EP 690 DI 10.1016/j.comppsych.2011.12.001 PG 12 WC Psychiatry SC Psychiatry GA 982FJ UT WOS:000307027900004 PM 22305866 ER PT J AU Ponnusamy, S Selvam, SP Mehrotra, S Kawamori, T Snider, AJ Obeid, LM Shao, Y Sabbadini, R Ogretmen, B AF Ponnusamy, Suriyan Selvam, Shanmugam Panneer Mehrotra, Shikhar Kawamori, Toshihiko Snider, Ashley J. Obeid, Lina M. Shao, Yuan Sabbadini, Roger Ogretmen, Besim TI Communication between host organism and cancer cells is transduced by systemic sphingosine kinase 1/sphingosine 1-phosphate signalling to regulate tumour metastasis SO EMBO MOLECULAR MEDICINE LA English DT Article DE lung metastasis; sphingolipids; sphingomab; sphingosine kinase 1; sphingosine 1-phosphate ID MYELOID-LEUKEMIA CELLS; IMATINIB-INDUCED APOPTOSIS; PROTEIN-COUPLED RECEPTOR; BREAST-CANCER; OVARIAN-CANCER; LUNG-CANCER; SPHINGOSINE-1-PHOSPHATE; BRMS1; MIGRATION; SURVIVAL AB Mechanisms by which cancer cells communicate with the host organism to regulate lung colonization/metastasis are unclear. We show that this communication occurs via sphingosine 1-phosphate (S1P) generated systemically by sphingosine kinase 1 (SK1), rather than via tumour-derived S1P. Modulation of systemic, but not tumour SK1, prevented S1P elevation, and inhibited TRAMP-induced prostate cancer growth in TRAMP+/+SK1-/- mice, or lung metastasis of multiple cancer cells in SK1-/- animals. Genetic loss of SK1 activated a master metastasis suppressor, Brms1 (breast carcinoma metastasis suppressor 1), via modulation of S1P receptor 2 (S1PR2) in cancer cells. Alterations of S1PR2 using pharmacologic and genetic tools enhanced Brms1. Moreover, Brms1 in S1PR2-/- MEFs was modulated by serum S1P alterations. Accordingly, ectopic Brms1 in MB49 bladder cancer cells suppressed lung metastasis, and stable knockdown of Brms1 prevented this process. Importantly, inhibition of systemic S1P signalling using a novel anti-S1P monoclonal antibody (mAb), Sphingomab, attenuated lung metastasis, which was prevented by Brms1 knockdown in MB49 cells. Thus, these data suggest that systemic SK1/S1P regulates metastatic potential via regulation of tumour S1PR2/Brms1 axis. C1 [Ponnusamy, Suriyan; Selvam, Shanmugam Panneer; Ogretmen, Besim] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Ponnusamy, Suriyan; Selvam, Shanmugam Panneer; Mehrotra, Shikhar; Kawamori, Toshihiko; Snider, Ashley J.; Obeid, Lina M.; Shao, Yuan; Ogretmen, Besim] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Mehrotra, Shikhar] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Kawamori, Toshihiko; Shao, Yuan] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Snider, Ashley J.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Snider, Ashley J.; Obeid, Lina M.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Sabbadini, Roger] Lpath Inc, San Diego, CA USA. RP Ogretmen, B (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM ogretmen@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [CA088932, DE016572, CA097165]; Biogen/IDEC, Inc. (San Diego, CA); CTSA/SCTR (MUSC); NIH [C06 RR015455, P30 CA138313] FX We thank Dr. Jennifer G. Schnellmann (Medical University of South Carolina, MUSC, Charleston, SC) for her editorial review. We also thank Dr. Yusuf A. Hannun (MUSC) for helpful discussions. SK1-/- and S1PR2-/- mice were kindly provided to us by Dr. Richard L. Proia (National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD). This work was supported by research grants obtained from the National Institutes of Health (CA088932, DE016572 and CA097165 to BO), Biogen/IDEC, Inc. (San Diego, CA) and CTSA/SCTR (MUSC). The core facilities utilized for animal studies, lipidomics and imaging were constructed using support from NIH (C06 RR015455, or P30 CA138313). NR 51 TC 50 Z9 52 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD AUG PY 2012 VL 4 IS 8 BP 761 EP 775 DI 10.1002/emmm.201200244 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 983LL UT WOS:000307120700011 PM 22707406 ER PT J AU Lynn, SK Zhang, X Barrett, LF AF Lynn, Spencer K. Zhang, Xuan Barrett, Lisa Feldman TI Affective State Influences Perception by Affecting Decision Parameters Underlying Bias and Sensitivity SO EMOTION LA English DT Article DE threat perception; valence; arousal; signal detection theory; utility ID MOOD; EMOTION; ATTENTION; CONTEXT AB Studies of the effect of affect on perception often show consistent directional effects of a person's affective state on perception. Unpleasant emotions have been associated with a "locally focused" style of stimulus evaluation, and positive emotions with a "globally focused" style. Typically, however, studies of affect and perception have not been conducted under the conditions of perceptual uncertainty and behavioral risk inherent to perceptual judgments outside the laboratory. We investigated the influence of perceivers' experienced affect (valence and arousal) on the utility of social threat perception by combining signal detection theory and behavioral economics. We compared 3 perceptual decision environments that systematically differed with respect to factors that underlie uncertainty and risk: the base rate of threat, the costs of incorrect identification threat, and the perceptual similarity of threats and nonthreats. We found that no single affective state yielded the best performance on the threat perception task across the 3 environments. Unpleasant valence promoted calibration of response bias to base rate and costs, high arousal promoted calibration of perceptual sensitivity to perceptual similarity, and low arousal was associated with an optimal adjustment of bias to sensitivity. However, the strength of these associations was conditional upon the difficulty of attaining optimal bias and high sensitivity, such that the effect of the perceiver's affective state on perception differed with the cause and/or level of uncertainty and risk. C1 [Lynn, Spencer K.; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Zhang, Xuan] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Boston, MA 02115 USA. RP Lynn, SK (reprint author), Northeastern Univ, Dept Psychol, 360 Huntington Ave, Boston, MA 02115 USA. EM s.lynn@neu.edu FU NIH HHS [DP1OD003312, DP1 OD003312] NR 38 TC 13 Z9 13 U1 1 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD AUG PY 2012 VL 12 IS 4 BP 726 EP 736 DI 10.1037/a0026765 PG 11 WC Psychology, Experimental SC Psychology GA 982ZN UT WOS:000307085800009 PM 22251054 ER PT J AU Ditre, JW Oliver, JA Myrick, H Henderson, S Saladin, ME Drobes, DJ AF Ditre, Joseph W. Oliver, Jason A. Myrick, Hugh Henderson, Scott Saladin, Michael E. Drobes, David J. TI Effects of Divalproex on Smoking Cue Reactivity and Cessation Outcomes Among Smokers Achieving Initial Abstinence SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE smoking; cessation; craving; cue reactivity; divalproex ID BRAIN REWARD AREAS; TOBACCO DEPENDENCE; SELF-QUITTERS; NICOTINE; RELAPSE; WITHDRAWAL; CIGARETTE; ALCOHOL; URGES; PHARMACOTHERAPY AB Divalproex, a GABA agonist, may be a useful agent in the treatment of tobacco dependence. Cue reactivity assessment paradigms are ideally suited to explore basic mechanisms underlying the pharmacological effects of medications that purport to have efficacy for smoking cessation. Our primary goal in the current study was to examine the effects of divalproex on in-treatment reactivity to smoking-relevant and affective cues, and to determine if these reactions were predictive of posttreatment smoking behavior. There were 120 nicotine dependent smokers enrolled in an 8-week double-blind clinical trial and randomly assigned to either divalproex or placebo conditions. Of these, 72 smokers (60% female) who achieved a minimal level of abstinence underwent an in-treatment cue reactivity assessment. Contrary to expectations, divalproex was associated with greater craving and arousal during smoking cue presentation. Divalproex also inhibited cardiovascular response to pleasant cues. Although no significant differences in cessation-related outcomes between divalproex- and placebo-treated participants were observed, cue-elicited craving to smoke predicted end-of-treatment and posttreatment smoking rates. These findings suggest that in-treatment cue reactivity assessment may proactively and dynamically inform ongoing treatment as well as provide a tool for screening potential medications for smoking cessation. C1 [Ditre, Joseph W.] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Oliver, Jason A.; Drobes, David J.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Oliver, Jason A.; Drobes, David J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Drobes, David J.] Univ S Florida, Dept Oncol Sci, Tampa, FL USA. [Myrick, Hugh; Henderson, Scott] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Myrick, Hugh; Henderson, Scott; Saladin, Michael E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Drobes, DJ (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Tobacco Res & Intervent Program, 4115 E Fowler Ave, Tampa, FL 33617 USA. EM david.drobes@moffitt.org FU Abbott Pharmaceutical FX This study was supported by a grant from Abbott Pharmaceutical, who had no role in the study beyond financial support. All authors made substantive contributions and approved the manuscript. There are no conflicts of interest to report. We thank Cynthia Myers, Laura Juliano, Suzanne Wise, and Beth Platz for their assistance in conducting the study and preparing the manuscript. NR 57 TC 8 Z9 8 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD AUG PY 2012 VL 20 IS 4 BP 293 EP 301 DI 10.1037/a0027789 PG 9 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 986CZ UT WOS:000307319700006 PM 22468897 ER PT J AU Riemer, AB Keskin, DB Reinherz, EL AF Riemer, Angelika B. Keskin, Derin B. Reinherz, Ellis L. TI Identification and validation of reference genes for expression studies in human keratinocyte cell lines treated with and without interferon-gamma - a method for qRT-PCR reference gene determination SO EXPERIMENTAL DERMATOLOGY LA English DT Review DE endogenous control; interferon-gamma (IFN-?); immunology; inflammatory milieu; keratinocyte; normalization; real-time polymerase chain reaction (RT-PCR) ID REAL-TIME PCR; HUMAN EPIDERMAL-KERATINOCYTES; CANDIDATE HOUSEKEEPING GENES; HUMAN-PAPILLOMAVIRUS TYPE-16; RT-PCR; BETA-ACTIN; NORMALIZATION; SELECTION; CARCINOMA; MODEL AB Based on the exquisite sensitivity, reproducibility and wide dynamic range of quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR), it is currently the gold standard for gene expression studies. Target gene expression is calculated relative to a stably expressed reference gene. An ideal reference should be uniformly expressed during all experimental conditions within the given experimental system. However, no commonly applicable best reference gene has been identified. Thus, endogenous controls must be determined for every experimental system. As no appropriate reference genes have been reported for immunological studies in keratinocytes, we aimed at identifying and validating a set of endogenous controls for these settings. An extensive validation of sixteen possible endogenous controls in a panel of 8 normal and transformed keratinocyte cell lines in experimental conditions with and without interferon-? was performed. RNA and cDNA quality was stringently controlled. Candidate reference genes were assessed by TaqMan (R) qRT-PCR. Two different statistical algorithms were used to determine the most stably and reproducibly expressed housekeeping genes. mRNA abundance was compared and reference genes with widely different ranges of expression than possible target genes were excluded. Subsequent geNorm and NormFinder analyses identified GAPDH, PGK1, IPO8 and PPIA as the most stably expressed genes in the keratinocyte panel under the given experimental conditions. We conclude that the geometric means of expression values of these four genes represents a robust normalization factor for qRT-PCR analyses in interferon-?-dependent gene expression studies in keratinocytes. The methodology and results herein may help other researchers by facilitating their choice of reference genes. C1 [Riemer, Angelika B.] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Riemer, Angelika B.; Reinherz, Ellis L.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Riemer, Angelika B.; Keskin, Derin B.; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Riemer, Angelika B.; Keskin, Derin B.; Reinherz, Ellis L.] Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, Boston, MA 02115 USA. RP Riemer, AB (reprint author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM a.riemer@dkfz.de FU Erwin Schrodinger fellowship of the Austrian Science Fund; DoD; NIH FX A.B. Riemer (ABR) performed the research and analysed the data; ABR, D. B. Keskin and E. L. Reinherz (ELR) designed the research study and wrote the paper. ABR was supported by an Erwin Schrodinger fellowship of the Austrian Science Fund. This work was supported by DoD & NIH grants to ELR. The authors want to thank Mel Hernandez for excellent technical and scientific advice, and Linda K. Clayton for expert scientific advice and proofreading of the manuscript. NR 32 TC 10 Z9 11 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD AUG PY 2012 VL 21 IS 8 BP 625 EP 629 DI 10.1111/j.1600-0625.2012.01537.x PG 5 WC Dermatology SC Dermatology GA 971RY UT WOS:000306222700011 PM 22775998 ER PT J AU Doyle, JO Attaman, JA Styer, AK Sabatini, ME Petrozza, JC Toth, TL AF Doyle, Joseph O'Brien Attaman, Jill Amanda Styer, Aaron Kyle Sabatini, Mary Elizabeth Petrozza, John Christopher Toth, Thomas Louis TI Rescue human chorionic gonadotropin for false empty follicle syndrome: optimism for successful pregnancy outcome SO FERTILITY AND STERILITY LA English DT Article DE False empty follicle syndrome; rescue hCG; live birth ID CONTROVERSIAL SYNDROME AB Objective: To describe two cases of successful pregnancy after a rescue course of hCG in the setting of false empty follicle syndrome. Design: Case report. Setting: Academic medical center. Patient(s): Two patients undergoing ultrasound-guided oocyte retrieval with failure to obtain oocytes during oocyte retrieval. Intervention(s): Rescue course of hCG with second oocyte retrieval 35 hours later. Main Outcome Measure(s): Live birth. Result(s): Two live-birth pregnancies. Conclusion(s): Live-birth pregnancies are a realistic possibility after administration of a rescue course of hCG and repeat oocyte retrieval in the setting of false empty follicle syndrome. (Fertil Steril (R) 2012;98:450-2. (C) 2012 by American Society for Reproductive Medicine.) C1 [Doyle, Joseph O'Brien; Attaman, Jill Amanda; Styer, Aaron Kyle; Sabatini, Mary Elizabeth; Petrozza, John Christopher; Toth, Thomas Louis] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Fertil Ctr, Boston, MA 02114 USA. RP Doyle, JO (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Fertil Ctr, 55 Fruit St, Boston, MA 02114 USA. EM jodoyle@partners.org NR 10 TC 1 Z9 2 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 2012 VL 98 IS 2 BP 450 EP 452 DI 10.1016/j.fertnstert.2012.04.043 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 981NP UT WOS:000306975400033 PM 22608311 ER PT J AU Fallon, EM Nehra, D Le, HD Nedder, AP Guo, L Mitchell, PD Rueda, BR Puder, M AF Fallon, Erica M. Nehra, Deepika Le, Hau D. Nedder, Arthur P. Guo, Lankai Mitchell, Paul D. Rueda, Bo R. Puder, Mark TI Effect of sunitinib on functional reproductive outcome in a rabbit model SO FERTILITY AND STERILITY LA English DT Article DE Adhesion; uterine abrasion; reproductive function; animal ID POSTSURGICAL ADHESION FORMATION; INTESTINAL-OBSTRUCTION; CLINICAL-SIGNIFICANCE; ABDOMINAL ADHESIONS; SURGERY; PREVENTION; REDUCTION; PATHOGENESIS; ETIOLOGY AB Objective: To determine the effect of sunitinib (Sutent; SU11248; Pfizer), a US Food and Drug Administration-approved receptor tyrosine kinase inhibitor previously shown to reduce de novo pelvic adhesion formation, on reproductive function after surgical uterine abrasion in a rabbit model. Design: Randomized placebo-controlled study. Setting: Large animal facility within an academic hospital. Animal(s): Thirty New Zealand White adult female rabbits (2.2-3.0 kg). Intervention(s): Administration of 11 doses (one preoperative and 10 postoperative) of oral sunitinib (10 mg/kg/d) or placebo. Main Outcome Measure(s): Effect of short-term postoperative sunitinib administration on reproductive function after surgical uterine abrasion. Result(s): All animals were impregnated and survived until designated euthanasia. Sunitinib-treated animals had a larger average litter size (7.7 +/- 1.9 vs. 5.6 +/- 2.7 kits) and offspring viability (7.1 +/- 2.7 vs. 3.5 +/- 3.2 kits) compared with placebo-treated animals. There was no difference in gestational length or aberration in the maintainence of fertility. There were no gross abnormalities, detectable birth defects, or growth disparity in offspring from sunitinib versus placebo-treated mothers. The adhesion burden identified at euthanasia after parturition was lower in sunitinib compared with placebo-treated animals (N = 10/group). Conclusion(s): Sunitinib ameliorated adhesion-induced reproductive aberrations after surgical uterine abrasion and may be an efficacious strategy to reduce postoperative pelvic adhesions. (Fertil Steril (R) 2012;98:496-502. (C) 2012 by American Society for Reproductive Medicine.) C1 [Fallon, Erica M.; Nehra, Deepika; Le, Hau D.; Puder, Mark] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Fallon, Erica M.; Nehra, Deepika; Le, Hau D.; Puder, Mark] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Fallon, Erica M.; Nehra, Deepika; Le, Hau D.; Guo, Lankai; Rueda, Bo R.; Puder, Mark] Harvard Univ, Sch Med, Boston, MA USA. [Nedder, Arthur P.] Anim Resources Childrens Hosp Boston, Boston, MA USA. [Guo, Lankai; Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Mitchell, Paul D.] Childrens Hosp, Clin Res Ctr, Design & Anal Core, Boston, MA 02115 USA. RP Puder, M (reprint author), 300 Longwood Ave,Fegan 3, Boston, MA 02115 USA. EM mark.puder@childrens.harvard.edu FU Congressionally Funded Project entitled "Angiogenesis and Tissue Engineering Research" [W81XWH-05-1-0115, 76344-01]; Children's Hospital Surgical Foundation; Vascular Biology Program, Boston, MA; Joshua Ryan Rappaport Fellowship; National Institutes of Health [T32DK007754-12]; Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA FX Supported by a Congressionally Funded Project entitled "Angiogenesis and Tissue Engineering Research," grant W81XWH-05-1-0115, fund 76344-01; the Children's Hospital Surgical Foundation and The Vascular Biology Program, Boston, MA (E. M. F., D.N., H. D. L., M. P.); the Joshua Ryan Rappaport Fellowship (E. M. F., H. D. L.); the National Institutes of Health grant T32DK007754-12 (D.N.); and Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA (L.G., B.R.R.). NR 29 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 2012 VL 98 IS 2 BP 496 EP 502 DI 10.1016/j.fertnstert.2012.05.020 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 981NP UT WOS:000306975400039 PM 22698641 ER PT J AU Merchant, FM Ikeda, T Pedretti, RFE Salerno-Uriarte, JA Chow, T Chan, PS Bartone, C Hohnloser, SH Cohen, RJ Armoundas, AA AF Merchant, Faisal M. Ikeda, Takanori Pedretti, Roberto F. E. Salerno-Uriarte, Jorge A. Chow, Theodore Chan, Paul S. Bartone, Cheryl Hohnloser, Stefan H. Cohen, Richard J. Armoundas, Antonis A. TI Clinical utility of microvolt T-wave alternans testing in identifying patients at high or low risk of sudden cardiac death SO HEART RHYTHM LA English DT Article DE T-wave alternans; Arrhythmia; Sudden cardiac death; Risk stratification; ICD; heart failure ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; DILATED CARDIOMYOPATHY; PREDICTIVE-VALUE; ARRHYTHMIA VULNERABILITY; ISCHEMIC CARDIOMYOPATHY; SYSTOLIC DYSFUNCTION; EJECTION FRACTION AB BACKGROUND Previous studies have demonstrated that microvolt T-wave alternans (MTWA) testing is a robust predictor of ventricular tachyarrhythmias and sudden cardiac death (SCD) in at-risk patients. However, recent studies have suggested that MTWA testing is not as good a predictor of "appropriate" implantable cardioverter-defibrillator (ICD) therapy as it is a predictor of SCD in patients without ICDs. OBJECTIVE To evaluate the utility of MTWA testing for SCD risk stratification in patients without ICDs. METHODS Patient-level data were obtained from 5 prospective studies of MTWA testing in patients with no history of ventricular arrhythmia or SCD. In these studies, ICDs were implanted in only a minority of patients and patients with ICDs were excluded from the analysis. We conducted a pooled analysis and examined the 2-year risk for SCD based on the MTWA test result. RESULTS The pooled cohort included 2883 patients. MTWA testing was positive in 856 (30%), negative in 1627 (56%), and indeterminate in 400 (14%) patients. Among patients with a left ventricular ejection fraction (LVEF) of <= 35%, annual SCD event rates were 4.0%, 0.9%, and 4.6% among groups with MTWA positive, negative, and indeterminate test results. The SCD rate was significantly lower among patients with a negative MTWA test result than in patients with either positive or indeterminate MTWA test results (P < .001 for both comparisons). In patients with an LVEF of >35%, annual SCD event rates were 3.0%, 0.3%, and 0.3% among the groups with MTWA positive, negative, and indeterminate test results. The SCD rate associated with a positive MTWA test result was significantly higher than that associated with either negative (P < .001) or indeterminate MTWA test results (P = .003). CONCLUSIONS In patients without ICDs, MTWA testing is a powerful predictor of SCD. Among patients with an LVEF of <= 35%, a negative MTWA test result is associated with a low risk for SCD. Conversely, among patients with an LVEF of >35%, a positive MTWA test result identifies patients at significantly heightened SCD risk. These findings may have important implications for refining primary prevention ICD treatment algorithms. C1 [Merchant, Faisal M.; Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02129 USA. [Merchant, Faisal M.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Ikeda, Takanori] Toho Univ, Med Ctr, Dept Cardiovasc Med, Tokyo, Japan. [Pedretti, Roberto F. E.] IRCCS Fdn Salvatore Maugeri, Sci Inst Tradate, Div Cardiol, Tradate, Italy. [Salerno-Uriarte, Jorge A.] Univ Insubria, Osped Circolo & Fdn Macchie, Dept Heart Sci, Varese, Italy. [Chow, Theodore] Reg Med Ctr San Jose, San Jose, CA USA. [Chan, Paul S.] Univ Missouri, Kansas City, MO 64110 USA. [Chan, Paul S.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Bartone, Cheryl] Christ Hosp, Heart & Vasc Ctr, Cincinnati, OH 45219 USA. [Hohnloser, Stefan H.] Goethe Univ Frankfurt, Dept Cardiol, Div Clin Electrophysiol, Frankfurt, Germany. [Cohen, Richard J.; Armoundas, Antonis A.] MIT, Cambridge, MA 02139 USA. [Cohen, Richard J.; Armoundas, Antonis A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, 149 13th St, Boston, MA 02129 USA. EM aarmoundas@partners.org FU National Institute of Aging (NIA) [1R21AG035128]; NIH [1RO1HL103961]; Center for Integration of Medicine and Innovative Technology (CIMIT); Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Cardiovascular Research Society; National Heart, Lung, And Blood Institute [K23HL102224] FX The work was supported by National Institute of Aging (NIA) grant 1R21AG035128 and NIH 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 Chow is associated with Medtronic, Inc, and Dr Cohen is associated with Cambridge Heart, Inc. Dr Chan was supported by Grant Number K23HL102224 from the National Heart, Lung, And Blood Institute. Address for reprint requests and correspondence: Dr Antonis A. Armoundas, PhD, Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129. E-mail address: aarmoundas@partners.org. NR 36 TC 23 Z9 23 U1 0 U2 1 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 AUG PY 2012 VL 9 IS 8 BP 1256 EP + DI 10.1016/j.hrthm.2012.03.014 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 982UT UT WOS:000307071600014 PM 22406384 ER PT J AU Lee, SE Lee, EH Park, H Sung, JY Lee, HW Kang, SY Seo, S Kim, BH Lee, H Seo, AN Ahn, G Choi, YL AF Lee, Seung Eun Lee, Eun Hee Park, Heejung Sung, Ji-Youn Lee, Hyoun Wook Kang, So Young Seo, Sungwook Kim, Byung Heon Lee, Hyojin Seo, An Na Ahn, Geunghwan Choi, Yoon-La TI The diagnostic utility of the GNAS mutation in patients with fibrous dysplasia: meta-analysis of 168 sporadic cases SO HUMAN PATHOLOGY LA English DT Article DE Fibrous dysplasia; GNAS; Mutation ID MCCUNE-ALBRIGHT-SYNDROME; ACTIVATING G(S)ALPHA MUTATION; STIMULATORY G-PROTEIN; ALPHA-SUBUNIT; BONE; GENE; LESIONS; CELLS AB GNAS mutations have been implicated in the development of fibrous dysplasia and multiple endocrinopathies of the Albright-McCune syndrome. To investigate the diagnostic utility of GNAS mutations in patients with fibrous dysplasia, we performed mutational analyses of histologically confirmed fibrous dysplasia and conducted a meta-analysis of the literature. We collected 48 cases of fibrous dysplasia from 3 institutions from 2002 to 2011 and performed polymerase chain reaction and direct bidirectional sequencing of exons 8 and 9 of GNAS using paraffin-embedded tissues. We searched MEDLINE, PubMed, and the KoreaMed databases from 1997 to 2011 and included an additional 155 cases of fibrous dysplasia from 8 representative studies to conduct a meta-analysis. In our sample, 28 (58.3%) of 48 cases showed point mutations of codon 201 at exon 8. Twenty-five cases had a substitution of arginine at codon 201 for histidine (p.R201H), and 3 cases had a substitution for cysteine (p.R201C). One case had a new mutation at codon 224 (p.V224A). The incidence of GNAS mutations was significantly greater in cases that involved long bones than in cases that involved flat bones (P = .017) and was higher in polyostotic cases than in monostotic cases (P = .067). In meta-analysis, 9 studies and 203 patients were included. The overall positive rate of GNAS mutation in fibrous dysplasia was 71.9% (146/203). The major types of mutations were missense mutations such as R201H (66.4%) and R201C (30.8%). As a result, the detection of GNAS mutation could be a valuable adjunct to conventional histopathologic diagnosis of fibrous dysplasia. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lee, Seung Eun; Sung, Ji-Youn; Kang, So Young; Choi, Yoon-La] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul 135710, South Korea. [Lee, Eun Hee; Lee, Hyoun Wook; Kim, Byung Heon] Sungkyunkwan Univ, Samsung Changwon Hosp, Sch Med, Dept Pathol, Chang Won 630732, South Korea. [Park, Heejung] Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea. [Seo, Sungwook] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Orthoped Surg, Seoul 135710, South Korea. [Lee, Hyojin] Natl Police Hosp, Seoul 138708, South Korea. [Seo, An Na] Kyungpook Natl Univ, Sch Med, Dept Pathol, Taegu 700721, South Korea. [Ahn, Geunghwan] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. [Choi, Yoon-La] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Inst Refractory Canc Res, Seoul 135710, South Korea. RP Choi, YL (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Irwon Ro 81, Seoul 135710, South Korea. EM ylachoi@skku.edu RI Sung, Ji-Youn/I-5016-2013 OI Sung, Ji-Youn/0000-0002-6607-2117 FU Ministry for Health and Welfare Affairs [A092255]; National Research Foundation [NRF-M1AXA002-2010-0029795]; Ministry of Education, Science, and Technology, South Korea FX Grant support: This work was supported by a grant (A092255) from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare Affairs, and by the Global Frontier (NRF-M1AXA002-2010-0029795) grant of National Research Foundation funded by the Ministry of Education, Science, and Technology, South Korea. NR 22 TC 22 Z9 24 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 2012 VL 43 IS 8 BP 1234 EP 1242 DI 10.1016/j.humpath.2011.09.012 PG 9 WC Pathology SC Pathology GA 981OX UT WOS:000306979800011 PM 22245114 ER PT J AU Mahalingam, M Richards, JE Selim, MA Muzikansky, A Hoang, MP AF Mahalingam, Meera Richards, Joanna E. Selim, M. Angelica Muzikansky, Alona Hoang, Mai P. TI An immunohistochemical comparison of cytokeratin 7, cytokeratin 15, cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in differentiating porocarcinoma from squamous cell carcinoma SO HUMAN PATHOLOGY LA English DT Article DE Porocarcinoma; Cytokeratin 19; Cytokeratin 7; Cytokeratin 15; CAM5.2; Nestin; Carcinoembryonic antigen ID EPITHELIAL MEMBRANE ANTIGEN; MALIGNANT ECCRINE POROMA; FOLLICULAR STEM-CELLS; MONOCLONAL-ANTIBODY; DIAGNOSTIC UTILITY; KERATIN EXPRESSION; BASAL-CELL; SKIN; MARKERS; P63 AB The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of cytokeratin 7, cytokeratin 15, cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, cytokeratin 19, cytokeratin 7, CAM 5.2, cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By chi(2) test, statistically significant P values (<.05) were observed for cytokeratin 7, cytokeratin 19, and nestin in the distinction of porocarcinoma from squamous cell carcinoma. However, in a logistic regression and stepwise selection for predicting a porocarcinoma, statistical significance was observed only for cytokeratin 19 (P = .0003). In conclusion, we found cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include cytokeratin 7, cytokeratin 19, and nestin. (C) 2012 Elsevier Inc. All rights reserved. C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Muzikansky, Alona; Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Selim, M. Angelica] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Mahalingam, Meera; Richards, Joanna E.] Boston Univ, Sch Med, Dept Dermatol, Dermatopathol Sect, Boston, MA 02118 USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM mhoang@partners.org OI Mahalingam, Meera/0000-0002-2800-9985 NR 38 TC 18 Z9 19 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 2012 VL 43 IS 8 BP 1265 EP 1272 DI 10.1016/j.humpath.2011.10.005 PG 8 WC Pathology SC Pathology GA 981OX UT WOS:000306979800015 PM 22285043 ER PT J AU Foland-Ross, LC Brooks, JO Mintz, J Bartzokis, G Townsend, J Thompson, PM Altshuler, LL AF Foland-Ross, Lara C. Brooks, John O., III Mintz, Jim Bartzokis, George Townsend, Jennifer Thompson, Paul M. Altshuler, Lori L. TI Mood-state effects on amygdala volume in bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Depression; Magnetic resonance imaging; MRI; Amygdala ID TEMPORAL-LOBE STRUCTURES; RATING-SCALE; DEPRESSION; MANIA; SCHIZOPHRENIA; MRI; MATTER; CORTEX AB Background: Prior structural neuroimaging studies of the amygdala in patients with bipolar disorder have reported higher or lower volumes, or no difference relative to healthy controls. These inconsistent findings may have resulted from combining subjects in different mood states. The prefrontal cortex has recently been reported to have a lower volume in depressed versus euthymic bipolar patients. Here we examined whether similar mood state-dependent volumetric differences are detectable in the amygdala. Methods: Forty subjects, including 28 with bipolar disorder type I (12 depressed and 16 euthymic), and 12 healthy comparison subjects were scanned on a 3 T magnetic resonance image (MRI) scanner. Amygdala volumes were manually traced and compared across subject groups, adjusting for sex and total brain volume. Results: Statistical analyses found a significant effect of mood state and hemisphere on amygdala volume. Subsequent comparisons revealed that amygdala volumes were significantly lower in the depressed bipolar group compared to both the euthymic bipolar (p =0.005) and healthy control (p = 0.043) groups. Limitations: Our study was cross-sectional and some patients were medicated. Conclusions: Our results suggest that mood state influences amygdala volume in subjects with bipolar disorder. Future studies that replicate these findings in unmedicated patient samples scanned longitudinally are needed. Published by Elsevier B.V. C1 [Altshuler, Lori L.] Univ Calif Los Angeles, Mood Disorders Res Program, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Foland-Ross, Lara C.; Thompson, Paul M.] Univ Calif Los Angeles, Lab Neuro Imaging, Dept Neurol, Sch Med, Los Angeles, CA 90095 USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Altshuler, Lori L.] W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, Mood Disorders Res Program, Semel Inst Neurosci & Human Behav, 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Bartzokis, George/K-2409-2013 FU National Institutes of Health [MH078556, MH075944, MH001848, EB001561, RR019771]; National Institute on Aging [AG016570]; National Association for Research on Schizophrenia and Affective Disorders (NARSAD); Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family and Northstar Fund; National Center for Research Resources [RR012169, RR013642, RR000865]; Abbott Laboratories; Pfizer Inc. FX Funding for this study was provided by the National Institutes of Health [MH078556 (LCFR), MH075944 (LLA), MH001848 (LEA) EB001561 (PMT), RR019771 (PMT)]. The National Institute on Aging provided additional support for algorithm development (AG016570). For their generous support, the authors also thank the National Association for Research on Schizophrenia and Affective Disorders (NARSAD), the Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, the Ahmanson Foundation, the William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family and Northstar Fund and the National Center for Research Resources (RR012169, RR013642 and RR000865). The study design was peer-reviewed by the National Institutes of Health. Funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.; Dr. Altshuler has received past (and potential future) funding from Abbott Laboratories (research support and consulting honoraria); Forest Laboratories (consulting and speakers bureau honoraria); GlaxoSmithKline (speakers bureau honoraria); and no past, but potential future honoraria from Astra-Zeneca (speakers bureau) and Merck and Co. (consulting). Dr. Brooks has received funding from Pfizer Inc. (research support), Merck (speakers bureau), and Sunovion (speakers bureau). NR 25 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG PY 2012 VL 139 IS 3 BP 298 EP 301 DI 10.1016/j.jad.2012.03.003 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 981QM UT WOS:000306984500012 PM 22521854 ER PT J AU Marques, L Porter, E Keshaviah, A Pollack, MH Van Ameringen, M Stein, MB Simon, NM AF Marques, Luana Porter, Eliora Keshaviah, Aparna Pollack, Mark H. Van Ameringen, Michael Stein, Murray B. Simon, Naomi M. TI Avoidant personality disorder in individuals with generalized social anxiety disorder: What does it add? SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Generalized social anxiety disorder (GSAD); Avoidant personality disorder (AvPD); Severity continuum hypothesis; Major depressive disorder (MMD); Social phobia; Anxiety ID OF-MENTAL-DISORDERS; DSM-IV; PSYCHOMETRIC PROPERTIES; INTERNAL CONSISTENCY; PHOBIA; CRITERIA; VALIDITY; DISTINCTION; SCHIZOTYPAL; OUTPATIENTS AB Avoidant personality disorder (AvPD) has a high level of symptom overlap and comorbidity with generalized social anxiety disorder (GSAD). We examined whether the presence of comorbid AvPD adds significant clinically relevant information for individuals seeking treatment for GSAD. Results suggested that AvPD was significantly associated with poorer quality of life and greater disability in univariate, but not multivariate analyses. Endorsement of more AvPD symptoms was associated with increased disability, increased risk of intimacy, and lower social support, even after covariate adjustment. Specifically, AvPD item 3, hard to be "open" even with people you are close to, was most strongly correlated with quality of life and disability. A binary diagnosis of AvPD alone adds little beyond a marker of greater GSAD severity and depression among patients with GSAD, while a specific feature of AvPD not captured by the GSAD diagnosis, namely emotional guardedness, may be associated with greater impairment. Published by Elsevier Ltd. C1 [Marques, Luana; Porter, Eliora; Keshaviah, Aparna; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Porter, Eliora] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Pollack, Mark H.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Van Ameringen, Michael] St Josephs Healthcare Hamilton, Dept Psychiat & Behav Neurosci, Hamilton, ON L8P 3B5, Canada. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. RP Marques, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM lmarques@partners.org FU NIMH NIH HHS [R01 MH070501, R01MH70919, R01MH70501, R01 MH070917, R01MH70917, R01 MH070919, K23 MH096029] NR 32 TC 14 Z9 14 U1 5 U2 29 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 AUG PY 2012 VL 26 IS 6 BP 665 EP 672 DI 10.1016/j.janxdis.2012.05.004 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 981QU UT WOS:000306985300005 PM 22705954 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 Atrial Fibrillation SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 16th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 09-12, 2012 CL Seattle, WA SP Heart Failure Soc Amer C1 [Bui, Anh L.] Kaiser Permanente Med Ctr, Los Angeles, CA 90034 USA. [Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Durham, NC USA. [Yancy, Clyde W.] Northwestern Univ, Chicago, IL 60611 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.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2012 VL 18 IS 8 SU 1 MA 237 BP S73 EP S74 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991CS UT WOS:000307679700238 ER PT J AU Kapuku, G Davis, H Choksy, P Januzzi, J Harshfield, G AF Kapuku, Gaston Davis, Harry Choksy, Pratik Januzzi, James Harshfield, Gregory TI Brain Natriuretic Hormone Predicts Stress Induced Alterations in Diastolic Function SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 16th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 09-12, 2012 CL Seattle, WA SP Heart Failure Soc Amer C1 [Kapuku, Gaston; Davis, Harry; Choksy, Pratik; Harshfield, Gregory] Georgia Hlth Sci Univ, Georgia Prevent Ctr, Augusta, GA USA. [Januzzi, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2012 VL 18 IS 8 SU 1 MA 032 BP S11 EP S12 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991CS UT WOS:000307679700033 ER PT J AU Krim, SR Vivo, RP Krim, NR Qian, F Cox, M Ventura, H Hernandez, AF Bhatt, DL Fonarow, GC AF Krim, Selim R. Vivo, Rey P. Krim, Nassim R. Qian, Feng Cox, Margueritte Ventura, Hector Hernandez, Adrian F. Bhatt, Deepak L. Fonarow, Gregg C. TI Do BNP Levels and Prognostic Value Vary by Race/Ethnicity in Patients Hospitalized With Heart Failure? SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 16th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 09-12, 2012 CL Seattle, WA SP Heart Failure Soc Amer C1 [Krim, Selim R.; Ventura, Hector] Ochsner Heart & Vasc Inst, New Orleans, LA USA. [Vivo, Rey P.] Univ Texas Med Branch, Methodist DeBakey Heart & Vasc Ctr, Galveston, TX USA. [Krim, Nassim R.] Bronx Lebanon Hosp Ctr, Montefiore Med Ctr, Bronx, NY 10467 USA. [Qian, Feng] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Cox, Margueritte; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare System, Boston, MA 02115 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RI Ventura, Hector/A-7691-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2012 VL 18 IS 8 SU 1 MA 260 BP S80 EP S81 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991CS UT WOS:000307679700261 ER PT J AU Parks, K Castrillo, C Canteli-Alvarez, A Wood, M Mahmud, A Malhotra, R Semigran, MJ AF Parks, Kimberly Castrillo, Cristina Canteli-Alvarez, Angela Wood, Malissa Mahmud, Asma Malhotra, Rajeev Semigran, Marc J. TI Allograft Left Ventricular Hypertrophy after Cardiac Transplantation SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 16th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 09-12, 2012 CL Seattle, WA SP Heart Failure Soc Amer C1 [Parks, Kimberly; Wood, Malissa; Mahmud, Asma; Malhotra, Rajeev; Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Castrillo, Cristina; Canteli-Alvarez, Angela] Univ Hosp Marques de Valdecilla, Inst Formac & Invest, Santander, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2012 VL 18 IS 8 SU 1 MA 247 BP S76 EP S76 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991CS UT WOS:000307679700248 ER PT J AU Shalaby, AA Gorcsan, J Fonarow, G Singh, J Bersohn, M Halilovic, J Gupta, M Sonel, A Saba, S Abraham, W Kadish, A AF Shalaby, Alas A. Gorcsan, John Fonarow, Gregg Singh, Jagmeet Bersohn, Malcolm Halilovic, Jasmina Gupta, Manish Sonel, Ali Saba, Samir Abraham, William Kadish, Alan TI Results of the RISK Trial: Renal Function and Female Gender Are Strongly Associated with Early Response to Cardiac Resynchronization Therapy SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 16th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 09-12, 2012 CL Seattle, WA SP Heart Failure Soc Amer C1 [Shalaby, Alas A.; Gorcsan, John; Sonel, Ali; Saba, Samir] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Fonarow, Gregg; Bersohn, Malcolm] Univ Calif Los Angeles, Los Angeles, CA USA. [Singh, Jagmeet] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Halilovic, Jasmina; Gupta, Manish] St Jude Med, Sunnyvale, CA USA. [Abraham, William] Ohio State Univ, Columbus, OH 43210 USA. [Kadish, Alan] Touro Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2012 VL 18 IS 8 SU 1 MA 184 BP S58 EP S58 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991CS UT WOS:000307679700185 ER PT J AU Zavin, A Daniels, K Arena, R Lecker, S Allsup, K Joseph, J Lazzari, A Davis, S Schulze, PC Forman, DE AF Zavin, Alexandra Daniels, Karla Arena, Ross Lecker, Stewart Allsup, Kelly Joseph, Jacob Lazzari, Antonio Davis, Samuel Schulze, P. Christian Forman, Daniel E. TI Adiponectin is Associated With Reduced Muscular Strength in Elderly Heart Failure Patients SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 16th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 09-12, 2012 CL Seattle, WA SP Heart Failure Soc Amer C1 [Zavin, Alexandra; Allsup, Kelly; Lazzari, Antonio; Davis, Samuel; Forman, Daniel E.] VA Boston Healthcare Syst, Boston, MA USA. [Daniels, Karla; Joseph, Jacob; Forman, Daniel E.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Sch Med, Boston, MA 02115 USA. [Arena, Ross] Univ New Mexico, Sch Med, Dept Orthopaed, Albuquerque, NM 87131 USA. [Arena, Ross] Univ New Mexico, Sch Med, Rehabil Phys Therapy Program, Albuquerque, NM 87131 USA. [Arena, Ross] Univ New Mexico, Sch Med, Dept Internal Med, Div Cardiol, Albuquerque, NM 87131 USA. [Lecker, Stewart] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Nephrol, Boston, MA 02215 USA. [Joseph, Jacob; Forman, Daniel E.] VA Boston Healthcare Syst, Div Cardiovas Med, Boston, MA USA. [Lazzari, Antonio] Boston Univ, Sch Med, Boston, MA 02118 USA. [Schulze, P. Christian] Columbia Univ, Div Cardiol, Med Ctr, New York, NY USA. RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 NR 0 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2012 VL 18 IS 8 SU 1 MA 092 BP S29 EP S30 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 991CS UT WOS:000307679700093 ER PT J AU Eberling, J Medhurst, A Nash, K Gill, A Pollack, S Cronk, D Bacskai, B Mathis, C Mach, R AF Eberling, Jamie Medhurst, Andrew Nash, Kevin Gill, Andrew Pollack, Scott Cronk, David Bacskai, Brian Mathis, Chester Mach, Robert TI Consortium to develop an alpha-synuclein imaging agent SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Eberling, Jamie] Michael J Fox Fdn, New York, NY USA. [Medhurst, Andrew; Nash, Kevin; Gill, Andrew; Pollack, Scott; Cronk, David] BioFocus, Cambridge, England. [Bacskai, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mathis, Chester] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Mach, Robert] Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2012 VL 32 SU 1 BP S125 EP S126 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000128 ER PT J AU Hansen, HD Sander, C Mandeville, JB Vanduffel, W Catana, C Hooker, J Rosen, B Knudsen, GM AF Hansen, Hanne D. Sander, Christin Mandeville, Joseph B. Vanduffel, Wim Catana, Ciprian Hooker, Jacob Rosen, Bruce Knudsen, Gitte M. TI Optimized bolus/infusion scheme and determination of in vivo K-d for [C-11]AZ10419369 in non-human primates SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Hansen, Hanne D.; Knudsen, Gitte M.] Rigshosp, Copenhagen Univ Hosp, Neurobiol Res Unit, DK-2100 Copenhagen, Denmark. [Sander, Christin; Mandeville, Joseph B.; Vanduffel, Wim; Catana, Ciprian; Hooker, Jacob; Rosen, Bruce] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. RI Hansen, Hanne Demant/C-9029-2013 OI Hansen, Hanne Demant/0000-0001-5564-7627 NR 2 TC 0 Z9 0 U1 0 U2 4 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 AUG PY 2012 VL 32 SU 1 BP S127 EP S127 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000130 ER PT J AU Hicks, J Sadovski, O Parkes, J Fowler, C Houle, S Tong, JC Vasdev, N Wilson, A AF Hicks, Justin Sadovski, Oleg Parkes, Jun Fowler, Chris Houle, Sylvain Tong, Junchao Vasdev, Neil Wilson, Alan TI Evaluation of a small library of carbamates and ureas, including PF-04457845, as potential imaging agents for fatty acid amide hydrolase (FAAH) SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Hicks, Justin; Sadovski, Oleg; Parkes, Jun; Houle, Sylvain; Tong, Junchao; Wilson, Alan] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Vasdev, Neil] Mass Gen Hosp, Boston, MA USA. [Fowler, Chris] Umea Univ, S-90187 Umea, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2012 VL 32 SU 1 BP S17 EP S17 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000006 ER PT J AU Ishibashi, K Robertson, C London, E Mandelkern, M AF Ishibashi, Kenji Robertson, Chelsea London, Edythe Mandelkern, Mark TI Is the cerebellum the best reference region for a PET study with [F-18]-fallypride? SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Ishibashi, Kenji] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Ishibashi, Kenji] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Ishibashi, Kenji; Mandelkern, Mark] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Robertson, Chelsea; London, Edythe] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2012 VL 32 SU 1 BP S178 EP S179 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000187 ER PT J AU Ishibashi, K Robertson, C Brown, A Morgan, A Farahi, J Mandelkern, M Sabb, F Cannon, T London, E AF Ishibashi, Kenji Robertson, Chelsea Brown, Amira Morgan, Andrew Farahi, Judah Mandelkern, Mark Sabb, Fred Cannon, Tyrone London, Edythe TI Differential roles of dopamine D1-and D2-like receptors in impulsivity: a preliminary PET study SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Ishibashi, Kenji; Brown, Amira; Morgan, Andrew; Sabb, Fred; Cannon, Tyrone; London, Edythe] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Ishibashi, Kenji; Brown, Amira; Morgan, Andrew; Sabb, Fred; Cannon, Tyrone; London, Edythe] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Ishibashi, Kenji; Morgan, Andrew; Farahi, Judah; Mandelkern, Mark] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Robertson, Chelsea] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. [Cannon, Tyrone] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 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 AUG PY 2012 VL 32 SU 1 BP S82 EP S83 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000080 ER PT J AU Normandin, M Sander, C Catana, C Hooker, J Jenkins, B Vanduffel, W El Fakhri, G Rosen, B Alpert, N Mandeville, J AF Normandin, Marc Sander, Christin Catana, Ciprian Hooker, Jacob Jenkins, Bruce Vanduffel, Wim El Fakhri, Georges Rosen, Bruce Alpert, Nathaniel Mandeville, Joseph TI A kinetic model for mapping dopamine function with simultaneous PET/MR SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Normandin, Marc; Catana, Ciprian; Hooker, Jacob; Jenkins, Bruce; Vanduffel, Wim; El Fakhri, Georges; Rosen, Bruce; Alpert, Nathaniel; Mandeville, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Sander, Christin] MIT, Cambridge, MA 02139 USA. NR 2 TC 0 Z9 0 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 AUG PY 2012 VL 32 SU 1 BP S176 EP S177 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000185 ER PT J AU Ouyang, J Keeler, ML Bonab, AA Domigan, P Zhu, XP Normandin, M Brady, T El Fakhri, G AF Ouyang, Jinsong Keeler, Matthew L. Bonab, Ali A. Domigan, Paul Zhu, Xuping Normandin, Marc Brady, Thomas El Fakhri, Georges TI Evaluation of the performance of a novel mobile brain PET-CT SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Ouyang, Jinsong; Bonab, Ali A.; Zhu, Xuping; Normandin, Marc; Brady, Thomas; El Fakhri, Georges] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keeler, Matthew L.; Domigan, Paul] PhotoDiagnost Syst Inc, Boxboro, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 AUG PY 2012 VL 32 SU 1 BP S175 EP S176 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000184 ER PT J AU Robertson, C Ishibashi, K Brown, A Morgan, A Ghahremani, D Congdon, E Farahi, J Mandelkern, M Cannon, T Sabb, F London, E AF Robertson, Chelsea Ishibashi, Kenji Brown, Amira Morgan, Andrew Ghahremani, Dara Congdon, Eliza Farahi, Judah Mandelkern, Mark Cannon, Tyrone Sabb, Fred London, Edythe TI Relationships of D1-and D2-like receptor availability and response inhibition in the stop-signal task: a preliminary PET study SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Robertson, Chelsea; London, Edythe] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Ishibashi, Kenji; Brown, Amira; Morgan, Andrew; Ghahremani, Dara; Congdon, Eliza; Cannon, Tyrone; Sabb, Fred; London, Edythe] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Ishibashi, Kenji; Brown, Amira; Morgan, Andrew; Ghahremani, Dara; Congdon, Eliza; Cannon, Tyrone; Sabb, Fred; London, Edythe] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Morgan, Andrew; Farahi, Judah; Mandelkern, Mark] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. [London, Edythe] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Cannon, Tyrone] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2012 VL 32 SU 1 BP S14 EP S15 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000003 ER PT J AU Sander, CY Hooker, JM Catana, C Normandin, M Vanduffel, W Rosen, BR Mandeville, JB AF Sander, Christin Y. Hooker, Jacob M. Catana, Ciprian Normandin, Marc Vanduffel, Wim Rosen, Bruce R. Mandeville, Joseph B. TI Coupling of neurovascular response and receptor occupancy with simultaneous PET/fMRI SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM) CY AUG 09-11, 2012 CL Baltimore, MD C1 [Sander, Christin Y.; Hooker, Jacob M.; Catana, Ciprian; Vanduffel, Wim; Rosen, Bruce R.; Mandeville, Joseph B.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sander, Christin Y.] MIT, Cambridge, MA 02139 USA. [Normandin, Marc] Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. [Rosen, Bruce R.] Harvard MIT, Hlth Sci & Technol, Cambridge, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 4 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 AUG PY 2012 VL 32 SU 1 BP S177 EP S178 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 983SC UT WOS:000307138000186 ER PT J AU Chinman, M Hannah, G McCarthy, S AF Chinman, Matthew Hannah, Gordon McCarthy, Sharon TI Lessons Learned from a Quality Improvement Intervention with Homeless Veteran Services SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Quality improvement; homeless people; veterans; evidence-based practice; capacity building ID CRITICAL TIME INTERVENTION; SUPPORTED EMPLOYMENT; IMPLEMENTATION; OUTCOMES; PROGRAM; DIFFUSION; DISSEMINATION; PREDICTORS; DISCHARGE; MATTERS AB Homeless veterans are a vulnerable population, with high mortality and morbidity rates. Evidence-based practices for homelessness have been challenging to implement. This study engaged staff members from three VA homeless programs to improve their quality using Getting-To-Outcomes (GTO), a model and intervention of trainings and technical assistance that builds practitioner capacity to plan, implement, and self-evaluate evidence-based practices. Primarily used in community-based, non-VA settings, this study piloted GTO in VA by creating a GTO project within each homeless program and one across all three. The feasibility and acceptability of GTO in VA is examined using the results of the projects, time spent on GTO, and data from focus groups and interviews. With staff members averaging 33 minutes per week on GTO, each team made significant programmatic changes. Homeless staff stated GTO was helpful, and that high levels of communication, staff member commitment to the program, and technical assistance were critical. C1 [Chinman, Matthew; Hannah, Gordon; McCarthy, Sharon] VA Pittsburgh Healthcare Syst, MIRECC, VISN 4, Pittsburgh, PA 15206 USA. RP Chinman, M (reprint author), VA Pittsburgh Healthcare Syst, MIRECC, VISN 4, 7180 Highland Dr 151-R, Pittsburgh, PA 15206 USA. EM chinman@rand.org NR 39 TC 3 Z9 3 U1 2 U2 12 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 2012 VL 23 IS 3 SU S BP 210 EP 224 PG 15 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 987JR UT WOS:000307413700019 PM 22864498 ER PT J AU Yeung, A Feldman, G Pedrelli, P Hails, K Fava, M Reyes, T Mundt, JC AF Yeung, Albert Feldman, Gregory Pedrelli, Paola Hails, Kate Fava, Maurizio Reyes, Tracy Mundt, James C. TI The Quick Inventory of Depressive Symptomatology, Clinician Rated and Self-report A Psychometric Assessment in Chinese Americans With Major Depressive Disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Depression; Chinese; psychometrics; severity of illness index; psychiatric status rating scales ID SEQUENCED TREATMENT ALTERNATIVES; REPORT QIDS-SR; PRIMARY-CARE; TRIAL AB This study aimed to investigate the psychometric properties of the Chinese translations of the Quick Inventory of Depressive Symptomatology (QIDS(16)), including the Clinician-Rated (QIDS-C-16), Self-report (QIDS-SR16), and Interactive Voice Response (QIDS-SR-IVR16) formats. Thirty depressed Chinese Americans were assessed with Chinese translations of the QIDS-SR16, QIDS-SR-IVR16, and QIDS-C-16. Cronbach alpha estimates of internal scale consistency on the QIDS-SR16, QIDS-SR-IVR16, and QIDS-C-16 were 0.70, 0.74, and 0.79, respectively. Intercorrelations among the measures were QIDS-SR16 and QIDS-SR-IVR16, r = 0.79; QIDS-SR16 and QIDS-C-16, r = 0.61; and QIDS-SR-IVR16 and QIDS-C-16, r = 0.69 (all p values < 0.01). The areas under the curve for the receiver operating characteristics of the QIDS-SR16 and QIDS-SR-IVR16 were 0.78 (95% confidence interval, 0.61-0.95) and 0.81 (95% confidence interval, 0.65-0.96), respectively. The respective screening sensitivities/specificities were 0.73/0.74 and 0.86/0.58. The Chinese translations of the QIDS(16) have adequate psychometric properties and may be useful tools for depression screening. C1 [Yeung, Albert; Feldman, Gregory; Pedrelli, Paola; Hails, Kate; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Feldman, Gregory] Simmons Coll, Boston, MA 02115 USA. [Reyes, Tracy; Mundt, James C.] Ctr Psychol Consulting, Madison, WI USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq 6-F, Boston, MA 02114 USA. EM ayeung@partners.org FU National Institutes of Mental Health [R44MH068950, R01MH079831] FX This project was supported by grants R44MH068950 and R01MH079831 from the National Institutes of Mental Health. The authors declare no conflict of interest. NR 21 TC 3 Z9 3 U1 1 U2 4 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 AUG PY 2012 VL 200 IS 8 BP 712 EP 715 DI 10.1097/NMD.0b013e318261413d PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 983NJ UT WOS:000307125700010 PM 22850307 ER PT J AU Sher, L AF Sher, Leo TI Mind and Brain: A Critical Appraisal of Cognitive Neuroscience SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 [Sher, Leo] Mt Sinai Sch Med, New York, NY 10029 USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. RP Sher, L (reprint author), Mt Sinai Sch Med, New York, NY 10029 USA. NR 1 TC 0 Z9 0 U1 1 U2 3 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 AUG PY 2012 VL 200 IS 8 BP 735 EP 736 DI 10.1097/NMD.0b013e31826143cf PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 983NJ UT WOS:000307125700017 ER PT J AU Chun, SY Reese, TG Ouyang, JS Guerin, B Catana, C Zhu, XP Alpert, NM El Fakhri, G AF Chun, Se Young Reese, Timothy G. Ouyang, Jinsong Guerin, Bastien Catana, Ciprian Zhu, Xuping Alpert, Nathaniel M. El Fakhri, Georges TI MRI-Based Nonrigid Motion Correction in Simultaneous PET/MRI SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE lesion detection; motion correction; PET/MRI ID IMAGE-RECONSTRUCTION; ATTENUATION-CORRECTION; EMISSION-TOMOGRAPHY; PET IMAGES; GATED PET; REGISTRATION; MODEL; COMPENSATION; FEASIBILITY; SEQUENCES AB Respiratory and cardiac motion is the most serious limitation to whole-body PET, resulting in spatial resolution close to 1 cm. Furthermore, motion-induced inconsistencies in the attenuation measurements often lead to significant artifacts in the reconstructed images. Gating can remove motion artifacts at the cost of increased noise. This paper presents an approach to respiratory motion correction using simultaneous PET/MRI to demonstrate initial results in phantoms, rabbits, and nonhuman primates and discusses the prospects for clinical application. Methods: Studies with a deformable phantom, a free-breathing primate, and rabbits implanted with radioactive beads were performed with simultaneous PET/MRI. Motion fields were estimated from concurrently acquired tagged MR images using 2 B-spline nonrigid image registration methods and incorporated into a PET list-mode ordered-subsets expectation maximization algorithm. Using the measured motion fields to transform both the emission data and the attenuation data, we could use all the coincidence data to reconstruct any phase of the respiratory cycle. We compared the resulting SNR and the channelized Hotelling observer (CHO) detection signal-to-noise ratio (SNR) in the motion-corrected reconstruction with the results obtained from standard gating and uncorrected studies. Results: Motion correction virtually eliminated motion blur without reducing SNR, yielding images with SNR comparable to those obtained by gating with 5-8 times longer acquisitions in all studies. The CHO study in dynamic phantoms demonstrated a significant improvement (166%-276%) in lesion detection SNR with MRI-based motion correction as compared with gating (P < 0.001). This improvement was 43%-92% for large motion compared with lesion detection without motion correction (P < 0.001). CHO SNR in the rabbit studies confirmed these results. Conclusion: Tagged MRI motion correction in simultaneous PET/MRI significantly improves lesion detection compared with respiratory gating and no motion correction while reducing radiation dose. In vivo primate and rabbit studies confirmed the improvement in PET image quality and provide the rationale for evaluation in simultaneous whole-body PET/MRI clinical studies. C1 [Chun, Se Young; Ouyang, Jinsong; Guerin, Bastien; Zhu, Xuping; Alpert, Nathaniel M.; El Fakhri, Georges] Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Radiol Sci Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Reese, Timothy G.; Catana, Ciprian] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr, Boston, MA 02114 USA. [Chun, Se Young; Reese, Timothy G.; Ouyang, Jinsong; Guerin, Bastien; Catana, Ciprian; Zhu, Xuping; Alpert, Nathaniel M.; El Fakhri, Georges] Harvard Univ, Sch Med, Boston, MA USA. RP El Fakhri, G (reprint author), Massachusetts Gen Hosp, Ctr Adv Radiol Sci, Radiol Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM elfakhri@pet.mgh.harvard.edu RI Chun, Se Young/B-6653-2013; Guerin, Bastien/P-1412-2014; OI Chun, Se Young/0000-0001-8739-8960 FU [NIH-R21-EB012326]; [R01-CA165221] FX We thank Dr. Koen Nelissen, Daniel Chonde, and Dr. Elie Moussallem for their help with the animal studies. This work was supported in part by NIH-R21-EB012326 and R01-CA165221. No other potential conflict of interest relevant to this article was reported. NR 34 TC 76 Z9 76 U1 1 U2 19 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 2012 VL 53 IS 8 BP 1284 EP 1291 DI 10.2967/jnumed.111.092353 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 984OT UT WOS:000307201300031 PM 22743250 ER PT J AU Harris, RS Winkler, T Venegas, JG Medoff, B AF Harris, R. Scott Winkler, Tilo Venegas, Jose G. Medoff, Benjamin TI F-18-FDG Uptake to Assess Eosinophilic Inflammation in Asthma: Would SUV at Late Imaging Be Relevant? REPLY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter C1 [Harris, R. Scott] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Harris, RS (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM rsharris@mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 2 TC 1 Z9 1 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 2012 VL 53 IS 8 BP 1328 EP 1329 DI 10.2967/jnumed.112.104018 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 984OT UT WOS:000307201300036 ER PT J AU Osei-Bonsu, PE Spiro, A Schultz, MR Ryabchenko, KA Smith, E Herz, L Eisen, SV AF Osei-Bonsu, Princess E. Spiro, Avron, III Schultz, Mark R. Ryabchenko, Karen A. Smith, Eric Herz, Lawrence Eisen, Susan V. TI Is DSM-IV criterion A2 associated with PTSD diagnosis and symptom severity? SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; EMOTIONAL RESPONSE; SINGLE QUESTION; VETERANS; VIETNAM; TRAUMA; PREVALENCE; LIFETIME; SAMPLE AB The diagnostic criteria for posttraumatic stress disorder (PTSD) have received significant scrutiny. Several studies have investigated the utility of Criterion A2, the subjective emotional response to a traumatic event. The American Psychiatric Association (APA) has proposed elimination of A2 from the PTSD diagnostic criteria for DSM-5; however, there is mixed support for this recommendation and few studies have examined A2 in samples at high risk for PTSD such as veterans. In the current study of 908 veterans who screened positive for a traumatic event, A2 was not significantly associated with having been told by a doctor that the veteran had PTSD. Those who endorsed A2, however, reported greater PTSD symptom severity in the 3 DSM-IV symptom clusters of reexperiencing (d = 0.45), avoidance (d = 0.61), and hyperarousal (d = 0.44), and A2 was significantly associated with PTSD symptom severity for all 3 clusters (R2 = .25, .25, and .27, respectively) even with trauma exposure in the model. Thus, although A2 may not be a necessary criterion for PTSD diagnosis, its association with PTSD symptom severity warrants further exploration of its utility. C1 [Osei-Bonsu, Princess E.; Schultz, Mark R.; Smith, Eric; Eisen, Susan V.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Spiro, Avron, III; Ryabchenko, Karen A.] VA Boston Healthcare Syst, Boston, MA USA. [Eisen, Susan V.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Spiro, Avron, III; Ryabchenko, Karen A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Smith, Eric] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Herz, Lawrence] Edith Nourse Rogers Mem Vet Hosp, MH Serv Line Gen Psychiat, Bedford, MA 01730 USA. RP Eisen, SV (reprint author), Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd 152, Bedford, MA 01730 USA. EM susan.eisen@va.gov OI Spiro III, Avron/0000-0003-4080-8621 NR 42 TC 6 Z9 6 U1 3 U2 6 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 AUG PY 2012 VL 25 IS 4 BP 368 EP 375 DI 10.1002/jts.21720 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 983HI UT WOS:000307110000002 PM 22806767 ER PT J AU Marx, BP Bovin, MJ Suvak, MK Monson, CM Sloan, DM Fredman, SJ Humphreys, KL Kaloupek, DG Keane, TM AF Marx, Brian P. Bovin, Michelle J. Suvak, Michael K. Monson, Candice M. Sloan, Denise M. Fredman, Steffany J. Humphreys, Kathryn L. Kaloupek, Danny G. Keane, Terence M. TI Concordance between physiological arousal and subjective distress among vietnam combat veterans undergoing challenge testing for PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDERS; INDIVIDUAL-DIFFERENCES; REACTIVITY; VALIDITY; THERAPY; EMOTION AB This study examined concordance between physiological arousal and subjective distress during a laboratory challenge task. Data were collected during the multisite VA Cooperative Study 334 in the early 1990s examining psychophysiological arousal among combat-exposed Vietnam veterans with (n = 775) and without (n = 369) posttraumatic stress disorder (PTSD). Study participants were presented with 6 standardized neutral scenes and 6 standardized combat scenes. Participants provided a subjective rating of distress after each slide. During the presentation, levels of heart rate (HR) and skin conductance (SC) were recorded. Using linear mixed effects modeling, both HR level and SC level exhibited significant positive associations with subjective distress ratings (pr = .33, p < .001 and pr = .19, p < .001, respectively). Individuals with PTSD demonstrated greater concordance between their distress ratings and SC level during exposure to combat slides than participants without PTSD (pr = .28, p < .001 vs. pr = .18, p < .001). Although a significant association was found between subjective distress and HR reactivity and SC reactivity, these findings were not moderated by PTSD status. The results of these analyses suggest that patients' reports of distress during exposure-based treatments might serve as approximate measures of actual physiological arousal. C1 [Marx, Brian P.; Bovin, Michelle J.; Suvak, Michael K.; Monson, Candice M.; Sloan, Denise M.; Fredman, Steffany J.; Kaloupek, Danny G.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Marx, Brian P.; Sloan, Denise M.; Fredman, Steffany J.; Kaloupek, Danny G.; Keane, Terence M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Humphreys, Kathryn L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst 116B 4, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM brian.marx@va.gov OI Sloan, Denise/0000-0002-0962-478X; Kaloupek, Danny/0000-0002-0795-593X NR 41 TC 6 Z9 6 U1 3 U2 8 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 AUG PY 2012 VL 25 IS 4 BP 416 EP 425 DI 10.1002/jts.21729 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 983HI UT WOS:000307110000008 PM 22848013 ER PT J AU Marx, BP Jackson, JC Schnurr, PP Murdoch, M Sayer, NA Keane, TM Friedman, MJ Greevy, RA Owen, RR Sinnott, PL Speroff, T AF Marx, Brian P. Jackson, James C. Schnurr, Paula P. Murdoch, Maureen Sayer, Nina A. Keane, Terence M. Friedman, Matthew J. Greevy, Robert A. Owen, Richard R. Sinnott, Patricia L. Speroff, Theodore TI The reality of malingered PTSD among veterans: Reply to McNally and Frueh (2012) SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; US VETERANS; DISABILITY; PARTICIPATION; THERAPY; VIETNAM; SERVICE; SEEKING; HEALTH AB In this reply to McNally and Frueh (2012), we offer some additional insight into the studies they use to support their argument that we should be worried about malingering among veterans. We also describe other research on the disability system of the Department of Veterans Affairs and compensation-seeking behavior that challenges their conclusions. C1 [Marx, Brian P.; Keane, Terence M.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA USA. [Marx, Brian P.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Jackson, James C.; Speroff, Theodore] VA Tennessee Valley Healthcare Syst, GRECC, Ctr Hlth Serv Res, Nashville, TN USA. [Jackson, James C.] Vanderbilt Univ, Sch Med, Div Allergy Pulm Crit Care Med, Nashville, TN 37212 USA. [Schnurr, Paula P.; Friedman, Matthew J.] White River Junct VA Med Ctr, VA Natl Ctr PTSD, White River Jct, VT USA. [Schnurr, Paula P.; Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. [Murdoch, Maureen; Sayer, Nina A.] Minneapolis VA Med Ctr, Gen Internal Med Sect, Minneapolis, MN USA. [Murdoch, Maureen; Sayer, Nina A.] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Murdoch, Maureen; Sayer, Nina A.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Murdoch, Maureen; Sayer, Nina A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Pharmacol & Toxicol, Hanover, NH USA. [Greevy, Robert A.; Speroff, Theodore] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Owen, Richard R.] Cent Arkansas VA Healthcare Syst, VA Mental Hlth Qual Enhancement Res Initiat MH QU, N Little Rock, AR USA. [Owen, Richard R.] Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA. [Sinnott, Patricia L.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Palo Alto, CA USA. [Sinnott, Patricia L.] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, San Francisco, CA 94143 USA. [Speroff, Theodore] Vanderbilt Univ, Sch Med, Dept Med, Div Gen Internal Med, Nashville, TN 37212 USA. RP Marx, BP (reprint author), 150 S Huntington Ave,116B-4, Boston, MA 02130 USA. EM brian.marx@va.gov RI Sayer, Nina/E-3249-2016 NR 22 TC 8 Z9 8 U1 1 U2 4 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 AUG PY 2012 VL 25 IS 4 BP 457 EP 460 DI 10.1002/jts.21714 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 983HI UT WOS:000307110000014 ER PT J AU Lenhardt, JM Howard, JM Taft, CT Kaloupek, DG Keane, TM AF Lenhardt, Jenna M. Howard, Jamie M. Taft, Casey T. Kaloupek, Danny G. Keane, Terence M. TI Examining aggression in male vietnam veterans who receive VA services: The role of traumatic events and combat exposure SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIOLENCE; ABUSE AB We examined the relationship between trauma exposure and the perpetration of aggression by male Vietnam veterans (N = 1,328) using archival data from a multisite study conducted by the Cooperative Studies Program of the Department of Veteran Affairs (CSP-334) in the early 1990s. Both traumatic events in civilian life and combat exposure were examined as correlates of aggression. Results indicated that pre- and postmilitary traumatic events and combat exposure were all related to perpetration of aggression at the bivariate level; r = .07, r = .20, and r = .13, respectively. When these variables were examined simultaneously, only combat exposure (beta = .14, p < .001) and postmilitary traumatic events (beta = .20, p < .001) were associated with aggression. No interaction effects were found for civilian traumatic events and combat in relation to aggression. Results highlight the importance of attending to the psychological aftermath of exposure to traumatic events experienced during and following deployment before aggressive patterns develop. C1 [Taft, Casey T.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Howard, Jamie M.; Taft, Casey T.; Kaloupek, Danny G.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychol, Boston, MA 02118 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. EM Casey.Taft@va.gov OI Kaloupek, Danny/0000-0002-0795-593X NR 13 TC 1 Z9 1 U1 1 U2 4 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 AUG PY 2012 VL 25 IS 4 BP 461 EP 464 DI 10.1002/jts.21717 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 983HI UT WOS:000307110000015 PM 22786658 ER PT J AU Steenkamp, MM Dickstein, BD Salters-Pedneault, K Hofmann, SG Litz, BT AF Steenkamp, Maria M. Dickstein, Benjamin D. Salters-Pedneault, Kristalyn Hofmann, Stefan G. Litz, Brett T. TI Trajectories of PTSD symptoms following sexual assault: Is resilience the modal outcome? SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOMETRIC PROPERTIES; TRAUMA; PSYCHOPATHOLOGY; DEPRESSION; COMMUNITY; SURVIVORS; SCALES AB Theoretical frameworks positing qualitatively distinct trajectories of posttrauma outcome have received initial empirical support, but have not been investigated in cases of severe interpersonal trauma. To address this limitation, we conducted latent class growth analysis with longitudinal data collected from 119 female sexual assault survivors at 1-, 2-, 3-, and 4-months postassault. Participants' mean age was 33 years; 63% were White. We hypothesized that given the severity of exposure associated with sexual assault, resilience would not be the modal course of adaptation. Four distinct PTSD growth trajectories, representing unique latent classes of participants, best fit the data: a high chronic trajectory, a moderate chronic trajectory, a moderate recovery trajectory, and a marked recovery trajectory. Contrary to previous studies and recent theoretical models, resilience and resistance trajectories were not observed, as high levels of distress were evident in nearly all participants at 1-month postassault. These results suggest that theoretical models of posttrauma response positing resilience as the modal outcome may not generalize to cases of sexual assault. C1 [Steenkamp, Maria M.; Dickstein, Benjamin D.; Hofmann, Stefan G.; Litz, Brett T.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Steenkamp, Maria M.; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Salters-Pedneault, Kristalyn] Eastern Connecticut State Univ, Dept Psychol, Willimantic, CT 06226 USA. RP Steenkamp, MM (reprint author), Boston Dept Vet Affairs Med Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM maria.steenkamp2@va.gov RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 22 TC 20 Z9 20 U1 1 U2 21 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 AUG PY 2012 VL 25 IS 4 BP 469 EP 474 DI 10.1002/jts.21718 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 983HI UT WOS:000307110000017 PM 22807251 ER PT J AU Funnell, APW Norton, LJ Mak, KS Burdach, J Artuz, CM Twine, NA Wilkins, MR Power, CA Hung, TT Perdomo, J Koh, P Bell-Anderson, KS Orkin, SH Fraser, ST Perkins, AC Pearson, RCM Crossley, M AF Funnell, Alister P. W. Norton, Laura J. Mak, Ka Sin Burdach, Jon Artuz, Crisbel M. Twine, Natalie A. Wilkins, Marc R. Power, Carl A. Hung, Tzong-Tyng Perdomo, Jose Koh, Philip Bell-Anderson, Kim S. Orkin, Stuart H. Fraser, Stuart T. Perkins, Andrew C. Pearson, Richard C. M. Crossley, Merlin TI The CACCC-Binding Protein KLF3/BKLF Represses a Subset of KLF1/EKLF Target Genes and Is Required for Proper Erythroid Maturation In Vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KRUPPEL-LIKE FACTOR; EKLF-NULL MICE; TRANSCRIPTION FACTOR; BETA-THALASSEMIA; DEFICIENT MICE; CO-REPRESSOR; GLOBAL ROLE; CHIP-SEQ; CELLS; DIFFERENTIATION AB The CACCC-box binding protein erythroid Kruppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Kruppel-like factor, or KLF3. We have now tested the in vivo role of KLF3 in erythroid cells by examining Klf3 knockout mice. KLF3-deficient adults exhibit a mild compensated anemia, including enlarged spleens, increased red pulp, and a higher percentage of erythroid progenitors, together with elevated reticulocytes and abnormal erythrocytes in the peripheral blood. Impaired erythroid maturation is also observed in the fetal liver. We have found that KLF3 levels rise as erythroid cells mature to become TER119(+). Consistent with this, microarray analysis of both TER119(-) and TER119(+) erythroid populations revealed that KLF3 is most critical at the later stages of erythroid maturation and is indeed primarily a transcriptional repressor. Notably, many of the genes repressed by KLF3 are also known to be activated by EKLF. However, the majority of these are not currently recognized as erythroid-cell-specific genes. These results reveal the molecular and physiological function of KLF3, defining it as a feedback repressor that counters the activity of EKLF at selected target genes to achieve normal erythropoiesis. C1 [Funnell, Alister P. W.; Norton, Laura J.; Mak, Ka Sin; Burdach, Jon; Artuz, Crisbel M.; Twine, Natalie A.; Wilkins, Marc R.; Pearson, Richard C. M.; Crossley, Merlin] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia. [Power, Carl A.; Hung, Tzong-Tyng] Univ New S Wales, Mark Wainwright Analyt Ctr, Sydney, NSW, Australia. [Perdomo, Jose] Univ New S Wales, Dept Med, St George Clin Sch, Sydney, NSW, Australia. [Koh, Philip; Perkins, Andrew C.] Univ Queensland, Div Mol Genet & Dev, Inst Mol Biosci, Brisbane, Qld, Australia. [Bell-Anderson, Kim S.] Univ Sydney, Sch Mol Biosci, Sydney, NSW 2006, Australia. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Childrens Hosp Boston,Harvard S, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Fraser, Stuart T.] Univ Sydney, Discipline Physiol, Sch Med Sci, Sydney, NSW 2006, Australia. [Perkins, Andrew C.] Mater Med Res Inst, Brisbane, Qld, Australia. RP Crossley, M (reprint author), Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia. EM m.crossley@unsw.edu.au RI Pearson, Richard/J-4411-2012; Burdach, Jon/B-4378-2012; Crossley, Merlin/D-7888-2011; Perkins, Andrew/M-3216-2014; OI Pearson, Richard/0000-0002-7918-9111; Crossley, Merlin/0000-0003-2057-3642; Perkins, Andrew/0000-0003-3644-7093; Fraser, Stuart/0000-0003-3795-9461; Funnell, Alister/0000-0002-1062-5296; Hung, Tzong/0000-0002-2904-2664 FU Australian Research Council; National Health and Medical Research Council FX This work is supported by funding from the National Health and Medical Research Council and the Australian Research Council. NR 34 TC 18 Z9 18 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2012 VL 32 IS 16 BP 3281 EP 3292 DI 10.1128/MCB.00173-12 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 984PM UT WOS:000307203500008 PM 22711990 ER PT J AU Blattler, SM Verdeguer, F Liesa, M Cunningham, JT Vogel, RO Chim, H Liu, HF Romanino, K Shirihai, OS Vazquez, F Ruegg, MA Shi, Y Puigserver, P AF Blaettler, Sharon M. Verdeguer, Francisco Liesa, Marc Cunningham, John T. Vogel, Rutger O. Chim, Helen Liu, Huifei Romanino, Klaas Shirihai, Orian S. Vazquez, Francisca Rueegg, Markus A. Shi, Yang Puigserver, Pere TI Defective Mitochondrial Morphology and Bioenergetic Function in Mice Lacking the Transcription Factor Yin Yang 1 in Skeletal Muscle SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FACTOR YY1; OXIDATIVE-PHOSPHORYLATION; PGC-1 COACTIVATORS; FACTOR YIN-YANG-1; GENE-EXPRESSION; ERR-ALPHA; IN-VIVO; BIOGENESIS; DISEASE; PGC-1-ALPHA AB The formation, distribution, and maintenance of functional mitochondria are achieved through dynamic processes that depend strictly on the transcription of nuclear genes encoding mitochondrial proteins. A large number of these mitochondrial genes contain binding sites for the transcription factor Yin Yang 1 (YY1) in their proximal promoters, but the physiological relevance is unknown. We report here that skeletal-muscle-specific YY1 knockout (YY1mKO) mice have severely defective mitochondrial morphology and oxidative function associated with exercise intolerance, signs of mitochondrial myopathy, and short stature. Gene set enrichment analysis (GSEA) revealed that the top pathways downregulated in YY1mKO mice were assigned to key metabolic and regulatory mitochondrial genes. This analysis was consistent with a profound decrease in the level of mitochondrial proteins and oxidative phosphorylation (OXPHOS) bioenergetic function in these mice. In contrast to the finding for wild-type mice, inactivation of the mammalian target of rapamycin (mTOR) did not suppress mitochondrial genes in YY1mKO mice. Mechanistically, mTOR-dependent phosphorylation of YY1 resulted in a strong interaction between YY1 and the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator la (PGC1 alpha), a major regulator of mitochondrial function. These results underscore the important role of YY1 in the maintenance of mitochondrial function and explain how its inactivation might contribute to exercise intolerance and mitochondrial myopathies. C1 [Blaettler, Sharon M.; Verdeguer, Francisco; Cunningham, John T.; Vogel, Rutger O.; Chim, Helen; Vazquez, Francisca; Puigserver, Pere] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Blaettler, Sharon M.; Verdeguer, Francisco; Cunningham, John T.; Vogel, Rutger O.; Chim, Helen; Liu, Huifei; Vazquez, Francisca; Shi, Yang; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Liesa, Marc; Shirihai, Orian S.] Boston Univ, Sch Med, Dept Med, Mitochondria ARC,Evans Biomed Res Ctr, Boston, MA 02118 USA. [Romanino, Klaas; Rueegg, Markus A.] Univ Basel, Biozentrum, Dept Neurobiol, Basel, Switzerland. RP Puigserver, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM Pere_Puigserver@dfci.harvard.edu OI Liesa Roig, Marc/0000-0002-5909-8570; Cunningham, John/0000-0001-6490-4533 FU postdoctoral fellowship from the Swiss National Science Foundation; NIH/NIDDK grant [RO1 DK081418]; Muscular Dystrophy Association grant [MDA202237] FX These studies were supported by a postdoctoral fellowship from the Swiss National Science Foundation (to S.M.B.) and by NIH/NIDDK grant RO1 DK081418 and Muscular Dystrophy Association grant MDA202237 (to P.P.). NR 52 TC 30 Z9 31 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2012 VL 32 IS 16 BP 3333 EP 3346 DI 10.1128/MCB.00337-12 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 984PM UT WOS:000307203500012 PM 22711985 ER PT J AU Dunn, GP Fecci, PE Curry, WT AF Dunn, Gavin P. Fecci, Peter E. Curry, William T. TI Cancer Immunoediting in Malignant Glioma SO NEUROSURGERY LA English DT Review DE Cancer immunoediting; Elimination; Equilibrium; Glioma; Immunotherapy; Tumor escape ID REGULATORY T-CELLS; PRIMARY INTRACRANIAL TUMORS; GROWTH-FACTOR-RECEPTOR; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; MAJOR HISTOCOMPATIBILITY COMPLEX; GLIOBLASTOMA-MULTIFORME PATIENTS; KIDNEY-TRANSPLANT RECIPIENTS; IMMUNOLOGICAL SELF-TOLERANCE; NEWLY-DIAGNOSED GLIOBLASTOMA AB Significant work from many laboratories over the last decade in the study of cancer immunology has resulted in the development of the cancer immunoediting hypothesis. This contemporary framework of the naturally arising immune system-tumor interaction is thought to comprise 3 phases: elimination, wherein immunity subserves an extrinsic tumor suppressor function and destroys nascent tumor cells; equilibrium, wherein tumor cells are constrained in a period of latency under immune control; and escape, wherein tumor cells outpace immunity and progress clinically. In this review, we address in detail the relevance of the cancer immunoediting concept to neurosurgeons and neuro-oncologists treating and studying malignant glioma by exploring the de novo immune response to these tumors, how these tumors may persist in vivo, the mechanisms by which these cells may escape/attenuate immunity, and ultimately how this concept may influence our immunotherapeutic approaches. C1 [Curry, William T.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Pappas Ctr Neurooncol,Sch Med, Boston, MA 02114 USA. RP Curry, WT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Pappas Ctr Neurooncol,Sch Med, 55 Fruit St,Y9E, Boston, MA 02114 USA. EM wcurry@partners.org NR 317 TC 22 Z9 22 U1 5 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 2012 VL 71 IS 2 BP 201 EP 222 DI 10.1227/NEU.0b013e31824f840d PG 22 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 983HB UT WOS:000307109300136 PM 22353795 ER PT J AU Markun, LC Starr, PA Air, EL Marks, WJ Volz, MM Ostrem, JL AF Markun, Leslie C. Starr, Philip A. Air, Ellen L. Marks, William J., Jr. Volz, Monica M. Ostrem, Jill L. TI Shorter Disease Duration Correlates With Improved Long-term Deep Brain Stimulation Outcomes in Young-Onset DYT1 Dystonia SO NEUROSURGERY LA English DT Article DE Deep brain stimulation; DYT1 dystonia; Globus pallidus; Pediatrics ID GLOBUS-PALLIDUS INTERNUS; PRIMARY GENERALIZED DYSTONIA; TORSION DYSTONIA; FOLLOW-UP; EFFICACY AB BACKGROUND: Treatment with deep brain stimulation (DBS) of the globus pallidus internus in children with DYT1 primary torsion dystonia is highly effective; however, individual response to stimulation is variable, and a greater understanding of predictors of long-term outcome is needed. OBJECTIVE: To report the long-term outcomes of subjects with young-onset DYT1 primary torsion dystonia treated with bilateral globus pallidus DBS. METHODS: Fourteen subjects (7 male, 7 female) treated consecutively from 2000 to 2010 at our center were included in this retrospective study. The Burke-Fahn-Marsden Dystonia Rating Scale was performed at baseline and at 1, 2, and up to 6 years postoperatively. RESULTS: Pallidal DBS was well tolerated and highly effective, with mean Burke-Fahn-Marsden Dystonia Rating Scale movement scores improving from baseline by 61.5% (P < .001) at 1 year, 64.4% (P < .001) at 2 years, and 70.3% (P < .001) at the final follow-up visit (mean, 32 months; range, 7-77 months). Disability scores also improved significantly. Multiple linear regression analysis revealed a significant influence of duration of disease as a predictor of percent improvement in Burke-Fahn-Marsden Dystonia Rating Scale movement score at long-term follow-up (duration of disease, P < .05). Subjects with fixed orthopedic deformities (4) had less improvement in these regions. Location of the active DBS electrode used at final follow-up visit was not predictive of clinical outcome. CONCLUSION: Our findings highlight the sustained benefit from DBS and the importance of early referral for DBS in children with medically refractory DYT1 primary torsion dystonia, which can lead to improved long-term benefits. C1 [Markun, Leslie C.; Marks, William J., Jr.; Volz, Monica M.; Ostrem, Jill L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Starr, Philip A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Markun, Leslie C.; Starr, Philip A.; Marks, William J., Jr.; Volz, Monica M.; Ostrem, Jill L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Air, Ellen L.] Univ Cincinnati, Dept Neurol Surg, Cincinnati, OH USA. RP Ostrem, JL (reprint author), UCSF Mt Zion, Dept Neurol, Box 1838,1635 Divisadero St,5th Floor,Ste 520-530, San Francisco, CA 94115 USA. EM Jill.Ostrem@ucsf.edu NR 21 TC 26 Z9 27 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 2012 VL 71 IS 2 BP 325 EP 330 DI 10.1227/NEU.0b013e318258e21b PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 983HB UT WOS:000307109301022 PM 22811083 ER PT J AU Carmody, TP McFall, M Saxon, AJ Malte, CA Chow, B Joseph, AM Beckham, JC Cook, JW AF Carmody, Timothy P. McFall, Miles Saxon, Andrew J. Malte, Carol A. Chow, Bruce Joseph, Anne M. Beckham, Jean C. Cook, Jessica W. TI Smoking Outcome Expectancies in Military Veteran Smokers With Posttraumatic Stress Disorder SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CONSEQUENCES QUESTIONNAIRE-ADULT; ADMINISTERED PTSD SCALE; MENTAL-HEALTH-CARE; NEGATIVE AFFECT; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; SELF-EFFICACY; MOTIVATION; CESSATION; RELAPSE AB Introduction: Smoking outcome expectancies were investigated in treatment-seeking military Veteran smokers with post-traumatic stress disorder (PTSD). The investigation of smoking outcome expectancies may enhance our understanding of the relationship between PTSD and cigarette smoking. Methods: Participants were 943 military Veterans with a diagnosis of PTSD who were current smokers enrolled in a randomized multisite effectiveness trial to test whether the integration of smoking cessation treatment into mental health care (integrated care) improves prolonged abstinence rates compared with referral to specialized smoking cessation clinics (usual care). Using confirmatory factor analysis (CFA), we evaluated the conceptual model of smoking outcome expectancies measured on the Smoking Consequences Questionnaire Adult (SCQ-A) version. The Kraemer method of mediation analysis was used to investigate the role of smoking outcome expectancies in mediating relationships between PTSD symptoms and smoking behavior, tobacco dependence, and abstinence self-efficacy. Results: The CFA supported the 10-factor structure of the SCQ-A in smokers with PTSD. Relationships between measures of PTSD symptoms and tobacco dependence were mediated by the smoking outcome expectancy regarding negative affect reduction. This same smoking outcome expectancy mediated relationships between PTSD symptoms and smoking abstinence self-efficacy. Conclusions: The findings support the use of the SCQ-A as a valid measure of smoking outcome expectancies in military Veteran smokers with PTSD. Moreover, they suggest that smoking outcome expectancies may play an important role in explaining the relationship between PTSD and cigarette smoking. C1 [Carmody, Timothy P.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Carmody, Timothy P.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [McFall, Miles; Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Malte, Carol A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA USA. [Chow, Bruce] VA Palo Alto Hlth Care Syst, Vet Affairs Cooperat Studies Program, Palo Alto, CA USA. [Joseph, Anne M.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Beckham, Jean C.] Durham Vet Affairs Med Ctr, Vet Affairs Mid Atlantic Reg Mental Illness Res E, Durham, NC USA. [Beckham, Jean C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Cook, Jessica W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Carmody, TP (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.carmody@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Cooperative Studies Program [519] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Cooperative Studies Program, Study #519. NR 51 TC 11 Z9 11 U1 6 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD AUG PY 2012 VL 14 IS 8 BP 919 EP 926 DI 10.1093/ntr/ntr304 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 987PX UT WOS:000307430700005 PM 22271610 ER PT J AU Udoetuk, JD Dai, Y Ying, GS Daniel, E Gangaputra, S Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Jabs, DA Levy-Clarke, GA Nussenblatt, RB Kempen, JH AF Udoetuk, Joshua D. Dai, Yang Ying, Gui-Shuang Daniel, Ebenezer Gangaputra, Sapna Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Kempen, John H. CA Systemic Immunosuppressive Therapy TI Risk of Corticosteroid-Induced Hyperglycemia Requiring Medical Therapy among Patients with Inflammatory Eye Diseases SO OPHTHALMOLOGY LA English DT Article ID INDUCED DIABETES-MELLITUS; PREVALENCE; GLUCOCORTICOIDS; MANAGEMENT; UVEITIS AB Objective: To identify the incidence and risk factors for corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases. Design: Retrospective cohort study. Participants: Patients with ocular inflammation followed at 5 United States tertiary centers that initially were neither diabetic nor taking hypoglycemic medications. Methods: Eligible patients who used oral corticosteroids during follow-up were identified and followed longitudinally for initiation of hypoglycemic medication over 1 year after beginning corticosteroids. The remaining eligible patients were followed for 1 year after their initial visit. Survival analysis was used to calculate the risk of hyperglycemia requiring medical therapy and to identify potential risk factors. Main Outcome Measures: Initiation of hypoglycemic medications. Results: Among 2073 non-diabetic patients treated with oral corticosteroids, 25 (1.21%) initiated hypoglycemic therapy compared with 5 of 2666 patients (0.19%) not treated with oral corticosteroids (relative risk [RR], 4.39; 95% confidence interval [CI], 1.68-11.5). The RR tended to be higher in association with higher initial doses (for initial doses <40 mg of prednisone per day: RR, 3.23; 95% CI, 1.08-9.64; for initial prednisone dose >= 40 mg/d: RR, 5.51; 95% CI, 2.01-15.1). Other risk factors for the initiation of hypoglycemic therapy included older age (RR [per each additional 10 years], 1.46; 95% CI, 1.15-1.85; P = 0.002) and African-American race (RR, 2.94; 95% CI, 1.34-6.43; P = 0.007). Conclusions: These results suggest that the absolute risk of corticosteroid-induced hyperglycemia that is detected and treated with hypoglycemic therapy in the tertiary ocular inflammation setting is low (an excess cumulative risk on the order of 1% within 1 year), although on a relative scale it is approximately 4.4-fold higher than in patients not treated with oral corticosteroids. Older age and African-American race also were risk factors. Physicians who use systemic corticosteroids for ocular inflammatory diseases should be aware of this risk, and should consider surveillance for hyperglycemia among high-risk patients. However, given the low absolute risk, routine laboratory monitoring or referral for monitoring may not be necessary for low-risk patients. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:1569-1574 (C) 2012 by the American Academy of Ophthalmology. C1 [Kempen, John H.] Univ Penn, Sch Med, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Udoetuk, Joshua D.; Dai, Yang; Ying, Gui-Shuang; Daniel, Ebenezer; Kempen, John H.] Univ Penn, Ocular Inflammat Serv, Philadelphia, PA 19104 USA. [Ying, Gui-Shuang; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Udoetuk, Joshua D.] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. [Daniel, Ebenezer; Gangaputra, Sapna] Univ Wisconsin, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI USA. [Gangaputra, Sapna; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Kempen, JH (reprint author), Univ Penn, Sch Med, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Eye Institute [EY014943]; Research to Prevent Blindness; Paul and Evanina Mackall Foundation; R.P.B. James S. Adams Special Scholar Award; R.P.B. Harrington Special Scholar Award; Department of Veterans' Affairs FX Supported primarily by National Eye Institute Grant EY014943 (J.H.K.). Additional support was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. J.H.K. was an R.P.B. James S. Adams Special Scholar Award recipient, J.E.T. was an R.P.B. Harrington Special Scholar Award recipient, and D.A.J. and J.T.R. were Research to Prevent Blindness Senior Scientific Investigator Award recipients during the course of the study. G. A. L.-C. was previously supported by and R.B.N. continues to be supported by intramural funds of the National Eye Institute. E. B. S. receives support from the Department of Veterans' Affairs. None of the sponsors had any role in the design and conduct of the report; collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of this manuscript. NR 13 TC 5 Z9 5 U1 1 U2 1 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 AUG PY 2012 VL 119 IS 8 BP 1569 EP 1574 DI 10.1016/j.ophtha.2012.01.043 PG 6 WC Ophthalmology SC Ophthalmology GA 982YA UT WOS:000307080100012 PM 22484116 ER PT J AU Christen, WG Glynn, RJ Sesso, HD Kurth, T MacFadyen, J Bubes, V Buring, JE Manson, JE Gaziano, JM AF Christen, William G. Glynn, Robert J. Sesso, Howard D. Kurth, Tobias MacFadyen, Jean Bubes, Vadim Buring, Julie E. Manson, JoAnn E. Gaziano, J. Michael TI Vitamins E and C and Medical Record-Confirmed Age-related Macular Degeneration in a Randomized Trial of Male Physicians SO OPHTHALMOLOGY LA English DT Article ID BETA-CAROTENE; CARDIOVASCULAR-DISEASE; US PHYSICIANS; EYE DISEASE; SUPPLEMENTATION; MACULOPATHY; PREVENTION; HEALTH; MEN; CATARACT AB Purpose: To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of the diagnosis of age-related macular degeneration (AMD) in a large-scale randomized trial of male physicians. Design: Randomized, double-masked, placebo-controlled trial. Participants: We included 14 236 apparently healthy United States male physicians aged >= 50 years who did not report a diagnosis of AMD at baseline. Methods: Participants were randomly assigned to receive 400 international units (IU) of vitamin E or placebo on alternate days, and 500 mg of vitamin C or placebo daily. Participants reported new diagnoses of AMD on annual questionnaires and medical record data were collected to confirm the reports. Main Outcome Measures: Incident diagnosis of AMD responsible for a reduction in best-corrected visual acuity to <= 20/30. Results: After 8 years of treatment and follow-up, a total of 193 incident cases of visually significant AMD were documented. There were 96 cases in the vitamin E group and 97 in the placebo group (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.78-1.37). For vitamin C, there were 97 cases in the active group and 96 in the placebo group (HR, 0.99; 95% CI, 0.75-1.31). Conclusions: In a large-scale, randomized trial of United States male physicians, alternate-day use of 400 IU of vitamin E and/or daily use of 500 mg of vitamin C for 8 years had no appreciable beneficial or harmful effect on risk of incident diagnosis of AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:1642-1649 (C) 2012 by the American Academy of Ophthalmology. C1 [Christen, William G.; Glynn, Robert J.; Sesso, Howard D.; Kurth, Tobias; MacFadyen, Jean; Bubes, Vadim; Buring, Julie E.; Manson, JoAnn E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Sesso, Howard D.; Kurth, Tobias; Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Dis, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Sesso, Howard D.; Kurth, Tobias; Buring, Julie E.; Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kurth, Tobias] INSERM, Unit Neuroepidemiol 708, Paris, France. RP Christen, WG (reprint author), 900 Commonwealth Ave E, Boston, MA 02215 USA. EM wchristen@rics.bwh.harvard.edu OI Kurth, Tobias/0000-0001-7169-2620 FU National Institutes of Health (Bethesda, MD) [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; BASF Corporation (Florham Park, NJ); National Eye Institute; National Institute on Aging FX This work was supported by grants CA 97193 (which included funding from the National Eye Institute and the National Institute on Aging), CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health (Bethesda, MD), and an investigator-initiated grant from BASF Corporation (Florham Park, NJ). Study agents and packaging were provided by Wyeth Pharmaceuticals (Madison, NJ), BASF Corporation, and DSM Nutritional Products Inc (formerly Roche Vitamins; Parsippany, NJ). Wyeth Pharmaceuticals, BASF Corporation, and DSM Nutritional Products, Inc, had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. Trial registration: clinicaltrials.gov Identifier: NCT00270647 Dr. Christen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 20 TC 11 Z9 11 U1 1 U2 10 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 AUG PY 2012 VL 119 IS 8 BP 1642 EP 1649 DI 10.1016/j.ophtha.2012.01.053 PG 8 WC Ophthalmology SC Ophthalmology GA 982YA UT WOS:000307080100023 PM 22503302 ER PT J AU Gerweck, LE AF Gerweck, Leo E. TI Modification of Cell Lethality at Elevated Temperatures The pH Effect SO RADIATION RESEARCH LA English DT Article ID CHINESE-HAMSTER CELLS; INTRACELLULAR PH; HYPERTHERMIA; SENSITIVITY; HEAT; MULTIPLICATION; RADIATION; VIABILITY; INVITRO; TUMORS AB Gerweck, L. E. Modification of Cell Lethality at Elevated Temperatures. The pH Effect. Radiat. Res. 70, 224-235 (1977). The lethal response of Chinese hamster ovary cells to hyperthermia was determined at selected extracellular pH. Decreasing pH from 7.6 to 6.7 increased the lethal response of cells over the temperature range of 41 to 44 degrees C. Cell viability was not effected over this pH range at 37 degrees C. The pH sensitizing affect was most prominent at temperatures which were marginally lethal at normal pH (7.4). Four hours of exposure to 42 degrees C decreased survival to 10% at pH 7.4 and 0.01% at pH 6.7. Enhanced cell killing was observed when the cells were exposed to reduced pH and elevated temperatures simultaneously. Prolonging the time of pH exposure before and after hyperthermia did not influence survival. High-density culturing increased the sensitivity of cells to hyperthermia. This affect was due to metabolic acidification of the medium and could be reversed by adjusting the pH. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Radiat Biol,Dept Radiat Med, Boston, MA 02114 USA. RP Gerweck, LE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Radiat Biol,Dept Radiat Med, Boston, MA 02114 USA. FU National Cancer Institute, DHEW [CA05163-01, CA13311] FX This investigation was supported by Grants number CA05163-01 and CA13311 awarded by the National Cancer Institute, DHEW. NR 22 TC 0 Z9 0 U1 1 U2 5 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD AUG PY 2012 VL 178 IS 2 BP AV198 EP AV203 DI 10.1667/RRAV16.1 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 981PZ UT WOS:000306983000017 PM 22870970 ER PT J AU Zhu, AX AF Zhu, Andrew X. TI Molecularly Targeted Therapy for Advanced Hepatocellular Carcinoma in 2012: Current Status and Future Perspectives SO SEMINARS IN ONCOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; PHASE-II TRIAL; PROGNOSTIC-SIGNIFICANCE; FACTOR-ALPHA; ANTITUMOR-ACTIVITY; TUMOR PROGRESSION; OPEN-LABEL; EXPRESSION; BEVACIZUMAB C1 Harvard Univ, Ctr Canc, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Ctr Canc, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,LH POB 232, Boston, MA 02114 USA. EM azhu@partners.org FU Bayer; Onyx; ImClone-Lilly; Novartis FX Advisory/consulting roles: Sanofi-Aventis, Abbott, Bristol-Myers Squibb, Eisai. Research support: Bayer, Onyx, ImClone-Lilly, Novartis. NR 65 TC 37 Z9 39 U1 0 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2012 VL 39 IS 4 BP 493 EP 502 DI 10.1053/j.seminoncol.2012.05.014 PG 10 WC Oncology SC Oncology GA 987PO UT WOS:000307429800013 PM 22846866 ER PT J AU Kokel, D Rennekamp, AJ Shah, AH Liebel, U Peterson, RT AF Kokel, David Rennekamp, Andrew J. Shah, Asmi H. Liebel, Urban Peterson, Randall T. TI Behavioral barcoding in the cloud: embracing data-intensive digital phenotyping in neuropharmacology SO TRENDS IN BIOTECHNOLOGY LA English DT Review DE chemobehavioral data; data-intensive digital phenotyping; dataset mining; neuroscience; pharmacology; high-thoughput screen ID MINIMUM INFORMATION; LARVAL ZEBRAFISH; SMALL MOLECULES; DROSOPHILA; IDENTIFICATION; MODULATION; DISCOVERY; PHENOMICS; SEARCH; SCREEN AB For decades, studying the behavioral effects of individual drugs and genetic mutations has been at the heart of efforts to understand and treat nervous system disorders. High-throughput technologies adapted from other disciplines (e.g., high-throughput chemical screening, genomics) are changing the scale of data acquisition in behavioral neuroscience. Massive behavioral datasets are beginning to emerge, particularly from zebrafish labs, where behavioral assays can be performed rapidly and reproducibly in 96-well, high-throughput format. Mining these datasets and making comparisons across different assays are major challenges for the field. Here, we review behavioral barcoding, a process by which complex behavioral assays are reduced to a string of numeric features, Facilitating analysis and comparison within and across datasets. C1 [Kokel, David; Rennekamp, Andrew J.; Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Kokel, David; Rennekamp, Andrew J.; Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Charlestown, MA 02129 USA. [Kokel, David; Rennekamp, Andrew J.; Peterson, Randall T.] Broad Inst, Cambridge, MA 02142 USA. [Shah, Asmi H.] KIT Karlsruhe Inst Technol, ITG, Karlsruhe, Germany. [Liebel, Urban] KIT Karlsruhe Inst Technol, IAI, Karlsruhe, Germany. RP Peterson, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM peterson@cvrc.mgh.harvard.edu OI Rennekamp , Andrew /0000-0001-6174-7253; kokel, david/0000-0002-1981-1511 FU National Institutes of Health [K01MH091449, T32HL07208, MH086867, MH085205]; BOLD Marie Curie Initial Training Network [238821]; KIT Biointerfaces program; Charles and Ann MGH Research Scholars Award FX This work was supported by National Institutes of Health grants K01MH091449 (D.K.), T32HL07208 (A.J.R.), MH086867 and MH085205 (R.T.P.), the BOLD Marie Curie Initial Training Network grant 238821 (A.H.S.), the KIT Biointerfaces program (U.L.), and by the Charles and Ann MGH Research Scholars Award (R.T.P.). NR 39 TC 23 Z9 23 U1 1 U2 14 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD AUG PY 2012 VL 30 IS 8 BP 421 EP 425 DI 10.1016/j.tibtech.2012.05.001 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 980JD UT WOS:000306888500005 PM 22652049 ER PT J AU Jones, RC Capen, DE AF Jones, Rosemary C. Capen, Diane E. TI A quantitative ultrastructural study of circulating (monocytic) cells interacting with endothelial cells in high oxygen-injured and spontaneously re-forming (FVB) mouse lung capillaries SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE Endothelial-monocytic cell fusion; circulating monocytic cell morphology; capillary remodeling in high oxygen; angiogenic-immunogenic remodeling of lung capillaries ID HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW; STEM-CELLS; PULMONARY-HYPERTENSION; PERIPHERAL-BLOOD; NEOVASCULARIZATION MODEL; HYPEROXIC INJURY; PRECURSOR CELLS; GROWTH-FACTOR; ADULT LUNG AB The present study demonstrates the fine structure of blood-borne (monocytic) circulating cells (CCs), and their interaction with endothelial cells, in a mouse model of lung capillary injury and repair. Quantitative analysis highlights the diversity of CC profiles entering the lung, where they form contact and adhesion/fusion sites to endothelial plasmalemmal membranes, and to complexes of endothelial/basement membrane remnants, as capillary networks reorganize over time. Temporal patterns of CC influx and efflux in the lung, changing CC phenotypes, and the range of CC interactions with endothelium, underscore the potential for a complex angiogenic/immunogenic response, as capillary networks stabilize and undergo expansion and growth. C1 [Jones, Rosemary C.; Capen, Diane E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02115 USA. RP Jones, RC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02115 USA. EM rcjones@partners.org FU NIH [HL R01 089252] FX Supported by NIH HL R01 089252. We thank Drs Rakesh Jain, Dai Fukumura and Dan Duda (Department of Radiation Oncology, Harvard Medical School, and Steele Laboratory for Tumor Biology, Massachusetts General Hospital, Boston, MA) for providing FVB-Tie2 and FVB-WT mice and for helpful advice in the course of the study. NR 44 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0191-3123 EI 1521-0758 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD AUG PY 2012 VL 36 IS 4 BP 260 EP 279 DI 10.3109/01913123.2012.662820 PG 20 WC Microscopy; Pathology SC Microscopy; Pathology GA 981LA UT WOS:000306968500009 PM 22849528 ER PT J AU Widera, EW Block, SD AF Widera, Eric W. Block, Susan D. TI Managing Grief and Depression at the End of Life SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID ADVANCED CANCER-PATIENTS; TERMINALLY-ILL; PALLIATIVE CARE; OF-LIFE; MENTAL-HEALTH; DEATH; SYMPTOMS; METHYLPHENIDATE; METAANALYSIS; BEREAVEMENT AB Psychological distress is common in terminally ill persons and can be a source of great suffering. Grief is an adaptive, universal, and highly personalized response to the multiple losses that occur at the end of life. This response may be intense early on after a loss manifesting itself physically, emotionally, cognitively, behaviorally, and spiritually; however, the impact of grief on daily life generally decreases with time. Although pharmacologic interventions are not warranted for uncomplicated grief, physicians are encouraged to support patients by acknowledging their grief and encouraging the open expression of emotions. It is important for the physician to distinguish uncomplicated grief reactions from more disabling psychiatric disorders such as major depression. The symptoms of grief may overlap with those of major depression or a terminal illness or its treatment; however, grief is a distinct entity. Feelings of pervasive hopelessness, helplessness, worthlessness, guilt, lack of pleasure, and suicidal ideation are present in patients with depression, but not in those experiencing grief. Psychotherapy and antidepressant medications reduce symptoms of distress and improve quality of life for patients with depression. Physicians may consider psychostimulants, such as methylphenidate, for patients who have depression with a life expectancy of only days to weeks. (Am Fam Physician. 2012;86(3):259-264. Copyright (c) 2012 American Academy of Family Physicians.) C1 [Widera, Eric W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Widera, Eric W.] San Francisco VA Med Ctr, Hosp & Palliat Care Serv, San Francisco, CA USA. [Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA USA. [Block, Susan D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Block, Susan D.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Widera, EW (reprint author), 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM eric.widera@ucsf.edu NR 39 TC 4 Z9 4 U1 1 U2 17 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD AUG 1 PY 2012 VL 86 IS 3 BP 259 EP 264 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 983XR UT WOS:000307152500008 PM 22962989 ER PT J AU Lai, PS Fresco, JM Pinilla, MA Macias, AA Brown, RD Englert, JA Hofmann, O Lederer, JA Hide, W Christiani, DC Cernadas, M Baron, RM AF Lai, Peggy S. Fresco, Jennifer M. Pinilla, Miguel A. Macias, Alvaro A. Brown, Ronald D. Englert, Joshua A. Hofmann, Oliver Lederer, James A. Hide, Winston Christiani, David C. Cernadas, Manuela Baron, Rebecca M. TI Chronic Endotoxin Exposure Produces Airflow Obstruction and Lung Dendritic Cell Expansion SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE airway resistance; inhalation; neutrophils; macrophages; dendritic cells; endotoxin ID COTTON TEXTILE WORKERS; ALVEOLAR MACROPHAGE ELIMINATION; REGULATORY T-CELLS; IN-VIVO; FUNGAL-INFECTION; CIGARETTE-SMOKE; IMMUNE-RESPONSE; LPS INHALATION; RETINOIC-ACID; MICE AB Little is known about the mechanisms of persistent airflow obstruction that result from chronic occupational endotoxin exposure. We sought to analyze the inflammatory response underlying persistent airflow obstruction as a result of chronic occupational endotoxin exposure. We developed a murine model of daily inhaled endotoxin for periods of 5 days to 8 weeks. We analyzed physiologic lung dysfunction, lung histology, bronchoalveolar lavage fluid and total lung homogenate inflammatory cell and cytokine profiles, and pulmonary gene expression profiles. We observed an increase in airway hyperresponsiveness as a result of chronic endotoxin exposure. After 8 weeks, the mice exhibited an increase in bronchoalveolar lavage and lung neutrophils that correlated with an increase in proinflammatory cytokines. Detailed analyses of inflammatory cell subsets revealed an expansion of dendritic cells (DCs), and in particular, proinflammatory DCs, with a reduced percentage of macrophages. Gene expression profiling revealed the up-regulation of a panel of genes that was consistent with DC recruitment, and lung histology revealed an accumulation of DCs in inflammatory aggregates around the airways in 8-week-exposed animals. Repeated, low-dose LPS inhalation, which mirrors occupational exposure, resulted in airway hyperresponsiveness, associated with a failure to resolve the proinflammatory response, an inverted macrophage to DC ratio, and a significant rise in the inflammatory DC population. These findings point to a novel underlying mechanism of airflow obstruction as a result of occupational LPS exposure, and suggest molecular and cellular targets for therapeutic development. C1 [Fresco, Jennifer M.; Pinilla, Miguel A.; Brown, Ronald D.; Englert, Joshua A.; Hofmann, Oliver; Hide, Winston; Cernadas, Manuela; Baron, Rebecca M.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Macias, Alvaro A.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Lederer, James A.] Brigham & Womens Hosp, Div Immunol, Dept Surg, Boston, MA 02115 USA. [Lai, Peggy S.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lai, Peggy S.; Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Baron, RM (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. EM rbaron@partners.org RI Hofmann, Oliver/F-1800-2013; OI Hofmann, Oliver/0000-0002-7738-1513; Lai, Peggy/0000-0001-9501-8606; Hide, Winston/0000-0002-8621-3271 FU National Institutes of Health (National Institute of Allergy and Infectious Diseases) grant [K08 AI054465]; National Institutes of Health (National Heart, Lung, and Blood Institute) grant [R01 HL091957]; Centers for Disease Control (National Institute for Occupational Safety and Health) grants [R01 OH 002421, T42OH008416]; National Institutes of Health (National Institute of Environmental Health Sciences) grant [P42 00002] FX This work was supported by National Institutes of Health (National Institute of Allergy and Infectious Diseases) grant K08 AI054465 (R.M.B.), National Institutes of Health (National Heart, Lung, and Blood Institute) grant R01 HL091957 (R.M.B.), Centers for Disease Control (National Institute for Occupational Safety and Health) grants R01 OH 002421 (D.C.C.) and T42OH008416 (D.C.C.), and National Institutes of Health (National Institute of Environmental Health Sciences) grant P42 00002 (D.C.C.). NR 50 TC 10 Z9 10 U1 0 U2 9 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 2012 VL 47 IS 2 BP 209 EP 217 DI 10.1165/rcmb.2011-0447OC PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 986SQ UT WOS:000307365300010 PM 22517795 ER PT J AU Liu, Q Rehman, H Krishnasamy, Y Haque, K Schnellmann, RG Lemasters, JJ Zhong, Z AF Liu, Q. Rehman, H. Krishnasamy, Y. Haque, K. Schnellmann, R. G. Lemasters, J. J. Zhong, Z. TI Amphiregulin Stimulates Liver Regeneration After Small-for-Size Mouse Liver Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Growth factor; liver graft survival; liver regeneration; liver transplantation; living donor transplantation; small-for-size syndrome ID MITOCHONDRIAL PERMEABILITY TRANSITION; GROWTH-FACTOR-ALPHA; N-TERMINAL-KINASE; RAT-LIVER; CYCLIN D1; GENE-EXPRESSION; FACTOR RECEPTOR; GRAFT INJURY; IN-VIVO; MICE AB This study investigated whether amphiregulin (AR), a ligand of the epidermal growth factor receptor (EGFR), improves liver regeneration after small-for-size liver transplantation. Livers of male C57BL/6 mice were reduced to similar to 50% and similar to 30% of original sizes and transplanted. After transplantation, AR and AR mRNA increased in 50% but not in 30% grafts. 5-Bromodeoxyuridine (BrdU) labeling, proliferating cell nuclear antigen (PCNA) expression and mitotic index increased substantially in 50% but not 30% grafts. Hyperbilirubinemia and hypoalbuminemia occurred and survival decreased after transplantation of 30% but not 50% grafts. AR neutralizing antibody blunted regeneration in 50% grafts whereas AR injection (5 mu g/mouse, iv) stimulated liver regeneration, improved liver function and increased survival after transplantation of 30% grafts. Phosphorylation of EGFR and its downstream signaling molecules Akt, mTOR, p70S6K, ERK and JNK increased markedly in 50% but not 30% grafts. AR stimulated EGFR phosphorylation and its downstream signaling pathways. EGFR inhibitor PD153035 suppressed regeneration of 50% grafts and largely abrogated stimulation of regeneration of 30% grafts by AR. AR also increased cyclin D1 and cyclin E expression in 30% grafts. Together, liver regeneration is suppressed in small-for-size grafts, as least in part, due to decreased AR formation. AR supplementation could be a promising therapy to stimulate regeneration of partial liver grafts. C1 [Liu, Q.; Rehman, H.; Krishnasamy, Y.; Haque, K.; Schnellmann, R. G.; Lemasters, J. J.; Zhong, Z.] Med Univ S Carolina, Dept Pharmaceut, Charleston, SC 29425 USA. [Liu, Q.; Rehman, H.; Krishnasamy, Y.; Haque, K.; Schnellmann, R. G.; Lemasters, J. J.; Zhong, Z.] Med Univ S Carolina, Dept Biomed Sci, Charleston, SC 29425 USA. [Liu, Q.] Dalian Med Univ, Affiliated Hosp 2, Dept Gen Surg, Dalian, Peoples R China. [Schnellmann, R. G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lemasters, J. J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Lemasters, J. J.; Zhong, Z.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. RP Zhong, Z (reprint author), Med Univ S Carolina, Dept Pharmaceut, Charleston, SC 29425 USA. EM zhong@musc.edu FU National Institutes of Health [DK70844, DK70844S1, DK084632, DK037034] FX This study was supported, in part, by Grants DK70844, DK70844S1, DK084632 and DK037034 from the National Institutes of Health. NR 64 TC 10 Z9 11 U1 3 U2 8 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 AUG PY 2012 VL 12 IS 8 BP 2052 EP 2061 DI 10.1111/j.1600-6143.2012.04069.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 980OT UT WOS:000306903400014 PM 22694592 ER PT J AU Lee, KM Kim, JI Stott, R Soohoo, J O'Connor, MR Yeh, H Zhao, G Eliades, P Fox, C Cheng, N Deng, S Markmann, JF AF Lee, K. M. Kim, J. I. Stott, R. Soohoo, J. O'Connor, M. R. Yeh, H. Zhao, G. Eliades, P. Fox, C. Cheng, N. Deng, S. Markmann, J. F. TI Anti-CD45RB/Anti-TIM-1-Induced Tolerance Requires Regulatory B Cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Allograft; anti-CD45RB; regulatory B; TIM-1; tolerance ID ANTIGEN-PRESENTING CELLS; ALLOGRAFT-REJECTION; T-CELLS; IN-VIVO; PROTEIN ANTIGENS; ISLET ALLOGRAFTS; RESPONSES; LYMPHOCYTES; IL-10; INTERLEUKIN-10 AB The role of B cells in transplant tolerance remains unclear. Although B-cell depletion often prolongs graft survival, sometimes it results in more rapid rejection, suggesting that B cells may have regulatory activity. We previously demonstrated that tolerance induction by anti-CD45RB antibody requires recipient B cells. Here, we show that anti-CD45RB in combination with anti-TIM-1 antibody has a synergistic effect, inducing tolerance in all recipients in a mouse islet allograft model. This effect depends on the presence of recipient B cells, requires B-cell IL-10 activity, and is antigen-specific. These data suggest the existence of a regulatory B-cell population that promotes tolerance via an IL-10-dependent pathway. C1 [Lee, K. M.; Kim, J. I.; Stott, R.; Soohoo, J.; O'Connor, M. R.; Yeh, H.; Zhao, G.; Eliades, P.; Fox, C.; Cheng, N.; Deng, S.; Markmann, J. F.] Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Zhao, G.; Deng, S.] Sichuan Prov Peoples Hosp, Dept Surg, Chengdu, Sichuan Provinc, Peoples R China. [Zhao, G.; Deng, S.] Sichuan Acad Med Sci, Chengdu, Sichuan Provinc, Peoples R China. RP Markmann, JF (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jkim35@partners.org; jmarkmann@partners.org OI Eliades, Philip/0000-0002-7985-6471 FU NIH [RO1AI057851-05, K01DK079207] FX This work was supported in part by NIH grant RO1AI057851-05 (JFM) and K01DK079207 (JIK). NR 30 TC 34 Z9 38 U1 1 U2 6 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 AUG PY 2012 VL 12 IS 8 BP 2072 EP 2078 DI 10.1111/j.1600-6143.2012.04055.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 980OT UT WOS:000306903400016 PM 22494812 ER PT J AU Porcheray, F DeVito, J Helou, Y Dargon, I Fraser, JW Nobecourt, P Ferdman, J Germana, S Girouard, TC Kawai, T Saidman, SL Wong, W Colvin, RB Leguern, C Zorn, E AF Porcheray, F. DeVito, J. Helou, Y. Dargon, I. Fraser, J. W. Nobecourt, P. Ferdman, J. Germana, S. Girouard, T. C. Kawai, T. Saidman, S. L. Wong, W. Colvin, R. B. Leguern, C. Zorn, E. TI Expansion of Polyreactive B Cells Cross-Reactive to HLA and Self in the Blood of a Patient With Kidney Graft Rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Human; humoral rejection; polyreactive antibodies ID CORONARY-ARTERY-DISEASE; TRANSPLANT GLOMERULOPATHY; MONOCLONAL-ANTIBODIES; CLINICAL-IMPLICATIONS; ALLOGRAFT-REJECTION; ENDOTHELIAL-CELLS; DONOR; IMMUNOGLOBULIN; RECOMBINATION; REPERTOIRE AB Antibody rejection is often accompanied by nondonor HLA specific antibodies (NDSA) and self-reactive antibodies that develop alongside donor-specific antibodies (DSA). To determine the source of these antibodies, we immortalized 107 B-cell clones from a kidney transplant recipient with humoral rejection. Two of these clones reacted to HLA class I or MICA. Both clones were also reactive to self-antigens and a lysate of a kidney cell line, hence revealing a pattern of polyreactivity. Monoclonality was verified by the identification of a single rearranged immunoglobulin heavy chain variable region (VH) sequence for each clone. By tracking their unique CDR3 sequence, we found that one such polyreactive clone was highly expanded in the patient blood, representing similar to 0.2% of circulating B cells. The VH sequence of this clone showed evidence of somatic mutations that were consistent with its memory phenotype and its expansion. Lastly, the reactivity of the expanded polyreactive B-cell clone was found in the patient serum at time of rejection. In conclusion, we provide here proof of principle at the clonal level that human antibodies can cross-react to HLA and self. Our findings strongly suggest that polyreactive antibodies contribute to DSA, NDSA as well as autoantibodies, in transplant recipients. C1 [Porcheray, F.; DeVito, J.; Helou, Y.; Dargon, I.; Fraser, J. W.; Nobecourt, P.; Ferdman, J.; Germana, S.; Kawai, T.; Leguern, C.; Zorn, E.] Harvard Univ, Sch Med, Dept Surg, Transplant Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Girouard, T. C.; Saidman, S. L.; Colvin, R. B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wong, W.] Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Zorn, E (reprint author), Harvard Univ, Sch Med, Dept Surg, Transplant Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM ezorn@partners.org FU Fahd and Nadia Alireza's Research Fund; Roche Organ Transplantation Research Foundation (ROTRF); National Institute of Health, National Institute of Diabetes, Digestive and Kidney Diseases [DK083352] FX This work was supported by the Fahd and Nadia Alireza's Research Fund, the Roche Organ Transplantation Research Foundation (ROTRF) and the National Institute of Health, National Institute of Diabetes, Digestive and Kidney Diseases Grant DK083352. NR 34 TC 15 Z9 15 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 AUG PY 2012 VL 12 IS 8 BP 2088 EP 2097 DI 10.1111/j.1600-6143.2012.04053.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 980OT UT WOS:000306903400018 PM 22510337 ER PT J AU Venkataramani, AS Martin, EG Vijayan, A Wellen, JR AF Venkataramani, A. S. Martin, E. G. Vijayan, A. Wellen, J. R. TI The Impact of Tax Policies on Living Organ Donations in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Living organ donation; state policy; tax; United States ID KIDNEY DONORS; TRANSPLANTATION; INCENTIVES; ATTITUDES; INCREASE; REGISTRY; LIVE AB In an effort to increase living organ donation, fifteen states passed tax deductions and one a tax credit to help defray potential medical, lodging and wage loss costs between 2004 and 2008. To assess the impact of these policies on living donation rates, we used a differences-in-differences strategy that compares the pre- and postlegislation change in living donations in states that passed legislation against the same change in those states that did not. We found no statistically significant effect of these tax policies on donation rates. Furthermore, we found no evidence of any lagged effects, differential impacts by gender, race or donor relationship, or impacts on deceased donation. Possible hypotheses to explain our findings are: the cash value of the tax deduction may be too low to defray costs faced by donors, lack of public awareness about the existence of these policies, and that states that were proactive enough to pass tax policy laws may have already depleted donor pools with previous interventions. C1 [Venkataramani, A. S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Martin, E. G.] SUNY Albany, Rockefeller Coll Publ Affairs & Policy, New York, NY USA. [Martin, E. G.] SUNY Albany, Nelson A Rockefeller Inst Govt, New York, NY USA. [Vijayan, A.] Washington Univ, Sch Med, Dept Med, Div Renal Dis, St Louis, MO 63110 USA. [Wellen, J. R.] Washington Univ, Sch Med, Dept Surg, Sect Transplantat, St Louis, MO 63110 USA. RP Venkataramani, AS (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM avenkataramani@partners.org NR 32 TC 9 Z9 9 U1 1 U2 7 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 AUG PY 2012 VL 12 IS 8 BP 2133 EP 2140 DI 10.1111/j.1600-6143.2012.04044.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 980OT UT WOS:000306903400023 PM 22487077 ER PT J AU Petri, M Orbai, AM Alarcon, GS Gordon, C Merrill, JT Fortin, PR Bruce, IN Isenberg, D Wallace, DJ Nived, O Sturfelt, G Ramsey-Goldman, R Bae, SC Hanly, JG Sanchez-Guerrero, J Clarke, A Aranow, C Manzi, S Urowitz, M Gladman, D Kalunian, K Costner, M Werth, VP Zoma, A Bernatsky, S Ruiz-Irastorza, G Khamashta, MA Jacobsen, S Buyon, JP Maddison, P Dooley, MA van Vollenhoven, RF Ginzler, E Stoll, T Peschken, C Jorizzo, JL Callen, JP Lim, SS Fessler, BJ Inanc, M Kamen, DL Rahman, A Steinsson, K Franks, AG Sigler, L Hameed, S Fang, H Pham, N Brey, R Weisman, MH McGwin, G Magder, LS AF Petri, Michelle Orbai, Ana-Maria Alarcon, Graciela S. Gordon, Caroline Merrill, Joan T. Fortin, Paul R. Bruce, Ian N. Isenberg, David Wallace, Daniel J. Nived, Ola Sturfelt, Gunnar Ramsey-Goldman, Rosalind Bae, Sang-Cheol Hanly, John G. Sanchez-Guerrero, Jorge Clarke, Ann Aranow, Cynthia Manzi, Susan Urowitz, Murray Gladman, Dafna Kalunian, Kenneth Costner, Melissa Werth, Victoria P. Zoma, Asad Bernatsky, Sasha Ruiz-Irastorza, Guillermo Khamashta, Munther A. Jacobsen, Soren Buyon, Jill P. Maddison, Peter Dooley, Mary Anne van vollenhoven, Ronald F. Ginzler, Ellen Stoll, Thomas Peschken, Christine Jorizzo, Joseph L. Callen, Jeffrey P. Lim, S. Sam Fessler, Barri J. Inanc, Murat Kamen, Diane L. Rahman, Anisur Steinsson, Kristjan Franks, Andrew G., Jr. Sigler, Lisa Hameed, Suhail Fang, Hong Ngoc Pham Brey, Robin Weisman, Michael H. McGwin, Gerald, Jr. Magder, Laurence S. TI Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATISM-ASSOCIATION CRITERIA; OF-RHEUMATOLOGY CRITERIA; WEIGHTED CRITERIA; REVISED CRITERIA; ANTIBODIES; NEPHRITIS; ARTHRITIS AB Objective The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. Methods The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Results Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). Conclusion The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or antidouble-stranded DNA antibodies. C1 [Petri, Michelle] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Alarcon, Graciela S.; Fessler, Barri J.; McGwin, Gerald, Jr.] Univ Alabama Birmingham, Birmingham, AL USA. [Gordon, Caroline] Univ Birmingham, Birmingham, W Midlands, England. [Merrill, Joan T.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Fortin, Paul R.] Univ Laval, Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. [Bruce, Ian N.] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Bruce, Ian N.] Univ Manchester, Manchester, Lancs, England. [Isenberg, David; Rahman, Anisur] UCL, London, England. [Wallace, Daniel J.; Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Wallace, Daniel J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Nived, Ola; Sturfelt, Gunnar] Univ Lund Hosp, S-22185 Lund, Sweden. [Ramsey-Goldman, Rosalind] Northwestern Univ, Chicago, IL 60611 USA. [Bae, Sang-Cheol] Hanyang Univ Hosp Rheumat Dis, Seoul, South Korea. [Hanly, John G.] Dalhousie Univ, Halifax, NS, Canada. [Hanly, John G.] Capital Hlth, Halifax, NS, Canada. [Sanchez-Guerrero, Jorge] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Sanchez-Guerrero, Jorge] Univ Hlth Network, Toronto, ON, Canada. [Clarke, Ann; Bernatsky, Sasha] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Aranow, Cynthia] Feinstein Inst Med Res, Manhasset, NY USA. [Manzi, Susan] Allegheny Singer Res Inst, Pittsburgh, PA 15212 USA. [Manzi, Susan] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Urowitz, Murray; Gladman, Dafna] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Urowitz, Murray; Gladman, Dafna] Univ Toronto, Toronto, ON, Canada. [Kalunian, Kenneth] Univ Calif San Diego, La Jolla, CA 92093 USA. [Costner, Melissa] N Dallas Dermatol Associates, Dallas, TX USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Philadelphia, PA 19104 USA. [Zoma, Asad] Lanarkshire Ctr Rheumatol, E Kilbride, Lanark, Scotland. [Zoma, Asad] Hairmyres Hosp, E Kilbride, Lanark, Scotland. [Ruiz-Irastorza, Guillermo] Hosp Univ Cruces, Baracaldo, Spain. [Ruiz-Irastorza, Guillermo] Univ Basque Country, Baracaldo, Spain. [Khamashta, Munther A.] Rayne Inst, London, England. [Khamashta, Munther A.] St Thomas Hosp, London, England. [Jacobsen, Soren] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark. [Buyon, Jill P.; Franks, Andrew G., Jr.] NYU, New York, NY USA. [Maddison, Peter] Ysbyty Gwynedd, Bangor, Gwynedd, Wales. [Dooley, Mary Anne] Univ N Carolina, Chapel Hill, NC USA. [van vollenhoven, Ronald F.] Karolinska Univ Hosp, Stockholm, Sweden. [Ginzler, Ellen] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Stoll, Thomas] Kantonsspital Schaffhausen, Schaffhausen, Switzerland. [Peschken, Christine] Univ Manitoba, Winnipeg, MB, Canada. [Jorizzo, Joseph L.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Callen, Jeffrey P.] Univ Louisville, Louisville, KY 40292 USA. [Lim, S. Sam] Emory Univ, Atlanta, GA 30322 USA. [Inanc, Murat] Istanbul Univ, Istanbul, Turkey. [Kamen, Diane L.] Med Univ S Carolina, Charleston, SC USA. [Steinsson, Kristjan] Landspitali Univ Hosp, Reykjavik, Iceland. [Brey, Robin] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Magder, Laurence S.] Univ Maryland, Baltimore, MD 21201 USA. RP Petri, M (reprint author), Johns Hopkins Univ, Sch Med, 1830 E Monument St,Suite 7500, Baltimore, MD 21205 USA. EM mpetri@jhmi.edu RI inanc, murat/I-3444-2012; Ruiz-Irastorza, Guillermo/P-7058-2014; , Ivan/D-6804-2012; OI Ruiz-Irastorza, Guillermo/0000-0001-7788-1043; Peschken, Christine/0000-0002-4269-5213; Isenberg, David/0000-0001-9514-2455; , Ivan/0000-0002-3108-058X; Franks, Andrew/0000-0001-5427-6369; Bruce, Ian/0000-0003-3047-500X FU NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [R01-AR-043727]; Lupus Foundation of America; Human Genome Sciences; NIH [T32-AR-048522]; GlaxoSmithKline; Roche; Abbott; MSD; Pfizer; UCB Pharma; Amgen; LEO Pharma; Warner Chilcott FX Supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R01-AR-043727), the Lupus Foundation of America, and Human Genome Sciences (unrestricted research grant). Dr. Orbai's work was supported by the NIH (grant T32-AR-048522).; Dr. Fortin has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline (less than $10,000). Dr. Bruce has received consulting fees, speaking fees, and/or honoraria from Human Genome Sciences, GlaxoSmithKline, and Roche (less than $10,000 each). Dr. Nived has received speaking fees from GlaxoSmithKline (less than $10,000). Dr. van Vollenhoven has received honoraria from Abbott, GlaxoSmithKline, MSD, Pfizer, Roche, and UCB Pharma (less than $10,000 each) and research support from Abbott, GlaxoSmithKline, MSD, Pfizer, Roche, and UCB Pharma. Dr. Jorizzo has received consulting fees, speaking fees, and/or honoraria from Amgen, LEO Pharma, and Warner Chilcott (less than $10,000 each). NR 33 TC 460 Z9 514 U1 10 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD AUG PY 2012 VL 64 IS 8 BP 2677 EP 2686 DI 10.1002/art.34473 PG 10 WC Rheumatology SC Rheumatology GA 980PX UT WOS:000306906500028 PM 22553077 ER PT J AU Maleki, N Linnman, C Brawn, J Burstein, R Becerra, L Borsook, D AF Maleki, Nasim Linnman, Clas Brawn, Jennifer Burstein, Rami Becerra, Lino Borsook, David TI Her versus his migraine: multiple sex differences in brain function and structure SO BRAIN LA English DT Article DE migraine; headache; pain; sex differences; fMRI; morphometry; precuneus; insula ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; VOXEL-BASED MORPHOMETRY; GREY-MATTER CHANGES; GENDER-DIFFERENCES; GRAY-MATTER; GEOMETRICALLY ACCURATE; CORTICAL THICKNESS; NEUROPATHIC PAIN; VISCERAL STIMULI AB Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs. C1 [Maleki, Nasim] Harvard Univ, Sch Med, Dept Anaesthesia, Childrens Hosp Boston,CHB, Boston, MA 02115 USA. [Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Becerra, Lino; Borsook, David] Childrens Hosp, Dept Radiol, Ctr Pain & Brain, MCL,MGH, Boston, MA 02115 USA. [Burstein, Rami; Borsook, David] Harvard Univ, Sch Med, Dept Anaesthesia, Beth Israel Deaconess Hosp, Boston, MA 02115 USA. [Becerra, Lino] McLean Hosp, Dept Psychiat, PAIN Grp, Boston, MA 02478 USA. [Becerra, Lino] Harvard Univ, Sch Med, Boston, MA 02478 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02114 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02114 USA. RP Maleki, N (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Childrens Hosp Boston,CHB, Boston, MA 02115 USA. EM nasim.maleki@childrens.harvard.edu FU NIH [K24 NS064050, R01-NS056195, R01-NS073997]; IASP Early Career Grant; Swedish Society for Medical Research (SSMF) FX The work was supported in by grants from NIH (K24 NS064050 (NINDS), R01-NS056195 (NINDS) and R01-NS073997 (NINDS) to D. B. C. L. received support from the IASP Early Career Grant and the Swedish Society for Medical Research (SSMF). NR 92 TC 53 Z9 58 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD AUG PY 2012 VL 135 BP 2546 EP 2559 DI 10.1093/brain/aws175 PN 8 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 984DQ UT WOS:000307170300033 PM 22843414 ER PT J AU Bosco, JLF Palmer, JR Boggs, DA Hatch, EE Rosenberg, L AF Bosco, Jaclyn L. F. Palmer, Julie R. Boggs, Deborah A. Hatch, Elizabeth E. Rosenberg, Lynn TI Cardiometabolic factors and breast cancer risk in U.S. black women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Metabolic syndrome; Obesity; Insulin resistance; Breast cancer ID BODY-FAT DISTRIBUTION; DENSITY-LIPOPROTEIN CHOLESTEROL; NUTRITION EXAMINATION SURVEY; POPULATION-BASED COHORT; 3RD NATIONAL-HEALTH; WAIST-HIP RATIO; METABOLIC SYNDROME; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; UNITED-STATES AB Previous studies have suggested that metabolic syndrome may be associated with an increased risk of breast cancer, particularly in postmenopausal women, but U.S. black women have not been assessed. We examined the associations of abdominal obesity, type 2 diabetes, hypertension, and high cholesterol individually and in combination with breast cancer incidence in the Black Women's Health Study. By means of Cox regression models, we estimated incidence rate ratios (IRR) and 95 % confidence intervals (CI) for the associations of baseline and time-dependent values of self-reported abdominal obesity, type 2 diabetes, hypertension, and high cholesterol with breast cancer incidence. During 516,452 person years of follow-up (mean years = 10.5; standard deviation = 2.9) from 1995 to 2007, 1,228 breast cancer cases were identified. After adjustment for age, education, body mass index at age 18, physical activity, and individual cardiometabolic factors, neither individual nor combinations of cardiometabolic factors were associated with breast cancer incidence overall; the multivariable IRR was 1.04 (95 % CI 0.86-1.25) for the combination of a parts per thousand yen3 factors relative to the absence of all factors, and 1.17 (0.85-1.60) for having all four factors. Among postmenopausal women, however, the comparable IRRs were 1.23 (0.93-1.62) and 1.63 (1.12-2.37), respectively. Our findings provide some support for an association between cardiometabolic factors and breast cancer incidence among postmenopausal U.S. black women. C1 [Bosco, Jaclyn L. F.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Bosco, Jaclyn L. F.] Boston Univ, Sch Med, Dept Med, Sect Geriatr, Boston, MA 02118 USA. [Palmer, Julie R.; Boggs, Deborah A.; Rosenberg, Lynn] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Hatch, Elizabeth E.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Bosco, JLF (reprint author), Dana Farber Canc Inst, 450 Brookline Ave LW519, Boston, MA 02215 USA. EM jaclyn_bosco@dfci.harvard.edu OI Hatch, Elizabeth/0000-0001-7901-3928; Palmer, Julie/0000-0002-6534-335X FU National Institutes of Health; National Cancer Institute [R01 CA058420] FX The authors gratefully acknowledge the contributions of the participants and the staff of the BWHS. This study was supported by the National Institutes of Health, and the National Cancer Institute grant R01 CA058420. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Cancer Institute or the National Institutes of Health. Although data on breast cancer pathology were obtained from several state cancer registries (AZ, CA, CO, CT, DE, DC, FL, GA, IL, IN, KY, LA, MD, MA, MI, NJ, NY, NC, OK, PA, SC, TN, TX, and VA), the results reported do not necessarily represent their views. NR 74 TC 6 Z9 6 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2012 VL 134 IS 3 BP 1247 EP 1256 DI 10.1007/s10549-012-2131-4 PG 10 WC Oncology SC Oncology GA 985NL UT WOS:000307273300033 PM 22710709 ER PT J AU Ligibel, JA O'Malley, AJ Fisher, M Daniel, GW Winer, EP Keating, NL AF Ligibel, Jennifer A. O'Malley, A. James Fisher, Maxine Daniel, Gregory W. Winer, Eric P. Keating, Nancy L. TI Patterns of bone density evaluation in a community population treated with aromatase inhibitors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Aromatase inhibitor; Breast cancer; Bone density ID EARLY BREAST-CANCER; RECEIVING ADJUVANT LETROZOLE; POSTMENOPAUSAL WOMEN; ZOLEDRONIC ACID; PRACTICAL GUIDANCE; RANDOMIZED-TRIAL; ZO-FAST; TAMOXIFEN; HEALTH; ANASTROZOLE AB Aromatase inhibitors (AIs) increase the risk of bone loss and fracture. Guidelines recommend routine bone density screening for women on AIs, but there are few data regarding the incorporation of these guidelines into clinical practice. We assessed bone density testing in a community-based cohort of breast cancer patients treated with AIs. By means of encounter and pharmacy data from WellPoint plans in the HealthCore Integrated Research Database, we assessed bone density testing among 9,138 women aged a parts per thousand yen50 years with breast cancer who were treated with AIs between 2002 and 2008. We used multivariable logistic regression to identify factors associated with baseline bone density testing in women initiating an AI, and among a subset of 2,086 women treated with AIs for at least 2 years, with testing during the first 2 years of therapy. Only 41.6 % of women underwent bone density testing when initiating AI therapy. Rates of bone density testing increased over time, but were lower for women who were older, lived in the Northeast (vs. other regions), had been treated with prior proton pump inhibitor or tamoxifen therapy, lived in areas with lower educational attainment, or were enrolled in a health maintenance organization (vs. other insurance types) (all P < 0.05). Among women treated with AIs for at least 2 years, 59.9 % of women underwent bone density testing during the first 2 years of AI therapy. Rates of testing were lower for women living in the Midwest or West (vs. Northeast), living in areas with lower education levels, enrolled in health maintenance organizations (vs. other insurance types), and with prior tamoxifen use. In conclusion, most women initiating AI therapy, and 40 % of those on long-term therapy, did not undergo recommended bone density evaluation in this community-based population. Attention is needed to insure that unnecessary fractures are avoided in breast cancer patients taking AIs. C1 [Ligibel, Jennifer A.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02215 USA. [O'Malley, A. James; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Fisher, Maxine] HealthCore Inc, Newark, DE USA. [Daniel, Gregory W.] Brookings Inst, Washington, DC 20036 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ligibel, JA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jligibel@partners.org FU National Institutes of Health [R01 CA127652] FX This work was funded by the National Institutes of Health (R01 CA127652 to Dr. Keating). NR 28 TC 5 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2012 VL 134 IS 3 BP 1305 EP 1313 DI 10.1007/s10549-012-2151-0 PG 9 WC Oncology SC Oncology GA 985NL UT WOS:000307273300039 PM 22791365 ER PT J AU Lynch, M Dahlin, C Bakitas, M AF Lynch, Maureen Dahlin, Constance Bakitas, Marie TI Bowel Obstruction and Delirium: Managing Difficult Symptoms at the End of Life SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID PALLIATIVE CARE; ADVANCED CANCER; MANAGEMENT; PATIENT AB Palliative care has become an essential component of oncology care, with a focus on maximizing quality of life and optimizing function, as well as promoting pain and symptom management. This article focuses on the care of a patient experiencing bowel obstruction and delirium, two common issues in patients with advanced cancer, and demonstrates the integration of palliative care and oncology care to achieve an individualized care plan. Management focuses on identifying and treating reversible causes and improving quality of life while respecting the patient's values and goals. Sometimes the causes are not easily identified or treatment of the cause may impair quality of life, at least temporarily. At other times, the causes may be irreversible and the focus is exclusively on quality of life. Determination of best care for individual patients requires synthesis of data from holistic assessment, including the patient's goals of care and values, as well as knowledge of the patient's disease state with evidence-based approaches to management. C1 [Lynch, Maureen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bakitas, Marie] Dartmouth Hitchcock Med Ctr, Sect Palliat Med, Lebanon, NH 03766 USA. [Bakitas, Marie] Dartmouth Hitchcock Med Ctr, Dept Anesthesiol, Lebanon, NH 03766 USA. RP Lynch, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM mtlynch@partners.org OI Bakitas, Marie/0000-0002-2913-2053 NR 32 TC 2 Z9 2 U1 0 U2 2 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD AUG PY 2012 VL 16 IS 4 BP 391 EP 398 DI 10.1188/12.CJON.391-398 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 981AL UT WOS:000306937500012 PM 22842690 ER PT J AU Sheldon, LK Leonard, K Gross, A Hartnett, E Poage, E Squires, J Ullemeyer, V Schueller, M Stary, S Miller, MA AF Sheldon, Lisa Kennedy Leonard, Kathleen Gross, Anne Hartnett, Erin Poage, Ellen Squires, Jennifer Ullemeyer, Vicki Schueller, Mary Stary, Susan Miller, Mary Alice TI Oncology Nursing in Cuba: Report of the Delegation SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Editorial Material AB In December 2011, the first delegation of oncology nurses from the United States visited Havana, Cuba. The delegation included oncology nurses, educators, and leaders from across America and provided opportunities to learn about the healthcare system, cancer, and oncology nursing in Cuba. Delegation members attended lectures, toured facilities, and enjoyed Cuban culture. This exchange highlighted the similarities in cancer care and oncology nursing between countries and opened doors for future collaborations. C1 [Sheldon, Lisa Kennedy] Univ Massachusetts, Boston, MA 02125 USA. [Leonard, Kathleen; Hartnett, Erin] NYU, Langone Med Ctr, New York, NY USA. [Gross, Anne] Dana Farber Canc Inst, Boston, MA USA. [Poage, Ellen] Rehabil Associates Naples, Ft Myers, FL USA. [Squires, Jennifer] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Ullemeyer, Vicki] Novartis Pharmaceut, Ft Myers, FL USA. [Schueller, Mary] St Nicholas Hosp, Sheboygan, WI USA. [Stary, Susan] Univ Texas MD Anderson Phys Network, Houston, TX USA. [Miller, Mary Alice] Permanente Med Grp Inc, San Rafael, CA USA. RP Sheldon, LK (reprint author), Univ Massachusetts, Harbor Campus, Boston, MA 02125 USA. EM lisa.kennedysheldon@umb.edu OI Sheldon, Lisa Kennedy/0000-0002-5958-8529 NR 15 TC 1 Z9 1 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD AUG PY 2012 VL 16 IS 4 BP 421 EP 424 DI 10.1188/12.CJON.421-424 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 981AL UT WOS:000306937500017 PM 22842695 ER PT J AU Zhao, KQ Cowan, AT Lee, RJ Goldstein, N Droguett, K Chen, B Zheng, CQ Villalon, M Palmer, JN Kreindler, JL Cohen, NA AF Zhao, Ke-Qing Cowan, Andrew T. Lee, Robert J. Goldstein, Natalia Droguett, Karla Chen, Bei Zheng, Chunquan Villalon, Manuel Palmer, James N. Kreindler, James L. Cohen, Noam A. TI Molecular modulation of airway epithelial ciliary response to sneezing SO FASEB JOURNAL LA English DT Article DE chronic rhinosinusitis; mucociliary clearance; ATP; calcium ID BEAT FREQUENCY; EXTRACELLULAR ATP; CHRONIC RHINOSINUSITIS; MUCOCILIARY TRANSPORT; INTRACELLULAR CALCIUM; PROTEIN-KINASE; CA2+ RELEASE; CELLS; STIMULATION; RECEPTOR AB Our purpose was to evaluate the effect of the mechanical force of a sneeze on sinonasal cilia function and determine the molecular mechanism responsible for eliciting the ciliary response to a sneeze. A novel model was developed to deliver a stimulation simulating a sneeze (55 mmHg for 50 ms) at 26 degrees C to the apical surface of mouse and human nasal epithelial cells. Ciliary beating was visualized, and changes in ciliary beat frequency (CBF) were determined. To interrogate the molecular cascades driving sneeze-induced changes of CBF, pharmacologic manipulation of intra- and extracellular calcium, purinergic, PKA, and nitric oxide (NO) signaling were performed. CBF rapidly increases by >= 150% in response to a sneeze, which is dependent on the release of adenosine triphosphate (ATP), calcium influx, and PKA activation. Furthermore, apical release of ATP is independent of calcium influx, but calcium influx and subsequent increase in CBF are dependent on the ATP release. Lastly, we observed a blunted ciliary response in surgical specimens derived from patients with chronic rhinosinusitis compared to control patients. Apical ATP release with subsequent calcium mobilization and PKA activation are involved in sinonasal ciliary response to sneezing, which is blunted in patients with upper-airway disease.-Zhao, K.-Q., Cowan, A. T., Lee, R. J., Goldstein, N., Droguett, K., Chen, B., Zheng, C., Villalon, M., Palmer, J. N., Kreindler, J. L., Cohen, N. A. Molecular modulation of airway epithelial ciliary response to sneezing. FASEB J. 26, 3178-3187 (2012). www.fasebj.org C1 [Zhao, Ke-Qing; Lee, Robert J.; Goldstein, Natalia; Chen, Bei; Palmer, James N.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Zhao, Ke-Qing; Zheng, Chunquan] Fudan Univ, Dept Otorhinolaryngol Head & Neck Surg, Sch Shanghai Med, Eye & Ear Nose & Throat Hosp, Shanghai 200433, Peoples R China. [Cowan, Andrew T.] Temple Univ, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19122 USA. [Droguett, Karla; Villalon, Manuel] Pontificia Univ Catolica Chile, Dept Physiol, Santiago, Chile. [Goldstein, Natalia] Pontificia Univ Catolica Chile, Dept Med Sci, Santiago, Chile. [Kreindler, James L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kreindler, James L.] Univ Penn, Dept Pediat, Sch Med, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932; Lee, Robert/0000-0001-5826-6686 FU Flight Attendant Medical Research Institute (FAMRI) Clinical Innovator Award (CIA) grant [082478]; Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) grant [1080679]; Proyecto Anillo ACT-79; Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) grant [24090041] FX Financial support for these experiments was provided by Flight Attendant Medical Research Institute (FAMRI) Clinical Innovator Award (CIA) grant 082478 to N.A.C., Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) grant 1080679 to M.V., Proyecto Anillo ACT-79 to K.D., and Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) grant 24090041 to M.V. NR 58 TC 10 Z9 10 U1 0 U2 8 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 AUG PY 2012 VL 26 IS 8 BP 3178 EP 3187 DI 10.1096/fj.11-202184 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 984BI UT WOS:000307162800009 PM 22516297 ER PT J AU Schurpf, T Chen, Q Liu, JH Wang, R Springer, TA Wang, JH AF Schuerpf, Thomas Chen, Qiang Liu, Jin-huan Wang, Rui Springer, Timothy A. Wang, Jia-huai TI The RGD finger of Del-1 is a unique structural feature critical for integrin binding SO FASEB JOURNAL LA English DT Article DE crystal structure; cell adhesion; innate immunity; extracellular matrix protein ID EPIDERMAL-GROWTH-FACTOR; DEVELOPMENTAL ENDOTHELIAL LOCUS-1; FACTOR-LIKE DOMAIN; CRYSTAL-STRUCTURE; APOPTOTIC CELLS; PROTEIN; RECEPTOR; ALPHA-V-BETA-3; ANGIOGENESIS; RECOGNITION AB Developmental endothelial cell locus-1 (Del-1) glycoprotein is secreted by endothelial cells and a subset of macrophages. Del-1 plays a regulatory role in vascular remodeling and functions in innate immunity through interaction with integrin alpha(v)beta 3. Del-1 contains 3 epidermal growth factor (EGF)-like repeats and 2 discoidin-like domains. An Arg-Gly-Asp (RGD) motif in the second EGF domain (EGF2) mediates adhesion by endothelial cells and phagocytes. We report the crystal structure of its 3 EGF domains. The RGD motif of EGF2 forms a type II' beta turn at the tip of a long protruding loop, dubbed the RGD finger. Whereas EGF2 and EGF3 constitute a rigid rod via an interdomain calcium ion binding site, the long linker between EGF1 and EGF2 lends considerable flexibility to EGF1. Two unique O-linked glycans and 1 N-linked glycan locate to the opposite side of EGF2 from the RGD motif. These structural features favor integrin binding of the RGD finger. Mutagenesis data confirm the importance of having the RGD motif at the tip of the RGD finger. A database search for EGF domain sequences shows that this RGD finger is likely an evolutionary insertion and unique to the EGF domain of Del-1 and its homologue milk fat globule-EGF 8.-Schurpf, T., Chen, Q., Liu, J., Wang, R., Springer, T. A., Wang, J. The RGD finger of Del-1 is a unique structural feature critical for integrin binding. FASEB J. 26, 3412-420 (2012). www.fasebj.org C1 [Chen, Qiang; Liu, Jin-huan; Wang, Jia-huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Schuerpf, Thomas; Wang, Rui; Springer, Timothy A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu OI Chen, Qiang/0000-0002-2398-4482 FU U.S. National Institutes of Health [HL103526] FX The authors acknowledge U.S. National Institutes of Health grant HL103526 to T.A.S. and J.-H.W. The authors also thank the staff members at Advanced Photon Source beamlines 24-ID and 19-ID (Argonne National Laboratory, Argonne, IL, USA) for the help in X-ray data collection. Structural data have been deposited in the Protein Data Bank (PDB code 4D90). NR 48 TC 12 Z9 14 U1 0 U2 5 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 AUG PY 2012 VL 26 IS 8 BP 3412 EP 3420 DI 10.1096/fj.11-202036 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 984BI UT WOS:000307162800028 PM 22601780 ER PT J AU Roosli, C Chhan, D Halpin, C Rosowski, JJ AF Roeoesli, Christof Chhan, David Halpin, Christopher Rosowski, John J. TI Comparison of umbo velocity in air- and bone-conduction SO HEARING RESEARCH LA English DT Article ID DOPPLER VIBROMETER LDV; MIDDLE-EAR; FLUID PATHWAY; HEARING; STIMULATION; THRESHOLDS; MOTION; SOUND; PRESSURE; HUMANS AB This study investigates the ossicular motion produced by bone-conducted (BC) sound in live human ears. Laser Doppler Vibrometry was used to measure air conduction (AC)- and BC-induced umbo velocity (V-U) in both ears of 10 subjects, 20 ears total. Sound pressure in the ear canal (P-EC) was measured simultaneously. For air conduction, V-U at standard hearing threshold level was calculated. For BC, Delta V was defined as the difference between V-U and the tympanic ring velocity (an estimate of the skull velocity measured in the ear canal). Delta V and P-EC at BC standard hearing threshold were calculated. Delta V at standard BC threshold was significantly smaller than Vu at standard AC threshold between 500 Hz and 2000 Hz. Ear canal pressure at BC threshold tended to be smaller than for AC below 3000 Hz (with significant differences at 1000 Hz and 2000 Hz). Our results are most consistent with inertia of the ossicles and cochlear fluid driving BC hearing below 500 Hz, but with other mechanisms playing a significant role at higher frequencies. Sound radiated into the external ear canal might contribute to BC hearing at 3000 Hz and above. (C) 2012 Elsevier B.V. All rights reserved. C1 [Roeoesli, Christof; Chhan, David; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Roeoesli, Christof; Halpin, Christopher; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Roeoesli, Christof] Univ Zurich Hosp, Clin Otorhinolaryngol Head & Neck Surg, CH-8091 Zurich, Switzerland. [Chhan, David; Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Halpin, Christopher] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Roosli, C (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM christof_roosli@meei.harvard.edu FU NIDCD NIH HHS [R01 DC004798, R01 DC000194] NR 25 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD AUG PY 2012 VL 290 IS 1-2 BP 83 EP 90 DI 10.1016/j.heares.2012.04.011 PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 983PS UT WOS:000307131800009 PM 22609771 ER PT J AU Westover, MB Eiseman, NA Bianchi, MT AF Westover, M. Brandon Eiseman, Nathaniel A. Bianchi, Matt T. TI Should risky treatments be reserved for secondary prevention? Theoretical considerations regarding risk-benefit tradeoffs SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Clinical trials; Human; Trial design; Public health; Prevention; Risk ID MEDICAL DECISION-ANALYSIS; CORONARY-HEART-DISEASE; COST-EFFECTIVENESS; PRIMER; GUIDELINES; ASPIRIN; STATINS; WORKING; STROKE AB Objective: Clinical intuition suggests that risk-reducing treatments are more beneficial for patients with greater risk of disease. This intuition contributes to our rationale for tolerating greater adverse event risk in the setting of secondary prevention of certain diseases such as myocardial infarction or stroke. However, under certain conditions treatment benefits may be greater in primary prevention, even when the treatment carries harmful adverse effect potential. Study Design and Setting: We present simple decision-theoretic models that illustrate conditions of risk and benefit under which a treatment is predicted to be more beneficial in primary than in secondary prevention. Results: The models cover a spectrum of possible clinical circumstances, and demonstrate that net benefit in primary prevention can occur despite no benefit (or even net harm) in secondary prevention. Conclusion: This framework provides a rationale for extending the familiar concept of balancing risks and benefits to account for disease-specific considerations of primary vs. secondary prevention. (C) 2012 Elsevier Inc. All rights reserved. C1 [Westover, M. Brandon; Eiseman, Nathaniel A.; Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center; Pfizer, Inc.; Merck Co. FX The authors are supported by the Department of Neurology, Massachusetts General Hospital (M.T.B. and M.B.W.), and the Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center, in collaboration with Pfizer, Inc. and Merck & Co. (M.T.B.). The funding sources had no role in the design, interpretation, or publication of this work. NR 22 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 2012 VL 65 IS 8 BP 877 EP 886 DI 10.1016/j.jclinepi.2012.02.011 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 987KC UT WOS:000307414800010 PM 22640567 ER PT J AU Taulli, R Pandolfi, PP AF Taulli, Riccardo Pandolfi, Pier Paolo TI "Snorkeling" for missing players in cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID SMALL NUCLEOLAR RNAS; SNORNA HOST GENES; NONCODING RNA; MULTIPLE-MYELOMA; MICRORNA; GROWTH; MMSET; GAS5; PTEN AB Small nucleolar RNAs (snoRNAs) are emerging as an important new class of genes deregulated in cancer. Orphans snoRNAs are encoded outside of ribosomal protein genes and are involved in either gene splicing or are microRNA precursors. In this issue of JCI, Chu et al. find that ACA11, an orphan snoRNA encoded in an intron of the WHSC1 gene, is aberrantly overexpressed in t(4;14)-positive patients with multiple myeloma (MM), in which it influences growth of MM cells, resistance to chemotherapy, and oxidative stress. These findings represent the first identification of a snoRNA overexpressed as a consequence of a chromosomal translocation, a potent driving force of the neoplastic process in general and hematopoietic malignancies in particular. C1 [Taulli, Riccardo; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Canc Genet Program, Sch Med,Dept Med, Boston, MA 02215 USA. [Taulli, Riccardo; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Taulli, Riccardo] Univ Turin, Dept Anat Pharmacol & Forens Med, Turin, Italy. [Taulli, Riccardo] Univ Turin, Ctr Expt Res & Med Studies, Turin, Italy. RP Pandolfi, PP (reprint author), BIDMC, 3 Blackfan Circle,CLS 401, Boston, MA 02115 USA. EM ppandolf@bidmc.harvard.edu NR 23 TC 8 Z9 8 U1 0 U2 6 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 AUG PY 2012 VL 122 IS 8 BP 2765 EP 2768 DI 10.1172/JCI63549 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 983OM UT WOS:000307128600011 PM 22751102 ER PT J AU Strong, A Ding, QR Edmondson, AC Millar, JS Sachs, KV Li, XY Kumaravel, A Wang, MY Ai, D Guo, L Alexander, ET Nguyen, D Lund-Katz, S Phillips, MC Morales, CR Tall, AR Kathiresan, S Fisher, EA Musunuru, K Rader, DJ AF Strong, Alanna Ding, Qiurong Edmondson, Andrew C. Millar, John S. Sachs, Katherine V. Li, Xiaoyu Kumaravel, Arthi Wang, Margaret Ye Ai, Ding Guo, Liang Alexander, Eric T. Nguyen, David Lund-Katz, Sissel Phillips, Michael C. Morales, Carlos R. Tall, Alan R. Kathiresan, Sekar Fisher, Edward A. Musunuru, Kiran Rader, Daniel J. TI Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; FAMILIAL COMBINED HYPERLIPIDEMIA; PLURIPOTENT STEM-CELLS; LYSOSOMAL TRAFFICKING; INSULIN-RESISTANCE; PROTEIN; DEGRADATION; CHOLESTEROL; RECEPTOR; TRIGLYCERIDE AB Genome-wide association studies (GWAS) have identified a genetic variant at a locus on chromosome 1p13 that is associated with reduced risk of myocardial infarction, reduced plasma levels of LDL cholesterol (LDL-C), and markedly increased expression of the gene sortilin-1 (SORT1) in liver. Sortilin is a lysosomal sorting protein that binds ligands both in the Golgi apparatus and at the plasma membrane and traffics them to the lysosome. We previously reported that increased hepatic sortilin expression in mice reduced plasma LDL-C levels. Here we show that increased hepatic sortilin not only reduced hepatic apolipoprotein B (APOB) secretion, but also increased LDL catabolism, and that both effects were dependent on intact lysosomal targeting. Loss-of-function studies demonstrated that sortilin serves as a bona fide receptor for LDL in vivo in mice. Our data are consistent with a model in which increased hepatic sortilin binds intracellular APOB-containing particles in the Golgi apparatus as well as extracellular LDL at the plasma membrane and traffics them to the lysosome for degradation. We thus provide functional evidence that genetically increased hepatic sortilin expression both reduces hepatic APOB secretion and increases LDL catabolism, providing dual mechanisms for the very strong association between increased hepatic sortilin expression and reduced plasma LDL-C levels in humans. C1 [Rader, Daniel J.] Univ Penn, Perelman Sch Med, Div Translat Med & Human Genet, Translat Res Ctr 11 125,Inst Translat Med,Cardiov, Philadelphia, PA 19104 USA. [Ding, Qiurong; Musunuru, Kiran] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Ai, Ding; Tall, Alan R.] Columbia Univ, Dept Med, Div Mol Med, Med Ctr, New York, NY USA. [Guo, Liang; Fisher, Edward A.] NYU, Sch Med, Dept Med, Leon H Charney Div Cardiol, New York, NY USA. [Alexander, Eric T.; Nguyen, David; Lund-Katz, Sissel; Phillips, Michael C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Morales, Carlos R.] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada. [Kathiresan, Sekar] Massachusetts Gen Hosp, Dept Med, Cambridge, MA USA. RP Rader, DJ (reprint author), Univ Penn, Perelman Sch Med, Div Translat Med & Human Genet, Translat Res Ctr 11 125,Inst Translat Med,Cardiov, Bldg 421,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM rader@mail.med.upenn.edu OI Guo, Liang/0000-0003-1633-1544; Fisher, Edward/0000-0001-9802-143X FU American Heart Association (AHA) [10PRE3010061]; National Heart, Lung and Blood Institute (NHLBI) [RC2HL101864, R01HL109489, K99 HL098364] FX We acknowledge Hui Li, Aisha Wilson, Edwige Eduoard, and Mao-Sen Sun for their help with the animal studies; Deborah Cromley for her help with lipid measurements; and Jeffrey Billheimer, William Lagor, Ilia Fuki, Robert Brown, and Jane Glick for scientific discussions and mentorship. This work was supported by 10PRE3010061 from the American Heart Association (AHA) (to A. Strong), RC2HL101864 and R01HL109489 from the National Heart, Lung and Blood Institute (NHLBI) (to D.J. Rader), and K99 HL098364 from the NHLBI (to K. Musunuru). We would also like to acknowledge the NHLBI Gene Therapy Resource Program for providing support for the vector production as well as the Vector Core Laboratory of the University of Pennsylvania for producing the vectors. NR 41 TC 70 Z9 70 U1 0 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2012 VL 122 IS 8 BP 2807 EP 2816 DI 10.1172/JCI63563 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 983OM UT WOS:000307128600018 PM 22751103 ER PT J AU Kim, H Chen, L Lim, G Sung, B Wang, SX McCabe, MF Rusanescu, G Yang, LL Tian, YH Mao, JR AF Kim, Hyangin Chen, Lucy Lim, Grewo Sung, Backil Wang, Shuxing McCabe, Michael F. Rusanescu, Gabriel Yang, Liling Tian, Yinghong Mao, Jianren TI Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HIPPOCAMPAL SLICE CULTURES; PERIPHERAL-NERVE INJURY; LOW-BACK-PAIN; QUINOLINIC ACID; DENDRITIC CELLS; SICKNESS BEHAVIOR; NEUROPATHIC PAIN; KYNURENIC ACID; OPEN-FIELD; RATS AB Pain and depression are frequently comorbicl disorders, but the mechanism underlying this association is unknown. Here, we report that brain indoleamine 2,3-dioxygenase 1 (ID01), a rate-limiting enzyme in tryptophan metabolism, plays a key role in this comorbidity. We found that chronic pain in rats induced depressive behavior and IDO1 upregulation in the bilateral hippocampus. Upregulation of IDO1 resulted in the increased kynurenine/tryptophan ratio and decreased serotonin/tryptophan ratio in the bilateral hippocampus. We observed elevated plasma IDO activity in patients with both pain and depression, as well as in rats with anhedonia induced by chronic social stress. Intra-hippocampal administration of IL-6 in rats, in addition to in vitro experiments, demonstrated that IL-6 induces IDO1 expression through the JAK/STAT pathway. Further, either Ido1 gene knockout or pharmacological inhibition of hippocampal IDO1 activity attenuated both nociceptive and depressive behavior. These results reveal an ID01-mediated regulatory mechanism underlying the comorbidity of pain and depression and suggest a new strategy for the concurrent treatment of both conditions via modulation of brain IDO1 activity. C1 [Kim, Hyangin; Chen, Lucy; Lim, Grewo; Sung, Backil; Wang, Shuxing; McCabe, Michael F.; Rusanescu, Gabriel; Yang, Liling; Tian, Yinghong; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. EM jmao@partners.org FU NIH [R01DE18214, R01DE18538, P20DA26002] FX This study was supported by NIH grants R01DE18214, R01DE18538, and P20DA26002 (to J. Mao). NR 79 TC 101 Z9 107 U1 2 U2 28 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 AUG PY 2012 VL 122 IS 8 BP 2940 EP 2954 DI 10.1172/JCI61884 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 983OM UT WOS:000307128600030 PM 22751107 ER PT J AU Lee, RS Stewart, C Carter, SL Ambrogio, L Cibulskis, K Sougnez, C Lawrence, MS Auclair, D Mora, J Golub, TR Biegel, JA Getz, G Roberts, CWM AF Lee, Ryan S. Stewart, Chip Carter, Scott L. Ambrogio, Lauren Cibulskis, Kristian Sougnez, Carrie Lawrence, Michael S. Auclair, Daniel Mora, Jaume Golub, Todd R. Biegel, Jaclyn A. Getz, Gad Roberts, Charles W. M. TI A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CELL CARCINOMA; MUTATIONS; TUMOR; SNF5; TUMORIGENESIS; SMARCB1/INI1; ARID1A; MICE AB Cancer is principally considered a genetic disease, and numerous mutations are thought essential to drive its growth. However, the existence of genomically stable cancers and the emergence of mutations in genes that encode chromatin remodelers raise the possibility that perturbation of chromatin structure and epigenetic regulation are capable of driving cancer formation. Here we sequenced the exomes of 35 rhabdoid tumors, highly aggressive cancers of early childhood characterized by biallelic loss of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. We identified an extremely low rate of mutation, with loss of SMARCB1 being essentially the sole recurrent event. Indeed, in 2 of the cancers there were no other identified mutations. Our results demonstrate that high mutation rates are dispensable for the genesis of cancers driven by mutation of a chromatin remodeling complex. Consequently, cancer can be a remarkably genetically simple disease. C1 [Biegel, Jaclyn A.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Lee, Ryan S.; Golub, Todd R.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Lee, Ryan S.; Golub, Todd R.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Boston, MA USA. [Stewart, Chip; Carter, Scott L.; Ambrogio, Lauren; Cibulskis, Kristian; Sougnez, Carrie; Lawrence, Michael S.; Auclair, Daniel; Golub, Todd R.; Getz, Gad] Broad Inst, Cambridge, MA 02142 USA. [Mora, Jaume] Hosp St Joan de Deu, Dept Pediat Oncol, Barcelona, Spain. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Biegel, Jaclyn A.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Roberts, Charles W. M.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Biegel, JA (reprint author), Childrens Hosp Philadelphia, Div Human Genet, ARC Room 1002,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM biegel@mail.med.upenn.edu; gadgetz@broadinstitute.org; Charles_Roberts@dfci.harvard.edu FU Carlos Slim Health Institute; NSF; Garrett B. Smith Foundation; PHS awards [R01CA113794, U01-1156106]; American Association of Cancer Research; NIH [R01CA46274] FX We are graceful to K. Eaton and L. Tooke for technical assistance, A. Sivachenko for indel detection, A. McKenna for germ line mutation calling, C. Zhang for SegSeq, G. Saksema for SNP array processing, P. Stojanov for MutSig advice, and M. Meyerson and T. Pugh for fruitful discussions. We also thank all the members of the Broad Institute's Biological Samples, Genetic Analysis, and Genomic Sequencing Platforms. This project is part of the Slim Initiative for Genomic Medicine, a joint US-Mexico project funded by the Carlos Slim Health Institute. R.S. Lee is partly supported by a NSF Graduate Research Fellowship. C.W.M. Roberts is partly supported by the Garrett B. Smith Foundation, PHS awards R01CA113794 and U01-1156106, and a Stand Up to Cancer Innovative Research Grant from the American Association of Cancer Research. J.A. Biegel is partly supported by NIH grant R01CA46274. NR 25 TC 139 Z9 142 U1 0 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2012 VL 122 IS 8 BP 2983 EP 2988 DI 10.1172/JCI64400 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 983OM UT WOS:000307128600033 PM 22797305 ER PT J AU Deshpande, V Huck, A Ooi, E Stone, JH Faquin, WC Nielsen, GP AF Deshpande, Vikram Huck, Amelia Ooi, Esther Stone, John H. Faquin, William C. Nielsen, G. Petur TI Fibrosing variant of Hashimoto thyroiditis is an IgG4 related disease SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID IGG4-RELATED SYSTEMIC-DISEASE; AUTOIMMUNE PANCREATITIS; SCLEROSING CHOLANGITIS; RIEDELS STRUMA; HYPOTHYROIDISM; PREVALENCE AB Hashimoto thyroiditis (HT) and the fibrosing variant of Hashimoto thyroiditis (FVHT) are immune-mediated tumefactive lesions of the thyroid. Immunoglobulin G4-related disease (IgG4-RD) is now a widely recognised multi-organ system disease characterised by elevated serum and tissue concentrations of IgG4. In this study, the authors address several unresolved questions pertaining to the relationship between HT and FVHT, and the association of each of these diseases with IgG4-RD. The authors evaluated 28 consecutive cases of HT and nine cases of FVHT. The clinical, demographic and serological data were recorded. The slides were stained immunohistochemically using antibodies to IgG4 and IgG and the quantitative analysis was recorded. Data on thyroid function tests were available on seven cases of FVHT and 14 cases of HT. Based on the availability of data, hypothyroidism was noted in 62% (9/14) of HT and 86% of FVHT (6/7). FVHT demonstrated an exaggerated lobular pattern with lobules separated by cellular storiform-type fibrosis, resembling fibrosis seen in other forms of IgG-RD. The median IgG4 counts per high power field (x40) in HT and FVHT were 2.3 and 22, respectively. The median IgG4: IgG ratios in HT and FVHT were 0.11 and 0.58, respectively. The authors propose that FVHT belongs to the spectrum of IgG4-RD. Although a proportion of cases of HT show elevated numbers of IgG4 positive plasma cells, these cases lack the histological features typically associated with IgG4-RD, and thus the relationship between HT and IgG4-RD remains unproven. C1 [Deshpande, Vikram; Huck, Amelia; Faquin, William C.; Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ooi, Esther] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Stone, John H.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM vdeshpande@partners.org RI Ooi, Esther/B-3257-2011 OI Ooi, Esther/0000-0002-2097-633X FU National Health and Medical Research Council of Australia FX Esther Ooi is supported by a National Health and Medical Research Council of Australia Postdoctoral Research Fellowship. NR 23 TC 26 Z9 27 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD AUG PY 2012 VL 65 IS 8 BP 725 EP 728 DI 10.1136/jclinpath-2011-200485 PG 4 WC Pathology SC Pathology GA 983LJ UT WOS:000307120500010 PM 22659333 ER PT J AU Lou, E Sumrall, AL Turner, S Peters, KB Desjardins, A Vredenburgh, JJ McLendon, RE Herndon, JE McSherry, F Norfleet, J Friedman, HS Reardon, DA AF Lou, Emil Sumrall, Ashley L. Turner, Scott Peters, Katherine B. Desjardins, Annick Vredenburgh, James J. McLendon, Roger E. Herndon, James E., II McSherry, Frances Norfleet, Julie Friedman, Henry S. Reardon, David A. TI Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Meningioma; Angiogenesis; Vascular endothelial growth factor; Bevacizumab ID ENDOTHELIAL GROWTH-FACTOR; RECURRENT MENINGIOMA; PHASE-II; INTRACRANIAL MENINGIOMAS; BRAIN EDEMA; HYDROXYUREA; ANGIOGENESIS; EXPRESSION; CHEMOTHERAPY; PROGRESSION AB Intracranial meningiomas are often indolent tumors which typically grow over years to decades. Nonetheless, meningiomas that progress after maximum safe resection and radiation therapy pose a significant therapeutic challenge and effective therapies have yet to be identified. Preclinical studies implicate angiogenesis in the pathophysiology of more aggressive meningiomas, suggesting that anti-angiogenic therapies may be of utility in this setting. We performed a retrospective review of fourteen patients with recurrent meningioma treated at Duke University Medical Center with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, administered either alone or in combination with chemotherapy. Most patients were heavily pre-treated. Progression-free survival at 6 months was 86 % and was comparable regardless of meningioma grade and whether bevacizumab was administered as monotherapy or in combination with chemotherapy. Most toxicities were mild however single patients developed CNS hemorrhage (grade 1) and intestinal perforation (grade 4), respectively. Bevacizumab can be administered safely to patients with meningioma and appears to be associated with encouraging anti-tumor effect when administered as either a single agent or in combination with chemotherapy. Phase II trials investigating bevacizumab in patients with progressive/recurrent meningioma are warranted. C1 [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Friedman, Henry S.; Reardon, David A.] Duke Univ, Med Ctr, Dept Pediat, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. [Herndon, James E., II; McSherry, Frances] Duke Univ, Med Ctr, Canc Ctr Biostat, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Lou, Emil; Sumrall, Ashley L.; Turner, Scott; Norfleet, Julie; Friedman, Henry S.; Reardon, David A.] Duke Univ, Med Ctr, Dept Surg, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. [Peters, Katherine B.; Desjardins, Annick; Vredenburgh, James J.] Duke Univ, Med Ctr, Dept Med, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. [McLendon, Roger E.] Duke Univ, Med Ctr, Dept Pathol, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave SW,460G, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu FU NIH [5P50-NS-20023, 5 R37 CA11898, MO1 RR 30]; GCRC Program; NCRR; NCI SPORE [1 P20 CA096890]; Genentech Pharmaceuticals FX This work was supported by NIH Grants 5P50-NS-20023 and 5 R37 CA11898; NIH Grant MO1 RR 30, GCRC Program, NCRR; and NCI SPORE 1 P20 CA096890; and a grant from Genentech Pharmaceuticals. NR 42 TC 51 Z9 51 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD AUG PY 2012 VL 109 IS 1 BP 63 EP 70 DI 10.1007/s11060-012-0861-0 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 981FU UT WOS:000306953100008 PM 22535433 ER PT J AU Nayak, L Iwamoto, FM Rudnick, JD Norden, AD Lee, EQ Drappatz, J Omuro, A Kaley, TJ AF Nayak, Lakshmi Iwamoto, Fabio M. Rudnick, Jeremy D. Norden, Andrew D. Lee, Eudocia Quant Drappatz, Jan Omuro, Antonio Kaley, Thomas J. TI Atypical and anaplastic meningiomas treated with bevacizumab SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Meningioma; Atypical; Anaplastic; Bevacizumab; Vascular endothelial growth factor (VEGF) ID RECURRENT MENINGIOMA; PHASE-II AB Atypical and anaplastic (WHO Grades II and III) meningiomas are aggressive tumors, and patients often progress despite surgery and radiation. There is no known effective chemotherapeutic option for these patients. Meningiomas have a high expression of vascular endothelial growth factor receptor (VEGFR). We sought to retrospectively study the activity of bevacizumab, which is an anti-angiogenic agent targeting the VEGF pathway in these tumors. This is a retrospective review of WHO Grade II and III meningiomas treated at four institutions, selecting only those patients who received bevacizumab. We analyzed radiographic response according to standard RANO criteria, progression-free survival (PFS) and overall survival from the initiation of bevacizumab therapy using Kaplan-Meier statistics. We identified 15 patients across four institutions who carried a diagnosis of atypical or anaplastic meningioma and were treated with bevacizumab. Best radiographic response was stable disease. MR perfusion studies showed decreased tumor blood volume in one patient. Three patients developed non-fatal intratumoral hemorrhage. Median PFS was 26 weeks (95 % CI, 10-29 weeks). Six month PFS rate was 43.8 % (95 % CI, 15.7-69.1 %). Bevacizumab was well-tolerated in our patients, and may be considered in patients who have exhausted radiation and surgical options. Prospective studies are required to define the safety and efficacy of bevacizumab in atypical and anaplastic meningiomas. C1 [Nayak, Lakshmi; Omuro, Antonio; Kaley, Thomas J.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. [Iwamoto, Fabio M.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Rudnick, Jeremy D.] Cedars Sinai Med Ctr, Dept Neurol & Neurosurg, Los Angeles, CA 90048 USA. [Norden, Andrew D.; Lee, Eudocia Quant; Drappatz, Jan] Univ Pittsburgh, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Kaley, TJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA. EM Kaleyt@mskcc.org OI Kaley, Thomas/0000-0002-2540-8518; Omuro, Antonio/0000-0003-4299-3664 FU NCI NIH HHS [P30 CA008748] NR 10 TC 51 Z9 51 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD AUG PY 2012 VL 109 IS 1 BP 187 EP 193 DI 10.1007/s11060-012-0886-4 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 981FU UT WOS:000306953100023 PM 22544653 ER PT J AU Han, SS Nam, EC Won, JY Lee, KU Chun, W Choi, HK Levine, RA AF Han, Seon-Sook Nam, Eui-Cheol Won, Jun Yeon Lee, Kang Uk Chun, Wanjoo Choi, Hyun Kyung Levine, Robert Aaron TI Clonazepam Quiets tinnitus: a randomised crossover study with Ginkgo Biloba SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID ANIMAL-MODEL; ALPRAZOLAM AB Objective To assess the effect of Ginkgo biloba and clonazepam, a gamma-aminobutyric acid (GABA)-receptor agonist, upon tinnitus. Methods This was an open-label, randomised, crossover study. 27 men and 11 women (aged 16-80 (mean 58)) with tinnitus for more than 2 months were enrolled. Participants were randomised to either clonazepam or G biloba for the first 3 weeks. For the next 2 weeks of washout no medication was taken. For the final 3 weeks, subjects were given the other drug. The initial dose of clonazepam and G biloba was one tablet daily (clonazepam 0.5 mg; G biloba 40 mg). Subjects were instructed to increase the dose by one tablet every 3 days to a maximum of four tablets daily until they perceived a satisfactory decrease in tinnitus loudness or intolerable side effects. Tinnitus was assessed with pitch and loudness matching, tinnitus handicap inventory, and visual analogue scales of loudness, duration and annoyance. Results Comparing before and after each drug, clonazepam significantly improved tinnitus loudness (74% of subjects), duration (63%), annoyance (79%), and tinnitus handicap inventory score (61%), whereas the G biloba showed no significant differences on any of these measures. Conclusion Clonazepam is effective in treating tinnitus; G biloba is ineffective. C1 [Nam, Eui-Cheol; Won, Jun Yeon] Kangwon Natl Univ, Dept Otolaryngol, Sch Med, Chunchon 200701, Kangwon Do, South Korea. [Han, Seon-Sook] Kangwon Natl Univ, Dept Internal Med, Sch Med, Chunchon 200701, Kangwon Do, South Korea. [Nam, Eui-Cheol; Chun, Wanjoo] Kangwon Natl Univ, Inst Med Sci, Sch Med, Chunchon 200701, Kangwon Do, South Korea. [Lee, Kang Uk] Kangwon Natl Univ, Dept Psychiat, Sch Med, Chunchon 200701, Kangwon Do, South Korea. [Chun, Wanjoo] Kangwon Natl Univ, Dept Pharmacol, Sch Med, Chunchon 200701, Kangwon Do, South Korea. [Choi, Hyun Kyung] Kangwon Natl Univ Hosp, Dept Otolaryngol, Chunchon, South Korea. [Levine, Robert Aaron] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, Boston, MA 02114 USA. [Levine, Robert Aaron] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Levine, Robert Aaron] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Nam, EC (reprint author), Kangwon Natl Univ, Dept Otolaryngol, Sch Med, 1 Kangwondaehak Gil, Chunchon 200701, Kangwon Do, South Korea. EM birdynec@kangwon.ac.kr FU Basic Science Research Program through the National Research Foundation (NRF) of Korea; Ministry of Education, Science and Technology [2011-0006602] FX This research was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (2011-0006602). NR 23 TC 17 Z9 19 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD AUG PY 2012 VL 83 IS 8 BP 821 EP 827 DI 10.1136/jnnp-2012-302273 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 985QJ UT WOS:000307282600013 PM 22626945 ER PT J AU Kassam-Adams, N Palmieri, PA Rork, K Delahanty, DL Kenardy, J Kohser, KL Landolt, MA Le Brocque, R Marsac, ML Meiser-Stedman, R Nixon, RDV Bui, E McGrath, C AF Kassam-Adams, Nancy Palmieri, Patrick A. Rork, Kristine Delahanty, Douglas L. Kenardy, Justin Kohser, Kristen L. Landolt, Markus A. Le Brocque, Robyne Marsac, Meghan L. Meiser-Stedman, Richard Nixon, Reginald D. V. Bui, Eric McGrath, Caitlin TI Acute Stress Symptoms in Children: Results From an International Data Archive SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE acute stress disorder; DSM-5; diagnostic criteria ID MOTOR-VEHICLE ACCIDENTS; POSTTRAUMATIC-STRESS; INJURED CHILDREN; EVENT SCALE; DISORDER; PTSD; INTERVENTION; YOUTH; ADOLESCENTS; IMPACT AB Objective: To describe the prevalence of acute stress disorder (ASD) symptoms and to examine proposed DSM-5 symptom criteria in relation to concurrent functional impairment in children and adolescents. Method: From an international archive, datasets were identified that included assessment of acute traumatic stress reactions and concurrent impairment in children and adolescents 5 to 17 years of age. Data came from 15 studies conducted in the United States, United Kingdom, Australia, and Switzerland and included 1,645 children and adolescents. Dichotomized items were created to indicate the presence or absence of each of the 14 proposed ASD symptoms and functional impairment. The performance of a proposed diagnostic criterion (number of ASD symptoms required) was examined as a predictor of concurrent impairment. Results: Each ASD symptom was endorsed by 14% to 51% of children and adolescents; 41% reported clinically relevant impairment. Children and adolescents reported from 0 to 13 symptoms (mean = 3.6). Individual ASD symptoms were associated with greater likelihood of functional impairment. The DSM-5 proposed eight-symptom requirement was met by 202 individuals (12.3%) and had low sensitivity (0.25) in predicting concurrent clinically relevant impairment. Requiring fewer symptoms (three to four) greatly improved sensitivity while maintaining moderate specificity. Conclusions: This group of symptoms appears to capture aspects of traumatic stress reactions that can create distress and interfere with children's and adolescents' ability to function in the acute post-trauma phase. Results provide a benchmark for comparison with adult samples; a smaller proportion of children and adolescents met the eight-symptom criterion than reported for adults. Symptom requirements for the ASD diagnosis may need to be lowered to optimally identify children and adolescents whose acute distress warrants clinical attention. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(8):812-820. C1 [Kassam-Adams, Nancy] Childrens Hosp Philadelphia, Ctr Injury Res & Prevent, Philadelphia, PA 19104 USA. [Kassam-Adams, Nancy] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Rork, Kristine] Case Western Reserve Univ, Univ Hosp, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Delahanty, Douglas L.] Kent State Univ, Kent, OH USA. [Kenardy, Justin; Le Brocque, Robyne; McGrath, Caitlin] Univ Queensland, Brisbane, Qld 4072, Australia. [Landolt, Markus A.] Univ Childrens Hosp Zurich, Zurich, Switzerland. [Meiser-Stedman, Richard] Med Res Council Cognit & Brain Sci Unit, Cambridge, England. [Nixon, Reginald D. V.] Flinders Univ S Australia, Adelaide, SA, Australia. [Bui, Eric] Univ Toulouse, Toulouse, France. [Bui, Eric] Ctr Hosp Univ CHU Toulouse, Toulouse, France. [Bui, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bui, Eric] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kassam-Adams, N (reprint author), Childrens Hosp Philadelphia, Ctr Injury Res & Prevent, 3535 Market St,Suite 1150, Philadelphia, PA 19104 USA. EM nlkaphd@mail.med.upenn.edu RI Le Brocque, Robyne/F-4848-2010; Meiser-Stedman, Richard/F-7478-2013; Nixon, Reginald/A-6095-2015; Bui, Eric/J-8347-2015; Meiser-Stedman, Richard/B-6128-2016; OI Le Brocque, Robyne/0000-0002-4574-1254; Meiser-Stedman, Richard/0000-0002-0262-623X; Nixon, Reginald/0000-0003-1507-8428; Bui, Eric/0000-0002-1413-6473; Meiser-Stedman, Richard/0000-0002-0262-623X; Landolt, Markus/0000-0003-0760-5558 FU National Institute of Mental Health [R21MH086304] FX This work was supported by grant R21MH086304 from the National Institute of Mental Health. NR 33 TC 9 Z9 9 U1 0 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2012 VL 51 IS 8 BP 812 EP 820 DI 10.1016/j.jaac.2012.05.013 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 983OJ UT WOS:000307128300009 PM 22840552 ER PT J AU Kortagere, S Madani, N Mankowski, MK Schon, A Zentner, I Swaminathan, G Princiotto, A Anthony, K Oza, A Sierra, LJ Passic, SR Wang, XZ Jones, DM Stavale, E Krebs, FC Martin-Garcia, J Freire, E Ptak, RG Sodroski, J Cocklin, S Smith, AB AF Kortagere, Sandhya Madani, Navid Mankowski, Marie K. Schoen, Arne Zentner, Isaac Swaminathan, Gokul Princiotto, Amy Anthony, Kevin Oza, Apara Sierra, Luz-Jeannette Passic, Shendra R. Wang, Xiaozhao Jones, David M. Stavale, Eric Krebs, Fred C. Martin-Garcia, Julio Freire, Ernesto Ptak, Roger G. Sodroski, Joseph Cocklin, Simon Smith, Amos B., III TI Inhibiting Early-Stage Events in HIV-1 Replication by Small-Molecule Targeting of the HIV-1 Capsid SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; CA PROTEIN; BINDING; ENTRY; INTEGRATION; INFECTION; LIGANDS; REVEAL; DOMAIN AB The HIV-1 capsid (CA) protein plays essential roles in both early and late stages of virl replication and has emerged as a novel drug target. We report hybrid structure-based virtual screening to identify small molecules with the potential to interact with the N-terminal domain (NTD) of HIV-1 CA and disrupt early, preintegration steps of the HIV-1 replication cycle. The small molecule 4,4'-[dibenzo[b,d]furan-2,8-diylbis(5-phenyl-1H-imidazole-4,2-diyl)]dibenzoic acid (CK026), which had anti-HIV-1 activity in single- and multiple-round infections but failed to inhibit viral replication in peripheral blood mononuclear cells (PBMCs), was identified. Three analogues of CK026 with reduced size and better drug-like properties were synthesized and assessed. Compound I-XW-053 (4-(4,5-diphenyl-1H-imidazol-2-yl)benzoic acid) retained all of the antiviral activity of the parental compound and inhibited the replication of a diverse panel of primary HIV-1 isolates in PBMCs, while displaying no appreciable cytotoxicity. This antiviral activity was specific to HIV-1, as I-XW-053 displayed no effect on the replication of SIV or against a panel of nonretroviruses. Direct interaction of I-XW-053 was quantified with wild-type and mutant CA protein using surface plasmon resonance and isothermal titration calorimetry. Mutation of Ile37 and Arg173, which are required for interaction with compound I-XW-053, crippled the virus at an early, preintegration step. Using quantitative PCR, we demonstrated that treatment with I-XW-053 inhibited HIV-1 reverse transcription in multiple cell types, indirectly pointing to dysfunction in the uncoating process. In summary, we have identified a CAs-pecific compound that targets and inhibits a novel region in the NTD-NTD interface, affects uncoating, and possesses broad-spectrum anti-HIV-1 activity. C1 [Zentner, Isaac; Cocklin, Simon] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA. [Kortagere, Sandhya; Swaminathan, Gokul; Oza, Apara; Sierra, Luz-Jeannette; Passic, Shendra R.; Krebs, Fred C.; Martin-Garcia, Julio] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Madani, Navid; Princiotto, Amy] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, Boston, MA 02115 USA. [Mankowski, Marie K.; Ptak, Roger G.; Sodroski, Joseph] So Res Inst, Dept Infect Dis Res, Frederick, MD USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Wang, Xiaozhao; Jones, David M.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Anthony, Kevin; Stavale, Eric] USA IBT Bioservices, Baltimore, MD USA. RP Cocklin, S (reprint author), Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA. EM simon.cocklin@drexelmed.edu; smithab@sas.upenn.edu RI Martin-Garcia, Julio/A-5666-2009 OI Martin-Garcia, Julio/0000-0001-5450-5029 FU Pennsylvania Department of Health FX This project was funded by a grant obtained from the Pennsylvania Department of Health (Tobacco Settlement Formula Funds, SK and SC). NR 44 TC 19 Z9 20 U1 1 U2 21 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2012 VL 86 IS 16 BP 8472 EP 8481 DI 10.1128/JVI.05006-11 PG 10 WC Virology SC Virology GA 984NS UT WOS:000307198300013 PM 22647699 ER PT J AU Kumthip, K Chusri, P Jilg, N Zhao, L Fusco, DN Zhao, H Goto, K Cheng, D Schaefer, EA Zhang, LL Pantip, C Thongsawat, S O'Brien, A Peng, LF Maneekarn, N Chung, RT Lin, WY AF Kumthip, Kattareeya Chusri, Pattranuch Jilg, Nikolaus Zhao, Lei Fusco, Dahlene N. Zhao, Hong Goto, Kaku Cheng, Du Schaefer, Esperance A. Zhang, Leiliang Pantip, Chansom Thongsawat, Satawat O'Brien, Amornrat Peng, Lee F. Maneekarn, Niwat Chung, Raymond T. Lin, Wenyu TI Hepatitis C Virus NS5A Disrupts STAT1 Phosphorylation and Suppresses Type I Interferon Signaling SO JOURNAL OF VIROLOGY LA English DT Article ID NONSTRUCTURAL 5A PROTEIN; SENSITIVITY-DETERMINING REGION; RIBAVIRIN COMBINATION THERAPY; PEGINTERFERON ALPHA-2B; INHIBITOR BMS-790052; RNA REPLICATION; HCV GENOTYPE-2; PLUS RIBAVIRIN; IFN-ALPHA; INFECTION AB Responses to alpha interferon (IFN-alpha)-based treatment are dependent on both host and viral factors and vary markedly among patients infected with different hepatitis C virus (HCV) genotypes (GTs). Patients infected with GT3 viruses consistently respond better to IFN treatment than do patients infected with GT1 viruses. The mechanisms underlying this difference are not well understood. In this study, we sought to determine the effects of HCV NS5A proteins from different genotypes on IFN signaling. We found that the overexpression of either GT1 or GT3 NS5A proteins significantly inhibited IFN-induced IFN-stimulated response element (ISRE) signaling, phosphorylated STAT1 (P-STAT1) levels, and IFN-stimulated gene (ISG) expression compared to controls. GT1 NS5A protein expression exhibited stronger inhibitory effects on IFN signaling than did GT3 NS5A protein expression. Furthermore, GT1 NS5A bound to STAT1 with a higher affinity than did GT3 NS5A. Domain mapping revealed that the C-terminal region of NS5A conferred these inhibitory effects on IFN signaling. The overexpression of HCV NS5A increased HCV replication levels in JFH1-infected cells through the further reduction of levels of P-STAT1, ISRE signaling, and downstream ISG responses. We demonstrated that the overexpression of GT1 NS5A proteins resulted in less IFN responsiveness than did the expression of GT3 NS5A proteins through stronger binding to STAT1. We confirmed that GT1 NS5A proteins exerted stronger IFN signaling inhibition than did GT3 NS5A proteins in an infectious recombinant JFH1 virus. The potent antiviral NS5A inhibitor BMS-790052 did not block NS5A-mediated IFN signaling suppression in an overexpression model, suggesting that NS5A's contributions to replication are independent of its subversive action on IFN. We propose a model in which the binding of the C-terminal region of NS5A to STAT1 leads to decreased levels of P-STAT1, ISRE signaling, and ISG transcription and, ultimately, to preferential GT1 resistance to IFN treatment. C1 [Kumthip, Kattareeya; Chusri, Pattranuch; Jilg, Nikolaus; Zhao, Lei; Fusco, Dahlene N.; Zhao, Hong; Goto, Kaku; Cheng, Du; Schaefer, Esperance A.; Zhang, Leiliang; Peng, Lee F.; Chung, Raymond T.; Lin, Wenyu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02115 USA. [Kumthip, Kattareeya; Chusri, Pattranuch; Pantip, Chansom; O'Brien, Amornrat; Maneekarn, Niwat] Chiang Mai Univ, Fac Med, Dept Microbiol, Chiang Mai 50000, Thailand. [Thongsawat, Satawat] Chiang Mai Univ, Fac Med, Dept Internal Med, Chiang Mai 50000, Thailand. [Zhao, Hong] Peking Univ, Hosp 1, Dept Infect Dis, Beijing 100871, Peoples R China. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02115 USA. EM rtchung@partners.org FU NIH [AI069939, AI082630]; NIH-MGH Center for Human Immunology pilot/feasibility study grant; Royal Golden Jubilee Ph.D. Program of Thailand Research Fund; German Research Foundation (Deutsche Forschungsgemeinschaft) [Ji 145/1-1] FX This work was supported in part by NIH grants AI069939 (R.T.C.) and AI082630 (R.T.C.), an NIH-MGH Center for Human Immunology pilot/feasibility study grant (W.L.), the Royal Golden Jubilee Ph.D. Program of Thailand Research Fund (K.K.), and German Research Foundation (Deutsche Forschungsgemeinschaft) grant Ji 145/1-1 (N.J.). NR 50 TC 36 Z9 38 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2012 VL 86 IS 16 BP 8581 EP 8591 DI 10.1128/JVI.00533-12 PG 11 WC Virology SC Virology GA 984NS UT WOS:000307198300024 PM 22674974 ER PT J AU Chavarri-Guerra, Y Villarreal-Garza, C Liedke, PER Knaul, F Mohar, A Finkelstein, DM Goss, PE AF Chavarri-Guerra, Yanin Villarreal-Garza, Cynthia Liedke, Pedro E. R. Knaul, Felicia Mohar, Alejandro Finkelstein, Dianne M. Goss, Paul E. TI Breast cancer in Mexico: a growing challenge to health and the health system SO LANCET ONCOLOGY LA English DT Review ID NEEDLE-ASPIRATION-CYTOLOGY; LATIN-AMERICA; UNITED-STATES; CONSERVING THERAPY; CERVICAL-CANCER; WOMEN; DIAGNOSIS; COUNTRIES; RISK; MORTALITY AB Breast cancer is a major public health issue in low-income and middle-income countries. In Mexico, incidence and mortality of breast cancer have risen in the past few decades. Changes in health-care policies in Mexico have incorporated programmes for access to early diagnosis and treatment of this disease. This Review outlines the status of breast cancer in Mexico, regarding demographics, access to care, and strategies to improve clinical outcomes. We identify factors that contribute to the existing disease burden, such as low mammography coverage, poor quality control, limited access to diagnosis and treatment, and insufficient physical and human resources for clinical care. C1 [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Avon Int Breast Canc Res Program, Boston, MA 02114 USA. [Chavarri-Guerra, Yanin] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Hematol Oncol Dept, Mexico City, DF, Mexico. [Villarreal-Garza, Cynthia] Inst Nacl Cancerol, Breast Canc Dept, Mexico City, DF, Mexico. [Chavarri-Guerra, Yanin; Liedke, Pedro E. R.; Knaul, Felicia; Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA USA. [Knaul, Felicia] Harvard Global Equ Initiat, Boston, MA USA. [Knaul, Felicia] Mexican Hlth Fdn, Mexico City, DF, Mexico. [Knaul, Felicia] Tomatelo Pecho, Mexico City, DF, Mexico. [Mohar, Alejandro] Univ Nacl Autonoma Mexico, Unidad Invest Biomed Canc, Mexico City 04510, DF, Mexico. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Avon Int Breast Canc Res Program, Boston, MA 02114 USA. EM pgoss@partners.org FU GlaxoSmithKline; National Council of Science and Technology (CONACYT) [85055] FX FK is the wife of Julio Frenk, former Secretary of Health of Mexico; participated in the design and research of Seguro Popular; and is a co-investigator in a study funded by GlaxoSmithKline. All other authors declare that they have no conflicts of interest.; PEG, DMF, PERL, and YC-G thank the Avon Foundation New York. We thank the National Council of Science and Technology (CONACYT) for their finacial support to breast-cancer research (grant number 85055, Sector Research Fund for Education), and Gustavo Nigenda and Hector Arreola for reviewing the manuscript. NR 74 TC 41 Z9 43 U1 2 U2 36 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 AUG PY 2012 VL 13 IS 8 BP E335 EP E343 PG 9 WC Oncology SC Oncology GA 981MU UT WOS:000306973200020 PM 22846838 ER PT J AU Sugarbaker, PH Ryan, DP AF Sugarbaker, Paul H. Ryan, David P. TI Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? SO LANCET ONCOLOGY LA English DT Article ID INTRAPERITONEAL CHEMOTHERAPY; SYSTEMIC CHEMOTHERAPY; OVARIAN-CANCER; HEPATIC RESECTION; RANDOMIZED-TRIAL; CARCINOMATOSIS; SURVIVAL; FLUOROURACIL; OXALIPLATIN; LEUCOVORIN AB Peritoneal carcinomatosis is a common presentation in patients with metastatic colorectal cancer and the overall survival is poor. In most patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery and hyperthermic perioperative chemotherapy as the standard approach for selected patients with peritoneal metastases from colorectal cancer. Overall, very promising long-term survival has been shown in a subset of patients with a limited extent of peritoneal disease before treatment. Whether randomised, controlled trials are needed to definitively show the magnitude of benefit, if any, of this approach is an important question. This Debate outlines the arguments on each side of this issue. C1 [Sugarbaker, Paul H.] Washington Canc Inst, Washington, DC USA. [Ryan, David P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Sugarbaker, PH (reprint author), Washington Canc Inst, Washington, DC USA. EM paul.sugarbaker@Medstar.net; dpryan@partners.org NR 44 TC 35 Z9 35 U1 0 U2 6 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 AUG PY 2012 VL 13 IS 8 BP E362 EP E369 PG 8 WC Oncology SC Oncology GA 981MU UT WOS:000306973200023 PM 22846841 ER PT J AU Zhou, XH Ma, YB AF Zhou XiaoHua Ma YunBei TI BATE curve in assessment of clinical utility of predictive biomarkers SO SCIENCE CHINA-MATHEMATICS LA English DT Article DE predictive biomarker; cutoff points; interaction; BATE curve; time-to-event outcome ID CONFIDENCE BANDS; TRIAL DESIGNS; SURVIVAL-DATA; COX MODEL; REGRESSION; VALIDATION; SUBSETS AB In this paper, for time-to-event data, we propose a new statistical framework for casual inference in evaluating clinical utility of predictive biomarkers and in selecting an optimal treatment for a particular patient. This new casual framework is based on a new concept, called Biomarker Adjusted Treatment Effect (BATE) curve. The BATE curve can be used for assessing clinical utility of a predictive biomarker, for designing a subsequent confirmation trial, and for guiding clinical practice. We then propose semi-parametric methods for estimating the BATE curves of biomarkers and establish asymptotic results of the proposed estimators for the BATE curves. We also conduct extensive simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrate the application of the proposed method in a real-world data set. C1 [Zhou XiaoHua] VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA 98198 USA. [Zhou XiaoHua] Univ Washington, Dept Biostat, Seattle, WA 98198 USA. [Zhou XiaoHua] Peking Univ, Beijing Int Ctr Math Res, Beijing 100871, Peoples R China. [Ma YunBei] Princeton Univ, Dept Operat Res & Financial Engn, Princeton, NJ 08540 USA. [Ma YunBei] SW Univ Finance & Econ, Sch Stat, Chengdu 611130, Peoples R China. RP Zhou, XH (reprint author), VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA 98198 USA. EM azhou@u.washington.edu; jamie82.ma@gmail.com FU Department of Veterans Affairs Medical Center, Seattle, WA; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [XVA 61-036]; [RCS OS-196] FX This work was supported by a Core Investigator, Research Career Scientist (Grant No. RCS OS-196), Biostatistics Unit Director at the Northwest HSR&D Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA and Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, project (Grant No. XVA 61-036). The views expressed in this article are those of the authors, and do not necessarily represent the views of the Department of Veterans Affairs. The authors are grateful to Dr. Yi Li for the data analyzed in the paper. We would also like to thank an associated editor and two reviewers for their valuable comments and suggestions, which have helped us to improve the paper. NR 19 TC 1 Z9 1 U1 2 U2 9 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7283 J9 SCI CHINA MATH JI Sci. China-Math. PD AUG PY 2012 VL 55 IS 8 BP 1529 EP 1552 DI 10.1007/s11425-012-4473-0 PG 24 WC Mathematics, Applied; Mathematics SC Mathematics GA 985OX UT WOS:000307277600002 ER PT J AU Souza, D Ledbetter, S AF Souza, Daniel Ledbetter, Stephen TI Diagnostic Errors in the Evaluation of Nontraumatic Aortic Emergencies SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID MULTIDETECTOR-ROW CT; INTRAMURAL HEMATOMA; IMPENDING RUPTURE; DISTINGUISH TRUE; THORACIC AORTA; FALSE LUMEN; SPIRAL CT; DISSECTION; ANGIOGRAPHY; ANEURYSMS AB Nontraumatic aortic emergencies (NTAE) are a complex and dynamic group of serious, potentially fatal conditions affecting the aorta. These entities most often present in the emergency department setting, and include aortic dissection, intramural hematoma, penetrating atherosclerotic ulcer, as well as aortic rupture and impending rupture. The radiologist plays a critical role in prompt diagnosis and evaluation since presenting signs and symptoms are often nonspecific. This article focuses on the potential sources of error in the imaging evaluation of patients presenting with NTAE. Semin Ultrasound CT MRI 33:318-336 (c) 2012 Elsevier Inc. All rights reserved. C1 [Ledbetter, Stephen] Harvard Univ, Sch Med, Faulkner Hosp Brigham & Womens Hlth Care, Boston, MA 02115 USA. [Ledbetter, Stephen] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Souza, Daniel] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP Souza, D (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp & Canc Imaging, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM dasouza@partners.org NR 40 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD AUG PY 2012 VL 33 IS 4 BP 318 EP 336 DI 10.1053/j.sult.2012.02.001 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 983ZS UT WOS:000307157800007 PM 22824122 ER PT J AU Khan, MAS Farkhondeh, M Crombie, J Jacobson, L Kaneki, M Martyn, JAJ AF Khan, Mohammed Abdul Sattar Farkhondeh, Mina Crombie, Jennifer Jacobson, Leslie Kaneki, Masao Martyn, J. A. Jeevendra TI LIPOPOLYSACCHARIDE UPREGULATES alpha 7 ACETYLCHOLINE RECEPTORS: STIMULATION WITH GTS-21 MITIGATES GROWTH ARREST OF MACROPHAGES AND IMPROVES SURVIVAL IN BURNED MICE SO SHOCK LA English DT Article DE alpha 7 acetylcholine receptor agonist; alpha 7 acetylcholine receptor antagonists; alpha-bungarotoxin; tumor necrosis factor alpha; upregulation; vecuronium ID TUMOR-NECROSIS-FACTOR; CHOLINERGIC ANTIINFLAMMATORY PATHWAY; SKELETAL-MUSCLE; AGONIST; INJURY; INFLAMMATION; EXPRESSION; SEPSIS; TARGET; TISSUE AB Nicotinic stimulation of the alpha 7 acetylcholine receptors (alpha 7AChRs) mitigates the lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) and other cytokines release in macrophages. This effect is blocked by alpha 7AChR antagonist, alpha-bungarotoxin (BTX). We tested and confirmed the hypotheses that LPS upregulates alpha 7AChRs, and the prototypical alpha 7AChR antagonists, vecuronium and BTX, do not block the effects of GTS-21, a specific alpha 7AChR agonist, on TNF-alpha release. With the knockdown of alpha 7AChR expression by short interference RNA, GTS-21 effects on inhibition of TNF-alpha release were not demonstrable. In addition, GTS-21 mitigated the LPS-induced growth arrest of macrophages in vitro in J774A.1 cells and ex vivo in peritoneal macrophages obtained from mice at 3 days after burn. Moreover, GTS-21 reduced mortality after burn injury in mice. These results indicate that (i) LPS upregulates alpha 7AChRs; (ii) the therapeutic beneficial effects of GTS-21 on cytokine release are specifically mediated via alpha 7AChRs and are preserved even when cotreated with prototypical antagonist, BTX, or clinically used muscle nicotinic antagonist, vecuronium; (iii) activation of alpha 7AChRs by GTS-21 partially reverses the LPS-induced proliferation arrest; and (iv) GTS-21 reduces mortality in mice with burn injury. The in vivo beneficial effects of GTS-21 in burn injury warrant further studies. C1 [Martyn, J. A. Jeevendra] Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Martyn, JAJ (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesia Crit Care & Pain Med, 51 Blossom St,Room 206, Boston, MA 02114 USA. EM jmartyn@partners.org FU National Institutes of Health [RO1-055082, P50-2500]; Shriners Hospitals for Children FX This work was supported by grants from the National Institutes of Health RO1-055082 and P50-2500 project IV and from Shriners Hospitals for Children. NR 29 TC 14 Z9 17 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD AUG PY 2012 VL 38 IS 2 BP 213 EP 219 DI 10.1097/SHK.0b013e31825d628c PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 977PO UT WOS:000306677100014 PM 22683726 ER PT J AU Mejia, P Davis, AE AF Mejia, Pedro Davis, Alvin E., III TI C1 INHIBITOR SUPPRESSES THE ENDOTOXIC ACTIVITY OF A WIDE RANGE OF LIPOPOLYSACCHARIDES AND INTERACTS WITH LIVE GRAM-NEGATIVE BACTERIA SO SHOCK LA English DT Article DE LPS neutralization; endotoxin shock protection; suppression of inflammation; protein-bacteria interactions ID N-LINKED GLYCOSYLATION; SALMONELLA-TYPHIMURIUM; MEDIATED PROTECTION; SEPTIC SHOCK; SEPSIS; CORE; DEFECTS; MUTANT; LPS AB Human C1 inhibitor (C1INH) prevents endotoxin shock via a direct interaction with Gram-negative bacterial lipopolysaccharide (LPS) and improves survival in animal models of sepsis. In this report, we further characterize the interaction of C1INH with LPS and whole live bacteria. We investigate C1INH interactions with LPS from five different strains of Gram-negative enteric bacteria known to participate in the pathogenesis of human sepsis. Treatment with C1INH improved survival in mice with endotoxin shock induced by LPS from Salmonella enterica serovar typhimurium as previously shown, as well as LPS from Escherichia coli O55:B5 and Pseudomonas aeruginosa, and a trend to improved survival was observed when Klebsiella pneumoniae and Serratia marcescens LPS were used. Enzyme-linked immunosorbent assay and native polyacrylamide gel electrophoresis shift experiments demonstrated a direct interaction of C1INH with LPS from all the strains studied. The binding of both native and reactive center-cleaved, inactive C1INH results in inhibition of LPS-induced proinflammatory cytokine production. Furthermore, we demonstrate the ability of C1INH to bind at the surface of only a restricted number of whole live Gram-negative bacteria as well as mutant bacteria expressing a truncated LPS lacking the O-antigen. These data reveal the interaction of C1INH with a wide range of enteric bacterial LPS and strongly suggest that the interaction between C1INH and the surface of Gram-negative microorganisms is determined by the length of the polysaccharide chain of the endotoxin molecule. C1 [Mejia, Pedro; Davis, Alvin E., III] Harvard Univ, Sch Med, Immune Dis Inst, Program Cellular & Mol Med,Childrens Hosp Boston, Boston, MA 02115 USA. RP Mejia, P (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave,Bldg 2,1st Floor,Room 127, Boston, MA 02115 USA. EM pmejia@hsph.harvard.edu NR 22 TC 6 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD AUG PY 2012 VL 38 IS 2 BP 220 EP 225 DI 10.1097/SHK.0b013e31825bf40e PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 977PO UT WOS:000306677100015 PM 22576004 ER PT J AU Padmanabhan, S Newton-Cheh, C Dominiczak, AF AF Padmanabhan, Sandosh Newton-Cheh, Christopher Dominiczak, Anna F. TI Genetic basis of blood pressure and hypertension SO TRENDS IN GENETICS LA English DT Review DE hypertension; blood pressure; genetics; sodium; artery; kidney ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; WILL UNLOCK; RISK LOCI; EXPRESSION; DISEASE; POPULATION; HERITABILITY; METAANALYSIS; MUTATIONS AB Blood pressure (BP) is a complex trait regulated by an intricate network of physiological pathways involving extracellular fluid volume homeostasis, cardiac contractility and vascular tone through renal, neural or endocrine systems. Untreated high BP, or hypertension (HTN), is associated with increased mortality, and thus a better understanding of the pathophysiological and genetic underpinnings of BP regulation will have a major impact on public health. However, identifying genes that contribute to BP and HTN has proved challenging. In this review we describe our current understanding of the genetic architecture of BP and HTN, which has accelerated over the past five years primarily owing to genome-wide association studies (GWAS) and the continuing progress in uncovering rare gene mutations, epigenetic markers and regulatory pathways involved in the physiology of BP. We also look ahead to future studies characterizing novel pathways that affect BP and HTN and discuss strategies for translating current findings to the clinic. C1 [Padmanabhan, Sandosh; Dominiczak, Anna F.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland. [Newton-Cheh, Christopher] Harvard Univ, Broad Inst, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Newton-Cheh, Christopher] MIT, Boston, MA 02114 USA. RP Dominiczak, AF (reprint author), Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland. EM Anna.Dominiczak@glasgow.ac.uk RI Padmanabhan, Sandosh/S-3963-2016; OI Padmanabhan, Sandosh/0000-0003-3869-5808 NR 69 TC 53 Z9 57 U1 3 U2 32 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD AUG PY 2012 VL 28 IS 8 BP 397 EP 408 DI 10.1016/j.tig.2012.04.001 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 983ZR UT WOS:000307157700006 PM 22622230 ER PT J AU Ebrahimi-Fakhari, D Wahlster, L McLean, PJ AF Ebrahimi-Fakhari, Darius Wahlster, Lara McLean, Pamela J. TI Protein degradation pathways in Parkinson's disease: curse or blessing SO ACTA NEUROPATHOLOGICA LA English DT Review DE Parkinson's disease; Neurodegeneration; alpha-Synuclein; Autophagy; Lysosome; Ubiquitin-proteasome system; Molecular chaperones ID CHAPERONE-MEDIATED AUTOPHAGY; LEWY BODY DISEASE; UBIQUITIN-PROTEASOME SYSTEM; ALPHA-SYNUCLEIN AGGREGATION; APOPTOTIC CELL-DEATH; NIGRA-PARS-COMPACTA; REPEAT KINASE 2; IN-VIVO MODELS; HUNTINGTONS-DISEASE; SUBSTANTIA-NIGRA AB Protein misfolding, aggregation and deposition are common disease mechanisms in many neurodegenerative diseases including Parkinson's disease (PD). Accumulation of damaged or abnormally modified proteins may lead to perturbed cellular function and eventually to cell death. Thus, neurons rely on elaborated pathways of protein quality control and removal to maintain intracellular protein homeostasis. Molecular chaperones, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are critical pathways that mediate the refolding or removal of abnormal proteins. The successive failure of these protein degradation pathways, as a cause or consequence of early pathological alterations in vulnerable neurons at risk, may present a key step in the pathological cascade that leads to spreading neurodegeneration. A growing number of studies in disease models and patients have implicated dysfunction of the UPS and ALP in the pathogenesis of Parkinson's disease and related disorders. Deciphering the exact mechanism by which the different proteolytic systems contribute to the elimination of pathogenic proteins, like alpha-synuclein, is therefore of paramount importance. We herein review the role of protein degradation pathways in Parkinson's disease and elaborate on the different contributions of the UPS and the ALP to the clearance of altered proteins. We examine the interplay between different degradation pathways and provide a model for the role of the UPS and ALP in the evolution and progression of alpha-synuclein pathology. With regards to exciting recent studies we also discuss the putative potential of using protein degradation pathways as novel therapeutic targets in Parkinson's disease. C1 [Ebrahimi-Fakhari, Darius; Wahlster, Lara; McLean, Pamela J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA. [Ebrahimi-Fakhari, Darius] Univ Heidelberg, Inst Anat & Cell Biol, D-69120 Heidelberg, Germany. [Wahlster, Lara] Univ Heidelberg, Inst Physiol & Pathophysiol, D-69120 Heidelberg, Germany. [McLean, Pamela J.] Mayo Clin Florida, Dept Neurosci, Jacksonville, FL 32224 USA. RP McLean, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM ebrahimi@stud.uni-heidelberg.de; wahlster@stud.uni-heidelberg.de; mclean.pamela@mayo.edu OI Ebrahimi-Fakhari, Darius/0000-0002-0026-4714 FU NIH [NS063963, NS073740]; German National Academic Foundation (Studienstiftung des deutschen Volkes); Hamburg Foundation for International Research and Studies; Parkinson's Disease Foundation FX We thank the peer reviewers for their valuable and thoughtful comments, which have led to a substantial improvement of the manuscript. This work was supported by NIH NS063963 and NS073740 (P.J.M.), the German National Academic Foundation (Studienstiftung des deutschen Volkes to D.E.-F. and L. W.), the Hamburg Foundation for International Research and Studies (D.E.-F.) and the Parkinson's Disease Foundation (D.E-F.). NR 180 TC 81 Z9 84 U1 2 U2 36 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD AUG PY 2012 VL 124 IS 2 BP 153 EP 172 DI 10.1007/s00401-012-1004-6 PG 20 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 976LQ UT WOS:000306586600001 PM 22744791 ER PT J AU Kim, LA D'Amore, PA AF Kim, Leo A. D'Amore, Patricia A. TI A Brief History of Anti-VEGF for the Treatment of Ocular Angiogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; VASCULAR-PERMEABILITY FACTOR; RETINAL-PIGMENT EPITHELIUM; DIABETIC MACULAR EDEMA; IRIS NEOVASCULARIZATION; ISCHEMIC RETINOPATHY; TUMOR ANGIOGENESIS; RANDOMIZED-TRIAL; NONHUMAN PRIMATE AB In 1994, The American Journal of Pathology published a key article reporting that hypoxic retina produces vascular endothelial growth factor (VEGF), suggesting a role for VEGF in ocular neovascularization. Subsequent developments in anti-VEGF treatment for neovascular eye disease have improved visual outcomes and changed the standard of care in retinal medicine and ophthalmology. (Am J Pathol 2012, 181: 376-379; http://dx.doi.org/10.1016/j.ajpath.2012.06.006) C1 [Kim, Leo A.; D'Amore, Patricia A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. RP D'Amore, PA (reprint author), Schepens Eye Inst, 20 Staniford St, Boston, MA 02114 USA. EM patricia.damore@schepens.harvard.edu FU NEI NIH HHS [R01 EY015435, EY05318, K12-EY16335, R01 EY005318, K12 EY016335, EY015435] NR 40 TC 30 Z9 30 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2012 VL 181 IS 2 BP 376 EP 379 DI 10.1016/j.ajpath.2012.06.006 PG 4 WC Pathology SC Pathology GA 983TO UT WOS:000307141800001 PM 22749677 ER PT J AU Vinjamoori, AH Jagannathan, JP Shinagare, AB Taplin, ME Oh, WK Van den Abbeele, AD Ramaiya, NH AF Vinjamoori, Anant H. Jagannathan, Jyothi P. Shinagare, Atul B. Taplin, Mary-Ellen Oh, William K. Van den Abbeele, Annick D. Ramaiya, Nikhil H. TI Atypical Metastases From Prostate Cancer: 10-Year Experience at a Single Institution SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE atypical metastatic sites; oncologic imaging; osseous metastases; prostate cancer ID RADICAL PROSTATECTOMY; UNITED-STATES; MORTALITY; PATTERNS; TRENDS; RECURRENCE; CARCINOMA AB OBJECTIVE. The purpose of the study was to retrospectively review the frequency, sites, and patterns of atypical metastases from prostate cancer and to determine whether any correlation exists between the atypical sites and biochemical or histologic variables. MATERIALS AND METHODS. All available imaging studies of 620 consecutive patients with biopsy-proven prostate carcinoma seen at our institute between 1999 and 2009 were reviewed. Eighty-two patients (mean age, 72 years; age range, 58-87 years) with atypical sites of metastases were identified. Patients were separated into groups on the basis of the presence or absence of concurrent osseous metastasis and high or low Gleason grade, and metastatic patterns were compared using the Fisher exact test. The maximum prostate-specific antigen (PSA) level for each patient was recorded and correlated with metastatic pattern using the Mann-Whitney test. RESULTS. The most frequent sites of atypical metastases were the lungs and pleura (40%, 33/82), liver (37%, 30/82), supradiaphragmatic lymph nodes (34%, 28/82), and adrenal glands (15%, 12/82). Supradiaphragmatic lymphadenopathy was more common in patients with osseous metastases (45%, 25/56) than in patients without concurrent osseous involvement (12%, 3/26; p < 0.05). There was no significant correlation between the other atypical metastatic sites and osseous metastases. Abdominal visceral metastasis occurred more frequently in patients with a high Gleason grade (25/43, 58%) than in patients with a low Gleason grade (9/29, 31%; p < 0.05). There was no significant correlation between metastatic pattern and PSA level. CONCLUSION. The lungs and pleura, liver, supradiaphragmatic lymph nodes, and adrenal glands are the most common extranodal metastatic sites of prostate cancer. Supradiaphragmatic lymphadenopathy was strongly associated with concurrent osseous metastases. C1 [Vinjamoori, Anant H.; Jagannathan, Jyothi P.; Shinagare, Atul B.; Taplin, Mary-Ellen; Oh, William K.; Van den Abbeele, Annick D.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging,Med Sch, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging,Med Sch, 450 Brookline Ave, Boston, MA 02115 USA. EM ashinagare@partners.org RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 26 TC 17 Z9 18 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2012 VL 199 IS 2 BP 367 EP 372 DI 10.2214/AJR.11.7533 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 977SY UT WOS:000306686200033 PM 22826398 ER PT J AU Bakri, A Shinagare, AB Krajewski, KM Howard, SA Jagannathan, JP Hornick, JL Ramaiya, NH AF Bakri, Amit Shinagare, Atul B. Krajewski, Katherine M. Howard, Stephanie A. Jagannathan, Jyothi P. Hornick, Jason L. Ramaiya, Nikhil H. TI Synovial Sarcoma: Imaging Features of Common and Uncommon Primary Sites, Metastatic Patterns, and Treatment Response SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; MRI; PET/CT; synovial sarcoma AB OBJECTIVE. The purpose of this review is to describe the imaging features, common and uncommon sites, metastatic pattern, and treatment response of synovial sarcoma. CONCLUSION. Synovial sarcoma primarily occurs in young adults, most commonly in the lower extremities; presents as a large, noninfiltrative, well-circumscribed mass adjacent to joints, often with punctuate calcifications; and may exhibit a triple signal pattern on T2-weighted images. Small synovial sarcomas can mimic benign lesions. This tumor has a propensity for late local recurrence and metastasis, most commonly to lung. C1 [Bakri, Amit; Shinagare, Atul B.; Krajewski, Katherine M.; Howard, Stephanie A.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Bakri, Amit] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Hornick, Jason L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM ashinagare@partners.org NR 21 TC 14 Z9 18 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2012 VL 199 IS 2 BP W208 EP W215 DI 10.2214/AJR.11.8039 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 977SY UT WOS:000306686200009 PM 22826423 ER PT J AU Kaewlai, R Abujudeh, H AF Kaewlai, Rathachai Abujudeh, Hani TI Peer Review in Clinical Radiology Practice SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE peer review; performance evaluation; quality assurance ID PERFORMANCE IMPROVEMENT; AMERICAN-COLLEGE; ASSOCIATION; STANDARDS C1 [Abujudeh, Hani] Ramathibodi Hosp, Dept Radiol, Div Emergency Radiol, Bangkok, Thailand. [Abujudeh, Hani] Mahidol Univ, Bangkok 10700, Thailand. [Kaewlai, Rathachai] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, H (reprint author), Ramathibodi Hosp, Dept Radiol, Div Emergency Radiol, Bangkok, Thailand. EM habujudeh@partners.org OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 20 TC 10 Z9 10 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2012 VL 199 IS 2 BP W158 EP W162 DI 10.2214/AJR.11.8143 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 977SY UT WOS:000306686200002 PM 22826416 ER PT J AU Zukotynski, K Lewis, A O'Regan, K Jacene, H Sakellis, C Krajewski, K Israel, D AF Zukotynski, Katherine Lewis, Aaron O'Regan, Kevin Jacene, Heather Sakellis, Christopher Krajewski, Katherine Israel, David TI PET/CT and Renal Pathology: A Blind Spot for Radiologists? Part 1, Primary Pathology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE FDG PET/CT; oncology; renal pathology ID CELL CARCINOMA; FDG PET/CT AB OBJECTIVE. PET/CT with F-18-FDG shows metabolically active disease and is widely used for the diagnosis and follow-up of patients with cancer. Nonmetabolically active renal pathology may be missed without close attention to the CT portion of the study, whereas metabolically active pathology may be missed on PET because of physiologic tracer excretion in the kidneys. This article illustrates primary lesions of the kidney on FDG PET/CT with emphasis on key anatomic features and the appearance of tracer uptake. CONCLUSION. Close attention to both the FDG PET and CT portions of the study is essential to interpret renal pathology correctly on FDG PET/CT examinations. C1 [Zukotynski, Katherine; Lewis, Aaron; O'Regan, Kevin; Jacene, Heather; Sakellis, Christopher; Krajewski, Katherine; Israel, David] Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zukotynski, K (reprint author), Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM kzukotynski@partners.org NR 15 TC 11 Z9 11 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2012 VL 199 IS 2 BP W163 EP W167 DI 10.2214/AJR.11.7790 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 977SY UT WOS:000306686200003 PM 22826417 ER PT J AU Zukotynski, K Lewis, A O'Regan, K Jacene, H Sakellis, C Almodovar, S Israel, D AF Zukotynski, Katherine Lewis, Aaron O'Regan, Kevin Jacene, Heather Sakellis, Christopher Almodovar, Samuel Israel, David TI PET/CT and Renal Pathology: A Blind Spot for Radiologists? Part 2-Lymphoma, Leukemia, and Metastatic Disease SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE FDG PET/CT; oncology; renal pathology ID NON-HODGKINS-LYMPHOMA; FDG-PET; GRANULOCYTIC SARCOMA; MALIGNANT-LYMPHOMA; CELL-CARCINOMA; CT; INVOLVEMENT; SPECTRUM; LESIONS; KIDNEY AB OBJECTIVE. PET/CT with F-18-FDG is a powerful tool to evaluate patients with hematologic malignancy or to assess the burden of metastatic disease from solid tumors. Metabolically active renal pathology associated with lymphoma, leukemia, or metastatic disease can be missed without close attention to both the PET and CT portions of the study because of physiologic FDG excretion in the kidneys. This article illustrates the appearance of tracer uptake and the key anatomic features of lymphoma, leukemia, and metastatic disease involving the kidney on FDG PET/CT. CONCLUSION. Close attention to both the FDG PET and CT portions of an FDG PET/CT study is essential to evaluate the kidneys in oncology patients. C1 [Zukotynski, Katherine; Lewis, Aaron; O'Regan, Kevin; Jacene, Heather; Sakellis, Christopher; Israel, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Almodovar, Samuel] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. RP Zukotynski, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM kzukotynski@partners.org NR 28 TC 7 Z9 7 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2012 VL 199 IS 2 BP W168 EP W174 DI 10.2214/AJR.11.7923 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 977SY UT WOS:000306686200004 PM 22826418 ER PT J AU Tan, KM Shishkov, M Chee, A Applegate, MB Bouma, BE Suter, MJ AF Tan, K. M. Shishkov, M. Chee, A. Applegate, M. B. Bouma, B. E. Suter, M. J. TI Flexible transbronchial optical frequency domain imaging smart needle for biopsy guidance SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID COHERENCE TOMOGRAPHY; BRONCHIAL LESIONS; PROBE; BRONCHOSCOPY; DIAGNOSIS AB Transbronchial needle aspiration (TBNA) is a procedure routinely performed to diagnose peripheral pulmonary lesions. However, TBNA is associated with a low diagnostic yield due to inappropriate needle placement. We have developed a flexible transbronchial optical frequency domain imaging (TB-OFDI) catheter that functions as a "smart needle" to confirm the needle placement within the target lesion prior to biopsy. The TB-OFDI smart needle consists of a flexible and removable OFDI catheter (430 mu m dia.) that operates within a standard 21-gauge TBNA needle. The OFDI imaging core is based on an angle polished ball lens design with a working distance of 160 mu m from the catheter sheath and a spot size of 25 mu m. To demonstrate the potential of the TB-OFDI smart needle for transbronchial imaging, an inflated excised swine lung was imaged through a standard bronchoscope. Cross-sectional and longitudinal OFDI results reveal the detailed network of alveoli in the lung parenchyma suggesting that the TB-OFDI smart needle may be a useful tool for guiding biopsy acquisition to increase the diagnostic yield. (C) 2012 Optical Society of America C1 [Tan, K. M.; Chee, A.; Applegate, M. B.; Suter, M. J.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Tan, K. M.; Shishkov, M.; Chee, A.; Applegate, M. B.; Bouma, B. E.; Suter, M. J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tan, K. M.; Shishkov, M.; Chee, A.; Bouma, B. E.; Suter, M. J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tan, KM (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 40 Blossom St, Boston, MA 02114 USA. EM bbouma@partners.org; msuter@partners.org FU American Lung Association Biomedical Research Grant [RG-194681-N]; National Institutes of Health [R00CA134920, P41EB015903] FX This work was funded in part by the American Lung Association Biomedical Research Grant (RG-194681-N) and the National Institutes of Health (R00CA134920 and P41EB015903). NR 23 TC 17 Z9 17 U1 0 U2 6 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 AUG 1 PY 2012 VL 3 IS 8 BP 1947 EP 1954 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 983JY UT WOS:000307116800016 PM 22876357 ER PT J AU Martelon, M Wilens, TE Anderson, JP Morrison, NR Wozniak, J AF Martelon, MaryKate Wilens, Timothy E. Anderson, Jesse P. Morrison, Nicholas R. Wozniak, Janet TI Are obstetrical, perinatal, and infantile difficulties associated with pediatric bipolar disorder? SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; obstetrical complications; perinatal ID SUBSTANCE USE DISORDERS; MAJOR AFFECTIVE-DISORDERS; SPECTRUM DISORDERS; COMPLICATIONS; CHILDREN; SCHIZOPHRENIA; ADOLESCENTS; RISK; INTERVIEW; FAMILY AB Martelon MK, Wilens TE, Anderson JP, Morrison NR, Wozniak J. Are obstetrical, perinatal, and infantile difficulties associated with pediatric bipolar disorder? Bipolar Disord 2012: 14: 507514. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: Despite increasing acknowledgement of bipolar disorder (BD) in childhood, there is a paucity of literature that has investigated obstetrical, perinatal, and infantile difficulties and their potential link with BD. To this end, we examined difficulties during delivery, immediate post-birth, and infancy and the association with BD in childhood. Methods: From two similarly designed, ongoing, longitudinal, case-control family studies of pediatric BD (N = 327 families), we analyzed 338 children and adolescents [mean (+/- standard deviation) age: 12.00 +/- 3.37 years]. We stratified them into three groups: healthy controls (N = 98), BD probands (N = 120), and their non-affected siblings (N = 120). All families were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and substance use. Mothers were directly questioned regarding the pregnancy, delivery, and infancy difficulties that occurred with each child using a module from the Diagnostic Interview for Children and Adolescents-Parent Version (DICA-P). Results: Mothers of BD subjects were more likely to report difficulties during infancy than mothers of controls [odds ratio (95% confidence interval) = 6.6 (3.0, 14.6)]. Specifically, children with BD were more likely to have been reported as a stiffened infant [7.2 (1.1, 47.1)] and more likely to have experienced other infantile difficulties [including acting colicky; 4.9 (1.3, 18.8)] compared to controls. We found no significant differences between groups in regards to obstetrical or perinatal difficulties (all p values > 0.05). Conclusions: While our results add to previous literature on obstetrical and perinatal difficulties and BD, they also highlight characteristics in infancy that may be prognostic indicators for pediatric BD. C1 [Martelon, MaryKate; Wilens, Timothy E.; Anderson, Jesse P.; Morrison, Nicholas R.; Wozniak, Janet] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Parkman St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org FU NIH [RO1 DA12945, K24 DA016264, NIH R01 MH066237]; Abbott; AstraZeneca; Eli Lilly Co.; McNeil; NextWave; NIH/NIDA; Novartis; Merck; Shire; Boehringer-Ingelheim; Axon Labs; GlaxoSmithKline; UCB (Schwarz) Pharma; Sanofi-aventis; Sepracor; Jazz Pharmaceuticals; Neurogen; Pfizer; Takeda FX This study was supported by NIH RO1 DA12945 (TW), K24 DA016264 (TW), and NIH R01 MH066237 (JW).; TEW receives or has received research support from, has been a speaker for, or is or has been on the advisory boards of Abbott, AstraZeneca, Eli Lilly & Co., McNeil, NextWave, NIH/NIDA, Novartis, Merck, and Shire; and has published the book Straight Talk about Psychiatric Medications for Kids with Guilford Press. JW is the author of Is Your Child Bipolar?, published in May 2008 by Bantam Books; and her spouse, John Winkelman, M.D., Ph.D., receives research support, is a speaker for, or is on the advisory board of Boehringer-Ingelheim, Axon Labs, GlaxoSmithKline, UCB (Schwarz) Pharma, Sanofi-aventis, Sepracor, Jazz Pharmaceuticals, Novartis, Neurogen, Pfizer, and Takeda. MKM, JPA, and NRM declare that they have no conflicts of interest to report. NR 41 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2012 VL 14 IS 5 BP 507 EP 514 DI 10.1111/j.1399-5618.2012.01027.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 979GI UT WOS:000306805000006 PM 22642419 ER PT J AU McAdam, AJ Hooper, DC DeMaria, A Limbago, BM O'Brien, TF McCaughey, B AF McAdam, Alexander J. Hooper, David C. DeMaria, Alfred Limbago, Brandi M. O'Brien, Thomas F. McCaughey, Betsy TI Antibiotic Resistance: How Serious Is the Problem, and What Can Be Done? SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [McAdam, Alexander J.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [DeMaria, Alfred] Massachusetts Dept Publ Hlth, Bur Infect Dis, Boston, MA USA. [Limbago, Brandi M.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA USA. [O'Brien, Thomas F.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [O'Brien, Thomas F.] Alliance Prudent Use Antibiot, Boston, MA USA. [McCaughey, Betsy] Comm Reduce Infect Deaths RID, New York, NY USA. RP McAdam, AJ (reprint author), Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA. EM alexander.mcadam@childrens.harvard.edu NR 0 TC 11 Z9 12 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD AUG PY 2012 VL 58 IS 8 BP 1182 EP 1186 DI 10.1373/clinchem.2011.181636 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 982JW UT WOS:000307040300004 ER PT J AU Crepeau, R Matar, A Spitzer, TR Robson, S Pathiraja, V Sachs, DH Huang, CA Duran-Struuck, R AF Crepeau, Rebecca Matar, Abraham Spitzer, Thomas R. Robson, Simon Pathiraja, Vimukthi Sachs, David H. Huang, Christene A. Duran-Struuck, Raimon TI Edema and Tetraparesis in a Miniature Pig after Allogeneic Hematopoietic Cell Transplantation SO COMPARATIVE MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; ESCHERICHIA-COLI; LYMPHOPROLIFERATIVE DISEASE; SHIGA TOXIN; SWINE; INFECTION; DIARRHEA; GENES; MODEL AB A 3-mo-old, 12-kg, intact, miniature pig presented with severe neurologic signs on day 8 after hematopoietic cell transplantation. This pig had received an immunosuppressive regimen before transplantation that included an antiCD3 immunotoxin for T-cell depletion, 100 cGy of total-body irradiation, and cyclosporine for 45 d. The pig began exhibiting erythematous lesions on post-transplantation day 7. He also demonstrated increased conscious proprioceptive deficits and recumbency but normal mentation. Neurologic signs worsened over several days; the pig became lethargic but remained afebrile. Conjunctival swelling developed on posttransplantation day 9, which subsequently spread to the animal's head, ears and hocks by day 10. Analgesics were given for pain, and cyclosporine levels were decreased. Despite the measures taken, neurologic signs progressed. Given the worsening subcutaneous edema and neurologic status, Escherichia coli infection was suspected, and treatment with a third-generation cephalosporin was instituted. The clinical signs resolved within 12 h after the start of antibiotics. 'Shiga-like' toxin from E. coli can cause peracute toxemia and induce ataxia, paralysis, and recumbency. Other common and pathognomonic findings include periocular edema and variable edema in other subcutaneous regions. A fecal sample demonstrated an overgrowth of gram-negative, lactose-fermenting colonies. On the basis of the clinical presentation, exclusion of other potential conditions compatible with edema and neurologic diseases, physical exam findings, microbiology and the resolution of signs after therapy, the pig was diagnosed with edema disease. C1 [Crepeau, Rebecca; Matar, Abraham; Spitzer, Thomas R.; Pathiraja, Vimukthi; Sachs, David H.; Huang, Christene A.; Duran-Struuck, Raimon] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Robson, Simon] Beth Israel Deaconess Med Ctr Boston, Boston, MA USA. RP Duran-Struuck, R (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM Raimon.Duran-Struuck@tbrc.mgh.harvard.edu FU NIAID NIH HHS [R01 AI084657] NR 36 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2012 VL 62 IS 4 BP 298 EP 302 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 983YP UT WOS:000307154900009 PM 23043783 ER PT J AU Singh, JP Mela, T AF Singh, Jagmeet P. Mela, Theofanie TI Anatomical left ventricular lead location and clinical outcome: not a one size fit all strategy SO EUROPACE LA English DT Editorial Material ID CARDIAC-RESYNCHRONIZATION THERAPY; HEART-FAILURE PATIENTS; ELECTRICAL DELAY; PLACEMENT; SITE C1 [Singh, Jagmeet P.; Mela, Theofanie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. EM jsingh@partners.org NR 16 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD AUG PY 2012 VL 14 IS 8 BP 1076 EP 1078 DI 10.1093/europace/eus239 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 980WU UT WOS:000306925700003 PM 22832575 ER PT J AU Biteker, M Ilhan, E Biteker, G Duman, D Bozkurt, B AF Biteker, Murat Ilhan, Erkan Biteker, Gul Duman, Dursun Bozkurt, Biykem TI Delayed recovery in peripartum cardiomyopathy: an indication for long-term follow-up and sustained therapy SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Peripartum cardiomyopathy; Late recovery; Treatment ID ECHOCARDIOGRAPHY; RECOMMENDATIONS; PREDICTORS; PROGNOSIS; SOCIETY; HEART AB Persistence of left ventricular (LV) systolic dysfunction after 6 months of diagnosis is believed to be a marker of an irreversible cardiomyopathy in peripartum cardiomyopathy (PPCM). We sought to determine the length of time required for recovery of LV systolic function (LVSF) in patients with PPCM. Forty-two consecutive women with PPCM were enrolled in this prospective study. The minimum required time of follow-up for inclusion was 30 months. Each patient underwent transthoracic echocardiography, and plasma brain natriuretic peptide (BNP) and C-reactive protein measurement at admission, and every 3 months. Early recovery was defined as normalization of LVSF at 6 months post-diagnosis. Delayed recovery was defined if the length of time required for recovery of LVSF was longer than 6 months. Persistent left ventricular dysfunction (PLVD) was defined as an ejection fraction of 50 at the end of follow-up. Twenty patients (47.6) recovered completely, 10 died (23.8), and 12 (28.6) had PLVD. Average time to complete recovery was 19.3 months after initial diagnosis (342 months). Early recovery was observed only in six patients (30), whereas delayed recovery was observed in 14 out of 20 patients (70). Patients with complete recovery were more likely to have a higher LV ejection fraction and smaller LV end-systolic dimensions at baseline. Full recovery of LVSF in PPCM patients often requires longer than 6 months. C1 [Biteker, Murat; Duman, Dursun] Haydarpasa Numune Educ & Res Hosp, Dept Cardiol, Istanbul, Turkey. [Ilhan, Erkan] Siyami Ersek Cardiovasc Surg Ctr, Dept Cardiol, Istanbul, Turkey. [Biteker, Gul] Ortaca Yucelen Hosp, Dept Obstet & Gynecol, Istanbul, Turkey. [Bozkurt, Biykem] Baylor Coll Med, Dept Med, Cardiol Sect, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Bozkurt, Biykem] Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. RP Biteker, M (reprint author), 4-7 Cevizli Kartal, Istanbul, Turkey. EM murbit2@yahoo.com NR 19 TC 25 Z9 27 U1 0 U2 1 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 AUG PY 2012 VL 14 IS 8 BP 895 EP 901 DI 10.1093/eurjhf/hfs070 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 980WM UT WOS:000306924900006 PM 22588321 ER PT J AU Costanzo, MR Heywood, JT Massie, BM Iwashita, J Henderson, L Mamatsashvili, M Sisakian, H Hayrapetyan, H Sager, P van Veldhuisen, DJ Albrecht, D AF Costanzo, Maria Rosa Heywood, J. Thomas Massie, Barry M. Iwashita, Julie Henderson, Lee Mamatsashvili, Merab Sisakian, Hamayak Hayrapetyan, Hamlet Sager, Philip van Veldhuisen, Dirk J. Albrecht, Detlef TI A double-blind, randomized, parallel, placebo-controlled study examining the effect of cross-linked polyelectrolyte in heart failure patients with chronic kidney disease SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Chronic kidney disease; Cross-linked polyelectrolyte; Potassium ID LEFT-VENTRICULAR DYSFUNCTION; EUROPEAN-SOCIETY; 6-MINUTE WALK; MORTALITY; OUTCOMES; ADHERE; ASSOCIATION; CARDIOLOGY; MORBIDITY; STATEMENT AB This double-blind, randomized, parallel, placebo-controlled investigation evaluated the effects of cross-linked polyelectrolyte (CLP) on serum potassium and measures of congestion in patients with heart failure (HF) and chronic kidney disease (CKD). The primary endpoint was change in serum potassium over time. Exploratory endpoints included: weight, physician and patient assessment of exertional dyspnoea, effect on N-terminal pro brain natriuretic peptide (NT-proBNP) levels, New York Heart Association (NYHA) classification, 6 min walk test (6MWT), and quality of life by Kansas City Cardiomyopathy Questionnaire (KCCQ). Serum potassium was similar in CLP (n 59) and placebo (n 52) groups throughout the 8-week study. Weight loss was greater in the CLP than in the placebo group at Weeks 1 (P 0.014) and 2 (P 0.004), and this trend continued until the end of the study. After 8 weeks, by physician assessment, the percentage of patients experiencing marked or disabling dyspnoea tended to be lower in the CLP than in the placebo group (7.3 vs. 23.9, P 0.128). Fewer patients in the CLP than in the placebo group had NT-proBNP levels 1000 pg/mL at Week 4 (P 0.039) and Week 8 (P 0.065). The proportion of patients improving by at least one NYHA functional class over the study was higher in the CLP than in the placebo group (48.8 vs. 17.4; P 0.002). Effects on 6MWT at Week 8 (p 0.072) and quality of life (overall KCCQ score) at Week 4 (p 0.005) and 8 (P 0.062) all favoured the CLP cohort. Four treatment-unrelated deaths occurred in the CLP group and none in the placebo group (P 0.056). In advanced, symptomatic HF with CKD, CLP is associated with beneficial clinical effects without significant serum potassium changes. Trial registration: NCT01265524. C1 [Costanzo, Maria Rosa] Edward Heart Hosp, Midwest Heart Fdn, Naperville, IL 60566 USA. [Heywood, J. Thomas] Scripps Clin, La Jolla, CA 92037 USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Iwashita, Julie; Henderson, Lee; Albrecht, Detlef] Sorbent Therapeut Inc, Sunnyvale, CA USA. [Mamatsashvili, Merab] Adapti Angiocardiol Clin, Tbilisi, Rep of Georgia. [Sisakian, Hamayak] Yerevan State Med Univ, Yerevan, Armenia. [Hayrapetyan, Hamlet] Erebouni Med Ctr, Yerevan, Armenia. [Sager, Philip] Sager Consulting Experts Inc, San Francisco, CA USA. [van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. RP Costanzo, MR (reprint author), Edward Heart Hosp, Midwest Heart Fdn, POB 3226, Naperville, IL 60566 USA. EM mariarosa.costanzo@advocatehealth.com RI van Veldhuisen, Dirk Jan/E-8967-2014 FU Sorbent Therapeutics, Inc. FX Sorbent Therapeutics, Inc. NR 30 TC 11 Z9 11 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 AUG PY 2012 VL 14 IS 8 BP 922 EP 930 DI 10.1093/eurjhf/hfs074 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 980WM UT WOS:000306924900010 PM 22613585 ER PT J AU Ghio, S Bonderman, D Felix, SB Ghofrani, HA Michelakis, ED Mitrovic, V Oudiz, RJ Frey, R Roessig, L Semigran, MJ AF Ghio, Stefano Bonderman, Diana Felix, Stephan B. Ghofrani, Hossein A. Michelakis, Evangelos D. Mitrovic, Veselin Oudiz, Ronald J. Frey, Reiner Roessig, Lothar Semigran, Marc J. TI Left ventricular systolic dysfunction associated with pulmonary hypertension riociguat trial (LEPHT): rationale and design SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Pulmonary hypertension; Systolic heart failure; Clinical trial; Soluble guanylate cyclase stimulator; Riociguat ID CHRONIC HEART-FAILURE; SOLUBLE GUANYLATE-CYCLASE; ARTERIAL-HYPERTENSION; MEDIATED VASODILATION; DIAGNOSIS; CARDIOMYOPATHY; ENDOTHELIUM; GUIDELINES; PRESSURE; SURVIVAL AB Pulmonary hypertension (PH) due to systolic left ventricular dysfunction (PH-sLVD) frequently complicates heart failure (HF), and greatly worsens the prognosis of patients with sLVD, but as yet has no approved treatment. The LEPHT study aims to characterize the haemodynamic profile, safety, tolerability, and pharmacokinetic profile of riociguat (BAY 63-2521), an oral stimulator of soluble guanylate cyclase, in patients with PH-sLVD. This 16-week, phase IIb, randomized, placebo-controlled, double-blind study enrols patients with PH-sLVD, defined as left ventricular ejection fraction (LVEF) 40 and mean pulmonary arterial pressure (PAP(mean)) epsilon 25 mmHg at rest. Patients using optimized HF medication will receive placebo or riociguat 0.5 mg, 1 mg, or up to 2 mg three times daily. The dose will be titrated for 8 weeks, based on systolic blood pressure and well-being, followed by 8 weeks of treatment at a stable dose. The primary efficacy variable is PAP(mean), while secondary efficacy endpoints include LVEF, exercise capacity, quality of life, and other haemodynamic and echocardiographic measurements. Safety and pharmacokinetics will also be assessed. After the 16-week study, patients will have the opportunity to be treated with riociguat in a long-term extension phase. The LEPHT study will provide valuable information on the haemodynamic, echocardiographic, and preliminary clinical effects of riociguat in patients with PH-sLVD. NCT01065454. C1 [Semigran, Marc J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Ghio, Stefano] Univ Hosp, Fdn IRCCS Policlin San Matteo, Dept Cardiol, Pavia, Italy. [Bonderman, Diana] Med Univ Vienna, Dept Internal Med 2, Vienna, Austria. [Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Univ Med, Dept Cardiol & Internal Med B, D-17487 Greifswald, Germany. [Ghofrani, Hossein A.] Univ Giessen, Univ Hosp Giessen & Marburg GmbH, D-35390 Giessen, Germany. [Michelakis, Evangelos D.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Mitrovic, Veselin] Kerckhoff Klin Forsch Gesell mbH, Bad Nauheim, Germany. [Oudiz, Ronald J.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Frey, Reiner] Bayer Pharma AG Berlin, Clin Pharmacol, Berlin, Germany. [Roessig, Lothar] Bayer Pharma AG Berlin, Global Clin Dev, Berlin, Germany. [Semigran, Marc J.] Harvard Univ, Sch Med, Boston, MA USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. EM msemigran@partners.org FU Bayer; Actelion; Gilead; Medtronic; Novartis; Pfizer; United Therapeutics FX The LEPHT study is funded by Bayer.; G. and S. B. F. have received lecture honoraria from Bayer, Actelion, and Pfizer. H. A. G. has received honoraria for consultations and lecturing from Bayer, Actelion, Encysive, Pfizer, Ergonex, Lilly, and Novartis, and is also a member of advisory boards for GSK, Lilly, and Merck. V. M. has received research grants from Bayer and consults for CardioPep and Daiichi-Sankyo. R.J.O. has received speaker, consulting, and/or research support from Actelion, Bayer, Gilead, Medtronic, Novartis, Pfizer, and United Therapeutics. E. D. M. has received consultant honoraria from Merck, Bayer, and United Therapeutics. R. F. and L. R. are full-time employees of Bayer. D. B. and M.J.S. have received research support from Bayer. NR 35 TC 15 Z9 16 U1 0 U2 6 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 AUG PY 2012 VL 14 IS 8 BP 946 EP 953 DI 10.1093/eurjhf/hfs071 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 980WM UT WOS:000306924900013 PM 22719060 ER PT J AU Carroll, K Dovey, M Cutting, C Gorelick, D Harris, J Sheward, L Halpern, M Goessling, W North, T AF Carroll, Kelli Dovey, Michael Cutting, Claire Gorelick, Daniel Harris, James Sheward, Lea Halpern, Marnie Goessling, Wolfram North, Trista TI EXPOSURE TO EXOGENOUS ESTROGENS IMPAIRS FORMATION OF THE HEMATOPOIETIC NICHE IN EMBRYONIC ZEBRAFISH VIA INHIBITION OF NOTCH SIGNALING SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Carroll, Kelli; Dovey, Michael; Harris, James; Sheward, Lea; North, Trista] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Cutting, Claire; Goessling, Wolfram] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goessling, Wolfram] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Boston, MA USA. [Gorelick, Daniel; Halpern, Marnie] Carnegie Inst Sci, Baltimore, MD USA. [North, Trista] Harvard Stem Cell Inst, Cambridge, MA 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S20 EP S21 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600034 ER PT J AU Ernst, P Mishra, B Zaffuto, K Li, B Chen, YF Myerson, M Artinger, E AF Ernst, Patricia Mishra, Bibhu Zaffuto, Kristin Li, Bin Chen, Yufei Myerson, Matthew Artinger, Erika TI MLL1 IS A MASTER COORDINATOR OF HSC FATE, PROLIFERATION, AND SELF-RENEWAL SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Ernst, Patricia; Mishra, Bibhu; Zaffuto, Kristin; Li, Bin; Chen, Yufei; Artinger, Erika] Geisel Sch Med Dartmouth, Hanover, NH USA. [Myerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S12 EP S12 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600019 ER PT J AU Esain, V Sheward, L Goessling, W North, T AF Esain, Virginie Sheward, Lea Goessling, Wolfram North, Trista TI REGULATION OF HEMATOPOIETIC STEM CELL FORMATION BY MEDIATORS OF INFLAMMATION SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Esain, Virginie; Sheward, Lea; North, Trista] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goessling, Wolfram] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram; North, Trista] Harvard Univ, Sch Med, Boston, MA USA. [North, Trista] Harvard Stem Cell Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S11 EP S12 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600018 ER PT J AU Etzrodt, M Cortez-Retamozo, V Pittet, M AF Etzrodt, Martin Cortez-Retamozo, Virna Pittet, Mikael TI EXTRA MEDULLARY ORIGIN OF TUMOR-ASSOCIATED MACROPHAGES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Etzrodt, Martin; Cortez-Retamozo, Virna; Pittet, Mikael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. RI Etzrodt, Martin/P-3325-2015 OI Etzrodt, Martin/0000-0003-1928-3904 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S126 EP S126 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600196 ER PT J AU Etzrodt, M Cortez-Retamozo, V Baltimore, D Weissleder, R Pittet, M AF Etzrodt, Martin Cortez-Retamozo, Virna Baltimore, David Weissleder, Ralph Pittet, Mikael TI REGULATION OF THE LY-6CHI MONOCYTE RESPONSE BY MIR-146A SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Etzrodt, Martin; Cortez-Retamozo, Virna; Weissleder, Ralph; Pittet, Mikael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Baltimore, David] CALTECH, Div Biol, Pasadena, CA 91125 USA. RI Etzrodt, Martin/P-3325-2015 OI Etzrodt, Martin/0000-0003-1928-3904 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S75 EP S75 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600119 ER PT J AU Liddicoat, B Hartner, J Lu, J Walkley, C Orkin, S AF Liddicoat, Brian Hartner, Jochen Lu, Jun Walkley, Carl Orkin, Stuart TI ADAR1 IS ESSENTIAL FOR ERYTHROID DEVELOPMENT SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Liddicoat, Brian; Walkley, Carl] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Hartner, Jochen; Walkley, Carl; Orkin, Stuart] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hartner, Jochen; Walkley, Carl] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Orkin, Stuart] Howard Hughes Med Inst, Boston, MA 02115 USA. [Orkin, Stuart] Harvard Stem Cell Inst, Boston, MA USA. [Lu, Jun] Yale Univ, Yale Stem Cell Ctr, New Haven, CT 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S54 EP S54 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600086 ER PT J AU Liddicoat, B Hartner, J Lu, J Walkley, C Orkin, S AF Liddicoat, Brian Hartner, Jochen Lu, Jun Walkley, Carl Orkin, Stuart TI ADAR1 IS ESSENTIAL FOR ERYTHROID DEVELOPMENT SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Liddicoat, Brian; Walkley, Carl] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Hartner, Jochen; Walkley, Carl; Orkin, Stuart] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hartner, Jochen; Walkley, Carl] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Orkin, Stuart] Howard Hughes Med Inst, Boston, MA 02115 USA. [Orkin, Stuart] Harvard Stem Cell Inst, Boston, MA USA. [Lu, Jun] Yale Univ, Yale Stem Cell Ctr, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S33 EP S34 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600057 ER PT J AU Millerl, C Serwold, T Wagers, A AF Millerl, Christine Serwold, Thomas Wagers, Amy TI ERYTHROPOIETIC POTENTIAL OF IPS CELLS DERIVED FROM SWACHMAN-DIAMOND SYNDROME SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Millerl, Christine; Serwold, Thomas; Wagers, Amy] Joslin Diabet Ctr, Boston, MA 02215 USA. [Millerl, Christine; Wagers, Amy] Howard Hughes Med Inst, Cambridge, MA USA. [Millerl, Christine; Wagers, Amy] Harvard Univ, Cambridge, MA 02138 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S54 EP S54 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600087 ER PT J AU Nombela-Arrieta, C Pivarnik, G Winkel, B Harley, B Mahoney, J Lu, JY Protopopov, A Silberstein, L AF Nombela-Arrieta, Cesar Pivarnik, Gegory Winkel, Beatrice Harley, Brendan Mahoney, John Lu, Jiayun Protopopov, Alexei Silberstein, Les TI HYPOXIC HEMATOPOIETIC STEM AND PROGENITOR CELLS RESIDE IN STRUCTURALLY DIVERSE PERIVASCULAR NICHES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [Nombela-Arrieta, Cesar; Pivarnik, Gegory; Winkel, Beatrice; Lu, Jiayun; Silberstein, Les] Childrens Hosp, Boston, MA 02115 USA. [Harley, Brendan] Univ Illinois, Dept Chem & Biomol Engn, Champaign, IL 61820 USA. [Mahoney, John; Protopopov, Alexei] Dana Farber Canc Ctr, Div Hematol Malignancies, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S48 EP S49 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600080 ER PT J AU North, T Harris, J Harris, L Frechette, G Garnaas, M Cox, A Cortes, M Carroll, K Esain, V Cutting, C Paw, B Vander Heiden, M Goessling, W AF North, Trista Harris, James Harris, Lauren Frechette, Gregory Garnaas, Maija Cox, Andrew Cortes, Mauricio Carroll, Kelli Esain, Virginie Cutting, Claire Paw, Barry Vander Heiden, Mathew Goessling, Wolfram TI ENHANCED METABOLIC ACTIVITY IN RESPONSE TO GLYCEMIC STATE DETERMINES THE TIMING AND MAGNITUDE OF HSC INDUCTION SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 41st Annual Scientific Meeting of the Society-for-Hematology-and-Stem-Cells CY AUG 23-26, 2012 CL Amsterdam, NETHERLANDS SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol C1 [North, Trista; Harris, James; Harris, Lauren; Frechette, Gregory; Cortes, Mauricio; Carroll, Kelli; Esain, Virginie] Harvard Univ, Sch Med, Dept Pathol, BIDMC, Boston, MA 02115 USA. [Garnaas, Maija; Cox, Andrew; Cutting, Claire; Paw, Barry; Goessling, Wolfram] Harvard Univ, Sch Med, Div Genet & Gastroenterol, Boston, MA USA. [Vander Heiden, Mathew] MIT, Koch Inst, Cambridge, MA 02139 USA. [North, Trista; Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2012 VL 40 IS 8 SU 1 BP S18 EP S18 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 986CY UT WOS:000307319600030 ER PT J AU Mack, JW Smith, TJ AF Mack, Jennifer W. Smith, Thomas J. TI Reasons Why Physicians Do Not Have Discussions About Poor Prognosis, Why It Matters, and What Can Be Improved SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; ADVANCED CANCER; LUNG-CANCER; PALLIATIVE CARE; PATIENT; HOPE; HOSPICE; COMMUNICATION; INFORMATION; SURVIVAL C1 [Mack, Jennifer W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mack, Jennifer W.] Childrens Hosp, Boston, MA 02115 USA. [Smith, Thomas J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 32 TC 73 Z9 73 U1 1 U2 3 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 AUG 1 PY 2012 VL 30 IS 22 BP 2715 EP 2717 DI 10.1200/JCO.2012.42.4564 PG 3 WC Oncology SC Oncology GA 981FK UT WOS:000306952100007 PM 22753911 ER PT J AU Mauguen, A Le Pechoux, C Saunders, MI Schild, SE Turrisi, AT Baumann, M Sause, WT Ball, D Belani, CP Bonner, JA Zajusz, A Dahlberg, SE Nankivell, M Mandrekar, SJ Paulus, R Behrendt, K Koch, R Bishop, JF Dische, S Arriagada, R De Ruysscher, D Pignon, JP AF Mauguen, Audrey Le Pechoux, Cecile Saunders, Michele I. Schild, Steven E. Turrisi, Andrew T. Baumann, Michael Sause, William T. Ball, David Belani, Chandra P. Bonner, James A. Zajusz, Aleksander Dahlberg, Suzanne E. Nankivell, Matthew Mandrekar, Sumithra J. Paulus, Rebecca Behrendt, Katarzyna Koch, Rainer Bishop, James F. Dische, Stanley Arriagada, Rodrigo De Ruysscher, Dirk Pignon, Jean-Pierre TI Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-III TRIAL; COOPERATIVE-ONCOLOGY-GROUP; TWICE-DAILY RADIOTHERAPY; THORACIC RADIOTHERAPY; RADIATION-THERAPY; FRACTIONATED RADIOTHERAPY; RANDOMIZED-TRIALS; MULTICENTER TRIAL; DOSE-ESCALATION; CELL AB Purpose In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation. Material and Methods We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy. Results In non-small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio [HR] = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non-lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities. Conclusion Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity. C1 [Pignon, Jean-Pierre] Inst Cancerol Gustave Roussy, Dept Biostat & Epidemiol, Meta Anal Unit, F-94805 Villejuif, France. [Saunders, Michele I.; Dische, Stanley] Univ Coll London, Northwood Middlesex, England. [Saunders, Michele I.; Dische, Stanley] Mt Vernon Hosp, Marie Curie Res Wing, Northwood Middlesex, England. [Nankivell, Matthew] MRC, Clin Trials Unit, London, England. [Schild, Steven E.] Mayo Clin, Phoenix, AZ USA. [Turrisi, Andrew T.] Sinai Grace Hosp, Detroit, MI USA. [Baumann, Michael; Koch, Rainer] Univ Hosp, Dresden, Germany. [Baumann, Michael; Koch, Rainer] Med Fac Carl Gustav Carus, Dresden, Germany. [Sause, William T.] Intermt Med Ctr, Murray, UT USA. [Ball, David] Univ Melbourne, Melbourne, Vic, Australia. [Bishop, James F.] Victorian Comprehens Canc Ctr, Melbourne, Vic, Australia. [Belani, Chandra P.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Paulus, Rebecca] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Bonner, James A.] Univ Alabama Birmingham, Birmingham, AL USA. [Zajusz, Aleksander; Behrendt, Katarzyna] Maria Sklodowska Curie Mem Canc Ctr, Gliwice Branch, Gliwice, Poland. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mandrekar, Sumithra J.] Mayo Clin, Rochester, MN USA. [Mandrekar, Sumithra J.] N Cent Canc Treatment Grp, Rochester, MN USA. [Arriagada, Rodrigo] Karolinska Inst, Stockholm, Sweden. [De Ruysscher, Dirk] Maastricht Univ, Med Ctr, Maastricht, Netherlands. RP Pignon, JP (reprint author), Inst Cancerol Gustave Roussy, Dept Biostat & Epidemiol, Meta Anal Unit, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM jppignon@igr.fr OI Belani, Chandra/0000-0001-5049-5329; schild, steven/0000-0002-2850-4126; Arriagada, Rodrigo/0000-0002-3134-1735; Mauguen, Audrey/0000-0003-3236-6093 FU French Programme Hospitalier de Recherche Clinique; Ligue Nationale Contre le Cancer; sanofi-aventis FX Supported by unrestricted grants from French Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, and sanofi-aventis (J.-P.P.). The funding sources had no role in study design, data collection, data analysis, data interpretation, or manuscript writing.; Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: None Honoraria: None Research Funding: Jean-Pierre Pignon, sanofi-aventis Expert Testimony: None Other Remuneration: None NR 40 TC 90 Z9 92 U1 0 U2 12 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 AUG 1 PY 2012 VL 30 IS 22 BP 2788 EP 2797 DI 10.1200/JCO.2012.41.6677 PG 10 WC Oncology SC Oncology GA 981FK UT WOS:000306952100018 PM 22753901 ER PT J AU Mullins, CD Abernethy, AP Hussain, A Montgomery, RW Pearson, SD Tunis, S AF Mullins, C. Daniel Abernethy, Amy P. Hussain, Arif Montgomery, Russ W. Pearson, Steven D. Tunis, Sean TI Tackling Off-Label Use of Anticancer Drugs Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CANCER C1 [Mullins, C. Daniel; Montgomery, Russ W.; Tunis, Sean] Ctr Med Technol Policy, Baltimore, MD USA. [Mullins, C. Daniel; Hussain, Arif] Univ Maryland, Baltimore, MD 21201 USA. [Abernethy, Amy P.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. [Abernethy, Amy P.] Duke Univ, Sch Med, Durham, NC USA. [Hussain, Arif] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA. [Montgomery, Russ W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Pearson, Steven D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pearson, Steven D.] Harvard Univ, Sch Med, Boston, MA USA. RP Mullins, CD (reprint author), Ctr Med Technol Policy, Baltimore, MD USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2012 VL 30 IS 22 BP 2801 EP 2801 DI 10.1200/JCO.2012.43.3854 PG 1 WC Oncology SC Oncology GA 981FK UT WOS:000306952100021 ER PT J AU Serrano-Pozo, A Mielke, ML Muzitansky, A Gomez-Isla, T Growdon, JH Bacskai, BJ Betensky, RA Frosch, MP Hyman, BT AF Serrano-Pozo, Alberto Mielke, Matthew L. Muzitansky, Alona Gomez-Isla, Teresa Growdon, John H. Bacskai, Brian J. Betensky, Rebecca A. Frosch, Matthew P. Hyman, Bradley T. TI Stable Size Distribution of Amyloid Plaques Over the Course of Alzheimer Disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Amyloid plaques; APOE genotype; Dense-core plaques; Plaque growth; Plaque size ID APOLIPOPROTEIN-E GENOTYPE; BETA-PROTEIN FIBRILLOGENESIS; MILD COGNITIVE IMPAIRMENT; SENILE PLAQUES; A-BETA; PATHOLOGICAL-CHANGES; CEREBRAL-CORTEX; MOUSE MODEL; DEPOSITION; GROWTH AB Amyloid A plaques are a key pathologic feature of Alzheimer disease (AD), but whether plaque sizes increase or stabilize over the course of AD is unknown. We measured the size distribution of total immunoreactive (10D5-positive) and dense-core (Thioflavin S-positive) plaques in the temporal neocortex of a large group of subjects with AD and age-matched plaque-bearing subjects without dementia to test the hypothesis that amyloid plaques continue to grow along with the progression of the disease. The size of amyloid beta (10D5)-positive plaques did not differ between groups, whereas dense-core plaques from the group with AD were slightly larger than those from the group without dementia (similar to 25%-30%, p - 0.01). Within the group with AD, dense-core plaque size did not independently correlate with duration of clinical disease (from 4 to 21 years, p = 0.68), whereas 10D5-positive plaque size correlated negatively with disease duration (p = 0.01). By contrast, an earlier age of symptom onset strongly predicted a larger postmortem plaque size; this effect was independent of disease duration and the presence of the APOE epsilon 4 allele (p = 0.0001). We conclude that plaques vary in size among patients, with larger size distributions correlating with an earlier age of onset, but plaques do not substantially increase in size over the clinical course of the disease. C1 [Serrano-Pozo, Alberto; Mielke, Matthew L.; Gomez-Isla, Teresa; Growdon, John H.; Bacskai, Brian J.; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, Massachusetts Alzheimer Dis Res Ctr, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. [Muzitansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Hyman, BT (reprint author), Bldg 114,16th St 2009, Charlestown, MA 02129 USA. EM bhyman@partners.org RI SERRANO-POZO, ALBERTO/F-5119-2013; OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU National Institutes of Health [P50AG05134, AG08487]; Fundacion Alfonso Martin Escudero (Madrid, Spain) FX This work was funded by the National Institutes of Health (Grants P50AG05134 and AG08487). Dr Alberto Serrano-Pozo was funded by a Research Fellowship from Fundacion Alfonso Martin Escudero (Madrid, Spain). NR 62 TC 12 Z9 12 U1 0 U2 10 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 AUG PY 2012 VL 71 IS 8 BP 694 EP 701 DI 10.1097/NEN.0b013e31825e77de PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 981NI UT WOS:000306974700002 PM 22805771 ER PT J AU Sheehan, JP Tanaka, S Link, MJ Pollock, BE Kondziolka, D Mathieu, D Duma, C Young, AB Kaufmann, AM McBride, H Weisskopf, PA Xu, ZY Kano, H Yang, HC Lunsford, LD AF Sheehan, Jason P. Tanaka, Shota Link, Michael J. Pollock, Bruce E. Kondziolka, Douglas Mathieu, David Duma, Christopher Young, A. Byron Kaufmann, Anthony M. McBride, Heyoung Weisskopf, Peter A. Xu, Zhiyuan Kano, Hideyuki Yang, Huai-che Lunsford, L. Dade TI Gamma Knife surgery for the management of glomus tumors: a multicenter study Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE stereotactic radiosurgery; Gamma Knife; glomus tumor ID SKULL-BASE SURGERY; LONG-TERM CONTROL; JUGULARE TUMORS; STEREOTACTIC RADIOSURGERY; SURGICAL-MANAGEMENT; RADIATION-THERAPY; RADIOTHERAPY; NECK; HEAD; PARAGANGLIOMAS AB Object. Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors of this study examine the outcomes after radiosurgery in a large, multicenter patient population. Methods. Under the auspices of the North American Gamma Knife Consortium, 8 Gamma Knife surgery centers that treat glomus tumors combined their outcome data retrospectively. One hundred thirty-four patient procedures were included in the study (134 procedures in 132 patients, with each procedure being analyzed separately). Prior resection was performed in 51 patients, and prior fractionated external beam radiotherapy was performed in 6 patients. The patients' median age at the time of radiosurgery was 59 years. Forty percent had pulsatile tinnitus at the time of radiosurgery. The median dose to the tumor margin was 15 Gy. The median duration of follow-up was 50.5 months (range 5-220 months). Results. Overall tumor control was achieved in 93% of patients at last follow-up; actuarial tumor control was 88% at 5 years postradiosurgery. Absence of trigeminal nerve dysfunction at the time of radiosurgery (p = 0.001) and higher number of isocenters (p = 0.005) were statistically associated with tumor progression free tumor survival. Patients demonstrating new or progressive cranial nerve deficits were also likely to demonstrate tumor progression (p = 0.002). Pulsatile tinnitus improved in 49% of patients who reported it at presentation. New or progressive cranial nerve deficits were noted in 15% of patients; improvement in preexisting cranial nerve deficits was observed in 11% of patients. No patient died as a result of tumor progression. Conclusions. Gamma Knife surgery was a well-tolerated management strategy that provided a high rate of long-term glomus tumor control. Symptomatic tinnitus improved in almost one-half of the patients. Overall neurological status and cranial nerve function were preserved or improved in the vast majority of patients after radiosurgery. (http://thejns.org/doi/abs/10.3171/2012.4.JNS11214) C1 [Sheehan, Jason P.; Xu, Zhiyuan] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA 22908 USA. [Tanaka, Shota] Massachusetts Gen Hosp, Neurooncol Program, Boston, MA 02114 USA. [Link, Michael J.; Pollock, Bruce E.] Mayo Clin, Dept Neurol Surg, Rochester, MN USA. [Kondziolka, Douglas; Kano, Hideyuki; Yang, Huai-che; Lunsford, L. Dade] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Mathieu, David] Univ Sherbrooke, Div Neurosurg, Quebec City, PQ, Canada. [Duma, Christopher] Hoag Mem Hosp, Hoag Neurosci Inst, Newport Beach, CA USA. [Young, A. Byron] Univ Kentucky, Med Ctr, Dept Neurosurg, Lexington, KY USA. [Kaufmann, Anthony M.] Univ Manitoba, Neurosurg Sect, Winnipeg, MB, Canada. [McBride, Heyoung] Arizona Oncol Serv Fdn, Phoenix, AZ USA. [McBride, Heyoung] Barrow Neurol Inst, Sect Radiat Oncol, Phoenix, AZ 85013 USA. [Weisskopf, Peter A.] Barrow Neurol Inst, Sect Neurotol, Phoenix, AZ 85013 USA. RP Sheehan, JP (reprint author), Univ Virginia Hlth Syst, Dept Neurol Surg, Box 800212, Charlottesville, VA 22908 USA. EM jsheehan@virginia.edu RI Xu, Zhiyuan/J-8698-2013; OI Kaufmann, Anthony/0000-0001-6144-0382 NR 41 TC 16 Z9 17 U1 0 U2 0 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 AUG PY 2012 VL 117 IS 2 BP 246 EP 254 DI 10.3171/2012.4.JNS11214 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 978ST UT WOS:000306766800013 PM 22680240 ER PT J AU Flynn, TR Paster, BJ Stokes, LN Susarla, SM Shanti, RM AF Flynn, Thomas R. Paster, Bruce J. Stokes, Lauren N. Susarla, Srinivas M. Shanti, Rabie M. TI Molecular Methods for Diagnosis of Odontogenic Infections SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID RIBOSOMAL-RNA ANALYSIS; REFRACTORY PERIODONTITIS; OROFACIAL INFECTIONS; APICAL PERIODONTITIS; SUBGINGIVAL BIOFILM; BACTERIAL-FLORA; IDENTIFICATION; MICROBIOTA; DIVERSITY; IMPLANTS AB Purpose: Historically, the identification of microorganisms has been limited to species that could be cultured in the microbiology laboratory. The purpose of the present study was to apply molecular techniques to identify microorganisms in orofacial odontogenic infections (OIs). Materials and Methods: Specimens were obtained from subjects with clinical evidence of OI. To identify the microorganisms involved, 16S rRNA sequencing methods were used on clinical specimens. The name and number of the clones of each species identified and the combinations of species present were recorded for each subject. Descriptive statistics were computed for the study variables. Results: Specimens of pus or wound fluid were obtained from 9 subjects. A mean of 7.4 +/- 3.7 (standard deviation) species per case were identified. The predominant species detected in the present study that have previously been associated with OIs were Fusobacterium spp, Parvimonas micra, Porphyromonas endodontalis, and Prevotella oris. The predominant species detected in our study that have not been previously associated with OIs were Dialister pneumosintes and Eubacterium brachy. Unculturable phylotypes accounted for 24% of the species identified in our study. All species detected were obligate or facultative anaerobes. Streptococci were not detected. Conclusions: Molecular methods have enabled us to detect previously cultivated and not-yet-cultivated species in OIs; these methods could change our understanding of the pathogenic flora of orofacial OIs. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:1854-1859, 2012 C1 [Flynn, Thomas R.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Paster, Bruce J.; Stokes, Lauren N.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Susarla, Srinivas M.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Shanti, Rabie M.] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Oral & Maxillofacial Surg, Newark, NJ 07103 USA. RP Flynn, TR (reprint author), 1055 Waverly Dr, Reno, NV 89519 USA. EM thomasrflynndmd@gmail.com OI Susarla, Srinivas/0000-0003-0155-8260 FU Oral and Maxillofacial Research Foundation; Massachusetts General Hospital; Oral and Maxillofacial Surgery Education and Research Fund; Center for Applied Clinical Investigation; Oral and Maxillofacial Surgery Foundation FX This study was generously funded by the Oral and Maxillofacial Research Foundation, Massachusetts General Hospital, Oral and Maxillofacial Surgery Education and Research Fund and Center for Applied Clinical Investigation, and the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation. NR 41 TC 11 Z9 11 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2012 VL 70 IS 8 BP 1854 EP 1859 DI 10.1016/j.joms.2011.09.009 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 981UJ UT WOS:000306996100023 PM 22326175 ER PT J AU Peacock, ZS Jordan, RCK Schmidt, BL AF Peacock, Zachary S. Jordan, Richard C. K. Schmidt, Brian L. TI Giant Cell Lesions of the Jaws: Does the Level of Vascularity and Angiogenesis correlate With Behavior? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ANTIANGIOGENIC THERAPY; IN-VITRO; GRANULOMA; INTERFERON; EXPRESSION; CALCITONIN; MARKERS; TUMOR; CD34 AB Purpose: To compare vascularity and angiogenic activity in aggressive and nonaggressive giant cell lesions (GCLs) of the jaws. Materials and Methods: This is a retrospective study of 14 GCLs treated at the University of California, San Francisco. Immunohistochemistry was used to determine of the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), CD34, and CD31. VEGF and bFGF expression in giant cells (GCs) and surrounding mononuclear stroma was classified into 1) high immunoreactivity (>50% staining) and 2) low immunoreactivity (<50% staining). CD31- and CD34-stained vessels were counted at 200x magnification. Clinical and radiographic records were reviewed to classify lesions as aggressive or nonaggressive. Results: Of the lesions, 8 were aggressive and 6 were nonaggressive. High VEGF expression was found within the GCs in 4 of 8 aggressive lesions compared with 1 of 6 nonaggressive lesions. The stroma in both groups had low staining. High staining of the GCs for bFGF was found in 6 of 8 aggressive lesions compared with 3 of 6 nonaggressive lesions. The stroma of all aggressive cases showed high expression of bFGF compared with 3 of 6 nonaggressive cases. The aggressive group had a mean of 20.1 +/- 5.4 vessels/high-powered field (hpf) stained for CD31 compared with 11.5 +/- 5.6 vessels/hpf in the nonaggressive group. The aggressive group had 24.6 +/- 7.0 vessels/hpf stained with CD34 compared with 18.5 +/- 4.0 vessels/hpf in the nonaggressive group. Conclusions: The vascularity and level of angiogenesis within aggressive GCLs are higher than those in nonaggressive lesions. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:1860-1866, 2012 C1 [Peacock, Zachary S.] Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA USA. [Schmidt, Brian L.] NYU, Coll Dent, Dept Oral & Maxillofacial Surg, New York, NY USA. [Schmidt, Brian L.] NYU, Coll Dent, Bluestone Ctr Clin Res, New York, NY USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM zpeacock@partners.org OI Schmidt, Brian/0000-0002-2409-8984 NR 34 TC 3 Z9 3 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2012 VL 70 IS 8 BP 1860 EP 1866 DI 10.1016/j.joms.2011.08.020 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 981UJ UT WOS:000306996100024 PM 22104131 ER PT J AU Chen, AB Feng, Y Neuberg, D Recklitis, C Diller, LR Mauch, PN Ng, AK AF Chen, Aileen B. Feng, Yang Neuberg, Donna Recklitis, Christopher Diller, Lisa R. Mauch, Peter N. Ng, Andrea K. TI Employment and insurance in survivors of Hodgkin lymphoma and their siblings: a questionnaire study SO LEUKEMIA & LYMPHOMA LA English DT Article DE Employment; Hodgkin lymphoma; insurance; radiation therapy; survivorship ID CHILDHOOD-CANCER SURVIVOR; LONG-TERM SURVIVORS; QUALITY-OF-LIFE; ADULT SURVIVORS; DATA-BASE; DISEASE; RADIOTHERAPY; HEALTH; RETURN; WORK AB Using a questionnaire study, we compared the employment and insurance of Hodgkin lymphoma (HL) survivors versus their siblings. A total of 511 survivors and 224 siblings completed questionnaires. HL survivors were more likely to report job denial, difficulty obtaining insurance due to medical history, and difficulty changing jobs due to fear of losing insurance. On multivariable analysis, male gender, income and scarring of the head and neck were associated with job denial. Male gender and impairment interfering with a job were associated with difficulty obtaining health insurance. Survivors with >4 physician visits in 2 years, <10years from diagnosis, or with permanent hair loss from treatment were more likely to report inability to change jobs due to fear of losing insurance. Compared to their siblings, HL survivors may face greater challenges in obtaining employment and insurance. Late effects from treatment, including permanent cosmetic changes, may contribute to these differences. C1 [Chen, Aileen B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Chen, Aileen B.; Mauch, Peter N.; Ng, Andrea K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Diller, Lisa R.] Childrens Hosp, Boston, MA 02115 USA. RP Chen, AB (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave,D1111, Boston, MA 02215 USA. EM achen@lroc.harvard.edu OI Chen, Aileen/0000-0002-5385-3360 NR 31 TC 4 Z9 4 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 2012 VL 53 IS 8 BP 1474 EP 1480 DI 10.3109/10428194.2012.660629 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 976FJ UT WOS:000306566000010 PM 22280535 ER PT J AU Zhang, HJ Peng, C Hu, YG Li, HW Sheng, Z Chen, YY Sullivan, C Cerny, J Hutchinson, L Higgins, A Miron, P Zhang, XQ Brehm, MA Li, DG Green, MR Li, SG AF Zhang, Haojian Peng, Cong Hu, Yiguo Li, Huawei Sheng, Zhi Chen, Yaoyu Sullivan, Con Cerny, Jan Hutchinson, Lloyd Higgins, Anne Miron, Patricia Zhang, Xueqing Brehm, Michael A. Li, Dongguang Green, Michael R. Li, Shaoguang TI The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells SO NATURE GENETICS LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BCR-ABL; TYROSINE KINASE; IMATINIB MESYLATE; BETA-CATENIN; HEMATOPOIETIC PROGENITORS; IN-VITRO; CANCER; DIFFERENTIATION AB A therapeutic strategy for treating cancer is to target and eradicate cancer stem cells (CSCs) without harming their normal stem cell counterparts. The success of this approach relies on the identification of molecular pathways that selectively regulate CSC function. Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for CSCs, we show that BCR-ABL downregulates the Blk gene (encoding B-lymphoid kinase) through c-Myc in leukemic stem cells (LSCs) in CML mice and that Blk functions as a tumor suppressor in LSCs but does not affect normal hematopoietic stem cells (HSCs) or hematopoiesis. Blk suppresses LSC function through a pathway involving an upstream regulator, Pax5, and a downstream effector, p27. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. Blk also suppresses the proliferation of human CML stem cells. Our results show the feasibility of selectively targeting LSCs, an approach that should be applicable to other cancers. C1 [Zhang, Haojian; Peng, Cong; Li, Huawei; Chen, Yaoyu; Cerny, Jan; Li, Shaoguang] Univ Massachusetts, Sch Med, Dept Med, Div Hematol Oncol, Worcester, MA 01605 USA. [Hu, Yiguo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sheng, Zhi; Green, Michael R.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA USA. [Sheng, Zhi; Brehm, Michael A.; Green, Michael R.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA. [Sullivan, Con] Univ Maine, Dept Mol & Biomed Sci, Orono, ME USA. [Hutchinson, Lloyd; Higgins, Anne; Miron, Patricia] Univ Massachusetts, Dept Pathol, Div Anat Pathol, Mem Med Ctr, Worcester, MA 01605 USA. [Zhang, Xueqing] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Li, Dongguang] Edith Cowan Univ, Sch Comp & Informat Sci, Mt Lawley, WA, Australia. [Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. RP Li, SG (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Hematol Oncol, Worcester, MA 01605 USA. EM shaoguang.li@umassmed.edu RI Zhang, Haojian/H-7897-2013 FU Leukemia & Lymphoma Society; US National Institutes of Health (NIH) [R01-CA122142, R01-CA114199]; NIH [AI46629] FX We thank A. Tarakhovsky (Rockefeller University) for providing Blk-/- mice and K. Calame (Columbia University) for pGL3-Pax5 plasmid. We thank S. Deibler for editorial assistance. This work was supported by grants from the Leukemia & Lymphoma Society and the US National Institutes of Health (NIH) (R01-CA122142 and R01-CA114199) to S.L. M.A.B. was supported by the NIH (AI46629). S.L. is a Scholar of the Leukemia & Lymphoma Society. NR 59 TC 26 Z9 26 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2012 VL 44 IS 8 BP 861 EP + DI 10.1038/ng.2350 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 979WV UT WOS:000306854700009 PM 22797726 ER PT J AU Lu, XF Wang, LY Chen, SF He, L Yang, XL Shi, YY Cheng, J Zhang, L Gu, CC Huang, JF Wu, TC Ma, YT Li, JX Cao, J Chen, JC Ge, DL Fan, ZJ Li, Y Zhao, LC Li, HF Zhou, XY Chen, LY Liu, DH Chen, JP Duan, XF Hao, YC Wang, LG Lu, FH Liu, ZD Yao, CL Shen, C Pu, XD Yu, L Fang, XH Xu, LH Mu, JJ Wu, XP Zheng, RP Wu, NQ Zhao, Q Li, Y Liu, XL Wang, MP Yu, DH Hu, DS Ji, X Guo, DS Sun, DL Wang, QQ Yang, Y Liu, FC Mao, QX Liang, XH Ji, JF Chen, PP Mo, XB Li, DJ Chai, GP Tang, YD Li, XD Du, ZH Liu, XH Dou, CL Yang, ZL Meng, QJ Wang, D Wang, RP Yang, J Schunkert, H Samani, NJ Kathiresan, S Reilly, MP Erdmann, J Peng, XZ Wu, XG Liu, DP Yang, YJ Chen, RS Qiang, BQ Gu, DF AF Lu, Xiangfeng Wang, Laiyuan Chen, Shufeng He, Lin Yang, Xueli Shi, Yongyong Cheng, Jing Zhang, Liang Gu, C. Charles Huang, Jianfeng Wu, Tangchun Ma, Yitong Li, Jianxin Cao, Jie Chen, Jichun Ge, Dongliang Fan, Zhongjie Li, Ying Zhao, Liancheng Li, Hongfan Zhou, Xiaoyang Chen, Lanying Liu, Donghua Chen, Jingping Duan, Xiufang Hao, Yongchen Wang, Ligui Lu, Fanghong Liu, Zhendong Yao, Cailiang Shen, Chong Pu, Xiaodong Yu, Lin Fang, Xianghua Xu, Lihua Mu, Jianjun Wu, Xianping Zheng, Runping Wu, Naqiong Zhao, Qi Li, Yun Liu, Xiaoli Wang, Mengqin Yu, Dahai Hu, Dongsheng Ji, Xu Guo, Dongshuang Sun, Dongling Wang, Qianqian Yang, Ying Liu, Fangchao Mao, Qunxia Liang, Xiaohua Ji, Jingfeng Chen, Panpan Mo, Xingbo Li, Dianjiang Chai, Guoping Tang, Yida Li, Xiangdong Du, Zhenhan Liu, Xuehui Dou, Chenlong Yang, Zili Meng, Qingjie Wang, Dong Wang, Renping Yang, Jun Schunkert, Heribert Samani, Nilesh J. Kathiresan, Sekar Reilly, Muredach P. Erdmann, Jeanette Peng, Xiaozhong Wu, Xigui Liu, Depei Yang, Yuejin Chen, Runsheng Qiang, Boqin Gu, Dongfeng CA Coronary ARtery DIs Genome-Wide Re TI Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease SO NATURE GENETICS LA English DT Article ID BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; COMMON VARIANTS; EAST ASIANS; METAANALYSIS; POPULATION; SEQUENCE; ONSET AB We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 x 10(-8)). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population. C1 [Lu, Xiangfeng; Wang, Laiyuan; Chen, Shufeng; Yang, Xueli; Huang, Jianfeng; Li, Jianxin; Cao, Jie; Chen, Jichun; Ge, Dongliang; Li, Ying; Zhao, Liancheng; Chen, Lanying; Liu, Donghua; Chen, Jingping; Duan, Xiufang; Hao, Yongchen; Zhao, Qi; Yu, Dahai; Wang, Qianqian; Yang, Ying; Liu, Fangchao; Mao, Qunxia; Liang, Xiaohua; Ji, Jingfeng; Mo, Xingbo; Li, Dianjiang; Chai, Guoping; Li, Xiangdong; Du, Zhenhan; Wu, Xigui; Gu, Dongfeng] Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing 100730, Peoples R China. [Lu, Xiangfeng; Wang, Laiyuan; Chen, Shufeng; Yang, Xueli; Huang, Jianfeng; Li, Jianxin; Cao, Jie; Chen, Jichun; Ge, Dongliang; Li, Ying; Zhao, Liancheng; Chen, Lanying; Liu, Donghua; Chen, Jingping; Duan, Xiufang; Hao, Yongchen; Wu, Naqiong; Zhao, Qi; Yu, Dahai; Wang, Qianqian; Yang, Ying; Liu, Fangchao; Mao, Qunxia; Liang, Xiaohua; Ji, Jingfeng; Mo, Xingbo; Li, Dianjiang; Chai, Guoping; Tang, Yida; Li, Xiangdong; Du, Zhenhan; Peng, Xiaozhong; Wu, Xigui; Liu, Depei; Yang, Yuejin; Qiang, Boqin; Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China. [Wang, Laiyuan; Li, Hongfan; Liu, Xuehui; Dou, Chenlong] Natl Human Genome Ctr, Beijing, Peoples R China. [He, Lin; Shi, Yongyong] Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China. [Cheng, Jing; Zhang, Liang] NERCBBT, Beijing, Peoples R China. [Cheng, Jing] Tsinghua Univ, Med Syst Biol Res Ctr, Sch Med, Beijing 100084, Peoples R China. [Gu, C. Charles] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Wu, Tangchun; Wang, Ligui] Huazhong Univ Sci & Technol, Key Lab Environm & Hlth, Sch Publ Hlth, Tongji Med Coll, Wuhan 430074, Peoples R China. [Ma, Yitong] Xinjiang Med Univ, Dept Cardiol, Affiliated Hosp 1, Urumqi, Peoples R China. [Fan, Zhongjie] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Cardiol, Beijing 100730, Peoples R China. [Zhou, Xiaoyang] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430072, Peoples R China. [Lu, Fanghong; Liu, Zhendong] Shandong Acad Med Sci, Inst Basic Med, Cardiocerebrovasc Control & Res Ctr, Jinan, Peoples R China. [Yao, Cailiang; Shen, Chong] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China. [Pu, Xiaodong; Yu, Lin] Fujian Prov Peoples Hosp, Dept Cardiol, Fuzhou, Peoples R China. [Fang, Xianghua] Capital Med Univ, Xuanwu Hosp, Dept Epidemiol & Social Med, Beijing, Peoples R China. [Xu, Lihua] Beihua Univ, Affiliated Hosp, Dept Cardiol, Jilin, Peoples R China. [Mu, Jianjun] Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, Dept Cardiol, Xian 710049, Peoples R China. [Wu, Xianping] Sichuan Ctr Dis Control & Prevent, Ctr Chron & Noncommunicable Dis Control & Prevent, Chengdu, Peoples R China. [Zheng, Runping] Peking Univ, Shougang Hosp, Cardiovasc Dis Prevent Ctr, Beijing 100871, Peoples R China. [Wu, Naqiong; Tang, Yida; Yang, Yuejin] Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Dept Cardiol, Beijing 100730, Peoples R China. [Li, Yun] Hebei United Univ, Sch Publ Hlth, Tangshan, Peoples R China. [Liu, Xiaoli] Capital Med Univ, Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China. [Wang, Mengqin] Beijing Jishuitan Hosp, Dept Emergency Med, Beijing, Peoples R China. [Hu, Dongsheng] Zhengzhou Univ, Sch Publ Hlth, Zhengzhou, Peoples R China. [Hu, Dongsheng] Shenzhen Univ, Sch Med, Shenzhen, Peoples R China. [Ji, Xu] Xinle Red Cross Hosp, Dept Internal Med, Xinle, Peoples R China. [Guo, Dongshuang] Yuxian Renmin Hosp, Dept Internal Med, Yuxian, Peoples R China. [Sun, Dongling] Chinese Peoples Liberat Army PLA Gen Hosp, Inst Geriatr, Beijing, Peoples R China. [Chen, Panpan] Renqiu Heath Bur, Renqiu, Peoples R China. [Yang, Zili] Nantong Ctr Dis Control & Prevent, Nantong, Peoples R China. [Meng, Qingjie] Zhangqiu Heath Bur, Zhangqiu, Peoples R China. [Wang, Dong] Xinan Heath Bur, Xinan, Peoples R China. [Wang, Renping] Shijiazhuang Greatwall Hosp, Dept Internal Med, Shijiazhuang, Peoples R China. [Yang, Jun] Hanzhong Renmin Hosp, Dept Cardiol, Hanzhong, Peoples R China. [Schunkert, Heribert; Erdmann, Jeanette] Univ Lubeck, Med Klin 2, Lubeck, Germany. [Schunkert, Heribert; Erdmann, Jeanette] Univ Lubeck, Deutsch Zentrum Herz Kreislauf Forsch DZHK, Lubeck, Germany. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England. [Samani, Nilesh J.] Glenfield Hosp, Biomed Res Unit Cardiovasc Dis, Leicester Natl Inst Hlth Res, Leicester, Leics, England. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Peng, Xiaozhong; Liu, Depei; Qiang, Boqin] Chinese Acad Med Sci, Inst Basic Med Sci, Beijing 100730, Peoples R China. [Chen, Runsheng] Chinese Acad Sci, Inst Biophys, Beijing 100080, Peoples R China. RP Gu, DF (reprint author), Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing 100730, Peoples R China. EM gudongfeng@vip.sina.com RI Altshuler, David/A-4476-2009; Willenborg, Christina/D-2668-2012; Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015; Gu, Charles/A-7934-2010; Erdmann, Jeanette/P-7513-2014; OI Altshuler, David/0000-0002-7250-4107; Willenborg, Christina/0000-0001-5217-6882; Gudnason, Vilmundur/0000-0001-5696-0084; Gu, Charles/0000-0002-8527-8145; Erdmann, Jeanette/0000-0002-4486-6231; Kleber, Marcus/0000-0003-0663-7275 FU National Basic Research Program of China (973 Plan) from the Ministry of Science and Technology of China [2011CB503901, 2006CB503805]; National Science Foundation of China [30930047]; High-Tech Research and Development Program of China (863 Plan) [2009AA022703, 2012AA02A516, 2006AA02A406]; Ministry of Science and Technology of China [2006BAI01A01]; Biomedical Project from the Council of Science and Technology, Beijing [H020220030130] FX This study was funded by the National Basic Research Program of China (973 Plan) (2011CB503901 and 2006CB503805) from the Ministry of Science and Technology of China, by the National Science Foundation of China (30930047), by the High-Tech Research and Development Program of China (863 Plan) (2009AA022703, 2012AA02A516 and 2006AA02A406) and by a grant from the Ministry of Science and Technology of China (2006BAI01A01). This study was also supported by Biomedical Project from the Council of Science and Technology, Beijing (H020220030130). NR 40 TC 120 Z9 125 U1 4 U2 78 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD AUG PY 2012 VL 44 IS 8 BP 890 EP + DI 10.1038/ng.2337 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 979WV UT WOS:000306854700013 PM 22751097 ER PT J AU Riviere, JB Mirzaa, GM O'Roak, BJ Beddaoui, M Alcantara, D Conway, RL St-Onge, J Schwartzentruber, JA Gripp, KW Nikkel, SM Worthylake, T Sullivan, CT Ward, TR Butler, HE Kramer, NA Albrecht, B Armour, CM Armstrong, L Caluseriu, O Cytrynbaum, C Drolet, BA Innes, AM Lauzon, JL Lin, AE Mancini, GMS Meschino, WS Reggin, JD Saggar, AK Lerman-Sagie, T Uyanik, G Weksberg, R Zirn, B Beaulieu, CL Majewski, J Bulman, DE O'Driscoll, M Shendure, J Graham, JM Boycott, KM Dobyns, WB AF Riviere, Jean-Baptiste Mirzaa, Ghayda M. O'Roak, Brian J. Beddaoui, Margaret Alcantara, Diana Conway, Robert L. St-Onge, Judith Schwartzentruber, Jeremy A. Gripp, Karen W. Nikkel, Sarah M. Worthylake, Thea Sullivan, Christopher T. Ward, Thomas R. Butler, Hailly E. Kramer, Nancy A. Albrecht, Beate Armour, Christine M. Armstrong, Linlea Caluseriu, Oana Cytrynbaum, Cheryl Drolet, Beth A. Innes, A. Micheil Lauzon, Julie L. Lin, Angela E. Mancini, Grazia M. S. Meschino, Wendy S. Reggin, James D. Saggar, Anand K. Lerman-Sagie, Tally Uyanik, Goekhan Weksberg, Rosanna Zirn, Birgit Beaulieu, Chandree L. Majewski, Jacek Bulman, Dennis E. O'Driscoll, Mark Shendure, Jay Graham, John M., Jr. Boycott, Kym M. Dobyns, William B. CA Finding Rare Dis Genes FORGE Canad TI De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes SO NATURE GENETICS LA English DT Article ID MACROCEPHALY-CAPILLARY MALFORMATION; KINASE-B-GAMMA; GLUCOSE-HOMEOSTASIS; ACTIVATING MUTATION; INSULIN-RESISTANCE; CORPUS-CALLOSUM; CUTIS MARMORATA; COWDEN-DISEASE; GENE-MUTATIONS; HIGH-FREQUENCY AB Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features(1-5). We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism. C1 [Riviere, Jean-Baptiste; St-Onge, Judith; Sullivan, Christopher T.; Ward, Thomas R.; Butler, Hailly E.; Dobyns, William B.] Seattle Childrens Hosp, Ctr Integrat Brain Res, Seattle, WA USA. [Mirzaa, Ghayda M.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [O'Roak, Brian J.; Shendure, Jay] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Beddaoui, Margaret; Worthylake, Thea; Beaulieu, Chandree L.; Boycott, Kym M.] Univ Ottawa, Childrens Hosp, Eastern Ontario Res Inst, Ottawa, ON, Canada. [Alcantara, Diana; O'Driscoll, Mark] Univ Sussex, Genome Damage & Stabil Ctr, Brighton, E Sussex, England. [Conway, Robert L.] Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. [Schwartzentruber, Jeremy A.] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Gripp, Karen W.] Alfred I DuPont Hosp Children, Div Med Genet, Wilmington, DE USA. [Nikkel, Sarah M.; Boycott, Kym M.] Childrens Hosp Eastern Ontario, Div Genet, Ottawa, ON K1H 8L1, Canada. [Kramer, Nancy A.; Graham, John M., Jr.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Albrecht, Beate] Univ Hosp Essen, Dept Human Genet, Essen, Germany. [Armour, Christine M.] Queens Univ, Dept Paediat, Kingston, ON, Canada. [Armstrong, Linlea] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Caluseriu, Oana; Innes, A. Micheil; Lauzon, Julie L.] Univ Calgary, Dept Med Genet, Calgary, AB, Canada. [Cytrynbaum, Cheryl; Weksberg, Rosanna] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Drolet, Beth A.] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Drolet, Beth A.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Lin, Angela E.] MassGen Hosp Children, Dept Med Genet, Boston, MA USA. [Mancini, Grazia M. S.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Meschino, Wendy S.] N York Gen Hosp, Dept Genet, Toronto, ON, Canada. [Reggin, James D.] Providence Sacred Heart Med Ctr, Spokane, WA USA. [Reggin, James D.] Childrens Hosp, Spokane, WA USA. [Saggar, Anand K.] Univ London, St Georges Hosp, Dept Clin Genet, London, England. [Lerman-Sagie, Tally] Wolfson Med Ctr, Pediat Neurol Unit, Holon, Israel. [Uyanik, Goekhan] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany. [Zirn, Birgit] Univ Goettingen, Dept Neuropediat, Gottingen, Germany. [Majewski, Jacek] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Bulman, Dennis E.] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Dobyns, William B.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Dobyns, William B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Dobyns, WB (reprint author), Seattle Childrens Hosp, Ctr Integrat Brain Res, Seattle, WA USA. EM wbd@uw.edu RI Scherer, Stephen /B-3785-2013; innes, allan micheil/A-9955-2017; OI Scherer, Stephen /0000-0002-8326-1999; Innes, Micheil/0000-0001-9881-5467; O'Roak, Brian/0000-0002-4141-0095; Schwartzentruber, Jeremy/0000-0002-6183-2092; Shendure, Jay/0000-0002-1516-1865; Dobyns, William/0000-0002-7681-2844 FU US National Institutes of Health under National Institute of Neurological Disorders and Stroke (NINDS) grant [NS058721]; National Institute of Child Health & Human Development (NICHD) grant [HD36657]; National Institute of General Medical Sciences (NIGMS) grant [5-T32-GM08243]; Government of Canada (to FORGE) through Genome Canada; Canadian Institutes of Health Research (CIHR); Ontario Genomics Institute [OGI-049]; Genome Quebec and Genome British Columbia; Banting Postdoctoral Fellowship from the CIHR; Clinical Investigatorship Award from the CIHR Institute of Genetics; Cancer Research UK (CR-UK); Medical Research Council (UK); Leukaemia Lymphoma Research (UK); Simons Foundation Autism Research Initiative (SFARI) [191889]; NIEHS Environmental Genome Project [HHSN273200800010C]; NHLBI GO Exome Sequencing Project and its ongoing studies [HL-102923, HL-102925, HL-102926, HL-103010]; Women's Health Institute (WHI) [HL-102924] FX This work was funded by the US National Institutes of Health under National Institute of Neurological Disorders and Stroke (NINDS) grant NS058721 (to W.B.D.), National Institute of Child Health & Human Development (NICHD) grant HD36657 and National Institute of General Medical Sciences (NIGMS) grant 5-T32-GM08243 (to J.M.G.), the Government of Canada (to FORGE) through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049). Additional funding was provided to FORGE by Genome Quebec and Genome British Columbia. J.-B.R. is supported by a Banting Postdoctoral Fellowship from the CIHR. K.M.B. is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. The laboratory of M.O. is funded by Cancer Research UK (CR-UK), the Medical Research Council (UK) and Leukaemia Lymphoma Research (UK). M.O. is a Senior CR-UK Research Fellow. We would like to thank the Simons Foundation Autism Research Initiative (SFARI) for providing control exome data (grant 191889 to J.S.). We also thank the NIEHS Environmental Genome Project (contract HHSN273200800010C) and the NHLBI GO Exome Sequencing Project and its ongoing studies-Lung GO (HL-102923), Broad GO (HL-102925), Seattle GO (HL-102926), Heart GO (HL-103010) and the Women's Health Institute (WHI; HL-102924) Sequencing Projects-for providing exome variant calls for comparison. NR 55 TC 212 Z9 216 U1 2 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD AUG PY 2012 VL 44 IS 8 BP 934 EP + DI 10.1038/ng.2331 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 979WV UT WOS:000306854700021 PM 22729224 ER PT J AU Kim, JK Lee, WM Kim, P Choi, M Jung, K Kim, S Yun, SH AF Kim, Jun Ki Lee, Woei Ming Kim, Pilhan Choi, Myunghwan Jung, Keehoon Kim, Seonghoon Yun, Seok Hyun TI Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals SO NATURE PROTOCOLS LA English DT Article ID ENDOSCOPY; MICE; ENDOMICROSCOPY; MICROENDOSCOPY; RESOLUTION; CANCER; CELLS AB Intravital fluorescence microscopy has emerged as a powerful technique to visualize cellular processes in vivo. However, owing to their size, the objective lenses required have limited physical accessibility to various tissue sites in the internal organs of small animals. The use of small-diameter probes using graded-index (GRIN) lenses expands the capabilities of conventional intravital microscopes to minimally invasive imaging of internal organs. In this protocol, we describe the detailed steps for the fabrication of front-and side-view GRIN probes and the integration and operation of the probes in a confocal microscope to enable visualization of fluorescent cells and microvasculature in various mouse organs. Some experience in building an optical setup is required to complete the protocol. We also present longitudinal imaging of immune cells in renal allografts and tumor development in the colon. Fabrication and integration can be completed in 5-7 h, and a typical in vivo imaging session takes 1-2 h. C1 [Kim, Jun Ki; Lee, Woei Ming; Kim, Pilhan; Choi, Myunghwan; Jung, Keehoon; Kim, Seonghoon; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kim, Jun Ki; Lee, Woei Ming; Kim, Pilhan; Choi, Myunghwan; Jung, Keehoon; Kim, Seonghoon; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kim, Pilhan; Choi, Myunghwan; Kim, Seonghoon; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, Taejon 305701, South Korea. [Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM syun@hms.harvard.edu RI Kim, Pilhan/C-1836-2011; OI Kim, Pilhan/0000-0001-8388-1840; Lee, W M Steve/0000-0002-3912-6095; Choi, Myunghwan/0000-0002-4235-7003 FU US National Institutes of Health [R21AI081010, RC1DK086242, RC2DK088661, U54CA143837, R01AI081734, P41EB015903]; US Department of Defense [FA9550-10-1-0537]; National Research Foundation of Korea [WCU R31-2008-000-10071-0, 2009-352-C00042, 2011-0009503, WCI 2011-001] FX We thank R. Colvin and C. Chase for providing the mice with renal transplantation; R. Kucherlapati and K. Hung for the mouse model of spontaneous colorectal tumor; H. Ploegh for the MHCII-GFP mice; C. Lin, D. Cote, L. Kaplan, M. Ferrari and G. Y. Koh for discussions; and D. Stevenson for proofreading of the manuscript. This work was supported by grants from the US National Institutes of Health (R21AI081010, RC1DK086242, RC2DK088661, U54CA143837, R01AI081734, P41EB015903), the US Department of Defense (FA9550-10-1-0537) and the National Research Foundation of Korea (WCU R31-2008-000-10071-0, 2009-352-C00042, 2011-0009503, WCI 2011-001). NR 13 TC 29 Z9 29 U1 2 U2 14 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 AUG PY 2012 VL 7 IS 8 BP 1456 EP 1469 DI 10.1038/nprot.2012.078 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 979UK UT WOS:000306845200002 PM 22767088 ER PT J AU Rice, TR Sher, L AF Rice, Timothy R. Sher, Leo TI Educating non-mental healthcare providers about suicide-risk assessment in adolescents SO NEUROPSYCHIATRY LA English DT Editorial Material ID PSYCHOLOGICAL DISTRESS; EMERGENCY-DEPARTMENT; GENERAL-PRACTITIONERS; PEDIATRIC RESIDENTS; YOUTH SUICIDE; IDEATION; COMPLAINTS; BEHAVIOR C1 [Rice, Timothy R.; Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Rice, Timothy R.; Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Rice, TR (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1425 Madison Ave,Box 1230, New York, NY 10029 USA. EM timothy.rice@mssm.edu NR 31 TC 0 Z9 0 U1 1 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 EI 1758-2016 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD AUG PY 2012 VL 2 IS 4 BP 267 EP 270 DI 10.2217/NPY.12.33 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 980JF UT WOS:000306888700002 ER PT J AU Montastruc, F Schwarz, N Schmitt, L Bui, E AF Montastruc, Francois Schwarz, Noah Schmitt, Laurent Bui, Eric TI An overview of the symptoms and typical disorders associated with Alice in Wonderland syndrome SO NEUROPSYCHIATRY LA English DT Article ID BARR-VIRUS INFECTION; DEPRESSIVE DISORDER; PRESENTING SYMPTOM; H1N1 INFLUENZA; MIGRAINE; CHILDREN; HALLUCINATIONS; MONONUCLEOSIS; PATIENT; AURA AB The Alice in Wonderland syndrome refers to a set of symptoms characterized by perceptual distortions, such as visual distortions (i.e., metamorphopsia), body image and time distortions. The Alice in Wonderland syndrome has been described consistently over the past five decades in various cultural settings. Migraine headaches and epilepsy were the etiologies first described and most frequently reported in the literature; however, infectious, neurological, toxic and psychiatric causes have also been reported. Although little is known regarding the specific pathophysiological pathways, dysfunctions of the NMDA neurotransmission and inflammations, as well as edemas of cerebral regions close to the visual pathways may be implicated. C1 [Montastruc, Francois; Schmitt, Laurent; Bui, Eric] CHU Toulouse, Toulouse, France. [Montastruc, Francois; Schmitt, Laurent; Bui, Eric] Univ Toulouse, Toulouse, France. [Schwarz, Noah; Bui, Eric] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Schwarz, Noah; Bui, Eric] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bui, E (reprint author), CHU Toulouse, Toulouse, France. EM tebui@partners.org RI Schwarz, Noah/B-8525-2015; Bui, Eric/J-8347-2015 OI Schwarz, Noah/0000-0002-4604-1209; Bui, Eric/0000-0002-1413-6473 NR 45 TC 0 Z9 0 U1 0 U2 19 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 AUG PY 2012 VL 2 IS 4 BP 281 EP 289 DI 10.2217/NPY.12.37 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 980JF UT WOS:000306888700008 ER PT J AU McGuire, JF Lewin, AB Geller, DA Brown, A Ramsey, K Mutch, J Mittelman, A Micco, J Jordan, C Wilhelm, S Murphy, TK Small, BJ Storch, EA AF McGuire, Joseph F. Lewin, Adam B. Geller, Daniel A. Brown, Ashley Ramsey, Kesley Mutch, Jane Mittelman, Andrew Micco, Jamie Jordan, Cary Wilhelm, Sabine Murphy, Tanya K. Small, Brent J. Storch, Eric A. TI Advances in the treatment of pediatric obsessive-compulsive disorder: rationale and design for the evaluation of D-cycloserine with exposure and response prevention SO NEUROPSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; SOCIAL ANXIETY DISORDER; FACILITATES EXTINCTION; FUNCTIONAL IMPAIRMENT; CONDITIONED FEAR; ADVERSE EVENTS; OCD TREATMENT; CHILDREN; ADOLESCENTS AB Exposure-based cognitive-behavioral therapy and serotonin reuptake inhibitor medications are efficacious treatment options for the management of pediatric obsessive compulsive disorder. Despite established efficacy, many youths receiving either therapy remain symptomatic after acute treatment. Regardless of the rationale for persistent symptoms, a clear need emerges for treatment options that restore functioning efficiently to symptomatic youths. One innovative approach builds upon the identified role of NMDA receptors in the fear extinction process. Instead of breaking existing connections during fear extinction, new associations develop that eventually predominate over prior associations. Recent investigations have explored augmenting exposure-based cognitive-behavioral therapy with the NMDA partial agonist D-cycloserine, with preliminary results demonstrating expedited treatment gains and moderately larger effects above exposure and response prevention therapy alone. A large randomized clinical trial is underway to evaluate the efficacy and efficiency of this therapeutic combination in pediatric obsessive-compulsive disorder. Results from this trial may translate into improved management practices. C1 [McGuire, Joseph F.; Storch, Eric A.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [McGuire, Joseph F.; Lewin, Adam B.; Mutch, Jane; Jordan, Cary; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, Dept Pediactr, St Petersburg, FL 33701 USA. [Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, Dept Psychiat, St Petersburg, FL 33701 USA. [Geller, Daniel A.; Brown, Ashley; Ramsey, Kesley; Mittelman, Andrew; Micco, Jamie; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Geller, Daniel A.; Brown, Ashley; Ramsey, Kesley; Mittelman, Andrew; Micco, Jamie; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Small, Brent J.] Univ S Florida, Sch Aging Studies, Tampa, FL 33620 USA. RP Storch, EA (reprint author), Univ S Florida, Dept Psychol, 4202 E Fowler Ave, Tampa, FL 33620 USA. EM estorch@health.usf.edu RI Storch, Eric/I-4935-2012; Lewin, Adam/A-9832-2013; Murphy, Tanya/J-7079-2013; OI Small, Brent/0000-0002-7444-4689 FU NIH; Agency for Healthcare Research and Quality; National Alliance for Research on Schizophrenia, Affective Disorders; Boehringer Ingelheim; Janssen Pharmaceuticals; International OCD Foundation; Tourette Syndrome Association; All Children's Hospital Research Foundation; CDC; National Alliance for Research on Schizophrenia and Affective Disorders; Foundation for Research on Prader-Willi Syndrome; All Children's Hospital Guild Endowed Chair; Forest Laboratories FX AB Lewin receives grant funding from the NIH, Agency for Healthcare Research and Quality, National Alliance for Research on Schizophrenia, Affective Disorders and International OCD Foundation. He is also a consultant for Prophase, Inc. DA Geller has received grant funding in the last 3 years from the NIH. In the last 3 years DA Geller has received research support from Boehringer Ingelheim. In addition, he has received honoraria for speaking engagements from Eli Lily and has sat on the Eli Lily Bureau and Medical Advisory Board. S Wilhelm receives research funding from the NIH. She also receives royalties from Oxford University Press, New Harbinger Publications and Guilford Publications. S Wilhelm receives support in the form of free medication and matching placebo from Forest Laboratories for a clinical trial funded by the NIH. She also receives speaking honoraria from PRIMEDIA Healthcare, a publicly traded company working as a logistics collaborator for the Massachusetts General Hospital Psychiatry Academy (the education programs conducted by the Massachusetts General Hospital Psychiatry Academy were supported through Independent Medical Education grants from pharmaceutical companies co-supporting the overall program, along with participant tuition). She has also received speaking honoraria from various academic institutions. TK Murphy has received research support in the past 3 years from the NIH, Forest Laboratories, Janssen Pharmaceuticals, International OCD Foundation, Tourette Syndrome Association, All Children's Hospital Research Foundation, CDC and National Alliance for Research on Schizophrenia and Affective Disorders. TK Murphy is on the Medical Advisory Board for Tourette Syndrome Association. She receives textbook honorarium from Lawrence Erlbaum. BJ Small receives grant funding from the NIH. EA Storch has received grant funding in the last 3 years from the NIH, All Children's Hospital Research Foundation, CDC, Agency for Healthcare Research and Quality, National Alliance for Research on Schizophrenia and Affective Disorders, International OCD Foundation, Tourette Syndrome Association, Janssen Pharmaceuticals and Foundation for Research on Prader-Willi Syndrome. He receives textbook honorarium from Springer publishers, American Psychological Association and Lawrence Erlbaum. EA Scorch has been an educational consultant for Rogers Memorial Hospital. He is a consultant for Prophase, Inc. and CroNos, Inc., and is on the Speaker's Bureau and Scientific Advisory Board for the International OCD Foundation. He receives research support from the All Children's Hospital Guild Endowed Chair. 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 74 TC 5 Z9 5 U1 4 U2 8 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 AUG PY 2012 VL 2 IS 4 BP 291 EP 300 DI 10.2217/NPY.12.38 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 980JF UT WOS:000306888700009 ER PT J AU Wilens, TE Morrison, NR AF Wilens, Timothy E. Morrison, Nicholas R. TI Substance-use disorders in adolescents and adults with ADHD: focus on treatment SO NEUROPSYCHIATRY LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; OSMOTIC-RELEASE METHYLPHENIDATE; COMORBIDITY SURVEY REPLICATION; COGNITIVE-BEHAVIORAL THERAPY; PLACEBO-CONTROLLED TRIAL; PRESCRIPTION STIMULANTS; DOUBLE-BLIND; COLLEGE-STUDENTS AB A high prevalence of comorbidity of ADHD and substance-use disorders (SUDs) has been shown in the literature. In this article, the literature for the treatment of adolescents and adults with co-occurring ADHD and SUD is examined. Findings from pharmacotherapy suggest mild improvement in ADHD without demonstrable changes in SUD unless the addiction was stabilized prior to treating the ADHD. No unique adverse effects, worsening of SUD, misuse or diversion of stimulants are reported in the included studies. Treating ADHD pharmacologically in individuals with ADHD plus SUD only has a modest impact on ADHD and SUD that is not observed in controlled trials. Limited data in adults with ADHD and brief abstinence of their SUD showed improvements in both ADHD and SUD with treatment. Further studies of cognitive behavioral therapy, sequencing of therapies and longer term treatment outcomes for groups with ADHD and active SUD are necessary. C1 [Wilens, Timothy E.; Morrison, Nicholas R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Child Psychiat Serv,Ctr Addict Med, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Child Psychiat Serv,Ctr Addict Med, YAW 6A,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org FU NIH [K24 DA016264]; Abbott; Euthymics; McNeil; Lilly; NIH (NIDA); Merck; Novartis; Shire FX This research was supported by the NIH grant K24 DA016264 to TE Wilens. TE Wilens has received or receives grant support, has been a speaker for, or receives research support from Abbott, Euthymics, McNeil, Lilly, NIH (NIDA), Merck, Novartis and Shire. 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 71 TC 5 Z9 5 U1 3 U2 19 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 EI 1758-2016 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD AUG PY 2012 VL 2 IS 4 BP 301 EP 312 DI 10.2217/NPY.12.39 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 980JF UT WOS:000306888700010 PM 23105949 ER PT J AU Abramovitch, A Mittelman, A Henin, A Geller, D AF Abramovitch, Amitai Mittelman, Andrew Henin, Aude Geller, Daniel TI Neuroimaging and neuropsychological findings in pediatric obsessive-compulsive disorder: a review and developmental considerations SO NEUROPSYCHIATRY LA English DT Review ID CEREBRAL-BLOOD-FLOW; COGNITIVE-BEHAVIORAL THERAPY; TRAUMATIC BRAIN-INJURY; DEFICIT HYPERACTIVITY DISORDER; NONVERBAL MEMORY IMPAIRMENT; OSTERRIETH COMPLEX FIGURE; EXECUTIVE FUNCTION; NEUROCOGNITIVE ENDOPHENOTYPES; STRUCTURAL ABNORMALITIES; STREPTOCOCCAL INFECTION AB Obsessive-compulsive disorder (OCD) is one of the most prevalent psychiatric disorders affecting children and adolescents. In the last decade, our knowledge base of pediatric OCD has increased greatly. In examining pediatric OCD, neuropsychological performance may serve as a bridge between brain functioning and the phenomenology of the disorder. Recent advances in neuropsychological and neuroimaging techniques have led to significant interest in the neurobiological underpinnings of OCD. Although considerable research has been conducted on adults with this disorder, relatively little research has been directed towards similarly afflicted youth. Neurobiological research including lesion, structural and functional imaging studies are reviewed, along with the literature on neuropsychological testing and deficits associated with the disorder. Emphasizing both the neural and cognitive developmental processes within the pediatric population, these findings are examined and critiqued within a developmental framework. C1 [Abramovitch, Amitai; Henin, Aude; Geller, Daniel] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Abramovitch, Amitai; Mittelman, Andrew; Henin, Aude; Geller, Daniel] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Abramovitch, A (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. EM aabramovitch@partners.org RI Abramovitch, Amitai/I-3333-2012 OI Abramovitch, Amitai/0000-0001-9640-0970 FU AstraZeneca; Bristol-Myers Squibb; Forest Laboratories Inc.; Janssen; Lilly; McNeil Pediatrics; Pfizer; Prechter Foundation; Sanofi Aventis; Shire; Stanley Foundation; UCB Pharma, Inc.; Wyetb; NIH; Boehringer Ingelheim; Pharmacia FX A Henin has received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported, in part, through independent medical education grants from pharmaceutical companies, including AstraZeneca, Bristol-Myers Squibb, Forest Laboratories Inc., Janssen, Lilly, McNeil Pediatrics, Pfizer, Pharmacia, the Prechter Foundation, Sanofi Aventis, Shire, the Stanley Foundation, UCB Pharma, Inc. and Wyetb. In addition, A Henin has received honoraria from Shire, Abbott Laboratories and American Academy of Child and Adolescent Psychiatry and she receives royalties from Oxford University Press. She has been a consultant for Pfizer, Prophase and Concordant Rater Systems. D Geller has received grant funding in the last 3 years from the NIH. In the last 3 years D Geller has received research support from Boehringer Ingelheim. In addition, he has received honoraria for speaking engagements from Eli Lily and has sat on the Eli Lily Bureau and Medical Advisory Board. 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 162 TC 10 Z9 11 U1 10 U2 34 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 EI 1758-2016 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD AUG PY 2012 VL 2 IS 4 BP 313 EP 329 DI 10.2217/NPY.12.40 PG 17 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 980JF UT WOS:000306888700011 ER PT J AU Bacha, F Pyle, L Nadeau, K Cuttler, L Goland, R Haymond, M Levitsky, L Lynch, J Weinstock, RS White, NH Caprio, S Arslanian, S AF Bacha, Fida Pyle, Laura Nadeau, Kristen Cuttler, Leona Goland, Robin Haymond, Morey Levitsky, Lynne Lynch, Jane Weinstock, Ruth S. White, Neil H. Caprio, Sonia Arslanian, Silva CA TODAY Study Grp TI Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study SO PEDIATRIC DIABETES LA English DT Article DE disposition index; glycemic control; insulin secretion; insulin sensitivity; youth type 2 diabetes ID GLUCOSE-TOLERANCE TEST; BETA-CELL FUNCTION; INSULIN-RESISTANCE; OBESE YOUTH; FOLLOW-UP; SENSITIVITY; ADOLESCENTS; SECRETION; FAILURE; MELLITUS AB Objective To investigate insulin sensitivity and secretion indices and determinants of glycemic control in youth with recent-onset type 2 diabetes (T2DM) at randomization in the TODAY study, the largest study of youth with T2DM to date. Methods We examined estimates of insulin sensitivity [1/fasting insulin (1/IF), fasting glucose/insulin (GF/IF), 1/fasting C-peptide (1/CF), GF/CF], beta-cell function [insulinogenic index (?I30/?G30), and ?C30/?G30], and disposition index (DI) in the TODAY cohort of 704 youth (14.0 +/- 2.0 yr; diabetes duration 7.8 +/- 5.8 months; 64.9% female; 41.1% Hispanic, 31.5% Black, 19.6% White, 6.1% American Indian, and 1.7% Asian) according to hemoglobin A1c (HbA1c) quartiles at study randomization. The randomization visit followed a run-in period (median 71 d) during which glycemic control (HbA1c = 8% for at least 2 months) was achieved with metformin alone. These measures were also examined in relation to screening HbA1c levels before run-in. Results Insulin secretion indices declined with increasing HbA1c quartiles, at randomization (?C30/?G30: 0.11 +/- 0.09, 0.10 +/- 0.19, 0.07 +/- 0.06, and 0.03 +/- 0.03 ng/mL per mg/dL, p < 0.0001; DI: 0.03 +/- 0.03, 0.03 +/- 0.05, 0.02 +/- 0.02, and 0.01 +/- 0.01 mg/dL-1, p < 0.0001) and at screening, with no significant difference in insulin sensitivity. There were no significant differences in estimates of insulin sensitivity or secretion between genders or across the different racial groups. At randomization and screening, HbA1c correlated with DI (r = -0.3, p < 0.001), with ?C30/?G30, but not with insulin sensitivity estimates. Conclusions In youth with recent-onset T2DM treated with metformin, glycemic control, as measured by HbA1c, appears to be associated with residual beta-cell function and not insulin sensitivity. C1 [Pyle, Laura] George Washington Univ, Ctr Biostat, TODAY Study Grp, Rockville, MD 20853 USA. [Bacha, Fida; Arslanian, Silva] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Nadeau, Kristen] Univ Colorado, Childrens Hosp Colorado, Div Pediat Endocrinol, Denver, CO 80202 USA. [Cuttler, Leona] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Goland, Robin] Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY USA. [Bacha, Fida; Haymond, Morey] Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Levitsky, Lynne] Massachusetts Gen Hosp, Ctr Diabet, Pediat Endocrine Unit, Boston, MA 02114 USA. [Lynch, Jane] Univ Texas Hlth Sci Ctr San Antonio, Div Pediat Endocrinol, San Antonio, TX 78229 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA. [White, Neil H.] Washington Univ, Dept Pediat, St Louis, MO 63130 USA. [Caprio, Sonia] Yale Univ, Dept Pediat, New Haven, CT 06520 USA. RP Pyle, L (reprint author), George Washington Univ, Ctr Biostat, TODAY Study Grp, 6110 Execut Blvd,Suite 750, Rockville, MD 20853 USA. EM lpyle@bsc.gwu.edu OI Zeitler, Philip/0000-0001-5756-7858 FU Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc.; Pfizer; Sanofi-aventis; NIDDK/NIH [U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01DK61254]; National Center for Research Resources General Clinical Research Centers [M01-RR00036, M01-RR00043-45, M01RR00069, M01-RR00084, M01-RR01066, M01-RR00125, M01-RR14467]; NCRR [UL1-RR024134, UL1-RR024139, UL1-RR024153, UL1RR024989, UL1-RR024992, UL1-RR025758, UL1-RR025780] FX The TODAY Study Group thanks the following companies for donations in support of the study's efforts: Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc.; Pfizer; Sanofi-aventis. This work was completed with funding from NIDDK/NIH grant numbers U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01DK61254; from the National Center for Research Resources General Clinical Research Centers Program grant numbers M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Children's Hospital Los Angeles), M01RR00069 (University of Colorado Denver), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University), and M01-RR14467 (University of Oklahoma Health Sciences Center); and from the NCRR Clinical and Translational Science Awards grant numbers UL1-RR024134 (Children's Hospital of Philadelphia), UL1-RR024139 (Yale University), UL1-RR024153 (Children's Hospital of Pittsburgh), UL1RR024989 (Case Western Reserve University), UL1-RR024992 (Washington University), UL1-RR025758 (Massachusetts General Hospital), and UL1-RR025780 (University of Colorado Denver). NR 19 TC 12 Z9 12 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD AUG PY 2012 VL 13 IS 5 BP 377 EP 384 DI 10.1111/j.1399-5448.2011.00841.x PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 981HJ UT WOS:000306957300002 PM 22332798 ER PT J AU Laffel, L Chang, N Grey, M Hale, D Higgins, L Hirst, K Izquierdo, R Larking, M Macha, C Pham, T Wauters, A Weinstock, RS AF Laffel, Lori Chang, Nancy Grey, Margaret Hale, Dan Higgins, Laurie Hirst, Kathryn Izquierdo, Roberto Larking, Mary Macha, Christina Trang Pham Wauters, Aimee Weinstock, Ruth S. CA TODAY Study Grp TI Metformin monotherapy in youth with recent onset type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study SO PEDIATRIC DIABETES LA English DT Article DE clinical trial; hemoglobin A1c; metformin; pediatric onset; type 2 diabetes ID GLYCEMIC CONTROL; ADOLESCENTS; CHILDREN; INTERVENTION; PREVALENCE; MELLITUS; SEARCH; LIFE AB Background TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) is a federally funded multicenter randomized clinical trial comparing three treatments of youth onset type 2 diabetes. Objective To describe the experience of youth participating in a 26 month run-in period in preparation for randomization into TODAY. Subjects An ethnically diverse sample of 927 youth, 65.4% females, aged 13.7 +/- 2.0 yr old, with type 2 diabetes for a median of 2 months (0.77.8 months, 25th75th percentiles). Methods A run-in period was conducted to achieve HbA1c <8% with metformin monotherapy and diabetes education, and to evaluate adherence to pill taking, visit attendance, and other procedures. Results At entry, mean body mass index (BMI) and z-BMI were 35.6 +/- 7.7 and 2.3 +/- 0.4, respectively, mean HbA1c was 7.7 +/- 2.2%, only 42.5% were on a hypoglycemic treatment, and 35.6% had HbA1c =8%. Comorbid conditions were common; 18.8% had hypertension, 24.2% had elevated cholesterol, and 6.5% had abnormal liver enzymes. After a median 71 d of run-in, 90.9% had HbA1c <8%, 77.9% had HbA1c <7%, and 46.4% had HbA1c <6%. Of the 772 youth achieving the target HbA1c <8%, 704 (91.2%) were randomized; non-adherence to metformin treatment was the main cause for non-randomization. Youth proceeding to randomization decreased weight by 0.68?kg and HbA1c by 1.45% compared to a weight gain of 0.71?kg and HbA1c decrease of 0.74% in the non-randomized youth (p = 0.01 in both cases). However, change in z-BMI was not significantly different between the two groups. Conclusions Most youth with recent onset type 2 diabetes can achieve target HbA1c <8.0% with short-term metformin monotherapy and standard diabetes education ( identifier: NCT00081328). C1 [Hirst, Kathryn; Trang Pham] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Laffel, Lori; Higgins, Laurie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Chang, Nancy] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Grey, Margaret] Yale Univ, New Haven, CT 06519 USA. [Hale, Dan; Wauters, Aimee] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Izquierdo, Roberto; Weinstock, Ruth S.] SUNY Upstate Med Univ, Syracuse, NY 13214 USA. [Larking, Mary] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Macha, Christina] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. RP Hirst, K (reprint author), George Washington Univ, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM khirst@bsc.gwu.edu OI Zeitler, Philip/0000-0001-5756-7858 FU NIDDK/NIH [01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254]; National Center for Research Resources General Clinical Research Centers [M01-RR00036, M01-RR00043-45, M01-RR00069, M01-RR00084, M01-RR01066, M01-RR00125, M01-RR14467]; NCRR [UL1-RR024134, UL1-RR024139, UL1-RR024153, UL1-RR024989, UL1-RR024992, UL1-RR025758, UL1-RR025780]; Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; Eli Lilly and Company, GlaxoSmithKline; LifeScan, Inc.; Pfizer; Sanofi-Aventis FX This work was completed with funding from NIDDK/NIH grant numbers U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254; from the National Center for Research Resources General Clinical Research Centers Program grant numbers M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Childrens Hospital Los Angeles), M01-RR00069 (University of Colorado Denver), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University), and M01-RR14467 (University of Oklahoma Health Sciences Center); and from the NCRR Clinical and Translational Science Awards grant numbers UL1-RR024134 (Children's Hospital of Philadelphia), UL1-RR024139 (Yale University), UL1-RR024153 (Children's Hospital of Pittsburgh), UL1-RR024989 (Case Western Reserve University), UL1-RR024992 (Washington University), UL1-RR025758 (Massachusetts General Hospital), and UL1-RR025780 (University of Colorado Denver).; The TODAY Study Group thanks the following companies for donations in support of the study's efforts: Becton, Dickinson and Company, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, LifeScan, Inc., Pfizer, and Sanofi-Aventis. NR 17 TC 10 Z9 13 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD AUG PY 2012 VL 13 IS 5 BP 385 EP 391 DI 10.1111/j.1399-5448.2011.00846.x PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 981HJ UT WOS:000306957300003 PM 22369102 ER PT J AU Cooper, RA Grindle, GG Vazquez, JJ Xu, J Wang, H Candiotti, J Chung, C Salatin, B Houston, E Kelleher, A Cooper, R Teodorski, E Beach, S AF Cooper, Rory A. Grindle, G. G. Vazquez, J. J. Xu, J. Wang, H. Candiotti, J. Chung, C. Salatin, B. Houston, E. Kelleher, A. Cooper, R. Teodorski, E. Beach, S. TI Personal Mobility and Manipulation Appliance-Design, Development, and Initial Testing SO PROCEEDINGS OF THE IEEE LA English DT Article DE Electric powered wheelchair (EPW); manipulation; people with disabilities; rehabilitation; robotics ID ASSISTIVE TECHNOLOGY; WHEELCHAIR; REHABILITATION; ROBOT; USERS AB The ability to perform activities of daily living and mobility-related activities of daily living are substantial indicators of one's ability to live at home and to participate in one's community. Technologies to assist with mobility and manipulation are among the most important tools that clinicians can provide to people with disabilities to promote independence and community participation. For people with severe disabilities involving both the upper and lower extremities, there are few systems that provide practical and coordinated assistance with mobility and manipulation tasks. The personal mobility and manipulation appliance (PerMMA) was created in response to goals set forth by a team of clinicians and people with disabilities. C1 [Cooper, Rory A.; Grindle, G. G.; Vazquez, J. J.; Wang, H.; Candiotti, J.; Salatin, B.; Kelleher, A.; Cooper, R.; Teodorski, E.] Dept Vet Affairs, Human Engn Res Labs, Rehabil Res & Dev Serv, Pittsburgh, PA 15206 USA. [Cooper, Rory A.; Grindle, G. G.; Vazquez, J. J.; Xu, J.; Wang, H.; Candiotti, J.; Chung, C.; Salatin, B.; Houston, E.; Kelleher, A.; Cooper, R.; Teodorski, E.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Xu, J.; Chung, C.; Houston, E.] VA Pittsburgh Healthcare Syst, Rehabil Res & Dev Serv, Dept Vet Affairs VA, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Beach, S.] Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA 15260 USA. RP Cooper, RA (reprint author), Dept Vet Affairs, Human Engn Res Labs, Rehabil Res & Dev Serv, Pittsburgh, PA 15206 USA. EM RCOOPER@pitt.edu RI Wang, Hongwu/J-6133-2013 OI Wang, Hongwu/0000-0002-6567-9144 FU NSF-ERC Quality of Life Technology [EEC-0540865]; VA Rehabilitation Research & Development Center [B6789C] FX This work was supported in part by the NSF-ERC Quality of Life Technology (EEC-0540865) and the VA Rehabilitation Research & Development Center (B6789C). The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 12 TC 10 Z9 10 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9219 J9 P IEEE JI Proc. IEEE PD AUG PY 2012 VL 100 IS 8 SI SI BP 2505 EP 2511 DI 10.1109/JPROC.2012.2200537 PG 7 WC Engineering, Electrical & Electronic SC Engineering GA 976NV UT WOS:000306592500010 ER PT J AU Bartels, CM Kind, AJH Thorpe, CT Everett, CM Cook, RJ McBride, PE Smith, MA AF Bartels, Christie M. Kind, Amy J. H. Thorpe, Carolyn T. Everett, Christine M. Cook, Rachel J. McBride, Patrick E. Smith, Maureen A. TI Lipid Testing in Patients with Rheumatoid Arthritis and Key Cardiovascular-Related Comorbidities: A Medicare Analysis SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE rheumatoid arthritis; cardiovascular disease; prevention and control; preventive medicine; cholesterol ID QUALITY-OF-CARE; POSITIVE PREDICTIVE-VALUE; ADMINISTRATIVE DATA; ORTHOPEDIC-SURGERY; CLAIMS; RISK; MANAGEMENT; RECOMMENDATIONS; ASSOCIATION; SENSITIVITY AB Objective: For patients with rheumatoid arthritis (RA) and comorbid cardiovascular disease (CVD), diabetes, or hyperlipidemia, annual lipid testing is recommended to reduce morbidity and mortality from comorbidities. Given trends encouraging complex patients to receive care in "medical homes," we examined associations between regularly seeing a primary care provider (PCP) and lipid testing in RA patients with cardiovascular-related comorbidities. Methods: We performed a retrospective cohort study examining a 5% random USA Medicare sample (2004-06) of beneficiaries over 65 years old with RA and concomitant CVD, diabetes, or hyperlipidemia (n = 16,893). We examined the relationship between receiving lipid testing in 2006 and having at least 1 PCP visit per year in 2004, 2005, and 2006 using multivariate regression. Results: Ninety percent of patients had prevalent CVD; 46% had diabetes, and 64% had hyperlipidemia. However, annual lipid testing was only performed in 63% of these RA patients. Thirty percent of patients saw a PCP less than once per year, despite frequent visits (mean >9) with other providers. Patients without at least 1 annual PCP visit were 16% less likely to have lipid testing. Increased age, complexity scores, hospitalization, and large town residence predicted decreased lipid testing. Conclusions: Despite comorbid CVD, diabetes, or hyperlipidemia, 30% of Medicare RA patients saw a PCP less than once per year, and 1 in 3 lacked annual lipid testing. Findings support advocating primary care visits at least once per year. Remaining gaps in lipid testing suggest the need for additional strategies to improve lipid testing in at-risk RA patients. (C) 2012 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 42:9-16 C1 [Bartels, Christie M.] Univ Wisconsin, Rheumatol Sect, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Kind, Amy J. H.; Everett, Christine M.] Univ Wisconsin, Dept Med, Div Geriatr, Sch Med & Publ Hlth, Madison, WI USA. [Kind, Amy J. H.] William S Middleton Hosp, GRECC, US Dept Vet Affairs, Madison, WI USA. [Thorpe, Carolyn T.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Cook, Rachel J.] Univ Wisconsin, Dept Med, Hematol Oncol Sect, Sch Med & Publ Hlth, Madison, WI USA. [McBride, Patrick E.] Univ Wisconsin, Dept Med, Cardiovasc Div, Sch Med & Publ Hlth, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Family Med, Sch Med & Publ Hlth, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. RP Bartels, CM (reprint author), 1685 Highland Ave,Room 4132, Madison, WI 53705 USA. EM cb4@medicine.wisc.edu FU University of Wisconsin Institute for Clinical and Translational Research; National Center for Research Resources, National Institutes of Health [1UL1RR025011] FX This project was supported by a training grant and partnership with the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW-ICTR). Grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health. Additional support was provided by the UW School of Medicine and Public Health from the Wisconsin Partnership Program. The authors have no potential conflicts of interest. The Health Innovation Program assisted with data management and manuscript preparation. NR 38 TC 12 Z9 12 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0049-0172 EI 1532-866X J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD AUG PY 2012 VL 42 IS 1 BP 9 EP 16 DI 10.1016/j.semarthrit.2012.01.005 PG 8 WC Rheumatology SC Rheumatology GA 982GF UT WOS:000307030300002 PM 22424813 ER PT J AU Fukudome, EY Li, YQ Kochanek, AR Lu, J Smith, EJ Liu, BL Kim, K Velmahos, GC Demoya, MA Alam, HB AF Fukudome, Eugene Y. Li, Yongqing Kochanek, Ashley R. Lu, Jennifer Smith, Eleanor J. Liu, Baoling Kim, Kyuseok Velmahos, George C. deMoya, Marc A. Alam, Hasan B. TI Pharmacologic resuscitation decreases circulating cytokine-induced neutrophil chemoattractant-1 levels and attenuates hemorrhage-induced acute lung injury SO SURGERY LA English DT Article; Proceedings Paper CT 6th Annual Academic Surgical Congress CY FEB 01-03, 2011 CL Huntington Beach, CA SP Assoc Acad Surg (AAS), Soc Univ Surg (SUS) ID KERATINOCYTE-DERIVED CHEMOKINE; HISTONE DEACETYLASE ACTIVITY; VALPROIC ACID; FLUID RESUSCITATION; CARDIAC HISTONES; MESSENGER-RNA; SHOCK; RAT; ACETYLATION; IDENTIFICATION AB Background. Acute lung injury (ALI) is a complication of hemorrhagic shock (HS). Histone deacetylase inhibitors, such as valproic acid (VPA), can improve survival after HS; however, their effects on late organ injury are unknown. Herein, we have investigated the effects of HS and VPA treatment on ALI and circulating cytokines that may serve as biomarkers for the development of organ injury. Methods. Anesthetized Wistar-Kyoto rats (250-300 g) underwent 40% blood volume hemorrhage over 10 minutes followed by 30 minutes of unresuscitated shock and were treated with either VPA (300 mg/kg) or vehicle control. Blood samples were obtained at baseline, after shock, and before death (at 1, 4, and 20 hours; n = 3-4/timepoint/group). Serum samples were screened for possible biomarkers using a multiplex electrochemiluminescence detection assay, and results were confirmed using enzyme-linked immunosorbent assay (ELISA). In addition, lung tissue lysate was examined for chemokine and myeloperoxidase (MPO) levels as a marker for neutrophil infiltration and ALL Lung cytokine-induced neutrophil chemoattractant-1 (CINC-1; a chemokine belonging to the interleukin-8 family that promotes neutrophil chemotaxis) mRNA levels were measured by real-time polymerase chain reaction studies. Results. Serum screening revealed that hemorrhage rapidly altered levels of circulating CINC-1. ELISA confirmed that CINC-1 protein was significantly elevated in the serum as early as 4 hours and in the lung at 20 hours after hemorrhage, without any significant changes in CINC-1 mRNA expression. Lung MPO levels were also elevated at both 4 and 20 hours after hemorrhage. VPA treatment attenuated these changes. Conclusion. Hemorrhage resulted in the development of ALI, which was prevented with VPA treatment. Circulating CINC-1 levels rose rapidly after hemorrhage, and serum CINC-1 levels correlated with lung CINC-1 and MPO levels. This suggests that circulating CINC-1 levels could be used as an early marker for the subsequent development of organ inflammation and injury. (Surgery 2012;152:254-61.) C1 [Fukudome, Eugene Y.; Li, Yongqing; Kochanek, Ashley R.; Lu, Jennifer; Smith, Eleanor J.; Liu, Baoling; Kim, Kyuseok; Velmahos, George C.; deMoya, Marc A.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Sch Med,Dept Surg, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Sch Med,Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org OI Kim, Kyuseok/0000-0002-7991-9428 FU NIGMS NIH HHS [R01 GM084127] NR 37 TC 10 Z9 11 U1 3 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2012 VL 152 IS 2 BP 254 EP 261 DI 10.1016/j.surg.2012.03.013 PG 8 WC Surgery SC Surgery GA 983ZP UT WOS:000307157500016 PM 22657731 ER PT J AU Ginat, DT Mangla, R Yeaney, G Schaefer, PW Wang, H AF Ginat, Daniel T. Mangla, Rajiv Yeaney, Gabrielle Schaefer, Pamela W. Wang, Henry TI Correlation between Dynamic Contrast-enhanced Perfusion MRI Relative Cerebral Blood Volume and Vascular Endothelial Growth Factor Expression in Meningiomas SO ACADEMIC RADIOLOGY LA English DT Article DE Meningioma; dynamic-susceptibility contrast-enhanced MR perfusion; VEGF; CBV ID MALIGNANT MENINGIOMAS; ANGIOGENESIS; GLIOMAS; DIFFERENTIATION; PERMEABILITY; THERAPIES; EDEMA; GRADE AB Purpose: To determine whether there is a correlation between vascular endothelial growth factor (VEGF) expression and cerebral blood flow (CBV) measurements in dynamic contrast-enhanced susceptibility perfusion magnetic resonance imaging (MRI) and to correlate the perfusion characteristics in high- versus low-grade meningiomas. Methods and Materials: A total of 48 (24 high-grade and 24 low-grade) meningiomas with available dynamic susceptibility-weighted MRI were retrospectively reviewed for maximum CBV and semiquantitative VEGF immunoreactivity. Correlation between normalized CBV and VEGF was made using the Spearman rank test and comparison between CBV in high- versus low-grade meningiomas was made using the Wilcoxon test. Results: There was a significant (P =.01) correlation between normalized maximum CBV and VEGF scores with a Spearman correlation coefficient of 0.37. In addition, there was a significant (P <.01) difference in normalized maximum CBV ratios between high-grade meningiomas (mean 12.6; standard deviation 5.2) and low-grade meningiomas (mean 8.2; standard deviation 5.2). Conclusion: The data suggest that CBV accurately reflects VEGF expression and tumor grade in meningiomas. Perfusion-weighted MRI can potentially serve as a useful biomarker for meningiomas, pending prospective studies. C1 [Ginat, Daniel T.; Mangla, Rajiv; Wang, Henry] Univ Rochester, Med Ctr, Dept Imaging Sci, Rochester, NY 14642 USA. [Yeaney, Gabrielle] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA. [Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Univ Rochester, Med Ctr, Dept Imaging Sci, 601 Elmwood Ave, Rochester, NY 14642 USA. EM ginatd01@gmail.com FU SIR Grant [5-28644] FX From the Departments of Imaging Sciences (D.T.G., R.M., H.W.) and Pathology (G.Y.), University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642; Department of Radiology, Massachusetts General Hospital, Boston, MA (P.W.S.). Received January 30, 2012; accepted April 4, 2012. Funded by SIR Grant 5-28644. We also thank Rui Hu, PhD, for his assistance with the statistical analysis. Address correspondence to: D.T.G. e-mail: ginatd01@gmail.com NR 26 TC 6 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 2012 VL 19 IS 8 BP 986 EP 990 DI 10.1016/j.acra.2012.04.006 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 978DE UT WOS:000306720000011 PM 22591719 ER PT J AU Demidova-Rice, TN Hamblin, MR Herman, IM AF Demidova-Rice, Tatiana N. Hamblin, Michael R. Herman, Ira M. TI Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 2: Role of Growth Factors in Normal and Pathological Wound Healing: Therapeutic Potential and Methods of Delivery SO ADVANCES IN SKIN & WOUND CARE LA English DT Article DE acute wound healing; drug delivery; growth factors; wound healing ID SMOOTH-MUSCLE-CELLS; GENETICALLY DIABETIC MOUSE; GENE-TRANSFER; IN-VITRO; TGF-BETA; EXTRACELLULAR-MATRIX; COLLAGEN MATRICES; BIOLOGICAL-ACTIVITY; PDGF-BB; PHOTOCROSSLINKABLE CHITOSAN AB This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed. C1 [Herman, Ira M.] Tufts Univ, Sackler Sch Grad Biomed Sci, Program Cellular & Mol Physiol, Boston, MA 02111 USA. [Herman, Ira M.] Ctr Innovat Wound Healing Res, Boston, MA USA. [Demidova-Rice, Tatiana N.; Herman, Ira M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Demidova-Rice, Tatiana N.] Massachusetts Gen Hosp, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Herman, IM (reprint author), Tufts Univ, Sackler Sch Grad Biomed Sci, Program Cellular & Mol Physiol, Boston, MA 02111 USA. EM ira.herman@tufts.edu OI Hamblin, Michael/0000-0001-6431-4605 FU National Institutes of Health; Wound Care Partners, LLC FX Tatiana N. Demidova-Rice, PhD, was a postdoctoral Fellow at Tufts University School of Medicine, Boston, Massachusetts, when this article was submitted. She is a postdoctoral fellow at E. L. Steele Laboratory of Tumor Biology, Massachusetts General Hospital, Boston. Michael R. Hamblin, PhD, is Associate Professor, Department of Dermatology and Principal Investigator, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston. Ira M. Herman, PhD, is Professor and Director, Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences and The Center for Innovations in Wound Healing Research, and Tufts University School of Medicine, Boston, Massachusetts. Drs Demidova-Rice and Hamblin have disclosed they have no financial relationships related to this article. Dr Herman has disclosed that he is/was a recipient of grant/research funding from the National Institutes of Health, and Wound Care Partners, LLC; is/was a consultant/advisor to Healthpoint Biotherapeutics, Inc, and Nell One, Inc; was a consultant/advisor to Healthpro Bioventures and Amach Partners; and is a stock shareholder in Wound Care Partners, LLC. Correspondence may be sent to Dr Herman at ira.herman@tufts.edu. Submitted January 27, 2011; accepted in revised version June 8, 2011. NR 188 TC 25 Z9 25 U1 3 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-7941 J9 ADV SKIN WOUND CARE JI Adv. Skin Wound Care PD AUG PY 2012 VL 25 IS 8 BP 349 EP 370 DI 10.1097/01.ASW.0000418541.31366.a3 PG 22 WC Dermatology; Nursing; Surgery SC Dermatology; Nursing; Surgery GA 978MZ UT WOS:000306747500003 PM 22820962 ER PT J AU Byers, AL Covinsky, KE Barnes, DE Yaffe, K AF Byers, Amy L. Covinsky, Kenneth E. Barnes, Deborah E. Yaffe, Kristine TI Dysthymia and Depression Increase Risk of Dementia and Mortality Among Older Veterans SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Dementia; depression; dysthymia; mortality ID MILD COGNITIVE IMPAIRMENT; CARDIOVASCULAR HEALTH; LATE-LIFE; ALZHEIMERS-DISEASE; VASCULAR-DISEASE; ELDERLY PERSONS; SYMPTOMS; ASSOCIATION; WOMEN; DECLINE AB Objective: To determine whether less severe depression spectrum diagnoses such as dysthymia, as well as depression, are associated with risk of developing dementia and mortality in a "real-world" setting. Design: Retrospective cohort study conducted using the Department of Veterans Affairs (VA) National Patient Care Database (1997-2007). Setting: VA medical centers in the United States. Participants: A total of 281,540 veterans aged 55 years and older without dementia at study baseline (1997-2000). Measurements: Depression status and incident dementia were ascertained from International Classification of Diseases, Ninth Revision codes during study baseline (1997-2000) and follow-up (2001-2007), respectively. Mortality was ascertained by time of death dates in the VA Vital Status File. Results: Ten percent of veterans had baseline diagnosis of depression and nearly 1% had dysthymia. The unadjusted incidence of dementia was 11.2% in veterans with depression, 10.2% with dysthymia and 6.4% with neither. After adjusting for demographics and comorbidities, patients diagnosed with dysthymia or depression were twice as likely to develop incident dementia compared with those with no dysthymia/depression (adjusted dysthymia hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.71-2.25; and depression HR: 2.18, 95% CI: 2.08-2.28). Dysthymia and depression also were associated with increased risk of death (31.6% dysthymia and 32.9% depression versus 28.5% neither; adjusted dysthymia HR: 1.41, 95% CI: 1.31-1.53; and depression HR: 1.47, 95% CI: 1.43-1.51). Conclusions: Findings suggest that older adults with dysthymia or depression need to be monitored closely for adverse outcomes. Future studies should determine whether treatment of depression spectrum disorders may reduce risk of these outcomes. (Am J Geriatr Psychiatry 2012; 20:664-672) C1 [Byers, Amy L.; Covinsky, Kenneth E.; Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Byers, Amy L.; Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [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. RP Byers, AL (reprint author), San Francisco VA Med Ctr, 4150 Clement St 116H, San Francisco, CA 94121 USA. EM Amy.Byers@ucsf.edu FU Department of Defense [W81XWH-05-2-0094]; National Institute of Mental Health [K01 MH079093]; National Institute on Aging [AG031155, AG029812]; NARSAD FX This work was supported by the Department of Defense (W81XWH-05-2-0094 [KY]) and the National Institute of Mental Health (K01 MH079093 [ALB]). Drs. Yaffe and Covinsky are supported in part by K24 Midcareer Investigator Awards from the National Institute on Aging (AG031155 [KY] and AG029812 [KEC]). Dr. Barnes was supported in part by NARSAD. NR 40 TC 31 Z9 34 U1 4 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD AUG PY 2012 VL 20 IS 8 BP 664 EP 672 DI 10.1097/JGP.0b013e31822001c1 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 977UX UT WOS:000306691400004 PM 21597358 ER PT J AU Schneider, B Ercoli, L Siddarth, P Lavretsky, H AF Schneider, Brooke Ercoli, Linda Siddarth, Prabha Lavretsky, Helen TI Vascular Burden and Cognitive Functioning in Depressed Older Adults SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Cerebrovascular risk factors; cognitive impairment; geriatric depression; vascular disease ID LATE-LIFE DEPRESSION; PRIMARY-CARE PATIENTS; SUBCORTICAL ISCHEMIC DEPRESSION; CEREBROVASCULAR RISK-FACTORS; EXECUTIVE DYSFUNCTION; GERIATRIC DEPRESSION; NEUROPSYCHIATRIC SYMPTOMS; CARDIOVASCULAR HEALTH; RATING-SCALE; IMPAIRMENT AB Background: Vascular burden is known to contribute to geriatric depression and cognitive impairment. The objective of our study was to evaluate the relationship between vascular burden and pattern of cognitive impairment in older adults with depression. Methods: Ninety-four community-dwelling older adults (mean age = 70.8 years; SD = 7.63) diagnosed with major depression were recruited to participate in the tai chi complementary use study aimed to improve antidepressant response to an antidepressant medication. All participants received comprehensive evaluations of depression, apathy, and vascular risk factors, and completed a battery of cognitive measures of memory, cognitive control, verbal fluency, and attention. Results: The severity of vascular burden was significantly correlated with depression severity and impaired performance on measures of cognitive control (i.e., inhibition/mental flexibility), and attention, but not memory or verbal fluency. Neither the severity of comorbid apathy nor medical illness burden was related to cognitive impairment. Conclusions: Vascular burden in older depressed adults contributes to cognitive impairment, particularly in domains of attention and cognitive control. Our findings suggest that aggressive treatment of vascular risk factors may reduce risk for further cognitive decline in depressed older adults. (Am J Geriatr Psychiatry 2012; 20:673-681) C1 [Lavretsky, Helen] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Schneider, Brooke] Greater Los Angeles VA Healthcare Ctr, Psychol Serv, Los Angeles, CA USA. RP Lavretsky, H (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,C9-948A, Los Angeles, CA 90095 USA. EM hlavrets@ucla.edu RI Lavretsky, Helen/M-5711-2015 OI Lavretsky, Helen/0000-0001-9990-5085 FU NIH [MH077650, MH086481, AT003480]; Forest Research Institute; Alzheimer's Prevention Research Foundation FX This work was supported by the NIH grants MH077650, MH086481, and AT003480 to Dr. Lavretsky. Research grants from the Forest Research Institute; Alzheimer's Prevention Research Foundation. NR 65 TC 4 Z9 4 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD AUG PY 2012 VL 20 IS 8 BP 673 EP 681 DI 10.1097/JGP.0b013e31822ccd64 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 977UX UT WOS:000306691400005 PM 21857219 ER PT J AU Brenes, GA Miller, ME Williamson, JD McCall, WV Knudson, M Stanley, MA AF Brenes, Gretchen A. Miller, Michael E. Williamson, Jeff D. McCall, W. Vaughn Knudson, Mark Stanley, Melinda A. TI A Randomized Controlled Trial of Telephone-Delivered Cognitive-Behavioral Therapy for Late-Life Anxiety Disorders SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Anxiety; cognitive-behavioral therapy; elderly; generalized anxiety disorder; panic disorder; telephone-delivered psychotherapy ID WORKING ALLIANCE INVENTORY; OLDER-ADULTS; PRIMARY-CARE; PSYCHOMETRIC PROPERTIES; MENTAL-DISORDERS; HEALTH SURVEY; SHORT-FORM; VALIDATION; DEPRESSION; STATE AB Objectives: Older adults face a number of barriers to receiving psychotherapy, such as a lack of transportation and access to providers. One way to overcome such barriers is to provide treatment by telephone. The purpose of this study was to examine the effects of cognitive behavioral therapy delivered by telephone (CBT-T) to older adults diagnosed with an anxiety disorder. Design: Randomized controlled trial. Setting: Participants' homes. Participants: Sixty participants age 60 and older with a diagnosis of generalized anxiety disorder, panic disorder, or anxiety disorder not otherwise specified. Intervention: CBT-T versus information-only comparison. Measurements: Coprimary outcomes included worry (Penn State Worry Questionnaire) and general anxiety (State Trait Anxiety Inventory). Secondary outcomes included clinician-rated anxiety (Hamilton Anxiety Rating Scale), anxiety sensitivity (Anxiety Sensitivity Index), depressive symptoms (Beck Depression Inventory), quality of life (SF-36), and sleep (Insomnia Severity Index). Assessments were completed prior to randomization, immediately upon completion of treatment, and 6 months after completing treatment. Results: CBT-T was superior to information-only in reducing general anxiety (ES = 0.71), worry (ES = 0.61), anxiety sensitivity (ES = 0.85), and insomnia (ES = 0.82) at the posttreatment assessment; however, only the reductions in worry were maintained by the 6-month follow-up assessment (ES = 0.80). Conclusions: These results suggest that CBT-T may be efficacious in reducing anxiety and worry in older adults, but additional sessions may be needed to maintain these effects. (Am J Geriatr Psychiatry 2012; 20:707-716) C1 [Brenes, Gretchen A.; McCall, W. Vaughn] Wake Forest Univ, Bowman Gray Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC 27157 USA. [Miller, Michael E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Williamson, Jeff D.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA. [Knudson, Mark] Wake Forest Univ, Bowman Gray Sch Med, Dept Family & Community Med, Winston Salem, NC 27157 USA. [Stanley, Melinda A.] Houston Ctr Qual Care & Utilizat Studies, Menninger Dept Psychiat & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Brenes, GA (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Psychiat & Behav Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM gbrenes@wfubmc.edu FU National Institute of Mental Health [MH65281, MH53932]; Wake Forest University Claude D. Pepper Older Americans Independence Center [P30-AG21332]; VA HSR&D Houston Center of Excellence [HFP90-020] FX This research was supported by National Institute of Mental Health Grant MH65281 to Gretchen A. Brenes, Wake Forest University Claude D. Pepper Older Americans Independence Center (P30-AG21332), and National Institute of Mental Health Grant MH53932 to Melinda A. Stanley. It was also partly supported by the VA HSR&D Houston Center of Excellence (HFP90-020). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NIH, the Department of Veterans Affairs or Baylor College of Medicine. The NIMH had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; or the preparation, review or approval of the manuscript. NR 39 TC 17 Z9 17 U1 3 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD AUG PY 2012 VL 20 IS 8 BP 707 EP 716 DI 10.1097/JGP.0b013e31822ccd3e PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 977UX UT WOS:000306691400009 PM 22828172 ER PT J AU Smith, SE Mullen, TE Graham, D Sims, KB Rehm, HL AF Smith, Sharon E. Mullen, Thomas E. Graham, Dionne Sims, Katherine B. Rehm, Heidi L. TI Norrie disease: Extraocular clinical manifestations in 56 patients SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Norrie disease; hearing loss; congenital blindness; peripheral vascular disease; developmental delay; autism; pervasive developmental disorder; intellectual disability; erectile dysfunction ID VENOUS INSUFFICIENCY; VASCULAR DEVELOPMENT; RETINAL VASCULATURE; NDP GENE; PHENOTYPE; FRIZZLED-4; MUTATIONS; DELETION; MICE; ANGIOGENESIS AB Norrie disease (ND) is an X-linked recessive disorder characterized by congenital blindness, progressive sensorineural hearing loss and cognitive impairment. The ocular phenotype has been well described, while the extraocular manifestations of the disorder are not well understood. We present the data from the Norrie Disease Registry, which consists of 56 patients with detailed clinical histories and genotype data. This study represents the largest, detailed investigation into the phenotypic spectrum of ND to date and more importantly expands knowledge of the extraocular clinical manifestations. We identify several novel aspects of the syndrome that will improve the management of these patients. In particular, we expand our understanding of the neurologic manifestations in ND and identify a chronic seizure disorder in approximately 10% of all patients. In addition, details of the hearing phenotype are described including the median age of onset (12 years of age) and how genotype affects onset. Moreover, we find vascular disease to be a significant component of ND; and vascular health should be, in the future, a component of patient clinical care. In summary, the results expand our understanding of the phenotypic variability and genotypic heterogeneity in ND patients. (C) 2012 Wiley Periodicals, Inc. C1 [Smith, Sharon E.] Harvard Univ, Sch Med, Genet Training Program, Boston, MA USA. [Mullen, Thomas E.; Rehm, Heidi L.] Brigham & Womens Hosp, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Graham, Dionne] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sims, Katherine B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Rehm, HL (reprint author), Mol Med Lab, 65 Landsdowne St, Cambridge, MA 02139 USA. EM hrehm@partners.org NR 35 TC 8 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD AUG PY 2012 VL 158A IS 8 BP 1909 EP 1917 DI 10.1002/ajmg.a.35469 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 977IT UT WOS:000306651400016 PM 22786811 ER PT J AU Burris, HH Rifas-Shiman, SL Camargo, CA Litonjua, AA Huh, SY Rich-Edwards, JW Gillman, MW AF Burris, Heather H. Rifas-Shiman, Sheryl L. Camargo, Carlos A., Jr. Litonjua, Augusto A. Huh, Susanna Y. Rich-Edwards, Janet W. Gillman, Matthew W. TI Plasma 25-hydroxyvitamin D during pregnancy and small-for-gestational age in black and white infants SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Vitamin D; Infant; Small-for-gestational age; African continental ancestry group; Health status disparities; Pregnancy ID VITAMIN-D STATUS; INTRAUTERINE GROWTH-RETARDATION; OFFSPRING BIRTH SIZE; FETAL-GROWTH; D SUPPLEMENTATION; D DEFICIENCY; SERUM CONCENTRATIONS; D INSUFFICIENCY; WOMEN; OUTCOMES AB Purpose: In a prospective prenatal cohort study, we examined associations of second trimester and cord plasma 25-hydroxyvitamin D (25[OH]D) with small-for-gestational age (SGA) and the extent to which vitamin D might explain black/white differences in SGA. Methods: We studied 1067 white and 236 black mother-infant pairs recruited from eight obstetrical offices early in pregnancy in Massachusetts. We analyzed 25(OH)D levels using an immunoassay and performed multivariable logistic models to estimate the odds of SGA by category of 25(OH)D level. Results: Mean (SD) second trimester 25(OH)D level was 60 nmol/L (SD, 21) and was lower for black (46 nmol/L [SD, 221) than white (62 nmol/L [SD, 201) women. Fifty-nine infants were SGA (4.5%), and more black than white infants were SGA (8.5% vs. 3.7%). The odds of SGA were higher with maternal 25(OH)D levels less than 25 versus 25 nmol/L or greater (adjusted odds ratio, 3.17; 95% confidence interval, 1.16-8.63). The increased odds of SGA among black versus white participants decreased from an odds ratio of 2.04(1.04, 4.04) to 1.68(0.82, 3.46) after adjusting for 25(OH)D. Conclusions: Second trimester 25(OH)D levels less than 25 nmol/L were associated with higher odds of SGA. Our data raise the possibility that vitamin D status may contribute to racial disparities in SGA. (C) 2012 Elsevier Inc. All rights reserved. C1 [Burris, Heather H.] Harvard Univ, Dept Neonatol, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Burris, Heather H.] Harvard Univ, Childrens Hosp Boston, Div Newborn Med, Sch Med, Boston, MA 02215 USA. [Rifas-Shiman, Sheryl L.; Gillman, Matthew W.] Harvard Univ, Dept Populat Med, Obes Prevent Program, Sch Med, Boston, MA 02215 USA. [Rifas-Shiman, Sheryl L.; Gillman, Matthew W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Sch Med, Boston, MA 02215 USA. [Camargo, Carlos A., Jr.; Litonjua, Augusto A.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Charming Lab,Med Sch, Boston, MA 02215 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. [Huh, Susanna Y.] Harvard Univ, Childrens Hosp Boston, Div Gastroenterol & Nutr, Sch Med, Boston, MA 02215 USA. [Rich-Edwards, Janet W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens Hlth,Dept Med, Boston, MA 02215 USA. [Rich-Edwards, Janet W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Gillman, Matthew W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. RP Burris, HH (reprint author), Harvard Univ, Dept Neonatol, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave,RO 318, Boston, MA 02215 USA. EM heburris@bidmc.harvard.edu OI Burris, Heather/0000-0003-4510-9547; Litonjua, Augusto/0000-0003-0422-5875 FU U.S.National Institutes of Health [HD 034568, HL 068041, HL 064925]; Harvard Medical School; Harvard Pilgrim Health Care Foundation; Klarman Scholars Program at Beth Israel Deaconess Medical Center FX This work was supported by the U.S.National Institutes of Health (HD 034568, HL 068041, and HL 064925), Harvard Medical School, the Harvard Pilgrim Health Care Foundation, and the Klarman Scholars Program at Beth Israel Deaconess Medical Center. NR 50 TC 36 Z9 37 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD AUG PY 2012 VL 22 IS 8 BP 581 EP 586 DI 10.1016/j.annepidem.2012.04.015 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 978UH UT WOS:000306770800007 PM 22658824 ER PT J AU Yoon, SS AF Yoon, Sam S. TI Staging Gastric Cancer Patients after Complete Surgical Resection: Which System Should We Use? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID SURGERY; ADENOCARCINOMA; SURVIVAL; CARCINOMA; MORTALITY; EDITION; VOLUME C1 Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yoon, SS (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM syoon@partners.org NR 28 TC 2 Z9 2 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 AUG PY 2012 VL 19 IS 8 BP 2423 EP 2425 DI 10.1245/s10434-012-2405-4 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 979BD UT WOS:000306789000001 PM 22618720 ER PT J AU Hong, NJL Pandalai, PK Hornick, JL Shekar, PS Harmon, DC Chen, YL Butrynski, JE Baldini, EH Raut, CP AF Hong, Nicole J. Look Pandalai, Prakash K. Hornick, Jason L. Shekar, Prem S. Harmon, David C. Chen, Yen-Lin Butrynski, James E. Baldini, Elizabeth H. Raut, Chandrajit P. TI Cardiac Angiosarcoma Management and Outcomes: 20-Year Single-institution Experience SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the New-England-Surgical-Society CY SEP 23-25, 2011 CL Bretton Woods, NH SP New England Surg Soc ID HEART-TRANSPLANTATION; SURGICAL-TREATMENT; TERM SURVIVAL; TUMORS; SARCOMAS; PACLITAXEL; DOCETAXEL; DISEASE AB To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS). This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed. Main outcome measures included patient demographics, tumor characteristics, management strategies, disease response, and survival. Data from 18 patients (78 % male) were reviewed. Sixteen patients (89 %) had AS originating in the right atrium. At diagnosis, eight patients (44 %) had localized/locally advanced disease and ten patients (56 %) had metastatic disease. Initial treatment strategies included resection (44 %), chemotherapy (39 %), and radiotherapy (11 %). Of the eight patients with localized/locally advanced AS, two underwent macroscopically complete resection with negative microscopic margins, one underwent macroscopically complete resection with positive microscopic margins, one underwent macroscopically incomplete resection, two received chemotherapy followed by surgery and intraoperative radiotherapy, one received chemotherapy alone, and one died before planned radiotherapy. Median follow-up was 12 months. Median overall survival (OS) was 13 months for the entire cohort; median OS was 19.5 months for those presenting with localized/locally advanced AS and 6 months for those with metastatic disease at presentation (p = 0.08). Patients who underwent primary tumor resection had improved median OS compared with patients whose tumors remained in situ (17 vs. 5 months, p = 0.01). Cardiac AS is associated with poor prognosis. Resection of primary tumor should be attempted when feasible, as OS may be improved. Nevertheless, most patients die of disease progression. C1 [Hong, Nicole J. Look; Raut, Chandrajit P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Surg Oncol,Brigham & Womens Hosp,Ctr Sarcoma, Boston, MA 02115 USA. [Pandalai, Prakash K.] NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. [Hornick, Jason L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Brigham & Womens Hosp,Ctr Sarcoma & B, Boston, MA 02115 USA. [Shekar, Prem S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiac Surg, Boston, MA 02115 USA. [Harmon, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02115 USA. [Chen, Yen-Lin] Harvard Univ, Sch Med, Div Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Butrynski, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol,Brigham & Womens Hosp,Ctr Sarcoma &, Boston, MA 02115 USA. [Baldini, Elizabeth H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Radiat Oncol,Brigham & Womens Hosp,Ctr Sarcom, Boston, MA 02115 USA. RP Hong, NJL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Surg Oncol,Brigham & Womens Hosp,Ctr Sarcoma, 44 Binney St, Boston, MA 02115 USA. EM n.lookhong@utoronto.ca NR 38 TC 11 Z9 12 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD AUG PY 2012 VL 19 IS 8 BP 2707 EP 2715 DI 10.1245/s10434-012-2334-2 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 979BD UT WOS:000306789000040 ER PT J AU Bakaeen, FG Sethi, G Wagner, TH Kelly, R Lee, K Upadhyay, A Thai, H Juneman, E Goldman, S Holman, WL AF Bakaeen, Faisal G. Sethi, Gulshan Wagner, Todd H. Kelly, Rosemary Lee, Kelvin Upadhyay, Anjali Hoang Thai Juneman, Elizabeth Goldman, Steven Holman, William L. TI Coronary Artery Bypass Graft Patency: Residents Versus Attending Surgeons SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Late-Breaking Clinical Trial Abstract Session on Congenital Heart Surgery at the 48th Annual Meeting of the Society-of-Thoracic-Surgeons / Surgical Motion Picture Session CY JAN 28-FEB 01, 2012 CL Fort Lauderdale, FL SP Soc Thorac Surg ID VOLUME-OUTCOME RELATIONSHIP; TRAIN RESIDENTS; IMPACT; EXPERIENCE; LEVEL; SAFE AB Background. Data are limited regarding the patency of coronary artery bypass grafts performed by residents versus attending surgeons. Methods. We analyzed data from a multicenter, randomized Veterans Affairs Cooperative Study in which the left internal mammary artery was used preferentially to graft the left anterior descending coronary artery, and the best remaining coronary vessel received (per random assignment) either a radial artery or a saphenous vein graft. The study vessel's 1-year graft patency was the primary outcome measure. Secondary outcomes included operative times, operative morbidity, mortality, repeat revascularization, cost, angina symptoms, and quality of life. Multivariate analyses were used to compare patient outcomes for residents versus attendings. Results. Residents were designated as primary surgeons in 23% of cases (167 of 725). Among the 531 patients who had a 1-year angiogram, study graft patency rates for resident cases (n = 122) and attending cases (n = 409) were not significantly different (86% versus 90%, p = 0.22). Residents' cases had longer perfusion time (119 versus 105 minutes, p < 0.0001) and cross-clamp time (84 versus 68 minutes, p < 0.0001). After risk adjustment, all outcome measures did not differ between the two groups, and there was no apparent interaction effect between resident/attending designation and radial artery versus saphenous vein use or on-pump versus off-pump approach. Conclusions. Surgeons in training perform coronary artery bypass surgery without compromising graft patency or patient outcomes. Ongoing evaluation of residents' performance and surgical outcomes is needed, given the major changes that are occurring in residency training. (Ann Thorac Surg 2012;94:482-8) (c) 2012 by The Society of Thoracic Surgeons C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Cardiovasc Surg, Houston, TX USA. Univ Arizona, Hlth Sci Ctr, Dept Cardiothorac Surg, Tucson, AZ USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Univ Minnesota Hosp, Dept Cardiovasc Surg, Minneapolis, MN USA. So Arizona Vet Affairs Hlth Care Syst, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. Univ Alabama Birmingham, Div Cardiothorac Surg, Birmingham, AL USA. RP Bakaeen, FG (reprint author), Michael E DeBakey VAMC, Dept Cardiothorac Surg, OCL 112,2002 Holcombe Blvd, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 25 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2012 VL 94 IS 2 BP 482 EP 488 DI 10.1016/j.athoracsur.2012.04.039 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 977YA UT WOS:000306700100031 PM 22698772 ER PT J AU Jacobs, JP Shahian, DM Edwards, FH O'Brien, SM Blackstone, EH Puskas, JD Schaffer, J Grover, FL Mayer, JE AF Jacobs, Jeffrey P. Shahian, David M. Edwards, Fred H. O'Brien, Sean M. Blackstone, Eugene H. Puskas, John D. Schaffer, Justin Grover, Frederick L. Mayer, John E., Jr. TI Fundamental Flaw in a Fundamental Measure: Inaccuracies in Death Data Reporting Reply SO ANNALS OF THORACIC SURGERY LA English DT Letter C1 [Jacobs, Jeffrey P.] Univ S Florida, Congenital Heart Inst Florida, All Childrens Hosp, Coll Med, St Petersburg, FL 33701 USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Edwards, Fred H.] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA. [O'Brien, Sean M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Blackstone, Eugene H.] Cleveland Clin, Cleveland, OH 44106 USA. [Puskas, John D.] Emory Univ, Emory Univ Hosp Midtown, Atlanta, GA 30322 USA. [Schaffer, Justin] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Grover, Frederick L.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Mayer, John E., Jr.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. RP Jacobs, JP (reprint author), Univ S Florida, Congenital Heart Inst Florida, All Childrens Hosp, Coll Med, 625 6th Ave S,Ste 475, St Petersburg, FL 33701 USA. EM jeffjacobs@msn.com RI O'Brien, Sean/H-6268-2013 NR 5 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2012 VL 94 IS 2 BP 693 EP 694 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 977YA UT WOS:000306700100086 ER PT J AU Fu, K Tang, QZ Feng, JX Liu, XS Zhang, Y AF Fu, Kai Tang, Qianzi Feng, Jianxing Liu, X. Shirley Zhang, Yong TI DiNuP: a systematic approach to identify regions of differential nucleosome positioning SO BIOINFORMATICS LA English DT Article ID DYNAMIC NUCLEOSOMES; HIGH-RESOLUTION; HUMAN GENOME; GENE; CHROMATIN; TRANSCRIPTION; ORGANIZATION; PARTICLE; YEAST; MAP AB Motivation: With the rapid development of high-throughput sequencing technologies, the genome-wide profiling of nucleosome positioning has become increasingly affordable. Many future studies will investigate the dynamic behaviour of nucleosome positioning in cells that have different states or that are exposed to different conditions. However, a robust method to effectively identify the regions of differential nucleosome positioning (RDNPs) has not been previously available. Results: We describe a novel computational approach, DiNuP, that compares nucleosome profiles generated by high-throughput sequencing under various conditions. DiNuP provides a statistical P-value for each identified RDNP based on the difference of read distributions. DiNuP also empirically estimates the false discovery rate as a cutoff when two samples have different sequencing depths and differentiate reliable RDNPs from the background noise. Evaluation of DiNuP showed it to be both sensitive and specific for the detection of changes in nucleosome location, occupancy and fuzziness. RDNPs that were identified using publicly available datasets revealed that nucleosome positioning dynamics are closely related to the epigenetic regulation of transcription. C1 [Fu, Kai; Tang, Qianzi; Feng, Jianxing; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, 1239 Siping Rd, Shanghai 200092, Peoples R China. EM yzhang@tongji.edu.cn RI Zhang, Yong/B-4838-2011 OI Zhang, Yong/0000-0001-6316-2734 FU National Basic Research Program of China (973 Program) [2010CB944904, 2011CB965104]; National Natural Science Foundation of China [31071114]; Shanghai Rising-Star Program [10QA1407300]; New Century Excellent Talents in the University of China [NCET-11-0389]; Innovative Research Team Program Ministry of Education of China [IRT1168] FX The National Basic Research Program of China (973 Program; No. 2010CB944904 and 2011CB965104), the National Natural Science Foundation of China (31071114), the Shanghai Rising-Star Program (10QA1407300), the New Century Excellent Talents in the University of China (NCET-11-0389) and the Innovative Research Team Program Ministry of Education of China (IRT1168). NR 23 TC 8 Z9 8 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 1 PY 2012 VL 28 IS 15 BP 1965 EP 1971 DI 10.1093/bioinformatics/bts329 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 977TA UT WOS:000306686400003 PM 22668788 ER PT J AU Sarkar, U Bonacum, D Strull, W Spitzmueller, C Jin, N Lopez, A Giardina, TD Meyer, AND Singh, H AF Sarkar, Urmimala Bonacum, Doug Strull, William Spitzmueller, Christiane Jin, Nancy Lopez, Andrea Giardina, Traber Davis Meyer, Ashley N. D. Singh, Hardeep TI Challenges of making a diagnosis in the outpatient setting: a multi-site survey of primary care physicians SO BMJ QUALITY & SAFETY LA English DT Article ID ADVERSE EVENTS; MALPRACTICE CLAIMS; FOLLOW-UP; MEDICAL-RECORDS; ERRORS; NEGLIGENT; REFORM; SAFETY AB Background: Although misdiagnosis in the outpatient setting leads to significant patient harm and wasted resources, it is not well studied. The authors surveyed primary care physicians (PCPs) about barriers to timely diagnosis in the outpatient setting and assessed their perceptions of diagnostic difficulty. Methods: Surveys of PCPs practicing in an integrated health system across 10 geographically dispersed states in 2005. The survey elicited information on key cognitive failures (including in clinical knowledge or judgement) for a specific case, and solicited strategies for reducing diagnostic delays. Content analysis was used to categorise cognitive failures and strategies for improvement. The authors examined the extent and predictors of diagnostic difficulty, defined as reporting >5% patients difficult to diagnose. Results: Of 1817 physicians surveyed, 1054 (58%) responded; 848 (80%) respondents primarily practiced in outpatient settings and had an assigned patient panel (inclusion sample). Inadequate knowledge (19.9%) was the most commonly reported cognitive factor. Half reported >5% of their patients were difficult to diagnose; more experienced physicians reported less diagnostic difficulty. In adjusted analyses, problems with information processing (information availability and time to review it) and the referral process were associated with greater diagnostic difficulty. Strategies for improvement most commonly involved workload issues (panel size, non-visit tasks). Conclusions: PCPs report a variety of reasons for diagnostic difficulties in primary care practice. In this study, knowledge gaps appear to be a prominent concern. Interventions that address these gaps as well as practice level issues such as time to process diagnostic information and better subspecialty input may reduce diagnostic difficulties in primary care. C1 [Sarkar, Urmimala; Jin, Nancy; Lopez, Andrea] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Sarkar, Urmimala; Jin, Nancy; Lopez, Andrea] Univ Calif San Francisco, San Francisco Gen Hosp, Ctr Vulnerable Populat, San Francisco, CA 94143 USA. [Strull, William] Kaiser Permanente, Permanente Federat, Oakland, CA USA. [Spitzmueller, Christiane] Univ Houston, Houston, TX USA. [Giardina, Traber Davis; Meyer, Ashley N. D.; Singh, Hardeep] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Giardina, Traber Davis; Meyer, Ashley N. D.; Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Sarkar, U (reprint author), Univ Calif San Francisco, Dept Med, SFGH Div Gen Internal Med, Ward 13, Box 1364,1001 Potrero,Bldg 10,Floor 3, San Francisco, CA 94143 USA. EM usarkar@medsfgh.ucsf.edu OI Davis Giardina, Traber/0000-0002-9184-6524; Meyer, Ashley/0000-0001-7993-8584 FU Agency for Healthcare Research and Quality [K08 HS017594]; NIH [K23CA125585]; Houston VA HSR&D Center of Excellence [HFP90-020] FX Dr Sarkar is supported by the Agency for Healthcare Research and Quality K08 HS017594. Dr. Singh is supported by an NIH K23 career development award (K23CA125585), and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). Manuscript contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or any of the other funders. None of the funders had any role in design and conduct of the study; collection, management, analysis or interpretation of the data; or preparation, review or approval of the manuscript. NR 30 TC 17 Z9 17 U1 2 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD AUG PY 2012 VL 21 IS 8 BP 641 EP 648 DI 10.1136/bmjqs-2011-000541 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 977IH UT WOS:000306649700005 PM 22626738 ER PT J AU Fleming, LM Novack, V Novack, L Cohen, SA Negoita, M Cutlip, DE AF Fleming, Lisa M. Novack, Victor Novack, Lena Cohen, Sidney A. Negoita, Manuela Cutlip, Donald E. TI Frequency and impact of bleeding in elective coronary stent clinical trials-Utility of three commonly used definitions SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bleeding; stent ID SIROLIMUS-ELUTING STENTS; RANDOMIZED CONTROLLED-TRIAL; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; ACUITY TRIAL; INTERVENTION; PREDICTORS; MORTALITY; REGISTRY; LESIONS AB Background: Bleeding events are common after percutaneous coronary intervention (PCI) and have been shown to increase mortality in studies of acute coronary syndrome (ACS) and anti-thrombotic therapy. Despite this evidence, bleeding has not been included as a traditional major endpoint in clinical trials of low-risk populations enrolled in PCI clinical trials. Thus, the impact of specific bleeding definitions has not been evaluated fully among these patients. Methods and Results: Using patient-level pooled data from sirolimus and zotarolimus drug-eluting stent clinical trials, we identified bleeding events using three common definitions of bleeding, ACUITY, TIMI, and GUSTO, and assessed the impact on mortality and MI at 12 months after PCI. The GUSTO, ACUITY, and TIMI classifications identified bleeding rates of 2.3%, 1.9%, and 2.1%, respectively. The GUSTO criteria classified all 118 suspected bleeding events. There were 22 (18.6%) and 8 (6.8%) suspected bleeding events that did not meet ACUITY and TIMI criteria, respectively. The combined endpoint of all-cause death or myocardial infarction (MI) at 12 months was significantly higher for patients with a bleeding event compared with those who did not bleed [hazard ratio 1.95 (95% CI 1.063.60)]. Conclusion: There is a substantial variability in the utility and inclusiveness of three widely used bleeding definitions in identifying clinically significant bleeding events in clinical trials of low risk patients undergoing PCI with DES. Patients with bleeding after elective PCI have an increased one-year risk of death or MI compared to those patients who do not bleed. (C) 2012 Wiley Periodicals, Inc. C1 [Fleming, Lisa M.; Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Dept Cardiol, Boston, MA 02215 USA. [Novack, Victor; Novack, Lena; Cutlip, Donald E.] Harvard Clin Res Inst, Boston, MA USA. [Cohen, Sidney A.] Cordis Corp, Bridgewater, NJ USA. [Cohen, Sidney A.] Hosp Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. [Negoita, Manuela] Medtron Cardiovasc, Santa Rosa, CA USA. RP Fleming, LM (reprint author), BIDMC Med, 330 Brookline Ave,HCA Atrium Suite, Boston, MA USA. EM lisa.fleming04@gmail.com NR 35 TC 2 Z9 2 U1 0 U2 1 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 AUG 1 PY 2012 VL 80 IS 2 BP E23 EP E29 DI 10.1002/ccd.23332 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977GY UT WOS:000306645900005 PM 22109802 ER PT J AU Kulkarni, RN AF Kulkarni, Rohit N. TI Identifying Biomarkers of Subclinical Diabetes SO DIABETES LA English DT Editorial Material ID GIP; PROLIFERATION; POLYPEPTIDE; PROFILES; RECEPTOR; ISLET; MICE C1 [Kulkarni, Rohit N.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kulkarni, Rohit N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu FU NIDDK NIH HHS [R01-DK67536, R01 DK067536] NR 14 TC 4 Z9 6 U1 2 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2012 VL 61 IS 8 BP 1925 EP 1926 DI 10.2337/db12-0599 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980KC UT WOS:000306891100006 PM 22826312 ER PT J AU Greenbaum, CJ Beam, CA Boulware, D Gitelman, SE Gottlieb, PA Herold, KC Lachin, JM McGee, P Palmer, JP Pescovitz, MD Krause-Steinrauf, H Skyler, JS Sosenko, JM AF Greenbaum, Carla J. Beam, Craig A. Boulware, David Gitelman, Stephen E. Gottlieb, Peter A. Herold, Kevan C. Lachin, John M. McGee, Paula Palmer, Jerry P. Pescovitz, Mark D. Krause-Steinrauf, Heidi Skyler, Jay S. Sosenko, Jay M. CA Type 1 Diabet TrialNet Study Grp TI Fall in C-Peptide During First 2 Years From Diagnosis Evidence of at Least Two Distinct Phases From Composite Type 1 Diabetes Trial Net Data SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; ANTI-CD3 MONOCLONAL-ANTIBODY; NATURAL-HISTORY; TOLERANCE-TEST; DOUBLE-BLIND; ONSET; INSULIN; MELLITUS; THERAPY; RISK AB Interpretation of clinical trials to alter the decline in beta-cell function after diagnosis of type 1 diabetes depends on a robust understanding of the natural history of disease. Combining data from the Type 1 Diabetes TrialNet studies, we describe the natural history of beta-cell function from shortly after diagnosis through 2 years post study randomization, assess the degree of variability between patients, and investigate factors that may be related to C-peptide preservation or loss. We found that 93% of individuals have detectable C-peptide 2 years from diagnosis. In 11% of subjects, there was no significant fall from baseline by 2 years. There was a biphasic decline in C-peptide; the C-peptide slope was -0.0245 pmol/mL/month (95% CI -0.0271 to -0.0215) through the first 12 months and -0.0079 (-0.0113 to -0.0050) from 12 to 24 months (P < 0.001). This pattern of fall in C-peptide over time has implications for understanding trial results in which effects of therapy are most pronounced early and raises the possibility that there are time-dependent differences in pathophysiology. The robust data on the C-peptide obtained under clinical trial conditions should be used in planning and interpretation of clinical trials. Diabetes 61:2066-2073, 2012 C1 [Greenbaum, Carla J.] Benaroya Res Inst, Seattle, WA USA. [Beam, Craig A.; Boulware, David] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. [Gitelman, Stephen E.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Gottlieb, Peter A.] Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Herold, Kevan C.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Lachin, John M.; McGee, Paula; Krause-Steinrauf, Heidi] George Washington Univ, Ctr Biostat, Washington, DC USA. [Palmer, Jerry P.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Palmer, Jerry P.] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Pescovitz, Mark D.] Indiana Univ, Dept Surg, Indianapolis, IN 46204 USA. [Pescovitz, Mark D.] Indiana Univ, Dept Microbiol & Immunol, Indianapolis, IN 46204 USA. [Skyler, Jay S.; Sosenko, Jay M.] Univ Miami, Diabet Res Inst, Miami, FL USA. RP Greenbaum, CJ (reprint author), Benaroya Res Inst, Seattle, WA USA. EM cjgreen@benaroyaresearch.org RI Skyler, Jay/F-4211-2016; OI Lachin, John/0000-0001-9838-2841; Gallagher, Mary/0000-0002-5844-2309 FU National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, U01-DK-085509, HHSN267200800019C]; National Center for Research Resources [UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986]; General Clinical Research Center Award [M01-RR-00400]; Juvenile Diabetes Research Foundation International (JDRF); American Diabetes Association (ADA) FX The sponsor of the trial was the Type 1 Diabetes Trial Net Study Group. Type I Diabetes Trial Net Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through Cooperative Agreements U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, U01-DK-085509, and Contract HHSN267200800019C, the National Center for Research Resources, through Clinical Translational Science Awards UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986, and General Clinical Research Center Award M01-RR-00400, the Juvenile Diabetes Research Foundation International (JDRF), and the American Diabetes Association (ADA). NR 33 TC 85 Z9 86 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2012 VL 61 IS 8 BP 2066 EP 2073 DI 10.2337/db11-1538 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980KC UT WOS:000306891100022 PM 22688329 ER PT J AU Wang, ZW Cheng, ZY Cristofaro, V Li, JJ Xiao, XY Gomez, P Ge, RB Gong, E Strle, K Sullivan, MP Adam, RM White, MF Olumi, AF AF Wang, Zongwei Cheng, Zhiyong Cristofaro, Vivian Li, Jijun Xiao, Xingyuan Gomez, Pablo Ge, Rongbin Gong, Edward Strle, Klemen Sullivan, Maryrose P. Adam, Rosalyn M. White, Morris F. Olumi, Aria F. TI Inhibition of TNF-alpha Improves the Bladder Dysfunction That Is Associated With Type 2 Diabetes SO DIABETES LA English DT Article ID TRAIL-INDUCED APOPTOSIS; SMOOTH-MUSCLE; URINARY-BLADDER; ENDOTHELIAL-CELLS; IN-VITRO; MICE; RATS; KINASE; RHO; INFLAMMATION AB Diabetic bladder dysfunction (DBD) is common and affects 80% of diabetic patients. However, the molecular mechanisms underlying DBD remain elusive because of a lack of appropriate animal models. We demonstrate DBD in a mouse model that harbors hepatic-specific insulin receptor substrate 1 and 2 deletions (double knockout [DKO]), which develops type 2 diabetes. Bladders of DKO animals exhibited detrusor overactivity at an early stage: increased frequency of nonvoiding contractions during bladder filling, decreased voided volume, and dispersed urine spot patterns. In contrast, older animals with diabetes exhibited detrusor hypoactivity, findings consistent with clinical features of diabetes in humans. The tumor necrosis factor (TNF) superfamily genes were upregulated in DKO bladders. In particular, TNF-alpha was upregulated in serum and in bladder smooth muscle tissue. TNF-alpha augmented the contraction of primary cultured bladder smooth muscle cells through upregulating Rho kinase activity and phosphotylating myosin light chain. Systemic treatment of DKO animals with soluble TNF receptor 1 (TNFRI) prevented upregulation of Rho A signaling and reversed the bladder dysfunction, without affecting hyperglycemia. TNFRI combined with the antidiabetic agent, metfonnin, improved DBD beyond that achieved with metformin alone, suggesting that therapies targeting TNF-alpha may have utility in reversing the secondary urologic complications of type 2 diabetes. Diabetes 61:2134-2145,2012 C1 [Wang, Zongwei; Li, Jijun; Xiao, Xingyuan; Ge, Rongbin; Olumi, Aria F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02115 USA. [Cheng, Zhiyong; White, Morris F.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Endocrinol,Childrens Hosp Boston, Boston, MA 02115 USA. [Cristofaro, Vivian; Sullivan, Maryrose P.] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Boston, MA USA. [Li, Jijun] Shanghai Jiao Tong Univ, Sch Med, Dept Integrat Med, Shanghai Childrens Med Ctr, Shanghai 200030, Peoples R China. [Xiao, Xingyuan] Huazhong Univ Sci & Technol, Wuhan Union Hosp, Dept Urol, Wuhan 430074, Peoples R China. [Gomez, Pablo; Gong, Edward; Adam, Rosalyn M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Urol Res Ctr, Boston, MA USA. [Strle, Klemen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Allergy Immunol, Boston, MA USA. RP Olumi, AF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02115 USA. EM olumi.aria@mgh.harvard.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant [09MCG72]; American Urological Association/Pfizer Pharmaceutical Company FX This work was funded by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant (Animal Models of Diabetic Complications Pilot & Feasibility Project, 09MCG72) and the American Urological Association/Pfizer Pharmaceutical Company competitive grants to A.F.O. No other potential conflicts of interest relevant to this article were reported. NR 40 TC 17 Z9 19 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2012 VL 61 IS 8 BP 2134 EP 2145 DI 10.2337/db11-1763 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980KC UT WOS:000306891100029 PM 22688336 ER PT J AU Billings, LK Hsu, YH Ackerman, RJ Dupuis, J Voight, BF Rasmussen-Torvik, LJ Hercberg, S Lathrop, M Barnes, D Langenberg, C Hui, JN Fu, M Bouatia-Naji, N Lecoeur, C An, P Magnusson, PK Surakka, I Ripatti, S Christiansen, L Dalgard, C Folkersen, L Grundberg, E Eriksson, P Kaprio, J Kyvik, KO Pedersen, NL Borecki, IB Province, MA Balkau, B Froguel, P Shuldiner, AR Palmer, LJ Wareham, N Meneton, P Johnson, T Pankow, JS Karasik, D Meigs, JB Kiel, DP Florez, JC AF Billings, Liana K. Hsu, Yi-Hsiang Ackerman, Rachel J. Dupuis, Josee Voight, Benjamin F. Rasmussen-Torvik, Laura J. Hercberg, Serge Lathrop, Mark Barnes, Daniel Langenberg, Claudia Hui, Jennie Fu, Mao Bouatia-Naji, Nabila Lecoeur, Cecile An, Ping Magnusson, Patrik K. Surakkaza, Ida Ripatti, Samuli Christiansen, Lene Dalgard, Christine Folkersen, Lasse Grundberg, Elin Eriksson, Per Kaprio, Jaakko Kyvik, Kirsten Ohm Pedersen, Nancy L. Borecki, Ingrid B. Province, Michael A. Balkau, Beverley Froguel, Philippe Shuldiner, Alan R. Palmer, Lyle J. Wareham, Nick Meneton, Pierre Johnson, Toby Pankow, James S. Karasik, David Meigs, James B. Kiel, Douglas P. Florez, Jose C. CA MAGIC Investigators DIAGRAM Consortium MuTHER Consortium ASCOT Investigators GEFOS Consortium TI Impact of Common Variation in Bone-Related Genes on Type 2 Diabetes and Related Traits SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; MINERAL DENSITY; FRACTURE RISK; OSTEOPOROTIC FRACTURES; INSULIN-RESISTANCE; ENERGY-METABOLISM; FASTING GLUCOSE; LOCI; METAANALYSIS AB Exploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in similar to 19,000 individuals and assessed gene expression. We queried single nucleotide polymorphisms (SNPs) associated with BMD at levels of genome-wide significance, variants in linkage disequilibrium (r(2) > 0.5), and BMD candidate genes. SNP rs6867040, at the ITGA1 locus, was associated with a 0.0166 mmol/L (0.004) increase in fasting glucose per C allele in the combined analysis. Genetic variants in the ITGA1 locus were associated with its expression in the liver but not in adipose tissue. ITGA1 variants appeared among the top loci associated with type 2 diabetes, fasting insulin, beta-cell function by homeostasis model assessment, and 2-h post-oral glucose tolerance test glucose and insulin levels. ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in liver fibrosis, insulin secretion, and bone healing lends credence to its contribution to both osteoporosis and type 2 diabetes. These findings further underscore the link between skeletal and glucose metabolism and highlight a locus to direct future investigations. Diabetes 61:2176-2186, 2012 C1 [Billings, Liana K.; Ackerman, Rachel J.; Voight, Benjamin F.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Billings, Liana K.; Voight, Benjamin F.; Meigs, James B.; Kiel, Douglas P.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Billings, Liana K.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Hebrew Senior Life Inst Aging Res, Boston, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA. [Hsu, Yi-Hsiang; Dupuis, Josee; Karasik, David; Meigs, James B.; Kiel, Douglas P.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Voight, Benjamin F.; Florez, Jose C.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Rasmussen-Torvik, Laura J.; Florez, Jose C.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Hercberg, Serge] Univ Paris, INSERM, Natl Inst Agron Res, Bobigny, France. [Lathrop, Mark] Atom Energy Commiss, Natl Genotyping Ctr, Inst Genom, Evry, France. [Barnes, Daniel; Langenberg, Claudia; Wareham, Nick] Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England. [Hui, Jennie] PathWest Lab Med Western Australia, Nedlands, WA, Australia. [Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia. [Hui, Jennie] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Hui, Jennie] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn, Nedlands, WA 6009, Australia. [Fu, Mao; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Bouatia-Naji, Nabila; Lecoeur, Cecile; Froguel, Philippe] Lille Nord France Univ, Natl Ctr Sci Res, UMR 8199, Lille Pasteur Inst, Lille, France. [An, Ping; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [An, Ping; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Magnusson, Patrik K.; Pedersen, Nancy L.; Province, Michael A.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Surakkaza, Ida; Ripatti, Samuli; Kaprio, Jaakko] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Surakkaza, Ida; Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Christiansen, Lene] Univ So Denmark, Inst Publ Hlth, Danish Twin Registry, Odense, Denmark. [Dalgard, Christine] Univ So Denmark, Dept Environm Med, Inst Publ Hlth, Odense, Denmark. [Folkersen, Lasse; Eriksson, Per] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden. [Grundberg, Elin] Wellcome Trust Sanger Inst, Hinxton, England. [Grundberg, Elin] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. Erasmus Med Coll, Coordinating Ctr, Rotterdam, Netherlands. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Unit Child & Adolescent Mental Hlth, Helsinki, Finland. [Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Kyvik, Kirsten Ohm] Univ So Denmark, Inst Reg Hlth Serv Res, Odense, Denmark. [Kyvik, Kirsten Ohm] Odense Univ Hosp, Odense Patient Data Explorat Network, DK-5000 Odense, Denmark. [Balkau, Beverley] INSERM, CESP Ctr Res Epidemiol & Hlth Populat, U1018, Epidemiol Diabet Obes & Chron Kidney Dis Life Cou, Villejuif, France. [Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Shuldiner, Alan R.] Baltimore VA Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. [Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Meneton, Pierre] INSERM, Cordeliers Ctr Res, Paris, France. [Johnson, Toby] Queen Mary Univ London, Clin Pharmacol & Genome Ctr, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jcflorez@partners.org RI Palmer, Lyle/K-3196-2014; Ripatti, Samuli/H-9446-2014; Kyvik, Kirsten /K-5680-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Magnusson, Patrik/C-4458-2017; OI Kaprio, Jaakko/0000-0002-3716-2455; Pankow, James/0000-0001-7076-483X; Karasik, David/0000-0002-8826-0530; Folkersen, Lasse/0000-0003-0708-9530; Palmer, Lyle/0000-0002-1628-3055; Ripatti, Samuli/0000-0002-0504-1202; Kyvik, Kirsten /0000-0003-2981-0245; Bouatia-Naji, Nabila/0000-0001-5424-2134; Barnes, Daniel/0000-0002-3781-7570; Johnson, Toby/0000-0002-5998-3270; Dupuis, Josee/0000-0003-2871-3603; Kiel, Douglas/0000-0001-8474-0310 FU National Research Service Award Institutional Training Grant [T32-DK-007028-35]; National Institutes of Health (NIH) Loan Repayment Award National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1-L30-DK-089944-01]; Endocrine Society Lilly Endocrine Scholars Award; Doris Duke Charitable Foundation Distinguished Scientist Clinical Award; NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R21-AR-056405]; NIDDK [R0I-DK-078616, R01-DK-078616, NIDDK K24-DK-080140, 5-R01-DK-07568102, 5-R01-DK-06833603]; NIAMS; National Institute on Aging Grant [R01-AR/AG-41398]; Doris Duke Charitable Foundation Clinical Scientist Development Award; European Commission [HEALTH-F2-2008-201865-GEFOS, Health-F2-2008-200647]; National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN2682011000 06C, HHSN268201100007C, HEISN268201100008C, HHSN26 8201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01-HL-087641, R01-HL-59367, R01-HL-086694]; National Human Genome Research Institute contract [U01-HG-004402]; NIH [HHSN26 8200625226C, U01-HL-72515, R0I-DK-04261, R01-AG-18728]; Wellcome Trust; Medical Research Council; Healthway, Western Australia [199411995]; University of Maryland General Clinical Research Center Grant [M01-RR-16500]; Mid-Atlantic Nutrition and Obesity Research Center [P30-DK-072488]; Baltimore Diabetes Research and Training Center [P60-DK-079637]; Baltimore Veterans Administration Medical Center Geriatric Research and Education Clinical Center; Conseil Regional Nord-Pas-de-Calais: Fonds europeen de developpement economique et regional; Genome Quebec Genome Canada; British Medical Research Council; NIH from the NIMBI [5-R01-HL-08770003, 5-R01-BL-08821502]; European Commission under the program Quality of Life and Management of the Living Resources of Fifth Framework Programme [QLG2-CT-2002-01254]; European Community's Seventh Framework Programme [FP7/2007-2013]; ENGAGE Consortium; Danish Medical Research Council; Danish Heart Association; Danish Diabetes Association; GenomEUtwin; NHLBI's FHS [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; NIH National Center for Research Resources Shared Instrumentation Grant [1-S10-RR-163736-01A1]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Swedish Research Council [12660]; Swedish Heart-Lung Foundation; [HEALTH-F4-2007-201413] FX L.K.B. has received support from National Research Service Award Institutional Training Grant T32-DK-007028-35 to the Massachusetts General Hospital, National Institutes of Health (NIH) Loan Repayment Award National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1-L30-DK-089944-01, the Endocrine Society Lilly Endocrine Scholars Award, and a Doris Duke Charitable Foundation Distinguished Scientist Clinical Award to David Altshuler. Y.-H.H. was supported by NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Grant R21-AR-056405. J.D. has received support from NIDDK R0I-DK-078616. J.B.M. was supported by NIDDK R01-DK-078616 and NIDDK K24-DK-080140. D.P.K. has received support from NIAMS and National Institute on Aging Grant R01-AR/AG-41398. J.C.F. was supported by NIDDK R01-DK-078616 and a Doris Duke Charitable Foundation Clinical Scientist Development Award.; The authors would like to thank Denis Rybin at Boston University School of Public Health for creating Fig. 2. The authors acknowledge the contribution of the GIANT Consortium, which provided summary statistics for the association between selected SNPs and BMI. Individual cohort acknowledgments are as follows: GEFOS Consortium (www.gefos.org) is funded by the European Commission (HEALTH-F2-2008-201865-GEFOS). ARIC is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN2682011000 06C, HHSN268201100007C, HEISN268201100008C, HHSN26 8201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01-HL-087641, R01-HL-59367, and R01-HL-086694, National Human Genome Research Institute contract U01-HG-004402, and NIH contract HHSN26 8200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure of the ARIC study was partly supported by Grant UL1-RR-025005, a component of the NIH and NIH Roadmap for Medical Research. The Fenland Study is funded by the Wellcome Trust and the Medical Research Council. The authors are grateful to all the volunteers for their time and help and to the general practitioners and practice staff for help with recruitment The authors thank the Fen land Study Investigators, Fen land Study Co-ordination Team and the Epidemiology Field, Data, and Technical Teams. Biochemical assays were performed by the National Institute for Health Research, Cambridge Biomedical Research Centre, Core Biochemistry Assay Laboratory, and the Cambridge University Hospitals National Health Service Foundation Trust, Department of Clinical Biochemistry. The BHS acknowledges the generous support for the 199411995 follow-up study from Healthway, Western Australia, and the numerous Busselton community volunteers who assisted with data collection and the study participants from the Shire of Busselton. The BHS is supported by the Great Wine Estates of the Margaret River region of Western Australia The AMISH Cohort was supported by NIH research grants U01-HL-72515, R0I-DK-04261, and R01-AG-18728; University of Maryland General Clinical Research Center Grant M01-RR-16500; the Mid-Atlantic Nutrition and Obesity Research Center (P30-DK-072488); the Baltimore Diabetes Research and Training Center (P60-DK-079637); and the Baltimore Veterans Administration Medical Center Geriatric Research and Education Clinical Center. French genetic studies (DESIR and French Obese) were supported in part by the Conseil Regional Nord-Pas-de-Calais: Fonds europeen de developpement economique et regional, Genome Quebec Genome Canada and the British Medical Research Council. The authors acknowledge INSERM (employer of N.B.-N.). FamHS work was supported in part by NIH grants 5-R01-HL-08770003 and 5-R01-BL-08821502 from the NIMBI (to M.A.P.) and 5-R01-DK-07568102 and 5-R01-DK-06833603 from NIDDK (to I.B.B.). The GenomEUtwin project is supported by the European Commission under the program Quality of Life and Management of the Living Resources of Fifth Framework Programme (no. QLG2-CT-2002-01254) and the European Community's Seventh Framework Programme (FP7/2007-2013), ENGAGE Consortium, Grant Agreement HEALTH-F4-2007-201413. The Swedish Twin Cohort would like to acknowledge the Swedish Research Council and the Swedish Foundation for Strategic Research. The Finnish Twin Cohort would like to acknowledge the Center of Excellence in Complex Disease Genetics of the Academy of Finland.; The GEMINAKAR study was supported by the Danish Medical Research Council, the Danish Heart Association, the Danish Diabetes Association, and GenomEUtwin. The FHS component of this work was supported by the NHLBI's FHS (Contract N01-HC-25195), its contract with Affymetrix, Inc. for genotyping services (Contract N02-HL-6-4278), and the resources of the FHS SNP Health Association Resource (SHARe) project, the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the NIH National Center for Research Resources Shared Instrumentation Grant 1-S10-RR-163736-01A1, and the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The ASAP study liver eQTL data were supported by the Swedish Research Council (12660), the Swedish Heart-Lung Foundation, the European Commission (FAD, Health-F2-2008-200647), and a donation by Fredrik Lundberg. NR 51 TC 7 Z9 9 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD AUG PY 2012 VL 61 IS 8 BP 2176 EP 2186 DI 10.2337/db11-1515 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980KC UT WOS:000306891100033 PM 22698912 ER PT J AU Williams, WW Salem, RM McKnight, AJ Sandholm, N Forsblom, C Taylor, A Guiducci, C McAteer, JB McKay, GJ Isakova, T Brennan, EP Sadlier, DM Palmer, C Soderlund, J Fagerholm, E Harjutsalo, V Lithovius, R Gordin, D Hietala, K Kyto, J Parkkonen, M Rosengard-Barlund, M Thorn, L Syreeni, A Tolonen, N Saraheimo, M Waden, J Pitkaniemi, J Sarti, C Tuomilehto, J Tryggvason, K Osterholm, AM He, B Bain, S Martin, F Godson, C Hirschhorn, JN Maxwel, AP Groop, PH Florez, JC AF Williams, Winfred W. Salem, Rany M. McKnight, Amy Jayne Sandholm, Niina Forsblom, Carol Taylor, Andrew Guiducci, Candace McAteer, Jarred B. McKay, Gareth J. Isakova, Tamara Brennan, Eoin P. Sadlier, Denise M. Palmer, Cameron Soederlund, Jenny Fagerholm, Emma Harjutsalo, Valma Lithovius, Raija Gordin, Daniel Hietala, Kustaa Kyto, Janne Parkkonen, Maija Rosengard-Barlund, Milla Thorn, Lena Syreeni, Anna Tolonen, Nina Saraheimo, Markku Waden, Johan Pitkaniemi, Jamie Sarti, Cinzia Tuomilehto, Jaakko Tryggvason, Karl Osterholm, Anne-May He, Bing Bain, Steve Martin, Finian Godson, Catherine Hirschhorn, Joel N. Maxwel, Alexander P. Groop, Per-Henrik Florez, Jose C. CA GENIE Consortium TI Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; GENETIC SUSCEPTIBILITY; PIMA-INDIANS; POPULATION; DISEASE; LINKAGE; SCAN AB We formed the GEnetics of Nephropathy-an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 x 10(-9)). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated. Diabetes 61:2187-2194, 2012 C1 [Williams, Winfred W.; Taylor, Andrew; McAteer, Jarred B.; Godson, Catherine; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Williams, Winfred W.; Salem, Rany M.; Taylor, Andrew; Guiducci, Candace; McAteer, Jarred B.; Palmer, Cameron; Godson, Catherine; Hirschhorn, Joel N.; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Williams, Winfred W.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Williams, Winfred W.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Salem, Rany M.; Palmer, Cameron; Hirschhorn, Joel N.] Childrens Hosp, Dept Endocrinol, Endocrine Res Unit, Boston, MA 02115 USA. [McKnight, Amy Jayne; McKay, Gareth J.; Maxwel, Alexander P.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Sandholm, Niina; Forsblom, Carol; Soederlund, Jenny; Fagerholm, Emma; Harjutsalo, Valma; Lithovius, Raija; Gordin, Daniel; Hietala, Kustaa; Kyto, Janne; Parkkonen, Maija; Rosengard-Barlund, Milla; Thorn, Lena; Syreeni, Anna; Tolonen, Nina; Saraheimo, Markku; Waden, Johan; Sarti, Cinzia; Groop, Per-Henrik] Biomedicum, Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland. [Sandholm, Niina; Forsblom, Carol; Soederlund, Jenny; Fagerholm, Emma; Harjutsalo, Valma; Lithovius, Raija; Gordin, Daniel; Parkkonen, Maija; Rosengard-Barlund, Milla; Thorn, Lena; Syreeni, Anna; Tolonen, Nina; Saraheimo, Markku; Waden, Johan; Groop, Per-Henrik] Univ Helsinki, Cent Hosp, Dept Med, Div Nephrol, Helsinki, Finland. [Sandholm, Niina] Aalto Univ, Dept Biomed Engn & Computat Sci, Helsinki, Finland. [Taylor, Andrew; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Isakova, Tamara] Univ Miami, Miller Sch Med, Div Nephrol, Miami, FL 33136 USA. [Brennan, Eoin P.; Sadlier, Denise M.; Martin, Finian] Univ Coll Dublin, Conway Inst, UCD Diabet Res Ctr, Dublin 2, Ireland. [Brennan, Eoin P.; Sadlier, Denise M.; Godson, Catherine] Univ Coll Dublin, Sch Med, Dublin 2, Ireland. [Sadlier, Denise M.] Mater Univ Hosp, Dublin, Ireland. [Harjutsalo, Valma; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Welf & Hlth Promot Div, Dept Chron Dis Prevent, Helsinki, Finland. [Hietala, Kustaa; Kyto, Janne] Univ Helsinki, Cent Hosp, Dept Ophthalmol, Helsinki, Finland. [Kyto, Janne; Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Tryggvason, Karl; Osterholm, Anne-May; He, Bing] Karolinska Inst, Dept Med Biochem & Biophys, Div Matrix Biol, Stockholm, Sweden. [Bain, Steve] Swansea Univ, Inst Life Sci, Swansea, W Glam, Wales. [Martin, Finian] Univ Coll Dublin, Sch Biomol & Biomed Sci, Dublin 2, Ireland. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jcflorez@partners.org RI Tolonen, Nina/F-2819-2012; OI McKnight, Amy Jayne/0000-0002-7482-709X; Sandholm, Niina/0000-0003-4322-6942; Maxwell, Alexander P./0000-0002-6110-7253 FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Grant [R01-DK-081923]; Science Foundation Ireland U.S.-Ireland RD partnership; Health Research Board Ireland; Juvenile Diabetes Research Foundation postdoctoral fellowship [3-2011-70]; Folkhalsan Research Foundation; Wilhelm and Else Stockmann Foundation; Livoch Halsa Foundation; Helsinki University Central Hospital Research Funds; Sigrid Juselius Foundation; Signe and Arne Gyllenberg Foundation; Finska Lakaresallskapet; European Commission; European Union's Seventh Framework Program [IMI/115006] FX Funding for this study was provided by National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK-081923 to J.N.H., P.-H.G., and J.C.F., a Science Foundation Ireland U.S.-Ireland R&D partnership, and The Health Research Board Ireland. R.M.S. was supported by a Juvenile Diabetes Research Foundation postdoctoral fellowship (#3-2011-70). The Finn Diane Study was supported by grants from the Folkhalsan Research Foundation, the Wilhelm and Else Stockmann Foundation, Livoch Halsa Foundation, Helsinki University Central Hospital Research Funds (EVO), the Sigrid Juselius Foundation, the Signe and Arne Gyllenberg Foundation, Finska Lakaresallskapet, the European Commission, and the European Union's Seventh Framework Program (FP7/2007-2013) for the Innovative Medicine Initiative under Grant Agreement No. IMI/115006 (the Surrogate Markers for Micro- and Macro-vascular Hard Endpoints for Innovative Diabetes Tools [SUMMIT] consortium). NR 32 TC 40 Z9 41 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2012 VL 61 IS 8 BP 2187 EP 2194 DI 10.2337/db11-0751 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980KC UT WOS:000306891100034 PM 22721967 ER PT J AU Rovner, AJ Nansel, TR Mehta, SN Higgins, LA Haynie, DL Laffel, LM AF Rovner, Alisha J. Nansel, Tonja R. Mehta, Sanjeev N. Higgins, Laurie A. Haynie, Denise L. Laffel, Lori M. TI Development and Validation of the Type 1 Diabetes Nutrition Knowledge Survey SO DIABETES CARE LA English DT Article ID GLYCEMIC CONTROL; COMPLICATIONS TRIAL; CHILDREN; YOUTH; CARBOHYDRATE; ADOLESCENTS; BEHAVIORS; MELLITUS; THERAPY; OBESITY AB OBJECTIVE-The purpose of this study was to develop a survey of general and diabetes-specific nutrition knowledge for youth with type 1 diabetes and their parents and to assess the survey's psychometric properties. RESEARCH DESIGN AND METHODS-A multidisciplinary pediatric team developed the Nutrition Knowledge Survey (NKS) and administered it to youth with type I diabetes (n = 282,49% females, 13.3 +/- 2.9 years) and their parents (82% mothers). The NKS content domains included healthful eating, carbohydrate counting, blood glucose response to foods, and nutrition label reading. Higher NKS scores reflect greater nutrition knowledge (score range is 0-100%). In youths, glycemic control was assessed by A1C, and dietary quality was determined by the Healthy Eating Index-2005 (HEI-2005) derived from 3-day diet records. Validity was based on associations of NKS scores with A1C and dietary quality. Reliability was assessed using the Kuder-Richardson Formula 20 (KR-20) and correlations of domain scores to total score. RESULTS-Mean NKS scores (23 items) were 56.9 +/- 16.4% for youth and 73.4 +/- 12.5% for parents. The KR-20 was 0.70 for youth and 0.59 for parents, representing acceptable internal consistency of the measure. In multivariate analysis, controlling for youth age, family income, parent education, diabetes duration, and insulin regimen, parent NKS scores were associated with corresponding youth A1C (beta = -0.13, P = 0.03). Both parent (beta = 0.20, P = 0.002) and youth (beta = 0.25, P < 0.001) NKS scores were positively associated with youth HEI-2005 scores. CONCLUSIONS-The NKS appears to be a useful measure of general and diabetes-specific nutrition knowledge for youth with type 1 diabetes and their parents. C1 [Rovner, Alisha J.; Nansel, Tonja R.; Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. [Mehta, Sanjeev N.; Higgins, Laurie A.; Laffel, Lori M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02115 USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HH-SN-267200703434C] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract HH-SN-267200703434C). NR 20 TC 4 Z9 4 U1 0 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2012 VL 35 IS 8 BP 1643 EP 1647 DI 10.2337/dc11-2371 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980KD UT WOS:000306891200004 PM 22665217 ER PT J AU Garvey, KC Wolpert, HA Rhodes, ET Laffel, LM Kleinman, K Beste, MG Wolfsdorf, JI Finkelstein, JA AF Garvey, Katharine C. Wolpert, Howard A. Rhodes, Erinn T. Laffel, Lori M. Kleinman, Ken Beste, Margaret G. Wolfsdorf, Joseph I. Finkelstein, Jonathan A. TI Health Care Transition in Patients With Type 1 Diabetes Young adult experiences and relationship to glycemic control SO DIABETES CARE LA English DT Article ID FOLLOW-UP; ADOLESCENTS; MELLITUS; SYSTEMS; CHILDREN; PEOPLE; FAMILY; COHORT; YOUTH AB OBJECTIVE-To examine characteristics of the transition from pediatric to adult care in emerging adults with type 1 diabetes and evaluate associations between transition characteristics and glycemic control. RESEARCH DESIGN AND METHODS-We developed and mailed a survey to evaluate the transition process in emerging adults with type 1 diabetes, aged 22 to 30 years, receiving adult diabetes care at a single center. Current A1C data were obtained from the medical record. RESULTS-The response rate was 53% (258 of 484 eligible). The mean transition age was 19.5 +/- 2.9 years, and 34% reported a gap >6 months in establishing adult care. Common reasons for transition included feeling too old (44%), pediatric provider suggestion (41%), and college (33%). Less than half received an adult provider recommendation and <15% reported having a transition preparation visit or receiving written transition materials. The most recent A1C was 8.1 +/- 1.3%. Respondents who felt mostly/completely prepared for transition had lower likelihood of a gap >6 months between pediatric and adult care (adjusted odds ratio 0.47 [95% CI 0.25-0.88]). In multivariate analysis, pretransition A1C (beta = 0.49, P < 0.0001), current age (beta = -0.07, P = 0.03), and education (beta = -0.55, P = 0.01) significantly influenced current posttransition A1C. There was no independent association of transition preparation with posttransition A1C (beta = -0.17, P = 0.28). CONCLUSIONS-Contemporary transition practices may help prevent gaps between pediatric and adult care but do not appear to promote improvements in A1C. More robust preparation strategies and handoffs between pediatric and adult care should be evaluated. C1 [Garvey, Katharine C.; Rhodes, Erinn T.; Wolfsdorf, Joseph I.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Wolpert, Howard A.; Beste, Margaret G.] Joslin Diabet Ctr, Adult Sect, Boston, MA 02215 USA. [Laffel, Lori M.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Kleinman, Ken; Finkelstein, Jonathan A.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Finkelstein, Jonathan A.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. RP Garvey, KC (reprint author), Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. EM katharine.garvey@childrens.harvard.edu FU Agency for Healthcare Research and Quality as part of the Harvard Pediatric Health Services [T32-HS000063]; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007699-30]; William Randolph Hearst Foundation; National Institute of Child Health and Human Development [K24-HD-060786] FX K.C.G. was supported by the Agency for Healthcare Research and Quality (T32-HS000063) as part of the Harvard Pediatric Health Services Research Fellowship, as well as the National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007699-30) and the William Randolph Hearst Foundation. J.A.F. was funded by a grant from the National Institute of Child Health and Human Development (K24-HD-060786). NR 29 TC 38 Z9 41 U1 3 U2 14 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2012 VL 35 IS 8 BP 1716 EP 1722 DI 10.2337/dc11-2434 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980KD UT WOS:000306891200016 PM 22699289 ER PT J AU Laste, G Caumo, W Adachi, LNS Rozisky, JR de Macedo, IC Marques, PR Partata, WA Fregni, F Torres, ILS AF Laste, Gabriela Caumo, Wolnei Spezia Adachi, Lauren Naomi Rozisky, Joanna Ripoll de Macedo, Isabel Cristina Marques Filho, Paulo Ricardo Partata, Wania Aparecida Fregni, Felipe Torres, Iraci L. S. TI After-effects of consecutive sessions of transcranial direct current stimulation (tDCS) in a rat model of chronic inflammation SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Transcranial direct current stimulation (tDCS); Motor cortex; Neuromodulation; Inflammatory pain ID MOTOR CORTEX STIMULATION; CHRONIC NEUROPATHIC PAIN; DC-STIMULATION; BRAIN-STIMULATION; NERVE-TERMINALS; SPINAL-CORD; EXCITABILITY; MECHANISMS; MEMORY; HYPERSENSITIVITY AB Transcranial direct current stimulation (tDCS) induces cortical excitability changes in animals and humans that can last beyond the duration of stimulation. Preliminary evidence suggests that tDCS may have an analgesic effect; however, the timing of these effects, especially when associated with consecutive sessions of stimulation in a controlled animal experiment setting, has yet to be fully explored. To evaluate the effects of tDCS in inflammatory chronic pain origin immediately and 24 h after the last treatment session, complete Freund's adjuvant (CFA) was injected (100 mu l) in the right footpad to induce inflammation. On the 15th day after CFA injection, rats were divided into two groups: tDCS (n = 9) and sham (n = 9). The tDCS was applied for 8 days. The hot plate and Von Frey tests were applied immediately and 24 h after the last tDCS session. Eight 20-min sessions of 500 mu A anodal tDCS resulted in antinociceptive effects as assessed by the hot plate test immediately (P = 0.04) and 24 h after the last tDCS session (P = 0.006), for the active tDCS group only. There was increased withdrawal latency in the Von Frey test at 24 h after the last session (P = 0.01). Our findings confirm the hypothesis that tDCS induces significant, long-lasting, neuroplastic effects and expands these findings to a chronic pain model of peripheral inflammation, thus supporting the exploration of this technique in conditions associated with chronic pain and peripheral inflammation, such as osteoarthritis. C1 [Laste, Gabriela; Caumo, Wolnei; Spezia Adachi, Lauren Naomi; Rozisky, Joanna Ripoll; de Macedo, Isabel Cristina; Marques Filho, Paulo Ricardo; Torres, Iraci L. S.] Univ Fed Rio Grande do Sul, Dept Pharmacol, Inst Basic Hlth Sci, BR-90050170 Porto Alegre, RS, Brazil. [Laste, Gabriela; Caumo, Wolnei; Spezia Adachi, Lauren Naomi; Rozisky, Joanna Ripoll; de Macedo, Isabel Cristina; Marques Filho, Paulo Ricardo; Torres, Iraci L. S.] Anim Models Lab, Porto Alegre, RS, Brazil. [Laste, Gabriela; Caumo, Wolnei; Spezia Adachi, Lauren Naomi; Rozisky, Joanna Ripoll; Torres, Iraci L. S.] Univ Fed Rio Grande do Sul, Grad Program Med Sci, BR-90050170 Porto Alegre, RS, Brazil. [Laste, Gabriela; Spezia Adachi, Lauren Naomi; Rozisky, Joanna Ripoll; de Macedo, Isabel Cristina; Torres, Iraci L. S.] Hosp Clin Porto Alegre, Anim Experimentat Unit, Grad Res Grp, Porto Alegre, RS, Brazil. [Partata, Wania Aparecida] Univ Fed Rio Grande do Sul, Dept Physiol, Inst Biol Sci, BR-90050170 Porto Alegre, RS, Brazil. [Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Ctr Noninvas Brain Stimulat, Sch Med, Boston, MA 02215 USA. RP Torres, ILS (reprint author), Univ Fed Rio Grande do Sul, Dept Pharmacol, Inst Basic Hlth Sci, Rua Sarmento Leite,500 Sala 202, BR-90050170 Porto Alegre, RS, Brazil. EM gabrielalaste@gmail.com; caumo@cpovo.net; lauren_adachi@hotmail.com; joannarozisky@gmail.com; icc.macedo@gmail.com; paulo.prmf1@gmail.com; partataw@gmail.com; fregni.felipe@mgh.harvard.edu; iracitorres@gmail.com RI Torres, iraci/G-6693-2012; Laste, Gabriela/A-3033-2014; Rozisky, Joanna/F-6584-2015; OI Torres, iraci/0000-0002-3081-115X; Macedo, Isabel Cristina/0000-0001-6215-1371 FU National Council for Scientific and Technological Development-CNPq [307772/2008-0/2008]; PROPESQ/UFRGS/PIBIC/CNPq : Committee for the Development of Higher Education Personnel-CAPES; Graduate Research Group (GPPG) of Hospital de Clinicas de Porto Alegre-HCPA [100013] FX This study was supported by the following Brazilian funding agencies: National Council for Scientific and Technological Development-CNPq (Dr. I. L. S. Torres, Grant no. 307772/2008-0/2008, Dr. W. Caumo); PROPESQ/UFRGS/PIBIC/CNPq : Committee for the Development of Higher Education Personnel-CAPES (J.R. Rozisky, G. Laste, L.S.N. Adachi); and Graduate Research Group (GPPG) of Hospital de Clinicas de Porto Alegre-HCPA (Dr I. L. S. Torres-Grant 100013). We would like to thank the engineering staff of HCPA for developing the tDCS stimulator. NR 74 TC 14 Z9 15 U1 0 U2 5 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 AUG PY 2012 VL 221 IS 1 BP 75 EP 83 DI 10.1007/s00221-012-3149-x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 977WT UT WOS:000306696200009 PM 22752510 ER PT J AU Lionetto, L Casolla, B Mastropietri, F D'Alonzo, L Negro, A Simmaco, M Martelletti, P AF Lionetto, Luana Casolla, Barbara Mastropietri, Fabiola D'Alonzo, Lidia Negro, Andrea Simmaco, Maurizio Martelletti, Paolo TI Pharmacokinetic evaluation of zolmitriptan for the treatment of migraines SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE zolmitriptan; pharmacokinetics; pharmacodynamics; triptans; migraine; menstrual-related-migraine; cluster hedache ID ANTIMIGRAINE COMPOUND ZOLMITRIPTAN; DOUBLE-BLIND; PHARMACOLOGICAL-TREATMENT; ABSOLUTE BIOAVAILABILITY; MYOCARDIAL-INFARCTION; TRIPTAN FORMULATIONS; HEALTHY-VOLUNTEERS; 5-HT1B/1D AGONISTS; RECEPTOR AGONIST; CLUSTER HEADACHE AB Introduction: Migraine is a multifactorial neurovascular disorder characterized by recurrent episodes of disabling pain attacks, accompanied with gastrointestinal, neurological systems dysfunction. The pharmacologic treatment of migraine is classically divided in the management of the acute attack and preventive strategies. Acute treatments consist of triptan, ergot, opioid, antiemetic and NSAIDs. Areas covered: This article discusses pharmacodynamics and pharmacokinetics of zolmitriptan. The data were obtained by searching the following keywords in MEDLINE: zolmitriptan, pharmacokinetics, pharmacodynamics, triptans, migraine, menstrual-related migraine, cluster headache, relatively to the period 1989 - 2012. Expert opinion: Zolmitriptan has been considered effective treatment in the acute phase of migraine, menstrual-related migraine and cluster headache attacks. Pharmacokinetic parameters may vary as a consequence of gender differences, inter- and intra-subjects variability and delivery system. Zolmitriptan was developed with the aim of obtaining a lipophilic compound in order to be more rapidly absorbed and centrally active. Pharmacologically, pharmacokinetic parameters are responsible for its wide efficacy and the limited adverse effect profile. C1 [D'Alonzo, Lidia; Negro, Andrea; Martelletti, Paolo] Univ Roma La Sapienza, Reg Referral Headache Ctr, Dept Clin & Mol Med, I-00189 Rome, Italy. [Lionetto, Luana; Casolla, Barbara; Mastropietri, Fabiola; Simmaco, Maurizio] Univ Roma La Sapienza, St Andrea Hosp, Adv Mol Diagnost Unit, NESMOS Dept, I-00189 Rome, Italy. [Negro, Andrea] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Stroke & Neurovasc Regulat, Boston, MA 02115 USA. RP Martelletti, P (reprint author), Univ Roma La Sapienza, Reg Referral Headache Ctr, Dept Clin & Mol Med, Via Grottarossa 1035, I-00189 Rome, Italy. EM paolo.martelletti@uniroma1.it RI Lionetto, Luana/J-3632-2016 OI Lionetto, Luana/0000-0002-5272-6642 NR 52 TC 9 Z9 11 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD AUG PY 2012 VL 8 IS 8 BP 1043 EP 1050 DI 10.1517/17425255.2012.701618 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 975PT UT WOS:000306524000010 PM 22762358 ER PT J AU Ramanadhan, S Crisostomo, J Alexander-Molloy, J Gandelman, E Grullon, M Lora, V Reeves, C Savage, C Viswanath, K AF Ramanadhan, Shoba Crisostomo, Josephine Alexander-Molloy, Jaclyn Gandelman, Ediss Grullon, Milagro Lora, Vilma Reeves, Chrasandra Savage, Clara Viswanath, Kasisomayajula CA PLANET MassCONECT C-PAC TI Perceptions of evidence-based programs among community-based organizations tackling health disparities: a qualitative study SO HEALTH EDUCATION RESEARCH LA English DT Article ID PUBLIC-HEALTH; DISSEMINATION; INTERVENTIONS; PREVENTION; IMPLEMENTATION; TRANSLATION; POLICY; GAINS; GAP AB Dissemination of prevention-focused evidence-based programs (EBPs) from research to community settings may improve population health and reduce health disparities, but such flow has been limited. Academic-community partnerships using community-based participatory research (CBPR) principles may support increased dissemination of EBPs to community-based organizations (CBOs). This qualitative study examined the EBP-related perceptions and needs of CBOs targeting underserved populations. As part of PLANET MassCONECT, a CBPR study, we conducted six key informant interviews with community leaders and four focus groups with CBO staff members in Boston, Worcester and Lawrence, Massachusetts, in 2008. Working definitions of EBPs among CBO staff members varied greatly from typical definitions used by researchers or funders. Key barriers to using EBPs included: resource constraints, program adaptation challenges and conflicts with organizational culture. Important facilitators of EBP usage included: program supports for implementation and adaptation, collaborative technical assistance and perceived benefits of using established programs. This exploratory study highlights differences among key stakeholders regarding the role of evidence in program planning and delivery. An updated perspective should better incorporate CBO perspectives on evidence and place greater, and much needed, emphasis on the impact of context for EBP dissemination in community settings. C1 [Ramanadhan, Shoba; Crisostomo, Josephine; Alexander-Molloy, Jaclyn; Viswanath, Kasisomayajula; PLANET MassCONECT C-PAC] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Gandelman, Ediss] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Grullon, Milagro] Lawrence Community Connect, Lawrence, MA 01840 USA. [Lora, Vilma] YWCA Greater Lawrence City Lawrence Mayors Hlth T, Lawrence, KS 01840 USA. [Reeves, Chrasandra] Boston Alliance Community Hlth, Boston, MA 02118 USA. [Savage, Clara] Common Pathways, Worcester, MA 01609 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Ramanadhan, S (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM shoba_ramanadhan@dfci.harvard.edu FU NCI NIH HHS [R01 CA132651] NR 60 TC 4 Z9 4 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD AUG PY 2012 VL 27 IS 4 BP 717 EP 728 DI 10.1093/her/cyr088 PG 12 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 977HS UT WOS:000306647900014 PM 22012968 ER PT J AU Exner, DV Auricchio, A Singh, JP AF Exner, Derek V. Auricchio, Angelo Singh, Jagmeet P. TI Contemporary and future trends in cardiac resynchronization therapy to enhance response SO HEART RHYTHM LA English DT Article DE Biventricular pacing; Cardiac resynchronization therapy; Endocardial pacing; Epicardial pacing; Left ventricular lead; Transvenous pacing ID HEART-FAILURE PATIENTS; VENTRICULAR LEAD POSITION; POSTEROLATERAL SCAR TISSUE; ACUTE HEMODYNAMIC-RESPONSE; BUNDLE-BRANCH BLOCK; PACING SITES; IMPLANTABLE DEFIBRILLATOR; PREDICTS RESPONSE; ELECTRICAL DELAY; CORONARY-SINUS AB The rationale for cardiac resynchronization therapy (CRT), expectations in terms of patient benefit, patient selection for CRT, selection of a CRT pacemaker (CRT-P) vs CRT plus implantable cardioverter-defibrillator (CRT-D) platform, and studies evaluating device programming to enhance benefit from CRT are reviewed. The notion of an "optimal" left ventricular (LV) pacing site, the rationale for identifying and avoiding LV pacing in regions of scar, the use of anatomic, hemodynamic, and electrical parameters to identify an optimal LV pacing site, and the potential utility of multisite LV pacing to enhance benefit from CRT are discussed. Finally, the advantages and disadvantages of the various methods for LV lead delivery are reviewed. C1 [Exner, Derek V.] Univ Calgary, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada. [Auricchio, Angelo] Fdn Cardioctr Ticino, Lugano, Switzerland. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Exner, DV (reprint author), 3280 Hosp Dr NW,Room GE63, Calgary, AB T2N 4Z6, Canada. EM exner@ucalgary.ca FU Boehringer Ingelheim; GE Healthcare; Heart Force Medical; Medtronic; St. Jude; AudiCor; Cambridge Heart; St. Jude Medical; Sorin Group; Biotronik; EBR Systems; Merck Sharpe Dohme; Daiichi Sankyo; Impulse Dynamics; Abbott; Cordis; Boston Scientific Corp; CardioInsight; Thoratec; Biosense Webster; Guidant Corp FX Dr. Exner is a Clinical Scholar of Alberta Innovates Health Solutions and Canada Research Chair in Cardiovascular Clinical Trials. Dr. Exner has received consulting fees/honoraria (modest) from Boehringer Ingelheim, GE Healthcare, Heart Force Medical, Medtronic, and St. Jude; research support (modest) from AudiCor and Cambridge Heart; and research support (significant) from GE Healthcare, Heart Force Medical, Medtronic, and St. Jude Medical. Dr. Auricchio has received financial support (modest) from Sorin Group, Medtronic, Biotronik, EBR Systems, Merck Sharpe & Dohme, Daiichi Sankyo, Impulse Dynamics, St. Jude Medical, Abbott, and Cordis. Dr. Singh has received research grants (significant) from St. Jude Medical, Medtronic, Boston Scientific Corp, and Biotronik; advisory board/steering committee/consultant fees (modest) from Boston Scientific Corp, Biotronik, St. Jude Medical, Medtronic, CardioInsight, Thoratec, and Biosense Webster; and honoraria/speaker fees (modest) from Medtronic, Biotronik, Guidant Corp, St. Jude Medical, and Sorin Group. Address reprint requests and correspondence: Dr. Derek V. Exner, 3280 Hospital Dr NW, Room GE63, Calgary, AB Canada T2N 4Z6. E-mail address: exner@ucalgary.ca. NR 77 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2012 VL 9 IS 8 SU S BP S27 EP S35 DI 10.1016/j.hrthm.2012.04.022 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976TB UT WOS:000306606800005 PM 22521939 ER PT J AU Parks, KA Costanzo, MR AF Parks, Kimberly A. Costanzo, Maria Rosa TI Thinking beyond resynchronization therapy in the failing heart SO HEART RHYTHM LA English DT Article DE Artificial heart; Cardiac resynchronization therapy; Cardiac transplantation; End-stage heart failure; Ventricular assist device ID VENTRICULAR ASSIST DEVICE; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; TOTAL ARTIFICIAL-HEART; SUDDEN CARDIAC DEATH; INTERNATIONAL EXPERIENCE; CIRCULATORY SUPPORT; CATHETER ABLATION; SCREENING SCALE; FAILURE; TRANSPLANTATION C1 [Parks, Kimberly A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adv Heart Failure Sect, Boston, MA 02114 USA. [Costanzo, Maria Rosa] Edwards Heart Hosp, Midwest Heart Fdn, Ctr Adv Heart Failure, Lombard, IL USA. RP Parks, KA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adv Heart Failure Sect, 55 Fruit St,GB 800, Boston, MA 02114 USA. EM kaparks@partners.org FU Thoratec; St. Jude Medical; Paracor Medical; CardioMems; CHF Solutions; Medtronic FX Dr. Parks has received consultancy fees from Thoratec. Dr. Costanzo has received research support from St. Jude Medical, Paracor Medical, and CardioMems; honoraria from CHF Solutions, St. Jude Medical, and Gilead; and consultancy fees form CHF Solutions, Medtronic, and St. Jude Medical. Address reprint requests and correspondence: Dr. Kimberly Parks, Harvard Medical School, Massachusetts General Hospital, 55 Fruit St/GB 800, Boston, MA 02114-2621. E-mail address: kaparks@partners.org. NR 68 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2012 VL 9 IS 8 SU S BP S36 EP S44 DI 10.1016/j.hrthm.2012.04.025 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976TB UT WOS:000306606800006 PM 22521932 ER PT J AU Singh, JP AF Singh, Jagmeet P. TI Advances in electrical therapy for heart failure: Papers from the International ADVANCE CRT Summit SO HEART RHYTHM LA English DT Editorial Material DE sp. C1 [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. EM jsingh@partners.org 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2012 VL 9 IS 8 SU S BP S1 EP S2 DI 10.1016/j.hrthm.2012.04.023 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976TB UT WOS:000306606800001 PM 22521940 ER PT J AU Upadhyay, GA Steinberg, JS AF Upadhyay, Gaurav A. Steinberg, Jonathan S. TI Managing atrial fibrillation in the CRT patient: Controversy or consensus? SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Cardiac resynchronization therapy; Heart failure; Treatment strategies ID CARDIAC RESYNCHRONIZATION THERAPY; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ATRIOVENTRICULAR JUNCTION ABLATION; CONGESTIVE-HEART-FAILURE; PULMONARY-VEIN ISOLATION; LEFT-VENTRICULAR DYSFUNCTION; SINUS RHYTHM; LIFETIME RISK; MORTALITY; SURVIVAL AB The cumulative incidence of new onset atrial fibrillation (AF) in patients undergoing cardiac resynchronization therapy (CRT) is substantial, exceeding 25% in multiple recent studies. Although AF patients undergoing CRT show improved echocardiographic parameters, functional status, and quality of life in, they benefit to a lesser degree than do patients in normal sinus rhythm. They also exhibit a trend toward increased mortality. Understanding the barriers to response from CRT among AF patients is critical to addressing the needs of growing populations of patients with AF and HF. Foremost among these are suboptimal biventricular pacing, often characterized by fusion or pseudo-fusion complexes, leading to inefficient CRT delivery. Furthermore, AF increases the risk of inappropriate shocks, which lead to substantial psychiatric morbidity, increased risk of heart failure hospitalization, and may also increase mortality. Assiduous rate control is reasonable for all AF patients receiving CRT, but there is a paucity of data regarding specific antiarrhythmic drug therapy recommendations. For patients with permanent AF and severe symptoms, atrioventricular junction ablation appears effective in improving response by ensuring biventricular capture and reducing implantable cardioverter-defibrillator shock burden in selected patients. Catheter-based techniques such as pulmonary vein isolation appear more attractive and in the future may offer further advantages and lower risks, particularly for patients with paroxysmal AF. C1 [Upadhyay, Gaurav A.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. [Upadhyay, Gaurav A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Steinberg, Jonathan S.] Columbia Univ Coll Phys & Surg, Arrhythmia Inst Valley Hlth Syst, New York, NY 10032 USA. RP Upadhyay, GA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Gray Bigelow 109, Boston, MA 02114 USA. EM gaupadhyay@partners.org FU Biosense Webster; Cameron Health; Ambucor; Medtronic; St. Jude Medical; Sanofi-Aventis FX Dr. Upadhyay has no financial disclosures that are relevant to this publication. Dr. Steinberg is on the speakers' bureau for Sanofi-Aventis; receives consultant fees/honoraria from Biosense Webster, Cameron Health, Ambucor, Medtronic, St. Jude Medical, and Sanofi-Aventis; and receives research/research grants from Biosense Webster and Medtronic. Address reprint requests and correspondence: Dr. Gaurav A. Upadhyay, Division of Cardiology and the Cardiac Arrhythmia Service, Massachusetts General Hospital, Gray Bigelow 109, Boston, MA 02114. E-mail address: gaupadhyay@partners.org. NR 56 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2012 VL 9 IS 8 SU S BP S51 EP S59 DI 10.1016/j.hrthm.2012.04.030 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976TB UT WOS:000306606800008 PM 22521931 ER PT J AU Mihara, M Kisu, I Hara, H Iida, T Araki, J Shim, T Narushima, M Yamamoto, T Moriguchi, H Kato, Y Tonsho, M Banno, K Aoki, D Suganuma, N Kagawa, N Takehara, Y Kato, O Koshima, I AF Mihara, Makoto Kisu, Iori Hara, Hisako Iida, Takuya Araki, Jun Shim, Timothy Narushima, Mitsunaga Yamamoto, Takumi Moriguchi, Hisashi Kato, Yojiro Tonsho, Makoto Banno, Kouji Aoki, Daisuke Suganuma, Nobuhiko Kagawa, Noriko Takehara, Yuji Kato, Osamu Koshima, Isao TI Uterine autotransplantation in cynomolgus macaques: the first case of pregnancy and delivery SO HUMAN REPRODUCTION LA English DT Article DE uterine transplantation; cynomolgus macaque; indocyanine green angiography; ICG; autotransplantation ID UTERUS TRANSPLANTATION; SURGICAL TECHNIQUE; SURROGACY; FERTILITY; MODEL AB For women with congenital uterine infertility, or for those who have undergone hysterectomy, uterine transplantation is one of the potential treatments to regain fertility. In this study, we utilized a primate model of uterine transplantation, and evaluated the patency of our microsurgical anastomoses, and the perfusion of the transplanted uterus. Two female cynomolgus monkeys underwent surgery. We anastomosed two arteries and one vein in Case 1 and two arteries and two veins in Case 2. The arteries used were the uterine arteries and the anastomosis was done to the external iliac artery. We used one of the ovarian veins in both animals, but resected the ovary from the Fallopian tube. Uterine arterial blood flow and uterine size were determined by intraoperative indocyanine green (ICG) angiography and ultrasonography. The biopsy of the uterine cervix was performed after surgery. ICG angiography showed that the unilateral uterine artery perfused the bilateral uterine bodies and cervix. In Case 1, ICG angiography showed the occlusion of one of the anastomosed arteries during the operation and the uterus appeared atrophied 2 months after operation. In Case 2, the transplanted uterus survived and normal menstruation occurred. The animal achieved a natural pregnancy and was delivered by the Caeserean section due to early separation of the placenta. The newborn suffered fetal distress. These results show the anastomosis of at least the bilateral uterine arteries and the unilateral ovarian vein is required for uterus transplantation. This is the first report of a natural pregnancy in a primate following uterine autotransplantation. C1 [Mihara, Makoto; Hara, Hisako; Iida, Takuya; Araki, Jun; Shim, Timothy; Narushima, Mitsunaga; Yamamoto, Takumi; Moriguchi, Hisashi; Koshima, Isao] Univ Tokyo, Dept Plast & Reconstruct Surg, Tokyo, Japan. [Kisu, Iori; Banno, Kouji; Aoki, Daisuke] Keio Univ, Sch Med, Dept Obstet & Gynecol, Tokyo 160, Japan. [Kato, Yojiro] Columbia Univ, Dept Surg, Med Ctr, Ctr Liver Dis & Transplantat,CCTI, New York, NY USA. [Tonsho, Makoto] Massachusetts Gen Hosp, Dept Transplantat, Boston, MA 02114 USA. [Tonsho, Makoto] Harvard Univ, Sch Med, Boston, MA USA. [Suganuma, Nobuhiko] Kyoto Univ, Grad Sch Med, Dept Human Hlth Sci, Tokyo, Japan. [Kagawa, Noriko; Takehara, Yuji; Kato, Osamu] Kato Ladies Clin, Adv Res Inst Fertil, Tokyo, Japan. RP Mihara, M (reprint author), Univ Tokyo, Dept Plast & Reconstruct Surg, Tokyo, Japan. EM mihara@keiseigeka.name RI Banno, Kouji/C-9638-2014 FU Program for the Next Generation of World-leading Research of the Japanese Cabinet Office [LS039] FX The funding for this study was provided by the Program for the Next Generation of World-leading Research of the Japanese Cabinet Office (LS039). NR 26 TC 28 Z9 29 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD AUG PY 2012 VL 27 IS 8 BP 2332 EP 2340 DI 10.1093/humrep/des169 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 977HZ UT WOS:000306648600010 PM 22647448 ER PT J AU Hirsch, MS Kuritzkes, DR AF Hirsch, Martin S. Kuritzkes, Daniel R. TI The Future of HIV Treatment SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; HIV treatment; eradication; development of therapeutics ID INFECTION AB Antiretroviral therapy has transformed the management of HIV-infected individuals over the past quarter century. However, important challenges remain. These include attempts to eradicate HIV from reservoirs within the body, thereby eliminating the need for lifetime therapy. In addition, improvements in drug development, clinical trial, and regulatory pathways are necessary to expeditiously evaluate novel therapeutic regimens and strategies. Antiretroviral drug scarcity remains a major problem in underserved populations worldwide, and partnerships among pharmaceutical companies, academic investigators, and both governmental and nongovernmental agencies are necessary to improve access to these life-saving regimens. C1 [Hirsch, Martin S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hirsch, Martin S.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hirsch, Martin S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Kuritzkes, Daniel R.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Hirsch, MS (reprint author), 65 Landsdowne St,Room 419, Cambridge, MA 02139 USA. EM hirsch.martin@mgh.harvard.edu FU Gilead; Merck FX D.R.K. is a consultant to Abbott, Aileron, Avexa, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead, InnoVirVax, Merck, Pathogenica, Roche, Tobira, Vertex, Viiv, ViroStatics and VIRxSYS and has received grants from Gilead and Merck and speaking honorarium from Roche. M.S.H. has no funding or conflicts of interest to disclose. NR 12 TC 1 Z9 1 U1 0 U2 3 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 AUG 1 PY 2012 VL 60 SU 2 BP S39 EP S40 DI 10.1097/QAI.0b013e318258bc9f PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977GJ UT WOS:000306644400006 PM 22772389 ER PT J AU Mayer, KH Pape, JW Wilson, P Diallo, DD Saavedra, J Mimiaga, MJ Koenig, S Farmer, P AF Mayer, Kenneth H. Pape, Jean W. Wilson, Phill Diallo, Dazon D. Saavedra, Jorge Mimiaga, Matthew J. Koenig, Serena Farmer, Paul TI Multiple Determinants, Common Vulnerabilities, and Creative Responses: Addressing the AIDS Pandemic in Diverse Populations Globally SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE disparities; inequity; health care access; homophobia; sex inequality ID ACQUIRED IMMUNODEFICIENCY SYNDROME; HIV-INFECTION; RISK; HAITI; MEN; SETTINGS; EPIDEMIC; AFRICA; SEX AB The AIDS epidemic has been fueled by global inequities. Ranging from sexual inequality and underdevelopment to homophobia impeding health care access for men who have sex with men, imbalanced resource allocations, and social biases have potentiated the spread of the epidemic. However, recognition of culturally specific aspects of each microepidemic has yielded development of community-based organizations, which have resulted in locally effective responses to AIDS. This effective approach to HIV prevention, care, and treatment is illustrated through examples of community-based responses in Haiti, the United States, Africa, and other impoverished settings. C1 [Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Infect Dis, Sch Med, Boston, MA 02215 USA. [Pape, Jean W.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Pape, Jean W.] GHESKIO, Port Au Prince, Haiti. [Wilson, Phill] Black AIDS Inst, Los Angeles, CA USA. [Diallo, Dazon D.] SisterLove Inc, Atlanta, GA USA. [Saavedra, Jorge] AIDS Hlth Care Fdn, Los Angeles, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Koenig, Serena] Harvard Univ, Brigham & Womens Hosp, Div Global Hlth Equ, Sch Med, Boston, MA 02115 USA. [Koenig, Serena] Harvard Univ, Brigham & Womens Hosp, Div Infect Dis, Sch Med, Boston, MA 02115 USA. [Farmer, Paul] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Farmer, Paul] Partners Hlth, Boston, MA USA. RP Mayer, KH (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM mayer@fenwayhealth.org FU NIAID NIH HHS [UM1 AI069421, U01 AI069421] NR 25 TC 6 Z9 6 U1 1 U2 12 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 AUG 1 PY 2012 VL 60 SU 2 BP S31 EP S34 DI 10.1097/QAI.0b013e31825c16d9 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977GJ UT WOS:000306644400004 PM 22772387 ER PT J AU Bergevin, C Walsh, EJ McGee, J Shera, CA AF Bergevin, Christopher Walsh, Edward J. McGee, Joann Shera, Christopher A. TI Probing cochlear tuning and tonotopy in the tiger using otoacoustic emissions SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article ID AUDITORY-NERVE FIBERS; CHARACTERISTIC FREQUENCY; COHERENT REFLECTION; TRAVELING-WAVES; EAR; MECHANISMS; MAP; CHINCHILLA; HUMANS; CAT AB Otoacoustic emissions (sound emitted from the ear) allow cochlear function to be probed noninvasively. The emissions evoked by pure tones, known as stimulus-frequency emissions (SFOAEs), have been shown to provide reliable estimates of peripheral frequency tuning in a variety of mammalian and non-mammalian species. Here, we apply the same methodology to explore peripheral auditory function in the largest member of the cat family, the tiger (Panthera tigris). We measured SFOAEs in 9 unique ears of 5 anesthetized tigers. The tigers, housed at the Henry Doorly Zoo (Omaha, NE), were of both sexes and ranged in age from 3 to 10 years. SFOAE phase-gradient delays are significantly longer in tigers-by approximately a factor of two above 2 kHz and even more at lower frequencies-than in domestic cats (Felis catus), a species commonly used in auditory studies. Based on correlations between tuning and delay established in other species, our results imply that cochlear tuning in the tiger is significantly sharper than in domestic cat and appears comparable to that of humans. Furthermore, the SFOAE data indicate that tigers have a larger tonotopic mapping constant (mm/octave) than domestic cats. A larger mapping constant in tiger is consistent both with auditory brainstem response thresholds (that suggest a lower upper frequency limit of hearing for the tiger than domestic cat) and with measurements of basilar-membrane length (about 1.5 times longer in the tiger than domestic cat). C1 [Bergevin, Christopher] Columbia Univ, Dept Otolaryngol Head & Neck Surg, New York, NY 10032 USA. [Walsh, Edward J.; McGee, Joann] Boys Town Natl Res Hosp, Omaha, NE 68131 USA. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Shera, Christopher A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bergevin, C (reprint author), Columbia Univ, Dept Otolaryngol Head & Neck Surg, 630 W 168th St,P&S 11-452, New York, NY 10032 USA. EM dolemitecb@gmail.com FU National Science Foundation [0823417, 0602173]; Howard Hughes Medical Institute [52003749]; National Institutes of Health [R01 DC003687, P30 DC05209] FX The support, advice, and assistance of the veterinarians and staff of the Henry Doorly Zoo were invaluable to the completion of this study. All procedures were approved by the Institutional Animal Care and Use Committee. We thank Sebastiaan Meenderink and John Rosowski for helpful comments on the manuscript. The work was supported by the National Science Foundation (grants 0823417 and 0602173), the Howard Hughes Medical Institute (grant 52003749), and the National Institutes of Health (grants R01 DC003687 and P30 DC05209). NR 41 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD AUG PY 2012 VL 198 IS 8 BP 617 EP 624 DI 10.1007/s00359-012-0734-1 PG 8 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 977XM UT WOS:000306698200005 PM 22645048 ER PT J AU Hornsby, PJ AF Hornsby, Peter J. TI Adrenarche: a cell biological perspective SO JOURNAL OF ENDOCRINOLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; ADRENOCORTICAL-CELLS; STEROIDOGENIC CELLS; ZONA-RETICULARIS; DEHYDROEPIANDROSTERONE-SULFATE; ANDROGEN PRODUCTION; MESENCHYMAL CELLS; SONIC HEDGEHOG; IN-VIVO; DIFFERENTIATION AB Adrenarche is a cell biological and endocrinological puzzle. The differentiation of the zona reticularis in childhood in humans requires special techniques for study because it is confined to humans and possibly a small number of other primates. Despite the rapid progress in the definition of adrenocortical stem/progenitor cells in the mouse, the factors that cause the differentiation of adrenocortical cells into zonal cell types have not been identified. There are, however, many candidates in the Wnt, Hedgehog, and other families of signaling molecules. A suitable system for identifying authentic stem cells, capable of differentiation into all zones, has yet to be developed. It is proposed here that the in vitro differentiation of pluripotent cells, combined with appropriate in vitro and in vivo methods for validating authentic adrenocortical stem cells, is a promising approach to solving these questions. Journal of Endocrinology (2012) 214, 113-119 C1 [Hornsby, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Hornsby, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Hornsby, Peter J.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Hornsby, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM hornsby@uthscsa.edu NR 53 TC 4 Z9 4 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD AUG PY 2012 VL 214 IS 2 BP 113 EP 119 DI 10.1530/JOE-12-0022 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 976CR UT WOS:000306558600002 PM 22573830 ER PT J AU Rodriguez, L Irani, K Jiang, HY Goldstein, AM AF Rodriguez, Leonel Irani, Katayun Jiang, Hongyu Goldstein, Allan M. TI Clinical Presentation, Response to Therapy, and Outcome of Gastroparesis in Children SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE delayed gastric emptying; gastroparesis; nausea; prokinetic therapy; vomiting ID GASTRIC ELECTRICAL-STIMULATION; DIABETIC GASTROPARESIS; DOMPERIDONE; METOCLOPRAMIDE; ERYTHROMYCIN; SYMPTOMS; TERM; SCINTIGRAPHY; PROKINETICS; DYSPEPSIA AB Objectives: The aims of the present study was to define the clinical features, response to therapy, and outcome of pediatric gastroparesis. Methods: Retrospective review of 230 children with gastroparesis. Demographics, gastric emptying times, symptoms, response to medications, and outcome were determined for each of 3 groups (infants, children, and adolescents). Results: Mean age was 9 years, with boys predominating among infants and girls among adolescents. Postviral gastroparesis occurred in 18% and mitochondrial dysfunction (MD) in 8%. Symptoms varied with age, with children experiencing more vomiting and adolescents reporting more nausea and abdominal pain. The addition of promotility drugs was an effective therapy. Overall rates of symptom resolution were 22% at 6 months, 53% at 18 months, and 61% at 36 months, with median time to resolution of 14 months. Factors associated with symptom resolution included younger age, male sex, postviral gastroparesis, shorter duration of symptoms, response to addition of promotility therapy, and absence of MD. In multivariate analysis, longer duration of symptoms and MD both predicted lower rates of resolution, whereas younger age and response to addition of promotility therapy predicted a higher rate. Conclusions: Pediatric gastroparesis is a complex condition with variable symptomatology and outcome depending on multiple parameters. Understanding the clinical features and response to therapy will improve our diagnosis and treatment of this disorder. C1 [Rodriguez, Leonel] Childrens Hosp, Dept Med, Div Gastroenterol, Ctr Motil & Funct Gastrointestinal Disorders, Boston, MA 02115 USA. [Irani, Katayun; Goldstein, Allan M.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Jiang, Hongyu] Harvard Univ, Childrens Hosp, Sch Med, Dept Biostat Core, Boston, MA 02115 USA. RP Rodriguez, L (reprint author), Childrens Hosp, Dept Med, Div Gastroenterol, Ctr Motil & Funct Gastrointestinal Disorders, 300 Longwood Ave, Boston, MA 02115 USA. EM leonel.ro-driguez@childrens.harvard.edu NR 26 TC 11 Z9 11 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2012 VL 55 IS 2 BP 185 EP 190 DI 10.1097/MPG.0b013e318248ed3f PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 977ZM UT WOS:000306705400019 PM 22228004 ER PT J AU Germain, A Richardson, R Moul, D Mammen, O Haas, G Forman, S Rode, N Begley, A Nofzinger, E AF Germain, Anne Richardson, Robin Moul, Douglas Mammen, Oommen Haas, Gretchen Forman, Steven Rode, Noelle Begley, Amy Nofzinger, Eric TI Response to Dr. Mommersteeg and colleagues on Germain et al., "Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US Military Veterans" SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Letter ID QUALITY INDEX ADDENDUM; INSOMNIA; PTSD C1 [Germain, Anne] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Cleveland Clin Fdn, Sleep Disorders Ctr, Neurol Inst, Cleveland, OH 44195 USA. VA Pittsburgh Healthcare Syst, MIRECC VSN4, Pittsburgh, PA USA. RP Germain, A (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. EM germax@upmc.edu NR 10 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD AUG PY 2012 VL 73 IS 2 BP 154 EP 155 DI 10.1016/j.jpsychores.2012.05.004 PG 2 WC Psychiatry SC Psychiatry GA 977BZ UT WOS:000306632700014 ER PT J AU Little, EC Wang, CD Watson, PM Watson, DK Cole, DJ Camp, ER AF Little, Elizabeth C. Wang, Cindy Watson, Patricia M. Watson, Dennis K. Cole, David J. Camp, E. Ramsay TI Novel Immunocompetent Murine Models Representing Advanced Local and Metastatic Pancreatic Cancer SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE pancreatic cancer; murine model; gemcitabine ID IN-VIVO; TUMOR BURDEN; ANTITUMOR IMMUNITY; MOUSE MODELS; CELLS; MICE; GEMCITABINE; INDUCTION; SURVIVAL; GROWTH AB Background. The development of novel therapeutics for pancreatic cancer has been hindered by a lack of relevant preclinical models. The purpose of this study was to evaluate the clinical relevancy of two pancreatic cancer models using standard-of-care therapeutic agent gemcitabine. Materials and Methods. Murine Panc02 cells were injected directly into the spleen or pancreas of C57BL/6 mice to respectively create models of metastatic and locally advanced pancreatic cancer. Beginning 7 d post-Panc02 injection, treated mice received 20 mg/kg gemcitabine i.p. every 3 d. Animals were sacrificed when the untreated mice became moribund and tumor/liver weight used to assess tumor burden. Results. Untreated mice became moribund 22 d after pancreatic Panc02 injection. Gross analysis revealed localized pancreatic tumors weighing 1.063 g. Intrasplenic Panc02 injection produced extensive liver metastasis by d 15 when the untreated mice first became moribund. Liver weights at this time averaged 3.6 g compared with the average non-tumor-bearing weight of 1.23 g. Gemcitabine therapy resulted in a 54% decrease in localized pancreatic tumor weight and 62.5% decrease in metastatic liver weight. Additionally, gemcitabine therapy extended animal survival to 20.5 d compared with 18.0 d average for the untreated mice. Conclusions. We describe two models depicting both locally advanced and metastatic pancreatic cancer in immunocompetent mice. In efforts to establish baseline therapeutic efficacy, we determined that gemcitabine reduces tumor burden in both models and enhances survival in the metastatic model. These clinically relevant models provide valuable tools to evaluate novel therapeutics in pancreatic cancer. (C) 2012 Elsevier Inc. All rights reserved. C1 [Wang, Cindy; Cole, David J.; Camp, E. Ramsay] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Watson, Patricia M.; Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Little, Elizabeth C.; Cole, David J.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Little, Elizabeth C.; Wang, Cindy; Watson, Patricia M.; Watson, Dennis K.; Cole, David J.; Camp, E. Ramsay] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Camp, E. Ramsay] Ralph H Johnson VA Med Ctr, 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 National Institutes of Health [5R01CA123159-05, 1K08CA142904] FX The authors thank Dr. Michael Rosol at the Small Animal Imaging Core Facility at MUSC for his assistance with bioluminescence imaging. This research was supported by the National Institutes of Health, 5R01CA123159-05 (DJC, DKW) and 1K08CA142904 (ERC). NR 28 TC 8 Z9 9 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2012 VL 176 IS 2 BP 359 EP 366 DI 10.1016/j.jss.2011.10.025 PG 8 WC Surgery SC Surgery GA 975EC UT WOS:000306488700007 PM 22221605 ER PT J AU Davidson, BP Giraud, GD AF Davidson, Brian P. Giraud, George D. TI Left Ventricular Function and the Systemic Arterial Vasculature: Remembering What We Have Learned SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material ID PRESERVED EJECTION FRACTION; HEART-FAILURE; FILLING PRESSURE; INTACT HEART; FORCE; LOAD C1 [Giraud, George D.] Portland VA Med Ctr, Cardiol Sect, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Med, Div Cardiovasc Med, Portland, OR USA. RP Giraud, GD (reprint author), Portland VA Med Ctr, Cardiol Sect, P3Card,POB 1034, Portland, OR 97207 USA. EM giraudg@ohsu.edu FU NHLBI NIH HHS [T32 HL094294, T32HL094294, R01 HL102763, R21 HL093617]; NICHD NIH HHS [P01 HD 34430, P01 HD034430] NR 22 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD AUG PY 2012 VL 25 IS 8 BP 891 EP 894 DI 10.1016/j.echo.2012.06.020 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977KJ UT WOS:000306657900014 PM 22824174 ER PT J AU Schittone, SA Dionne, KR Tyler, KL Clarke, P AF Schittone, Stephanie A. Dionne, Kalen R. Tyler, Kenneth L. Clarke, Penny TI Activation of Innate Immune Responses in the Central Nervous System during Reovirus Myelitis SO JOURNAL OF VIROLOGY LA English DT Article ID TOLL-LIKE RECEPTOR; ACUTE FLACCID PARALYSIS; ASTROCYTIC METABOLIC PHENOTYPE; INTERFERON-STIMULATED GENES; THEILERS VIRUS-INFECTION; NECROSIS-FACTOR-ALPHA; SPINAL-CORD; NEURODEGENERATIVE DISEASES; MAMMALIAN REOVIRUS; ANIMAL-MODELS AB Reovirus infection of the murine spinal cord (SC) was used as a model system to investigate innate immune responses during viral myelitis, including the activation of glia (microglia and astrocytes) and interferon (IFN) signaling and increased expression of inflammatory mediators. Reovirus myelitis was associated with the pronounced activation of SC glia, as evidenced by characteristic changes in cellular morphology and increased expression of astrocyte and microglia-specific proteins. Expression of inflammatory mediators known to be released by activated glia, including interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), chemokine (C-C motif) ligand 5 (CCL 5), chemokine (C-X-C motif) ligand 10 (CXCL10), and gamma interferon (IFN-gamma), was also significantly upregulated in the SC of reovirus-infected animals compared to mock-infected controls. Reovirus infection of the mouse SC was also associated with increased expression of genes involved in IFN signaling, including IFN-stimulated genes (ISG). Further, reovirus infection of mice deficient in the expression of the IFN-alpha/beta receptor (IFNAR(-/-)) resulted in accelerated mortality, demonstrating that IFN signaling is protective during reovirus myelitis. Experiments performed in ex vivo SC slice cultures (SCSC) confirmed that resident SC cells contribute to the production of at least some of these inflammatory mediators and ISG during reovirus infection. Microglia, but not astrocytes, were still activated, and glia-associated inflammatory mediators were still produced in reovirus-infected INFAR(-/-) mice, demonstrating that IFN signaling is not absolutely required for these neuroinflammatory responses. Our results suggest that activated glia and inflammatory mediators contribute to a local microenvironment that is deleterious to neuronal survival. C1 [Schittone, Stephanie A.; Dionne, Kalen R.; Tyler, Kenneth L.; Clarke, Penny] Univ Colorado, Dept Neurol, Aurora, CO 80045 USA. [Schittone, Stephanie A.; Tyler, Kenneth L.] Univ Colorado, Dept Microbiol, Aurora, CO USA. [Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado, Dept Neurosci, Aurora, CO USA. [Tyler, Kenneth L.] Univ Colorado, Dept Med, Aurora, CO USA. [Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado, Med Scientist Training Program, Aurora, CO USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Clarke, P (reprint author), Univ Colorado, Dept Neurol, Anshutz Med Campus, Aurora, CO 80045 USA. EM Penny.Clarke@ucdenver.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NIH [R01 NS076512, F31 NS06258303, F30 NS071630, T32 GM008497]; VA merit grant; NIH/NCRR Colorado CTSI [UL1 RR025780] FX This publication was supported by NIH grants R01 NS076512 (K.L.T.), F31 NS06258303 (S.A.S.), F30 NS071630 (K.R.D.), and T32 GM008497 (K.R.D.) and by a VA merit grant (K.L.T.). K.L.T. is supported by the Reuler-Lewin Family Professorship. The Advanced Microscopy Core at the Division of Renal Disease and Hypertension, University of Colorado School of Medicine is funded by NIH/NCRR Colorado CTSI grant number UL1 RR025780. NR 80 TC 6 Z9 7 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2012 VL 86 IS 15 BP 8107 EP 8118 DI 10.1128/JVI.00171-12 PG 12 WC Virology SC Virology GA 976VE UT WOS:000306614400035 PM 22623770 ER PT J AU Bhattacharya, D Ansari, IH Mehle, A Striker, R AF Bhattacharya, Dipankar Ansari, Israrul H. Mehle, Andrew Striker, Rob TI Fluorescence Resonance Energy Transfer-Based Intracellular Assay for the Conformation of Hepatitis C Virus Drug Target NS5A SO JOURNAL OF VIROLOGY LA English DT Article ID NONSTRUCTURAL PROTEIN 5A; MEMBRANE ANCHOR; RNA REPLICATION; LIVING CELLS; DOMAIN 3; IDENTIFICATION; CYCLOPHILINS; INHIBITOR; SUBSTRATE; DYNAMICS AB Nonstructural protein 5A (NS5A) is essential for hepatitis C virus (HCV) replication and assembly and is a critical drug target. Biochemical data suggest large parts of NS5A are unfolded as an isolated protein, but little is known about its folded state in the cell. We used fluorescence resonance energy transfer (FRET) to probe whether or not different regions of NS5A are in close proximity within the cell. Twenty-three separate reporter constructs were created by inserting one or more fluorophores into different positions throughout the three domains of NS5A. FRET efficiency was maximal when donor and acceptor fluorophores were positioned next to each other but also could be observed when the two fluorophores flanked NS5A domain I or domain 3. Informatic and biochemical analysis suggests that large portions of the carboxy terminus of NS5A are in an unfolded and disordered state. Quercetin, a natural product known to disrupt NS5A function in cells, specifically disrupted a conformationally specific domain 3 FRET signal. Intermolecular FRET indicated that the NS5A amino termini, but not other regions, are in close proximity in multimeric complexes. Overall, this assay provides a new window on the intracellular conformation(s) of NS5A and how the conformation changes in response to cellular and viral components of the replication and assembly complex as well as antiviral drugs. C1 [Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Bhattacharya, Dipankar; Ansari, Israrul H.; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI USA. [Mehle, Andrew] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. RP Striker, R (reprint author), William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. EM rtstriker@wisc.edu FU American Cancer Society [07-077-01]; Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs; [R00GM088484] FX This work was supported by the American Cancer Society Research Scholar Grant (07-077-01) to R.S., by the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs, and by R00GM088484 to A.M. NR 38 TC 6 Z9 6 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2012 VL 86 IS 15 BP 8277 EP 8286 DI 10.1128/JVI.00645-12 PG 10 WC Virology SC Virology GA 976VE UT WOS:000306614400050 PM 22623794 ER PT J AU Shamsi, KS Pierce, A Ashton, AS Halade, DG Richardson, A Espinoza, SE AF Shamsi, Kinza S. Pierce, Anson Ashton, Aaron S. Halade, Dipti G. Richardson, Arlan Espinoza, Sara E. TI Proteomic Screening of Glycoproteins in Human Plasma for Frailty Biomarkers SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Proteomics; Frailty ID HUMAN SERUM; AFFINITY-CHROMATOGRAPHY; ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; OLDER-ADULTS; INFLAMMATION; COAGULATION; GLYCOSYLATION; ACTIVATION; AMERICAN AB The application of proteomics methodology for analyzing human blood samples is of increasing importance as a noninvasive method for understanding, detecting, and monitoring disease. In particular, glycoproteomic analysis may be useful in the study of age-related diseases and syndromes, such as frailty. This study demonstrates the use of methodology for isolating plasma glycoproteins using lectins, comparing the glycoproteome by frailty status using two-dimensional polyacrylamide gel electrophoresis and identifying glycoproteins using mass spectrometry. In a pilot study, we found seven glycoproteins to differ by at least twofold in prefrail compared with nonfrail older adults, including haptoglobin, transferrin, and fibrinogen, consistent with known inflammatory and hematologic changes associated with frailty. Enzyme-linked immunosorbent assay analysis found that plasma transferrin concentration was increased in frail and prefrail older adults compared with nonfrail, confirming our proteomic findings. This work provides evidence for using a reproducible methodology for conducting clinical proteomic comparative studies of age-related diseases. C1 [Espinoza, Sara E.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Div Geriatr Gerontol & Palliat Med, Dept Med, San Antonio, TX 78229 USA. [Shamsi, Kinza S.; Ashton, Aaron S.; Richardson, Arlan; Espinoza, Sara E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Pierce, Anson] Univ Texas Galveston, Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77550 USA. [Halade, Dipti G.; Richardson, Arlan; Espinoza, Sara E.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Halade, Dipti G.; Richardson, Arlan; Espinoza, Sara E.] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Espinoza, SE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Div Geriatr Gerontol & Palliat Med, Dept Med, 7703 Floyd Curl Dr,Mail Code 7875, San Antonio, TX 78229 USA. EM espinozas2@uthscsa.edu RI Pierce, Anson/D-1079-2012 OI Pierce, Anson/0000-0002-1383-0180 FU Veterans Affairs Research & Development (VISN 17 New Investigator Award) [10N17]; San Antonio Area Foundation; Biomedical Research Foundation of South Texas; University Research Council of the University of Texas Health Science Center at San Antonio; National Center for Research Resources [KL2 RR025766] FX This work was supported by Veterans Affairs Research & Development (VISN 17 New Investigator Award, #10N17), the San Antonio Area Foundation, the Biomedical Research Foundation of South Texas, The University Research Council of the University of Texas Health Science Center at San Antonio, and The Clinical and Translational Science Award (KL2 RR025766) from the National Center for Research Resources. NR 36 TC 9 Z9 10 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD AUG PY 2012 VL 67 IS 8 BP 853 EP 864 DI 10.1093/gerona/glr224 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 977CE UT WOS:000306633200005 PM 22219522 ER PT J AU Marcum, ZA Pugh, MJV Amuan, ME Aspinall, SL Handler, SM Ruby, CM Hanlon, JT AF Marcum, Zachary A. Pugh, Mary Jo V. Amuan, Megan E. Aspinall, Sherrie L. Handler, Steven M. Ruby, Christine M. Hanlon, Joseph T. TI Prevalence of Potentially Preventable Unplanned Hospitalizations Caused by Therapeutic Failures and Adverse Drug Withdrawal Events Among Older Veterans SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Drug-related problems; Hospitalizations; Veterans ID DISCONTINUING MEDICATIONS; CARE; QUALITY; POPULATION; ADMISSIONS; MORTALITY; INDICATOR; PEOPLE; RISK AB Background. Studies of drug-related hospitalizations have focused on adverse drug reactions, but few data are available on therapeutic failures (TFs) and adverse drug withdrawal events (ADWEs) leading to hospitalization among community-dwelling older adults. Thus, we sought to describe the prevalence of unplanned hospitalizations caused by TFs and ADWEs. In addition, we evaluated factors associated with these events in a nationally representative sample of older Veterans. Methods. This study included 678 randomly selected unplanned hospitalizations of older (age >= 65 years) Veterans between December 1, 2003, and November 9, 2006. The main outcomes were hospitalizations caused by a TF and/or an ADWE as determined by a pair of health professionals from review of medication charts and application of the Therapeutic Failure Questionnaire and/or Naranjo ADWE algorithm, respectively. Preventability (ie, medication error) of the admission was also assessed. Results. Thirty-four TFs and eight ADWEs involving 54 drugs were associated with 40 (5.9%) Veterans' hospitalizations; of these admissions, 90.0% (36/40) were rated as potentially preventable mostly due to medication nonadherence and suboptimal prescribing. The most common TFs that occurred were heart failure exacerbations (n = 8), coronary heart disease symptoms (n = 6), tachyarrhythmias (n = 3), and chronic obstructive pulmonary disease exacerbations (n = 3). Half (4/8) of the ADWEs that occurred were cardiovascular in nature. Multivariable logistic regression modeling indicated that black Veterans (adjusted odds ratio 2.92, 95% CI 1.25-6.80) were significantly more likely to experience a TF-related admission compared with white Veterans. Conclusions. TF-related unplanned hospitalizations occur more frequently than ADWE-related admissions among older Veterans. Almost all TFs and/or ADWEs are potentially preventable. C1 [Marcum, Zachary A.; Handler, Steven M.; Ruby, Christine M.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med Geriatr, Dept Med, Pittsburgh, PA 15213 USA. [Marcum, Zachary A.; Aspinall, Sherrie L.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. [Amuan, Megan E.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Aspinall, Sherrie L.; Ruby, Christine M.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Aspinall, Sherrie L.] Vet Affairs Ctr Medicat Safety, Hines, IL USA. [Handler, Steven M.] Univ Pittsburgh, Sch Med Biomed Informat, Dept Med, Pittsburgh, PA 15213 USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Dept Med Geriatr, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu OI Handler, Steven/0000-0002-3940-3224 FU VA Health Services Research and Development Service [IIR-06-062]; National Institute on Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695, R01HS018721]; National Institutes of Health, National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX This work was supported by a VA Health Services Research and Development Service grant (IIR-06-062). Study investigators were also supported by National Institute on Aging grants and contracts (R01AG027017 and P30AG024827, T32 AG021885, K07AG033174, and R01AG034056), a National Institute of Mental Health) grant (R34 MH082682), a National Institute of Nursing Research grant (R01 NR010135), and an Agency for Healthcare Research and Quality grant (R01 HS017695 and R01HS018721). This research was also supported in part by the Intramural Research program of the National Institutes of Health, National Institute on Aging (N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106). NR 35 TC 18 Z9 18 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD AUG PY 2012 VL 67 IS 8 BP 867 EP 874 DI 10.1093/gerona/gls001 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 977CE UT WOS:000306633200006 PM 22389461 ER PT J AU Li, H Hosseini, A Li, JS Gill, TJ Li, GA AF Li, Hong Hosseini, Ali Li, Jing-Sheng Gill, Thomas J. Li, Guoan TI Quantitative magnetic resonance imaging (MRI) morphological analysis of knee cartilage in healthy and anterior cruciate ligament-injured knees SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Article DE MRI; Cartilage; Knee; Anterior cruciate ligament ID BONE-MARROW LESIONS; ARTICULAR-CARTILAGE; DEFORMATIONAL BEHAVIOR; CONTACT DEFORMATION; JOINT CARTILAGE; SEX-DIFFERENCES; OSTEOARTHRITIS; THICKNESS; AGE; ASSOCIATION AB To analyze the morphological change in the cartilage of the knee after anterior cruciate ligament (ACL) injury by comparing with that of the intact contralateral knee. A total of 22 participants (12 male and 10 female patients) who had unilateral ACL injury underwent MRI scan of both the injured and intact contralateral knees. Sagittal plane images were segmented using a modeling software to determine cartilage volume and cartilage thickness in each part of the knee cartilage that were compared between the ACL-injured and the intact contralateral knees. Furthermore, the male and female patients' data were analyzed in subgroups. The ACL-injured knees had statistically significant lower total knee cartilage volume than the intact contralateral knees (P = 0.0020), but had similar mean thickness of total knee cartilage (not significant: n.s.). In the male subgroup, there was no significant difference in cartilage volume and thickness between normal and ACL-injured knees. In the female subgroup, the ACL-injured knees demonstrated statistically significant difference in total knee cartilage volume (P = 0.0004) and thickness (P = 0.0024) compared with the normal knees. The percentage change in the cartilage thickness in women was significantly greater than that in men. Cartilage volume was significantly smaller in the ACL-injured knees than in the contralateral intact knees in this cohort. Women tended to display greater cartilage volume and thickness change after ACL injury than men. These findings indicated that women might be more susceptible to cartilage alteration after ACL injuries. III. C1 [Li, Hong; Hosseini, Ali; Li, Jing-Sheng; Gill, Thomas J.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Li, Hong] Huashan Hosp, Dept Sports Med, Shanghai, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM ahosseini@partners.org; jli30@partners.org; tgill@partners.org; gli1@partners.org FU National Institutes of Health (NIH) [R01 AR055612] FX We would like to acknowledge the support of National Institutes of Health (NIH, Grant # R01 AR055612). NR 28 TC 9 Z9 9 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-2056 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD AUG PY 2012 VL 20 IS 8 BP 1496 EP 1502 DI 10.1007/s00167-011-1723-6 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 978II UT WOS:000306733600011 PM 22037812 ER PT J AU Desai, NR Morrow, DA AF Desai, Nihar R. Morrow, David A. TI Reducing door-to-balloon time for STEMI-success at a price SO NATURE REVIEWS CARDIOLOGY LA English DT Editorial Material ID PERCUTANEOUS CORONARY INTERVENTION; ST-SEGMENT ELEVATION; ACUTE MYOCARDIAL-INFARCTION; ASSOCIATION; GUIDELINES C1 [Desai, Nihar R.; Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Div Cardiovasc Med,Dept Med, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM dmorrow@partners.org NR 10 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 EI 1759-5010 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD AUG PY 2012 VL 9 IS 8 BP 437 EP 438 DI 10.1038/nrcardio.2012.95 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977TU UT WOS:000306688500002 PM 22751263 ER PT J AU Kramer, MA Cash, SS AF Kramer, Mark A. Cash, Sydney S. TI Epilepsy as a Disorder of Cortical Network Organization SO NEUROSCIENTIST LA English DT Review DE seizure; coupling; functional network; structural network; rhythms ID TEMPORAL-LOBE EPILEPSY; GRAPH-THEORETICAL ANALYSIS; SMALL-WORLD NETWORKS; HIGH-FREQUENCY OSCILLATIONS; COMPLEX BRAIN NETWORKS; FUNCTIONAL CONNECTIVITY; SEIZURE ONSET; INTRACRANIAL EEG; FOCAL SEIZURES; IN-VIVO AB The brain is naturally considered as a network of interacting elements which, when functioning properly, produces an enormous range of dynamic, adaptable behavior. However, when elements of this network fail, pathological changes ensue, including epilepsy, one of the most common brain disorders. This review examines some aspects of cortical network organization that distinguish epileptic cortex from normal brain as well as the dynamics of network activity before and during seizures, focusing primarily on focal seizures. The review is organized around four phases of the seizure: the interictal period, onset, propagation, and termination. For each phase, the authors discuss the most common rhythmic characteristics of macroscopic brain voltage activity and outline the observed functional network features. Although the characteristics of functional networks that support the epileptic seizure remain an area of active research, the prevailing trends point to a complex set of network dynamics between, before, and during seizures. C1 [Kramer, Mark A.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA. RP Kramer, MA (reprint author), Boston Univ, Dept Math & Stat 111, Cummington St, Boston, MA 02215 USA. EM mak@math.bu.edu RI Kramer, Mark/A-1291-2014 FU Scientific Interface from the Burroughs Wellcome Fund; National Institute of Neurological Disorders and Stroke [R01 NS062092] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: M. A. K. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. S. S. C. was supported by funds from the National Institute of Neurological Disorders and Stroke Grant R01 NS062092. NR 81 TC 88 Z9 89 U1 2 U2 30 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD AUG PY 2012 VL 18 IS 4 BP 360 EP 372 DI 10.1177/1073858411422754 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 978HW UT WOS:000306732400010 PM 22235060 ER PT J AU Jimenez, M Hu, FB Marino, M Li, Y Joshipura, KJ AF Jimenez, Monik Hu, Frank B. Marino, Miguel Li, Yi Joshipura, Kaumudi J. TI Prospective Associations Between Measures of Adiposity and Periodontal Disease SO OBESITY LA English DT Article ID MALE HEALTH-PROFESSIONALS; CORONARY-HEART-DISEASE; PHYSICAL-ACTIVITY; SYSTEMIC-DISEASE; SMOKING HISTORY; ORAL-HEALTH; OBESITY; VALIDITY; QUESTIONNAIRE; INFLAMMATION AB Obesity induced inflammation may promote periodontal tissue destruction and bone resorption inducing tooth loss. We examined the association between measures of adiposity and self-reported periodontal disease, using data from 36,910 healthy male participants of the Health Professionals Follow-Up Study (HPFS) who were free of periodontal disease at baseline and followed for <= 20 years (1986-2006). Self-reported height, weight, and periodontal disease data were collected at baseline, weight and periodontal disease were additionally collected on biennial follow-up questionnaires and waist and hip circumference were self-reported in 1987. These self-reported measures have been previously validated. The multivariable adjusted associations between BMI (kg/m(2)), waist circumference (WC), waist-to-hip ratio (WHR), and first report of periodontal disease diagnosis were evaluated using time-varying Cox models. We observed 2,979 new periodontal disease diagnoses during 596,561 person-years of follow-up. Significant associations and trends were observed between all measures of adiposity and periodontal disease after adjusting for age, smoking, race, dental profession, physical activity, fruit and vegetable intake, alcohol consumption, and diabetes status at baseline. BMI >= 30 kg/m(2) compared to BMI 18.5-24.9 kg/m(2) was significantly associated with greater risk of periodontal disease (hazard ratios (HR) = 1.30; 95% confidence interval (CI): 1.17-1.45). Elevated WC and WHR were significantly associated with a greater risk of periodontal disease (HR for extreme quintiles: WC = 1.27, 95% CI: 1.11-1.46; WHR = 1.34, 95% CI: 1.17-1.54). The associations of BMI and WC were significant even among nondiabetics and never smokers. Given the high prevalence of overweight, obesity, and periodontal disease this association may be of substantial public health importance. C1 [Hu, Frank B.; Joshipura, Kaumudi J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jimenez, Monik] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA USA. [Marino, Miguel; Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joshipura, Kaumudi J.] Univ Puerto Rico, Sch Dent, Ctr Clin Res & Hlth Promot, San Juan, PR 00936 USA. [Joshipura, Kaumudi J.] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. RP Joshipura, KJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM kaumudi.joshipura@upr.edu OI Joshipura, Kaumudi/0000-0003-1964-7579 FU NCI NIH HHS [CA55075, P01 CA055075]; NHLBI NIH HHS [R01 HL088521, R01HL088521]; NIDCR NIH HHS [K24 DE016884, K24DE016884, T32 DE007151, T32DE07151]; NIDDK NIH HHS [DK58845, R01 DK058845]; NIGMS NIH HHS [R25 GM055353, R25GM55353]; NIMHD NIH HHS [L32 MD006283] NR 39 TC 17 Z9 17 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD AUG PY 2012 VL 20 IS 8 BP 1718 EP 1725 DI 10.1038/oby.2011.291 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 980UY UT WOS:000306920900024 PM 21979390 ER PT J AU Halpin, C Shi, H Reda, D Antonelli, PJ Babu, S Carey, JP Gantz, BJ Goebel, JA Hammerschlag, PE Harris, JP Isaacson, B Lee, D Linstrom, CJ Parnes, LS Slattery, WH Telian, SA Vrabec, JT Rauch, S AF Halpin, Chris Shi, Helen Reda, Domenic Antonelli, Patrick J. Babu, Seilesh Carey, John P. Gantz, Bruce J. Goebel, Joel A. Hammerschlag, Paul E. Harris, Jeffrey P. Isaacson, Brandon Lee, Daniel Linstrom, Chris J. Parnes, Lorne S. Slattery, William H. Telian, Steven A. Vrabec, Jeffrey T. Rauch, Steven TI Audiology in the Sudden Hearing Loss Clinical Trial SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Audiometry; Sudden hearing loss; Word recognition AB Objective: To report the pretreatment and posttreatment population characteristics and the overall stability of the audiologic outcomes found during the Sudden Hearing Loss Clinical Trial (ClinicalTrials.gov: Identifier NCT00097448). Study Design: Multicenter, prospective randomized noninferiority trial of oral versus intratympanic (IT) steroid treatment of sudden sensorineural hearing loss (SSNHL). Setting: Fifteen academically based otology practices. Patients: Two hundred fifty patients with unilateral SSNHL presenting within 14 days of onset with 50 dBHL or greater pure tone average hearing threshold in the affected ear. Intervention: Either 60 mg/d oral prednisone for 14 days with a 5-day taper (121 patients) or 4 IT doses for 14 days of 40 mg/ml methylprednisolone (129 patients). Main Outcome Measure: Primary end point was change in hearing [dB PTA] at 2 months after treatment. Noninferiority was defined as less than 10 dB difference in hearing outcome between treatments. In this article, pretreatment and posttreatment hearing findings will be reported in detail. Results: A general (and stable) effect of treatment and a specific effect of greater improvement at low frequencies were found in both treatment groups. Conclusion: Hearing improvements are stable, and a significantly greater improvement occurs with lower frequency after either oral or IT steroid treatment of SSNHL. C1 [Halpin, Chris] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Halpin, Chris; Lee, Daniel; Rauch, Steven] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shi, Helen; Reda, Domenic] Hines Cooperat Studies Coordinating Ctr, Hines, IL USA. [Antonelli, Patrick J.] Univ Florida, Dept Otolaryngol, Gainesville, FL USA. [Babu, Seilesh] Michigan Ear Inst, Dept Otol Skull Base Surg, Farmington Hills, MI USA. [Carey, John P.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Gantz, Bruce J.] Univ Iowa Hosp & Clin, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. [Goebel, Joel A.] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. [Hammerschlag, Paul E.] NYU, Sch Med, Dept Otolaryngol, New York, NY USA. [Harris, Jeffrey P.] Univ Calif San Diego, Med Ctr, Div Otolaryngol Head & Neck Surg, San Diego, CA 92103 USA. [Isaacson, Brandon] Univ Texas SW Med Ctr Dallas, Dept Otolaryngol Head & Neck Surg, Dallas, TX 75390 USA. [Linstrom, Chris J.] New York Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, New York, NY 10003 USA. [Parnes, Lorne S.] London Hlth Sci Ctr Res Inc, Dept Otolaryngol, London, ON, Canada. [Slattery, William H.] Univ So Calif, House Ear Inst, Los Angeles, CA USA. [Telian, Steven A.] Univ Michigan, Dept Otolaryngol, Ann Arbor, MI 48109 USA. [Vrabec, Jeffrey T.] Baylor Coll Med, Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. RP Halpin, C (reprint author), Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. EM chris_halpin@meei.harvard.edu RI Isaacson, Brandon/A-6358-2013 FU NCATS NIH HHS [UL1 TR000064]; NIDCD NIH HHS [U01 DC006296, P50 DC000242] NR 10 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD AUG PY 2012 VL 33 IS 6 BP 907 EP 911 DI 10.1097/MAO.0b013e31825d9a44 PG 5 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 977ZD UT WOS:000306703900008 PM 22805100 ER PT J AU Plotkin, SR Merker, VL Halpin, C Jennings, D McKenna, MJ Harris, GJ Barker, FG AF Plotkin, Scott R. Merker, Vanessa L. Halpin, Chris Jennings, Dominique McKenna, Michael J. Harris, Gordon J. Barker, Fred G., II TI Bevacizumab for Progressive Vestibular Schwannoma in Neurofibromatosis Type 2: A Retrospective Review of 31 Patients SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Angiogenesis; Bevacizumab; Neurofibromatosis; Schwannoma; VEGF; Vestibular ID NATURAL-HISTORY CONSORTIUM; QUALITY-OF-LIFE; HEARING IMPAIRMENT; GROWTH; TRIAL; GLIOBLASTOMA; INHIBITION; REGRESSION; CRITERIA; DRUG AB Objective: Early studies suggest that bevacizumab treatment can result in tumor shrinkage and hearing improvement for some patients with neurofibromatosis type 2 (NF2). The aim of this study was to report extended follow-up in a larger cohort of similarly treated patients. \ Study Design: Retrospective study. Setting: Tertiary referral center Patients: Thirty-one consecutive NF2 patients who received bevacizumab for progressive vestibular schwannomas. Main Outcome Measure: Hearing improvement, defined as an improvement in word recognition score above the 95% critical difference compared with baseline, and radiographic response, defined as a 20% or greater decrease in tumor volume compared with baseline. Results: The median age was 26 years (range, 12-73 yr). The median volumetric tumor growth rate before treatment was 64% per year. At the time of analysis, the median duration of treatment was 14 months (range, 6-41 mo) with a total of 47 patient-years of follow-up. A hearing response occurred in 57% (13/23) of evaluable patients and a radiographic response in 55% (17/31) of target vestibular schwannomas. The median time to response was 3 months for both end points. The only clinical or radiographic feature at baseline that correlated with change in tumor volume at 3 months was the mean apparent diffusion coefficient value, a radiologic marker of edema (p = 0.036). Ninety percent of patients had stable or improved hearing after 1 year of treatment and 61% at 3 years; 88% of patients had stable or decreased tumor size after 1 year of treatment and 54% at 3 years. Overall, treatment was well tolerated. Conclusion: Bevacizumab treatment was followed by hearing improvement and tumor shrinkage in more than 50% of progressive vestibular schwannomas in NF2 patients. Stable or improved hearing was retained in the majority of patients. C1 [Plotkin, Scott R.; Merker, Vanessa L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Halpin, Chris] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Jennings, Dominique] AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Harris, Gordon J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org OI Merker, Vanessa/0000-0002-4542-5227 FU Department of Defense [NF050202]; Children's Tumor Foundation; National Institutes of Health FX Dr. Harris is a consultant for Fovia, Inc., and Tele3D Advantage. Dr. Plotkin has received grants from the Department of Defense (NF050202), Children's Tumor Foundation, and National Institutes of Health. NR 32 TC 57 Z9 58 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD AUG PY 2012 VL 33 IS 6 BP 1046 EP 1052 DI 10.1097/MAO.0b013e31825e73f5 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 977ZD UT WOS:000306703900031 PM 22805104 ER PT J AU Kilmer, G Bell, P Festa, F Rollins, S Jensen, P McBride, A Hommema, E Webb, B LaBaer, J Vattem, K AF Kilmer, Greg Bell, Peter Festa, Fernanda Rollins, Sean Jensen, Penny McBride, Aaron Hommema, Eric Webb, Brian LaBaer, Josh Vattem, Krishna TI Human In Vitro Translation Systems for Rapid and High Yield Expression of Functional Proteins SO PROTEIN SCIENCE LA English DT Meeting Abstract CT 26th Annual Symposium of the Protein-Society CY AUG 05-08, 2012 CL San Diego, CA SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst C1 [Kilmer, Greg; Bell, Peter; Jensen, Penny; McBride, Aaron; Hommema, Eric; Webb, Brian; Vattem, Krishna] Thermofisher, R&D, Rockford, IL USA. [Festa, Fernanda; LaBaer, Josh] Arizona State Univ, Biodesign Inst, Tempe, AZ USA. [Rollins, Sean] Massachusetts Gen Hosp, Div Infect Dis, 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 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 2012 VL 21 SU 1 SI SI BP 212 EP 212 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 982CR UT WOS:000307019800396 ER PT J AU Liu, J Kurella, V Lecour, L Worthylake, D AF Liu, Jing Kurella, Vinodh Lecour, Louis Worthylake, David TI Crystal structure and in vitro analysis of human IQGAP1 Calponin homology domain: implication for its interactions with Ca2+bound Calmodulin and F-actin SO PROTEIN SCIENCE LA English DT Meeting Abstract CT 26th Annual Symposium of the Protein-Society CY AUG 05-08, 2012 CL San Diego, CA SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst C1 [Liu, Jing; Lecour, Louis; Worthylake, David] LSU Sch Med New Orleans, New Orleans, LA 70112 USA. [Kurella, Vinodh] Dana Farber Canc Inst, Boston, MA 02115 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 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 2012 VL 21 SU 1 SI SI BP 227 EP 228 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 982CR UT WOS:000307019800433 ER PT J AU Horan, WP Foti, D Hajcak, G Wynn, JK Green, MF AF Horan, W. P. Foti, D. Hajcak, G. Wynn, J. K. Green, M. F. TI Impaired neural response to internal but not external feedback in schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Error-related negativity; event-related potential (ERP); feedback negativity; reward sensitivity; schizophrenia ID PSYCHIATRIC RATING-SCALE; STRIATAL REWARD PREDICTION; CINGULATE CORTEX ACTIVITY; ERROR-RELATED NEGATIVITY; QUALITY-ASSURANCE; BRAIN ACTIVITY; DYSFUNCTION; ACTIVATION; SENSITIVITY; PERFORMANCE AB Background. Accurate monitoring and integration of both internal and external feedback is crucial for guiding current and future behavior. These aspects of performance monitoring are commonly indexed by two event-related potential (ERP) components: error-related negativity (ERN) and feedback negativity (FN). The ERN indexes internal response monitoring and is sensitive to the commission of erroneous versus correct responses, and the FN indexes external feedback monitoring of positive versus negative outcomes. Although individuals with schizophrenia consistently demonstrate a diminished ERN, the integrity of the FN has received minimal consideration. Method. The current research sought to clarify the scope of feedback processing impairments in schizophrenia in two studies: study 1 examined the ERN elicited in a flanker task in 16 out-patients and 14 healthy controls; study 2 examined the EN on a simple monetary gambling task in expanded samples of 35 out-patients and 33 healthy controls. Results. Study 1 replicated prior reports of an impaired ERN in schizophrenia. By contrast, patients and controls demonstrated comparable FN differentiation between reward and non-reward feedback in study 2. Conclusions. The differential pattern across tasks suggests that basic sensitivity to external feedback indicating reward versus non-reward is intact in schizophrenia, at least under the relatively simple task conditions used in this study. Further efforts to specify intact and impaired reward-processing subcomponents in schizophrenia may help to shed light on the diminished motivation and goal-seeking behavior that are commonly seen in this disorder. C1 [Horan, W. P.; Wynn, J. K.; Green, M. F.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Foti, D.; Hajcak, G.] SUNY Stony Brook, Stony Brook, NY 11794 USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NARSAD Young Investigator Award; NIMH [MH043292, MH065707] FX Funding for this project came from a NARSAD Young Investigator Award (to W.P.H.) and NIMH grants MH043292 and MH065707 (to M.F.G.) NR 51 TC 18 Z9 18 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2012 VL 42 IS 8 BP 1637 EP 1647 DI 10.1017/S0033291711002819 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 980JS UT WOS:000306890100007 PM 22152069 ER PT J AU Sosnovik, DE Nahrendorf, M Caravan, P AF Sosnovik, David E. Nahrendorf, Matthias Caravan, Peter TI Science to Practice: How Will Myocardial Inflammation Be Imaged with MR Imaging? SO RADIOLOGY LA English DT Article ID INFARCTED MYOCARDIUM; IN-VIVO; RESONANCE; ATORVASTATIN; NANOPARTICLE; CLEARANCE; ISCHEMIA AB The elegant study by Naresh and colleagues (1) synthesizes many of the best aspects of molecular magnetic resonance (MR) imaging: Quantitative serial imaging of a well-defined molecular process is performed in vivo, and its results are correlated with sensitive measures of left ventricular function. The technique described adds a valuable tool to the molecular imaging armamentarium. How, then, will myocardial inflammation be imaged with MR imaging? The only clinical experience to date has been with iron oxide nanoparticles (2,3). Their excellent sensitivity, dynamic range, and safety record make them a highly appealing choice. It will be critical, however, for any iron oxide nanoparticle that is used clinically to be well studied and validated in animal models of the disease before it is used in humans. A "group effect" cannot be assumed, even in the case of fairly similar iron oxide nanoparticles. The use of MR imaging-detectable liposomes appears promising, and initial clinical studies with fluorine-containing liposomes are likely to begin shortly. The clinical use of gadolinium-labeled liposomes appears further away, and the approach described by Naresh and colleagues is thus likely to remain confined to preclinical investigation for the foreseeable future. The development of novel anti-inflammatory therapies, however, will require robust imaging tools to shepherd these agents through preclinical studies and into the clinical arena. The approach described by Naresh et al adds a valuable tool to the preclinical molecular imaging armamentarium. C1 [Sosnovik, David E.; Caravan, Peter] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA. RP Sosnovik, DE (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. FU Siemens Medical FX D.E.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is a consultant for Siemens Medical; institution has patent pending with Vital Imaging Agents and receives research support from Siemens Medical. Other relationships: none to disclose. M.N. No potential conflicts of interest to disclose. P.C. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution has grants or grants pending with Sanofi; holds stock or stock options in Collagen Medical, Factor 1A, and Catalyst Medical. Other relationships: none to disclose. NR 13 TC 1 Z9 1 U1 0 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2012 VL 264 IS 2 BP 309 EP 311 DI 10.1148/radiol.12121094 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 977KX UT WOS:000306660000001 PM 22821689 ER PT J AU Thrall, JH AF Thrall, James H. TI Radiation Exposure in CT Scanning and Risk: Where Are We? SO RADIOLOGY LA English DT Article ID IONIZING-RADIATION; DOSE REDUCTION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,FND 216, Boston, MA 02114 USA. EM jthrall@partners.org NR 20 TC 27 Z9 29 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2012 VL 264 IS 2 BP 325 EP 328 DI 10.1148/radiol.12121137 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 977KX UT WOS:000306660000004 PM 22821692 ER PT J AU Marconescu, P Graviss, EA Musher, DM AF Marconescu, Praveena Graviss, Edward A. Musher, Daniel M. TI Rates of killing of methicillin-resistant Staphylococcus aureus by ceftaroline, daptomycin, and telavancin compared to that of vancomycin SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IN-VITRO ACTIVITY; BACTEREMIA; INTERMEDIATE; STRAINS; IMPACT AB Treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) remains an important concern. In order to investigate new MRSA treatment modalities, we used standard time-kill assays to determine the in vitro killing rate of 22 strains of MRSA by vancomycin, telavancin, daptomycin, and ceftaroline. Studies were carried out with 7-10-times the minimum bactericidal concentrations of each antibiotic in broth culture for 24 h, with subculture at 4, 8, and 24 h. We found that killing by ceftaroline closely paralleled that of vancomycin. Telavancin killed bacteria significantly more slowly, whereas daptomycin killed significantly more rapidly. C1 [Marconescu, Praveena; Musher, Daniel M.] ME DeBakey Vet Affairs Med Ctr, Houston, TX 77040 USA. [Marconescu, Praveena] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Graviss, Edward A.; Musher, Daniel M.] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Graviss, Edward A.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Graviss, Edward A.] Methodist Hosp, Res Inst, Dept Pathol & Genom Med, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Musher, DM (reprint author), ME DeBakey Vet Affairs Med Ctr, 2002 Holcombe, Houston, TX 77040 USA. EM daniel.musher@va.gov NR 10 TC 11 Z9 11 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PD AUG PY 2012 VL 44 IS 8 BP 620 EP 622 DI 10.3109/00365548.2012.669843 PG 3 WC Infectious Diseases SC Infectious Diseases GA 976EL UT WOS:000306563500011 PM 22668202 ER PT J AU Ma, Y Shurin, GV Gutkin, DW Shurin, MR AF Ma, Yang Shurin, Galina V. Gutkin, Dmitriy W. Shurin, Michael R. TI Tumor associated regulatory dendritic cells SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Dendritic cells; Cancer; Immunosuppression; Immune escape; Tolerance; Immune regulatory cells ID EXPRESSING INDOLEAMINE 2,3-DIOXYGENASE; ANTITUMOR IMMUNE-RESPONSES; DRAINING LYMPH-NODES; CD4(+) T-CELLS; IN-VIVO; BREAST-CANCER; CUTTING EDGE; MULTIPLE-MYELOMA; OVARIAN-CANCER; LUNG-CANCER AB Immune effector and regulatory cells in the tumor microenvironment are key factors in tumor development and progression as the pathogenesis of cancer vitally depends on the multifaceted interactions between various microenvironmental stimuli provided by tumor-associated immune cells. Immune regulatory cells participate in all stages of cancer development from the induction of genomic instability to the maintenance of intratumoral angiogenesis, proliferation and spreading of malignant cells, and formation of premetastatic niches in distal tissues. Dendritic cells in the tumor microenvironment serve as a double-edged sword and, in addition to initiating potent anti-tumor immune responses, may mediate genomic damage, support neovascularization, block anti-tumor immunity and stimulate cancerous cell growth and spreading. Regulatory dendritic cells in cancer may directly and indirectly maintain antigen-specific and non-specific T cell unresponsiveness by controlling T cell polarization, MDSC and Treg differentiation and activity, and affecting specific microenvironmental conditions in premalignant niches. Understanding the mechanisms involved in regulatory dendritic cell polarization and operation and revealing pharmacological means for harnessing these pathways will provide additional opportunities for modifying the tumor microenvironment and improving the efficacy of different therapeutic approaches to cancer. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Ma, Yang; Shurin, Galina V.; Shurin, Michael R.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15261 USA. [Gutkin, Dmitriy W.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Shurin, Michael R.] Univ Pittsburgh, Med Ctr, Dept Immunol, Pittsburgh, PA USA. RP Shurin, MR (reprint author), Univ Pittsburgh, Med Ctr, Dept Pathol, 5735 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM shurinmr@upmc.edu FU NCI NIH HHS [R01 CA154369-01A1, R01 CA154369] NR 150 TC 34 Z9 40 U1 1 U2 30 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD AUG PY 2012 VL 22 IS 4 BP 298 EP 306 DI 10.1016/j.semcancer.2012.02.010 PG 9 WC Oncology SC Oncology GA 978FF UT WOS:000306725300005 PM 22414911 ER PT J AU Tao, WD Liu, M Fisher, M Wang, DR Li, J Furie, KL Hao, ZL Lin, S Zhang, CF Zeng, QT Wu, B AF Tao, Wen-Dan Liu, Ming Fisher, Marc Wang, De-Ren Li, Jie Furie, Karen L. Hao, Zi-Long Lin, Sen Zhang, Cai-Fei Zeng, Quan-Tao Wu, Bo TI Posterior Versus Anterior Circulation Infarction How Different Are the Neurological Deficits? SO STROKE LA English DT Article DE posterior circulation infarction; anterior circulation infarction; neurological deficits ID OXFORDSHIRE COMMUNITY STROKE; CEREBRAL-ARTERY OCCLUSION; PURE MOTOR HEMIPARESIS; RADIOLOGICAL CORRELATION; CLINICAL CLASSIFICATION; ISCHEMIC-STROKE; REGISTRY; TERRITORIES; DISABILITY; HEMIPLEGIA AB Background and Purpose-Distinguishing between symptoms of posterior circulation infarction (PCI) and anterior circulation infarction (ACI) can be challenging. This study evaluated the frequency of symptoms/signs in the 2 vascular territories to determine the diagnostic value of particular symptoms/signs for PCI. Methods-Neurological deficits were reviewed and compared from 1174 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. The diagnostic value of specific symptoms/signs for PCI was determined by measuring their sensitivity, specificity, positive predictive value (PPV), and the OR. Results-Homolateral hemiplegia (PCI, 53.6% versus ACI, 74.9%; P<0.001), central facial/lingual palsy (PCI, 40.7% versus ACI, 62.2%; P<0.001), and hemisensory deficits (PCI, 36.4% versus ACI, 34.2%; P=0.479) were the 3 most common symptoms/signs in PCI and ACI. The signs with the highest predictive values favoring a diagnosis of PCI were Horner's syndrome (4.0% versus 0%; P<0.001; PPV=100.0%; OR=4.00), crossed sensory deficits (3.0% versus 0%; P<0.001; PPV=100.0%; OR=3.98), quadrantanopia (1.3% versus 0%; P<0.001; PPV=100.0%; OR=3.93), oculomotor nerve palsy (4.0% versus 0%; P<0.001; PPV=100.0%; OR=4.00), and crossed motor deficits (4.0% versus 0.1%; P<0.001; PPV=92.3%; OR=36.04); however, all had a very low sensitivity, ranging from 1.3% to 4.0%. Conclusions-This study indicates that the symptoms/signs considered typical of PCI occur far less often than was expected. Inaccurate localization would occur commonly if clinicians relied on the clinical neurological deficits alone to differentiate PCI from ACI. Neuroimaging is vital to ensure accurate localization of cerebral infarction. (Stroke. 2012;43:2060-2065.) C1 [Tao, Wen-Dan; Liu, Ming; Wang, De-Ren; Li, Jie; Hao, Zi-Long; Lin, Sen; Zhang, Cai-Fei; Zeng, Quan-Tao; Wu, Bo] Sichuan Univ, W China Hosp, Dept Neurol, Stroke Clin Res Unit, Chengdu 610041, Sichuan Provinc, Peoples R China. [Liu, Ming] Sichuan Univ, W China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan Provinc, Peoples R China. [Liu, Ming] Sichuan Univ, W China Hosp, Ctr Canc, Chengdu 610041, Sichuan Provinc, Peoples R China. [Tao, Wen-Dan; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Fisher, Marc] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. RP Liu, M (reprint author), Sichuan Univ, W China Hosp, Dept Neurol, Stroke Clin Res Unit, 37 Guo Xue Xiang, Chengdu 610041, Sichuan Provinc, Peoples R China. EM wyplmh@hotmail.com OI Wang, Deren/0000-0002-2388-3585 FU Science and Technology Department of Sichuan Province of China [2011SZ0202] FX This work was funded by Science and Technology Department of Sichuan Province of China (Project No. 2011SZ0202). NR 29 TC 15 Z9 17 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2012 VL 43 IS 8 BP 2060 EP 2065 DI 10.1161/STROKEAHA.112.652420 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 977UC UT WOS:000306689300018 PM 22678088 ER PT J AU Silva, GS Farrell, S Shandra, E Viswanathan, A Schwamm, LH AF Silva, Gisele S. Farrell, Shawn Shandra, Emma Viswanathan, Anand Schwamm, Lee H. TI The Status of Telestroke in the United States A Survey of Currently Active Stroke Telemedicine Programs SO STROKE LA English DT Article DE telemedicine; telestroke; inventory; barriers ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; AMERICAN-HEART-ASSOCIATION; THROMBOLYSIS; BARRIERS; CARE; CENTERS; SYSTEMS; RATES AB Background and Purpose-Little is known about adoption or success of telestroke networks outside of published or federally funded programs. Under contract to the Health Resource Services Administration, we conducted an environmental scan of telestroke programs in the United States. Methods-An analyst contacted all potential programs identified in comprehensive online searches, interviewed respondents, and collected response data about structural and functional components of currently operating telestroke programs. Results-Among 97 potential programs contacted, 56 programs had confirmed telestroke activity, and 38 programs (68%) from 27 states participated. Hospital and community characteristics of nonparticipating programs were similar to those of participating ones. The top 3 clinical needs met by the telestroke were emergency department consultation (100%), patient triage (83.8%), and inpatient teleconsultation (46.0%). Telestroke programs were in operation a median of 2.44 years (interquartile range, 1.36-3.44 years); 94.6% used 2-way, real-time interactive video plus imaging, but only 44% used dedicated telemedicine consultation software. The mean number of spokes per hub increased significantly from 2007 to 2008 to 2009 (3.78 versus 7.60; P < 0.05), and >80% of spoke sites were rural or small hospitals. Reimbursement was absent for >40% of sites. Sites rated inability to obtain physician licensure (27.77%), lack of program funds (27.77%), and lack of reimbursement (19.44%) as the most important barriers to program growth. Conclusions-Telestroke is a widespread and growing practice model. Important barriers to expansion amenable to change relate to organizational, technical, and educational domains and external economic and regulatory forces. (Stroke. 2012;43:2078-2085.) C1 [Silva, Gisele S.] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. [Silva, Gisele S.] Albert Einstein Hosp, Neurol Program, Sao Paulo, Brazil. [Farrell, Shawn] Childrens Hosp, Ctr Innovat, Boston, MA 02115 USA. [Shandra, Emma] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Viswanathan, Anand; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Silva, GS (reprint author), Altino Arantes Ave,Apt 81, BR-04042033 Sao Paulo, Brazil. EM giselesampaio@hotmail.com OI Schwamm, Lee/0000-0003-0592-9145 FU Health Resource Services Administration Requisition [09-HRS9923-AB] FX This study was supported (Dr Silva, S. Farrell, MBA, Dr Schwamm) in part by a contract from Health Resource Services Administration Requisition 09-HRS9923-AB (Stroke and Traumatic Brain Injury Telehealth Services). NR 28 TC 55 Z9 55 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2012 VL 43 IS 8 BP 2078 EP U138 DI 10.1161/STROKEAHA.111.645861 PG 31 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 977UC UT WOS:000306689300021 PM 22700532 ER PT J AU Brouwers, HB Biffi, A McNamara, KA Ayres, AM Valant, V Schwab, K Romero, JM Viswanathan, A Greenberg, SM Rosand, J Goldstein, JN AF Brouwers, H. Bart Biffi, Alessandro McNamara, Kristen A. Ayres, Alison M. Valant, Valerie Schwab, Kristin Romero, Javier M. Viswanathan, Anand Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. TI Apolipoprotein E Genotype Is Associated With CT Angiography Spot Sign in Lobar Intracerebral Hemorrhage SO STROKE LA English DT Article DE APOE; CTA spot sign; genetics; hematoma expansion; intracerebral hemorrhage ID CEREBRAL AMYLOID ANGIOPATHY; PREDICTS HEMATOMA EXPANSION; CONTRAST EXTRAVASATION; IDENTIFIES PATIENTS; HIGHEST RISK; MORTALITY; GROWTH; SCORE AB Background and Purpose-The CT angiography (CTA) spot sign predicts hematoma expansion and poor outcome in patients with primary intracerebral hemorrhage (ICH). The biological underpinnings of the spot sign remain poorly understood; it may be that the underlying vasculopathy influences its presence. Therefore, we conducted a study to identify genetic predictors of the spot sign. Methods-In an ongoing prospective cohort study, we analyzed 371 patients with CTA and genetic data available. CTAs were reviewed for the spot sign by 2 experienced readers, blinded to clinical data, according to validated criteria. Analyses were stratified by ICH location. Results-In multivariate analysis, patients on warfarin were more likely to have a spot sign regardless of ICH location (OR, 3.85; 95% CI, 1.33-11.13 in deep ICH and OR, 2.86; 95% CI, 1.33-6.13 in lobar ICH). Apolipoprotein E epsilon 2, but not epsilon 4, was associated with the presence of a spot sign in lobar ICH (OR, 2.09; 95% CI, 1.05-4.19). There was no effect for epsilon 2 or epsilon 4 in deep ICH. Conclusions-Patients with ICH on warfarin are more likely to present with a spot sign regardless of ICH location. Among patients with lobar ICH, those who possess the apolipoprotein E epsilon 2 allele are more likely to have a spot sign. Given the established relationship between apolipoprotein E epsilon 2 and vasculopathic changes in cerebral amyloid angiopathy, our findings suggest that both hemostatic factors and vessel pathology influence spot sign presence. (Stroke. 2012;43:2120-2125.) C1 [Brouwers, H. Bart] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Rosand Lab, Boston, MA 02114 USA. [Brouwers, H. Bart; Biffi, Alessandro; McNamara, Kristen A.; Ayres, Alison M.; Valant, Valerie; Schwab, Kristin; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Brouwers, H. Bart; Biffi, Alessandro; McNamara, Kristen A.; Ayres, Alison M.; Schwab, Kristin; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Serv Neuroradiol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Dept Emergency Med, Boston, MA 02114 USA. [Brouwers, H. Bart; Biffi, Alessandro; Viswanathan, Anand; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurocrit Care & Emergency Neurol,Dept Neurol, Boston, MA 02114 USA. RP Brouwers, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Rosand Lab, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM brouwers@chgr.mgh.harvard.edu RI Goldstein, Joshua/H-8953-2016; OI Ayres, Alison/0000-0002-5492-1695 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [R01NS073344, R01NS059727, 5K23NS059774]; Edward and Maybeth Sonn Research Fund; NIH-NINDS Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) fellowship [P50NS051343]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; National Institutes of Health; American Heart Association; National Institute of Neurological Disorders and Stroke FX All funding entities had no involvement in study design, data collection, analysis, and interpretation, or writing of the article or in the decision to submit for publication. The project described was supported by National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) grants R01NS073344, R01NS059727, and 5K23NS059774 and the Edward and Maybeth Sonn Research Fund. Dr Brouwers was supported by the NIH-NINDS Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) fellowship grant P50NS051343. Dr Biffi was supported in part by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the NINDS.; J.M.R. is on the Imaging Committee of the Desmoteplase in Acute Ischemic Stroke Trial (DIAS) trial and on the advisory board of Lundbeck Pharmaceuticals. S.M.G. received a research grant the National Institutes of Health; received honoraria from Medtronic and Pfizer; and is a consultant/on the advisory board of Hoffman-La Roche, Janssen Alzheimer Immunotherapy, and Bristol-Myers Squibb Company. J.R. received research grants from the National Institutes of Health and the American Heart Association. J.N.G. received a research grant from the National Institute of Neurological Disorders and Stroke and is a consultant/on the advisory board of CSL Behring. NR 24 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2012 VL 43 IS 8 BP 2120 EP 2125 DI 10.1161/STROKEAHA.112.659094 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 977UC UT WOS:000306689300028 PM 22621984 ER PT J AU McKinney, JS Kostis, WJ AF McKinney, James S. Kostis, William J. TI Statin Therapy and the Risk of Intracerebral Hemorrhage A Meta-Analysis of 31 Randomized Controlled Trials SO STROKE LA English DT Article DE hemorrhagic stroke; intracerebral hemorrhage; meta-analysis; statin ID PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; AVERAGE CHOLESTEROL LEVELS; HIGH-DOSE ATORVASTATIN; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; PRIMARY PREVENTION; LDL CHOLESTEROL; BLOOD-PRESSURE; DOUBLE-BLIND AB Background and Purpose-Statin therapy decreases the risk of ischemic stroke. An increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue, we performed a meta-analysis of randomized controlled trials using statins that reported ICH. Methods-We performed a literature search of Medline, Web of Science, and The Cochrane Library through January 25, 2012, and identified additional randomized controlled trials by reviewing reference lists of retrieved studies and prior meta-analyses. All randomized controlled trials of statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. Thirty-one randomized controlled trials were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results-A total of 91 588 subjects were included in the active group and 91 215 in the control group. There was no significant difference in incidence of ICH observed in the active treatment group versus control (OR, 1.08; 95% CI, 0.88-1.32; P = 0.47). ICH risk was not related to the degree of low-density lipoprotein reduction or achieved low-density lipoprotein cholesterol. Total stroke (OR, 0.84; 95% CI, 0.78-0.91; P < 0.0001) and all-cause mortality (OR, 0.92; CI, 0.87-0.96; P = 0.0007) were significantly reduced in the active therapy group. There was no evidence of publication bias. Conclusions-Active statin therapy was not associated with significant increase in ICH in this meta-analysis of 31 randomized controlled trials of statin therapy. A significant reduction in all stroke and all-cause mortality was observed with statin therapy. (Stroke. 2012; 43: 2149-2156.) C1 [McKinney, James S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08901 USA. [McKinney, James S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Cardiovasc Inst New Jersey, New Brunswick, NJ 08901 USA. [Kostis, William J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP McKinney, JS (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, 125 Paterson St, New Brunswick, NJ 08901 USA. EM mckinnjs@umdnj.edu FU Robert Wood Johnson Foundation; Schering-Plough Foundation FX This study was funded in part by the Robert Wood Johnson Foundation and the Schering-Plough Foundation. NR 56 TC 90 Z9 92 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD AUG PY 2012 VL 43 IS 8 BP 2149 EP U238 DI 10.1161/STROKEAHA.112.655894 PG 21 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 977UC UT WOS:000306689300033 PM 22588266 ER PT J AU Cheung, JS Wang, EF Lo, EH Sun, PZ AF Cheung, Jerry S. Wang, Enfeng Lo, Eng H. Sun, Phillip Zhe TI Stratification of Heterogeneous Diffusion MRI Ischemic Lesion With Kurtosis Imaging Evaluation of Mean Diffusion and Kurtosis MRI Mismatch in an Animal Model of Transient Focal Ischemia SO STROKE LA English DT Article DE acute ischemia; diffusion; kurtosis ID CEREBRAL-ISCHEMIA; BRAIN; INJURY; DAMAGE; WATER AB Background and Purpose-Ischemic tissue damage is heterogeneous, resulting in complex patterns in the widely used diffusion-weighted MRI. Our study examined the spatiotemporal characteristics of diffusion kurtosis imaging in an animal model of transient middle cerebral artery occlusion. Methods-Adult male Wistar rats (N = 18) were subjected to 90 minutes middle cerebral artery occlusion. Multiparametric MR images were obtained during middle cerebral artery occlusion and 20 minutes after reperfusion with diffusion-weighted MRI obtained using 8 b-values from 250 to 3000 s/mm(2) in 6 diffusion gradient directions. Diffusion and kurtosis lesions were outlined in shuffled images by 2 investigators independently. T-2 MRI was obtained 24 hours after middle cerebral artery occlusion to evaluate stroke outcome. Results-Mean diffusion lesion (23.5% +/- 8.1%, percentage of the brain slice) was significantly larger than mean kurtosis lesion (13.2% +/- 2.0%) during middle cerebral artery occlusion. Mean diffusion lesion decreased significantly after reperfusion (13.8% +/- 4.3%), whereas mean kurtosis lesion showed little change (13.0% +/- 2.5%) with their lesion size difference being insignificant. Conclusions-We demonstrated that mean diffusion/mean kurtosis mismatch recovered reasonably well on reperfusion, whereas regions with concurrent mean diffusion and mean kurtosis deficits showed poor recovery. Diffusion kurtosis imaging may help stratify heterogeneous diffusion-weighted MRI lesions for enhanced characterization of ischemic tissue injury. (Stroke. 2012; 43: 2252-2254.) C1 [Cheung, Jerry S.; Wang, Enfeng; Sun, Phillip Zhe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Boston, MA 02114 USA. [Lo, Eng H.; Sun, Phillip Zhe] Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sun, PZ (reprint author), MGH, Martinos Ctr, Room 2301,149-13th St, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU National Science Foundation of China [30900365]; American Heart Association [0835384N]; National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering [1K01EB009771]; National Institutes of Health/National Canter for Research Resources [P41RR14075] FX This study was partially supported by National Science Foundation of China-30900365, American Heart Association/Scientist Development Grant-0835384N, National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering-1K01EB009771, and National Institutes of Health/National Canter for Research Resources-P41RR14075. NR 15 TC 39 Z9 44 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2012 VL 43 IS 8 BP 2252 EP U461 DI 10.1161/STROKEAHA.112.661926 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 977UC UT WOS:000306689300051 PM 22773558 ER PT J AU Small, W Strauss, JB Jhingran, A Yashar, CM Cardenes, HR Erickson-Wittmann, BA Gullett, N Kidd, E Lee, LJ Mayr, NA Moore, D Puthawala, AA Rao, GG Varia, MA Wahl, AO Wolfson, AH Yuh, W Gaffney, DK AF Small, William, Jr. Strauss, Jonathan B. Jhingran, Anuja Yashar, Catheryn M. Cardenes, Higinia R. Erickson-Wittmann, Beth A. Gullett, Norleena Kidd, Elizabeth Lee, Larissa J. Mayr, Nina A. Moore, David Puthawala, Ajmel A. Rao, Gautam G. Varia, Mahesh A. Wahl, Andrew O. Wolfson, Aaron H. Yuh, William Gaffney, David K. TI ACR Appropriateness Criteria (R) Definitive Therapy for Early-Stage Cervical Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE Appropriateness criteria; ACR; cervix; cancer; radiotherapy ID GYNECOLOGIC-ONCOLOGY-GROUP; INTENSITY-MODULATED RADIOTHERAPY; POSITRON-EMISSION-TOMOGRAPHY; EXTENDED-FIELD IRRADIATION; SQUAMOUS-CELL CARCINOMA; PARAAORTIC LYMPH-NODES; PHASE-III TRIAL; RADIATION-THERAPY; NEOADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL AB Objectives: The definitive treatment of early-stage cervical cancer involves multidisciplinary decision making. This expert panel was convened to reach consensus on the selection of appropriate therapies based on patient and disease characteristics at presentation. Methods: 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 the treatment. Results: Three clinical variants were developed to represent common scenarios in the treatment of early-stage cervical cancer. Group members reached consensus on the appropriateness of therapeutic options. This process yielded numerical ratings and descriptive commentary. Conclusions: This manuscript represents the consensus opinion of an expert panel based on a survey of all available medical literature. This manuscript may be used to inform the clinical decision making of physicians involved in the treatment of early-stage cervical cancer. C1 [Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Strauss, Jonathan B.] Northwestern Univ, Dept Radiat Oncol, Chicago, IL 60611 USA. [Jhingran, Anuja] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yashar, Catheryn M.] Univ Calif San Diego, Dept Radiat Oncol, San Diego, CA 92103 USA. [Kidd, Elizabeth] Stanford Canc Ctr, Stanford, CA USA. [Puthawala, Ajmel A.] Long Beach Mem Med Ctr, Long Beach, CA USA. [Cardenes, Higinia R.; Gullett, Norleena] Indiana Univ, Med Ctr, Indianapolis, IN USA. [Moore, David] Indiana Univ, Sch Med, Indianapolis, IN USA. [Erickson-Wittmann, Beth A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Lee, Larissa J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mayr, Nina A.] James Canc Hosp, Ohio State Comprehens Canc Ctr, Columbus, OH USA. [Yuh, William] Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. [Rao, Gautam G.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Varia, Mahesh A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Wahl, Andrew O.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Wolfson, Aaron H.] Univ Miami, Dept Radiat Oncol, Miami, FL USA. [Gaffney, David K.] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Moore, David] Amer Congress Obstetricians & Gynecologists, Washington, DC USA. [Rao, Gautam G.] Amer Soc Clin Oncol, Alexandria, VA USA. RP Small, W (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM wsmall@nmff.org OI Strauss, Jonathan/0000-0003-0175-7251 NR 63 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 2012 VL 35 IS 4 BP 399 EP 405 DI 10.1097/COC.0b013e3182610537 PG 7 WC Oncology SC Oncology GA 976QK UT WOS:000306599200017 PM 22810416 ER PT J AU Nishino, HT Wilbur, DC Tambouret, RH AF Nishino, Ha T. Wilbur, David C. Tambouret, Rosemary H. TI Low-Grade Squamous Intraepithelial Lesion, Cannot Exclude High-Grade Squamous Intraepithelial Lesion A Category With an Increased Outcome of High-Grade Lesions: Use as a Quality Assurance Measure SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE AP cytopathology; Cytology; AP gynecological; Quality control; Squamous intraepithelial lesion ID 2001 BETHESDA SYSTEM; UNDETERMINED SIGNIFICANCE; ASC/SIL RATIO; SIL RATIO; CYTOLOGY; TERMINOLOGY; DIAGNOSIS; CELLS; HPV AB "Low-grade squamous intraepithelial lesion (LSIL), cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) is an increasingly used, equivocal interpretive category in gynecologic cytology. In an effort to evaluate its potential usefulness as a measure of quality assurance, we studied patterns of use of the LSIL-H diagnosis compared with "LSIL" and "high-grade squamous intraepithelial lesion" (HSIL) with corresponding histologic outcomes for 10 cytopathologists in our practice. In our laboratory, while the overall rate of associated cervical intraepithelial neoplasia 2 or greater on histologic follow-up for LSIL-H was intermediate between that of LSIL and HSIL, the outcomes for individual cytopathologists varied widely. Monitoring this particular utilization-outcome data with periodic confidential feedback to individual cytopathologists offers an opportunity for practice improvement within a laboratory and serves as an additional measure of quality assurance. These data may be useful for establishing and/or realigning the diagnostic criteria for this equivocal cytologic interpretation endorsed by a pathology practice. C1 [Tambouret, Rosemary H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tambouret, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 125, Boston, MA 02114 USA. EM rtambouret@partners.org NR 16 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2012 VL 138 IS 2 BP 198 EP 202 DI 10.1309/AJCP8J4ROAVWOSHQ PG 5 WC Pathology SC Pathology GA 975UC UT WOS:000306536000005 PM 22904130 ER PT J AU Renella, R Stickney, C Keswani, M Mancuso, T Casavant, D Ferguson, M Narla, A AF Renella, Raffaele Stickney, Carolyn Keswani, Mahima Mancuso, Thomas Casavant, David Ferguson, Michael Narla, Anupama TI Fulminant thrombotic microangiopathy in Pediatrics: Where diagnostic and therapeutic dilemmas meet SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; THROMBOCYTOPENIC PURPURA; ECULIZUMAB; CHILDHOOD C1 [Renella, Raffaele; Narla, Anupama] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Stickney, Carolyn; Mancuso, Thomas; Casavant, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Crit Care Med, Boston, MA USA. [Keswani, Mahima; Ferguson, Michael] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Nephrol, Boston, MA USA. [Keswani, Mahima] Childrens Natl Med Ctr, Div Nephrol, Washington, DC 20010 USA. RP Renella, R (reprint author), Dana Farber Canc Inst, Jimmy Fund Clin, Dept Pediat Oncol, Dana 3,450 Brookline Ave, Boston, MA 02115 USA. EM raffaele.renella@childrens.harvard.edu OI Renella, Raffaele/0000-0002-5041-2308 NR 17 TC 0 Z9 0 U1 0 U2 2 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 AUG PY 2012 VL 87 IS 8 BP 816 EP 818 DI 10.1002/ajh.23166 PG 3 WC Hematology SC Hematology GA 975BW UT WOS:000306482700011 PM 22407784 ER PT J AU Terry, J Calicchio, ML Rodriguez-Galindo, C Perez-Atayde, AR AF Terry, Jefferson Calicchio, Monica L. Rodriguez-Galindo, Carlos Perez-Atayde, Antonio R. TI Immunohistochemical Expression of CRX in Extracranial Malignant Small Round Cell Tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE neuroblastoma; retinoblastoma; children; malignant small round cell tumor; PNET; Ewing; Wilms tumor; rhabdomyosarcoma; desmoplastic small round cell tumor; melanocytic neoplasm ID METASTATIC RETINOBLASTOMA; SURVIVORS; RISK AB Tumor-specific immunohistochemical markers are valuable in the differential diagnosis of malignant small round cell tumors (MSRCTs). The cone-rod homeobox-containing gene (CRX) is a transcription factor that is preferentially expressed in retinal photoreceptor cells. It has been shown that the CRX antibody is a good immunohistochemical marker to differentiate retinoblastoma from other intracranial MSRCTs. Outside of the central nervous system, however, the usefulness of CRX immunohistochemistry in establishing a diagnosis of metastatic retinoblastoma is uncertain, as the expression of CRX in primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES), neuroblastoma, and other MSRCTs is unknown. Archival specimens from resections, core biopsies, and bone marrow biopsies of 41 neuroblastomas, 24 PNET/ES, 19 embryonal rhabdomyosarcomas, 17 alveolar rhabdomyosarcomas, 17 Wilms tumors, 14 desmoplastic small round cell tumors, 20 medulloblastomas, 9 pineal tumors, 17 melanocytic tumors (compound and Spitz nevi), and 8 retinoblastomas were immunostained for CRX. All retinoblastomas had strong diffuse nuclear immunoreactivity for CRX; 8 of the 20 medulloblastomas showed strong nuclear immunoreactivity either in occasional clusters of tumor cells or in rare single scattered tumor cells; 3 of the 9 pineal tumors showed strong nuclear immunoreactivity in approximately 40% to 50% of the tumor cells. Neuroblastomas, PNET/ES, embryonal rhabdomyosarcomas, alveolar rhabdomyosarcomas, Wilms tumors, desmoplastic small round cell tumors, and melanocytic tumors were all negative. Scant nonspecific cytoplasmic staining was observed in some tumors, mostly PNET/ES. These findings suggest that CRX is a useful marker to discriminate metastatic retinoblastoma from other, more common, MSRCTs of childhood. C1 [Terry, Jefferson; Calicchio, Monica L.; Rodriguez-Galindo, Carlos; Perez-Atayde, Antonio R.] Childrens Hosp, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodriguez-Galindo, Carlos] Childrens Hosp, Dept Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Perez-Atayde, AR (reprint author), Childrens Hosp, Dept Pathol, Dana Farber Canc Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM antonio.perezatayde@childrens.harvard.edu OI Terry, Jefferson/0000-0001-5464-8679 NR 11 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2012 VL 36 IS 8 BP 1165 EP 1169 DI 10.1097/PAS.0b013e3182601d84 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 977JY UT WOS:000306656500007 PM 22790857 ER PT J AU Evans, AG French, CA Cameron, MJ Fletcher, CDM Jackman, DM Lathan, CS Sholl, LM AF Evans, Andrew G. French, Christopher A. Cameron, Michael J. Fletcher, Christopher D. M. Jackman, David M. Lathan, Christopher S. Sholl, Lynette M. TI Pathologic Characteristics of NUT Midline Carcinoma Arising in the Mediastinum SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE NUT midline carcinoma; mediastinum; squamous cell carcinoma ID UPPER AERODIGESTIVE TRACT; DIFFERENTIATION; REARRANGEMENT; INHIBITION; PROTEIN; KINASE AB NUT midline carcinomas (NMCs) comprise a group of highly aggressive tumors that have been reported primarily in the head, neck, and mediastinum of younger individuals. These tumors overexpress the nuclear protein in the testis (NUT), most commonly due to a chromosomal translocation that fuses the NUT gene on chromosome 15 with the BRD4 gene on chromosome 19. Although the earliest recognized cases were described in the thymus or mediastinum, an extensive survey for NMCs among malignant thymic or other mediastinal neoplasms has not been reported. We examined NUT expression in 114 cases of poorly differentiated carcinomas or unclassified mediastinal malignancies using a clinically validated NUT-specific monoclonal antibody. Four of 114 (3.5%) cases showed nuclear NUT expression. A NUT translocation was confirmed by fluorescence in situ hybridization in 3 of these cases. These tumors arose in 2 men and 2 women with a median age of 50 years (range, 28 to 68 y). Three of the tumors were originally diagnosed as undifferentiated epithelioid or round cell malignant neoplasms; 1 tumor contained focal squamous differentiation and was originally diagnosed as a poorly differentiated squamous carcinoma of probable thymic origin. We find that the incidence of NMC within the mediastinum, particularly among undifferentiated tumors, is similar to that reported at other anatomic sites. NMC should be considered in the differential diagnosis of any poorly differentiated epithelioid mediastinal tumor, regardless of age. C1 [Evans, Andrew G.; French, Christopher A.; Cameron, Michael J.; Fletcher, Christopher D. M.; Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jackman, David M.; Lathan, Christopher S.] Dana Farber Canc Inst, Dept Thorac Oncol, Boston, MA 02115 USA. RP Sholl, LM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lmsholl@partners.org FU Dana Farber/Harvard Cancer Center [5P30CA06516-44]; US National Institutes of Health [1R01CA124633]; Samuel Waxman Cancer Research Foundation Reprogramming the Cancer Cell; American Association for Cancer Research [10-20-03-FREN] FX Supported by a Dana Farber/Harvard Cancer Center Nodal Award 5P30CA06516-44 (C.A.F.), US National Institutes of Health grant 1R01CA124633 (C.A.F.), the Samuel Waxman Cancer Research Foundation Reprogramming the Cancer Cell, and the American Association for Cancer Research grant 10-20-03-FREN (C.A.F.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 20 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2012 VL 36 IS 8 BP 1222 EP 1227 DI 10.1097/PAS.0b013e318258f03b PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 977JY UT WOS:000306656500014 PM 22790861 ER PT J AU McGrath, LM Mustanski, B Metzger, A Pine, DS Kistner-Griffin, E Cook, E Wakschlag, LS AF McGrath, L. M. Mustanski, B. Metzger, A. Pine, D. S. Kistner-Griffin, E. Cook, E. Wakschlag, L. S. TI A latent modeling approach to genotype-phenotype relationships: maternal problem behavior clusters, prenatal smoking, and MAOA genotype SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Female problem behavior; Antisocial behavior; Prenatal smoking; Monoamine oxidase A (MAOA); Gene x environment interaction ID X-CHROMOSOME INACTIVATION; OXIDASE-A GENE; MONOAMINE-OXIDASE; ANTISOCIAL-BEHAVIOR; CONDUCT DISORDER; FUNCTIONAL POLYMORPHISM; EXTERNALIZING SPECTRUM; SCREENING-TEST; LUNG-FUNCTION; SEXUAL-ABUSE AB This study illustrates the application of a latent modeling approach to genotype-phenotype relationships and gene x environment interactions, using a novel, multidimensional model of adult female problem behavior, including maternal prenatal smoking. The gene of interest is the monoamine oxidase A (MAOA) gene which has been well studied in relation to antisocial behavior. Participants were adult women (N = 192) who were sampled from a prospective pregnancy cohort of non-Hispanic, white individuals recruited from a neighborhood health clinic. Structural equation modeling was used to model a female problem behavior phenotype, which included conduct problems, substance use, impulsive-sensation seeking, interpersonal aggression, and prenatal smoking. All of the female problem behavior dimensions clustered together strongly, with the exception of prenatal smoking. A main effect of MAOA genotype and a MAOA x physical maltreatment interaction were detected with the Conduct Problems factor. Our phenotypic model showed that prenatal smoking is not simply a marker of other maternal problem behaviors. The risk variant in the MAOA main effect and interaction analyses was the high activity MAOA genotype, which is discrepant from consensus findings in male samples. This result contributes to an emerging literature on sex-specific interaction effects for MAOA. C1 [McGrath, L. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Dept Psychiat, Boston, MA 02114 USA. [McGrath, L. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Mustanski, B.; Wakschlag, L. S.] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Metzger, A.] W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. [Pine, D. S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Kistner-Griffin, E.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Cook, E.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. RP McGrath, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Dept Psychiat, Simches Res Bldg,6th Floor,185 Cambridge St, Boston, MA 02114 USA. EM mcgrath@pngu.mgh.harvard.edu FU NIDA NIH HHS [R01 DA015223, R01 DA023653] NR 80 TC 13 Z9 13 U1 1 U2 8 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD AUG PY 2012 VL 15 IS 4 BP 269 EP 282 DI 10.1007/s00737-012-0286-y PG 14 WC Psychiatry SC Psychiatry GA 975CI UT WOS:000306484000004 PM 22610759 ER PT J AU Romeo, GR Lee, J Shoelson, SE AF Romeo, Giulio R. Lee, Jongsoon Shoelson, Steven E. TI Metabolic Syndrome, Insulin Resistance, and Roles of Inflammation - Mechanisms and Therapeutic Targets SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; immune system; anti-inflammatory agents; insulin resistance; leukocytes ID ADIPOSE-TISSUE MACROPHAGES; TYPE-2 DIABETES-MELLITUS; DIET-INDUCED OBESITY; T-CELLS; GLYCEMIC CONTROL; IMMUNE-RESPONSE; GENE-EXPRESSION; WEIGHT-LOSS; PPAR-GAMMA; IKK-BETA AB Obesity and its comorbidities, including type 2 diabetes mellitus and cardiovascular disease, are associated with a state of chronic low-grade inflammation that can be detected both systemically and within specific tissues. Areas of active investigation focus on the molecular bases of metabolic inflammation and potential pathogenic roles in insulin resistance, diabetes, and cardiovascular disease. An increased accumulation of macrophages occurring in obese adipose tissue has emerged as a key process in metabolic inflammation. Recent studies have also begun to unravel the heterogeneity of adipose tissue macrophages, and their physical and functional interactions with adipocytes, endothelial cells, and other immune cells within the adipose tissue microenvironment. Translating the information gathered from experimental models of insulin resistance and diabetes into meaningful therapeutic interventions is a tantalizing goal with long-term global health implications. In this context, ongoing clinical studies are testing the effects of targeting inflammation systemically on metabolic and cardiovascular outcomes. (Arterioscler Thromb Vasc Biol. 2012;32:1771-1776.) C1 [Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM steven.shoelson@joslin.harvard.edu FU JDRF-CDA [2-2004-609]; Pilot and Feasibility awards from the Joslin Diabetes Research Center [DK036836]; Boston Obesity Nutrition Research Center [DK046200]; NIH [DK51729, DK74556, DK90792] FX The authors were supported by grants JDRF-CDA 2-2004-609 and Pilot and Feasibility awards from the Joslin Diabetes Research Center DK036836 and the Boston Obesity Nutrition Research Center DK046200 to GRR and NIH grants DK51729, DK74556 and DK90792 to SES. NR 57 TC 139 Z9 143 U1 2 U2 40 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2012 VL 32 IS 8 BP 1771 EP 1776 DI 10.1161/ATVBAHA.111.241869 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 976CM UT WOS:000306558100013 PM 22815343 ER PT J AU Fuchs, TA Brill, A Wagner, DD AF Fuchs, Tobias A. Brill, Alexander Wagner, Denisa D. TI Neutrophil Extracellular Trap (NET) Impact on Deep Vein ThrombosisTobias SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE deep vein thrombosis; deoxyribonuclease; inflammation; mouse model; neutrophil extracellular traps; thrombolytic therapy ID VON-WILLEBRAND-FACTOR; PULMONARY-EMBOLISM; VENOUS THROMBOSIS; LEUKOCYTE ELASTASE; MITOCHONDRIAL-DNA; ENDOTHELIAL-CELLS; INNATE IMMUNITY; HUMAN-PLATELETS; CANCER-PATIENTS; RISK-FACTORS AB Deep vein thrombosis (DVT) is a major health problem that requires improved prophylaxis and treatment. Inflammatory conditions such as infection, cancer, and autoimmune diseases are risk factors for DVT. We and others have recently shown that extracellular DNA fibers produced in inflammation and known as neutrophil extracellular traps (NETs) contribute to experimental DVT. NETs stimulate thrombus formation and coagulation and are abundant in thrombi in animal models of DVT. It appears that, in addition to fibrin and von Willebrand factor, NETs represent a third thrombus scaffold. Here, we review how NETs stimulate thrombosis and discuss known and potential interactions of NETs with endothelium, platelets, red blood cells, and coagulation factors and how NETs could influence thrombolysis. We propose that drugs that inhibit NET formation or facilitate NET degradation may prevent or treat DVT. (Arterioscler Thromb Vasc Biol. 2012;32:1777-1783.) C1 [Wagner, Denisa D.] Immune Dis Inst, Boston, MA 02115 USA. Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Immune Dis Inst, 3 Blackfan Cir,3rd Floor, Boston, MA 02115 USA. EM wagner@idi.harvard.edu RI Fuchs, Tobias/F-1189-2013 FU National Heart, Lung, and Blood Institute of National Institutes of Health [R01 HL102101, R01 HL041002, R01 HL095091] FX The present study was supported by National Heart, Lung, and Blood Institute of National Institutes of Health grants R01 HL102101, R01 HL041002, and R01 HL095091 (to Dr Wagner). NR 81 TC 119 Z9 123 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2012 VL 32 IS 8 BP 1777 EP 1783 DI 10.1161/ATVBAHA.111.242859 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 976CM UT WOS:000306558100014 PM 22652600 ER PT J AU Brill, A Yesilaltay, A De Meyer, SF Kisucka, J Fuchs, TA Kocher, O Krieger, M Wagner, DD AF Brill, Alexander Yesilaltay, Ayce De Meyer, Simon F. Kisucka, Janka Fuchs, Tobias A. Kocher, Olivier Krieger, Monty Wagner, Denisa D. TI Extrahepatic High-Density Lipoprotein Receptor SR-BI and ApoA-I Protect Against Deep Vein Thrombosis in Mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE deep vein thrombosis; scavenger receptor class B type I; apolipoprotein A-I; high-density lipoprotein; endothelial nitric oxide synthase ID APOLIPOPROTEIN-A-I; CORONARY-HEART-DISEASE; VENOUS THROMBOEMBOLISM; DEFICIENT MICE; RISK-FACTORS; CHOLESTEROL; HDL; METABOLISM; PDZK1; EXPRESSION AB Objective-Deep vein thrombosis (DVT) and pulmonary embolism are frequent causes of morbidity and mortality. The goal of our study was to determine whether plasma high-density lipoprotein (HDL), which inversely correlates with the risk of cardiovascular events, affects DVT. Methods and Results-Using a murine DVT model of inferior vena cava stenosis, we demonstrated that deficiency of the HDL receptor, scavenger receptor class B type I (SR-BI), promotes venous thrombosis. As SR-BI-/- mice have increased plasma cholesterol levels and abnormal HDL particles, we tested SR-BI-/- mice with an SR-BI liver transgene that normalizes both parameters. These mice also exhibited increased susceptibility to DVT, indicating a protective role of extrahepatic SR-BI. Mice lacking the major HDL apolipoprotein apoA-I or endothelial nitric oxide synthase (eNOS) (a downstream target of endothelial SR-BI signaling) also had a prothrombotic phenotype. Intravenous infusion of human apoA-I, an HDL component and SR-BI ligend, prevented DVT in wild-type but not SR-BI-/- or eNOS(-/-) mice, suggesting that its effect is mediated by SR-BI and eNOS. Intravenous apoA-I infusion abolished histamine-induced platelet-endothelial interactions, which are important for DVT initiation. Conclusion-An apoA-I (HDL)-SR-BI-eNOS axis is highly protective in DVT and may provide new targets for prophylaxis and treatment of venous thrombosis. (Arterioscler Thromb Vasc Biol. 2012;32:1841-1848.) C1 [Brill, Alexander; De Meyer, Simon F.; Fuchs, Tobias A.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Brill, Alexander; De Meyer, Simon F.; Fuchs, Tobias A.; Wagner, Denisa D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Brill, Alexander; De Meyer, Simon F.; Fuchs, Tobias A.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Yesilaltay, Ayce; Kisucka, Janka; Krieger, Monty] MIT, Dept Biol, Cambridge, MA USA. [Kocher, Olivier] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Kocher, Olivier] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Vasc Biol Res Ctr, Boston, MA 02215 USA. [De Meyer, Simon F.] KULeuven, Lab Thrombosis Res, Kortrijk, Belgium. RP Wagner, DD (reprint author), 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM wagner@idi.harvard.edu RI Fuchs, Tobias/F-1189-2013 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [P01 HL066105, HL52212, R01 HL041002]; Fond voor Wetenschappelijk Onderzoek Vlaanderen (FWO) FX This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health grants P01 HL066105 (to M.K. and D.D.W.), HL52212 (to M.K.), and R01 HL041002 to (D.D.W.). S.F.D.M. is a postdoctoral fellow of the Fond voor Wetenschappelijk Onderzoek Vlaanderen (FWO). NR 52 TC 15 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2012 VL 32 IS 8 BP 1841 EP U308 DI 10.1161/ATVBAHA.112.252130 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 976CM UT WOS:000306558100022 PM 22652597 ER PT J AU De Meyer, SF Suidan, GL Fuchs, TA Monestier, M Wagner, DD AF De Meyer, Simon F. Suidan, Georgette L. Fuchs, Tobias A. Monestier, Marc Wagner, Denisa D. TI Extracellular Chromatin Is an Important Mediator of Ischemic Stroke in Mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE stroke; chromatin; histones; DNase 1 ID VON-WILLEBRAND-FACTOR; EARLY CEREBRAL STROKE; DEEP-VEIN THROMBOSIS; ACTIVATED PROTEIN-C; PLATELET POLYPHOSPHATES; MYOCARDIAL-INFARCTION; GLYCOPROTEIN-IIB/IIIA; PROGNOSTIC MARKER; LIVER-INJURY; IN-VIVO AB Objective-Recently, a growing number of studies have revealed a prothrombotic and cytotoxic role for extracellular chromatin. Cerebral ischemia/reperfusion injury is characterized by a significant amount of cell death and neutrophil activation, both of which may result in the release of chromatin. The goal of this study was to assess the effect of extracellular chromatin in ischemic stroke using a mouse model of transient middle cerebral artery occlusion. Methods and Results-Similar to reports in stroke patients, we observed increased levels of circulating nucleosomes and DNA after ischemic stroke in mice. In addition, we observed that general hypoxia also augmented extracellular chromatin. We hypothesized that targeting extracellular chromatin components would be protective in ischemic stroke. Indeed, treatment with recombinant human DNase 1 significantly improved stroke outcome. Neutralization of histones using an antihistone antibody was also protective as evidenced by smaller infarct volumes, whereas increasing levels of extracellular histones via histone infusion exacerbated stroke outcome by increasing infarct size and worsening functional outcome. Conclusion-Our results indicate that extracellular chromatin is generated and is detrimental during cerebral ischemia/reperfusion in mice. Targeting DNA and histones may be a new therapeutic strategy to limit injury resulting from ischemic stroke. (Arterioscler Thromb Vasc Biol. 2012;32:1884-1891.) C1 [Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [De Meyer, Simon F.; Suidan, Georgette L.; Fuchs, Tobias A.; Wagner, Denisa D.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [De Meyer, Simon F.; Suidan, Georgette L.; Fuchs, Tobias A.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [De Meyer, Simon F.] KULeuven Kulak, Lab Thrombosis Res, Kortrijk, Belgium. [Monestier, Marc] Temple Univ, Sch Med, Temple Autoimmun Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19122 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM wagner@idi.harvard.edu RI Ji, Haofeng/G-6206-2012; Fuchs, Tobias/F-1189-2013 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL041002, R01 HL102101]; Deutsche Forschungsgemeinschaft, Germany [FU 742/1-1] FX This research was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health grants R01 HL041002 and R01 HL102101 (to D.D.W.) and a fellowship from the Deutsche Forschungsgemeinschaft, Germany (FU 742/1-1) (to T.A.F.). S.F.D.M. is a postdoctoral fellow of the Research Foundation Flanders (Fonds voor Wetenschappelijk Onderzoek Vlaanderen). NR 55 TC 41 Z9 42 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2012 VL 32 IS 8 BP 1884 EP U394 DI 10.1161/ATVBAHA.112.250993 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 976CM UT WOS:000306558100027 PM 22628431 ER PT J AU An, XJ Jin, Y Philbrick, MJ Wu, JP Messmer-Blust, A Song, XX Cully, BL He, P Xu, M Duffy, HS Li, J AF An, Xiaojin Jin, Yi Philbrick, Melissa J. Wu, Jiaping Messmer-Blust, Angela Song, Xiaoxiao Cully, Brittany L. He, Ping Xu, Ming Duffy, Heather S. Li, Jian TI Endothelial Cells Require Related Transcription Enhancer Factor-1 for Cell-Cell Connections Through the Induction of Gap Junction Proteins SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE related transcription enhancer factor-1; endothelial cells; gap junctions; connexin 43; cell-cell connections ID OXYGEN-INDUCED RETINOPATHY; M-CAT ELEMENTS; VASCULAR DEVELOPMENT; VE-CADHERIN; ANGIOGENESIS; MOUSE; EXPRESSION; MICE; GENE; ETS AB Objective-Capillary network formation represents a specialized endothelial cell function and is a prerequisite to establish a continuous vessel lumen. Formation of endothelial cell connections that form the vascular structure is regulated, at least in part, at the transcriptional level. We report here that related transcription enhancer factor-1 (RTEF-1) plays an important role in vascular structure formation. Methods and Results-Knockdown of RTEF-1 by small interfering RNA or blockage of RTEF-1 function by the transcription enhancer activators domain decreased endothelial connections in a Matrigel assay, whereas overexpression of RTEF-1 in endothelial cells resulted in a significant increase in cell connections and aggregation. In a model of oxygen-induced retinopathy, endothelial-specific RTEF-1 overexpressing mice had enhanced angiogenic sprouting and vascular structure remodeling, resulting in the formation of a denser and more highly interconnected superficial capillary plexus. Mechanistic studies revealed that RTEF-1 induced the expression of functional gap junction proteins including connexin 43, connexin 40, and connexin 37. Blocking connexin 43 function inhibited RTEF-1-induced endothelial cell connections and aggregation. Conclusion-These findings provide novel insights into the transcriptional control of endothelial function in the coordination of cell-cell connections. (Arterioscler Thromb Vasc Biol. 2012;32:1951-1959.) C1 [Li, Jian] Harvard Univ, Sch Med, Div Cardiovasc Med, Beth Israel Deaconess Med Ctr,Cardiovasc Inst, Boston, MA 02115 USA. [An, Xiaojin; Jin, Yi; Li, Jian] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. RP Li, J (reprint author), Harvard Univ, Sch Med, Div Cardiovasc Med, Beth Israel Deaconess Med Ctr,Cardiovasc Inst, 3 Blackfan Circle, Boston, MA 02115 USA. EM JLi@BIDMC.Harvard.edu FU National Institutes of Health grant [HLR01082837]; China Scholarship Council FX This work was supported, in part, by National Institutes of Health grant HLR01082837 (to J.L.) and China Scholarship Council (to X.A. and Y.J.). NR 28 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2012 VL 32 IS 8 BP 1951 EP U523 DI 10.1161/ATVBAHA.112.250159 PG 14 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 976CM UT WOS:000306558100035 PM 22652601 ER PT J AU Salovich, JM Vinson, PN Sheffler, DJ Lamsal, A Utley, TJ Blobaum, AL Bridges, TM Le, U Jones, CK Wood, MR Daniels, JS Conn, PJ Niswender, CM Lindsley, CW Hopkins, CR AF Salovich, James M. Vinson, Paige N. Sheffler, Douglas J. Lamsal, Atin Utley, Thomas J. Blobaum, Anna L. Bridges, Thomas M. Le, Uyen Jones, Carrie K. Wood, Michael R. Daniels, J. Scott Conn, P. Jeffrey Niswender, Colleen M. Lindsley, Craig W. Hopkins, Corey R. TI Discovery of N-(4-methoxy-7-methylbenzo[d]thiazol-2-yl)isonicatinamide, ML293, as a novel, selective and brain penetrant positive allosteric modulator of the muscarinic 4 (M-4) receptor SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Positive allosteric modulator; M-4; ML293; CNS penetration; Muscarinic receptor 4 ID CENTRAL-NERVOUS-SYSTEM; ACETYLCHOLINE-RECEPTORS; KNOCKOUT MICE AB Herein we describe the discovery and development of a novel class of M-4 positive allosteric modulators, culminating in the discovery of ML293. ML293 exhibited modest potency at the human M4 receptor (EC50 = 1.3 mu M) and excellent efficacy as noted by the 14.6-fold leftward shift of the agonist concentration-response curve. ML293 was also selective versus the other muscarinic subtypes and displayed excellent in vivo PK properties in rat with low IV clearance (11.6 mL/min/kg) and excellent brain exposure (PO PBL, 10 mg/kg at 1 h, [Brain] = 10.3 mu M, B: P = 0.85). (C) 2012 Elsevier Ltd. All rights reserved. C1 [Salovich, James M.; Vinson, Paige N.; Sheffler, Douglas J.; Lamsal, Atin; Utley, Thomas J.; Blobaum, Anna L.; Bridges, Thomas M.; Le, Uyen; Jones, Carrie K.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Niswender, Colleen M.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Wood, Michael R.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Salovich, James M.; Vinson, Paige N.; Sheffler, Douglas J.; Lamsal, Atin; Utley, Thomas J.; Blobaum, Anna L.; Bridges, Thomas M.; Le, Uyen; Jones, Carrie K.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Niswender, Colleen M.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Salovich, James M.; Vinson, Paige N.; Sheffler, Douglas J.; Lamsal, Atin; Utley, Thomas J.; Blobaum, Anna L.; Bridges, Thomas M.; Le, Uyen; Jones, Carrie K.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Niswender, Colleen M.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Specialized Chem Ctr Probe Dev MLPCN, Nashville, TN 37232 USA. [Jones, Carrie K.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37232 USA. RP Hopkins, CR (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. EM corey.r.hopkins@vanderbilt.edu FU NIMH NIH HHS [R01 MH073676, U01 MH087965, U19 MH097056, U54 MH084659, U54MH084659] NR 15 TC 12 Z9 12 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 1 PY 2012 VL 22 IS 15 BP 5084 EP 5088 DI 10.1016/j.bmcl.2012.05.109 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 975BG UT WOS:000306481100034 PM 22738637 ER PT J AU Dording, CM Mischoulon, D Shyu, I Alpert, JE Papakostas, GI AF Dording, C. M. Mischoulon, D. Shyu, I. Alpert, J. E. Papakostas, G. I. TI SAMe and sexual functioning SO EUROPEAN PSYCHIATRY LA English DT Article DE Antidepressants; Side effects; Major Depressive Disorder; S-adenosyl methionine; Antidepressant-induced sexual dysfunction ID MAJOR DEPRESSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; ADENOSYL-L-METHIONINE; S-ADENOSYLMETHIONINE; DYSFUNCTION; TRIAL; RELAPSE; SAM AB Background: Sexual dysfunction is a known side effect of antidepressant treatment (ADT), affecting up to 58-73% of those who receive ADT, potentially affecting antidepressant adherence. Consequently, it is vital to develop novel treatments that target antidepressant-induced sexual dysfunction. Methods: We examined whether adjunctive S-adenosyl-L-methionine (SAMe) is associated with greater improvement in sexual functioning than adjunctive placebo by measuring changes in sexual functioning using the Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ) during a 6-week, single-center, randomized, double-blind trial of SAMe augmentation for SSRI/SNRI-nonresponders. Results: Controlling for the degree of arousal dysfunction at baseline as well as the degree of change in HDRS-17 scale scores during the course of the study, men treated with adjunctive SAMe demonstrated significantly lower arousal dysfunction at endpoint than those treated with adjunctive placebo. In addition, controlling for the degree of erectile dysfunction at baseline as well as the degree of change in HDRS-17 scale scores, men treated with adjunctive SAMe demonstrated significantly lower erectile dysfunction at endpoint than those treated with adjunctive placebo. Conclusions: In the present study, we have observed that adjunctive SAMe can have positive benefit on male arousal and erectile dysfunction, independent of improvement in depressive symptoms. These findings are preliminary, and warrant replication. C1 [Dording, C. M.; Mischoulon, D.; Shyu, I.; Alpert, J. E.; Papakostas, G. I.] Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. RP Dording, CM (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM cdording@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH [5K23 MH069629]; Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Eli Lilly Company; Forest Pharmaceuticals Inc.; GlaxoSmithkline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi-Aventis; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories FX This study was funded by NIMH grant 5K23 MH069629.; C. M. D. has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi-Aventis, Solvay Pharmaceuticals, Inc., Synthelabo, Wyeth-Ayerst Laboratories; has served as an advisor/consultant for Takeda; and has been a speaker for Wyeth-Ayerst Laboratories. NR 19 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD AUG PY 2012 VL 27 IS 6 BP 451 EP 454 DI 10.1016/j.eurpsy.2011.01.003 PG 4 WC Psychiatry SC Psychiatry GA 974ZP UT WOS:000306476500013 PM 21398094 ER PT J AU Foye, OT Huang, IF Chiou, CC Walker, WA Shi, HN AF Foye, Ondulla T. Huang, I-Fei Chiou, Christine C. Walker, W. Allan Shi, Hai Ning TI Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE probiotics; prebiotics; synbiotic; enteric pathogens; cell signaling ID NF-KAPPA-B; TGF-BETA; CITROBACTER-RODENTIUM; EPITHELIAL-CELLS; ESCHERICHIA-COLI; IMMUNE-RESPONSES; BOWEL-DISEASE; HUMAN-MILK; NEGATIVE REGULATION; GUT INFLAMMATION AB Immaturity of gut-associated immunity may contribute to pediatric mortality associated with enteric infections. A murine model to parallel infantile enteric disease was used to determine the effects of probiotic, Lactobacillus acidophilus (La), prebiotic, inulin, or both (synbiotic, syn) on pathogen-induced inflammatory responses, NF-?B, and Smad 7 signaling. Newborn mice were inoculated bi-weekly for 4 similar to weeks with La, inulin, or syn and challenged with Citrobacter rodentium (Cr) at 5 similar to weeks. Mouse intestinal epithelial cells (CMT93) were exposed to Cr to determine temporal alterations in NF-Kappa B and Smad 7 levels. Mice with pretreatment of La, inulin, and syn show reduced intestinal inflammation following Cr infection compared with controls, which is associated with significantly reduced bacterial colonization in La, inulin, and syn animals. Our results further show that host defense against Cr infection correlated with enhanced colonic IL-10 and transforming growth factor-beta expression and inhibition of NF-?B in syn-treated mice, whereas mice pretreated with syn, La, or inulin had attenuation of Cr-induced Smad 7 expression. There was a temporal Smad 7 and NF-?B intracellular accumulation post-Cr infection and post-tumor necrosis factor stimulation in CMT93 cells. These results, therefore, suggest that probiotic, La, prebiotic inulin, or synbiotic may promote host-protective immunity and attenuate Cr-induced intestinal inflammation through mechanisms affecting NF-?B and Smad 7 signaling. C1 [Foye, Ondulla T.; Huang, I-Fei; Walker, W. Allan; Shi, Hai Ning] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Foye, Ondulla T.; Huang, I-Fei; Walker, W. Allan; Shi, Hai Ning] Harvard Univ, Sch Med, Charlestown, MA USA. [Huang, I-Fei; Chiou, Christine C.] Kaohsiung Vet Gen Hosp, Dept Pediat, Kaohsiung, Taiwan. [Huang, I-Fei; Chiou, Christine C.] Natl Yang Ming Univ, Taipei 112, Taiwan. RP Shi, HN (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Bldg 114,16th St,Room 3504, Charlestown, MA 02129 USA. EM shiha@helix.mgh.harvard.edu FU Clinical Nutrition Research Center at Harvard [P30 DK040561]; Kaohsiung Veterans General Hospital, National Yang-Ming University, Taiwan; [R21DK074727]; [R01DK082427] FX This work was supported by R21DK074727 and R01DK082427 (to H.N.S.) and the Clinical Nutrition Research Center at Harvard (P30 DK040561) (to W. A. W.). I-F.H. is sponsored by Kaohsiung Veterans General Hospital, National Yang-Ming University, Taiwan. The authors also acknowledge Drs Bobby J. Cherayil and Michelle Conroy for their critical review of the manuscript. NR 63 TC 16 Z9 17 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0928-8244 EI 1574-695X J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD AUG PY 2012 VL 65 IS 3 BP 467 EP 480 DI 10.1111/j.1574-695X.2012.00978.x PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 975NA UT WOS:000306516800008 PM 22524476 ER PT J AU Abu Dayyeh, BK Jirapinyo, P Weitzner, Z Barker, C Flicker, MS Lautz, DB Thompson, CC AF Abu Dayyeh, Barham K. Jirapinyo, Pichamol Weitzner, Zachary Barker, Charlotte Flicker, Michael S. Lautz, David B. Thompson, Christopher C. TI Endoscopic sclerotherapy for the treatment of weight regain after Roux-en-Y gastric bypass: outcomes, complications, and predictors of response in 575 procedures SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID BARIATRIC SURGERY; DILATED GASTROJEJUNOSTOMY; ENERGY-EXPENDITURE; SODIUM MORRHUATE; GHRELIN; OBESITY; HYPERTENSION; TRENDS; STOMA; GAIN AB Background: Weight regain after Roux-en-Y gastric bypass (RYGB) is common. Endoscopic sclerotherapy is increasingly used to treat this weight regain. Objectives: To report safety, outcomes, durability, and predictors of response to sclerotherapy in a large prospective cohort. Design: Retrospective analysis of a prospective cohort study of patients with weight regain after RYGB. Patients: A total of 231 consecutive patients undergoing 575 sclerotherapy procedures between September 2008 and March 2011. Interventions: Single or multiple sclerotherapy procedures to inject sodium morrhuate into the rim of the gastrojejunal anastomosis. Main Outcome Measurements: We report weight loss, complications, and predictors of response. We also used Kaplan-Meier survival analysis and log-rank test to compare time to continuation of weight regain after sclerotherapy in patients undergoing a single versus multiple sclerotherapy procedures. Results: At 6 and 12 months from the last sclerotherapy procedure, weight regain stabilized in 92% and 78% of the cohort, respectively. Those who underwent 2 or 3 sclerotherapy sessions had significantly higher rates of weight regain stabilization than those who underwent a single session (90% vs 60% at 12 months; P = .003). The average weight loss at 6 months from the last sclerotherapy session for the entire cohort was 10 lb (standard deviation 16), representing 18% of the weight regained after RYGB. A subset of 73 patients (32% of the cohort) had greater weight loss at 6 months (26 lb, standard deviation 12), representing 61% of the weight regained. Predictors of a favorable outcome included greater weight regain and the number of sclerotherapy procedures. Bleeding was reported in 2.4% of procedures and transient diastolic blood pressure increases in 15%, without adverse health outcomes. No GI perforations were reported. Conclusions: Endoscopic sclerotherapy appears to be a safe and effective tool for the management of weight regain after RYGB. (Gastrointest Endosc 2012;76:275-82.) C1 [Abu Dayyeh, Barham K.; Jirapinyo, Pichamol; Weitzner, Zachary; Barker, Charlotte; Flicker, Michael S.; Thompson, Christopher C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Lautz, David B.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Abu Dayyeh, Barham K.; Jirapinyo, Pichamol; Flicker, Michael S.; Lautz, David B.; Thompson, Christopher C.] Harvard Univ, Sch Med, Boston, MA USA. [Abu Dayyeh, Barham K.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Abu Dayyeh, Barham K.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St,Thorn 14, Boston, MA 02115 USA. FU T32 National Institutes of Health [T32DK007191] FX The following author disclosed financial relationships relevant to this publication: Dr Thompson: consultant to and research grant from Olympus. The other authors disclosed no financial relationships relevant to this publication. This project was supported in part by a T32 National Institutes of Health training grant to the Massachusetts General Hospital and Dr. Abu Dayyeh (T32DK007191). NR 31 TC 16 Z9 16 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD AUG PY 2012 VL 76 IS 2 BP 275 EP 282 DI 10.1016/j.gie.2012.03.1407 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 975OK UT WOS:000306520400007 PM 22817783 ER PT J AU Babacan, SD Luessi, M Molina, R Katsaggelos, AK AF Babacan, S. Derin Luessi, Martin Molina, Rafael Katsaggelos, Aggelos K. TI Sparse Bayesian Methods for Low-Rank Matrix Estimation SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article DE Bayesian methods; low-rankness; matrix completion; outlier detection; robust principal component analysis; sparse Bayesian learning; sparsity; variational Bayesian inference ID PRINCIPAL COMPONENT ANALYSIS; APPROXIMATION AB Recovery of low-rank matrices has recently seen significant activity in many areas of science and engineering, motivated by recent theoretical results for exact reconstruction guarantees and interesting practical applications. In this paper, we present novel recovery algorithms for estimating low-rank matrices in matrix completion and robust principal component analysis based on sparse Bayesian learning (SBL) principles. Starting from a matrix factorization formulation and enforcing the low-rank constraint in the estimates as a sparsity constraint, we develop an approach that is very effective in determining the correct rank while providing high recovery performance. We provide connections with existing methods in other similar problems and empirical results and comparisons with current state-of-the-art methods that illustrate the effectiveness of this approach. C1 [Babacan, S. Derin] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Luessi, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, Cambridge, MA 02139 USA. [Molina, Rafael] Univ Granada, Dept Ciencias Comp & IA, E-18071 Granada, Spain. [Katsaggelos, Aggelos K.] Northwestern Univ, Dept Elect Engn & Comp Sci, Evanston, IL 60208 USA. RP Babacan, SD (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. EM dbabacan@illinois.edu; mluessi@nmr.mgh.harvard.edu; rms@decsai.ugr.es; aggk@eecs.northwestern.edu RI Katsaggelos, Aggelos/B-7233-2009; Katsaggelos, Aggelos/I-8002-2012; Molina Soriano, Rafael/B-1849-2012 OI Molina Soriano, Rafael/0000-0003-4694-8588 FU Beckman Institute; Ministerio de Ciencia e Innovacion [TIN2010-15137]; Spanish research program Consolider Ingenio: MIPRCV [CSD2007-00018]; Department of Energy [DE-NA0000457] FX This work was supported in part by the Beckman Institute postdoctoral fellowship, "Ministerio de Ciencia e Innovacion" under contract TIN2010-15137, the Spanish research program Consolider Ingenio 2010: MIPRCV (CSD2007-00018), and a grant from the Department of Energy (DE-NA0000457). NR 50 TC 62 Z9 66 U1 7 U2 35 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1053-587X J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD AUG PY 2012 VL 60 IS 8 BP 3964 EP 3977 DI 10.1109/TSP.2012.2197748 PG 14 WC Engineering, Electrical & Electronic SC Engineering GA 975NF UT WOS:000306517300004 ER PT J AU Smith, EG Zhao, SB Rosen, AK AF Smith, Eric G. Zhao, Shibei Rosen, Amy K. TI Using the patient safety indicators to detect potential safety events among US veterans with psychotic disorders: clinical and research implications SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE hospital care; quality indicators; patient outcomes (health status; quality of life; mortality); safety indicators; pressure ulcers; appropriateness; under-use and over-use; mental health disorders; psychosis; respiratory failure ID SERIOUS MENTAL-ILLNESS; HEALTH-CARE RESEARCH; QUALITY IMPROVEMENT; ADMINISTRATIVE DATA; ADVERSE EVENTS; MEDICAL COMORBIDITY; BIPOLAR DISORDER; INCREASED RISK; SCHIZOPHRENIA; MORTALITY AB Patients with psychotic disorders often experience poorer health outcomes, but whether they experience increased risks of medical errors/patient safety events is less clear. A single state-level US study found acute care inpatients with schizophrenia were at higher risk of incurring some of the Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs). We examined a nationwide sample of US Veterans Health Administration (VHA) acute care inpatients to determine the rates observed among patients with psychotic disorders for a larger set of PSIs. Retrospective cohort analysis using administrative data. Veterans with (n 50 328) and without (n 1 812 897) psychotic disorders (schizophrenia/schizoaffective disorder and other psychoses) admitted for acute care to US VHA hospitals during fiscal years 200306. PSI rates were calculated using AHRQs PSI software. Patients with psychotic disorders had significantly higher rates of postoperative respiratory failure, postoperative wound dehiscence and decubitus ulcer than those without psychotic disorders, although postoperative respiratory failures rates were not significantly higher among patients specifically diagnosed with schizophrenia. Patients with psychotic disorders had significantly lower rates of accidental puncture/laceration, foreign body left in during procedure and failure to rescue. However, the odds of failure to rescue were not significantly lower among surgical patients (the current focus of this PSI). Acute care inpatient veterans with psychotic disorders experienced higher rates of several PSIs, but lower rates of others. Whether lower rates of certain PSIs reflect better or worse care for this population is uncertain. C1 [Smith, Eric G.; Zhao, Shibei] ENRM VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Smith, Eric G.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Rosen, Amy K.] VA Boston HealthCare Syst, Ctr Org Leadership & Management Res, Boston, MA 02130 USA. [Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. RP Smith, EG (reprint author), Bedford VAMC 152, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd, Bedford, MA 01730 USA. EM eric.smith5@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR-02-44-1]; Veterans Health Administration Health Services Research and Development Service Career Development Award FX This work was supported by a grant (IIR-02-44-1, from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service), to A. M. R. E. G. S. is supported by a Veterans Health Administration Health Services Research and Development Service Career Development Award. NR 42 TC 2 Z9 2 U1 4 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD AUG PY 2012 VL 24 IS 4 BP 321 EP 329 DI 10.1093/intqhc/mzs026 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 974DX UT WOS:000306411100002 PM 22718516 ER PT J AU Grover, S Kastrinos, F Steyerberg, EW Cook, EF Dewanwala, A Burbidge, LA Wenstrup, RJ Syngal, S AF Grover, Shilpa Kastrinos, Fay Steyerberg, Ewout W. Cook, E. Francis Dewanwala, Akriti Burbidge, Lynn Anne Wenstrup, Richard J. Syngal, Sapna TI Prevalence and Phenotypes of APC and MUTYH Mutations in Patients With Multiple Colorectal Adenomas SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GERM-LINE MUTATIONS; MYH GENE-MUTATIONS; POLYPOSIS PATIENTS; CANCER PATIENTS; FAMILIES; FAP; CHROMOSOME-5Q21; IDENTIFICATION; EXPRESSION; GUIDELINES AB Context Patients with multiple colorectal adenomas may carry germline mutations in the APC or MUTYH genes. Objectives To determine the prevalence of pathogenic APC and MUTYH mutations in patients with multiple colorectal adenomas who had undergone genetic testing and to compare the prevalence and clinical characteristics of APC and MUTYH mutation carriers. Design, Setting, and Participants Cross-sectional study conducted among 8676 individuals who had undergone full gene sequencing and large rearrangement analysis of the APC gene and targeted sequence analysis for the 2 most common MUTYH mutations (Y179C and G396D) between 2004 and 2011. Individuals with either mutation underwent full MUTYH gene sequencing. APC and MUTYH mutation prevalence was evaluated by polyp burden; the clinical characteristics associated with a pathogenic mutation were evaluated using logistic regression analyses. Main Outcome Measure Prevalence of pathogenic mutations in APC and MUTYH genes. Results Colorectal adenomas were reported in 7225 individuals; 1457 with classic polyposis (>= 100 adenomas) and 3253 with attenuated polyposis (20-99 adenomas). The prevalence of pathogenic APC and biallelic MUTYH mutations was 95 of 119 (80% [95% CI, 71%-87%]) and 2 of 119 (2% [95% CI, 0.2%-6%]), respectively, among individuals with 1000 or more adenomas, 756 of 1338 (56% [95% CI, 54%-59%]) and 94 of 1338 (7% [95% CI, 6%-8%]) among those with 100 to 999 adenomas, 326 of 3253 (10% [95% CI, 9%-11%]) and 233 of 3253 (7% [95% CI, 6%-8%]) among those with 20 to 99 adenomas, and 50 of 970 (5% [95% CI, 4%-7%]) and 37 of 970 (4% [95% CI, 3%-5%]) among those with 10 to 19 adenomas. Adenoma count was strongly associated with a pathogenic mutation in multivariable analyses. Conclusions Among patients with multiple colorectal adenomas, pathogenic APC and MUTYH mutation prevalence varied considerably by adenoma count, including within those with a classic polyposis phenotype. APC mutations predominated in patients with classic polyposis, whereas prevalence of APC and MUTYH mutations was similar in attenuated polyposis. These findings require external validation. JAMA. 2012;308(5):485-492 www.jama.com C1 [Grover, Shilpa; Dewanwala, Akriti; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02215 USA. [Grover, Shilpa; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Grover, Shilpa; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Cook, E. Francis] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Grover, Shilpa] Massachusetts Gen Hosp, Program Canc Outcomes Res Training, Boston, MA 02114 USA. [Kastrinos, Fay] Columbia Univ, Med Ctr, New York, NY USA. [Kastrinos, Fay] Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Steyerberg, Ewout W.] Erasmus MC, Ctr Med Decis Making, Rotterdam, Netherlands. [Burbidge, Lynn Anne; Wenstrup, Richard J.] Myriad Genet Labs Inc, Salt Lake City, UT USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. EM ssyngal@partners.org OI Steyerberg, Ewout/0000-0002-7787-0122 FU National Cancer Institute [R25 CA 092203, K07 CA151769]; National Institutes of Health [K24113433]; Myriad Genetics Laboratories Inc. FX This study was supported by National Cancer Institute grants R25 CA 092203 (Dr Grover) and K07 CA151769 (Dr Kastrinos) and by National Institutes of Health grant K24113433 (Dr Syngal).; Independent Statistical Analysis: Data sets were forwarded by investigators at Myriad Genetics Laboratories Inc to independent investigators at the Dana-Farber Cancer Institute, Boston, Massachusetts (Drs Grover and Syngal) and the Herbert Irving Comprehensive Cancer Center, New York, New York (Dr Kastrinos). Drs Grover, Kastrinos, and Steyerberg (Center for Medical Decision Making, Erasmus Medical Center, Rotterdam, the Netherlands) performed independent statistical analyses. All results reported in the article are from the independent statistical analyses. None of the coauthors not employed by Myriad Genetics Laboratories Inc received any funding for the study from Myriad Genetics Laboratories Inc. NR 36 TC 47 Z9 47 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 1 PY 2012 VL 308 IS 5 BP 485 EP 492 DI 10.1001/jama.2012.8780 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 981DQ UT WOS:000306947400026 PM 22851115 ER PT J AU Teodorescu, M Polomis, DA Teodorescu, MC Gangnon, RE Peterson, AG Consens, FB Chervin, RD Jarjour, NN AF Teodorescu, Mihaela Polomis, David A. Teodorescu, Mihai C. Gangnon, Ronald E. Peterson, Andrea G. Consens, Flavia B. Chervin, Ronald D. Jarjour, Nizar N. TI Association of Obstructive Sleep Apnea Risk or Diagnosis with Daytime Asthma in Adults SO JOURNAL OF ASTHMA LA English DT Article DE asthma; asthma control; obstructive sleep apnea; obstructive sleep apnea risk; sleep ID POSITIVE AIRWAY PRESSURE; HYPOXIA SUPPRESSES; NOCTURNAL ASTHMA; INDUCED SPUTUM; DISEASE; QUESTIONNAIRE; INFLAMMATION; POPULATION; REFLUX; MODEL AB Objective. Obstructive sleep apnea (OSA) worsens nocturnal asthma, but its potential impact on daytime asthma remains largely unassessed. We investigated whether the sleep disorder is associated with daytime, in addition to nighttime, asthma symptoms. Methods. Asthma patients at tertiary-care centers completed the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ), and an asthma control questionnaire. SA-SDQ scores >= 36 for males and >= 32 for females defined high OSA risk. Medical records were reviewed for established diagnosis of OSA and continuous positive airway pressure (CPAP) use. Results. Among 752 asthma patients, high OSA risk was associated similarly with persistent daytime and nighttime asthma symptoms (p < .0001 for each). A diagnosis of OSA was robustly associated with persistent daytime (p < .0001) in addition to nighttime (p = .0008) asthma symptoms. In regression models that included obesity and other known asthma aggravators, high OSA risk retained associations with persistent daytime (odds ratio [OR] = 1.96 [95% confidence interval [CI] = 1.31-2.94]) and nighttime (1.97 [1.32-2.94]) asthma symptoms. Diagnosed OSA retained an association with persistent daytime (2.08 [1.13-3.82]) but not with nighttime (1.48 [0.82-2.69]) asthma symptoms. CPAP use was associated with lower likelihood of persistent daytime symptoms (0.46 [0.23-0.94]). Conclusions. Questionnaire-defined OSA risk and historical diagnosis were each associated with persistent daytime asthma symptoms, to an extent that matched or exceeded associations with nighttime asthma symptoms. Unrecognized OSA may be a reason for persistent asthma symptoms during the day as well as the night. C1 [Teodorescu, Mihaela; Polomis, David A.; Peterson, Andrea G.; Jarjour, Nizar N.] Univ Wisconsin, Sch Med & Publ Hlth, Sect Allergy Pulm & Crit Care Med, Madison, WI 53792 USA. [Teodorescu, Mihaela; Teodorescu, Mihai C.] William S Middleton Mem Vet Adm Med Ctr, Med Serv, Madison, WI USA. [Teodorescu, Mihai C.] Univ Wisconsin, Sch Med & Publ Hlth, Sect Geriatr & Gerontol, Madison, WI 53792 USA. [Gangnon, Ronald E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat & Populat Hlth Sci, Madison, WI 53792 USA. [Consens, Flavia B.; Chervin, Ronald D.] Univ Michigan Hlth Syst, Dept Neurol, Ann Arbor, MI USA. [Consens, Flavia B.; Chervin, Ronald D.] Univ Michigan Hlth Syst, Sleep Disorders Ctr, Ann Arbor, MI USA. RP Teodorescu, M (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Sect Allergy Pulm & Crit Care Med, K4-910 CSC 9988,600 Highland Ave, Madison, WI 53792 USA. EM mt3@medicine.wisc.edu FU National Institutes of Health [T32 NS007222, MO1 RR00042, 1UL1RR025011]; University of Wisconsin School of Medicine and Public Health, Medical Education and Research Committee-New Investigator Award; University of Wisconsin School of Medicine and Public Health Department of Medicine; University of Michigan Department of Neurology Training Grant [T32 NS007222]; General Clinical Research Center [MO1 RR00042]; University of Wisconsin School of Medicine and Public Health; Medical Education and Research Committee-New Investigator Award; Department of Medicine; Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health [1UL1RR025011]; William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin; National Institutes of Health; Fox Foundation; GlaxoSmithKline (GSK); Bristol Meyer Squib FX Received funding support from the National Institutes of Health (nos. T32 NS007222, MO1 RR00042, and 1UL1RR025011); the University of Wisconsin School of Medicine and Public Health, Medical Education and Research Committee-New Investigator Award; and the University of Wisconsin School of Medicine and Public Health Department of Medicine. Additional resources from the William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin.; Funding support for this study was from the University of Michigan Department of Neurology Training Grant (T32 NS007222) and General Clinical Research Center (MO1 RR00042); the University of Wisconsin School of Medicine and Public Health, Medical Education and Research Committee-New Investigator Award, Department of Medicine, and 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health; and the William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin.; Dr R.D. Chervin has received research support from the National Institutes of Health and Fox Foundation and has served on the advisory boards for Pavad Medical, not-for-profit Sweet Dreamzzz, and the NHLBI (Sleep Disorders Research Advisory Board). Chervin is a section editor for UpToDate, Inc.; received support for educational purposes from Philips Respironics, Inc. and Fisher Paykel, Inc.; and has consulted for Arena Pharmaceuticals, Proctor & Gamble, and Zansors. Chervin serves on the Board of Directors of the American Academy of Sleep Medicine and the International Pediatric Sleep Association and is named in University of Michigan patents for algorithms and devices to facilitate diagnosis and treatment of sleep disorders.; Dr N.N. Jarjour received funding support from the National Institutes of Health, GlaxoSmithKline (GSK), and Bristol Meyer Squib, and received honorarium <$5000 from the Saudi Thoracic Society for a GSK-supported continuing medical education program. NR 49 TC 15 Z9 18 U1 1 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0277-0903 EI 1532-4303 J9 J ASTHMA JI J. Asthma PD AUG PY 2012 VL 49 IS 6 BP 620 EP 628 DI 10.3109/02770903.2012.689408 PG 9 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 974IH UT WOS:000306426300011 PM 22742082 ER PT J AU Ferrer, RA Klein, WMP Zajac, LE Land, SR Ling, BS AF Ferrer, Rebecca A. Klein, William M. P. Zajac, Laura E. Land, Stephanie R. Ling, Bruce S. TI An affective booster moderates the effect of gain- and loss-framed messages on behavioral intentions for colorectal cancer screening SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Message framing; Anticipated emotion; Anticipatory emotion; Colorectal cancer screening ID RISK PERCEPTIONS; HEALTH BEHAVIOR; ANTICIPATED REGRET; DECISION-MAKING; INFLUENZA VACCINATION; FEAR APPEALS; BREAST; WORRY; MAMMOGRAPHY; PREVENTION AB Previous research has demonstrated that loss-framed messages are more effective than gain-framed messages in motivating detection behaviors such as screening. The present study examined whether affective context moderates the degree to which message frame is associated with behavioral intentions to engage in colorectal cancer screening. In particular, we buttressed a framing manipulation with an "affective booster" to increase anticipated and anticipatory emotions associated with the framed messages. Consistent with previous research, we found that loss-framed messages are more effective in increasing intentions to screen. However, we found that among individuals who received gain-framed messages (but not loss-framed messages), the affective booster increased message persuasiveness. This effect on intentions was partially mediated by self-efficacy for engaging in screening. This study indicates that in the presence of emotional boosters, loss-framed messages may lose their advantage over gain-framed messages in motivating detection behaviors, and that self-efficacy may partially explain these effects. C1 [Ferrer, Rebecca A.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Klein, William M. P.; Zajac, Laura E.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Land, Stephanie R.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Ling, Bruce S.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Ferrer, RA (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4083, Rockville, MD 20852 USA. EM ferrerra@mail.nih.gov NR 63 TC 8 Z9 8 U1 4 U2 27 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD AUG PY 2012 VL 35 IS 4 BP 452 EP 461 DI 10.1007/s10865-011-9371-3 PG 10 WC Psychology, Clinical SC Psychology GA 974KS UT WOS:000306434500009 PM 21850516 ER PT J AU Rowe, GC Vialou, V Sato, K Saito, H Yin, M Green, TA Lotinun, S Kveiborg, M Horne, WC Nestler, EJ Baron, R AF Rowe, Glenn C. Vialou, Vincent Sato, Kazusa Saito, Hiroaki Yin, Min Green, Thomas A. Lotinun, Sutada Kveiborg, Marie Horne, William C. Nestler, Eric J. Baron, Roland TI Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE AP-1; HYPOTHALAMUS; ENERGY EXPENDITURE; BONE FORMATION ID SYMPATHETIC-NERVOUS-SYSTEM; FOSB TRANSGENIC MICE; DELTA-FOSB; INSULIN SENSITIVITY; NUCLEUS-ACCUMBENS; EXPRESSION; MASS; BRAIN; LEPTIN; COCAINE AB The regulation of bone and fat homeostasis and its relationship to energy expenditure has recently been the focus of increased attention because of its potential relevance to osteoporosis, obesity, and diabetes. Although central effectors within the hypothalamus have been shown to contribute to the regulation of both energy balance and bone homeostasis, little is known of the underlying mechanisms, including the possible involvement of transcriptional factors within the hypothalamus. Transgenic mice overexpressing ?FosB, a splice variant of the AP-1 transcription factor FosB with mixed agonist-antagonistic properties, have increased energy expenditure and bone mass. Because these mice express ?FosB in bone, fat, and hypothalamus, we sought to determine 1) whether overexpression of ?FosB within the hypothalamus was sufficient to regulate energy expenditure and whether it would also regulate bone mass, and 2) whether these effects were the result of antagonism to AP-1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ?FosB to the ventral hypothalamus of wild-type mice induced a profound increase in both energy expenditure and bone formation and bone mass. This effect was phenocopied, at an even stronger level, by overexpression of a dominant-negative DNJunD, a pure AP-1 antagonist. Taken together, these results suggest that downregulation of AP-1 activity in the hypothalamus profoundly increases energy expenditure and bone formation, leading to both a decrease in adipose mass and an increase in bone mass. These findings may have physiological implications because ?FosB is expressed and regulated in the hypothalamus. (C) 2012 American Society for Bone and Mineral Research. C1 [Rowe, Glenn C.; Sato, Kazusa; Saito, Hiroaki; Yin, Min; Lotinun, Sutada; Kveiborg, Marie; Horne, William C.; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Rowe, Glenn C.; Sato, Kazusa; Saito, Hiroaki; Yin, Min; Lotinun, Sutada; Kveiborg, Marie; Horne, William C.; Baron, Roland] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02115 USA. [Vialou, Vincent; Green, Thomas A.; Nestler, Eric J.] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY USA. [Vialou, Vincent; Green, Thomas A.; Nestler, Eric J.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. RP Baron, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med, 188 Longwood Ave, Boston, MA 02115 USA. EM roland_baron@hsdm.harvard.edu RI vialou, vincent/F-2968-2013; OI vialou, vincent/0000-0002-8212-751X; Kveiborg, Marie/0000-0002-1293-1019; Lotinun, Sutada/0000-0002-5127-3039 FU NIA [AG 040222]; NIMH [MH51399]; UNCF-Merck Dissertation Fellowship; NIH, NIAMS [AR 048218] FX This work was supported by grants from the NIH, NIAMS (AR 048218), and NIA (AG 040222) to RB, NIMH (MH51399) to EJN, and a UNCF-Merck Dissertation Fellowship to GCR. NR 49 TC 5 Z9 5 U1 0 U2 6 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 AUG PY 2012 VL 27 IS 8 BP 1649 EP 1658 DI 10.1002/jbmr.1618 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 974XQ UT WOS:000306471300005 PM 22461201 ER PT J AU Yang, DQ Feng, SM Chen, W Zhao, HB Paulson, C Li, YP AF Yang, De-Qin Feng, Shengmei Chen, Wei Zhao, Haibo Paulson, Christie Li, Yi-Ping TI V-ATPase subunit ATP6AP1 (Ac45) regulates osteoclast differentiation, extracellular acidification, lysosomal trafficking, and protease exocytosis in osteoclast-mediated bone resorption SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE V-ATPase SUBUNIT ATP6AP1 (Ac45); OSTEOCLAST; LYSOSOMAL TRAFFICKING; PROTEASE EXOCYTOSIS; BONE RESORPTION ID VACUOLAR H+-ATPASE; INTRACELLULAR MEMBRANE TRAFFICKING; PROTON PUMP; RUFFLED BORDER; RESORBING OSTEOCLASTS; VESICULAR TRAFFICKING; ESSENTIAL COMPONENT; PLASMA-MEMBRANE; DC-STAMP; F-ACTIN AB Lysosomal trafficking and protease exocytosis in osteoclasts are essential for ruffled border formation and bone resorption. Yet the mechanism underlying lysosomal trafficking and the related process of exocytosis remains largely unknown. We found ATP6ap1 (Ac45), an accessory subunit of vacuolar-type H+-ATPases (V-ATPases), to be highly induced by receptor activator for nuclear factor kappa B ligand (RANKL) in osteoclast differentiation. Ac45 knockdown osteoclasts formed normal actin rings, but had severely impaired extracellular acidification and bone resorption. Ac45 knockdown significantly reduced osteoclast formation. The decrease in the number of osteoclasts does not result from abnormal apoptosis; rather, it results from decreased osteoclast precursor cell proliferation and fusion, which may be partially due to the downregulation of extracellular signal-regulated kinase (ERK) phosphorylation and FBJ osteosarcoma oncogene (c-fos), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and transmembrane 7 superfamily member 4 (Tm7sf4) expression. Notably, Ac45 knockdown osteoclasts exhibited impaired lysosomal trafficking and exocytosis, as indicated by the absence of lysosomal trafficking to the ruffled border and a lack of cathepsin K exocytosis into the resorption lacuna. Our data revealed that the impaired exocytosis is specifically due to Ac45 deficiency, and not the general consequence of a defective V-ATPase. Together, our results demonstrate the essential role of Ac45 in osteoclast-mediated extracellular acidification and protease exocytosis, as well as the ability of Ac45 to guide lysosomal intracellular trafficking to the ruffled border, potentially through its interaction with the small guanosine-5'-triphosphatase (GTPase) Rab7. Our work indicates that Ac45 may be a novel therapeutic target for osteolytic disease. (C) 2012 American Society for Bone and Mineral Research. C1 [Yang, De-Qin; Feng, Shengmei; Chen, Wei; Paulson, Christie; Li, Yi-Ping] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Yang, De-Qin; Feng, Shengmei; Chen, Wei; Paulson, Christie; Li, Yi-Ping] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Yang, De-Qin] Stomatol Hosp, Zunyi Med Coll, Zunyi, Guizhou Provinc, Peoples R China. [Yang, De-Qin] Chongqing Med Univ, Affiliated Hosp Stomatol, Chongqing, Peoples R China. [Feng, Shengmei] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Prevent & Treatment Bone & Joint, Shanghai Inst Trauma & Orthopaed,Ruijin Hosp, Shanghai 200030, Peoples R China. [Zhao, Haibo] Univ Arkansas Med Sci, Coll Med, Dept Internal Med, Little Rock, AR 72205 USA. RP Li, YP (reprint author), Univ Alabama Birmingham, Dept Pathol, SHEL 810,1825 Univ Blvd, Birmingham, AL 35294 USA. EM ypli@uab.edu FU NIH [AR-44741, AR-055307]; Talents Training Program for Western China of China Scholarship Council FX We express our deep gratitude to Dr. Weiguo Zou for his excellent help in the selection of siRNA. We also thank Dr. Lai Ding, Dr. Daniel Tom, and Dr. Shawn R Williams for their excellent technical assistance in confocal microscopy and three-dimensional reconstruction. We thank Dr. Peter V. Hauschka (Children's Hospital Boston) for providing us with dentin slices. This work was supported by NIH grants: AR-44741 (Y-PL) and AR-055307 (Y-PL), and by the Talents Training Program for Western China of China Scholarship Council. NR 40 TC 15 Z9 15 U1 4 U2 15 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 AUG PY 2012 VL 27 IS 8 BP 1695 EP 1707 DI 10.1002/jbmr.1623 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 974XQ UT WOS:000306471300009 PM 22467241 ER PT J AU Gill, JS Wang, HB Alston, TA AF Gill, Jatinder S. Wang, Haibin Alston, Theodore A. TI An Unusual Cause for an Irregularly Irregular Pulse SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE arrhythmia; electromechanical dissociation; pulseless electrical activity ID ELECTROMECHANICAL DISSOCIATION; AUTO-PEEP C1 [Gill, Jatinder S.; Wang, Haibin; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Gill, JS (reprint author), Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, 330 Brookline Ave, Boston, MA 02215 USA. EM jsgill@bidmc.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD AUG PY 2012 VL 26 IS 4 BP 751 EP 752 DI 10.1053/j.jvca.2011.04.004 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 974PK UT WOS:000306448500036 PM 21684765 ER PT J AU Sulemanji, DS Bloom, JD Dzik, WH Jiang, YD AF Sulemanji, Demet S. Bloom, Jonathan D. Dzik, Walter H. Jiang, Yandong TI New insights into the effect of rapid transfusion of fresh frozen plasma on ionized calcium SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Cardiac output; Citrate; Fresh frozen plasma; Hypocalcemia; Ionized calcium; Transfusion ID CARDIAC PURKINJE-CELL; VENTRICULAR PUMP PERFORMANCE; MASSIVE BLOOD-TRANSFUSIONS; SARCOPLASMIC-RETICULUM; ANESTHETIZED MAN; CAPILLARY BLOOD; SODIUM-CITRATE; SERUM; ION; HYPOCALCEMIA AB Study Objectives: 1) To develop an in vitro system to simulate the kinetics of ionized calcium in mixed venous blood during rapid transfusion of fresh frozen plasma (FFP) and 2) to use the in vitro data to estimate the effect of the transfusion rate relative to cardiac output (CO) on ionized calcium. Design: Experimental study. Setting: Research laboratory of an academic hospital. Measurements: Citrated FFP was mixed with compatible heparinized whole blood at various volume ratios in vitro to simulate the mixed venous blood obtained at various flow ratios of FFP transfusion to the recipient's venous system in vivo. Ionized calcium was measured after each mixture. Main Results: Mixing FFP and whole blood at volume ratios of 0:100, 5:95, 10:90, and 15:85 yielded ionized calcium levels (mean +/- SD, mmol/L) of 1.23, 0.81 +/- 0.02, 0.54 +/- 0.08, and 0.34 +/- 0.02, respectively. The 50% reduction in ionized calcium occurred at a volume ratio of 7:93. Conclusions: An instantaneous 50% reduction in ionized calcium occurs in vitro at a proportion equivalent to a transfusion rate of FFP representing 7% of CO. (C) 2012 Elsevier Inc. All rights reserved. C1 [Sulemanji, Demet S.; Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Sulemanji, Demet S.; Jiang, Yandong] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Bloom, Jonathan D.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15213 USA. [Dzik, Walter H.] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Jiang, YD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM yjiang@partners.org FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX Supported by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, only. NR 31 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 2012 VL 24 IS 5 BP 364 EP 369 DI 10.1016/j.jclinane.2011.10.008 PG 6 WC Anesthesiology SC Anesthesiology GA 974QK UT WOS:000306451200003 PM 22575605 ER PT J AU Lombardo, I Sachs, G Kolluri, S Kremer, C Yang, RY AF Lombardo, Ilise Sachs, Gary Kolluri, Sheela Kremer, Charlotte Yang, Ruoyong TI Two 6-Week, Randomized, Double-Blind, Placebo-Controlled Studies of Ziprasidone in Outpatients With Bipolar I Depression Did Baseline Characteristics Impact Trial Outcome? SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE bipolar depression; atypical antipsychotic; placebo response ID RATING-SCALE; MONOTHERAPY; QUETIAPINE; LAMOTRIGINE; REMISSION; EFFICACY; MANIA AB Two randomized, double-blind, placebo-controlled, 6-week studies comparing ziprasidone versus placebo for treatment of bipolar depression (BPD) failed to meet their primary study objectives, indicating that either ziprasidone is ineffective in the treatment of BPD or the study failed. Adult outpatients with bipolar I depression with 17-item Hamilton Rating Scale for Depression total score more than 20 at screening and baseline received either ziprasidone 40 to 80 mg/d, 120 to 160 mg/d, or placebo (study 1), or ziprasidone 40 to 160 mg/d or placebo (study 2). Primary efficacy measure in both studies was change from baseline in Montgomery-Asberg Depression Rating Scale total scores at week 6 (end of the study). Mixed-model repeated-measures methodology was used to analyze the primary efficacy measure in both studies. Secondary efficacy measures in both studies included Hamilton Rating Scale for Depression total score and Clinical Global Impression-Improvement score. Post hoc analyses were conducted for both studies to examine potential reasons for study failure. In both, ziprasidone treatment groups failed to separate statistically from placebo for change from baseline Montgomery-Asberg Depression Rating Scale score at week 6. Response rates were 49%, 53%, and 46% for placebo, ziprasidone 40 to 80 mg/d, and ziprasidone 120 to 160 mg/d, respectively (study 1), and 51% and 53% for placebo and ziprasidone 40 to 160 mg/d, respectively (study 2). Ziprasidone 40 to 160 mg/d did not show superiority over placebo at week 6 in the treatment of BPD. Post hoc analyses revealed serious inconsistencies in subject rating that may have limited the ability to detect a difference between drug and placebo response. Rating reliability warrants further investigation to improve clinical trial methodology in psychiatry. C1 [Lombardo, Ilise; Kolluri, Sheela; Kremer, Charlotte; Yang, Ruoyong] Pfizer Inc, New York, NY 10017 USA. [Sachs, Gary] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, Gary] Harvard Univ, Cambridge, MA 02138 USA. RP Lombardo, I (reprint author), Pfizer Inc, 235 E 42nd St, New York, NY 10017 USA. EM ilise.lombardo@pfizer.com FU Pfizer Inc.; Abbott; GlaxoSmithKline; Janssen; Pfizer FX This study was funded by Pfizer Inc. Editorial support was provided by Annie Neild, PhD, of PAREXEL and was funded by Pfizer Inc.; Drs Lombardo, Kolluri, Kremer, and Yang are employees of Pfizer Inc. Dr Sachs, owned stock in Concordant Rater Systems, Inc, and is now an employee of United BioSource Corporation. He has received grants for clinical research from Abbott, GlaxoSmithKline, Janssen, and Pfizer. Dr Sachs is on advisory boards for Abbott, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Otsuka, Pfizer, and Repligen. NR 25 TC 35 Z9 35 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2012 VL 32 IS 4 BP 470 EP 478 DI 10.1097/JCP.0b013e31825ccde5 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 970GE UT WOS:000306115300006 PM 22722504 ER PT J AU Hunt, KJ Gebregziabher, M Egede, LE AF Hunt, Kelly J. Gebregziabher, Mulugeta Egede, Leonard E. TI Racial and Ethnic Differences in Cardio-Metabolic Risk in Individuals with Undiagnosed Diabetes: National Health and Nutrition Examination Survey 1999-2008 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE undiagnosed diabetes; disparities; cardio-metabolic risk; HbA1c ID IMPAIRED GLUCOSE-TOLERANCE; CARDIOVASCULAR-DISEASE; FASTING GLUCOSE; CORONARY-DISEASE; US POPULATION; ADULTS; PREVALENCE; MELLITUS; BLACK; MEN AB Although early recognition and treatment of diabetes may be essential to prevent complications, roughly one-fifth of diabetes remains undiagnosed. Examine cardio-metabolic risk factors and their control in non-Hispanic white (NHW), non-Hispanic black (NHB) and Mexican American (MA) individuals with undiagnosed diabetes. Nationally representative cross-sectional study of participants in the National Health and Nutrition Examination Survey (NHANES) continuous cycles conducted 1999 through 2008. Of 22,621 non-pregnant individuals aged a parts per thousand yen20 years, 2521 had diagnosed diabetes. Of the remaining 20,100 individuals, 17,963 had HbA1c measured, 551 of whom were classified as having undiagnosed diabetes and comprise the study population. Undiagnosed diabetes was defined as HbA1c a parts per thousand yenaEuro parts per thousand 6.5% without a self-report of physician diagnosed diabetes. Cardio-metabolic risk factor control was examined using regression methods for complex survey data. Among individuals with undiagnosed diabetes, mean HbA1c level was 7.7% (95% CI: 7.5, 7.9), 19.3% (95% CI: 14.2, 24.3) smoked, 59.7% (95% CI: 54.5, 64.8%) had hypertension and 96.5% (95% CI: 94.6, 98.4%) had dyslipidemia. Lipid profiles were remarkably different across racial-ethnic groups: NHB had the highest LDL- and HDL-cholesterol, but the lowest triglycerides, while MA had the highest triglycerides and the lowest LDL-cholesterol. After adjusting for age, sex, NHANES examination cycle and use of either blood pressure or lipid medication, the odds of having blood pressure a parts per thousand yen130/80 mmHg was higher in NHB [1.92 (95% CI: 1.09, 3.55)] than NHW, while the odds of having LDL-cholesterol > 100 mg/dl was higher in NHW[2.93 (95% CI: 1.37, 6.24)] and NHB[3.34 (95% CI: 1.08, 10.3)] than MA. In a nationally representative sample of individuals with undiagnosed diabetes, cardio-metabolic risk factor levels were high across all racial/ethnic groups, but NHB and MA had poorer control compared to NHW. Interventions that target identification of diabetes and treatment of cardio-metabolic risk factors are needed. C1 [Hunt, Kelly J.; Gebregziabher, Mulugeta] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Hunt, Kelly J.; Gebregziabher, Mulugeta; Egede, Leonard E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Hunt, KJ (reprint author), Med Univ S Carolina, Div Biostat & Epidemiol, 135 Cannon St,Suite 302,POB 250835, Charleston, SC 29425 USA. EM huntke@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU Office of Research and Development; Department of Veterans Affairs; Ralph H. Johnson VAMC; VA HSRD REAP [IIR-06-219]; National Center on Minority Health and Health Disparities [R01-MD004251] FX This material is based upon work supported in part by the Office of Research and Development, Department of Veterans Affairs, and the Ralph H. Johnson VAMC. Further support is provided through VA HSR&D REAP Award (grant #IIR-06-219) as well as the National Center on Minority Health and Health Disparities (R01-MD004251). The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 40 TC 10 Z9 10 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2012 VL 27 IS 8 BP 893 EP 900 DI 10.1007/s11606-012-2023-7 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 974LB UT WOS:000306435500004 PM 22415867 ER PT J AU Zhang, Z Xie, DW Kurichi, JE Streim, J Zhang, GY Stineman, MG AF Zhang, Zi Xie, Dawei Kurichi, Jibby E. Streim, Joel Zhang, Guangyu Stineman, Margaret G. TI Mortality Predictive Indexes for the Community-Dwelling Elderly US Population SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE mortality; prediction; score system; community; instrumental activities of daily living. ID NURSING-HOME RESIDENTS; QUALITY-OF-LIFE; OLDER-ADULTS; INSTRUMENTAL ACTIVITIES; COGNITIVE IMPAIRMENT; FUNCTIONAL STATUS; METHODOLOGICAL STANDARDS; HOSPITAL DISCHARGE; ADVANCED DEMENTIA; PHYSICAL FUNCTION AB Few predictive indexes for long-term mortality have been developed for community-dwelling elderly populations. Parsimonious predictive indexes are important decision-making tools for clinicians, policy makers, and epidemiologists. To develop 1-, 5-, and 10-year mortality predictive indexes for nationally representative community-dwelling elderly people. Cohort study. The Second Longitudinal Study of Aging (LSOA II). Nationally representative civilian community-dwelling persons at least 70 years old. We randomly selected 60% of the sample for prediction development and used the remaining 40% for validation. Sociodemographics, impairments, and medical diagnoses were collected from the LSOA II baseline interviews. Instrumental activities of daily living (IADLs) stages were derived to measure functional status. All-cause mortality was obtained from the LSOA II Linked Mortality Public-use File. The analyses included 7,373 sample persons with complete data, among which mortality rates were 3.7%, 23.3%, and 49.8% for 1, 5, and 10 years, respectively. Four, eight, and ten predictors were identified for 1-, 5-, and 10-year mortality, respectively, in multiple logistic regression models to create three predictive indexes. Age, sex, coronary artery disease, and IADL stages were the most essential predictors for all three indexes. C-statistics of the three indexes were 0.72, 0.74, and 0.75 in the development cohort and 0.72, 0.72, and 0.74 in the validation cohort for 1-, 5-, and 10-year mortality, respectively. Five risk groups were defined based on the scores. The 1-, 5-, and 10-year mortality indexes include parsimonious predictor sets maximizing ease of mortality prediction in community settings. Thus, they may provide valuable information for prognosis of elderly patients and guide the comparison of alternative interventions. Including IADL stage as a predictor yields simplified mortality prediction when detailed disease information is not available. C1 [Zhang, Zi; Xie, Dawei; Kurichi, Jibby E.; Stineman, Margaret G.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Streim, Joel] Univ Penn, Dept Psychiat, Perelman Sch Med, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Streim, Joel] Philadelphia Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Zhang, Guangyu] Univ Maryland, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. [Stineman, Margaret G.] Univ Penn, Dept Phys Med & Rehabil, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Stineman, MG (reprint author), Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mstinema@exchange.upenn.edu FU National Institutes of Health [AG032420-01A1] FX The research for this manuscript was supported by the National Institutes of Health (AG032420-01A1). There are no personal conflicts of interest of any of the authors, and no authors reported disclosures beyond the funding source. The opinions and conclusions of the authors are not necessarily those of the sponsoring agency or of the NCHS who is responsible only for provision of the data. NR 57 TC 9 Z9 9 U1 4 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2012 VL 27 IS 8 BP 901 EP 910 DI 10.1007/s11606-012-2027-3 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 974LB UT WOS:000306435500005 PM 22422075 ER PT J AU Fowler, FJ Gallagher, PM Bynum, JPW Barry, MJ Lucas, FL Skinner, JS AF Fowler, Floyd J., Jr. Gallagher, Patricia M. Bynum, Julie P. W. Barry, Michael J. Lucas, F. Leslie Skinner, Jonathan S. TI Decision-Making Process Reported by Medicare Patients Who Had Coronary Artery Stenting or Surgery for Prostate Cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE shared decision making; decision quality; patient-centered care ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; PRIMARY-CARE; DISEASE; THERAPY; INTERVENTION; BENEFITS; OUTCOMES; PCI AB Patients facing decisions should be told about their options, have the opportunity to discuss the pros and cons, and have their preferences reflected in the final decision. To learn how decisions were made for two major preference-sensitive interventions. Mail survey of probability samples of patients who underwent the procedures. Fee-for-service Medicare beneficiaries who had surgery for prostate cancer or elective coronary artery stenting in the last half of 2008. Patients' reports of which options were presented for serious consideration, the amount of discussion of the pros and cons of the chosen option, and if they were asked about their preferences. The majority (64%) of prostate cancer surgery patients reported that at least one alternative to surgery was presented as a serious option. Almost all (94%) said they and their doctors discussed the pros, and 63% said they discussed the cons of surgery "a lot" or "some". Most (76%) said they were asked about their treatment preferences. Few who received stents said they were presented with options to seriously consider (10%). While most (77%) reported talking with doctors about the reasons for stents "a lot" or "some", few (19%) reported talking about the cons. Only 16% said they were asked about their treatment preferences. While prostate cancer surgery patients reported more involvement in decision making than elective stent patients, the reports of both groups document the need for increased efforts to inform and involve patients facing preference-sensitive intervention decisions. C1 [Fowler, Floyd J., Jr.; Gallagher, Patricia M.] Univ Massachusetts Boston, Survey Res Ctr, Boston, MA USA. [Fowler, Floyd J., Jr.; Barry, Michael J.] Fdn Informed Med Decis Making, Boston, MA USA. [Bynum, Julie P. W.] Dartmouth Hitchcock Med Ctr, Dept Gen Internal Med, Hanover, NH USA. [Barry, Michael J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Lucas, F. Leslie] Maine Med Ctr, Ctr Outcomes Res, Portland, ME 04102 USA. [Skinner, Jonathan S.] Dartmouth Coll, Dept Econ, Hanover, NH 03755 USA. [Bynum, Julie P. W.; Skinner, Jonathan S.] Dartmouth Coll, Dartmouth Inst, Hanover, NH 03755 USA. RP Fowler, FJ (reprint author), Univ Massachusetts Boston, Survey Res Ctr, Boston, MA USA. EM Floyd.fowler@umb.edu FU National Institutes on Aging (NIA) [PO1-AG19783, AG028947] FX The work reported in this paper was supported by Grant NoPO1-AG19783 to Dartmouth Medical School from the National Institutes on Aging (NIA). Dr. Bynum's time was supported by NIA K23 Grant No. AG028947. NR 28 TC 19 Z9 19 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2012 VL 27 IS 8 BP 911 EP 916 DI 10.1007/s11606-012-2009-5 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 974LB UT WOS:000306435500006 PM 22370767 ER PT J AU Momplaisir, F Long, JA Badolato, G Brady, KA AF Momplaisir, Florence Long, Judith A. Badolato, Gia Brady, Kathleen A. TI The Role of Primary Care Physicians in Improving Colorectal Cancer Screening in Patients with HIV SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal cancer screening; HIV; primary care; infectious diseases specialists; model of care ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; ADULTS; SPECIALIZATION; DEATH; OLDER; AIDS AB As HIV positive patients live longer, they become susceptible to the development of non-AIDS defining malignancies. Little is known about routine cancer screening practices in that population and the factors associated with cancer screening. Evaluate 1) the proportion of patients with HIV who had any type of colorectal cancer (CRC) screening and 2) whether having a primary care physician (PCP) or seeking care in an integrated care practice is associated with higher CRC screening. A cross-sectional chart abstraction study of patients with HIV enrolled in the Philadelphia Medical Monitoring Project (MMP). MMP participants age 50 and older. CRC screening defined as having a documented colonoscopy, sigmoidoscopy, barium enema, or fecal occult blood test after the age of 50. Out of 123 chart abstractions performed, 115 had a complete clinical record from MMP. The majority of the population was male (71.3%), Black/Hispanic (73.8%) and between the age of 50 and 59 (71.3%). 45.2% of patients did not have a PCP. The overall proportion of patients who received CRC screening was 46.9%. Having a documented PCP was the only factor strongly associated with CRC screening. Rates of screening were 66.7% among those with a PCP versus 28.5% among those without a PCP (chi(2) p < 0.001). After adjusting for race, socioeconomic status, substance and alcohol abuse, the odds of getting CRC screening in those with a PCP was 4.59 (95% CI 2.01-10.48, p < 0.001). The type of practice where patients were enrolled into care was not associated with CRC screening. Having a PCP significantly increases the likelihood of receiving CRC screening in patients with HIV. Competency in addressing primary care needs in HIV clinics will only become more important as patients with HIV age. C1 [Momplaisir, Florence; Long, Judith A.] Univ Penn, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Long, Judith A.] Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Badolato, Gia; Brady, Kathleen A.] Philadelphia Dept Publ Hlth, Philadelphia, PA USA. RP Momplaisir, F (reprint author), Univ Penn, Div Gen Internal Med, Perelman Sch Med, 423 Guardian Dr,13th Floor,Blockley Hall, Philadelphia, PA 19104 USA. EM fmo@mail.med.upenn.edu FU Philadelphia Department of Public Health [U62 PS001608-01]; Centers for Disease Control and Prevention [U62 PS001608-01] FX Supported by funding by a cooperative agreement between the Philadelphia Department of Public Health and the Centers for Disease Control and Prevention (grant # U62 PS001608-01). NR 14 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2012 VL 27 IS 8 BP 940 EP 944 DI 10.1007/s11606-012-2010-z PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 974LB UT WOS:000306435500010 PM 22370768 ER PT J AU Offutt-Powell, TN Ojha, RP Tota, JE Gurney, JG AF Offutt-Powell, Tabatha N. Ojha, Rohit P. Tota, Joseph E. Gurney, James G. TI Human Papillomavirus Infection and Bladder Cancer: An Alternate Perspective From a Modified Meta-Analysis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 [Offutt-Powell, Tabatha N.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Ojha, Rohit P.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Tota, Joseph E.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. [Ojha, Rohit P.; Gurney, James G.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. RP Offutt-Powell, TN (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 2103B McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. EM topowell@email.unc.edu OI Ojha, Rohit/0000-0003-0595-8990 NR 10 TC 0 Z9 1 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2012 VL 206 IS 3 BP 453 EP U184 DI 10.1093/infdis/jis364 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 973OI UT WOS:000306369100019 PM 22615320 ER PT J AU Gonzalez, RG AF Gonzalez, R. Gilberto TI Clinical MRI of acute ischemic stroke SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE ischemic stroke; MR angiography; diffusion MRI; perfusion MRI ID TISSUE-PLASMINOGEN ACTIVATOR; DIFFUSION-WEIGHTED MRI; THROMBOLYTIC THERAPY; CEREBRAL-ISCHEMIA; HYPERACUTE STROKE; ARTERY-OCCLUSION; PERFUSION MRI; DIFFUSION/PERFUSION MISMATCH; INTRAARTERIAL THROMBOLYSIS; INTERVENTIONAL MANAGEMENT AB The most important service that imaging provides to patients with ischemic stroke is to rapidly identify those patients who are most likely to benefit from immediate treatment. This group includes patients who have severe neurological symptoms due to an occlusion of a major artery, and who are candidates for recanalization using intravenous thrombolysis or intra-arterial intervention to remove the occlusion. Outcomes for these patients are determined by symptom severity, the artery that is occluded, the size of the infarct at the time of presentation, and the effect of treatment. MRI provides key physiological information through MR angiography and diffusion MRI that has been proven to be of high clinical value in identify patients who are in need of immediate treatment. Perfusion MRI provides information about the ischemic penumbra, but its clinical value is unproven. In current clinical practice, the time since stroke onset is dominant over physiologic information provided by MRI in treatment decisions. This will change only when clinical trials prove that stroke physiology as revealed by MRI is superior to time from stroke onset in promoting good clinical outcomes. J. Magn. Reson. Imaging 2012;36:259271. (c) 2012 Wiley Periodicals, Inc. C1 [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, Fruit St, Boston, MA 02114 USA. EM rggonzalez@partners.org FU NIH [NS050041, NS051343] FX Contract grant sponsor: NIH; Contract grant number: NS050041, NS051343. NR 61 TC 12 Z9 12 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD AUG PY 2012 VL 36 IS 2 BP 259 EP + DI 10.1002/jmri.23595 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 974ZA UT WOS:000306475000001 PM 22807220 ER PT J AU Tancredi, FB Gauthier, CJ Madjar, C Bolar, DS Fisher, JA Wang, DJJ Hoge, RD AF Tancredi, Felipe B. Gauthier, Claudine J. Madjar, Cecile Bolar, Divya S. Fisher, Joseph A. Wang, Danny J. J. Hoge, Richard D. TI Comparison of pulsed and pseudocontinuous arterial spin-labeling for measuring CO2-induced cerebrovascular reactivity SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE ASL; hypercapnia; cerebrovascular reactivity ID CEREBRAL-BLOOD-FLOW; TIDAL CARBON-DIOXIDE; TRANSIT-TIME; VISUAL-STIMULATION; BOLD; FMRI; METABOLISM; EFFICIENCY; FREQUENCY; RESPONSES AB Purpose: To compare the performance of pulsed and pseudocontinuous arterial spin-labeling (PASL and pCASL) methods in measuring CO2-induced cerebrovascular reactivity (CVR). Materials and Methods: Subjects were scanned using both ASL sequences during a controlled hypercapnia procedure and visual stimulation. CVR was computed as the percent CO2-induced increase in cerebral blood flow (?%CBF) per mmHg increase in end-tidal PCO2. Visually evoked responses were expressed as ?%CBF. Resting CBF and temporal signal-to-noise ratio were also computed. Regionally averaged values for the different quantities were compared in gray matter (GM) and visual cortex (VC) using t-tests. Results: Both PASL and pCASL yielded comparable respective values for resting CBF (56 +/- 3 and 56 +/- 4 mL/min/100g) and visually evoked responses (75 +/- 5% and 81 +/- 4%). Values of CVR determined using pCASL (GM 4.4 +/- 0.2, VC 8 +/- 1 ?%CBF/mmHg), however, were significantly higher than those measured using PASL (GM 3.0 +/- 0.6, VC 5 +/- 1 ?%CBF/mmHg) in both GM and VC. The percentage of GM voxels in which statistically significant hypercapnia responses were detected was also higher for pCASL (27 +/- 5% vs. 16 +/- 3% for PASL). Conclusion: pCASL may be less prone to underestimation of CO2-induced flow changes due to improved label timing control. J. Magn. Reson. Imaging 2012;36:312321. (c) 2012 Wiley Periodicals, Inc. C1 [Tancredi, Felipe B.; Hoge, Richard D.] Univ Montreal, Dept Physiol, Inst Genie Biomed, Montreal, PQ H3C 3J7, Canada. [Tancredi, Felipe B.; Gauthier, Claudine J.; Madjar, Cecile; Hoge, Richard D.] Inst Univ Geriatrie Montreal, Ctr Rech, Unite Neuroimagerie Fonct, Montreal, PQ, Canada. [Gauthier, Claudine J.; Hoge, Richard D.] Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada. [Bolar, Divya S.] Massachussets Gen Hosp, Athinoula A Matinos Ctr Biomed Imaging, Charlestown, MA USA. [Bolar, Divya S.] Harvard Univ, MIT, Sch Med, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Bolar, Divya S.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Fisher, Joseph A.] Univ Toronto, Dept Anesthesiol, Univ Hlth Network, Toronto, ON, Canada. [Wang, Danny J. J.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Tancredi, FB (reprint author), 4545 Queen Mary,M6808, Montreal, PQ H3W 1W5, Canada. EM felipe.tancredi@umontreal.ca RI Tancredi, Felipe/L-2187-2014 OI Tancredi, Felipe/0000-0002-4419-8245 FU Canadian Institutes for Health Research [MOP 84378]; Canadian Foundation for Innovation [17380]; Ministere du developpement economique, de l'innovation et de l'exportation [PSR-SIIRI-239] FX Contract grant sponsor: Canadian Institutes for Health Research; Contract grant number: MOP 84378 (Banting and Best Scholarship held by C.J.G.); Contract grant sponsor: Canadian Foundation for Innovation; Contract grant number: Leaders Opportunity Fund 17380; Contract grant sponsor: Ministere du developpement economique, de l'innovation et de l'exportation; Contract grant number: PSR-SIIRI-239. NR 31 TC 20 Z9 20 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD AUG PY 2012 VL 36 IS 2 BP 312 EP 321 DI 10.1002/jmri.23658 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 974ZA UT WOS:000306475000005 PM 22544711 ER PT J AU Li, X Wan, LY Geng, J Wu, CL Bai, XY AF Li, Xiao Wan, Liyan Geng, Jian Wu, Chin-Lee Bai, Xiaoyan TI Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE ALDH1A1; ALDEFLUOR assay; Small interfering RNA transfection; Tissue microarray; Prognosis ID GENE-EXPRESSION; CELL-LINES; ADENOCARCINOMA; PROGNOSIS; MARKER AB Introduction: Lung cancer contains a small population of cancer stem cells that contribute to its initiation and progression. We investigated the biological function and clinical significance of aldehyde dehydrogenase 1A1 (ALDH1A1) in non-small-cell lung carcinoma (NSCLC). Methods: ALDH1A1 assay or small interfering RNA transfection was employed to isolate ALDH1A1+ cells or knock down ALDH1A1 expression in H2087 cells, respectively. Biological functions of ALDH1A1+ and ALDH1A1 silenced cells were investigated using in vitro and in vivo methods. ALDH1A1 expression was analyzed using immunohistochemistry on tissue microarrays with 179 lung cancer tissues and 26 normal lung tissues. Results: The abilities of clone formation, proliferation, cell growth, and migration were increased in ALDH1A1+ and ALDH1A1 silenced cells. ALDH1A1+ lung cancer cells initiated tumors that resembled the histopathologic characteristics and heterogeneity of the parental lung cancer cells in mice. The silencing of ALDH1A1 expression in H2087 lung cancer cells inhibited cell proliferation and migration significantly. ALDH1A1 was expressed in 42% of normal lung tissues (11 of 26), with strong expression in the basal cells and globular cells of the normal bronchus and weak expression in the alveolar epithelial cells. Compared with normal lung tissues, 45% of NSCLC samples (81 of 179) were read as positive for ALDH1A1. Positive ALDH1A1 expression was correlated with patients' smoking status (p = 0.022), lymph-node metastasis (p = 0.006), clinical stage (p = 0.004), and a decreased overall survival time (p < 0.001). Positive ALDH1A1 expression in lung cancer tissues was an independent prognostic factor for NSCLC (odds ratio = 5.232, p < 0.001). Conclusion: Elucidating the biological functions of ALDH1A1 could be helpful in studying lung tumorigenesis and for developing new therapeutic approaches. C1 [Bai, Xiaoyan] So Med Univ, Nanfang Hosp, Guangdong Prov Inst Nephrol, Div Nephrol, Guangzhou 510515, Guangdong, Peoples R China. [Li, Xiao] So Med Univ, Nanfang Hosp, Dept Emergency, Guangzhou 510515, Guangdong, Peoples R China. [Wan, Liyan; Geng, Jian] So Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China. [Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. RP Bai, XY (reprint author), So Med Univ, Nanfang Hosp, Guangdong Prov Inst Nephrol, Div Nephrol, 1838 Guangzhou N Rd, Guangzhou 510515, Guangdong, Peoples R China. EM xiaoyanbai@fimmu.com FU National Natural Science Foundation of China [81100496] FX We thank Shan Wang from University of Texas Southwestern Medical Center, and John Basgen, from Charles R. Drew University of Medicine and Science for their critical reading of the manuscript. This study was supported by a grant (Grant No. 81100496) from the National Natural Science Foundation of China. NR 28 TC 28 Z9 29 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2012 VL 7 IS 8 BP 1235 EP 1245 DI 10.1097/JTO.0b013e318257cc6d PG 11 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 974TD UT WOS:000306459000010 PM 22617249 ER PT J AU Bui, AH Bonaca, MP Sabatine, MS Ray, KK Rifai, N Cannon, CP Morrow, DA AF Bui, An H. Bonaca, Marc P. Sabatine, Marc S. Ray, Kausik K. Rifai, Nader Cannon, Christopher P. Morrow, David A. TI Elevated concentration of placental growth factor (PlGF) and long term risk in patients with acute coronary syndrome in the PROVE IT-TIMI 22 trial SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE PlGF; Inflammation; Acute coronary syndrome; Prognosis ID C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; HEART-DISEASE; INFLAMMATION; RECEPTOR; REVASCULARIZATION; ATHEROSCLEROSIS; INHIBITION; EXPRESSION; DISORDERS AB Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, acts via the flt-1 receptor and promotes endothelial activation and macrophage recruitment into atherosclerotic lesions. We investigated the relationship of PlGF with cardiovascular outcomes in a large cohort of patients presenting across the spectrum of ACS. PlGF was measured at baseline (n = 3,761) and at four-months (n = 3,369) in patients randomized to atorvastatin 80 mg or pravastatin 40 mg after ACS in the PROVE IT-TIMI 22 trial. The primary endpoint was death, myocardial infarction (MI), unstable angina, revascularization or stroke (mean follow-up 24 months). Elevated baseline PlGF was associated with a higher incidence of the primary endpoint through 2 years (Q1 vs. Q5: 18.7 vs. 29.3%, p < 0.0001). The risk of death or MI was also higher in patients with elevated baseline PlGF (Q1 vs. Q5: 7.0 vs. 11.6%, p = 0.029). Adjusting for baseline characteristics and risk factors, elevated baseline PlGF was independently associated with the risk of the primary endpoint (adjusted-HR for Q5 vs. Q1 1.45; 95% CI 1.16-1.83; p = 0.001). Elevated PlGF at four months was associated with higher risk of death or MI (Adjusted HR Q5 vs. Q1 2.79, 95% CI: 1.37-5.68; p = 0.005), and higher risk of the primary endpoint (Adjusted HR Q5 vs. Q1 1.78, 95% CI: 1.26-2.51; p = 0.001). Higher concentration of PlGF after ACS is associated with long-term risk of recurrent cardiovascular events independent of traditional risk factors. This association is present early after ACS and appears to be stronger at four months. C1 [Bui, An H.; Bonaca, Marc P.; Sabatine, Marc S.; Cannon, Christopher P.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Bui, An H.; Bonaca, Marc P.; Sabatine, Marc S.; Cannon, Christopher P.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bonaca, Marc P.; Sabatine, Marc S.; Cannon, Christopher P.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Ray, Kausik K.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Rifai, Nader] Childrens Hosp, Dept Lab Med NR, Boston, MA 02115 USA. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Dept Med, Thrombolysis Myocardial Infarct TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mbonaca@partners.org FU Bristol Myers Squibb; Accumetrics; Astra-Zeneca; Bayer Healthcare; Beckman Coulter; Biosite; Bristol-Myers Squibb; CV Therapeutics; Daiichi Sankyo; Eli Lilly and Co; GlaxoSmithKline; Merck and Company; Nanosphere; Novartis Pharmaceuticals; Ortho-Clinical Diagnostics; Pfizer; Roche Diagnostics; Sanofi-Aventis; Schering-Plough; Siemens; Singulex; NHLBI [HHSN268201000033C]; Abbott; BRAHMS; Critical Diagnostics FX PROVE IT-TIMI 22 was funded by Bristol Myers Squibb. The TIMI Study Group has received significant research grant support from Accumetrics, Astra-Zeneca, Bayer Healthcare, Beckman Coulter, Biosite, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Eli Lilly and Co, GlaxoSmithKline, Merck and Company, Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Schering-Plough, Siemens, and Singulex. Dr Sabatine was supported in part by contract HHSN268201000033C from the NHLBI. Dr. Sabatine also receives research grant support from Abbott, BRAHMS, Critical Diagnostics, Nanosphere, and Roche Diagnostics. Dr. Ray received an unrestricted research grant support from Pfizer. Dr. Morrow has received honoraria for educational presentations from CV Therapeutics, and Sanofi-Aventis. He has served as a consultant for Beckman Coulter, Sanofi-Aventis, Schering Plough, and Siemens. Drs. Bonaca, Bui, Cannon, and Rifai have no additional relationships to report. NR 18 TC 4 Z9 5 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD AUG PY 2012 VL 34 IS 2 BP 222 EP 228 DI 10.1007/s11239-012-0704-z PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 974IR UT WOS:000306427900008 PM 22446996 ER PT J AU Vora, AN Bonaca, MP Ruff, CT Jarolim, P Murphy, S Croce, K Sabatine, MS Simon, DI Morrow, DA AF Vora, Amit N. Bonaca, Marc P. Ruff, Christian T. Jarolim, Petr Murphy, Sabina Croce, Kevin Sabatine, Marc S. Simon, Daniel I. Morrow, David A. TI Diagnostic evaluation of the MRP-8/14 for the emergency assessment of chest pain SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Biomarkers; Unstable angina; Myocardial infarction; Platelets ID ELEVATION MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; PLASMA-PROTEIN-A; CARDIOVASCULAR EVENTS; PRACTICE GUIDELINES; SENSITIVE MARKER; FOCUSED UPDATE; MYELOID-RELATED-PROTEIN-8/14; MANAGEMENT; OCCLUSION AB Elevated levels of myeloid-related protein (MRP)-8/14 (S100A8/A9) are associated with first cardiovascular events in healthy individuals and worse prognosis in patients with acute coronary syndrome (ACS). The diagnostic utility of MRP-8/14 in patients presenting to the emergency room with symptoms concerning for ACS is uncertain. MRP-8/14 was measured in serial serum and plasma samples in a single center prospective cohort-study of patients presenting to the emergency room with non-traumatic chest pain concerning for ACS. Final diagnosis was adjudicated by an endpoint committee. Of patients with baseline MRP-8/14 results (n = 411), the median concentration in serum was 1.57 mu g/ml (25th, 75th: 0.87, 2.68) and in plasma was 0.41 mu g/ml (< 0.4, 1.15) with only moderate correlation between serum and plasma (rho = 0.40). A final diagnosis of MI was made in 106 (26%). Peak serum MRP-8/14 was higher in patients presenting with MI (p < 0.001). However, the overall diagnostic performance of MRP-8/14 was poor: sensitivity 28% (95% CI 20-38), specificity 82% (78-86), positive predictive value 36% (26-47), and negative predictive value 77% (72-81). The area under the ROC curve for diagnosis of MI with MRP-8/14 was 0.55 (95% CI 0.51-0.60) compared with 0.95 for cTnI. The diagnostic performance was not improved in early-presenters, patients with negative initial cTnI, or using later MRP-8/14 samples. Patients presenting with MI had elevated levels of serum MRP-8/14 compared to patients with non-cardiac chest pain. However, overall diagnostic performance of MRP-8/14 was poor and neither plasma nor serum MRP-8/14 offered diagnostic utility comparable to cardiac troponin. C1 [Vora, Amit N.; Bonaca, Marc P.; Ruff, Christian T.; Murphy, Sabina; Sabatine, Marc S.; Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,TIMI Study Grp, Boston, MA 02115 USA. [Jarolim, Petr] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Croce, Kevin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02115 USA. [Simon, Daniel I.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Harrington McLaughlin Heart & Vasc Inst, Sch Med, Cleveland, OH 44106 USA. RP Bonaca, MP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM mbonaca@partners.org FU Accumetrics; Astra-Zeneca; Bayer Healthcare; Beckman Coulter; Biosite; Bristol-Myers Squibb; CV Therapeutics; Daiichi Sankyo; Eli Lilly and Co; GlaxoSmithKline; Merck and Company; Nanosphere; Novartis Pharmaceuticals; Ortho-Clinical Diagnostics; Pfizer; Roche Diagnostics; Sanofi-Aventis; Schering-Plough; Siemens; Singulex; Amgen; BRAMS; Abbott; Merck and Co.; NHLBI [K08HL086672, R01 HL096738, R01 HL098280, HHSN268201000033C]; BRAHMS; National Institutes of Health [HL57506] FX The TIMI Study Group has received significant research grant support from Accumetrics, Astra-Zeneca, Bayer Healthcare, Beckman Coulter, Biosite, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Eli Lilly and Co, GlaxoSmithKline, Merck and Company, Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Schering-Plough, Siemens, and Singulex. Dr. Jarolim has consulted for T2 Biosystems and Quanterix and has received grant support from Daiichi Sankyo, Roche Diagnostics, Amgen, BRAMS, Abbott, and Merck and Co. Dr. Croce was supported in part by NHLBI grant K08HL086672. Dr. Sabatine was supported in part by grant R01 HL096738, grant R01 HL098280, and contract HHSN268201000033C from the NHLBI. Dr. Sabatine also receives research grant support from Abbott, BRAHMS, Critical Diagnostics, Nanosphere, and Roche Diagnostics. Dr. Simon was supported in part by National Institutes of Health grant to DIS (HL57506 MERIT Award). Dr. Morrow has received honoraria for educational presentations from CV Therapeutics, and Sanofi-Aventis. He has served as a consultant for Beckman Coulter, Sanofi-Aventis, Schering Plough, and Siemens. Ms. Murphy and Drs. Bonaca, and Ruff have no additional relationships to report. NR 23 TC 9 Z9 11 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD AUG PY 2012 VL 34 IS 2 BP 229 EP 234 DI 10.1007/s11239-012-0705-y PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 974IR UT WOS:000306427900009 PM 22446997 ER PT J AU Navathe, AS Volpp, KG Konetzka, RT Press, MJ Zhu, JS Chen, W Lindrooth, RC AF Navathe, Amol S. Volpp, Kevin G. Konetzka, R. Tamara Press, Matthew J. Zhu, Jingsan Chen, Wei Lindrooth, Richard C. TI A Longitudinal Analysis of the Impact of Hospital Service Line Profitability on the Likelihood of Readmission SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE quality of care; Medicare; payment reform; intensity of services; service line profitability; readmission rates ID DUTY HOUR REFORM; BALANCED BUDGET ACT; LENGTH-OF-STAY; ADMINISTRATIVE DATA; MEDICARE BENEFICIARIES; COMORBIDITY MEASURES; PROSPECTIVE PAYMENT; STAFFING DECISIONS; COMPETING RISKS; COX REGRESSION AB Quality of care may be linked to the profitability of admissions in addition to level of reimbursement. Prior policy reforms reduced payments that differentially affected the average profitability of various admission types. The authors estimated a Cox competing risks model, controlling for the simultaneous risk of mortality post discharge, to determine whether the average profitability of hospital service lines to which a patient was admitted was associated with the likelihood of readmission within 30 days. The sample included 12,705,933 Medicare Fee for Service discharges from 2,438 general acute care hospitals during 1997, 2001, and 2005. There was no evidence of an association between changes in average service line profitability and changes in readmission risk, even when controlling for risk of mortality. These findings are reassuring in that the profitability of patients' admissions did not affect readmission rates, and together with other evidence may suggest that readmissions are not an unambiguous quality indicator for in-hospital care. C1 [Navathe, Amol S.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19146 USA. [Navathe, Amol S.] Dept Hlth & Human Serv, Washington, DC USA. [Navathe, Amol S.] Harvard Univ, Sch Med, Boston, MA USA. [Volpp, Kevin G.; Chen, Wei] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Konetzka, R. Tamara] Univ Chicago, Chicago, IL 60637 USA. [Press, Matthew J.] Weill Cornell Med Coll, New York, NY USA. [Lindrooth, Richard C.] Univ Colorado Denver, Aurora, CO USA. RP Navathe, AS (reprint author), Univ Penn, Wharton Sch, Dept Hlth Care Management, 3641 Locust Walk,Room 202, Philadelphia, PA 19146 USA. EM amol@wharton.upenn.edu RI Lindrooth, Richard/J-8607-2012; OI Lindrooth, Richard/0000-0001-9538-9749 FU Robert Wood Johnson Foundation's Health Care Financing and Organization program FX This research was funded, in part, by a grant from the Robert Wood Johnson Foundation's Health Care Financing and Organization program. NR 45 TC 3 Z9 3 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD AUG PY 2012 VL 69 IS 4 BP 414 EP 431 DI 10.1177/1077558712441085 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 976TW UT WOS:000306609400003 PM 22466577 ER PT J AU Singer, SJ Moore, SC Meterko, M Williams, S AF Singer, Sara J. Moore, Scott C. Meterko, Mark Williams, Sandra TI Development of a Short-Form Learning Organization Survey: The LOS-27 SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE organizational learning; psychometric analysis; survey ID INTENSIVE-CARE UNITS; PATIENT SAFETY; HEALTH-CARE; HOSPITALS; IMPROVE; IMPLEMENTATION; QUALITY; FAILURE; CLIMATE; WORK AB Despite urgent need for innovation, adaptation, and change in health care, few tools enable researchers or practitioners to assess the extent to which health care facilities perform as learning organizations or the effects of initiatives that require learning. This study's objective was to develop and test a short-form Learning Organization Survey to fill this gap. The authors applied exploratory factor analysis and confirmatory factor analysis to data from Veterans Health Administration personnel to derive a short-form survey and then conducted further confirmatory factor analysis and factor invariance testing on additional Veterans Health Administration data to evaluate the short form. Results suggest that a 27-item, 7-factor survey (2 environmental factors, 1 on leadership, and 4 on concrete learning processes and practices) reliably measures key features of organizational learning, allowing researchers to evaluate theoretical propositions about organizational learning, its antecedents, and outcomes and enabling managers to assess and enhance organizations' learning capabilities and performance. C1 [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Singer, Sara J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Singer, Sara J.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Moore, Scott C.] Vet Hlth Adm Natl Ctr Org Dev, Cincinnati, OH USA. [Meterko, Mark; Williams, Sandra] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Meterko, Mark] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Singer, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ssinger@hsph.harvard.edu FU Veterans Health Administration, Office of Academic Affiliations FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Development and validation of the revised instrument was financially supported by a grant from the Veterans Health Administration, Office of Academic Affiliations, as well as in-kind support from the Veterans Health Administration, National Center for Organization Development. NR 34 TC 13 Z9 13 U1 22 U2 45 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 AUG PY 2012 VL 69 IS 4 BP 432 EP 459 DI 10.1177/1077558712448135 PG 28 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 976TW UT WOS:000306609400004 PM 22635274 ER PT J AU Frazier-Wood, AC Garvey, WT Dall, T Honigberg, R Pourfarzib, R AF Frazier-Wood, Alexis C. Garvey, W. Timothy Dall, Tara Honigberg, Robert Pourfarzib, Ray TI Opportunities for Using Lipoprotein Subclass Profile by Nuclear Magnetic Resonance Spectroscopy in Assessing Insulin Resistance and Diabetes Prediction SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Review ID HOMEOSTASIS MODEL ASSESSMENT; LOW-DENSITY LIPOPROTEINS; PARTICLE-SIZE; METABOLIC SYNDROME; FASTING GLUCOSE; GLOBAL BURDEN; UNITED-STATES; FOLLOW-UP; RISK; ATHEROSCLEROSIS AB The incidence of type 2 diabetes mellitus (T2DM) has reached epidemic levels, and current trends indicate that its prevalence will continue to rise. The development of T2DM can be delayed by several years, and may even be prevented, by identifying individuals at risk for T2DM and treating them with lifestyle modification and/or pharmacological therapies. There are a number of methods available for assessing the insulin resistance (IR) that characterizes, and is the precursor to, T2DM. However, current clinical methods for assessing IR, based on measures of plasma glucose and/or insulin are either laborious and time-consuming or show a low specificity. IR manifests its earliest measurable abnormalities through changes in lipoproteins, and thus we propose that by examining lipoprotein subclass profile, it may be possible to alert physicians and patients to a heightened risk of developing diabetes. This will allow us to institute appropriate lifestyle changes and treatment potentially to delay the onset or possibly prevent the progression to diabetes. C1 [Frazier-Wood, Alexis C.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA. [Frazier-Wood, Alexis C.] Univ Alabama Birmingham, Sect Stat Genet, Birmingham, AL 35294 USA. [Frazier-Wood, Alexis C.] Univ Alabama Birmingham, Off Energet, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Honigberg, Robert; Pourfarzib, Ray] LipoScience Inc, Raleigh, NC USA. RP Frazier-Wood, AC (reprint author), Univ Alabama Birmingham, Dept Epidemiol, RPHB 230P, Birmingham, AL 35294 USA. EM lekkiwood@gmail.com RI Frazier-Wood, Alexis (Lekki)/B-8053-2010 OI Frazier-Wood, Alexis (Lekki)/0000-0001-7616-2119 FU National Institutes of Health (NIH) [DK-038764, DK-083562]; Merit Review program of the Department of Veterans Affairs; UAB Diabetes Research and Training Center [P60DK079626]; NIH National Heart, Lung, and Blood Institute grant [U01HL072524-04] FX The authors acknowledge research support from the National Institutes of Health (NIH; DK-038764, DK-083562) and the Merit Review program of the Department of Veterans Affairs. We also gratefully acknowledge the support of the UAB Diabetes Research and Training Center (P60DK079626). Dr. Frazier-Wood is supported by NIH National Heart, Lung, and Blood Institute grant U01HL072524-04. NR 37 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD AUG PY 2012 VL 10 IS 4 BP 244 EP 251 DI 10.1089/met.2011.0148 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 976OR UT WOS:000306594700002 PM 22533466 ER PT J AU Samkoe, KS Sexton, K Tichauer, KM Hextrum, SK Pardesi, O Davis, SC O'Hara, JA Hoopes, PJ Hasan, T Pogue, BW AF Samkoe, Kimberley S. Sexton, Kristian Tichauer, Kenneth M. Hextrum, Shannon K. Pardesi, Omar Davis, Scott C. O'Hara, Julia A. Hoopes, P. Jack Hasan, Tayyaba Pogue, Brian W. TI High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Three-compartment model; Epidermal growth factor receptor; Pancreatic tumor; Fluorescence imaging; Cellular associated rate constant ID EPIDERMAL-GROWTH-FACTOR; FACTOR-ALPHA; CANCER; THERAPY; GEMCITABINE; EXPRESSION; BLOCKADE; MODELS; AGENTS; MOUSE AB Cellular receptor targeted imaging agents present the potential to target extracellular molecular expression in cancerous lesions; however, the image contrast in vivo does not reflect the magnitude of overexpression expected from in vitro data. Here, the in vivo delivery and binding kinetics of epidermal growth factor receptor (EGFR) was determined for normal pancreas and AsPC-1 orthotopic pancreatic tumors known to overexpress EGFR. EGFR in orthotopic xenograft AsPC-1 tumors was targeted with epidermal growth factor (EGF) conjugated with IRDye800CW. The transfer rate constants (k (e,) K (12), k (21), k (23), and k (32)) associated with a three-compartment model describing the vascular delivery, leakage rate and binding of targeted agents were determined experimentally. The plasma excretion rate, k (e), was determined from extracted blood plasma samples. K (12), k (21), and k (32) were determined from ex vivo tissue washing studies at time points a parts per thousand yen24 h. The measured in vivo uptake of IRDye800CW-EGF and a non-targeted tracer dye, IRDye700DX-carboxylate, injected simultaneously was used to determined k (23). The vascular exchange of IRDye800CW-EGF in the orthotopic tumor (K (12) and k (21)) was higher than in the AsPC-1 tumor as compared to normal pancreas, suggesting that more targeted agent can be taken up in tumor tissue. However, the cellular associated (binding) rate constant (k (23)) was slightly lower for AsPC-1 pancreatic tumor (4.1 x 10(-4) s(-1)) than the normal pancreas (5.5 x 10(-4) s(-1)), implying that less binding is occurring. Higher vascular delivery but low cellular association in the AsPC-1 tumor compared to the normal pancreas may be indicative of low receptor density due to low cellular content. This attribute of the AsPC-1 tumor may indicate one contributing cause of the difficulty in treating pancreatic tumors with cellular targeted agents. C1 [Samkoe, Kimberley S.; Sexton, Kristian; Tichauer, Kenneth M.; Hextrum, Shannon K.; Pardesi, Omar; Davis, Scott C.; O'Hara, Julia A.; Hoopes, P. Jack; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Hoopes, P. Jack; Pogue, Brian W.] Dartmouth Med Sch, Dept Surg, Hanover, NH 03755 USA. [Hasan, Tayyaba; Pogue, Brian W.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Samkoe, KS (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. EM kimberley.s.samkoe@dartmouth.edu; brian.w.pogue@dartmouth.edu OI Tichauer, Kenneth/0000-0003-1667-3026 FU NIH [P01CA84201, R01CA109558, R01CA156177] FX This work was funded by NIH grants P01CA84201, R01CA109558, and R01CA156177. NR 30 TC 13 Z9 13 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD AUG PY 2012 VL 14 IS 4 BP 472 EP 479 DI 10.1007/s11307-011-0503-5 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 975YU UT WOS:000306548500012 PM 21847690 ER PT J AU Gavasso, S Gjertsen, BT Anderssen, E Myhr, KM Vedeler, C AF Gavasso, S. Gjertsen, B. T. Anderssen, E. Myhr, K. M. Vedeler, C. TI Immunogenic effects of recombinant interferon-beta therapy disrupt the JAK/STAT pathway in primary immune cells from patients with multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE interferon-beta; JAK/STAT signalling; immunogenicity; neutralizing antibodies; PBMC; phospho-flow cytometry ID RELAPSING-REMITTING MS; NEUTRALIZING ANTIBODIES; FLOW-CYTOMETRY; IFN-BETA; EXPRESSION; BIOACTIVITY; PROGRESSION; RESPONSES; IMPACT; TITER AB Background: Immunogenicity of recombinant interferon-beta (IFN-beta) is a known complication in the therapy of relapsing-remitting multiple sclerosis (RRMS). Neutralizing antibodies (NAbs) that can interfere with efficacy are quantified using in vitro bioassays; however, these assays do not reveal the immunogenic state of the patient and are not predictive of treatment outcome. Objective: Assessment of the impact of NAbs on IFN-beta responsive cells and signalling pathways in peripheral blood mononuclear cells (PBMCs) with phospho-specific flow cytometry. Method: PBMCs from 10 IFN-beta-treated patients with RRMS, two untreated patients, and two healthy controls were re-stimulated in autologous sera and media with a serial dilution of IFN-beta (0-8000 U/ml) and levels of phosphorylation of STAT1/3/4/5/6 transcription factors were quantified in PBMC subtypes (NAb titres 0 to > 6000 neutralizing units). Data was subjected to principal component analysis, Hotelling's T-2, and partial least squares analysis. Results: Three significantly distinct clusters of individuals were revealed in autologous sera: therapy-naive and healthy, treated NAb-negative, and treated NAb-positive. Compared with controls STATs signalling patterns were modulated in treated NAb-negative patients and inhibited in all treated NAb-positive patients independently of NAb titres. In media no clustering of patients could be found. The predictability of NAb titres based on the phospho-flow data was 74%. Conclusion: Phospho-specific flow cytometry can delineate subset-specific cell responses that can act as surrogates for NAb exposure in blood. Immunogenic effects alter the response in primary cells even at low NAb levels. Cell line-based immunogenicity testing is not readily transferable to the immunogenic response in patients. C1 [Gavasso, S.] Haukeland Hosp, Neurol Res Lab, Dept Neurol, N-5021 Bergen, Norway. [Gavasso, S.; Myhr, K. M.; Vedeler, C.] Univ Bergen, Inst Clin Med, N-5020 Bergen, Norway. [Gavasso, S.; Myhr, K. M.] Haukeland Hosp, Dept Neurol, Norwegian Multiple Sclerosis Competence Ctr, N-5021 Bergen, Norway. [Gjertsen, B. T.] Univ Bergen, Haematol Sect, Inst Med, N-5020 Bergen, Norway. [Gjertsen, B. T.] Haukeland Hosp, Dept Internal Med, N-5021 Bergen, Norway. [Anderssen, E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Myhr, K. M.; Vedeler, C.] Univ Bergen, KG Jebsen Ctr MS Res, Dept Clin Med, N-5020 Bergen, Norway. RP Gavasso, S (reprint author), Haukeland Hosp, Neurol Res Lab, Dept Neurol, N-5021 Bergen, Norway. EM sonia.gavasso@helse-bergen.no RI Gjertsen, Bjorn T/O-1542-2015 OI Gjertsen, Bjorn T/0000-0001-9358-9704 FU Norwegian Multiple Sclerosis Competence Center, Bergen, Norway; Research Council of Norway's National Program for Research in Functional Genomics; Bayer Health Care; Bayer Schering Pharma, Norway; Biogen Idec, Norway; Sanofi-Aventis, Norway FX This research was funded by the Norwegian Multiple Sclerosis Competence Center, Bergen, Norway; the Research Council of Norway's National Program for Research in Functional Genomics; and unrestricted grants from Bayer Health Care and Bayer Schering Pharma, Norway; Biogen Idec, Norway; and Sanofi-Aventis, Norway. NR 39 TC 4 Z9 4 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD AUG PY 2012 VL 18 IS 8 BP 1116 EP 1124 DI 10.1177/1352458511434066 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 975KQ UT WOS:000306510600010 PM 22287540 ER PT J AU Quintana, FJ Jin, HL Burns, EJ Nadeau, M Yeste, A Kumar, D Rangachari, M Zhu, C Xiao, S Seavitt, J Georgopoulos, K Kuchroo, VK AF Quintana, Francisco J. Jin, Hulin Burns, Evan J. Nadeau, Meghan Yeste, Ada Kumar, Deepak Rangachari, Manu Zhu, Chen Xiao, Sheng Seavitt, John Georgopoulos, Katia Kuchroo, Vijay K. TI Aiolos promotes T(H)17 differentiation by directly silencing Il2 expression SO NATURE IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; ARYL-HYDROCARBON RECEPTOR; TH17 CELLS; HELPER-CELLS; ROR-GAMMA; IN-VIVO; INTERLEUKIN-2; TRANSCRIPTION; GENE; IL-2 AB CD4(+) interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are instrumental in the immune response to pathogens. However, an overactive T(H)17 response results in tissue inflammation and autoimmunity, and therefore it is important to identify the molecular mechanisms that control the development of T(H)17 cells. IL-2 suppresses such development, but how IL-2 production is actively suppressed during T(H)7 differentiation is not understood. Here we report that under T(H)17-polarizing conditions, the transcription factors STAT3 and AhR upregulated the expression of Aiolos, a member of the Ikaros family of transcription factors. Using Aiolos-deficient mice, we demonstrated that Aiolos silenced the Il2 locus, promoting T(H)17 differentiation in vitro and in vivo. Thus, we have identified a module in the transcriptional program of T(H)17 cells that actively limits IL-2 production and promotes their differentiation. C1 [Quintana, Francisco J.; Jin, Hulin; Burns, Evan J.; Nadeau, Meghan; Yeste, Ada; Rangachari, Manu; Zhu, Chen; Xiao, Sheng; Kuchroo, Vijay K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Kumar, Deepak] Harvard Univ, Sch Med, Boston, MA USA. [Seavitt, John; Georgopoulos, Katia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Quintana, FJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. EM fquintana@rics.bwh.harvard.edu; vkuchroo@rics.bwh.harvard.edu FU US National Institutes of Health [P01AI073748, P01NS038037, P01AI056299, R01NS030843, AI075285, AI093903]; National Multiple Sclerosis Society [RG4111A1, FG1850-A-1]; Harvard Medical School Office for Diversity and Community Partnership FX We thank D. Kozoriz for cell sorting, and B. Waksman and I.R. Cohen for discussions. Supported by the US National Institutes of Health (P01AI073748, P01NS038037, P01AI056299 and R01NS030843 to V.K.K.; and AI075285 and AI093903 to F.J.Q.), the National Multiple Sclerosis Society (RG4111A1 to F.J.Q.), the Harvard Medical School Office for Diversity and Community Partnership (F.J.Q.) and the National Multiple Sclerosis Society (FG1850-A-1 to H.J.). NR 45 TC 83 Z9 89 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD AUG PY 2012 VL 13 IS 8 BP 770 EP + DI 10.1038/ni.2363 PG 9 WC Immunology SC Immunology GA 976GT UT WOS:000306569600013 PM 22751139 ER PT J AU O'Connor, S Ayres, A Cortellini, L Rosand, J Rosenthal, E Kimberly, WT AF O'Connor, Sydney Ayres, Alison Cortellini, Lynelle Rosand, Jonathan Rosenthal, Eric Kimberly, W. Taylor TI Process Improvement Methods Increase the Efficiency, Accuracy, and Utility of a Neurocritical Care Research Repository SO NEUROCRITICAL CARE LA English DT Article DE Neurocritical care; Research repository; Process improvement; Root-cause analysis; Plan-do-study-act AB Reliable and efficient data repositories are essential for the advancement of research in Neurocritical care. Various factors, such as the large volume of patients treated within the Neuro ICU, their differing length and complexity of hospital stay, and the substantial amount of desired information can complicate the process of data collection. We adapted the tools of process improvement to the data collection and database design of a research repository for a Neuroscience intensive care unit. By the Shewhart-Deming method, we implemented an iterative approach to improve the process of data collection for each element. After an initial design phase, we re-evaluated all data fields that were challenging or time-consuming to collect. We then applied root-cause analysis to optimize the accuracy and ease of collection, and to determine the most efficient manner of collecting the maximal amount of data. During a 6-month period, we iteratively analyzed the process of data collection for various data elements. For example, the pre-admission medications were found to contain numerous inaccuracies after comparison with a gold standard (sensitivity 71 % and specificity 94 %). Also, our first method of tracking patient admissions and discharges contained higher than expected errors (sensitivity 94 % and specificity 93 %). In addition to increasing accuracy, we focused on improving efficiency. Through repeated incremental improvements, we reduced the number of subject records that required daily monitoring from 40 to 6 per day, and decreased daily effort from 4.5 to 1.5 h/day. By applying process improvement methods to the design of a Neuroscience ICU data repository, we achieved a threefold improvement in efficiency and increased accuracy. Although individual barriers to data collection will vary from institution to institution, a focus on process improvement is critical to overcoming these barriers. C1 [O'Connor, Sydney; Ayres, Alison; Cortellini, Lynelle; Rosand, Jonathan; Rosenthal, Eric; Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Kimberly, WT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Lunder 644,45 Fruit St, Boston, MA 02114 USA. EM wtkimberly@partners.org OI Ayres, Alison/0000-0002-5492-1695; Rosenthal, Eric/0000-0003-3900-356X FU NIH [R01NS059727, R01NS073344, 1K23NS076597]; Beth Israel Deaconess Medical Center - Harvard Medical School; Pfizer Inc.; Merck Co FX Funded by NIH R01NS059727 (J. R.), NIH R01NS073344 (J. R.), NIH 1K23NS076597 (W. T. K.) and the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center - Harvard Medical School, in collaboration with Pfizer Inc. and Merck & Co (W.T.K.). NR 9 TC 0 Z9 0 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD AUG PY 2012 VL 17 IS 1 BP 90 EP 96 DI 10.1007/s12028-012-9689-x PG 7 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 976NG UT WOS:000306591000012 PM 22434546 ER PT J AU Wu, XB Tucker, JD Hong, FC Messina, J Lan, LN Hu, YF Feng, TJ Emch, ME Liu, XL Zhang, CL Wen, LZ AF Wu, Xiaobing Tucker, Joseph D. Hong, Fuchang Messina, Jane Lan, Lina Hu, Yufeng Feng, Tiejian Emch, Michael E. Liu, Xiaoli Zhang, Chunlai Wen, Lizhang TI Multilevel and spatial analysis of syphilis in Shenzhen, China, to inform spatially targeted control measures SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Article ID SEX WORK; HIV; RISK; MEN; SURVEILLANCE; PERCEPTIONS; INFECTIONS; BEHAVIORS; CONTEXT; HEALTH AB Objectives The present study investigates the varied spatial distribution of syphilis cases in Shenzhen, China, and explores the individual-, neighbourhood- and district-level factors affecting the distribution. Methods This study uses spatial analysis and multi-level generalised estimating equations to explore the spatial distribution of reported syphilis cases among individuals in Shenzhen, Guangdong Province, China. The spatial distribution of primary/secondary and latent cases was investigated using the Moran's I-statistic. Primary/secondary syphilis cases were compared with all syphilis cases using a three-level model with individual (n=6496), neighbourhood (n=55) and district (n=6) levels. Results A total of 6496 syphilis cases were reported in 2009 with 35.8% primary and secondary syphilis cases. Both primary/secondary syphilis cases (Moran's I value=0.33, p<0.01) and latent syphilis cases (Moran's I value=0.19, p<0.01) showed significant spatial clustering at the neighbourhood level. Adjusting for the number of reporting hospitals, the best model found that the following characteristics were associated with primary/secondary syphilis infection: individuals who are younger in age (p=0.003), male (p<0.001), migrant labourers (p=0.047) and those who live in districts with a higher gross domestic product (p<0.001). Conclusions There is substantial clustering of primary and secondary syphilis cases at the neighbourhood level in Shenzhen, suggesting the need for greater STD health service provision in these clustered neighbourhoods. Spatially targeted syphilis control measures may be useful to optimise testing, treatment and partner services. C1 [Wu, Xiaobing; Hong, Fuchang; Lan, Lina; Hu, Yufeng; Feng, Tiejian; Liu, Xiaoli; Zhang, Chunlai; Wen, Lizhang] Shenzhen Ctr Chron Dis Control, Shenzhen, Peoples R China. [Tucker, Joseph D.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Tucker, Joseph D.] Univ N Carolina, Sch Med, Div Infect Dis, Chapel Hill, NC USA. [Messina, Jane; Emch, Michael E.] Univ N Carolina, Dept Geog, Chapel Hill, NC USA. RP Feng, TJ (reprint author), Shenzhen Ctr Chron Dis Control & Prevent, 2021 Buxin Rd, Shenzhen, Peoples R China. EM tiejian.feng@gmail.com FU Shenzhen Municipal Health Bureau for STI Prevention and Control Program; Mega Project of China National Science Research for the 11th 5-year Plan [2008ZX10001-005]; NIH Fogarty Career Development Award [US NIH 1K01TW008200-01A1] FX This work was supported by grants from the Shenzhen Municipal Health Bureau for STI Prevention and Control Program, the Mega Project of China National Science Research for the 11th 5-year Plan (2008ZX10001-005) and an NIH Fogarty Career Development Award (US NIH 1K01TW008200-01A1). NR 28 TC 7 Z9 7 U1 1 U2 10 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD AUG PY 2012 VL 88 IS 5 BP 325 EP 329 DI 10.1136/sextrans-2011-050397 PG 5 WC Infectious Diseases SC Infectious Diseases GA 974CC UT WOS:000306406400005 PM 22378936 ER PT J AU Wang, AL Peng, RR Tucker, JD Cohen, MS Chen, XS AF Wang, Alberta L. Peng, Rui-Rui Tucker, Joseph D. Cohen, Myron S. Chen, Xiang-Sheng TI Partner notification uptake for sexually transmitted infections in China: a systematic literature review SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Review ID CHLAMYDIAL INFECTION; HIDDEN EPIDEMIC; SEX PARTNERS; DISEASES; HIV; MANAGEMENT; HIV/AIDS; TANZANIA; STIGMA; CARE AB Objective China's sexually transmitted infection (STI) epidemic requires comprehensive control programmes. Partner services are traditional pillars of STI control but have not been widely implemented in China. This study was a systematic literature review to examine STI partner notification (PN) uptake in China. Methods Four English and four Chinese language databases were searched up to March 2011 to identify articles on PN of STIs including HIV in China. PN uptake was defined as the number of partners named, notified, evaluated or diagnosed per index patient. Results A total of 11 studies met inclusion criteria. For STI (excluding HIV) PN, a median 31.6% (IQR 27.4%-65.8%) of named partners were notified, 88.8% (IQR 88.4%-90.8%) of notified partners were evaluated and 37.9% (IQR 33.1%-43.6%) of evaluated partners were diagnosed. For HIV PN, a median 15.7% (IQR 13.2%-36.5%) of named partners were notified, 86.7% (IQR 72.9%-90.4%) of notified partners were evaluated and 27.6% (IQR 24.1%-27.7%) of evaluated partners were diagnosed. A mean of 80.6% (SD=12.6%) of patients attempted PN, and 72.4% (IQR 63.8%=81.1%) chose self-referral when offered more than one method of PN. Perceived patient barriers included social stigma, fear of relationship breakdown, uncertainty of how to notify and lack of partner contact information. Perceived infrastructure barriers included limited time and trained staff, mistrust of health workers and lack of PN guidelines. Conclusion PN programmes are feasible in China. Further research on STI PN, particularly among men who have sex with men and other high-risk groups, is an important public health priority. PN policies and guidelines are urgently needed in China. C1 [Wang, Alberta L.; Peng, Rui-Rui; Chen, Xiang-Sheng] Chinese Acad Med Sci, Nanjing 210042, Jiangsu, Peoples R China. [Wang, Alberta L.; Peng, Rui-Rui; Chen, Xiang-Sheng] Peking Union Med Coll, Inst Dermatol, Nanjing 210042, Jiangsu, Peoples R China. [Wang, Alberta L.; Peng, Rui-Rui; Chen, Xiang-Sheng] Natl Ctr STD Control, Nanjing 210042, Jiangsu, Peoples R China. [Wang, Alberta L.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Tucker, Joseph D.; Cohen, Myron S.] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Tucker, Joseph D.] Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA USA. RP Chen, XS (reprint author), Chinese Acad Med Sci, 12 Jiangwangmiao St, Nanjing 210042, Jiangsu, Peoples R China. EM chenxs@ncstdlc.org FU National Institutes of Health; Office of the Director; Fogarty International Center; Office of AIDS Research; National Cancer Institute; National Eye Institute; National Heart, Blood and Lung Institute; National Institute of Dental & Craniofacial Research; National Institute On Drug Abuse; National Institute of Mental Health; National Institute of Allergy and Infectious Diseases Health, through the International Clinical Research Fellows Program at Vanderbilt University [R24 TW007988]; Mega Project of China National Science Research for the 11th Five-Year Plan [2008ZX10001-005] FX The authors thank Frank Wong at Emory University for his review and comments of the paper, Meridith Blevins at Vanderbilt University for statistical advice, and Yan Hong-Jing at the Jiangsu CDC and Jiang Ning at the Chinese National STD Control Center for PN policy information. NIMH International Clinical Research Fellows Program at Vanderbilt University and China Mega Project. Grant Number: R24 TW007988 and 2008ZX10001-005.; This study was funded by the National Institutes of Health; Office of the Director; Fogarty International Center; Office of AIDS Research; National Cancer Institute; National Eye Institute; National Heart, Blood and Lung Institute; National Institute of Dental & Craniofacial Research; National Institute On Drug Abuse; National Institute of Mental Health; and the National Institute of Allergy and Infectious Diseases Health, through the International Clinical Research Fellows Program at Vanderbilt University (R24 TW007988) and the Mega Project of China National Science Research for the 11th Five-Year Plan (2008ZX10001-005). NR 30 TC 8 Z9 11 U1 2 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD AUG PY 2012 VL 88 IS 5 BP 386 EP 393 DI 10.1136/sextrans-2011-050275 PG 8 WC Infectious Diseases SC Infectious Diseases GA 974CC UT WOS:000306406400020 PM 22427489 ER PT J AU Wilkinson, JE Burmeister, L Brooks, SV Chan, CC Friedline, S Harrison, DE Hejtmancik, JF Nadon, N Strong, R Wood, LK Woodward, MA Miller, RA AF Wilkinson, John E. Burmeister, Lisa Brooks, Susan V. Chan, Chi-Chao Friedline, Sabrina Harrison, David E. Hejtmancik, James F. Nadon, Nancy Strong, Randy Wood, Lauren K. Woodward, Maria A. Miller, Richard A. TI Rapamycin slows aging in mice SO AGING CELL LA English DT Article DE interventions; longevity pathology; TOR ID AMES DWARF MICE; GENETICALLY HETEROGENEOUS MICE; LIFE-SPAN EXTENSION; SIGNALING PATHWAY; CELL-CYCLE; TOR; TARGET; CANCER; AGE; RESTRICTION AB Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age-dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age-dependent decline in spontaneous activity, occur more slowly in rapamycin-treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue-specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action. C1 [Wilkinson, John E.; Burmeister, Lisa; Friedline, Sabrina; Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Burmeister, Lisa; Friedline, Sabrina; Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Wilkinson, John E.] Univ Michigan, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. [Brooks, Susan V.; Wood, Lauren K.] Univ Michigan, Dept Mol & Integrat Physiol & Biomed Engn, Ann Arbor, MI 48109 USA. [Chan, Chi-Chao] NEI, Histol Core, NIH, Bethesda, MD 20892 USA. [Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA. [Hejtmancik, James F.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Nadon, Nancy] NIA, Div Aging Biol, Bethesda, MD 20892 USA. [Woodward, Maria A.] Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA. [Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Miller, RA (reprint author), Univ Michigan, Dept Pathol, BSRB Room 3001,Box 2200,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM millerr@umich.edu OI Zaseck, Lauren/0000-0002-8604-0032 FU [AG022303]; [AG007996]; [AG013283] FX This work was supported by grants AG022303, AG007996, and AG013283. We thank Vivian Diaz, Lynn Winkleman, and Mike Astle for expert technical assistance. NR 35 TC 208 Z9 213 U1 2 U2 39 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD AUG PY 2012 VL 11 IS 4 BP 675 EP 682 DI 10.1111/j.1474-9726.2012.00832.x PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 973ZY UT WOS:000306400600014 PM 22587563 ER PT J AU Riegel, B Ratcliffe, SJ Sayers, SL Potashnik, S Buck, HG Jurkovitz, C Fontana, S Weaver, TE Weintraub, WS Goldberg, LR AF Riegel, Barbara Ratcliffe, Sarah J. Sayers, Steven L. Potashnik, Sheryl Buck, Harleah G. Jurkovitz, Claudine Fontana, Sarah Weaver, Terri E. Weintraub, William S. Goldberg, Lee R. TI Determinants of Excessive Daytime Sleepiness and Fatigue in Adults With Heart Failure SO CLINICAL NURSING RESEARCH LA English DT Article DE fatigue; physical activity; exercise; diuretics; functional class; excessive daytime sleepiness; heart failure ID RANDOMIZED CONTROLLED-TRIAL; MODERATE-INTENSITY EXERCISE; QUALITY-OF-LIFE; OLDER-ADULTS; WAKEFULNESS TEST; APNEA SYNDROME; RISK-FACTORS; CONSEQUENCES; DISORDERS; HEALTH AB Little is known about excessive daytime sleepiness (EDS) in heart failure (HF). The aim of this cross-sectional descriptive study was to describe the prevalence of EDS and factors associated with it in HF. A secondary purpose was to explore the correlates of fatigue. We enrolled a consecutive sample of 280 adults with a confirmed diagnosis of chronic HF from three outpatient settings in the northeastern United States. Patients with major depressive illness were excluded. Clinical, sociodemographic, behavioral, and perceptual factors were explored as possible correlates of EDS. Using an Epworth Sleepiness Scale score > 10, the prevalence of EDS was 23.6%. Significant determinants of EDS were worse sleep quality (p = .048), worse functional class (p = .004), not taking a diuretic (p = .005), and lack of physical activity (p = .04). Only sleep quality was associated with fatigue (p < .001). Sleep-disordered breathing was not significantly associated with EDS or with fatigue. These factors may be amenable to intervention. C1 [Riegel, Barbara] Univ Penn, Sch Nursing, Biobehav Res Ctr, Philadelphia, PA 19104 USA. [Sayers, Steven L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Ratcliffe, Sarah J.; Sayers, Steven L.; Goldberg, Lee R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Buck, Harleah G.] Penn State Univ, Sch Nursing, University Pk, PA 16802 USA. [Jurkovitz, Claudine; Weintraub, William S.] Christiana Care Hlth Syst, Christiana Care Ctr Outcomes Res, Newark, DE USA. [Weaver, Terri E.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Fontana, Sarah] Univ Penn, Heart Failure & Transplant Ctr, Philadelphia, PA 19104 USA. [Goldberg, Lee R.] Univ Penn, Med Ctr, Heart Lung Transplant Program, Philadelphia, PA 19104 USA. RP Riegel, B (reprint author), Univ Penn, Sch Nursing, Biobehav Res Ctr, 418 Curie Blvd, Philadelphia, PA 19104 USA. EM briegel@nursing.upenn.edu OI Goldberg, Lee/0000-0002-7906-9638 FU National Heart, Lung & Blood Institute [RO1 HL084394-01A1]; Philadelphia Veterans Affairs Medical Center; VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC) FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by a grant from the National Heart, Lung & Blood Institute (RO1 HL084394-01A1) and by the Philadelphia Veterans Affairs Medical Center, VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC). NR 65 TC 11 Z9 12 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1054-7738 J9 CLIN NURS RES JI Clin. Nurs. Res. PD AUG PY 2012 VL 21 IS 3 BP 271 EP 293 DI 10.1177/1054773811419842 PG 23 WC Nursing SC Nursing GA 973QL UT WOS:000306374800004 PM 21878581 ER PT J AU Forman, SA AF Forman, Stuart A. TI Monod-Wyman-Changeux allosteric mechanisms of action and the pharmacology of etomidate SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Review DE allosteric model; co-agonism; equilibrium; general anesthetic; Gibbs free energy; mutation ID GENERAL ANESTHETIC ETOMIDATE; GABA(A) RECEPTOR; A RECEPTOR; ACID; ACTIVATION; MUTATIONS; MODULATION; BINDING; SITES; MODEL AB Purpose of review Formal Monod-Wyman-Changeux allosteric mechanisms have proven valuable in framing research on the mechanism of etomidate action on its major molecular targets, gamma-aminobutyric acid type A (GABA(A)) receptors. However, the mathematical formalism of these mechanisms makes them difficult to comprehend. Recent findings We illustrate how allosteric models represent shifting equilibria between various functional receptor states (closed versus open) and how co-agonism can be readily understood as simply addition of gating energy associated with occupation of distinct agonist sites. We use these models to illustrate how the functional effects of a point mutation, alpha 1M236W, in GABA(A) receptors can be translated into an allosteric model phenotype. Summary Allosteric co-agonism provides a robust framework for design and interpretation of structure-function experiments aimed at understanding where and how etomidate affects its GABA(A) receptor target molecules. C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 444, Boston, MA 02114 USA. EM saforman@partners.org FU NIH [P01GM58448, R01GM089745] FX This work was supported by the NIH grants (P01GM58448 and R01GM089745). NR 27 TC 9 Z9 9 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0952-7907 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD AUG PY 2012 VL 25 IS 4 BP 411 EP 418 DI 10.1097/ACO.0b013e328354feea PG 8 WC Anesthesiology SC Anesthesiology GA 972JR UT WOS:000306273900003 PM 22614249 ER PT J AU Coppola, G Chinnathambi, S Lee, JJ Dombroski, BA Baker, MC Soto-Ortolaza, AI Lee, SE Klein, E Huang, AY Sears, R Lane, JR Karydas, AM Kenet, RO Biernat, J Wang, LS Cotman, CW DeCarli, CS Levey, AI Ringman, JM Mendez, MF Chui, HC Le Ber, I Brice, A Lupton, MK Preza, E Lovestone, S Powell, J Graff-Radford, N Petersen, RC Boeve, BF Lippa, CF Bigio, EH Mackenzie, I Finger, E Kertesz, A Caselli, RJ Gearing, M Juncos, JL Ghetti, B Spina, S Bordelon, YM Tourtellotte, WW Frosch, MP Vonsattel, JPG Zarow, C Beach, TG Albin, RL Lieberman, AP Lee, VM Trojanowski, JQ Van Deerlin, VM Bird, TD Galasko, DR Masliah, E White, CL Troncoso, JC Hannequin, D Boxer, AL Geschwind, MD Kumar, S Mandelkow, EM Wszolek, ZK Uitti, RJ Dickson, DW Haines, JL Mayeux, R Pericak-Vance, MA Farrer, LA Ross, OA Rademakers, R Schellenberg, GD Miller, BL Mandelkow, E Geschwind, DH AF Coppola, Giovanni Chinnathambi, Subashchandrabose Lee, Jason JiYong Dombroski, Beth A. Baker, Matt C. Soto-Ortolaza, Alexandra I. Lee, Suzee E. Klein, Eric Huang, Alden Y. Sears, Renee Lane, Jessica R. Karydas, Anna M. Kenet, Robert O. Biernat, Jacek Wang, Li-San Cotman, Carl W. DeCarli, Charles S. Levey, Allan I. Ringman, John M. Mendez, Mario F. Chui, Helena C. Le Ber, Isabelle Brice, Alexis Lupton, Michelle K. Preza, Elisavet Lovestone, Simon Powell, John Graff-Radford, Neill Petersen, Ronald C. Boeve, Bradley F. Lippa, Carol F. Bigio, Eileen H. Mackenzie, Ian Finger, Elizabeth Kertesz, Andrew Caselli, Richard J. Gearing, Marla Juncos, Jorge L. Ghetti, Bernardino Spina, Salvatore Bordelon, Yvette M. Tourtellotte, Wallace W. Frosch, Matthew P. Vonsattel, Jean Paul G. Zarow, Chris Beach, Thomas G. Albin, Roger L. Lieberman, Andrew P. Lee, Virginia M. Trojanowski, John Q. Van Deerlin, Vivianna M. Bird, Thomas D. Galasko, Douglas R. Masliah, Eliezer White, Charles L. Troncoso, Juan C. Hannequin, Didier Boxer, Adam L. Geschwind, Michael D. Kumar, Satish Mandelkow, Eva-Maria Wszolek, Zbigniew K. Uitti, Ryan J. Dickson, Dennis W. Haines, Jonathan L. Mayeux, Richard Pericak-Vance, Margaret A. Farrer, Lindsay A. Ross, Owen A. Rademakers, Rosa Schellenberg, Gerard D. Miller, Bruce L. Mandelkow, Eckhard Geschwind, Daniel H. CA Alzheimer's Dis Genetics Consortiu TI Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimers diseases SO HUMAN MOLECULAR GENETICS LA English DT Article ID FRONTOTEMPORAL DEMENTIA; COMMON VARIANTS; TAU-PROTEIN; AGGREGATION; ASSOCIATION; HAPLOTYPE; MUTATION; PHOSPHORYLATION; PARKINSONISM; INCLUSIONS AB Tau p.A152T significantly increases the risk for both FTD-s (n 2139, OR 3.0, CI: 1.65.6, P 0.0005) and Alzheimers disease (AD) (n 3345, OR 2.3, CI: 1.34.2, P 0.004) compared with 9047 controls. Functionally, p.A152T (i) decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently; and (ii) reduces the tendency to form abnormal fibers. However, there is a pronounced increase in the formation of tau oligomers. Importantly, these findings suggest that other regions of the tau protein may be crucial in regulating normal function, as the p.A152 residue is distal to the domains considered responsible for microtubule interactions or aggregation. These data provide both the first genetic evidence and functional studies supporting the role of MAPT p.A152T as a rare risk factor for both FTD-s and AD and the concept that rare variants can increase the risk for relatively common, complex neurodegenerative diseases, but since no clear significance threshold for rare genetic variation has been established, some caution is warranted until the findings are further replicated. C1 [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA. [Coppola, Giovanni; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Psychiat, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Lee, Suzee E.; Karydas, Anna M.; Boxer, Adam L.; Geschwind, Michael D.; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Cotman, Carl W.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [DeCarli, Charles S.] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Chinnathambi, Subashchandrabose; Biernat, Jacek; Kumar, Satish; Mandelkow, Eva-Maria; Mandelkow, Eckhard] German Ctr Neurodegenerat Dis, DZNE, D-53175 Bonn, Germany. [Chinnathambi, Subashchandrabose; Biernat, Jacek; Kumar, Satish; Mandelkow, Eva-Maria; Mandelkow, Eckhard] CAESAR Res Ctr, D-53175 Bonn, Germany. [Dombroski, Beth A.; Wang, Li-San; Lee, Virginia M.; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Schellenberg, Gerard D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Baker, Matt C.; Soto-Ortolaza, Alexandra I.; Graff-Radford, Neill; Wszolek, Zbigniew K.; Uitti, Ryan J.; Dickson, Dennis W.; Ross, Owen A.; Rademakers, Rosa] Mayo Clin Florida, Dept Neurosci, Jacksonville, FL USA. [Baker, Matt C.; Soto-Ortolaza, Alexandra I.; Graff-Radford, Neill; Wszolek, Zbigniew K.; Uitti, Ryan J.; Dickson, Dennis W.; Ross, Owen A.; Rademakers, Rosa] Mayo Clin Florida, Dept Neurol, Jacksonville, FL USA. [Baker, Matt C.; Soto-Ortolaza, Alexandra I.; Graff-Radford, Neill; Wszolek, Zbigniew K.; Uitti, Ryan J.; Dickson, Dennis W.; Ross, Owen A.; Rademakers, Rosa] Mayo Clin Florida, Dept Pathol, Jacksonville, FL USA. [Kenet, Robert O.] Weill Cornell Med Coll, New York Presbyterian Hosp, Dept Med, New York, NY USA. [Levey, Allan I.; Gearing, Marla; Juncos, Jorge L.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Levey, Allan I.; Gearing, Marla; Juncos, Jorge L.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [Levey, Allan I.; Gearing, Marla; Juncos, Jorge L.] Emory Univ, Sch Med, Dept Lab Med, Atlanta, GA 30322 USA. [Chui, Helena C.] Univ So Calif, Dept Neurol, Downey, CA USA. [Zarow, Chris] Univ So Calif, Rancho Amigos Natl Rehabil Ctr, Downey, CA USA. [Brice, Alexis] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, F-75013 Paris, France. [Lupton, Michelle K.; Preza, Elisavet; Lovestone, Simon; Powell, John] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Petersen, Ronald C.; Boeve, Bradley F.] Mayo Clin Rochester, Dept Neurol, Rochester, MN USA. [Lippa, Carol F.] Drexel Univ, Dept Neurol, Coll Med, Philadelphia, PA 19104 USA. [Bigio, Eileen H.] Northwestern Univ, Cognit Neurol & Alzheimer Dis Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Mackenzie, Ian] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. [Finger, Elizabeth; Kertesz, Andrew] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. [Caselli, Richard J.] Mayo Clin Scottsdale, Dept Neurol, Scottsdale, AZ USA. [Ghetti, Bernardino; Spina, Salvatore] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. [Tourtellotte, Wallace W.] Vet Affairs W Los Angeles Healthcare Ctr, Human Brain & Spinal Fluid Resource Ctr, Los Angeles, CA USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Boston, MA USA. [Vonsattel, Jean Paul G.; Mayeux, Richard] Columbia Univ, Dept Neurol, New York, NY USA. [Vonsattel, Jean Paul G.; Mayeux, Richard] Columbia Univ, Dept Pathol, New York, NY USA. [Vonsattel, Jean Paul G.; Mayeux, Richard] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Beach, Thomas G.] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA. [Albin, Roger L.; Lieberman, Andrew P.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Albin, Roger L.; Lieberman, Andrew P.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Albin, Roger L.; Lieberman, Andrew P.] VA Ann Arbor Hlth Syst, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. [Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas D.] Univ Washington, Dept Med Genet, Seattle, WA 98195 USA. [Galasko, Douglas R.; Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Galasko, Douglas R.; Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [White, Charles L.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Troncoso, Juan C.] Johns Hopkins Univ Sch Med, Dept Neurol, Baltimore, MD USA. [Hannequin, Didier] CHU Charles Nicolle, CNR MAJ, INSERM, U614, Rouen, France. [Hannequin, Didier] CHU Charles Nicolle, Dept Neurol, Rouen, France. [Haines, Jonathan L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Ctr Human Genet Res, Nashville, TN 37232 USA. [Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Pericak-Vance, Margaret A.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA. [Farrer, Lindsay A.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Med, Genet Program, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Ophthalmol, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Le Ber, Isabelle; Brice, Alexis] CNRS, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMRS975,INSERM,U975,UMR 7225, Paris, France. [Le Ber, Isabelle] Hop La Pitie Salpetriere, AP HP, Ctr Reference Demences Rares, F-75013 Paris, France. RP Geschwind, DH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA. EM dhg@ucla.edu RI Powell, John/G-4412-2011; Preza, Elisavet/C-1829-2013; Haines, Jonathan/C-3374-2012; Ross, Owen/D-7573-2013; Finger, Elizabeth/B-6453-2015; Sonnen, 37382016/H-3738-2016; OI Powell, John/0000-0001-6124-439X; Dickson, Dennis W/0000-0001-7189-7917; Sonnen, 37382016/0000-0001-9267-8705; Sears, Renee/0000-0003-0523-9291; Roberson, Erik/0000-0002-1810-9763; Farrer, Lindsay/0000-0001-5533-4225; Carroll, Steven/0000-0001-6714-4373; Demirci, F. Yesim/0000-0001-6907-9843; Kaye, Jeffrey/0000-0002-9971-3478; Kukull, Walter/0000-0001-8761-9014; Buros, Jacqueline/0000-0001-9588-4889; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460; Stern, Robert/0000-0002-5008-077X; Crane, Paul/0000-0003-4278-7465; Cruchaga, Carlos/0000-0002-0276-2899; Buxbaum, Joseph/0000-0001-8898-8313 FU National Institutes of Health [R01 AG026938, RC1AG035610, P50 AG-16570, AG13854, R37 AG11762, P50-AG05142, P50 AG025688, R01 AG038791, R01 NS078086, R01 NS065782, P50 AG023501, P50NS072187]; Tau Consortium; Irene and Abe Pollin Fund for CBD Research; CurePSP Foundation; Peebler PSP Research Foundation; NIHR Biomedical Research Centre for Mental Health at SLAM and KCL; Medical Research Council; Alzheimer's Research UK; European Union [HEALTH-F4-2009-242257]; Agence Nationale de la Recherche [R R08104DS]; National Institute on Aging (NIA) [U24 AG21886, P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]; Michael J. Fox Foundation for Parkinson's Research FX This work was supported by grants from the National Institutes of Health (grant numbers R01 AG026938 to D. H. G., RC1AG035610 to G. C., P50 AG-16570 to J.R., AG13854 to E. B., R37 AG11762 to G. D. S., P50-AG05142 to H. C. C., P50 AG025688 to A. I. L., R01 AG038791 to A. L. B., R01 NS078086 to O.A.R., R01 NS065782 to R. R., P50 AG023501 to B. L. M., Mayo Udall Center P50NS072187 to O.A.R., Z.K.W., R.J.U., D. W. D.); the Tau Consortium (G. C., R.O.K., S. E. L., E-M. M., B. L. M., E. M., D. H. G.); a gift from Carl Edward Bolch, Jr, and Susan Bass Bolch (O.A.R., Z. K. W., R.J.U., D. W. D.); the Irene and Abe Pollin Fund for CBD Research (A. L. B. and R. R.); the CurePSP Foundation (G. D. S.); the Peebler PSP Research Foundation (G. D. S.); the NIHR Biomedical Research Centre for Mental Health at SLAM and KCL (http://www.slam.nhs.uk/about-us/biomedical-research-centre/brc-home.asp x); the Medical Research Council (http://www.mrc.ac.uk/index.htm) through PhD studentship funding; the Alzheimer's Research UK (http://www.alzheimersresearchuk.org), the 7th framework program of the European Union (ADAMS project, http://www.adams-consortium.eu/, HEALTH-F4-2009-242257, to S. L. and J.P]; and the Agence Nationale de la Recherche (FTDGenes, R R08104DS, to I. L. B. and A. B.). In the NCRAD series, samples from the National Cell Repository for Alzheimer's Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. The National Cell Repository for Alzheimer's Disease (NCRAD) receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA). Costs for tissue samples submitted by T. G. B. were supported by the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinson's Research. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 46 TC 59 Z9 60 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2012 VL 21 IS 15 BP 3500 EP 3512 DI 10.1093/hmg/dds161 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 974FE UT WOS:000306414900017 PM 22556362 ER PT J AU Ibrahimi, OA On, SCJ Fung, MA Eisen, DB AF Ibrahimi, Omar A. On, Shelbi C. Jim Fung, Maxwell A. Eisen, Daniel B. TI A longstanding deep-seated nuchal tumor SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID DESMOID TUMORS C1 [Ibrahimi, Omar A.] Univ Connecticut, Dept Dermatol, Farmington, CT 06032 USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [On, Shelbi C. Jim] Univ Hawaii, Sch Med, Honolulu, HI 96822 USA. [Fung, Maxwell A.; Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. [Fung, Maxwell A.] Univ Calif Davis, Dept Pathol, Sacramento, CA 95817 USA. RP Ibrahimi, OA (reprint author), Univ Connecticut, Dept Dermatol, 21 South Rd, Farmington, CT 06032 USA. EM omar.ibrahimi@gmail.com OI Eisen, Daniel/0000-0001-6741-3182 NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD AUG PY 2012 VL 51 IS 8 BP 910 EP 912 DI 10.1111/j.1365-4632.2011.05364.x PG 3 WC Dermatology SC Dermatology GA 973RP UT WOS:000306377800003 PM 22788805 ER PT J AU Alexander, KA Coleman, CL Deatrick, JA Jemmott, LS AF Alexander, Kamila A. Coleman, Christopher L. Deatrick, Janet A. Jemmott, Loretta S. TI Moving beyond safe sex to women-controlled safe sex: a concept analysis SO JOURNAL OF ADVANCED NURSING LA English DT Article DE concept analysis; gender equity; HIV; AIDS; sexuality; sexually transmitted infections; unintended pregnancy; women-controlled safe sex ID FEMALE-CONDOM USE; RANDOMIZED CONTROLLED-TRIAL; RISK-REDUCTION HIERARCHY; FAMILY-PLANNING CLINICS; HIV PREVENTION METHODS; URBAN US WOMEN; VAGINAL MICROBICIDE; BARRIER METHODS; DIAPHRAGM USERS; UNITED-STATES AB alexander k.a., coleman c.l., deatrick j.a. & jemmott l.s. (2011) Moving beyond safe sex to women-controlled safe sex: a concept analysis. Journal of Advanced Nursing68(6), 18581869. Abstract Aim. This paper is a report of a conceptual analysis of women-controlled safe sex. Background. Women bear disproportionate burdens from sexually related health compromising outcomes. Imbalanced societal gender and power positions contribute to high morbidities. The expression, women-controlled safe sex, aims to empower women to gain control of their sexual lives. Few researchers focus on contextualized socio-cultural definitions of sexual safety among women. Data sources. The sample included scientific literature from Scopus, CINAHL, PubMed, PsychINFO and Sociological Abstracts. Papers were published 20002010. Review methods. Critical analyses of literature about women-controlled safe sex were performed in May 2011 using Rodgers evolutionary concept analysis methods. The search focused on social and cultural influences on sexual practices aimed at increasing womens control over their sexual safety. Results. The analysis uncovered five attributes of women-controlled safe sex: technology; access to choices; women at-risk; condom migration panic; and communication. Three antecedents included: male partner influence; body awareness; and self-efficacy. Consequences were categorized as positive or negative. Nine surrogate terms included: empowerment; gender power; female-controlled sexual barrier method; microbicides; diaphragm; sexual negotiation and communication; female condom; women-initiated disease transmission prevention; and spermicides. Finally, a consensus definition was identified: a socio-culturally influenced multi-level process for initiating sexual safety by women deemed at-risk for sexually related dangers, usually sexually transmitted infections and/or HIV/AIDS. Conclusion. This concept analysis described current significance, uses, and applications of women-controlled safe sex in the scientific literature. The authors clarified its limited nature and conclude that additional conceptual refinement in nursing is necessary to influence womens health. C1 [Alexander, Kamila A.; Deatrick, Janet A.; Jemmott, Loretta S.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. RP Alexander, KA (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. EM kamilaa@nursing.upenn.edu FU NINR/NIH [T32NR007100, F31NR013121] FX This work was supported by NINR/NIH Ruth L. Kirschstein NRSA Predoctoral Fellowship and Research Training to Promote Health in Vulnerable Populations (T32NR007100) and Award Number F31NR013121 (PI: Alexander). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. NR 77 TC 3 Z9 3 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD AUG PY 2012 VL 68 IS 8 BP 1858 EP 1869 DI 10.1111/j.1365-2648.2011.05881.x PG 12 WC Nursing SC Nursing GA 972IX UT WOS:000306271900018 PM 22111843 ER PT J AU Lin, SI Lo, CC Lin, PY Chen, JJJ AF Lin, Sang-I Lo, Chao-Chen Lin, Pei-Yi Chen, Jia-Jin J. TI Biomechanical assessments of the effect of visual feedback on cycling for patients with stroke SO JOURNAL OF ELECTROMYOGRAPHY AND KINESIOLOGY LA English DT Article DE Cycling; Electromyography; Visual feedback; Stroke ID LOWER-LIMB; POSTSTROKE HEMIPARESIS; KINEMATIC ANALYSIS; PEDALING EXERCISE; FORCE OUTPUT; REHABILITATION; MOVEMENT; GAIT; COORDINATION; ACTIVATION AB Stroke patients exhibit abnormal pattern in leg cycling exercise. The aim of this study was to investigate the effects of visual feedback on the control of cycling motion in stroke patients from kinesiological, kinematic and kinetic aspects. The cycling performance derived from cycling electromyography (EMG), cycling cadence, and torque of forty stroke subjects was evaluated under conditions with and without visual feedback of cycling cadence. Kinesiological indices, shape symmetry index (SSI) and area symmetry index (ASI) were extracted from EMG linear envelopes to evaluate the symmetry of muscle firing patterns during cycling. Roughness index (RI) was calculated from cycling cadence to represent cycling smoothness from kinematic aspects. Averaged cycling power (Pav), the product of cadence and torque, was used to represent force output. The rectus femoris EMG showed significantly greater ASI with visual feedback, however, the difference in SSI between the two conditions was not significant. For the biceps femoris, there was a significant decrease in SSI with visual feedback, while the ASI was not affected significantly by the task conditions. The cycling smoothness was better and the average power generated was larger when visual feedback was provided. This study found that the addition of visual feedback improved both neuromuscular control and overall performance. Such improvement is likely to be the result of better control of the rectus femoris muscle activation and coordination of both legs. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Lo, Chao-Chen; Lin, Pei-Yi; Chen, Jia-Jin J.] Natl Cheng Kung Univ, Dept Biomed Engn, Tainan 70101, Taiwan. [Lin, Sang-I] Natl Cheng Kung Univ, Dept Phys Therapy, Tainan 70101, Taiwan. [Lin, Pei-Yi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Chen, Jia-Jin J.] Natl Cheng Kung Univ, Med Device Innovat Ctr, Tainan 70101, Taiwan. RP Chen, JJJ (reprint author), Natl Cheng Kung Univ, Dept Biomed Engn, 1 Ta Hsueh Rd, Tainan 70101, Taiwan. EM jason@jason.bme.ncku.edu.tw FU National Health Research Institutes (NHRI) of R.O.C. [NHRI-EX99-9734EI, NSC 100-2321-B-006-018]; National Science Council (NSC) of R.O.C. [NHRI-EX99-9734EI, NSC 100-2321-B-006-018]; Medical Device Innovation Center (MDIC) FX The authors would like to appreciate the National Health Research Institutes (NHRI) and National Science Council (NSC) of R.O.C. for financially supporting this research under Contract Nos. NHRI-EX99-9734EI and NSC 100-2321-B-006-018, as well as Medical Device Innovation Center (MDIC). NR 35 TC 7 Z9 7 U1 2 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1050-6411 EI 1873-5711 J9 J ELECTROMYOGR KINES JI J. Electromyogr. Kinesiol. PD AUG PY 2012 VL 22 IS 4 BP 582 EP 588 DI 10.1016/j.jelekin.2012.03.009 PG 7 WC Neurosciences; Physiology; Rehabilitation; Sport Sciences SC Neurosciences & Neurology; Physiology; Rehabilitation; Sport Sciences GA 973RQ UT WOS:000306377900012 PM 22538084 ER PT J AU Li, WH Ahn, AC AF Li, Weihui Ahn, Andrew C. TI Pulsatile hemodynamics of hypertension: systematic review of aortic input impedance SO JOURNAL OF HYPERTENSION LA English DT Review DE characteristic impedance; hypertension; input impedance; wave reflection ID ISOLATED SYSTOLIC HYPERTENSION; PULSE-WAVE VELOCITY; ARTERIAL HEMODYNAMICS; PRESSURE; DETERMINANTS; NIFEDIPINE; STIFFNESS; LOAD; AGE AB Objective: Input impedance is the frequency-dependent afterload to pulsatile blood flow. Studies of input impedance have been performed as early as the 1960s and have been applied to hypertension (HTN). However, to date, these studies have not been systematically evaluated. This systematic review aims to summarize the literature, interpret existing data from the perspective of impedance theory, and to discuss their potential for generating physiological insights into HTN. Methods: We identified 11 studies wherein computed impedance moduli from both HTN and control (CNT) groups were reported. In addition, we performed bivariate analyses of raw data from three of these studies. Results: Major findings include HTN groups had consistently elevated impedance moduli at 0 Hz (Z(0)) and at heart rate frequency (Z(1)), an increased frequency wherein impedance phase first crosses 0 (f(0)), but no consistent pattern in characteristic impedance (Z(c)), when compared to CNT groups; SBP and DBP are highly correlated with Z(0) and Z(1), moderately correlated with f(0), less correlated with Z(c); the measurement and calculation methods for Z(c) are varied and inconsistent; and a not insignificant proportion of hypertensive individuals have 'normal' Z(0), Z(1) and Z(c) values. These findings are limited by the heterogeneous study populations and small sample sizes. Conclusion: These findings suggest that Z(0), Z(1) and f(0) are significantly associated with HTN, whereas the role of Z(c) is less clear. Additional studies are needed to evaluate these input impedance variables in order to generate substantial implications in clinic settings. C1 [Li, Weihui; Ahn, Andrew C.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ahn, Andrew C.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Li, WH (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St,Room 2328, Charlestown, MA 02129 USA. EM weihuil@gmail.com FU National Center for Complementary Alternative Medicine (NCCAM) [P30AT005895]; Clinical Translational Science Award from the National Center for Research Resources [UL1RR025758] FX This research was supported by grant number P30AT005895 of the National Center for Complementary Alternative Medicine (NCCAM). The project described was supported by Clinical Translational Science Award UL1RR025758 to Harvard University and Massachusetts General Hospital 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 Complementary Alternative Medicine or the National Center for Research Resources or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD AUG PY 2012 VL 30 IS 8 BP 1493 EP 1499 DI 10.1097/HJH.0b013e328354e81d PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 973PE UT WOS:000306371400001 PM 22635138 ER PT J AU He, SN Lamers, GEM Beenakker, JWM Cui, C Ghotra, VPS Danen, EHJ Meijer, AH Spaink, HP Snaar-Jagalska, BE AF He, Shuning Lamers, Gerda E. M. Beenakker, Jan-Willem M. Cui, Chao Ghotra, Veerander P. S. Danen, Erik H. J. Meijer, Annemarie H. Spaink, Herman P. Snaar-Jagalska, B. Ewa TI Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model SO JOURNAL OF PATHOLOGY LA English DT Article DE zebrafish; neutrophils; macrophages; tumour vascularization; micrometastasis; VEGFR inhibition ID ENDOTHELIAL GROWTH-FACTOR; BLOOD STEM-CELLS; TRANSGENIC ZEBRAFISH; IN-VIVO; MESENCHYMAL TRANSITION; DISEASE PROGRESSION; AORTIC ENDOTHELIUM; FACTOR RECEPTOR; MYELOID CELLS; TUMOR-GROWTH AB Inhibition of VEGF signalling effectively suppresses localized tumour growth but accelerates tumour invasiveness and micrometastasis by unknown mechanisms. To study the dynamic and reciprocal interactions between tumour cells and their microenvironment during these processes, we established a xenograft model by injecting tumour cells into the blood circulation of transparent zebrafish embryos. This reproducibly results in rapid simultaneous formation of a localized tumour and experimental micrometastasis, allowing time-resolved imaging of both processes at single-cell resolution within 1 week. The tumour vasculature was initiated de novo by remodelling of primitive endothelial cells into a functional network. Roles of myeloid cells in critical tumourigenesis steps such as vascularization and invasion were revealed by genetic and pharmaceutical approaches. We discovered that the physiological migration of neutrophils controlled tumour invasion by conditioning the collagen matrix and forming the metastatic niche, as detected by two-photon confocal microscopy and second harmonic generation. Administration of VEGFR inhibitors blocked tumour vascularization and a localized tumour growth but enhanced migration of neutrophils, which in turn promoted tumour invasion and formation of micrometastasis. This demonstrates the in vivo cooperation between VEGF signalling and myeloid cells in metastasis and provides a new mechanism underlying the recent findings that VEGFR targeting can promote tumour invasiveness. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [He, Shuning; Lamers, Gerda E. M.; Cui, Chao; Meijer, Annemarie H.; Spaink, Herman P.; Snaar-Jagalska, B. Ewa] Leiden Univ, Inst Biol, NL-2333 CC Leiden, Netherlands. [Beenakker, Jan-Willem M.] Leiden Univ, Leiden Inst Phys, NL-2300 RA Leiden, Netherlands. [Ghotra, Veerander P. S.; Danen, Erik H. J.] Leiden Univ, Div Toxicol, Leiden Amsterdam Ctr Drug Res, NL-2300 RA Leiden, Netherlands. [He, Shuning] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [He, Shuning] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. RP Snaar-Jagalska, BE (reprint author), Leiden Univ, Inst Biol, Einsteinweg 55, NL-2333 CC Leiden, Netherlands. EM b.e.snaar-jagalska@biology.leidenuniv.nl OI danen, erik/0000-0002-0491-6345 FU European Community [HEALTH-F2-2008-201439] FX We thank M Presta and P ten Dijke for providing cell lines; RC Hoeben for lentiviral viruses; B Weinstein and S Renshaw for providing zebrafish lines; A Huttenlocher for providing antibody; W van der Ent, MJ Rabelink and S Rueb for assistance in cell culture and generation of stable fluorescent cell lines; A van der Laan for support in two-photon second-harmonic generation microscopy; D de Witt and U Nehrdich for zebrafish maintenance; M Mione, P ten Dijke and T Oosterkamp for stimulating discussions; and EE Patton for critical reading of the manuscript. This project was financially supported by the European Community under the FP7 ZF-Cancer Project (Grant No. HEALTH-F2-2008-201439). NR 57 TC 52 Z9 52 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD AUG PY 2012 VL 227 IS 4 BP 431 EP 445 DI 10.1002/path.4013 PG 15 WC Oncology; Pathology SC Oncology; Pathology GA 971UJ UT WOS:000306229100008 PM 22374800 ER PT J AU Sylvia, LG Dupuy, JM Ostacher, MJ Cowperthwait, CM Hay, AC Sachs, GS Nierenberg, AA Perlis, RH AF Sylvia, Louisa G. Dupuy, Jamie M. Ostacher, Michael J. Cowperthwait, Colleen M. Hay, Aleena C. Sachs, Gary S. Nierenberg, Andrew A. Perlis, Roy H. TI Sleep disturbance in euthymic bipolar patients SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE Bipolar disorder; relapse prevention; sleep disturbance; treatment ID TREATMENT ENHANCEMENT PROGRAM; DISORDER STEP-BD; CIRCADIAN-RHYTHMS; DEPRESSED-PATIENTS; DEPRIVATION; MANIA; MOOD; RELIABILITY; IMPROVEMENT; INSOMNIA AB Sleep disturbance is a common feature during mood episodes in bipolar disorder. The aim of this study was to investigate the prevalence of such symptoms among euthymic bipolar patients, and their association with risk for mood episode recurrence. A cohort of bipolar I and II subjects participating in the Systematic Treatment Enhancement Program for Bipolar Disorder who were euthymic for at least 8 weeks were included in this analysis. Survival analysis was used to examine the association between sleep disturbance on the Montgomery-Asberg Depression Rating Scale (MADRS) and recurrence risk. A total of 73/483 bipolar I and II subjects reported at least mild sleep disturbance (MADRS sleep item >= 2) for the week prior to study entry. The presence of sleep problems was associated with a history of psychosis, number of previous suicide attempts, and anticonvulsant use. Sleep disturbance at study entry was significantly associated with risk for mood episode recurrence. Sleep disturbance is not uncommon between episodes for individuals with bipolar disorder and may be associated with a more severe course of illness. This suggests that sleep disturbance is an important prodromal symptom of bipolar disorder and should be considered a target for pharmacologic or psychosocial maintenance treatment. C1 [Sylvia, Louisa G.; Dupuy, Jamie M.; Hay, Aleena C.; Sachs, Gary S.; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. [Sylvia, Louisa G.; Dupuy, Jamie M.; Sachs, Gary S.; Nierenberg, Andrew A.; Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA USA. [Ostacher, Michael J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Ostacher, Michael J.] VA Palo Alto Heath Care Syst, Palo Alto, CA USA. [Cowperthwait, Colleen M.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Dept Psychiat, Boston, MA 02114 USA. RP Sylvia, LG (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, Dept Psychiat, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org OI Cowperthwait, Colleen/0000-0001-6190-7579; Ostacher, Michael/0000-0003-0353-7535 FU National Institute of Mental Health [N01MH80001]; Concordant Rater Systems; United BioSource Corporation; Bracket; Repligen; AHRQ; NIMH; PamLabs; Pfizer Pharmaceuticals; Shire; Wyss Institute for Biologically Inspired Engineering; AstraZeneca; Genomind; Proteus Biomedical; RIDVentures FX This study was funded by the National Institute of Mental Health (contract number N01MH80001).; In the past 12 months Dr Sylvia has received consulting fees from Concordant Rater Systems, United BioSource Corporation, and Bracket.; Dr Sachs is a full time Employee of Bracket. Dr Sachs has served on advisory/consulting boards of Abbott Laboratories, AstraZeneca Pharmaceuticals, Bristol Myers Squibb, Cephalon, CNS Response, Dianippon Sumitomo Pharmaceuticals, Elan Pharmaceuticals, Memory Pharmaceuticals, Merck, Novartis Pharmaceuticals, Organon, Otsuka, Pfizer, Schering Plough, Sepracor, Repligen, Sanofi-Aventis, Shire, Sigma-Tau, Solvay Pharmaceuticals, Takeda, and Wyeth. Dr Sachs and his spouse own stock in Medco. In the past 12 months, Dr Sachs has received research support from Repligen. In the past 12 months, Dr Sachs has served on the advisory/consulting boards of Concordant Rater Systems, Dianippon Sumitomo Pharmaceuticals, Merck, Otsuka, Pfizer, Takeda, and Repligen.; Dr Nierenberg has served as a consultant to: Appliance Computing Inc. (Mindsite), Medergy. Through the MGH Clinical Trials Network and Institute (CTNI), he has consulted for: Brain Cells, Inc, Johnson and Johnson, Labopharm, Merck, PGx Health, Ridge Diagnostics, Targacept, Takeda/Lundbeck Pharmaceuticals. He received grant/research support through MGH from: AHRQ, NIMH, PamLabs, Pfizer Pharmaceuticals, Shire, Wyss Institute for Biologically Inspired Engineering. He received honoraria from: American Soc Clinical Psychopharmacology, American Society for Clinical Psychopharmacology, APSARD, Belvior Publishing, Canadian Psychiatric Association, CNS Spectrums, Dartmouth Medical School, Johns Hopkins Medical School, MBL Publishing, Montreal McGill Douglas Hospital, Northeast Counseling Center Directors, PamLab, Physicians Postgraduate Press, SciMed, Slack Med, University of Florida, WebMD, Wolters Klower Publishing Dr Nierenberg is a presenter for: Massachusetts General Hospital Psychiatry Academy (MGHPA). The education programs conducted by the MGHPA and presented by Dr Nierenberg were supported through Independent Medical Education (IME) grants from the following pharmaceutical companies: AstraZeneca. He is on the advisory boards of: Appliance Computing, Inc., Brain Cells, Inc., InfoMedic, Johnson and Johnson, Takeda/Lundbeck Pharmaceuticals, Targacept. Dr Nierenberg owns stock options in: Appliance Computing, Inc. and Brain Cells, Inc. Through MGH, he is named for copyrights to: The Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery Asberg Depression Scale exclusively licensed to the CTNI.; In the past 12 months Dr Perlis has received consulting fees from Concordant Rater Systems, Genomind, Proteus Biomedical, and RIDVentures, grant support from Proteus Biomedical, and royalties from Concordant Rater Systems. NR 37 TC 31 Z9 32 U1 0 U2 11 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD AUG PY 2012 VL 26 IS 8 BP 1108 EP 1112 DI 10.1177/0269881111421973 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 975JX UT WOS:000306508700007 PM 21965189 ER PT J AU Hirschmann, JV Raugi, GJ AF Hirschmann, Jan V. Raugi, Gregory J. TI Lower limb cellulitis and its mimics Part II. Conditions that simulate lower limb cellulitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE carcinoma erysipeloides; dependent rubor; eczema; erythromelalgia; gout; hereditary periodic fevers; lymphedema; necrotizing soft tissue infections; venous disease ID SERUM URIC-ACID; NECROTIZING FASCIITIS; PERIODIC SYNDROME; ERYTHROMELALGIA; CARCINOMA; LIPODERMATOSCLEROSIS; ERYTHERMALGIA; MANAGEMENT; MORTALITY; RISK AB Several common conditions can mimic cellulitis, creating a potential for misdiagnosis and incorrect management. The most common disorders mistaken for lower limb cellulitis include venous eczema, lipodermatosclerosis, irritant dermatitis, and lymphedema. The dermatologist is often consulted when a patient has failed to respond to therapy, and a thorough knowledge of the differential diagnosis is essential. This article focuses on entities that can mimic cellulitis, with an emphasis of elements of the history and physical examination that can help to distinguish between lower limb cellulitis and its simulators. (J Am Acad Dermatol 2012; 67: 177. e1-9.) C1 [Raugi, Gregory J.] VA Puget Sound Hlth Care Syst, Dermatol 111D, Dept Dermatol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. RP Raugi, GJ (reprint author), VA Puget Sound Hlth Care Syst, Dermatol 111D, Dept Dermatol, 1660 Columbian Way S, Seattle, WA 98108 USA. EM gregory.raugi@va.gov NR 35 TC 2 Z9 2 U1 0 U2 2 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 AUG PY 2012 VL 67 IS 2 AR 177.e1 DI 10.1016/j.jaad.2012.03.023 PG 9 WC Dermatology SC Dermatology GA 973OD UT WOS:000306368600011 PM 22794816 ER PT J AU Waibel, J Wulkan, AJ Lupo, M Beer, K Anderson, RR AF Waibel, Jill Wulkan, Adam J. Lupo, Mary Beer, Kenneth Anderson, R. Rox TI Treatment of burn scars with the 1,550 nm nonablative fractional Erbium Laser SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE burn scars; nonablative fractional laser; keloid scars; hypertrophic scars; atrophic scars ID HYPERTROPHIC SCARS; KELOIDS; MANAGEMENT; TRIAL AB Background Scarring is a major source of morbidity in patients with burns. Burn scars are difficult to treat and are among the worst scars seen in clinical medicine. Fractional laser resurfacing is a promising treatment option because of its unique wound healing response and depth of penetration. Objective To evaluate the efficacy of nonablative fractional resurfacing as a therapeutic option for extensive cutaneous scarring in burn patients. Methods Prospective, single-arm, pilot study. Ten subjects with second and third degree burn scars were treated with five nonablative fractional resurfacing treatments given at 4-week intervals. Three independent investigators evaluated subject outcomes at 3 months post-treatment (primary outcome); patients also provided subjective assessments of improvement (secondary outcome). Results Nonablative fractional resurfacing resulted in overall improvement in 90% of subjects, as determined by independent investigators; improvements were moderate to excellent in 60%. Ninety percent of subjects had improved skin texture, 80% had improved dyschromia, and 80% had improved hypertrophy/atrophy. Patients' self-reports also revealed moderate to excellent improvements (on average) in burn scar area, and significant improvements in self-esteem at 3 months post-treatment (P?=?0.03). Limitations Small sample size and lack of control group. Conclusions Fractional resurfacing is a promising new treatment modality for burn scars. We should continue to identify novel approaches and management strategies for the spectrum of diverse burn scars so that we can better treat this patient population. Lasers Surg. Med. 44: 441446, 2012. (C) Wiley Periodicals, Inc. C1 [Waibel, Jill] Miami Dermatol & Laser Inst, Miami, FL 33173 USA. [Wulkan, Adam J.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Lupo, Mary] Lupo Ctr Aesthet & Gen Dermatol, New Orleans, LA 70124 USA. [Beer, Kenneth] Palm Beach Esthet Dermatol & Laser Ctr, W Palm Beach, FL 33401 USA. [Beer, Kenneth] Duke Univ, Dept Med, Durham, NC USA. [Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Deparment Dermatol, Boston, MA 02114 USA. [Anderson, R. Rox] Wellman Labs Photomed, Director Wellman Ctr, Dept Dermatol, Boston, MA 02114 USA. RP Waibel, J (reprint author), Miami Dermatol & Laser Inst, 7800 SW 87th Ave, Miami, FL 33173 USA. EM Jwaibelmd@MiamiDermLaser.com FU Reliant Technologies, Inc.; Reliant Technologies FX Contract grant sponsor: Reliant Technologies, Inc..; All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and have disclosed the following: Dr. Waibel and Dr. Beer received research grant from Reliant Technologies for this work. In addition Dr. Lupo, Dr. Beer, and Dr. Waibel have been speakers, and Dr. Anderson on Advisory Board for Solta Medical. No authors hold stock, or receive royalties from Solta Medical. NR 21 TC 27 Z9 27 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD AUG PY 2012 VL 44 IS 6 BP 441 EP 446 DI 10.1002/lsm.22038 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 972YL UT WOS:000306317500001 PM 22674649 ER PT J AU Huang, LY Xuan, Y Koide, Y Zhiyentayev, T Tanaka, M Hamblin, MR AF Huang, Liyi Xuan, Yi Koide, Yuichiro Zhiyentayev, Timur Tanaka, Masamitsu Hamblin, Michael R. TI Type I and Type II mechanisms of antimicrobial photodynamic therapy: An in vitro study on gram-negative and gram-positive bacteria SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE antimicrobial photodynamic inactivation; singlet oxygen; hydroxyl radical; sodium azide; gram-positive and gram-negative bacteria; antimicrobial photodynamic therapy; polyethylenimine chlorin(e6) conjugate; tris-cationic fullerene ID MESOSUBSTITUTED CATIONIC PORPHYRINS; SINGLET MOLECULAR-OXYGEN; STAPHYLOCOCCUS-AUREUS; PHOTOPHYSICAL PROPERTIES; ANTIBIOTIC ERA; INACTIVATION; AZIDE; RADICALS; INFECTIONS; FULLERENE AB Background and Objectives Antimicrobial photodynamic therapy (APDT) employs a non-toxic photosensitizer (PS) and visible light, which in the presence of oxygen produce reactive oxygen species (ROS), such as singlet oxygen (1O2, produced via Type II mechanism) and hydroxyl radical (HO., produced via Type I mechanism). This study examined the relative contributions of 1O2 and HO. to APDT killing of Gram-positive and Gram-negative bacteria. Study Design/Materials and Methods Fluorescence probes, 3'-(p-hydroxyphenyl)-fluorescein (HPF) and singlet oxygen sensor green reagent (SOSG) were used to determine HO. and 1O2 produced by illumination of two PS: tris-cationic-buckminsterfullerene (BB6) and a conjugate between polyethylenimine and chlorin(e6) (PEIce6). Dimethylthiourea is a HO. scavenger, while sodium azide (NaN3) is a quencher of 1O2. Both APDT and killing by Fenton reaction (chemical generation of HO.) were carried out on Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa). Results Conjugate PEI-ce6 mainly produced 1O2 (quenched by NaN3), while BB6 produced HO. in addition to 1O2 when NaN3 potentiated probe activation. NaN3 also potentiated HPF activation by Fenton reagent. All bacteria were killed by Fenton reagent but Gram-positive bacteria needed a higher concentration than Gram-negatives. NaN3 potentiated Fenton-mediated killing of all bacteria. The ratio of APDT killing between Gram-positive and Gram-negative bacteria was 2 or 4:1 for BB6 and 25:1 for conjugate PEI-ce6. There was a NaN3 dose-dependent inhibition of APDT killing using both PEI-ce6 and BB6 against Gram-negative bacteria while NaN3 almost failed to inhibit killing of Gram-positive bacteria. Conclusion Azidyl radicals may be formed from NaN3 and HO.. It may be that Gram-negative bacteria are more susceptible to HO. while Gram-positive bacteria are more susceptible to 1O2. The differences in NaN3 inhibition may reflect differences in the extent of PS binding to bacteria (microenvironment) or differences in penetration of NaN3 into cell walls of bacteria. Lasers Surg. Med. 44: 490499, 2012. (C) Wiley Periodicals, Inc. C1 [Huang, Liyi; Xuan, Yi; Koide, Yuichiro; Zhiyentayev, Timur; Tanaka, Masamitsu; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning 530021, Peoples R China. [Huang, Liyi; Tanaka, Masamitsu; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Xuan, Yi] Tufts Univ, Sch Engn, Medford, MA 02155 USA. [Koide, Yuichiro] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan. [Zhiyentayev, Timur] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. [Tanaka, Masamitsu] Natl Def Med Coll, Dept Orthopaed Surg, Tokorozawa, Saitama 3598513, Japan. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01A1050875]; US Air Force MFEL [FA9550-04-1-0079]; ASLMS FX Contract grant sponsor: NIH; Contract grant number: R01A1050875; Contract grant sponsor: US Air Force MFEL Program; Contract grant number: FA9550-04-1-0079.; This study was supported by NIH (R01A1050875 to M. R. H.) and US Air Force MFEL Program (FA9550-04-1-0079). These data were presented at ASLMS meeting in 2010 by Dr Huang who received a travel grant from ASLMS. This contribution satisfies the condition of the travel grant that a manuscript should be submitted to LSM within 1 year after the annual conference. NR 59 TC 51 Z9 54 U1 6 U2 81 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD AUG PY 2012 VL 44 IS 6 BP 490 EP 499 DI 10.1002/lsm.22045 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 972YL UT WOS:000306317500008 PM 22760848 ER PT J AU Kawakubo, M Eguchi, K Arai, T Kobayashi, K Hamblin, MR AF Kawakubo, Masayoshi Eguchi, Keisuke Arai, Tsunenori Kobayashi, Koichi Hamblin, Michael R. TI Surface layer-preserving photodynamic therapy (SPPDT) in a subcutaneous mouse model of lung cancer SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photodynamic therapy; taloporfin sodium; pulsed laser; surface layer preservation; trachbronchial cancer; lung cancer; Lewis lung carcinoma; pig tracheal cartilage; mediastinal lymph node ID ASPARTYL CHLORIN E6; PULSED-DYE-LASER; HYPERFRACTIONATED RADIATION-THERAPY; SQUAMOUS-CELL CARCINOMA; VENA-CAVA-SYNDROME; ARGON-DYE; TUMOR; CONCURRENT; PHOTOSENSITIZER; PHOTORADIATION AB Background and Objectives Photodynamic therapy (PDT) may be a less invasive treatment for lung cancer. Our newly developed surface layer-preserving PDT (SPPDT) technique enables us to irradiate deep tumor while preserving the overlying tissue. The aim of this basic study was to verify that the SPPDT technique might be applied to lung cancer. Study Design/Materials and Methods PDT with talaporfin sodium was performed using a pulsed laser with different pulse dose rates (PDRs, 2.520.0?mJ/cm2/pulse) in a mouse model of subcutaneous tumor. To mimic the tracheal wall structure and a thoracic tumor in the tracheobronchus, we also made a mouse model in which a piece of swine cartilage was placed between the dermis and the tumor, and PDT was carried out 2 weeks after implantation. In both experiments, the tissue samples were collected 48?hours after PDT and evaluated microscopically. Results SPPDT using a high-PDR laser damaged the underlying tissue but left the superficial tissue intact in the mouse subcutaneous tumor model. In SPPDT, a higher PDR produced a thicker layer of intact superficial tissue than a lower PDR, while a lower PDR produced a deeper layer of damaged tissue than a higher PDR. SPPDT was also able to preserve the superficial tissue and to damage the tumor tissue beneath the cartilage implant. Conclusion SPPDT was able to damage tumor beneath the superficial normal tissue layer, which included tracheal cartilage in the mouse model. The thickness control of SPPDT was provided by controlling laser pulse intensity. SPPDT is a new technology, whose future potential is unknown. The initial clinical application of this technology could be endoscopic treatment (e.g., palliative therapy of thoracic malignancies via bronchoscopy). Lasers Surg. Med. 44: 500507, 2012. (C) Wiley Periodicals, Inc. C1 [Kawakubo, Masayoshi; Eguchi, Keisuke; Kobayashi, Koichi] Keio Univ, Sch Med, Dept Thorac Surg, Tokyo, Japan. [Eguchi, Keisuke] Saitama Med Univ, Saitama Med Ctr, Kawagoe, Saitama, Japan. [Arai, Tsunenori] Keio Univ, Fac Sci & Technol, Dept Appl Phys & Physicoinformat, Yokohama, Kanagawa 223, Japan. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Kawakubo, M (reprint author), 40 Blossom St, Boston, MA 02114 USA. EM masayoshikaw@aol.com OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01A1050875] FX Contract grant sponsor: US NIH; Contract grant number: R01A1050875. NR 44 TC 2 Z9 2 U1 0 U2 4 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 AUG PY 2012 VL 44 IS 6 BP 500 EP 507 DI 10.1002/lsm.22046 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 972YL UT WOS:000306317500009 PM 22752880 ER PT J AU Tisdall, MD Hess, AT Reuter, M Meintjes, EM Fischl, B van der Kouwe, AJW AF Tisdall, M. Dylan Hess, Aaron T. Reuter, Martin Meintjes, Ernesta M. Fischl, Bruce van der Kouwe, Andre J. W. TI Volumetric navigators for prospective motion correction and selective reacquisition in neuroanatomical MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE prospective motion correction; navigator; brain morphometry; validation ID MAGNETIC-RESONANCE IMAGES; HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; HEAD MOTION; COORDINATE SYSTEM; BRAIN; ACCURATE; SEGMENTATION; REGISTRATION AB We introduce a novel method of prospectively compensating for subject motion in neuroanatomical imaging. Short three-dimensional echo-planar imaging volumetric navigators are embedded in a long three-dimensional sequence, and the resulting image volumes are registered to provide an estimate of the subject's location in the scanner at a cost of less than 500 ms, similar to 1% change in contrast, and similar to 3% change in intensity. This time fits well into the existing gaps in sequences routinely used for neuroimaging, thus giving a motion-corrected sequence with no extra time required. We also demonstrate motion-driven selective reacquisition of k-space to further compensate for subject motion. We perform multiple validation experiments to evaluate accuracy, navigator impact on tissue intensity/contrast, and the improvement in final output. The complete system operates without adding additional hardware to the scanner and requires no external calibration, making it suitable for high-throughput environments. Magn Reson Med, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Tisdall, M. Dylan; Fischl, Bruce; van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Tisdall, M. Dylan; Fischl, Bruce; van der Kouwe, Andre J. W.] Harvard Univ, Sch Med, Dept Radiol, Brookline, MA USA. [Hess, Aaron T.; Meintjes, Ernesta M.] Univ Cape Town, MRC UCT Med Imaging Res Unit, Dept Human Biol, ZA-7700 Rondebosch, South Africa. [Reuter, Martin] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Reuter, Martin] Harvard Univ, Sch Med, Dept Neurol, Brookline, MA USA. [Reuter, Martin; Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. RP Tisdall, MD (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA USA. EM tisdall@nmr.mgh.harvard.edu RI Reuter, Martin/B-3456-2010; OI Reuter, Martin/0000-0002-2665-9693; Hess, Aaron/0000-0002-9289-5619 FU Center for Functional Neuroimaging Technologies [P41RR14075]; National Center for Research Resources (NCRR), National Institutes of Health; NCRR [S10RR021110, S10RR023401]; NIH [5R21EB008547, 5R21AA017410, 5R21DA026104, 5R01NS055754]; Ellison Medical Foundation FX Grant sponsor: Center for Functional Neuroimaging Technologies; Grant number: P41RR14075 [a P41 Regional Resource supported by Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health]; Grant sponsors: NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; Grant numbers: S10RR021110, S10RR023401; Grant sponsor: NIH; Grant numbers: 5R21EB008547, 5R21AA017410, 5R21DA026104, and 5R01NS055754; Grant sponsor: Ellison Medical Foundation. NR 35 TC 57 Z9 57 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2012 VL 68 IS 2 BP 389 EP 399 DI 10.1002/mrm.23228 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 972YZ UT WOS:000306318900010 PM 22213578 ER PT J AU Sundara-Rajan, K Bestick, A Rowe, GI Klute, GK Ledoux, WR Wang, HC Mamishev, AV AF Sundara-Rajan, K. Bestick, A. Rowe, G. I. Klute, G. K. Ledoux, W. R. Wang, H. C. Mamishev, A. V. TI An interfacial stress sensor for biomechanical applications SO MEASUREMENT SCIENCE AND TECHNOLOGY LA English DT Article DE biomechanical interfaces; prosthesis; capacitive sensor; interfacial stress; pressure; sensor fabrication; shear stress ID PROSTHETIC SOCKET INTERFACE; TIBIAL AMPUTEE SUBJECTS; SHEAR STRESSES; PLANTAR SHEAR; RESIDUAL LIMB; PRESSURES; AMBULATION; SUCTION; FOOT; TIME AB This paper presents a capacitive sensor that measures interfacial forces in prostheses and is promising for other biomedical applications. These sensors can be integrated into prosthetic devices to measure both normal and shear stress simultaneously, allowing for the study of prosthetic limb fit, and ultimately for the ability to better adapt prosthetics to individual users. A sensing cell with a 1.0 cm(2) spatial resolution and a measurement range of 0-220 kPa of shear and 0-2 MPa of pressure was constructed. The cell was load tested and found to be capable of isolating the applied shear and pressure forces. This paper discusses the construction of the prototype, the mechanical and electrode design, fabrication and characterization. The work presented is aimed at creating a class of adaptive prosthetic interfaces using a capacitive sensor. C1 [Sundara-Rajan, K.; Bestick, A.; Rowe, G. I.; Mamishev, A. V.] Univ Washington, Dept Elect Engn, Sensors Energy & Automat Lab, Seattle, WA 98195 USA. [Klute, G. K.; Ledoux, W. R.] VA Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA USA. [Klute, G. K.; Ledoux, W. R.; Wang, H. C.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, W. R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Sundara-Rajan, K (reprint author), Univ Washington, Dept Elect Engn, Sensors Energy & Automat Lab, Seattle, WA 98195 USA. EM kishore@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU US National Institute of Health [R21HD052109-02]; Department of Veterans Affairs [A4843C]; Washington NASA Space Grant scholarships FX The authors would like to thank Dan Hemmons, Anthony Simon, John Thomson, Michael Fassbind and Shruti Pai for their help with sensor fabrication and the force measurement systems used in the experiments reported in this paper, and also STREAM Tools [47] for the guide to formatting documents in Word, and Meagan Schuver, Kenneth Yuen and Aaron Zielinski for editing. This work was supported in part by the US National Institute of Health under Grant R21HD052109-02, the Department of Veterans Affairs Grant A4843C and the Washington NASA Space Grant scholarships. NR 47 TC 6 Z9 6 U1 0 U2 21 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-0233 EI 1361-6501 J9 MEAS SCI TECHNOL JI Meas. Sci. Technol. PD AUG PY 2012 VL 23 IS 8 AR 085701 DI 10.1088/0957-0233/23/8/085701 PG 10 WC Engineering, Multidisciplinary; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA 973NJ UT WOS:000306366600053 ER PT J AU Goroll, AH AF Goroll, Allan H. TI Risk Adjustment for Primary Care An Essential Tool for Health System Reform SO MEDICAL CARE LA English DT Editorial Material ID PAYMENT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goroll, AH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ahgoroll@partners.org 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 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 2012 VL 50 IS 8 BP 637 EP 639 DI 10.1097/MLR.0b013e31825cb499 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 973KX UT WOS:000306360100003 PM 22683594 ER PT J AU Yoon, J Yano, EM Altman, L Cordasco, KM Stockdale, SE Chow, A Barnett, PG Rubenstein, LV AF Yoon, Jean Yano, Elizabeth M. Altman, Lisa Cordasco, Kristina M. Stockdale, Susan E. Chow, Adam Barnett, Paul G. Rubenstein, Lisa V. TI Reducing Costs of Acute Care for Ambulatory Care-sensitive Medical Conditions The Central Roles of Comorbid Mental Illness SO MEDICAL CARE LA English DT Article DE mental health; primary care; avoidable admissions; ED visits ID HEALTH-CARE; PREVENTABLE HOSPITALIZATIONS; VETERANS-AFFAIRS; COLLABORATIVE CARE; DEPRESSION; DISORDERS; BENEFICIARIES; QUALITY; ACCESS; IMPACT AB Background: New patient-centered models of ambulatory care aim to substitute better primary care for preventable acute care within existing primary care practices. This study aims to identify whether mental illness and other characteristics of primary care patients are related to risk for an acute event for an ambulatory care-sensitive condition (ACSC). Methods: We conducted a 2-year, longitudinal analysis comparing ambulatory care-sensitive admissions and emergency department (ED) visits for a cohort of 18,526 primary care patients followed in 5 veterans affairs (VA) primary care sites. We compared rates, risks, and costs of ACSC-related acute events during a follow-up year for patients with and without mental illness seen during the previous year in primary care. Results: The 12-month rate of ACSC admissions was 31.7 admissions per 1000 patients with mental health diagnoses compared with 21.0 admissions per 1000 patients without (P=0.0009). The ACSC-associated ED visit rate was also significantly higher (P<0.0001). In adjusted analyses controlling for demographics, chronic disease, illness severity, and prior ambulatory care, those with depression or drug use disorders had higher odds of receiving ACSC-related acute care (odds ratio=1.10, 95% confidence interval: 1.03, 1.17 for depression; odds ratio=1.48, 95% confidence interval: 1.05, 1.99 for drug use disorders). Costs per admission and ED visit were similar across patient groups. Higher medication use and lower medication regimen complexity were significantly associated with decreased risk for ACSC events. Conclusions: Prior mental health diagnoses and medication use were independent risk factors for ACSC-related acute care. These risk factors require focused attention if the full benefits of new primary care models are to be achieved. C1 [Yoon, Jean; Chow, Adam; Barnett, Paul G.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA 94025 USA. [Yano, Elizabeth M.; Cordasco, Kristina M.; Stockdale, Susan E.; Rubenstein, Lisa V.] VA Greater Los Angeles, Ctr Excellence Study Healthcare Provider Behav, North Hills, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Altman, Lisa] VA Greater Los Angeles, Dept Ambulatory Care, North Hills, CA USA. [Cordasco, Kristina M.; Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Cordasco, Kristina M.; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Barnett, Paul G.] Stanford Univ, Hlth Res & Policy Dept, Stanford, CA 94305 USA. RP Yoon, J (reprint author), VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM jean.yoon@va.gov FU Department of Veteran Affairs, Veterans Health Administration, Patient Care Services, the VA Improvement and Assessment Laboratory [XVA 65-018] FX The authors declare no conflict of interest. Funding for this study was provided by the Department of Veteran Affairs, Veterans Health Administration, Patient Care Services, the VA Improvement and Assessment Laboratory (Project XVA 65-018). NR 47 TC 19 Z9 19 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 2012 VL 50 IS 8 BP 705 EP 713 DI 10.1097/MLR.0b013e31824e3379 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 973KX UT WOS:000306360100013 PM 22437618 ER PT J AU Rubin, KM Vona, K Madden, K McGettigan, S Braun, IM AF Rubin, Krista M. Vona, Karen Madden, Kathleen McGettigan, Suzanne Braun, Ilana M. TI Side effects in melanoma patients receiving adjuvant interferon alfa-2b therapy: a nurse's perspective SO SUPPORTIVE CARE IN CANCER LA English DT Review DE Adjuvant; Adverse effects; Interferon alfa; Therapy management ID HIGH-RISK MELANOMA; DOSE INTERFERON-ALPHA-2B; CANCER-PATIENTS; PEGYLATED INTERFERON-ALPHA-2B; DEPRESSIVE SYMPTOMS; MALIGNANT-MELANOMA; FATIGUE INVENTORY; III MELANOMA; ALPHA; MANAGEMENT AB The aim of this review was to examine the toxicity profile of adjuvant interferon (IFN) alfa-2b in melanoma patients from a nursing perspective and to summarize practical information to guide the effective management of common IFN toxicities to improve patient comfort. This is a narrative summary of both research and review articles identified by searching PubMed, National Cancer Institute, and American Cancer Society websites. It also assesses recognized guidelines on the management of adjuvant IFN toxicity relevant to nurses who are caring for patients receiving adjuvant IFN therapy. Adjuvant high-dose IFN alfa-2b (HDI) as compared with observation significantly prolongs relapse-free survival in patients with melanoma at high risk for recurrence after surgical resection; however, treatment compliance and patient quality of life can be compromised by its toxicity profile. HDI toxicities affect a number of organ systems and the majority of patients will experience some side effects. Common toxicities such as flu-like symptoms, fatigue, anorexia, neuropsychiatric symptoms, and laboratory abnormalities are discussed, along with both pharmacological and nonpharmacological management strategies. The considerable side effects of HDI can be managed using established strategies. Oncology nurses play a significant role in the management of patients with melanoma receiving adjuvant HDI, and their prompt recognition of side effects, together with an understanding of effective pharmacological and nonpharmacological interventions, will improve patient comfort; this has the potential to positively influence treatment adherence and completion of the recommended treatment course. C1 [Rubin, Krista M.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA 02114 USA. [Vona, Karen] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Madden, Kathleen] NYU, Langone Med Ctr, Ctr Clin Canc, New York, NY USA. [McGettigan, Suzanne] Univ Penn Hlth Syst, Abramson Canc Ctr, Philadelphia, PA USA. [Braun, Ilana M.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Rubin, KM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, 55 Fruit St,Yawkey Bldg,Suite 9E, Boston, MA 02114 USA. EM kmrubin@partners.org NR 58 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD AUG PY 2012 VL 20 IS 8 BP 1601 EP 1611 DI 10.1007/s00520-012-1473-0 PG 11 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 970LG UT WOS:000306129600002 PM 22562583 ER PT J AU Lalla, RV Gordon, GB Schubert, M Silverman, S Hutten, M Sonis, ST LeVeque, F Peterson, DE AF Lalla, Rajesh V. Gordon, Gary B. Schubert, Mark Silverman, Sol, Jr. Hutten, Mark Sonis, Stephen T. LeVeque, Francis Peterson, Douglas E. TI A randomized, double-blind, placebo-controlled trial of misoprostol for oral mucositis secondary to high-dose chemotherapy SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Misoprostol; Prostaglandin E1; Mucositis; Chemotherapy ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; MUCOSAL INJURY; PROSTAGLANDIN-E1 ANALOG; CANCER-PATIENTS; INFECTION; RADIATION; SEVERITY; PATIENT AB Misoprostol, a synthetic analog of prostaglandin E1, has anti-inflammatory and mucosa-protecting properties. The objective of this study was to evaluate the efficacy of misoprostol oral rinse in reducing the severity of oral mucosal injury caused by high-dose chemotherapy. The study used a randomized, double-blind, placebo-controlled, parallel-group design. Oncology patients receiving myeloablative high-dose chemotherapy, in preparation for a hematopoietic stem cell transplant, were randomized to misoprostol or placebo rinse. The primary outcome measure was the severity of oral mucositis, measured using the modified Oral Mucositis Index. Additional outcome measures included the severity of mouth pain (measured using a Visual Analog Scale and the Pain Affect Faces Scale), duration of hospital stay, and days on total parenteral nutrition. This study was originally planned to accrue 160 subjects but was terminated early due to revised sponsor research priorities. The intent-to-treat population consisted of 22 subjects randomized to misoprostol rinse and 26 subjects randomized to placebo rinse. There was no significant difference between the two groups in mucositis or pain severity. In both groups, duration of hospital stay was approximately 19 days, and number of days on total parenteral nutrition was 17-18 days. There were no serious adverse events attributable to misoprostol rinse. Although this study did not find a beneficial effect of a misoprostol rinse in mucositis secondary to high-dose chemotherapy, the small sample size limits the strength of this conclusion. Given the proposed importance of the prostaglandin pathway in the pathogenesis of oral mucositis, additional studies are warranted. C1 [Lalla, Rajesh V.; Peterson, Douglas E.] Univ Connecticut, Ctr Hlth, Sect Oral Med, Farmington, CT USA. [Lalla, Rajesh V.; Peterson, Douglas E.] Univ Connecticut, Ctr Hlth, Neag Comprehens Canc Ctr, Farmington, CT USA. [Gordon, Gary B.] GD Searle, Skokie, IL USA. [Schubert, Mark] Univ Washington, Seattle, WA 98195 USA. [Schubert, Mark] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Silverman, Sol, Jr.] Univ Calif San Francisco, Sch Dent, Dept Orofacial Sci, San Francisco, CA USA. [Hutten, Mark] Northwestern Univ, Feinberg Sch Med, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60611 USA. [Sonis, Stephen T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. [LeVeque, Francis] Wayne State Univ, Sch Med, Detroit, MI USA. RP Lalla, RV (reprint author), Univ Connecticut, Ctr Hlth, Sect Oral Med, Farmington, CT USA. EM Lalla@nso2.uchc.edu FU G.D. Searle and Company, Pfizer, Inc. FX This study was supported by G.D. Searle and Company, now a component of Pfizer, Inc. The authors acknowledge the contributions of the subjects who participated in this study. NR 32 TC 6 Z9 8 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD AUG PY 2012 VL 20 IS 8 BP 1797 EP 1804 DI 10.1007/s00520-011-1277-7 PG 8 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 970LG UT WOS:000306129600024 PM 21964618 ER PT J AU Biederman, J AF Biederman, Joseph TI Is ADHD Overdiagnosed in Scandinavia? SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Editorial Material C1 [Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu NR 5 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD AUG PY 2012 VL 126 IS 2 BP 85 EP 86 DI 10.1111/j.1600-0447.2012.01878.x PG 2 WC Psychiatry SC Psychiatry GA 970IO UT WOS:000306121800002 PM 22764752 ER PT J AU Angin, M Streeck, H Wen, F King, M Pereyra, F Altfeld, M Walker, BD Addo, MM AF Angin, Mathieu Streeck, Hendrik Wen, Fang King, Melanie Pereyra, Florencia Altfeld, Marcus Walker, Bruce D. Addo, Marylyn M. TI Regulatory T Cell Frequencies Do Not Correlate with Breadth or Magnitude of HIV-1-Specific T Cell Responses SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Letter ID HIV-INFECTED INDIVIDUALS; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; ACTIVATION; SUPPRESSION; DEPLETION; CD4(+) C1 [Angin, Mathieu; Streeck, Hendrik; Wen, Fang; King, Melanie; Pereyra, Florencia; Altfeld, Marcus; Walker, Bruce D.; Addo, Marylyn M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Addo, Marylyn M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Addo, MM (reprint author), Ragon Inst MGH MIT & Harvard, 149 13th St,6th Floor,Suite 6620, Charlestown, MA 02129 USA. EM maddo@partners.org OI Angin, Mathieu/0000-0002-6867-4680 FU NIAID NIH HHS [AI074405-03S1, KO8 AI074405, P01 AI074415, P30AI 060354, R01 AI091450] NR 14 TC 3 Z9 4 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 2012 VL 28 IS 8 BP 749 EP 751 DI 10.1089/aid.2011.0353 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 977SA UT WOS:000306683600002 PM 22214208 ER PT J AU Wanderer, J Forman, S Baker, K AF Wanderer, Jonathan Forman, Stuart Baker, Keith TI RESIDENTS HELPING IN NAVIGATING OR SCHEDULING (RHINOS): FACILITATING SELF-DIRECTED LEARNING SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 [Wanderer, Jonathan; Forman, Stuart; Baker, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 2012 VL 115 SU 1 PG 1 WC Anesthesiology SC Anesthesiology GA V45WM UT WOS:000209846700036 ER PT J AU Fagenholz, PJ Bowler, GMR Carnochan, FM Walker, WS AF Fagenholz, P. J. Bowler, G. M. R. Carnochan, F. M. Walker, W. S. TI Systemic local anaesthetic toxicity from continuous thoracic paravertebral block SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthetic techniques; regional; thoracic; anaesthetics local; bupivacaine; complications; death; surgery; thoracic ID RANDOMIZED-TRIALS; BUPIVACAINE; THORACOTOMY; ROPIVACAINE; ANALGESIA; PHARMACOKINETICS; ENANTIOMERS; EFFICACY; INFUSION; PAIN AB Continuous paravertebral block is commonly used for post-thoracotomy analgesia and compares favourably with other systemic and regional methods with regard to safety and efficacy. No major complications of continuous paravertebral block for post-thoracotomy analgesia have been reported previously. We report here a case of systemic local anaesthetic toxicity from continuous paravertebral block administration after thoracotomy and lobectomy leading to seizure, aspiration, and ultimately, death. Potential contributing factors in this case included small patient size, concomitant antifungal therapy, extensive surgical disruption of the pleurae, and inappropriate paravertebral bolus administration. Postoperative delirium was a diagnostic confounder. We discuss the potential causes and means of avoiding similar complications in the future. C1 [Fagenholz, P. J.; Bowler, G. M. R.; Carnochan, F. M.; Walker, W. S.] Royal Infirm Edinburgh NHS Trust, Dept Anaesthesia Theatres & Pain Med, Edinburgh EH16 4SU, Midlothian, Scotland. [Fagenholz, P. J.; Bowler, G. M. R.; Carnochan, F. M.; Walker, W. S.] Royal Infirm Edinburgh NHS Trust, Dept Cardiothorac Surg, Edinburgh EH16 4SU, Midlothian, Scotland. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Crit Care, CPZ 810,165 Cambridge St, Boston, MA 02114 USA. EM pfagenholz@partners.org NR 15 TC 13 Z9 13 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD AUG PY 2012 VL 109 IS 2 BP 260 EP 262 DI 10.1093/bja/aes126 PG 3 WC Anesthesiology SC Anesthesiology GA 973MJ UT WOS:000306363900020 PM 22581806 ER PT J AU Keliher, EJ Reiner, T Thurber, GM Upadhyay, R Weissleder, R AF Keliher, Edmund J. Reiner, Thomas Thurber, Greg M. Upadhyay, Rabi Weissleder, Ralph TI Efficient F-18-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells SO CHEMISTRYOPEN LA English DT Article DE F-18-trans-cyclooctene; cancer; diabetes; exendin-4; insulinoma; positron emission tomography ID IN-VIVO; RECEPTOR; INSULINOMA; PEPTIDE; GLP-1; MASS AB A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with F-18-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging. C1 [Keliher, Edmund J.; Reiner, Thomas; Thurber, Greg M.; Upadhyay, Rabi; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Keliher, EJ (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu OI Reiner, Thomas/0000-0002-7819-5480; Thurber, Greg/0000-0001-7570-2080 FU National Institutes of Health (NIH) [P01 AI54904, U24 CA092782, K01 1KO1K093766-01]; German Academy of Sciences [2009-24] FX The authors thank Jessica Truelove (Center for Systems Biology, Massachusetts General Hospital (CSB, MGH)) for image processing and generation, Rostic Gorbatov (CSB, MGH) for surgery, Dr. Yvonna Fisher-Jeffes (CSB, MGH) for critical review of the article and Dr. Ralph Mazitschek (CSB, MGH) for many helpful discussions. We especially recognize the many helpful discussions with Drs. Diane Mathis, Christophe Benoist (Department of Pathology, Harvard Medical School) and Jason Gaglia (Joslin Diabetes Center, Harvard Medical School). This work was supported, in part, by the following grants: National Institutes of Health (NIH) Grants P01 AI54904 (to R. W.), U24 CA092782 (to R. W.), K01 1KO1K093766-01 (to G. M. T.). R. U. is a Howard Hughes Medical Institute Medical Research Fellow. T. R. was supported by German Academy of Sciences Leopoldina Grant LPDS 2009-24. NR 28 TC 25 Z9 25 U1 0 U2 14 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 2191-1363 J9 CHEMSTRYOPEN JI ChemistryOpen PD AUG PY 2012 VL 1 IS 4 BP 177 EP 183 DI 10.1002/open.201200014 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 274LY UT WOS:000328609200004 PM 23997998 ER PT J AU Moed, BR Vrahas, MS AF Moed, Berton R. Vrahas, Mark S. TI Disruptions of the Pelvic Ring: An Update: Editorial Comment SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Editorial Material C1 [Moed, Berton R.] St Louis Univ, Sch Med, Dept Orthopaed Surg, St Louis, MO 63110 USA. [Vrahas, Mark S.] Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Moed, BR (reprint author), St Louis Univ, Sch Med, Dept Orthopaed Surg, 3635 Vista Ave,7th Floor,Desloge Towers, St Louis, MO 63110 USA. EM moedbr@slu.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 2012 VL 470 IS 8 BP 2073 EP 2074 DI 10.1007/s11999-012-2365-9 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 971PD UT WOS:000306215400001 PM 22528391 ER PT J AU Weaver, MJ Bruinsma, W Toney, E Dafford, E Vrahas, MS AF Weaver, Michael J. Bruinsma, Wendy Toney, Eugene Dafford, Erica Vrahas, Mark S. TI What Are the Patterns of Injury and Displacement Seen in Lateral Compression Pelvic Fractures? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SACRAL FRACTURES; RING; BURGESS; YOUNG AB Lateral compression (LC)-type pelvic fractures encompass a wide spectrum of injuries. Current classification systems are poorly suited to help guide treatment and do not adequately describe the wide range of injuries seen in clinical practice. We therefore (1) defined the spectrum of injuries that compose LC fractures with respect to both anterior and posterior ring injuries, with particular focus on the morphology of sacral fractures, and (2) identified fracture patterns associated with displacement at presentation. We retrospectively reviewed 318 LC pelvic fractures. Displacement of the anterior pelvic ring was identified and measured on plain radiographs and posterior displacement was identified by CT. All 318 patients had an anterior injury and all but 13 (4%) had a posterior injury; 263 of the 318 fractures (87%) included a sacral fracture, with 162 of 318 (51%) having an anterior incomplete sacral fracture, 53 (17%) a complete simple fracture, and 48 (15%) a complete comminuted fracture. Forty-two of 318 (13%) had a crescent fracture. One hundred six of 318 (33%) were displaced at presentation. There was a higher incidence of initial displacement observed in fractures including bilateral rami fractures, a comminuted sacral fracture, or a crescent fracture. LC pelvic fractures represent a heterogeneous group of injuries with a wide range of associated fracture patterns. In particular, there is a wide range of fracture types represented by injuries classified as LC1 (involving any sacral fracture). Fractures with more complex sacral fractures, crescent fractures, or bilateral pubic rami fractures tend to have higher degrees of initial displacement. Level IV, diagnostic study. See Instructions for Authors for a complete description of levels of evidence. C1 [Bruinsma, Wendy; Dafford, Erica; Vrahas, Mark S.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weaver, Michael J.; Toney, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Vrahas, MS (reprint author), Harvard Univ, Sch Med, Dept Orthopaed Surg, Massachusetts Gen Hosp, 55 Fruit St,YAW 3, Boston, MA 02114 USA. EM mvrahas@partners.org NR 14 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 2012 VL 470 IS 8 BP 2104 EP 2110 DI 10.1007/s11999-012-2364-x PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 971PD UT WOS:000306215400008 PM 22585347 ER PT J AU Shazly, TA Latina, MA Dagianis, JJ Chitturi, S AF Shazly, Tarek A. Latina, Mark A. Dagianis, John J. Chitturi, Satyakant TI Effect of Central Corneal Thickness on the Long-Term Outcome of Selective Laser Trabeculoplasty as Primary Treatment for Ocular Hypertension and Primary Open-Angle Glaucoma SO CORNEA LA English DT Article DE selective laser trabeculoplasty; central corneal thickness; ocular hypertension; primary open-angle glaucoma; intraocular pressure ID RANDOMIZED CLINICAL-TRIAL; INTRAOCULAR-PRESSURE; SUCCESS AB Purpose: To determine if central corneal thickness (CCT) impacts the intraocular pressure (IOP)-lowering effect of selective laser trabeculoplasty (SLT) in patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG). Methods: A retrospective chart review of consecutive patients, who underwent SLT as primary treatment for OHT and POAG, between 2002 and 2005, was performed. Partial correlation analysis was performed to correlate the CCT to the percentage of IOP reduction at 3 to 30 months after SLT. Independent samples t test was performed to compare mean percentage of IOP reduction in eyes with CCT less than 555 mu m versus CCT 555 mu m or greater. Results: Eighty eyes of 47 patients were identified. The partial correlation coefficient value between the CCT and percentage of IOP reduction after SLT at 3 months was -0.253 (P = 0.025), at 12 months it was -0.22 (P = 0.049), and at 30 months it was 0.301 (P = 0.007). Independent samples t test showed that the mean percentage of IOP reduction in eyes with thinner corneas (CCT, 555 mu m) was greater than that in thicker corneas (CCT >= 555 mu m) at 3-, 6-, 9-, 12-, and 30-month post-SLT (P < 0.05). Conclusions: In patients with POAG and OHT, percentage of IOP reduction after SLT was significantly greater in eyes with thinner corneas (CCT, 555 mu m). These findings indicate that patients treated with SLT as primary therapy who had thinner corneas demonstrated better IOP control for at least 30 months after SLT. C1 [Shazly, Tarek A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Shazly, Tarek A.] Assiut Univ Hosp, Dept Ophthalmol, Assiut, Egypt. [Latina, Mark A.] Reading Hlth Ctr, Reading, MA USA. [Dagianis, John J.] Nashua Eye Associates, Nashua, NH USA. [Chitturi, Satyakant] Andhra Med Coll, Visakhapatnam, Andhra Pradesh, India. RP Shazly, TA (reprint author), 20 Pondmeadow Dr,Suite 203, Reading, MA 01867 USA. EM shazlyt@gmail.com NR 21 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD AUG PY 2012 VL 31 IS 8 BP 883 EP 886 DI 10.1097/ICO.0b013e318243f684 PG 4 WC Ophthalmology SC Ophthalmology GA 973BG UT WOS:000306325500008 PM 22525783 ER PT J AU Sepulcre, J Sabuncu, MR Johnson, KA AF Sepulcre, Jorge Sabuncu, Mert R. Johnson, Keith A. TI Network assemblies in the functional brain SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE brain connectome; brain network; functional connectivity; graph theory; neuroimaging ID DEFAULT MODE; NEUROCOGNITIVE NETWORKS; CORTICAL CONNECTIONS; CEREBRAL-CORTEX; ORGANIZATION; COGNITION; MRI; HUBS; PRINCIPLES; DISEASE AB Purpose of review This review focuses on recent advances in functional connectivity MRI and renewed interest in studying the large-scale functional network assemblies in the brain. We also consider some methodological aspects of graph theoretical analysis. Recent findings Recent years have witnessed a rapid increase in the number of studies that apply network science to neuroscience. A major motivation comes from the fields of neurology and psychiatry, where a central goal is the characterization of the functional connectome of the brain under normal and pathological conditions. Recent findings have provided new insights into the pivotal role of network epicenters and specific configurations of large-scale functional networks in the brain. Summary Functional connectivity MRI and corresponding analytical tools continue to reveal novel properties of the functional organization of the brain, which will in turn be key for understanding pathologies in neurology. C1 [Sepulcre, Jorge; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Cambridge, MA 02138 USA. [Sepulcre, Jorge; Johnson, Keith A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Sepulcre, Jorge; Sabuncu, Mert R.] Athinioula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Johnson, Keith A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sepulcre, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, 52 Oxford St,Northwest Bldg,280-02, Cambridge, MA 02138 USA. EM sepulcre@nmr.mgh.harvard.edu FU Alzheimer's Association [NIRG-11-205690, ZEN-10-174210]; NIH [K25EB013649-01, R01AG037497, R01AG036694] FX We thank Randy L. Buckner and Fenna Krienen for generously providing the raw data used in Fig. 4, and Emily Shire for her helpful comments to the article. This work was supported by the Alzheimer's Association (NIRG-11-205690 to JS; ZEN-10-174210 to KAJ) and the NIH (K25EB013649-01 to MRS; R01AG037497 and R01AG036694 to KAJ). NR 64 TC 20 Z9 22 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD AUG PY 2012 VL 25 IS 4 BP 384 EP 391 DI 10.1097/WCO.0b013e328355a8e8 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 970KB UT WOS:000306125900003 PM 22766721 ER PT J AU Pike, MC Kelley, L AF Pike, Marilyn C. Kelley, Lexy TI Data Quality Challenges in Systemic Lupus Erythematosus Trials: How Can This Be Optimized? SO CURRENT RHEUMATOLOGY REPORTS LA English DT Article DE Systemic lupus erythematosus; SLE; Data quality; Challenge; New agents; Therapy; Central adjudication committees; Disease Activity Index; Trials; Optimize ID B-LYMPHOCYTE STIMULATOR; DISEASE-ACTIVITY INDEX; INTERNATIONAL CLINICAL-TRIAL; INFARCTION END-POINTS; RHEUMATOID-ARTHRITIS; INITIAL VALIDATION; THERAPY; BILAG; SLE; ADJUDICATION AB Major scientific advances in basic science, pharmacology, and translational medicine have allowed the discovery of new molecular targets whose manipulation by new chemical entities has led to treatments for inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Development of new agents for systemic lupus erythematosus (SLE) has lagged, however, because the protean manifestations of SLE present challenges for measuring therapeutic effects in a consistent manner. Composite end points combining several Disease Activity Indices (DAIs) are being used in ongoing global studies, but the uniform application of these complex DAIs across large numbers of clinical sites has proven difficult. We describe herein approaches that are being utilized to facilitate collection, review, and analysis of the clinical measures utilizing independent central adjudication committees. C1 [Pike, Marilyn C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol, Boston, MA USA. [Pike, Marilyn C.] MedPharm Consulting, Cambridge, MA 02138 USA. [Kelley, Lexy] ReS Pharmaceut Serv, Ft Washington, PA 19034 USA. RP Pike, MC (reprint author), MedPharm Consulting, 8 Craigie St, Cambridge, MA 02138 USA. EM mp@marilynpike.com; lkelley@rpsweb.com FU UCB Pharma, Inc.; MedImmune, Inc.; RPS, Inc. FX MCP receives consultancy fees from UCB Pharma, Inc., MedImmune, Inc. and RPS, Inc. LK is a current employee of RPS, Inc. and a former employee of UCB Pharma, Inc. NR 55 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3774 J9 CURR RHEUMATOL REP JI Curr. Rheumatol. Rep. PD AUG PY 2012 VL 14 IS 4 BP 324 EP 333 DI 10.1007/s11926-012-0261-7 PG 10 WC Rheumatology SC Rheumatology GA 225UX UT WOS:000324990600005 PM 22580894 ER PT J AU Yoon, WJ Brugge, WR AF Yoon, Won Jae Brugge, William R. TI Endoscopic Ultrasound and Pancreatic Cystic Lesions-Diagnostic and Therapeutic Applications SO ENDOSCOPIC ULTRASOUND LA English DT Review DE endosonography; pancreatic cyst AB Pancreatic cystic lesions are being detected with an increasing frequency. Endoscopic ultrasound (EUS) provides both diagnostic and therapeutic means for pancreatic cystic lesions. Detailed imaging and EUS-guided fine-needle aspiration provide additional information on pancreatic cystic lesions. EUS-guided pseudocyst drainage has advantages over conventional drainage modalities. EUS-guided cyst ablation is a promising therapeutic modality C1 [Yoon, Won Jae; Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Brugge, William R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org NR 48 TC 5 Z9 6 U1 0 U2 1 PU SPRING MEDIA PI HONG KONG PA BLDG 8, WANG KWUN RD, KIN BAY, HONG KONG, SAR 00000, PEOPLES R CHINA SN 2303-9027 EI 2226-7190 J9 ENDOSC ULTRASOUND JI Endosc. Ultrasound PD AUG PY 2012 VL 1 IS 2 BP 75 EP 79 DI 10.7178/eus.02.004 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V31PG UT WOS:000208894900004 PM 24949341 ER PT J AU Doba, N Tokuda, Y Goldstein, NE Kushiro, T Hinohara, S AF Doba, Nobutaka Tokuda, Yasuharu Goldstein, Nathan E. Kushiro, Toshio Hinohara, Shigeaki TI A pilot trial to predict frailty syndrome: The Japanese Health Research Volunteer Study SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Frailty; Prediction; Gait speed; Pulse pressure; Cognitive deficits; Hearing deficits ID COMPREHENSIVE GERIATRIC ASSESSMENT; ANDROGEN-DEPRIVATION THERAPY; DWELLING OLDER-PEOPLE; IANA TASK-FORCE; BODY-COMPOSITION; PROSTATE-CANCER; GAIT SPEED; DISEASE; MANAGEMENT; PROMOTION AB Most definitions of frailty utilize US populations in their development. The concept of frailty has not been well studied in Japan, which has the largest percentage of older patients ( per capita) in the world. We created a 5-year prospective cohort study of community-dwelling older Japanese adults. Participants were not frail at baseline, based on our definition adapted from the Canadian Study for Health and Aging Clinical Frailty Scale. Participants underwent a comprehensive geriatric assessment (CGA) at baseline, and final assessments were either in person or via mailed survey. We enrolled 407 individuals (184 men, mean age 78 +/- 4 years; 223 women, mean age 77 +/- 4 years). Sixty-five participants met criteria for frailty by the end of the study. In univariate analyses, eighteen separate parameters were associated with frailty, some of which included: age, gender, handgrip, timed walk, systolic blood pressure, pulse pressure, cognitive status, living alone, and hearing deficits. In multivariate analyses, the following elements remained associated with frailty: timed walk, pulse pressure, cognition deficits and hearing deficits. We established cut-off points for timed walk (5 m/3 s) and pulse pressure (60 mm Hg). We then created a simple additive score for these four factors (present = 1; absent = 0). A score of 0 had a 93% negative predictive value for frailty while a score of 4 had a 70% positive predictive value. While further study is needed, this work creates an easy-to-administer tool that may be generalizable to other populations. (C) 2012 Elsevier Inc. All rights reserved. C1 [Doba, Nobutaka] Sasakawa Kinen Kaikan, Life Planning Ctr Fdn, Div Res & Educ, Minato Ku, Tokyo 1080073, Japan. [Tokuda, Yasuharu] Univ Tsukuba, Mito Kyodo Gen Hosp, Dept Med, Mito, Ibaraki 3100015, Japan. [Goldstein, Nathan E.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr Bronx, Bronx, NY USA. [Kushiro, Toshio] Nihon Univ, Sch Med, Ctr Hlth Evaluat & Promot, Chiyoda Ku, Tokyo 1010062, Japan. [Hinohara, Shigeaki] Sasakawa Kinen Kaikan, Life Planning Ctr Fdn, Minato Ku, Tokyo 1080073, Japan. RP Doba, N (reprint author), Sasakawa Kinen Kaikan, Life Planning Ctr Fdn, Div Res & Educ, Minato Ku, 11th Floor,12-12,Mita 3 Chome, Tokyo 1080073, Japan. EM doba@krd.biglobe.ne.jp; yasuharu.tokuda@gmail.com; Nathan.goldstein@mssm.edu; Kushiro@med.nihon-u.ac.jp; shosler@mrj.biglobe.ne.jp FU Life Planning Center FX The research reported in this paper was supported by the institutional research fund from the Life Planning Center, a not-for-profit organization. The authors have no conflict of interest to disclose. We thank all the participants who joined the study as well as the members of the study committee. Also we express our gratitude to other research members at the LPC for their professional and technical assistance. NR 43 TC 15 Z9 16 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD AUG PY 2012 VL 47 IS 8 BP 638 EP 643 DI 10.1016/j.exger.2012.05.016 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 970CU UT WOS:000306106500014 PM 22664579 ER PT J AU Rose, AJ Petrakis, BA Callahan, P Mambourg, S Patel, D Hylek, EM Bokhour, BG AF Rose, Adam J. Petrakis, Beth Ann Callahan, Patricia Mambourg, Scott Patel, Dimple Hylek, Elaine M. Bokhour, Barbara G. TI Organizational Characteristics of High- and Low-Performing Anticoagulation Clinics in the Veterans Health Administration SO HEALTH SERVICES RESEARCH LA English DT Article DE Qualitative research; quality of health care; anticoagulants; pharmacists; organization and administration ID VITAMIN-K ANTAGONISTS; THERAPY; WARFARIN; QUALITY AB Objective Anticoagulation clinics (ACCs) can improve anticoagulation control and prevent adverse events. However, ACCs vary widely in their performance on anticoagulation control. Our objective was to compare the organization and management of top-performing with that of bottom-performing ACCs. Data Sources/Study Setting Three high outlier and three low outlier ACCs in the Veterans Health Administration (VA). Study Design Site visits with qualitative data collection and analysis. Data Collection/Extraction Methods We conducted semi-structured interviews with ACC staff regarding work flow, staffing, organization, and quality assurance efforts. We also observed ACC operations and collected documents, such as the clinic protocol. We used grounded thematic analysis to examine site-level factors associated with high and low outlier status. Principal Findings High outlier sites were characterized by (1) adequate (pharmacist) staffing and effective use of (nonpharmacist) support personnel; (2) innovation to standardize clinical practice around evidence-based guidelines; (3) the presence of a quality champion for the ACC; (4) higher staff qualifications; (5) a climate of ongoing group learning; and (6) internal efforts to measure performance. Although high outliers had all of these features, no low outlier had more than two of them. Conclusions The top-performing ACCs in the VA system shared six relatively recognizable characteristics. Efforts to improve performance should focus on these domains. C1 [Rose, Adam J.; Petrakis, Beth Ann; Hylek, Elaine M.; Bokhour, Barbara G.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Rose, Adam J.; Hylek, Elaine M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Rose, Adam J.; Petrakis, Beth Ann; Callahan, Patricia; Mambourg, Scott; Patel, Dimple; Hylek, Elaine M.; Bokhour, Barbara G.] US Dept Vet Affairs, Washington, DC USA. [Bokhour, Barbara G.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Rose, AJ (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70, Bedford, MA 01730 USA. EM adamrose@bu.edu OI Bokhour, Barbara/0000-0001-8238-0745 FU VA Stroke Quality Enhancement Research Initiative (QUERI) [RRP-10-054]; VA HSR&D Career Development Award [CDA-2-08-017] FX This study was funded by the VA Stroke Quality Enhancement Research Initiative (QUERI), Project RRP-10-054. Dr. Rose is supported by a VA HSR&D Career Development Award (CDA-2-08-017). The authors thank Russell Buono, Mitchell Finkel, Elizabeth Goy, and Anthony Vo for their help collecting the data. The authors thank Steve Spear, Rani Elwy, Dan Berlowitz, Arlene Ash, and Vicky Parker for their helpful comments on the manuscript. The authors thank all the interviewees for participating. NR 19 TC 15 Z9 15 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2012 VL 47 IS 4 BP 1541 EP 1560 DI 10.1111/j.1475-6773.2011.01377.x PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 970OL UT WOS:000306141500009 PM 22299722 ER PT J AU Ryan, A Burgess, J Strawderman, R Dimick, J AF Ryan, Andrew Burgess, James Strawderman, Robert Dimick, Justin TI What Is the Best Way to Estimate Hospital Quality Outcomes? A Simulation Approach SO HEALTH SERVICES RESEARCH LA English DT Article DE Biostatistical methods; incentives in health care; hospitals; Medicare; patient outcomes; functional status; ADLs; IADLs; quality of care; patient safety (measurement) ID MORTALITY-RATES; HEALTH-CARE; PERFORMANCE-MEASURES; SURGICAL MORTALITY; COMPOSITE MEASURES; ACCURACY; MODEL AB Objective To test the accuracy of alternative estimators of hospital mortality quality using a Monte Carlo simulation experiment. Data Sources Data are simulated to create an admission-level analytic dataset. The simulated data are validated by comparing distributional parameters (e.g., mean and standard deviation of 30-day mortality rate, hospital sample size) with the same parameters observed in Medicare data for acute myocardial infarction (AMI) inpatient admissions. Study Design We perform a Monte Carlo simulation experiment in which true quality is known to test the accuracy of the Observed-over-Expected estimator, the Risk Standardized Mortality Rate (RSMR), the Dimick and Staiger (DS) estimator, the Hierarchical Poisson estimator, and the Moving Average estimator using hospital 30-day mortality for AMI as the outcome. Estimator accuracy is evaluated for all hospitals and for small, medium, and large hospitals. Data Extraction Methods Data are simulated. Principal Findings Significant and substantial variation is observed in the accuracy of the tested outcome estimators. The DS estimator is the most accurate for all hospitals and for small hospitals using both accuracy criteria (root mean squared error and proportion of hospitals correctly classified into quintiles). Conclusions The mortality estimator currently in use by Medicare for public quality reporting, the RSMR, has been shown to be less accurate than the DS estimator, although the magnitude of the difference is not large. Pending testing and validation of our findings using current hospital data, CMS should reconsider the decision to publicly report mortality rates using the RSMR. C1 [Ryan, Andrew] Weill Cornell Med Coll, Dept Publ Hlth, Div Outcomes & Effectiveness, New York, NY 10065 USA. [Burgess, James] Boston Univ, Ctr Org Leadership & Management Res, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Burgess, James] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Strawderman, Robert] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA. [Strawderman, Robert] Cornell Univ, Dept Stat Sci, Ithaca, NY USA. [Dimick, Justin] Univ Michigan, Taubman Hlth Care Ctr, Ann Arbor, MI 48109 USA. RP Ryan, A (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, Div Outcomes & Effectiveness, 402 E 67th St, New York, NY 10065 USA. EM amr2015@med.cornell.edu OI Burgess, James/0000-0002-6646-7071 FU Agency for Healthcare Research and Quality [1 K01 HS018546-01A1, K08 HS017765]; Clinical and Translational Science Center at Weill Cornell Medical College FX Funding for Dr. Ryan was supported by a career development award from the Agency for Healthcare Research and Quality (1 K01 HS018546-01A1). Dr. Dimick was supported by a career development award from the Agency for Healthcare Research and Quality (K08 HS017765). Dr. Dimick is a paid consultant and equity owner in Arbor-Metrix, Inc., a company that provides software and analytic services for assessing hospital quality and efficiency. Dr. Strawderman was supported by a grant from the Clinical and Translational Science Center at Weill Cornell Medical College. The opinions are solely those of the authors and do not reflect those of the US Department of Veterans Affairs, Centers for Medicare and Medicaid Services, the United States government, Boston University, Cornell University, or Weill Cornell Medical College. NR 31 TC 8 Z9 8 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2012 VL 47 IS 4 BP 1699 EP 1718 DI 10.1111/j.1475-6773.2012.01382.x PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 970OL UT WOS:000306141500017 PM 22352894 ER PT J AU Maliha, G Morgan, J Vrahas, M AF Maliha, George Morgan, Jordan Vrahas, Mark TI Transient osteoporosis of pregnancy SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Review DE Transient osteoporosis; Pregnancy ID DISPLACED SUBCAPITAL FRACTURE; REGIONAL OSTEOPOROSIS; AVASCULAR NECROSIS; FOLLOW-UP; HIP AB Transient osteoporosis of pregnancy (TOP) is a rare yet perhaps under-reported condition that has affected otherwise healthy pregnancies throughout the world. The condition presents suddenly in the third trimester of a usually uneventful pregnancy and progressively immobilizes the mother. Radiographic studies detect drastic loss of bone mass, elevated rates of turnover in the bone, and oedema in the affected portion. Weakness of the bone can lead to fractures during delivery and other complications for the mother. Then, within weeks of labour, symptoms and radiological findings resolve. Aetiology is currently unknown, although neural, vascular, haematological, endocrine, nutrient-deficiency, and other etiologies have been proposed. Several treatments have also been explored, including simple bed rest, steroids, bisphosphonates, calcitonin, induced termination of pregnancy, and surgical intervention. The orthopedist plays an essential role in monitoring the condition (and potential complications) as well as ensuring satisfactory outcomes for both the mother and newborn. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Maliha, George; Morgan, Jordan; Vrahas, Mark] Massachusetts Gen Hosp, Harvard Orthopaed Trauma Serv, Boston, MA 02114 USA. RP Morgan, J (reprint author), Massachusetts Gen Hosp, Orthopaed Trauma Serv, Yawkey Ctr, Suite 3C,55 Fruit St, Boston, MA 02114 USA. EM gmaliha@princeton.edu; jhmorgan@partners.org; mvrahas@partners.org NR 40 TC 8 Z9 9 U1 0 U2 3 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 AUG PY 2012 VL 43 IS 8 BP 1237 EP 1241 DI 10.1016/j.injury.2012.03.009 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 970FG UT WOS:000306112900002 PM 22464203 ER PT J AU Halasz, LM Jacene, HA Catalano, PJ Van den Abbeele, AD LaCasce, A Mauch, PM Ng, AK AF Halasz, Lia M. Jacene, Heather A. Catalano, Paul J. Van den Abbeele, Annick D. LaCasce, Ann Mauch, Peter M. Ng, Andrea K. TI Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Combined modality treatment; FDG-PET; non-Hodgkin lymphoma ID POSITRON-EMISSION-TOMOGRAPHY; B-CELL LYMPHOMA; COOPERATIVE-ONCOLOGY-GROUP; RESPONSE ASSESSMENT; INTERNATIONAL WORKSHOP; AGGRESSIVE LYMPHOMA; CHEMOTHERAPY; RADIOTHERAPY; CHOP; RADIATION AB Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [F-18]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT. (C) 2012 Elsevier Inc. C1 [Mauch, Peter M.; Ng, Andrea K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Halasz, Lia M.] Harvard Radiat Oncol Program, Boston, MA USA. [Jacene, Heather A.; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Jacene, Heather A.; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [LaCasce, Ann] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 27 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2012 VL 83 IS 5 BP E647 EP E654 DI 10.1016/j.ijrobp.2012.01.060 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 970KT UT WOS:000306128100013 PM 22607911 ER PT J AU Ackerman, RH AF Ackerman, Robert H. TI Celebrating the life of C. Miller Fisher SO INTERNATIONAL JOURNAL OF STROKE LA English DT Editorial Material C1 [Ackerman, Robert H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ackerman, Robert H.] Harvard Univ, Sch Med, Boston, MA USA. RP Ackerman, RH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 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 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD AUG PY 2012 VL 7 IS 6 BP 444 EP 446 DI 10.1111/j.1747-4949.2012.00877.x PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 974AM UT WOS:000306402100005 PM 22805573 ER PT J AU Goveas, JS Hogan, PE Kotchen, JM Smoller, JW Denburg, NL Manson, JE Tummala, A Mysiw, WJ Ockene, JK Woods, NF Espeland, MA Wassertheil-Smoller, S AF Goveas, Joseph S. Hogan, Patricia E. Kotchen, Jane M. Smoller, Jordan W. Denburg, Natalie L. Manson, JoAnn E. Tummala, Aruna Mysiw, W. Jerry Ockene, Judith K. Woods, Nancy F. Espeland, Mark A. Wassertheil-Smoller, Sylvia TI Depressive symptoms, antidepressant use, and future cognitive health in postmenopausal women: the Women's Health Initiative Memory Study SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE antidepressants; selective serotonin reuptake inhibitors; late-life depression; cognitive decline; mild cognitive impairment; dementia ID LATE-LIFE DEPRESSION; ALZHEIMERS-DISEASE; GERIATRIC DEPRESSION; PROBABLE DEMENTIA; IMPAIRMENT; RISK; OUTCOMES; DECLINE; METAANALYSIS; THERAPY AB Background: Antidepressants are commonly prescribed medications in the elderly, but their relationship with incident mild cognitive impairment (MCI) and probable dementia is unknown. Methods: The study cohort included 6,998 cognitively healthy, postmenopausal women, aged 65-79 years, who were enrolled in a hormone therapy clinical trial and had baseline depressive symptoms and antidepressant use history assessments at enrollment, and at least one postbaseline cognitive measurement. Participants were followed annually and the follow-up averaged 7.5 years for MCI and probable dementia outcomes. A central adjudication committee classified the presence of MCI and probable dementia based on extensive neuropsychiatric examination. Results: Three hundred and eighty-three (5%) women were on antidepressants at baseline. Antidepressant use was associated with a 70% increased risk of MCI, after controlling for potential covariates including the degree of depressive symptom severity. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) were both associated with MCI (SSRIs: hazard ratios (HR), 1.78 [95% CI, 1.01-3.13]; TCAs: HR, 1.78 [95% CI, 0.99-3.21]). Depressed users (HR, 2.44 [95% CI, 1.24-4.80]), non-depressed users (HR, 1.79 [95% CI, 1.13-2.85]), and depressed non-users (HR, 1.62 [95% CI, 1.13-2.32]) had increased risk of incident MCI. Similarly, all three groups had increased risk of either MCI or dementia, relative to the control cohort. Conclusions: Antidepressant use and different levels of depression severity were associated with subsequent cognitive impairment in a large cohort of postmenopausal women. Future research should examine the role of antidepressants in the depression-dementia relationship and determine if antidepressants can prevent incident MCI and dementia in individuals with late-life depression subtypes with different levels of severity. C1 [Goveas, Joseph S.; Tummala, Aruna] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. [Hogan, Patricia E.; Espeland, Mark A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Kotchen, Jane M.] Med Coll Wisconsin, Dept Populat Hlth, Milwaukee, WI 53226 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Denburg, Natalie L.] Univ Iowa, Coll Med, Dept Neurol, Iowa City, IA 52242 USA. [Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Mysiw, W. Jerry] Ohio State Univ, Med Ctr, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. [Ockene, Judith K.] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01605 USA. [Woods, Nancy F.] Univ Washington, Seattle, WA 98195 USA. [Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. RP Goveas, JS (reprint author), Med Coll Wisconsin, Dept Psychiat & Behav Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM jgoveas@mcw.edu RI Mysiw, Walter/E-3724-2011 FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122]; Wyeth Pharmaceuticals FX The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, and 32122. The active study drug and placebo were supplied by Wyeth-Ayerst Research Laboratories, Philadelphia, PA. The Women's Health Initiative Memory Study was funded in part by Wyeth Pharmaceuticals as an ancillary study to the WHI. Wyeth Pharmaceuticals did not participate in the design and conduct of the studies, in the collection, analysis, and interpretation of the data, nor in the preparation, review, or approval of this paper. NR 35 TC 9 Z9 9 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD AUG PY 2012 VL 24 IS 8 SI SI BP 1252 EP 1264 DI 10.1017/S1041610211002778 PG 13 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 971LZ UT WOS:000306206700007 PM 22301077 ER PT J AU Chow, FC Regan, S Feske, S Meigs, JB Grinspoon, SK Triant, VA AF Chow, Felicia C. Regan, Susan Feske, Steven Meigs, James B. Grinspoon, Steven K. Triant, Virginia A. TI Comparison of Ischemic Stroke Incidence in HIV-Infected and Non-HIV-Infected Patients in a US Health Care System SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; stroke; cerebrovascular; cardiovascular; vascular risk factors ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MYOCARDIAL-INFARCTION RATES; DEFICIENCY-SYNDROME AIDS; CORONARY-HEART-DISEASE; T-CELL COUNT; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ENDOTHELIAL DYSFUNCTION; CEREBROVASCULAR-DISEASE; METABOLIC SYNDROME AB Background: Cardiovascular disease is increased among HIV-infected patients, but little is known regarding ischemic stroke rates. We sought to compare stroke rates and determine stroke risk factors in HIV-infected versus non-HIV-infected patients. Methods: An HIV cohort and matched non-HIV comparator cohort seen between 1996 and 2009 were identified from a Boston health care system. The primary endpoint was ischemic stroke, defined using International Classification of Diseases (ICD) codes. Unadjusted stroke incidence rates were calculated. Cox proportional hazards modeling was used to determine adjusted hazard ratios (HRs). Results: The incidence rate of ischemic stroke was 5.27 per 1000 person-years in HIV-infected compared with 3.75 in non-HIV-infected patients, with an unadjusted HR of 1.40 [95% confidence interval (CI): 1.17 to 1.69, P, 0.001]. HIV remained an independent predictor of stroke after controlling for demographics and stroke risk factors (HR: 1.21, 95% CI: 1.01 to 1.46, P = 0.043). The relative increase in stroke rates (HIV vs. non-HIV) was significantly higher in younger HIV patients (incidence rate ratio: 4.42, 95% CI: 1.56 to 11.09, age 18-29; 2.96, 1.69-4.96, age: 30-39; 1.53, 1.06-2.17, age: 40-49), and in women [HR: 2.16 (95% CI: 1.53 to 3.04) for women vs. HR: 1.18 (95% CI: 0.95 to 1.47) for men]. Among HIV patients, increased HIV RNA (HR: 1.10, 95% CI: 1.04 to 1.17, P = 0.001) was associated with an increased risk of stroke. Conclusions: Stroke rates were increased among HIV-infected patients, independent of common stroke risk factors, particularly among young patients and women. C1 [Triant, Virginia A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Chow, Felicia C.; Feske, Steven] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Chow, Felicia C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Regan, Susan; Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. RP Triant, VA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,LON207, Boston, MA 02114 USA. EM vtriant@partners.org FU National Institutes of Health [5T32MH090847, K01 AI073109] FX Supported in part by National Institutes of Health grant numbers 5T32MH090847 (F.C.C.) and K01 AI073109 (V.A.T.). NR 48 TC 74 Z9 74 U1 1 U2 6 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 AUG 1 PY 2012 VL 60 IS 4 BP 351 EP 358 DI 10.1097/QAI.0b013e31825c7f24 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 971YF UT WOS:000306242300009 PM 22580566 ER PT J AU Kaplan, RC Landay, AL Hodis, HN Gange, SJ Norris, PJ Young, M Anastos, K Tien, PC Xue, XN Lazar, J Parrinello, CM Benning, L Tracy, RP AF Kaplan, Robert C. Landay, Alan L. Hodis, Howard N. Gange, Stephen J. Norris, Philip J. Young, Mary Anastos, Kathryn Tien, Phyllis C. Xue, Xiaonan Lazar, Jason Parrinello, Christina M. Benning, Lorie Tracy, Russell P. TI Potential Cardiovascular Disease Risk Markers Among HIV-Infected Women Initiating Antiretroviral Treatment SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; cardiovascular diseases; cytokines; hemostasis; HIV; inflammation ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTIMA-MEDIA THICKNESS; T-CELL-ACTIVATION; INTERAGENCY HIV; CAROTID-ARTERY; COAGULATION BIOMARKERS; THERAPY EXPOSURE; SOLUBLE CD14; COHORT; ATHEROSCLEROSIS AB Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). Methods: In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound. Results: Relative to HIV-uninfected controls, HAART-naive HIVinfected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-alpha (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemo-attractant protein 1 (190 vs 163 pg/mL, P, 0.0001), and D-dimer (0.43 vs 0.31 mu g/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-alpha levels remained elevated compared with HIV-uninfected women (+ 0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness. Conclusions: Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-alpha), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy. C1 [Kaplan, Robert C.; Anastos, Kathryn; Xue, Xiaonan; Parrinello, Christina M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Landay, Alan L.] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL USA. [Hodis, Howard N.] Univ So Calif, Atherosclerosis Res Unit, Los Angeles, CA 90089 USA. [Gange, Stephen J.; Benning, Lorie] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Norris, Philip J.] Univ Calif San Francisco, Dept Lab Med, Blood Syst Res Inst, San Francisco, CA 94143 USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lazar, Jason] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. RP Kaplan, RC (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer 1306C, Bronx, NY 10461 USA. EM Robert.kaplan@einstein.yu.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; National Heart, Lung and Blood Institute [1R01HL095140, 1R01HL083760]; University of Washington's CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center [5R01HL095126] FX Supported by the National Institutes of Health. The Women's Interagency HIV Study is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study was cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding was also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). Additional cofunding was provided by the National Heart, Lung and Blood Institute (1R01HL095140, 1R01HL083760 to R.C.K.). Partial funding for laboratory work and assistance with general study coordination was provided by the University of Washington's CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center (5R01HL095126). NR 36 TC 25 Z9 26 U1 0 U2 3 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 AUG 1 PY 2012 VL 60 IS 4 BP 359 EP 368 DI 10.1097/QAI.0b013e31825b03be PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 971YF UT WOS:000306242300010 PM 22592585 ER PT J AU Medapalli, RK Parikh, CR Gordon, K Brown, ST Butt, AA Gibert, CL Rimland, D Rodriguez-Barradas, MC Chang, CCH Justice, AC He, JCJ Wyatt, CM AF Medapalli, Raj K. Parikh, Chirag R. Gordon, Kirsha Brown, Sheldon T. Butt, Adeel A. Gibert, Cynthia L. Rimland, David Rodriguez-Barradas, Maria C. Chang, Chung-Chou H. Justice, Amy C. He, John Cijiang Wyatt, Christina M. TI Comorbid Diabetes and the Risk of Progressive Chronic Kidney Disease in HIV-Infected Adults: Data From the Veterans Aging Cohort Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE non-AIDS complications; HIV; chronic kidney disease; diabetes; risk factors ID GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; ANTIRETROVIRAL THERAPY; DATA-COLLECTION; ADVERSE EVENTS; HEPATITIS-C; MELLITUS; RATES AB Introduction: Approximately, 15% of HIV-infected individuals have comorbid diabetes. Studies suggest that HIV and diabetes have an additive effect on chronic kidney disease (CKD) progression; however, this observation may be confounded by differences in traditional CKD risk factors. Methods: We studied a national cohort of HIV-infected and matched HIV-uninfected individuals who received care through the Veterans Healthcare Administration. Subjects were divided into 4 groups based on baseline HIV and diabetes status, and the rate of progression to an estimated glomerular filtration rate (eGFR) <45 mL/min/ 1.73m(2) was compared using Cox-proportional hazards modeling to adjust for CKD risk factors. Results: About 31,072 veterans with baseline eGFR >= 45 mL/min/1.73m(2) (10,626 with HIV only, 5088 with diabetes only, and 1796 with both) were followed for a median of 5 years. Mean baseline eGFR was 94 mL/min/1.73m(2), and 7% progressed to an eGFR < 45 mL/min/1.73m(2). Compared with those without HIV or diabetes, the relative rate of progression was increased in individuals with diabetes only [adjusted hazard ratio (HR) 2.48; 95% confidence interval (CI): 2.19 to 2.80], HIV only [HR: 2.80, 95% CI: 2.50 to 3.15], and both HIV and diabetes [HR: 4.47, 95% CI: 3.87 to 5.17]. Discussion: Compared with patients with only HIV or diabetes, patients with both diagnoses are at significantly increased risk of progressive CKD even after adjusting for traditional CKD risk factors. Future studies should evaluate the relative contribution of complex comorbidities and accompanying polypharmacy to the risk of CKD in HIV-infected individuals and prospectively investigate the use of cART, glycemic control, and adjunctive therapy to delay CKD progression. C1 [Medapalli, Raj K.; He, John Cijiang; Wyatt, Christina M.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Parikh, Chirag R.] Yale Univ, Dept Med, Nephrol Sect, New Haven, CT 06520 USA. [Parikh, Chirag R.; Gordon, Kirsha] W Haven VA Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT USA. [Brown, Sheldon T.] James J Peters VA Med Ctr, Dept Med, Div Infect Dis, Bronx, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY 10029 USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Dept Med, Div Infect Dis, Pittsburgh, PA USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA USA. [Butt, Adeel A.] Dept Med, Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Gibert, Cynthia L.] VA Med Ctr, Dept Med, Div Infect Dis, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Dept Med, Div Infect Dis, Washington, DC 20037 USA. [Rimland, David] VA Med Ctr, Dept Med, Div Infect Dis, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Dept Med, Infect Dis Sect, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Justice, Amy C.] W Haven VA Med Ctr, Dept Med, New Haven, CT USA. [He, John Cijiang] James J Peters VA Med Ctr, Dept Med, Div Nephrol, Bronx, NY USA. RP Wyatt, CM (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM christina.wyatt@mssm.edu FU National Institutes of Health, National Institute of Alcohol and Alcohol Abuse [U01 AA13566]; Office of Research and Development, Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Disease [P01DK056492, R01DK088541, R01DK078897, K23DK077568] FX The Veterans Aging Cohort Study is supported by the National Institutes of Health, National Institute of Alcohol and Alcohol Abuse (U01 AA13566) and by the Office of Research and Development, Department of Veterans Affairs. This work was also supported in part by the National Institute of Diabetes and Digestive and Kidney Disease (P01DK056492, R01DK088541, R01DK078897, and K23DK077568). NR 22 TC 24 Z9 24 U1 1 U2 5 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 AUG 1 PY 2012 VL 60 IS 4 BP 393 EP 399 DI 10.1097/QAI.0b013e31825b70d9 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 971YF UT WOS:000306242300014 PM 22592587 ER PT J AU Zhang, LT Zhang, LJ Zhou, KY Ye, XX Zhang, JJ Xie, AM Chen, LY Kang, JX Cai, C AF Zhang, Liangtao Zhang, Lijian Zhou, Keyuan Ye, Xiaoxia Zhang, Junjie Xie, Aimei Chen, Liyu Kang, Jing X. Cai, Chun TI Simultaneous Determination of Global DNA Methylation and Hydroxymethylation Levels by Hydrophilic Interaction Liquid Chromatography-Tandem Mass Spectrometry SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE DNA methylation; DNA hydroxymethylation; hydrophilic interaction liquid chromatography-MS/MS ID 5-HYDROXYMETHYLCYTOSINE; CELLS; 5-METHYLCYTOSINE; CONVERSION; PATTERNS; GENE AB Methylation of DNA at the 5-position of cytosine (Cyt) is a well-studied epigenetic pathway implicated in gene silencing and embryogenesis. Recently, in addition to 5-methylcytosine (5mC), substantial amounts of 5-hydroxymethylcytosine (5hmC) have been detected in certain mammalian tissues. Here, we developed and validated a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for the simultaneous determination of Cyt, 5mC, and 5hmC levels in biological samples. DNA was extracted with phenol-chloroform, hydrolyzed using 88% formic acid at 140 C, separated using a bridged ethylene hybrid HILIC column, and analyzed by tandem MS. The linearity was established over the concentration range of 1 to 500 ng/mL for Cyt, 0.2 to 100 ng/mL for 5mC, and 0.1 to 50 ng/mL for 5hmC, and the correlation coefficients were all >0.99. Limits of detection were 1 pg/mL for Cyt, 45 pg/mL for 5mC, and 57 pg/mL for 5hmC, and the limit of quantification values for Cyt, 5mC, and 5hmC were 2 pg/mL, 90 pg/mL, and 100 pg/mL, respectively. The relative standard deviation (RSD) of the intraday precision ranged from 1.87% to 4.84% and the interday precision from 2.69% to 4.98%. The recovery of the method varied from 88.25% to 104.39%. The method was then applied to the analysis of DNA from biological samples, establishing its potential for helping researchers understand the roles of modified nucleobases in DNA. C1 [Zhang, Liangtao; Zhang, Lijian; Zhou, Keyuan; Ye, Xiaoxia; Zhang, Junjie; Xie, Aimei; Chen, Liyu; Cai, Chun] Guangdong Med Coll, Zhanjiang 524023, Guangdong, Peoples R China. [Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA USA. RP Cai, C (reprint author), Guangdong Med Coll, Zhanjiang 524023, Guangdong, Peoples R China. EM caichun2006@tom.com FU Guangdong Medical College; National Natural Science Foundation of China [30672741] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from Guangdong Medical College; and the National Natural Science Foundation of China (30672741). NR 24 TC 10 Z9 12 U1 2 U2 22 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD AUG PY 2012 VL 17 IS 7 BP 877 EP 884 DI 10.1177/1087057112447946 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 973AX UT WOS:000306324500003 PM 22644266 ER PT J AU Abraham, BP Mehta, S El-Serag, HB AF Abraham, Bincy P. Mehta, Seema El-Serag, Hashem B. TI Natural History of Pediatric-onset Inflammatory Bowel Disease A Systematic Review SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE natural history; pediatric IBD; long-term risk; growth failure; disease reclassification; disease extension; hospitalization; cancer; death ID POPULATION-BASED COHORT; 10 YEARS OLD; CROHNS-DISEASE; ULCERATIVE-COLITIS; GROWTH FAILURE; CLINICAL-FEATURES; ADULT LIFE; FOLLOW-UP; CHILDREN; PROGNOSIS AB Background/Aims: There has been no systematic review of natural history studies of pediatric-onset inflammatory bowel disease (IBD). We conducted a systematic review focused on understanding the long-term risks of growth failure, disease reclassification and extension, hospitalizations, cancer and death among patients with childhood IBD. Methods: PubMed searches and subsequent data abstraction were performed by 2 independent investigators. Studies published full in english with a 5-year minimum average follow-up in at least 30 patients with IBD onset before age 18 years. Results: We evaluated 41 total studies (only 2 population-based studies) with 3505 Crohn's disease (CD) patients, 2071 ulcerative colitis (UC) patients, and 461 indeterminate colitis (IC). Growth failure was reported in CD (10% and 56%) more often than UC (0% to 10%) or non-IBD controls. Improvements in growth occurred after surgical resection in patients with CD. There was an increase in disease reclassification over time from UC and indeterminate colitis diagnosis to CD diagnosis. Patients with CD had higher number of hospitalizations and hospital days per year in comparison with UC patients in most studies. The reported surgery rates in CD ranged between 10% and 72%; the colectomy rates in UC ranged between 0% and 50%. Cancers were reported in 6 CD patients during a total 18,270 patient-years (PY) follow-up, and 8 UC patients in 18,115 PY. Deaths directly related to IBD were 63 during 39,719 PY. Conclusions: Childhood-onset IBD patients had growth failure reported in patients with CD more often than those with UC, had a reclassification of disease type to CD over time. Higher rates of surgery and hospitalizations were found with CD than with UC. The risk of cancer and death is low in this population. C1 [Abraham, Bincy P.; Mehta, Seema; El-Serag, Hashem B.] Texas Childrens Hosp, Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Abraham, BP (reprint author), 1709 Dryden St,Suite 800, Houston, TX 77030 USA. EM bincya@bcm.edu FU Houston VA HSR&D Center of Excellence [HFP90-020]; NIH/National Institute of Diabetes and Digestive and Kidney Disease, Center [P30 DK56338] FX Supported by Houston VA HSR&D Center of Excellence (HFP90-020) and NIH/National Institute of Diabetes and Digestive and Kidney Disease, Center Grant P30 DK56338. NR 58 TC 40 Z9 43 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD AUG PY 2012 VL 46 IS 7 BP 581 EP 589 DI 10.1097/MCG.0b013e318247c32f PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972OY UT WOS:000306287600010 PM 22772738 ER PT J AU Hurrell, MJ Monk, TG Nicol, A Norton, AN Reich, DL Walsh, JL AF Hurrell, M. J. Monk, T. G. Nicol, A. Norton, A. N. Reich, D. L. Walsh, J. L. TI Implementation of a standards-based anaesthesia record compliant with the health level 7 (HL7) clinical document architecture (CDA) SO JOURNAL OF CLINICAL MONITORING AND COMPUTING LA English DT Article DE Anesthetic record; HL7; CDA; XML; ISO 11073; IOTA; APSF DDTF AB With the increasing use of anaesthesia information management systems (AIMS) there is the opportunity for different institutions to aggregate and share information both nationally and internationally. Potential uses of such aggregated data include outcomes research, benchmarking and improvement in clinical practice and patient safety. However, these goals can only be achieved if data contained in records from different sources are truly comparable and there is semantic inter-operability. This paper describes the development of a standard terminology for anaesthesia and also a Domain Analysis Model and implementation guide to facilitate a standard representation of AIMS records as extensible markup language documents that are compliant with the Health Level 7 Version 3 clinical document architecture. A representation of vital signs that is compliant with the International Standards Organization 11073 standard is also discussed. C1 [Hurrell, M. J.; Nicol, A.] Informat CIS Ltd, Glasgow, Lanark, Scotland. [Monk, T. G.] Duke Univ, Med Ctr, Durham, NC USA. [Norton, A. N.] Pilgrim Hosp, Boston, MA USA. [Reich, D. L.] Mt Sinai Sch Med, New York, NY USA. [Walsh, J. L.] Massachussets Gen Hosp, Boston, MA USA. RP Hurrell, MJ (reprint author), Informat CIS Ltd, Glasgow, Lanark, Scotland. EM martinhurrell@gmail.com NR 17 TC 3 Z9 3 U1 1 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1387-1307 J9 J CLIN MONIT COMPUT JI J. Clin. Monitor. Comp. PD AUG PY 2012 VL 26 IS 4 BP 295 EP 304 DI 10.1007/s10877-012-9360-2 PG 10 WC Anesthesiology SC Anesthesiology GA 970KZ UT WOS:000306128800007 PM 22614336 ER PT J AU Blagev, DP Hirshberg, EL Sward, K Thompson, BT Brower, R Truwit, J Hite, D Steingrub, J Orme, JF Clemmer, TP Weaver, LK Thomas, F Grissom, CK Sorenson, D Sittig, DF Wallace, CJ East, TD Warner, HR Morris, AH AF Blagev, Denitza P. Hirshberg, Eliotte L. Sward, Katherine Thompson, B. Taylor Brower, Roy Truwit, Jonathon Hite, Duncan Steingrub, Jay Orme, James F., Jr. Clemmer, Terry P. Weaver, Lindell K. Thomas, Frank Grissom, Colin K. Sorenson, Dean Sittig, Dean F. Wallace, C. Jane East, Thomas D. Warner, Homer R. Morris, Alan H. TI The evolution of eProtocols that enable reproducible clinical research and care methods SO JOURNAL OF CLINICAL MONITORING AND COMPUTING LA English DT Article DE Insulin; Decision support; Clinical decision support; Electronic decision support tools; Quality improvement; Intensive care unit glucose control; Integration of clinical decision support programs with electronic medical record; Translation of clinical research into clinical practice ID ACUTE LUNG INJURY; COMPUTERIZED DECISION-SUPPORT; RESPIRATORY-DISTRESS-SYNDROME; INVERSE RATIO VENTILATION; CRITICALLY-ILL PATIENTS; BLOOD-GLUCOSE CONTROL; MECHANICAL VENTILATION; PROTOCOL; OUTCOMES; TRIAL AB Unnecessary variation in clinical care and clinical research reduces our ability to determine what healthcare interventions are effective. Reducing this unnecessary variation could lead to further healthcare quality improvement and more effective clinical research. We have developed and used electronic decision support tools (eProtocols) to reduce unnecessary variation. Our eProtocols have progressed from a locally developed mainframe computer application in one clinical site (LDS Hospital) to web-based applications available in multiple languages and used internationally. We use eProtocol-insulin as an example to illustrate this evolution. We initially developed eProtocol-insulin as a local quality improvement effort to manage stress hyperglycemia in the adult intensive care unit (ICU). We extended eProtocol-insulin use to translate our quality improvement results into usual clinical care at Intermountain Healthcare ICUs. We exported eProtocol-insulin to support research in other US and international institutions, and extended our work to the pediatric ICU. We iteratively refined eProtocol-insulin throughout these transitions, and incorporated new knowledge about managing stress hyperglycemia in the ICU. Based on our experience in the development and clinical use of eProtocols, we outline remaining challenges to eProtocol development, widespread distribution and use, and suggest a process for eProtocol development. Technical and regulatory issues, as well as standardization of protocol development, validation and maintenance, need to be addressed. Resolution of these issues should facilitate general use of eProtocols to improve patient care. C1 [Blagev, Denitza P.] Sorenson Heart Lung Ctr, Pulm Crit Care Div, Murray, UT 84157 USA. [Blagev, Denitza P.; Hirshberg, Eliotte L.; Orme, James F., Jr.; Clemmer, Terry P.; Weaver, Lindell K.; Thomas, Frank; Grissom, Colin K.; Sorenson, Dean; Morris, Alan H.] Intermt Healthcare Urban Cent Reg, Div Pulm, Dept Med, Salt Lake City, UT USA. [Blagev, Denitza P.; Hirshberg, Eliotte L.; Orme, James F., Jr.; Clemmer, Terry P.; Weaver, Lindell K.; Thomas, Frank; Grissom, Colin K.; Sorenson, Dean; Morris, Alan H.] Intermt Healthcare Urban Cent Reg, Crit Care Div, Dept Med, Salt Lake City, UT USA. [Sward, Katherine; Warner, Homer R.] Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA. [Hirshberg, Eliotte L.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Hirshberg, Eliotte L.] Primary Childrens Med Ctr, Pediat Crit Care Div, Salt Lake City, UT 84103 USA. [Sward, Katherine] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Brower, Roy] Johns Hopkins Univ, Baltimore, MD USA. [Truwit, Jonathon] Univ Virginia, Charlottesville, VA USA. [Hite, Duncan] Wake Forest Univ Hlth Sci, Sect Pulm & Crit Care, Winston Salem, NC USA. [Steingrub, Jay] Baystate Med Ctr, Div Crit Care Med, Springfield, MA USA. [Sittig, Dean F.] Univ Texas Mem Hermann, Ctr Healthcare Qual & Safety, Houston, TX USA. [East, Thomas D.] Northshore Univ Hlth Syst, Chicago, IL USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Blagev, DP (reprint author), Sorenson Heart Lung Ctr, Pulm Crit Care Div, 6th Floor Intermt Med Ctr,5121 S Cottonwood St, Murray, UT 84157 USA. EM denitza.blagev@imail.org FU NIH [HL36787, HHSN268200425210C/NO1-HC-45210, HHSN268200425210C/N01-HR-56171, HHSN2682 00536179C/N01-HR-56179, HHSN268200536170C/N01-HR-56170, HHSN268200536175C/N01-HR-56175, HHSN268200536165C/N01-HR-56165]; Deseret Foundation; Intermountain Healthcare, Inc. FX We are indebted to our many RN, RRT, and MD clinician colleagues who enabled the execution of our eProtocol work. Funded in part by the NIH (HL36787, HHSN268200425210C/NO1-HC-45210, HHSN268200425210C/N01-HR-56171, HHSN2682 00536179C/N01-HR-56179, HHSN268200536170C/N01-HR-56170, HHSN268200536175C/N01-HR-56175, HHSN268200536165C/N01-HR-56165), the Deseret Foundation, and Intermountain Healthcare, Inc. NR 57 TC 6 Z9 6 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1387-1307 J9 J CLIN MONIT COMPUT JI J. Clin. Monitor. Comp. PD AUG PY 2012 VL 26 IS 4 BP 305 EP 317 DI 10.1007/s10877-012-9356-y PG 13 WC Anesthesiology SC Anesthesiology GA 970KZ UT WOS:000306128800008 PM 22491960 ER PT J AU Demetriou, SK Ona-Vu, K Teichert, AE Cleaver, JE Bikle, DD Oh, DH AF Demetriou, Stephanie K. Ona-Vu, Katherine Teichert, Arnaud E. Cleaver, James E. Bikle, Daniel D. Oh, Dennis H. TI Vitamin D Receptor Mediates DNA Repair and Is UV Inducible in Intact Epidermis but Not in Cultured Keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID MOUSE SKIN; DOSE UVB; GENE; SUSCEPTIBILITY; EXPRESSION; PROTEIN; MICE C1 [Demetriou, Stephanie K.; Ona-Vu, Katherine; Oh, Dennis H.] San Francisco VA Med Ctr, Dermatol Res Unit, San Francisco, CA 94121 USA. [Demetriou, Stephanie K.; Ona-Vu, Katherine; Cleaver, James E.; Bikle, Daniel D.; Oh, Dennis H.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Teichert, Arnaud E.; Bikle, Daniel D.] San Francisco VA Med Ctr, Endocrine Unit, San Francisco, CA USA. [Bikle, Daniel D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Demetriou, SK (reprint author), San Francisco VA Med Ctr, Dermatol Res Unit, San Francisco, CA 94121 USA. EM ohd@derm.ucsf.edu FU BLRD VA [I01 BX001066]; NIAMS NIH HHS [R01 AR050023, R01AR050023, R01 AR050023-05] NR 15 TC 18 Z9 18 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2012 VL 132 IS 8 BP 2097 EP 2100 DI 10.1038/jid.2012.107 PG 4 WC Dermatology SC Dermatology GA 974CT UT WOS:000306408100024 PM 22495177 ER PT J AU Hirschmann, JV Raugi, GJ AF Hirschmann, Jan V. Raugi, Gregory J. TI Lower limb cellulitis and its mimics Part I. Lower limb cellulitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE beta-hemolytic streptococci; Cryptococcus neoformans; Gram-negative bacilli; lower limb cellulitis; Staphylococcus aureus; Streptococcus pneumoniae ID SOFT-TISSUE INFECTIONS; LOWER-EXTREMITY CELLULITIS; FINE-NEEDLE-ASPIRATION; BETA-HEMOLYTIC STREPTOCOCCI; RANDOMIZED CONTROLLED-TRIAL; GRAM-NEGATIVE CELLULITIS; CORONARY-BYPASS SURGERY; ACUTE LEG CELLULITIS; RECURRENT ERYSIPELAS; RISK-FACTORS AB An aging population and obesity have both contributed to a rising incidence of lower limb cellulitis; the most important predisposing factors include older age, obesity, venous insufficiency, saphenous venectomy, and edema. Streptococci are the most commonly implicated pathogen, and often reside in the interdigital toes spaces. Any disruption of the skin surface can allow the organism to invade. Effective management requires an appropriate antibiotic and attention to the predisposing factors. This article summarizes the epidemiology and treatment of this common infection. (J Am Acad Dermatol 2012; 67: 163. e1-12.) C1 [Raugi, Gregory J.] VA Puget Sound Hlth Care Syst, Dermatol 111D, Dept Dermatol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. RP Raugi, GJ (reprint author), VA Puget Sound Hlth Care Syst, Dermatol 111D, Dept Dermatol, 1660 Columbian Way S, Seattle, WA 98108 USA. EM gregory.raugi@va.gov NR 111 TC 0 Z9 1 U1 2 U2 11 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 AUG PY 2012 VL 67 IS 2 AR 163.e1 DI 10.1016/j.jaad.2012.03.024 PG 12 WC Dermatology SC Dermatology GA 973OD UT WOS:000306368600010 PM 22794815 ER PT J AU Boyer, NM Laskey, WK Cox, M Hernandez, AF Peterson, ED Bhatt, DL Cannon, CP Fonarow, GC AF Boyer, Nathan M. Laskey, Warren K. Cox, Margueritte Hernandez, Adrian F. Peterson, Eric D. Bhatt, Deepak L. Cannon, Christopher P. Fonarow, Gregg C. TI Trends in Clinical, Demographic, and Biochemical Characteristics of Patients With Acute Myocardial Infarction From 2003 to 2008: A Report From the American Heart Association Get With The Guidelines Coronary Artery Disease Program SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE coronary disease; epidemiology; myocardial infarction; population; risk factors ID BODY-MASS INDEX; RISK-FACTORS; US ADULTS; CARDIOVASCULAR HEALTH; METABOLIC SYNDROME; NATIONAL-HEALTH; 52 COUNTRIES; PREVALENCE; MORTALITY; REGISTRY AB Background-An analysis of the changes in the clinical and demographic characteristics of patients with acute myocardial infarction could identify successes and failures of risk factor identification and treatment of patients at increased risk for cardiovascular events. Methods and Results-We reviewed data collected from 138 122 patients with acute myocardial infarction admitted from 2003 to 2008 to hospitals participating in the American Heart Association Get With The Guidelines Coronary Artery Disease program. Clinical, demographic, and laboratory characteristics were analyzed for each year stratified on the electrocardiogram at presentation. Patients with non-ST-segment-elevation myocardial infarction were older, more likely to be women, and more likely to have hypertension, diabetes mellitus, and a history of past cardiovascular disease than were patients with ST-elevation myocardial infarction. In the overall patient sample, significant trends were observed of an increase over time in the proportions of non-ST-segment-elevation myocardial infarction, patient age of 45 to 65 years, obesity, and female sex. The prevalence of diabetes mellitus decreased over time, whereas the prevalences of hypertension and smoking were substantial and unchanging. The prevalence of "low" high-density lipoprotein increased over time, whereas that of "high" low-density lipoprotein decreased. Stratum-specific univariate analysis revealed quantitative and qualitative differences between strata in time trends for numerous demographic, clinical, and biochemical measures. On multivariable analysis, there was concordance between strata with regard to the increase in prevalence of patients 45 to 65 years of age, obesity, and "low" high-density lipoprotein and the decrease in prevalence of "high" low-density lipoprotein. However, changes in trends in age distribution, sex ratio, and prevalence of smokers and the magnitude of change in diabetes mellitus prevalence differed between strata. Conclusions-There were notable differences in risk factors and patient characteristics among patients with ST-elevation myocardial infarction and those with non-ST-segment-elevation myocardial infarction. The increasing prevalence of dysmetabolic markers in a growing proportion of patients with acute myocardial infarction suggests further opportunities for risk factor modification. C1 [Boyer, Nathan M.; Laskey, Warren K.] Univ New Mexico, Albuquerque, NM 87131 USA. [Cox, Margueritte; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Laskey, WK (reprint author), Univ New Mexico, MSC 10-5550, Albuquerque, NM 87131 USA. EM wlaskey@salud.unm.edu FU AHA Pharmaceutical Roundtable; Merck; Robert S. Flinn Endowment for Cardiovascular Medicine (University of New Mexico School of Medicine) FX The GWTG-CAD program was supported, in part, through the AHA Pharmaceutical Roundtable and an unrestricted educational grant from Merck. Drs Boyer and Laskey were supported, in part, by the Robert S. Flinn Endowment for Cardiovascular Medicine (University of New Mexico School of Medicine). NR 37 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2012 VL 1 IS 4 AR UNSP e001206 DI 10.1161/JAHA.112.001206 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243RO UT WOS:000326334800003 PM 23130159 ER PT J AU Hilgendorf, I Swirski, FK AF Hilgendorf, Ingo Swirski, Filip K. TI Folate Receptor: A Macrophage "Achilles' Heel"? SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Editorial Material DE editorials; atherosclerosis; folate; folate receptor; immunotoxins; macrophages ID RHEUMATOID-ARTHRITIS; ACTIVATED MACROPHAGES; BETA; MICE; ATHEROSCLEROSIS; THERAPEUTICS; THROMBOSIS; RATIONALE; PLAQUES; EVENTS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL095612] NR 20 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2012 VL 1 IS 4 AR UNSP e004036 DI 10.1161/JAHA.112.004036 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243RO UT WOS:000326334800013 PM 23130179 ER PT J AU Lin, CB Peterson, ED Smith, EE Saver, JL Liang, L Xian, Y Olson, DM Shah, BR Hernandez, AF Schwamm, LH Fonarow, GC AF Lin, Cheryl B. Peterson, Eric D. Smith, Eric E. Saver, Jeffrey L. Liang, Li Xian, Ying Olson, DaiWai M. Shah, Bimal R. Hernandez, Adrian F. Schwamm, Lee H. Fonarow, Gregg C. TI Patterns, Predictors, Variations, and Temporal Trends in Emergency Medical Service Hospital Prenotification for Acute Ischemic Stroke SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE stroke; emergency medicine; hospitals; registries ID TISSUE-PLASMINOGEN ACTIVATOR; QUALITY-OF-CARE; PREHOSPITAL NOTIFICATION; ASSOCIATION; GUIDELINES; STATEMENT; OUTCOMES; MANAGEMENT; COUNCIL; PROGRAM AB Background-Emergency medical services (EMS) hospital prenotification of an incoming stroke patient is guideline recommended as a means of increasing the timeliness with which stroke patients are evaluated and treated. Still, data are limited with regard to national use of, variations in, and temporal trends in EMS prenotification and associated predictors of its use. Methods and Results-We examined 371 988 patients with acute ischemic stroke who were transported by EMS and enrolled in 1585 hospitals participating in Get With The Guidelines-Stroke from April 1, 2003, through March 31, 2011. Prenotification occurred in 249 197 EMS-transported patients (67.0%) and varied widely by hospital (range, 0% to 100%). Substantial variations by geographic regions and by state, ranging from 19.7% in Washington, DC, to 93.4% in Montana, also were noted. Patient factors associated with lower use of prenotification included older age, diabetes mellitus, and peripheral vascular disease. Prenotification was less likely for black patients than for white patients (adjusted odds ratio 0.94, 95% confidence interval 0.92-0.97, P<0.0001). Hospital factors associated with greater EMS prenotification use were absence of academic affiliation, higher annual volume of tissue plasminogen activator administration, and geographic location outside the Northeast. Temporal improvements in prenotification rates showed a modest general increase, from 58.0% in 2003 to 67.3% in 2011 (P temporal trend <0.0001). Conclusions-EMS hospital prenotification is guideline recommended, yet among patients transported to Get With The Guidelines-Stroke hospitals it is not provided for 1 in 3 EMS-arriving patients with acute ischemic stroke and varies substantially by hospital, state, and region. These results support the need for enhanced implementation of stroke systems of care. C1 [Lin, Cheryl B.] Duke Natl Univ Singapore, Singapore, Singapore. [Peterson, Eric D.; Liang, Li; Xian, Ying; Olson, DaiWai M.; Shah, Bimal R.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Fonarow, GC (reprint author), Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, 10833 LeConte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu FU Bristol-Myers Squibb / Sanofi Pharmaceuticals Partnership; AHA Pharmaceutical Roundtable; Boehringer Ingelheim; Merck FX The GWTG-Stroke program is provided by the AHA/ASA. The GWTG-Stroke program currently is supported in part by a charitable contribution from the Bristol-Myers Squibb / Sanofi Pharmaceuticals Partnership and the AHA Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer Ingelheim and Merck. NR 21 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2012 VL 1 IS 4 AR UNSP e002345 DI 10.1161/JAHA.112.002345 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243RO UT WOS:000326334800017 PM 23130167 ER PT J AU Wisco, BE Marx, BP Keane, TM AF Wisco, Blair E. Marx, Brian P. Keane, Terence M. TI Screening, Diagnosis, and Treatment of Post-Traumatic Stress Disorder SO MILITARY MEDICINE LA English DT Article AB Post-traumatic stress disorder (PTSD) is a prevalent problem among military personnel and veterans. Identification of effective screening tools, diagnostic technologies, and treatments for PTSD is essential to ensure that all individuals in need of treatment are offered interventions with proven efficacy. Well-validated methods for screening and diagnosing PTSD are now available, and effective pharmacological and psychological treatments can be offered. Despite these advances, many military personnel and veterans do not receive evidence-based care. We review the literature on screening, diagnosis, and treatment of PTSD in military populations, and discuss the challenges to implementing the best evidence-based practices in clinical settings. C1 [Wisco, Blair E.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02130 USA. RP Wisco, BE (reprint author), VA Boston Healthcare Syst, VA Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. NR 56 TC 9 Z9 9 U1 3 U2 9 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD AUG PY 2012 VL 177 IS 8 SU S SI SI BP 7 EP 13 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA V33OB UT WOS:000209027000003 PM 22953436 ER PT J AU Hawkins, EJ Grossbard, J Benbow, J Nacev, V Kivlahan, DR AF Hawkins, Eric J. Grossbard, Joel Benbow, Jim Nacev, Vladimir Kivlahan, Daniel R. TI Evidence-Based Screening, Diagnosis, and Treatment of Substance Use Disorders Among Veterans and Military Service Personnel SO MILITARY MEDICINE LA English DT Article AB Substance use disorders (SUDs) are among the most common and costly conditions in veterans and active duty military personnel, adversely affecting their health and occupational and personal functioning. The pervasive burden of SUD has been a continuing concern for the Department of Veterans Affairs (VA) and Department of Defense (DoD), particularly as large numbers of service members return from Operations Enduring and Iraqi Freedom. The VA and DoD have prioritized implementation of evidence-based practices and treatment services to enhance the recognition and management of SUD in general medical and SUD specialty-care settings. This article summarizes the clinical practice guidelines for identifying, diagnosing, and treating SUD in VA and DoD general medical and SUD specialty-care settings, highlights evidence-based pharmacotherapy and psychosocial interventions for managing SUD, and describes barriers to successful treatment of veterans and service members at risk for SUD in VA and DoD health care systems. C1 [Hawkins, Eric J.; Grossbard, Joel; Benbow, Jim; Kivlahan, Daniel R.] VA Puget Sound Healthcare Syst, Ctr Excellence Substance Abuse Treatment & Educ, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Nacev, Vladimir] Def Ctr Excellence Psychol Hlth & Traumat Brain I, Resilience & Prevent Directorate, Silver Spring, MD 20910 USA. RP Hawkins, EJ (reprint author), VA Puget Sound Healthcare Syst, Ctr Excellence Substance Abuse Treatment & Educ, Hlth Serv Res & Dev, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 75 TC 9 Z9 9 U1 2 U2 5 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD AUG PY 2012 VL 177 IS 8 SU S SI SI BP 29 EP 38 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA V33OB UT WOS:000209027000006 PM 22953439 ER PT J AU Tollison, SJ Henderson, RC Baer, JS Saxon, AJ AF Tollison, Sean J. Henderson, Ryan C. Baer, Johns S. Saxon, Andrew J. TI Next Steps in Addressing the Prevention, Screening, and Treatment of Substance Use Disorder in Active Duty and Veteran Operation Enduring Freedom and Operation Iraqi Freedom Populations SO MILITARY MEDICINE LA English DT Article AB The two articles presented previously in this volume provide state-of-the-art reviews of the etiology, epidemiology, screening and treatment of substance use disorder (SUD). This article identifies next steps in research and development for understanding and treating SUD in Operation Enduring Freedom/Operation Iraqi Freedom service members and veterans. Four promising areas are reviewed: advances in psychopharmacological treatment of SUD, innovations in behavioral treatments, the use of technological advances for the screening and treatment of SUD, and integration of treatment services. Future directions are explored and suggestions for research, development and implementation of each of these trends are discussed. C1 [Tollison, Sean J.; Henderson, Ryan C.; Baer, Johns S.; Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA 98108 USA. RP Tollison, SJ (reprint author), VA Puget Sound Hlth Care Syst, CESATE, 1660 South Columbian Way, Seattle, WA 98108 USA. FU Center of Excellence in Substance Abuse Treatment and Education at VA Puget Sound Health Care System; Research and Development Service, Department of Veterans Affairs FX This work was supported by the Center of Excellence in Substance Abuse Treatment and Education at VA Puget Sound Health Care System and by the Research and Development Service, Department of Veterans Affairs. NR 68 TC 1 Z9 1 U1 2 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD AUG PY 2012 VL 177 IS 8 SU S SI SI BP 39 EP 46 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA V33OB UT WOS:000209027000007 PM 22953440 ER PT J AU Yoder, JS Verani, J Heidman, N Hoppe-Bauer, J Alfonso, EC Miller, D Jones, DB Bruckner, D Langston, R Jeng, BH Joslin, CE Tu, E Colby, K Vetter, E Ritterband, D Mathers, W Kowalski, RP Acharya, NR Limaye, AP Leiter, C Roy, S Lorick, S Roberts, J Beach, MJ AF Yoder, Jonathan S. Verani, Jennifer Heidman, Nancy Hoppe-Bauer, Joan Alfonso, Eduardo C. Miller, Darlene Jones, Dan B. Bruckner, David Langston, Roger Jeng, Bennie H. Joslin, Charlotte E. Tu, Elmer Colby, Kathryn Vetter, Emily Ritterband, David Mathers, William Kowalski, Regis P. Acharya, Nisha R. Limaye, Ajit P. Leiter, Charles Roy, Sharon Lorick, Suchita Roberts, Jacquelin Beach, Michael J. TI Acanthamoeba keratitis: The Persistence of Cases Following a Multistate Outbreak SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE Acanthamoeba keratitis; Surveillance; Epidemiology; Contacts lens; Outbreak ID CONTACT-LENS SOLUTION; WATER; PREVALENCE; AMEBAS AB Purpose: To describe the trend of Acanthamoeba keratitis case reports following an outbreak and the recall of a multipurpose contact lens disinfection solution. Acanthamoeba keratitis is a serious eye infection caused by the free-living amoeba Acanthamoeba that primarily affects contact lens users. Methods: A convenience sample of 13 ophthalmology centers and laboratories in the USA, provided annual numbers of Acanthamoeba keratitis cases diagnosed between 1999-2009 and monthly numbers of cases diagnosed between 2007-2009. Data on ophthalmic preparations of anti-Acanthamoeba therapies were collected from a national compounding pharmacy. Results: Data from sentinel site ophthalmology centers and laboratories revealed that the yearly number of cases gradually increased from 22 in 1999 to 43 in 2003, with a marked increase beginning in 2004 (93 cases) that continued through 2007 (170 cases; p < 0.0001). The outbreak identified from these sentinel sites resulted in the recall of a contact lens disinfecting solution. There was a statistically significant (p <= 0.0001) decrease in monthly cases reported from 28 cases in June 2007 (following the recall) to seven cases in June 2008, followed by an increase (p = 0.0004) in reported cases thereafter; cases have remained higher than pre-outbreak levels. A similar trend was seen in prescriptions for Acanthamoeba keratitis chemotherapy. Cases were significantly more likely to be reported during summer than during other seasons. Conclusion: The persistently elevated number of reported cases supports the need to understand the risk factors and environmental exposures associated with Acanthamoeba keratitis. Further prevention efforts are needed to reduce the number of cases occurring among contact lens wearers. C1 [Yoder, Jonathan S.; Verani, Jennifer; Roy, Sharon; Lorick, Suchita; Roberts, Jacquelin; Beach, Michael J.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Hoppe-Bauer, Joan] Barnes Jewish Hosp, St Louis, MO USA. [Alfonso, Eduardo C.; Miller, Darlene] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Coral Gables, FL 33124 USA. [Jones, Dan B.] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. [Jones, Dan B.] Baylor Coll Med, Cullen Eye Inst, Houston, TX 77030 USA. [Bruckner, David] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Langston, Roger; Jeng, Bennie H.] Cleveland Clin, Cole Eye Inst, Cleveland, OH USA. [Joslin, Charlotte E.; Tu, Elmer] Univ Illinois, Chicago, IL USA. [Colby, Kathryn] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Vetter, Emily] Mayo Clin, Rochester, MN USA. [Ritterband, David] New York Eye & Ear Infirm, New York, NY USA. [Mathers, William] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kowalski, Regis P.] Univ Pittsburgh, Med Ctr, Charles T Campbell Lab, Pittsburgh, PA 15260 USA. [Acharya, Nisha R.] Univ Calif San Francisco, Proctor Fdn, San Francisco, CA 94143 USA. [Jeng, Bennie H.; Limaye, Ajit P.] Univ Washington, Seattle, WA 98195 USA. [Leiter, Charles] Leiters Pharm, San Jose, CA USA. RP Yoder, JS (reprint author), 1600 Clifton Rd NE,MS C-09, Atlanta, GA 30333 USA. EM jyoder@cdc.gov RI Miller, Darlene /C-9053-2013; OI Ritterband, David/0000-0001-7139-878X FU FDA; NEI FX No authors are employed by corporations financially impacted by the results reported in this manuscript. Some authors are employed by the US Government and some authors receive funding from FDA and NEI. Some authors report consulting fees for Bausch and Lomb, BioTissue, Foresight, VisionCare, Inspire, Kimberly Clark, Alcon, Santen, Crofessionals; lecture fees for Alcon; and royalties from Roche Diagnostics. Detailed information is available on request. NR 20 TC 31 Z9 32 U1 1 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD AUG PY 2012 VL 19 IS 4 BP 221 EP 225 DI 10.3109/09286586.2012.681336 PG 5 WC Ophthalmology SC Ophthalmology GA 971GH UT WOS:000306191300008 PM 22775278 ER PT J AU Hyle, EP Shu, B Lindstrom, S Klimov, A Hancock, K Ferraro, MJ Traum, AZ Michelow, IC AF Hyle, Emily P. Shu, Bo Lindstrom, Stephen Klimov, Alexander Hancock, Kathy Ferraro, Mary J. Traum, Avram Z. Michelow, Ian C. TI A severely immunocompromised child with uncomplicated oseltamivir-resistant 2009 H1N1 pandemic influenza infection SO PEDIATRIC TRANSPLANTATION LA English DT Article DE viral infection; kidney transplant; immunosuppression ID VIRUS AB Hyle EP, Shu B, Lindstrom S, Klimov A, Hancock K, Ferraro MJ, Traum AZ, Michelow IC. A severely immunocompromised child with uncomplicated oseltamivir-resistant 2009 H1N1 pandemic influenza infection. Abstract: 2009 H1N1 pandemic influenza was associated with increased risk for severe disease in children and the immunosuppressed. We report a case of uncomplicated pneumonia because of infection with oseltamivir-resistant 2009 H1N1 virus in an immunosuppressed pediatric renal transplant patient. Innate immunity and/or altered viral fitness may be responsible for the mild clinical phenotype of the case. C1 [Hyle, Emily P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Shu, Bo; Lindstrom, Stephen; Klimov, Alexander; Hancock, Kathy] Ctr Dis Control, Atlanta, GA 30333 USA. [Ferraro, Mary J.; Traum, Avram Z.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Michelow, Ian C.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Hyle, EP (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM ehyle@partners.org NR 10 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD AUG PY 2012 VL 16 IS 5 BP E158 EP E161 DI 10.1111/j.1399-3046.2011.01490.x PG 4 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 970LW UT WOS:000306131700006 PM 21429059 ER PT J AU Fu, SN Fan, J Blanco, J Gimenez-Cassina, A Danial, NN Watkins, SM Hotamisligil, GS AF Fu, Suneng Fan, Jason Blanco, Joshua Gimenez-Cassina, Alfredo Danial, Nika N. Watkins, Steve M. Hotamisligil, Goekhan S. TI Polysome Profiling in Liver Identifies Dynamic Regulation of Endoplasmic Reticulum Translatome by Obesity and Fasting SO PLOS GENETICS LA English DT Article ID FARNESOID-X-RECEPTOR; RAT SKELETAL-MUSCLE; BILE-ACID SYNTHESIS; PROTEIN-SYNTHESIS; MESSENGER-RNA; GLUCOSE-HOMEOSTASIS; INSULIN-TREATMENT; MAMMALIAN TARGET; DIABETIC-RATS; AMINO-ACIDS AB Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER)-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation. We discovered that ER from livers of obese mice exhibits a general reduction in protein synthesis, and comprehensive analysis of polysome-bound transcripts revealed extensive down-regulation of protein synthesis machinery, mitochondrial components, and bile acid metabolism in the obese translatome. Nutrient availability also plays an important but distinct role in remodeling the hepatic ER translatome in lean and obese mice. Fasting in obese mice partially reversed the overall translatomic differences between lean and obese nonfasted controls, whereas fasting of the lean mice mimicked many of the translatomic changes induced by the development of obesity. The strongest examples of such regulations were the reduction in Cyp7b1 and Slco1a1, molecules involved in bile acid metabolism. Exogenous expression of either gene significantly lowered plasma glucose levels, improved hepatic steatosis, but also caused cholestasis, indicating the fine balance bile acids play in regulating metabolism and health. Together, our work defines dynamic regulation of the liver translatome by obesity and nutrient availability, and it identifies a novel role for bile acid metabolism in the pathogenesis of metabolic abnormalities associated with obesity. C1 [Fu, Suneng; Fan, Jason; Blanco, Joshua; Watkins, Steve M.; Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Fu, Suneng; Fan, Jason; Blanco, Joshua; Watkins, Steve M.; Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Gimenez-Cassina, Alfredo; Danial, Nika N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hotamisligil, Goekhan S.] Broad Inst Harvard & MIT, Boston, MA USA. RP Fu, SN (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM ghotamis@hsph.harvard.edu OI Gimenez-Cassina, Alfredo/0000-0002-2768-2350 FU National Institutes of Health [DK52539, 1RC4-DK090942, R01DK078081]; NIH/NIEHS [T32ES007155]; Naomi Berrie fellowship award FX This work is supported in part by grants from the National Institutes of Health to GSH (DK52539 and 1RC4-DK090942) and NND (R01DK078081). SF was supported in part by the NIH/NIEHS postdoctoral training grant (T32ES007155) and currently the recipient of the Naomi Berrie fellowship award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 21 Z9 21 U1 3 U2 12 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 AUG PY 2012 VL 8 IS 8 AR e1002902 DI 10.1371/journal.pgen.1002902 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 002JX UT WOS:000308529300056 PM 22927828 ER PT J AU Zhang, XY Chen, DC Xiu, MH Tang, W Zhang, FX Liu, LJ Chen, YL Liu, JH Yao, JK Kosten, TA Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Xiu, Mei Hong Tang, Wei Zhang, Feixue Liu, LianJing Chen, Yuanling Liu, JiaHong Yao, Jeffrey K. Kosten, Therese A. Kosten, Thomas R. TI Plasma total antioxidant status and cognitive impairments in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Cognition; Oxidative stress; Psychopathology ID SUPEROXIDE DISMUTASE/CATALASE MIMETICS; BRAIN OXIDATIVE STRESS; FREE-RADICAL PATHOLOGY; AGE-RELATED-CHANGES; NEUROPSYCHOLOGICAL PROFILES; THERAPEUTIC IMPLICATIONS; REPEATABLE BATTERY; TARDIVE-DYSKINESIA; LIPID-PEROXIDATION; DIFFERENT FORMS AB Oxidative stress-induced damage to neurons may contribute to cognitive deficits during aging and in neurodegenerative disorders. Schizophrenia has a range of cognitive deficits that may evolve from oxidative stress, and this study examines this association of oxidative stress with cognitive deficits in schizophrenia. We recruited 296 chronic schizophrenia patients and 181 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and plasma total antioxidant status (TAS) in both groups. Schizophrenia symptoms were assessed using the positive and negative syndrome scale (PANSS). Our results showed that TAS levels were significantly lower in patients than controls (179.6 +/- 81.0 U/ml vs. 194.8 +/- 46.0 U/ml, p<0.05). Cognitive scores on the RBANS and nearly all of its five subscales (all p<0.001) except for the Visuospatial/Constructional index (p>0.05) were significantly lower in schizophrenia patients than normal controls. For the patients, TAS was inversely associated with some domains of cognitive deficits in schizophrenia, such as Attention and Immediate Memory. Our findings suggest that oxidative stress may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment. (C) 2012 Elsevier B.V. All rights reserved. C1 [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; Kosten, Thomas R.] Beijing Hui Long Guan Hosp, Psychiat Res Ctr, Beijing, Peoples R China. [Tang, Wei; Zhang, Feixue; Liu, LianJing; Chen, Yuanling; Liu, JiaHong] Kangning Hosp, Dept Psychiat, Wenzhou, Zhejiang, Peoples R China. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs; VISN 16; Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX Funding for this study was provided by grants from the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VA Senior Research Career Scientist Award (JKY), VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. These sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The contents of this article do not represent the views of the VA or the United States Government. NR 71 TC 27 Z9 28 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2012 VL 139 IS 1-3 BP 66 EP 72 DI 10.1016/j.schres.2012.04.009 PG 7 WC Psychiatry SC Psychiatry GA 970JO UT WOS:000306124400011 PM 22555016 ER PT J AU Lin, YC Wynn, JK Hellemann, G Green, MF AF Lin, Yu-chung Wynn, Jonathan K. Hellemann, Gerhard Green, Michael F. TI Factor structure of emotional intelligence in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; MSCEIT; Emotional intelligence; Factor analysis ID PSYCHIATRIC RATING-SCALE; QUALITY-ASSURANCE; SOCIAL COGNITION AB Social cognition, which includes emotional intelligence, is impaired in schizophrenia. The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) is a widely-used assessment of emotional intelligence, with a four-factor structure in healthy individual. However, a recent factor analysis in schizophrenia patients revealed a two-factor structure of the MSCEIT. The current study aimed to replicate this finding in a larger, more diverse, schizophrenia sample (n=194). Our findings revealed an identical two-factor structure as in the previously-reported study, indicating that emotional intelligence is organized in a different manner in schizophrenia than it is in healthy controls. Published by Elsevier B.V. C1 [Wynn, Jonathan K.; Green, Michael F.] MIRECC, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Hellemann, Gerhard; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Lin, Yu-chung] China Med Univ, Grad Inst Clin Med Sci, Taichung, Taiwan. RP Wynn, JK (reprint author), MIRECC, VA Greater Los Angeles Healthcare Syst, Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [MH043292] FX Funding for this study was provided by the National Institute of Mental Health grant MH043292 to Michael F. Green. The funding agency had no further role in the analysis or interpretation of data, in writing the report, or in the decision to submit the paper for publication. NR 19 TC 9 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2012 VL 139 IS 1-3 BP 78 EP 81 DI 10.1016/j.schres.2012.04.013 PG 4 WC Psychiatry SC Psychiatry GA 970JO UT WOS:000306124400013 PM 22584064 ER PT J AU Galvez-Buccollini, JA Proal, AC Tomaselli, V Trachtenberg, M Coconcea, C Chun, J Manschreck, T Fleming, J Delisi, LE AF Galvez-Buccollini, Juan A. Proal, Ashley C. Tomaselli, Veronica Trachtenberg, Melissa Coconcea, Cristinel Chun, Jinsoo Manschreck, Theo Fleming, Jerry Delisi, Lynn E. TI Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Cannabis; Psychosis; Age; Sex; Schizophrenia ID SUBSTANCE USE; SCHIZOPHRENIA AB Introduction: Several studies have associated cannabis use with the development of schizophrenia. However, it has been difficult to disentangle the effects of cannabis from that of other illicit drugs, as previous studies have not evaluated pure cannabis users. To test whether the onset of cannabis use had an effect on the initiation of psychosis, we examined the time relationship between onset of use and onset of psychosis, restricting our analysis to a cohort of individuals who only used cannabis and no other street drugs. Methods: Fifty-seven subjects with non-affective psychoses who used cannabis prior to developing a psychosis were interviewed using the Diagnostic Interview for Genetic Studies (DIGS). The Family Interview for Genetic Studies (FIGS) was also used to interview a family informant about psychiatric illness in the patient and the entire family. Multiple linear regression techniques were used to estimate the association between variables. Results: After adjusting for potential confounding factors such as sex, age, lifetime diagnosis of alcohol abuse or dependence, and family history of schizophrenia, the age at onset of cannabis was significantly associated with age at onset of psychosis (beta=0.4, 95% CI=0.1-0.7, p=0.004) and age at first hospitalization (beta=0.4, 95% CI=0.1-0.8, p=0.008). The mean time between beginning to use cannabis and onset of psychosis was 7.0 +/- 4.3. Age at onset of alcohol use was not associated with age at onset of psychosis or age at first hospitalization. Conclusion: Age at onset of cannabis is directly associated with age at onset of psychosis and age at first hospitalization. These associations remain significant after adjusting for potential confounding factors and are consistent with the hypothesis that cannabis could cause or precipitate the onset of psychosis after a prolonged period of time. Published by Elsevier B.V. C1 [Galvez-Buccollini, Juan A.; Proal, Ashley C.; Fleming, Jerry; Delisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Galvez-Buccollini, Juan A.; Delisi, Lynn E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tomaselli, Veronica] Columbia Univ, St Lukes Roosevelt Hosp, New York, NY 10027 USA. [Tomaselli, Veronica; Trachtenberg, Melissa; Delisi, Lynn E.] NYU, Langone Sch Med, New York, NY 10016 USA. [Coconcea, Cristinel; Chun, Jinsoo; Manschreck, Theo] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Galvez-Buccollini, JA (reprint author), VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM Juan_Galvez-Buccollini@hms.harvard.edu; Ashley_Proal@hms.harvard.edu; veronica.tomaselli@gmail.com; ccoconce@bidmc.harvard.edu; jchun1@bidmc.harvard.edu; manschreck@aol.com; Jerry.Fleming@va.gov; Lynn.DeLisi@VA.gov FU National Institute of Drug Abuse [R01 DA 021576]; NIH, NIDA [R01 DA 021576] FX This project was funded through the National Institute of Drug Abuse (R01 DA 021576; LE DeLisi, P.I.).; Funding for this study was provided by NIH, NIDA (R01 DA 021576). The funding agency played no role in the direction of this project. NR 14 TC 29 Z9 29 U1 2 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 AUG PY 2012 VL 139 IS 1-3 BP 157 EP 160 DI 10.1016/j.schres.2012.06.007 PG 4 WC Psychiatry SC Psychiatry GA 970JO UT WOS:000306124400025 PM 22727454 ER PT J AU Holman, KM Wolff, M Sena, AC Martin, DH Behets, F Van Damme, K Leone, P McNeil, L Gehrig, ML Hook, EW AF Holman, Katherine M. Wolff, Mark Sena, Arlene C. Martin, David H. Behets, Frieda Van Damme, Kathleen Leone, Peter McNeil, Linda Gehrig, Meredyth L. Hook, Edward W., III TI Rapid Plasma Reagin Titer Variation in the 2 Weeks After Syphilis Therapy SO SEXUALLY TRANSMITTED DISEASES LA English DT Article AB Background: Serologic tests for syphilis results at the time of diagnosis are the basis for evaluating response to syphilis therapy. After treatment, however, serologic tests for syphilis titers may continue to increase for several weeks. We evaluated rapid plasma reagin (RPR) titer variation during the 14 days after therapy using data from a recent large, prospective randomized controlled trial. Methods: Prospectively enrolled participants in North America and Madagascar with primary, secondary, or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy), or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 posttreatment. All RPR titers were determined simultaneously at a central laboratory. Results: Four hundred and seventy patients had data available for at least 2 of 3 RPR measurements. Overall, 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy. The greatest proportion of titer increases following therapy was observed in patients with primary syphilis. Comparing outcome of therapy using the initial (day 0) RPR titer versus the maximal RPR titer (during 14 days) resulted in outcome reclassification in 2.98% of participants. Conclusions: Despite the fact that about 20% of early syphilis patients had increases in RPR titers immediately after treatment, these changes rarely influenced assessment of therapeutic outcome. Only 3% of patients treated would have been reclassified. C1 [Holman, Katherine M.; Hook, Edward W., III] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA. [Holman, Katherine M.] Birmingham VA Med Ctr, Dept Qual Management, Birmingham, AL USA. [Wolff, Mark; Gehrig, Meredyth L.] Emmes Corp, Rockville, MD USA. [Sena, Arlene C.; Behets, Frieda; Leone, Peter] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA. [Martin, David H.] Louisiana State Univ, Div Infect Dis, Dept Med, Baton Rouge, LA 70803 USA. [Behets, Frieda; Van Damme, Kathleen] Univ N Carolina Madagascar, Dept Med, Antananarivo, Madagascar. [Behets, Frieda; Van Damme, Kathleen] Univ N Carolina Madagascar, Dept Epidemiol, Antananarivo, Madagascar. [McNeil, Linda] Family Hlth Int, Res Triangle Pk, NC 27709 USA. RP Holman, KM (reprint author), Univ Alabama Birmingham, Div Infect Dis, Dept Med, 1900 Univ Blvd,THT 229, Birmingham, AL 35294 USA. EM holmkm@uab.edu; ehook@uab.edu FU National Institute of Allergy and Infectious Diseases at the National Institutes of Health [N01 A1 75329]; STI Clinical Trials Group [HHSN 26620040073C]; GSK; Abbott Diagnostics; Norvartis; Trinity Diagnostics; GenProbe; Becton-Dickinson; Roche Molecular Diagnostics; Siemens Diagnostics FX Supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grant number N01 A1 75329, Myron Cohen, MD, PI) and the STI Clinical Trials Group (grant number HHSN 26620040073C, Edward W. Hook, III, MD, PI).; K.H., M. W., A. S., F. B., K. V. D, L. M., and M. G. declare no conflict of interest. D. M. is a share holder in Merck and has been a consultant to Cempra Pharma. P. L. has received research funding from GSK, Abbott Diagnostics, Norvartis and Trinity Diagnostics and has been on the speakers' bureaus for GSK, Norvartis and Abbott Diagnostics. E. W. has received research funding from GenProbe, Becton-Dickinson, Roche Molecular Diagnostics, Siemens Diagnostics, and has been on the speakers' bureaus for GSK, Norvartis and Abbott Diagnostics. NR 7 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD AUG PY 2012 VL 39 IS 8 BP 645 EP 647 DI 10.1097/OLQ.0b013e3182536574 PG 3 WC Infectious Diseases SC Infectious Diseases GA 974FA UT WOS:000306414300013 PM 22801348 ER PT J AU Lohmann, AE Saini, KS Metzger, O AF Lohmann, Ana Elisa Saini, Kamal S. Metzger-Filho, Otto TI Pertuzumab in metastatic breast cancer: unanswered questions SO TRANSLATIONAL CANCER RESEARCH LA English DT Article C1 [Lohmann, Ana Elisa] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Saini, Kamal S.] Inst Jules Bordet, Breast Int Grp, B-1000 Brussels, Belgium. [Metzger-Filho, Otto] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Lohmann, AE (reprint author), BC Canc Agcy, 600 W,10th Ave, Vancouver, BC V5Z 4E6, Canada. EM ana.lohmann@bccancer.bc.ca NR 13 TC 2 Z9 2 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-676X EI 2219-6803 J9 TRANSL CANCER RES JI Transl. Cancer Res. PD AUG PY 2012 VL 1 IS 2 BP 122 EP 124 DI 10.3978/j.issn.2218-676X.2012.04.03 PG 3 WC Oncology SC Oncology GA V42VZ UT WOS:000209642600010 ER PT J AU Juillerat, P Schneeweiss, S Cook, EF Ananthakrishnan, AN Mogun, H Korzenik, JR AF Juillerat, P. Schneeweiss, S. Cook, E. F. Ananthakrishnan, A. N. Mogun, H. Korzenik, J. R. TI Drugs that inhibit gastric acid secretion may alter the course of inflammatory bowel disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROTON PUMP INHIBITORS; CROHNS-DISEASE; RISK-FACTOR; OMEPRAZOLE; GASTROENTERITIS; CIMETIDINE; RECEPTORS; HISTAMINE; DESIGN; SCORES AB Background Recent data suggest that acid suppressive medications may alter factors central to the pathophysiology of inflammatory bowel diseases (IBD), whether through shifts in the intestinal microbiome due to acid suppression or effects on immune function. Aim To assess the relationship between the use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2Ra) and incidence of flares (hospitalisation/surgery and change in medication). Methods We conducted a new user cohort study including individuals diagnosed with IBD in British Columbia using linked healthcare utilisation databases (available from July 1996 through April 2006). Propensity-score matched incidence rates during a 6-month follow-up period and rate ratios (RR) and 95% CI were calculated. Results Among 16 151 IBD patients, 1307 Crohn's disease (CD) and 996 ulcerative colitis (UC) patients experienced a new use of PPIs, whereas 741 CD and 738 UC used H2Ra. All IBD subgroups were matched separately to an equal number of unexposed IBD patients. H2Ra use in CD doubled the risk of hospitalisation/surgery (RR = 1.94; 95%CI 1.243.10) and numerically less so in UC patients (RR = 1.11) with widely overlapping CIs (0.612.03). Proton pump inhibitors use was associated with medication change in UC (RR = 1.39; 95%CI 1.201.62), but without meaningfully, increased risk of hospitalisation/surgery for UC or CD patients. Extending follow-up showed persistence, but attenuation, of all effects. Conclusions Initiation of PPIs or H2Ra may be associated with short-term changes in the course of IBD. Although confounding by indication was adjusted using propensity score matching, residual confounding may persist and findings need to be interpreted cautiously. C1 [Juillerat, P.; Ananthakrishnan, A. N.; Korzenik, J. R.] Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Dept Gastroenterol & Hepatol, Boston, MA 02114 USA. [Juillerat, P.; Schneeweiss, S.; Ananthakrishnan, A. N.; Mogun, H.; Korzenik, J. R.] Harvard Univ, Sch Med, Boston, MA USA. [Juillerat, P.] Inselspital Bern, Univ Hosp, Div Gastroenterol, Clin Visceral Surg & Med, CH-3010 Bern, Switzerland. [Schneeweiss, S.; Mogun, H.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol, Boston, MA 02115 USA. [Cook, E. F.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Juillerat, P (reprint author), Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Dept Gastroenterol & Hepatol, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM pjuillerat@partners.org RI Schneeweiss, Sebastian/C-2125-2013 FU Swiss National Science Foundation (SNF) [PBLAP3-124341]; Foundation for Clinical Research in Inflammatory Bowel Diseases, New York City; National Institutes of Health [RO1-LM010213, RC1-RR028231] FX Declaration of personal interests: Dr Schneeweiss has received an investigator-initiated research grant from Pfizer on the safety of selective cox-2 inhibitors. Dr Korzenik has been a consultant for Procter and Gamble, Shire Pharmaceuticals, CytokinePharma, and receives research support from Procter and Gamble and Warner Chilcott. We gratefully acknowledge the contribution of Susan Giddons for editorial assistance. Declaration of funding interests: This study was supported by the Swiss National Science Foundation (SNF) (grant number PBLAP3-124341) and the Foundation for Clinical Research in Inflammatory Bowel Diseases, New York City (http://www.myIBD.org) with additional support from the National Institutes of Health to Dr Schneeweiss (grant number RO1-LM010213, RC1-RR028231). NR 35 TC 8 Z9 9 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD AUG PY 2012 VL 36 IS 3 BP 239 EP 247 DI 10.1111/j.1365-2036.2012.05173.x PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 966FW UT WOS:000305824200004 PM 22670722 ER PT J AU Richter, JM Kushkuley, S Barrett, JA Oster, G AF Richter, J. M. Kushkuley, S. Barrett, J. A. Oster, G. TI Treatment of new-onset ulcerative colitis and ulcerative proctitis: a retrospective study SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; PRACTICE GUIDELINES; MESALAZINE; MAINTENANCE; MANAGEMENT; THERAPY; COHORT AB Background Although guidelines recommend use of oral 5-aminosalicylates (5-ASAs) as first-line therapy in patients with mild to moderate ulcerative colitis (UC) and ulcerative proctitis (UP) and steroids with or without 5-ASAs in those more severely ill, little is known about how UC and UP are actually treated. Aim To document treatment of new-onset UC and UP in routine clinical practice. Methods Using a large US health insurance database, we identified all persons with new-onset UC or UP between 1 January 2005 and 31 December 2007, based on: (i) initial receipt of an oral 5ASA, mesalazine (mesalamine) suppository, 5-ASA enema, steroid, antimetabolite, budesonide or TNF inhibitor; (ii) sigmoidoscopy/colonoscopy in prior 30 days resulting in a new diagnosis of UC or UP and (iii) no prior encounters for Crohn's disease. We examined patterns of pharmacotherapy over 1 year. Results We identified 1516 UC patients and 636 UP patients who met study entry criteria. In UC, initial therapies most frequently used were oral 5-ASAs (53% of patients), oral 5-ASAs and systemic steroids (12%), systemic steroids (8%) and mesalazine suppositories (6%); in UP, mesalazine suppositories (42%) and oral 5-ASAs (19%) were most often used, followed by combination therapy (14%), mesalazine enema (11%) and rectal steroids (10%). Few patients received maintenance therapy, and there was limited use of antimetabolites and biological agents. Conclusions Oral 5-ASAs and systemic steroids are the mainstay of treatment in patients with new-onset ulcerative colitis; in those with new-onset ulcerative proctitis, it is mesalazine suppositories. Care of these patients appears consistent with treatment guidelines. C1 [Kushkuley, S.; Oster, G.] Policy Anal Inc, Brookline, MA 02445 USA. [Barrett, J. A.] Aptalis Pharma Inc, Mt St Hilaire, PQ, Canada. [Richter, J. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richter, J. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Oster, G (reprint author), Policy Anal Inc, 4 Davis Court, Brookline, MA 02445 USA. EM goster@pai2.com FU Donaldson Foundation; Aptalis FX Declaration of personal interests: James M. Richter has served as a consultant to the US Department of Justice and Policy Analysis Inc., and has received research funding from the Donaldson Foundation. He is an employee of the Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Sophie Kushkuley is a graduate student at Brandeis University, and was an employee of Policy Analysis Inc. at the time the study was conducted. Jeannette A. Barrett was an employee of Aptalis (formerly, Axcan) at the time the study was conducted, and currently is employed by Actavis Inc. Gerry Oster has served as a speaker, consultant and advisory board member for many biomedical companies. He is an employee of Policy Analysis Inc., which has received research funding from Aptalis (formerly, Axcan) as well as other healthcare companies and governmental organizations. Dr Oster owns stock in other healthcare companies in his retirement accounts. Declaration of funding interests: This study was funded in full by Aptalis (formerly, Axcan) under a research contract. Study design, analysis and interpretation of data, and manuscript preparation were undertaken by the study authors and the authors only. NR 21 TC 10 Z9 10 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD AUG PY 2012 VL 36 IS 3 BP 248 EP 256 DI 10.1111/j.1365-2036.2012.05175.x PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 966FW UT WOS:000305824200005 PM 22690748 ER PT J AU Hayes-Skelton, SA Usmani, A Lee, JK Roemer, L Orsillo, SM AF Hayes-Skelton, Sarah A. Usmani, Aisha Lee, Jonathan K. Roemer, Lizabeth Orsillo, Susan M. TI A Fresh Look at Potential Mechanisms of Change in Applied Relaxation for Generalized Anxiety Disorder: A Case Series SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE applied relaxation; mindfulness; decentering; acceptance; GAD ID COGNITIVE-BEHAVIORAL THERAPY; STATE WORRY QUESTIONNAIRE; PSYCHOMETRIC PROPERTIES; COMMITMENT THERAPY; STRESS SCALES; MINDFULNESS; DEPRESSION; VALIDATION; ACCEPTANCE; AVOIDANCE AB Applied relaxation (AR), which involves noticing early signs of anxiety and responding with a relaxation response, is an empirically supported treatment for generalized anxiety disorder (GAD). However, research on hypothesized mechanisms of AR (e.g., reduced muscle tension) has been mixed, making it likely that additional mechanisms are contributing to the efficacy of AR. Stemming from more recent conceptualizations of GAD, it is hypothesized that mindfulness, decentering, and acceptance may be potential mechanisms of change in AR. Outcome, mechanism data, and case descriptions from three individuals diagnosed with GAD who received 16 weeks of AR as part of a larger randomized controlled trial are presented to demonstrate the ways that AR may lead to clinical improvement through mindfulness, decentering, and acceptance. C1 [Hayes-Skelton, Sarah A.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Usmani, Aisha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Lee, Jonathan K.; Orsillo, Susan M.] Suffolk Univ, Boston, MA USA. RP Hayes-Skelton, SA (reprint author), Univ Massachusetts, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA. EM sarah.hayes@umb.edu OI Roemer, Lizabeth/0000-0002-2453-5435 FU NIMH NIH HHS [K99 MH085060, R00 MH085060, R01 MH074589] NR 51 TC 14 Z9 14 U1 3 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2012 VL 19 IS 3 BP 451 EP 462 PG 12 WC Psychology, Clinical SC Psychology GA 967OU UT WOS:000305918500008 PM 23888107 ER PT J AU Auriel, E Greenberg, SM AF Auriel, Eitan Greenberg, Steven Mark TI The Pathophysiology and Clinical Presentation of Cerebral Amyloid Angiopathy SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Cerebral amyloid angiopathy; Intracerebral hemorrhage; Vascular dementia; Stroke ID RECURRENT INTRACEREBRAL HEMORRHAGE; ALZHEIMERS-DISEASE; MOUSE MODEL; COGNITIVE IMPAIRMENT; CEREBROVASCULAR PATHOLOGY; SUBARACHNOID HEMORRHAGE; SUPERFICIAL SIDEROSIS; BETA-AMYLOIDOSIS; LOBAR HEMORRHAGE; MICROBLEEDS AB Cerebral amyloid angiopathy (CAA) is defined as the deposition of amyloid peptide within leptomeningial and cortical vessels, likely reflecting an imbalance between A beta production and clearance. Amyloid buildup triggers a series of destructive alterations in the cerebral vascular architecture, leading to a spectrum of neurological events including lobar intracerebral hemorrhage, brain ischemia and cognitive decline. Although traditionally diagnosed pathologically, neuroimaging has taken a central role in defining CAA. This review will discuss the pathological, clinical and radiological aspects of CAA. C1 [Auriel, Eitan; Greenberg, Steven Mark] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Auriel, Eitan; Greenberg, Steven Mark] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org NR 85 TC 21 Z9 22 U1 0 U2 10 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 J9 CURR ATHEROSCLER REP JI Curr. Atherosclerol. Rep. PD AUG PY 2012 VL 14 IS 4 BP 343 EP 350 DI 10.1007/s11883-012-0254-z PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 968BT UT WOS:000305952700008 PM 22565298 ER PT J AU Bayliss, G Weinrauch, LA D'Elia, JA AF Bayliss, George Weinrauch, Larry A. D'Elia, John A. TI Pathophysiology of Obesity-Related Renal Dysfunction Contributes to Diabetic Nephropathy SO CURRENT DIABETES REPORTS LA English DT Article DE Obesity; Obstructive sleep apnea; Proteinuria; Insulin resistance; Podocyte; Nephrin; Adipocyte; Diabetes; Renal dysfunction; Diabetic nephropathy ID OBSTRUCTIVE SLEEP-APNEA; CHRONIC KIDNEY-DISEASE; FETUIN-A; METABOLIC SYNDROME; NEPHROTIC SYNDROME; MASSIVE OBESITY; WEIGHT-LOSS; ADIPONECTIN; ASSOCIATION; PROTEINURIA AB Recent studies have demonstrated the role of insulin resistance in renal injury related to obesity, with hyperfiltration leading to glomerulomegaly in a pattern similar to that found in diabetic nephropathy. Similarities in the histologic patterns of damage from obesity and diabetes point to overlapping mechanisms of injury. In this review, we will examine the hormonal mechanisms, signaling pathways and injury patterns in renal injury resulting from obesity and attempt to draw conclusions on the reasons for these similarities. C1 [Bayliss, George] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Bayliss, George] Rhode Isl & Miriam Hosp, Div Kidney Dis & Hypertens, Providence, RI USA. [Weinrauch, Larry A.; D'Elia, John A.] Harvard Univ, Sch Med, Boston, MA USA. [D'Elia, John A.] Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. RP Bayliss, G (reprint author), Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. EM gbayliss@lifespan.org OI D'Elia, John/0000-0001-9482-581X; Weinrauch, Larry/0000-0003-1357-9528 FU Pat Covelli Foundation; Amgen Corp.; Bayer Laboratories FX G. Bayliss: none; L. A. Weinrauch: none; J.A. D'Elia: has received grant support from the Pat Covelli Foundation, Amgen Corp., and Bayer Laboratories as investigator-initiated research. NR 42 TC 14 Z9 18 U1 0 U2 9 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD AUG PY 2012 VL 12 IS 4 BP 440 EP 446 DI 10.1007/s11892-012-0288-1 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 968BW UT WOS:000305953000014 PM 22638939 ER PT J AU Chen, XQ Wu, GH Schwarzschild, MA AF Chen, Xiqun Wu, Guanhui Schwarzschild, Michael A. TI Urate in Parkinson's Disease: More Than a Biomarker? SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Urate; Parkinson's disease; Oxidative stress; Clinical trial; Antioxidant; Neuroprotectant; Neurodegeneration; Neuroprotection; Biomarker; Disease modifier; Neurodegenerative diseases; Purine; Risk factor ID URIC-ACID LEVELS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MILD COGNITIVE IMPAIRMENT; ISCHEMIC BRAIN-INJURY; SUBSTANTIA-NIGRA; OXIDATIVE STRESS; PLASMA URATE; IN-VIVO; DOPAMINERGIC-NEURONS; ANTIOXIDANT CAPACITY AB Parkinson's disease (PD) is a progressive neurodegenerative disease with characteristic motor manifestations. Although appreciation of PD as a multisystem disorder has grown, loss of dopaminergic neurons in the substantia nigra remains a pathological and neurochemical hallmark, accounting for the substantial symptomatic benefits of dopamine replacement therapies. However, currently no treatment has been shown to prevent or forestall the progression of the disease in spite of tremendous efforts. Among multiple environmental and genetic factors that have been implicated in the pathogenesis of PD, oxidative stress is proposed to play a critical role. A recent confluence of clinical, epidemiological, and laboratory evidence identified urate, an antioxidant and end product of purine metabolism, as not only a molecular predictor for both reduced risk and favorable progression of PD but also a potential neuroprotectant for the treatment of PD. This review summarizes recent findings on urate in PD and their clinical implications. C1 [Chen, Xiqun; Wu, Guanhui; Schwarzschild, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Charlestown, MA 02129 USA. [Wu, Guanhui] Suzhou Municipal Hosp, Suzhou, Peoples R China. RP Chen, XQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, 114 16th St, Charlestown, MA 02129 USA. EM xchen17@partners.org; gwu4@partners.org; michaels@helix.mgh.harvard.edu FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [K24NS060991]; US Department of Defense [W81XWH-11-1-0150] FX This paper is supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke grant K24NS060991 and the US Department of Defense grant W81XWH-11-1-0150. NR 98 TC 20 Z9 20 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD AUG PY 2012 VL 12 IS 4 BP 367 EP 375 DI 10.1007/s11910-012-0282-7 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 966HW UT WOS:000305829500005 PM 22580741 ER PT J AU Sonpavde, G Bellmunt, J Schutz, F Choueiri, TK AF Sonpavde, Guru Bellmunt, Joaquim Schutz, Fabio Choueiri, Toni K. TI The Double Edged Sword of Bleeding and Clotting from VEGF Inhibition in Renal Cancer Patients SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Renal cell carcinoma; VEGF inhibitors; Bleeding; Thrombosis ID RANDOMIZED PHASE-II; ARTERIAL THROMBOEMBOLIC EVENTS; ANTIANGIOGENIC AGENT SU5416; MOLECULAR-WEIGHT HEPARIN; CELL-CARCINOMA; VENOUS THROMBOEMBOLISM; INTERFERON-ALPHA; BEVACIZUMAB; TRIAL; RISK AB Vascular endothelial growth factor (VEGF) inhibitors have significantly improved outcomes in patients with advanced renal cell carcinoma (RCC). Multiple VEGF inhibiting orally administered tyrosine kinase inhibitors (TKIs) have been approved including sunitinib, sorafenib, pazopanib and most recently, axitinib. One VEGF inhibiting monoclonal antibody, bevacizumab, is approved in combination with interferon. However, these agents, besides the known progression-free survival benefits, are associated with a small but real risk of potentially life threatening and contrasting toxicities of thrombosis (both venous and arterial) and bleeding. Appropriate patient selection for VEGF inhibitors and prevention as well as prompt intervention to manage thrombosis and bleeding are necessary to forestall serious morbidities and mortality. C1 [Bellmunt, Joaquim] UPF Univ, Univ Hosp Del Mar IMIM, Barcelona, Spain. [Sonpavde, Guru] Vet Affairs Med Ctr, Houston, TX 77030 USA. [Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA. [Schutz, Fabio] Beneficencia Portuguesa Sao Paulo, Sao Jose Hosp, Sao Paulo, Brazil. [Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Sonpavde, Guru] Texas Oncol, Houston, TX USA. RP Bellmunt, J (reprint author), UPF Univ, Univ Hosp Del Mar IMIM, Paseig Maritim 25-29, Barcelona, Spain. EM jbellmunt@parcdesalutmar.cat FU Novartis; Celgene; Teva; BMS; Pfizer FX G. Sonpavde: research support from Novartis, Celgene, Teva, BMS, and Pfizer, and speaking honoraria from Novartis and GSK; T. K. Choueiri: research support from Pfizer, and advisory board for Pfizer, GSK, Novartis, Aveo, and Bayer/Onyx; F. Schutz: none; J. Bellmunt: advisory board for Pfizer, GSK, Novartis, Aveo, and Bayer/Onyx. NR 60 TC 8 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD AUG PY 2012 VL 14 IS 4 BP 295 EP 306 DI 10.1007/s11912-012-0237-9 PG 12 WC Oncology SC Oncology GA 968CB UT WOS:000305953500003 PM 22532265 ER PT J AU Kargi, AY Merriam, GR AF Kargi, Atil Y. Merriam, George R. TI Testing for growth hormone deficiency in adults: doing without growth hormone-releasing hormone SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE growth hormone; growth hormone deficiency; growth hormone stimulation testing ID INSULIN TOLERANCE-TEST; GLUCAGON STIMULATION TEST; BONE-MINERAL DENSITY; IGF-I LEVELS; GH-DEFICIENCY; (GH)-RELEASING HORMONE; REPLACEMENT THERAPY; PITUITARY DISEASE; CUTOFF LIMITS; PLUS ARGININE AB Purpose of review This article summarizes recent advances in testing for growth hormone deficiency (GHD) in adults, focusing on critical appraisal of existing growth hormone (GH) provocative tests as well as newer tests in development. Recent findings The diagnosis of GHD can be challenging and often requires the use of GH provocative testing. The most widely validated of these is insulin-induced hypoglycemia (ITT), which requires close supervision and has significant contraindications and side-effects. The arginine-growth hormone-releasing hormone (GHRH) test had become widely used as a safe and accurate alternative to the ITT, but GHRH is currently unavailable for clinical use in the USA. On the basis of review of recent literature we recommend that in the absence of GHRH, glucagon stimulation testing should be the preferred alternative to ITT. Several synthetic GH secretagogues that mimic the gastric peptide ghrelin are currently in development and may become available for use in the diagnosis of GHD in the near future. Other GH provocative tests suitable for use in children lack adequate specificity for the diagnosis of GHD in adults. Summary Due to the current unavailability of the arginine-GHRH test in the USA, when ITT is contraindicated or impractical we recommend the glucagon stimulation testing as the GH provocative test of choice. There remains a need for a simple, safe and accurate test for the diagnosis of GHD. C1 [Kargi, Atil Y.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA. [Merriam, George R.] Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98493 USA. RP Merriam, GR (reprint author), VA Puget Sound Healthcare Syst A 151, Seattle, WA 98493 USA. EM merriam@uw.edu FU Ardana Biosciences; Aeterna Zentaris FX A.Y.K. has nothing to disclose. G. R. M. received research grant support from Ardana Biosciences and from Aeterna Zentaris. NR 62 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD AUG PY 2012 VL 19 IS 4 BP 300 EP 305 DI 10.1097/MED.0b013e32835430da PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 970FX UT WOS:000306114600008 PM 22596248 ER PT J AU Desai, GS Uppot, RN Yu, EW Kambadakone, AR Sahani, DV AF Desai, Gaurav S. Uppot, Raul N. Yu, Elaine W. Kambadakone, Avinash R. Sahani, Dushyant V. TI Impact of iterative reconstruction on image quality and radiation dose in multidetector CT of large body size adults SO EUROPEAN RADIOLOGY LA English DT Article DE Iterative reconstruction; Computed tomography; Image quality; Radiation dose; Obesity ID TUBE CURRENT MODULATION; AUTOMATIC EXPOSURE CONTROL; ABDOMINAL CT; COMPUTED-TOMOGRAPHY; PATIENT SIZE; OBESITY; REDUCTION; ALGORITHM; PHANTOM; MDCT AB To compare image quality and radiation dose using Adaptive Statistical Iterative Reconstruction (ASiR) and Filtered Back Projection (FBP) in patients weighing a parts per thousand yen91 kg. In this Institution Review Board-approved retrospective study, single-phase contrast-enhanced abdominopelvic CT examinations of 100 adults weighing a parts per thousand yen91 kg (mean body weight: 107.6 +/- 17.4 kg range: 91-181.9 kg) with (1) ASiR and (2) FBP were reviewed by two readers in a blinded fashion for subjective measures of image quality (using a subjective standardized numerical scale and objective noise) and for radiation exposure. Imaging parameters and radiation dose results of the two techniques were compared within weight and BMI sub-categories. All examinations were found to be of adequate quality. Both subjective (mean = 1.4 +/- 0.5 vs. 1.6 +/- 0.6, P < 0.05) and objective noise (13.0 +/- 3.2 vs.19.5 +/- 5.7, P < 0.0001) were lower with ASiR. Average radiation dose reduction of 31.5 % was achieved using ASiR (mean CTDIvol. ASiR: 13.5 +/- 7.3 mGy; FBP: 19.7 +/- 9.0 mGy, P < 0.0001). Other measures of image quality were comparable between the two techniques. Trends for all parameters were similar in patients across weight and BMI sub-categories. In obese individuals, abdominal CT images reconstructed using ASiR provide diagnostic images with reduced image noise at lower radiation dose. aEuro cent CT images in obese adults are noisy, even with high radiation dose. aEuro cent Newer iterative reconstruction techniques have theoretical advantages in obese patients. aEuro cent Adaptive statistical iterative reconstruction should reduce image noise and radiation dose. aEuro cent This has been proven in abdominopelvic CT images of obese patients. C1 [Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Dept Radiol, Boston, MA 02114 USA. [Desai, Gaurav S.; Uppot, Raul N.; Kambadakone, Avinash R.; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Yu, Elaine W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 57 TC 51 Z9 53 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD AUG PY 2012 VL 22 IS 8 BP 1631 EP 1640 DI 10.1007/s00330-012-2424-3 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 967LQ UT WOS:000305909800003 PM 22527370 ER PT J AU Denecke, T Steffen, IG Agarwal, S Seehofer, D Kroncke, T Hanninen, EL Kramme, IB Neuhaus, P Saini, S Hamm, B Grieser, C AF Denecke, Timm Steffen, Ingo G. Agarwal, Sheela Seehofer, Daniel Kroencke, Thomas Haenninen, Enrique Lopez Kramme, Incken-Birthe Neuhaus, Peter Saini, Sanjay Hamm, Bernd Grieser, Christian TI Appearance of hepatocellular adenomas on gadoxetic acid-enhanced MRI SO EUROPEAN RADIOLOGY LA English DT Article DE MRI; Hepatocellular adenoma; Adenoma; Liver; Gadoxetic acid ID FOCAL NODULAR HYPERPLASIA; GD-EOB-DTPA; CONTRAST AGENT; LIVER ADENOMATOSIS; HEPATIC ADENOMA; SUBTYPE CLASSIFICATION; PATHOLOGICAL FINDINGS; INITIAL OBSERVATIONS; IMAGING FEATURES; MANAGEMENT AB The purpose of this study was to evaluate enhancement characteristics of hepatocellular adenomas (HCAs) using gadoxetic acid as a hepatocyte-specific MR contrast agent. Twenty-four patients with histopathologically proven HCAs were retrospectively identified. MRI consisted of T1- and T2-weighted (w) sequences with and without fat saturation (fs), multiphase dynamic T1-w images, and fs T1-w images during the hepatobiliary phase. Standard of reference was surgical resection (n = 19) or biopsy (n = 5). Images were analysed for morphology and contrast behaviour including signal intensity (SI) measurement on T1-w images normalised to the pre-contrast base line. In total 34 HCAs were evaluated. All HCAs showed enhancement in the arterial phase; 38 % of HCAs showed reduced contrast enhancement ("wash-out") in the venous phase. All HCAs showed enhancement (SI increase, 56 +/- 53 %; P < 0.001) in the hepatobiliary phase, although liver uptake was stronger (96 +/- 58 %). Thus, 31 of all HCAs (91 %) appeared hypointense to the surrounding liver in the hepatobiliary phase, while 3 out of 34 lesions were iso-/hyperintense. Gadoxetic acid accumulates in HCAs in the hepatobiliary phase, although significantly less than in surrounding liver. Thus, HCA appears in the vast majority of cases as a hypointense lesion on hepatobiliary phase images. aEuro cent Magnetic resonance-specific contrast agents are now available for hepatic imaging. aEuro cent Hepatocellular adenomas enhance with gadoxetic acid as in previous CT/MRI experience. aEuro cent Enhancement during the hepatobiliary phase is less in HCAs than in liver. aEuro cent Typical HCAs appear as hypointense lesions on T1-w hepatobiliary phase images. aEuro cent True hyperintense HCA enhancement can occasionally occur during the hepatobiliary phase. C1 [Denecke, Timm; Steffen, Ingo G.; Kroencke, Thomas; Haenninen, Enrique Lopez; Hamm, Bernd; Grieser, Christian] Charite, Campus Virchow Klinikum, Radiol Klin, D-13353 Berlin, Germany. [Seehofer, Daniel; Neuhaus, Peter] Charite, Campus Virchow Klinikum, Klin Allgemein Viszeral & Transplantat Chirurg, D-13353 Berlin, Germany. [Kramme, Incken-Birthe] Charite, Campus Virchow Klinikum, Inst Pathol, D-13353 Berlin, Germany. [Agarwal, Sheela; Saini, Sanjay] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Agarwal, Sheela; Saini, Sanjay] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grieser, C (reprint author), Charite, Campus Virchow Klinikum, Radiol Klin, Augustenburger Pl 1, D-13353 Berlin, Germany. EM christian.grieser@charite.de RI Kroencke, Thomas/H-6423-2011; OI Denecke, Timm/0000-0003-3313-3208 NR 36 TC 16 Z9 20 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD AUG PY 2012 VL 22 IS 8 BP 1769 EP 1775 DI 10.1007/s00330-012-2422-5 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 967LQ UT WOS:000305909800019 PM 22437921 ER PT J AU Efstathiou, JA Shipley, WU Zietman, AL AF Efstathiou, Jason A. Shipley, William U. Zietman, Anthony L. TI Reply to Neeraj Kumar Goyal, Manish Garg, and Apul Goel's Letter to the Editor re: Re: Jason A. Efstathiou, Daphna Y. Spiegel, William U. Shipley, et al. Long-Term Outcomes of Selective Bladder Preservation by Combined-Modality Therapy for Invasive Bladder Cancer: The MGH Experience. Eur Urol 2012;61:705-11 SO EUROPEAN UROLOGY LA English DT Letter C1 [Efstathiou, Jason A.; Shipley, William U.; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD AUG PY 2012 VL 62 IS 2 BP E42 EP E42 DI 10.1016/j.eururo.2012.04.055 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 966MF UT WOS:000305841100006 ER PT J AU Maciejewski, ML Liu, CF Kavee, AL Olsen, MK AF Maciejewski, Matthew L. Liu, Chuan-Fen Kavee, Andrew L. Olsen, Maren K. TI HOW PRICE RESPONSIVE IS THE DEMAND FOR SPECIALTY CARE? SO HEALTH ECONOMICS LA English DT Article DE costs; longitudinal; mixed model; random effects; health econometrics; zero-inflated data; specialty care; co-payment; cost sharing ID HEALTH MAINTENANCE ORGANIZATION; OFFICE VISIT COPAYMENTS; RISK ADJUSTMENT; PREVENTIVE SERVICES; EMERGENCY; OUTCOMES; IMPACT; COSTS; COINSURANCE; PERFORMANCE AB Objectives Outpatient visit co-payments have increased in recent years. We estimate the patient response to a price change for specialty care, based on a co-payment increase from $15 to $50 per visit for veterans with hypertension. Design, Setting, and Patients A retrospective cohort of veterans required to pay co-payments was compared with veterans exempt from co-payments whose nonequivalence was reduced via propensity score matching. Specialty care expenditures in 20002003 were estimated via a two-part mixed model to account for the correlation of the use and level outcomes over time, and results from this correlated two-part model were compared with an uncorrelated two-part model and a correlated random intercept two-part mixed model. Results A $35 specialty visit co-payment increase had no impact on the likelihood of seeking specialty care but induced lower specialty expenditures over time among users who were required to pay co-payments. The log ratio of price responsiveness (semi-elasticity) for specialty care increased from -0.25 to -0.31 after the co-payment increase. Estimates were similar across the three models. Conclusion A significant increase in specialty visit co-payments reduced specialty expenditures among patients obtaining medications at the Veterans Affairs medical centers. Longitudinal expenditure analysis may be improved using recent advances in two-part model methods. Published 2011. This article is a US Government work and is in the public domain in the USA. C1 [Maciejewski, Matthew L.; Kavee, Andrew L.; Olsen, Maren K.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Div Gen Internal Med, Durham, NC USA. [Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Olsen, Maren K.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, 205 Fulton St, Durham, NC USA. EM mlm34@duke.edu FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 03-200]; Department of Veterans Affairs [RCS 10-391]; Novartis; Takeda Pharmaceuticals; Surgical Review Corporation FX This work was supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, project number IIR 03-200. Dr Maciejewski was also supported by a Research Career Scientist award from the Department of Veterans Affairs (RCS 10-391). The authors are grateful for the helpful comments from the editor, two reviewers, Jim Burgess, Steve Pizer, Anirban Basu, Courtney Van Houtven, Santanu Datta, Valerie Smith, and the seminar participants at the ASA Health Policy Statistics meeting in 2008. Dr Maciejewski has received consultation funds from Novartis, Takeda Pharmaceuticals, Surgical Review Corporation, and owns a stock in Amgen. The views expressed are those of the authors and do not reflect the views of the Department of Veterans Affairs, the Duke University, or the University of Washington. NR 44 TC 3 Z9 3 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD AUG PY 2012 VL 21 IS 8 BP 902 EP 912 DI 10.1002/hec.1759 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 967KT UT WOS:000305907400002 PM 21755570 ER PT J AU Yokoe, DS Khan, Y Olsen, MA Hooper, DC Greenbaum, M Vostok, J Lankiewicz, J Fraser, VJ Stevenson, KB AF Yokoe, Deborah S. Khan, Yosef Olsen, Margaret A. Hooper, David C. Greenbaum, Maurice Vostok, Johanna Lankiewicz, Julie Fraser, Victoria J. Stevenson, Kurt B. CA Ctr Dis Control Prevention TI Enhanced Surgical Site Infection Surveillance Following Hysterectomy, Vascular, and Colorectal Surgery SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CARE-ASSOCIATED INFECTIONS; ADMINISTRATIVE CODING DATA; POSTOPERATIVE INFECTIONS; IDENTIFICATION AB OBJECTIVE. To evaluate the use of inpatient pharmacy and administrative data to detect surgical site infections (SSIs) following hysterectomy and colorectal and vascular surgery. DESIGN. Retrospective cohort study. SETTING. Five hospitals affiliated with academic medical centers. PATIENTS. Adults who underwent abdominal or vaginal hysterectomy, colorectal surgery, or vascular surgery procedures between July 1, 2003, and June 30, 2005. methods. We reviewed the medical records of weighted, random samples drawn from 3,079 abdominal and vaginal hysterectomy, 4,748 colorectal surgery, and 3,332 vascular surgery procedures. We compared routine surveillance with screening of inpatient pharmacy data and diagnosis codes and then performed medical record review to confirm SSI status. RESULTS. Medical records from 823 hysterectomy, 736 colorectal surgery, and 680 vascular surgery procedures were reviewed. SSI rates determined by antimicrobial-and/or diagnosis code-based screening followed by medical record review (enhanced surveillance) were substantially higher than rates determined by routine surveillance (4.3% [95% confidence interval, 3.6%-5.1%] vs 2.7% for hysterectomies, 7.1% [95% confidence interval, 6.7%-8.2%] vs 2.0% for colorectal procedures, and 2.3% [95% confidence interval, 1.9%-2.9%] vs 1.4% for vascular procedures). Enhanced surveillance had substantially higher sensitivity than did routine surveillance to detect SSI (92% vs 59% for hysterectomies, 88% vs 22% for colorectal procedures, and 72% vs 43% for vascular procedures). A review of medical records confirmed SSI for 31% of hysterectomies, 20% of colorectal procedures, and 31% of vascular procedures that met the enhanced screening criteria. CONCLUSION. Antimicrobial-and diagnosis code-based screening may be a useful method for enhancing and streamlining SSI surveillance for a variety of surgical procedures, including those procedures targeted by the Centers for Medicare and Medicaid Services. Infect Control Hosp Epidemiol 2012;33(8):768-773 C1 [Yokoe, Deborah S.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Yokoe, Deborah S.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Yokoe, Deborah S.; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Khan, Yosef; Stevenson, Kurt B.] Ohio State Univ, Coll Med, Div Infect Dis, Columbus, OH 43210 USA. [Khan, Yosef; Stevenson, Kurt B.] Ohio State Univ, Div Epidemiol, Coll Publ Hlth, Columbus, OH 43210 USA. [Olsen, Margaret A.; Fraser, Victoria J.] Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA. [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Greenbaum, Maurice] N Shore Med Ctr, Div Infect Dis, Salem, MA USA. [Vostok, Johanna; Lankiewicz, Julie] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Fraser, Victoria J.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Stevenson, Kurt B.] Ohio State Univ, Med Ctr, Dept Clin Epidemiol, Columbus, OH 43210 USA. RP Yokoe, DS (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM dyokoe@partners.org FU CDC [U01 CI000344, CI000333, CI000328] FX This study was funded by the CDC Prevention Epicenters Program (U01 CI000344, CI000333, and CI000328). NR 11 TC 25 Z9 25 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2012 VL 33 IS 8 BP 768 EP 773 DI 10.1086/666626 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 970CQ UT WOS:000306106100002 PM 22759543 ER PT J AU Shenoy, ES Walensky, RP Lee, H Orcutt, B Hooper, DC AF Shenoy, Erica S. Walensky, Rochelle P. Lee, Hang Orcutt, Benjamin Hooper, David C. TI Resource Burden Associated with Contact Precautions for Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus: The Patient Access Managers' Perspective SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article AB We surveyed patient access managers on the impact of contact precautions (CP) for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) on time to bed assignment, and we investigated the factors influencing infection control policies allowing for discontinuation of CP. The majority of respondents reported an increase in time to bed assignment for patients with a history of MRSA and/or VRE infection or colonization. Infect Control Hosp Epidemiol 2012;33(8):849-852 C1 [Shenoy, Erica S.; Walensky, Rochelle P.; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Shenoy, Erica S.; Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Orcutt, Benjamin] Massachusetts Gen Hosp, Admitting Serv, Boston, MA 02114 USA. RP Shenoy, ES (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Bulfinch 340, Boston, MA 02114 USA. EM eseiguershenoy@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institutes of Health (NIH) [T32 A107061]; MGH Clinical Innovation Award; Harvard Catalyst (NIH) [UL1 RR 025758]; Harvard University and its affiliated academic healthcare centers FX E.S.S. was supported by the National Institutes of Health (NIH; grant T32 A107061) and a 2010 MGH Clinical Innovation Award. H. L. was supported by Harvard Catalyst (NIH Award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centers). NR 8 TC 11 Z9 12 U1 2 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2012 VL 33 IS 8 BP 849 EP 852 DI 10.1086/666629 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 970CQ UT WOS:000306106100014 PM 22759555 ER PT J AU Faris, JE Arnott, J Zheng, H Ryan, DP Abrams, TA Blaszkowsky, LS Clark, JW Enzinger, PC Hezel, AF Ng, K Wolpin, BM Kwak, EL AF Faris, Jason E. Arnott, Jamie Zheng, Hui Ryan, David P. Abrams, Thomas A. Blaszkowsky, Lawrence S. Clark, Jeffrey W. Enzinger, Peter C. Hezel, Aram F. Ng, Kimmie Wolpin, Brian M. Kwak, Eunice L. TI A phase 2 study of oral MKC-1, an inhibitor of importin-beta, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Pancreatic cancer; Phase II; MKC-1; Importin; Tubulin ID SOLID TUMORS; III TRIAL; GEMCITABINE; CARCINOMA; THERAPY; PLACEBO AB Background MKC-1 is an orally available cell cycle inhibitor with downstream targets that include tubulin and the importin-beta family. We conducted an open-label Phase II study with MKC-1 in patients with advanced pancreatic cancer. Methods Eligibility criteria included unresectable or metastatic pancreatic cancer, performance status of 1 or better, and failure of at least one prior regimen of chemotherapy. MKC-1 was administered orally, twice daily, initially at 100 mg/m(2) dosing for 14 consecutive days of a 28-day cycle. This schedule was modified during the trial to fixed and continuous dosing of 150 mg per day. Results 20 of an original target of 33 patients were accrued, with a median age of 61 (range 44-81). No objective responses were observed, with one patient demonstrating stable disease. Overall survival was 101 days from the start of MKC-1 administration, and median time to progression was 42 days. The most common adverse events listed as related or possibly related to MKC-1 administration were hematologic toxicities and fatigue. One patient developed grade 5 (fatal) pancytopenia. Grade 3 and 4 events included cytopenias (lymphopenia, anemia), hyperbilirubinemia, pneumonia, mucositis, fatigue, infusion reaction, anorexia, and hypoalbuminemia. Conclusions MKC-1 administration was associated with substantial toxicity and did not demonstrate sufficient activity in patients with advanced pancreatic cancer to justify further exploration in this patient population. C1 [Faris, Jason E.; Ryan, David P.; Blaszkowsky, Lawrence S.; Clark, Jeffrey W.; Kwak, Eunice L.] Massachusetts Gen Hosp, Dept Med Oncol, Ctr Canc, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Arnott, Jamie] Entremed Inc, Durham, NC USA. [Abrams, Thomas A.; Enzinger, Peter C.; Ng, Kimmie; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hezel, Aram F.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. RP Kwak, EL (reprint author), Massachusetts Gen Hosp, Dept Med Oncol, Ctr Canc, Yawkey 7E, Boston, MA 02114 USA. EM ekwak@partners.org FU NCI NIH HHS [K07 CA140790, K07 CA148894] NR 17 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD AUG PY 2012 VL 30 IS 4 BP 1614 EP 1620 DI 10.1007/s10637-011-9708-3 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 968CT UT WOS:000305955300037 PM 21800081 ER PT J AU Ozanne, EM O'Connell, A Bouzan, C Bosinoff, P Rourke, T Dowd, D Drohan, B Millham, F Griffin, P Halpern, EF Semine, A Hughes, KS AF Ozanne, Elissa M. O'Connell, Adrienne Bouzan, Colleen Bosinoff, Phil Rourke, Taryn Dowd, Dana Drohan, Brian Millham, Fred Griffin, Pat Halpern, Elkan F. Semine, Alan Hughes, Kevin S. TI Bias in the Reporting of Family History: Implications for Clinical Care SO JOURNAL OF GENETIC COUNSELING LA English DT Article DE Cancer; Family history; Self-reporting; Data collection ID BREAST-CANCER; OVARIAN-CANCER; GENETIC RISK; POPULATION; MANAGEMENT; COMMUNICATION; PREVALENCE; VALIDATION; HEALTH; WOMEN AB Family history of cancer is critical for identifying and managing patients at risk for cancer. However, the quality of family history data is dependent on the accuracy of patient self reporting. Therefore, the validity of family history reporting is crucial to the quality of clinical care. A retrospective review of family history data collected at a community hospital between 2005 and 2009 was performed in 43,257 women presenting for screening mammography. Reported numbers of breast, colon, prostate, lung, and ovarian cancer were compared in maternal relatives vs. paternal relatives and in first vs. second degree relatives. Significant reporting differences were found between maternal and paternal family history of cancer, in addition to degree of relative. The number of paternal family histories of cancer was significantly lower than that of maternal family histories of cancer. Similarly, the percentage of grandparents' family histories of cancer was significantly lower than the percentage of parents' family histories of cancer. This trend was found in all cancers except prostate cancer. Self-reported family history in the community setting is often influenced by both bloodline of the cancer history and the degree of relative affected. This is evident by the underreporting of paternal family histories of cancer, and also, though to a lesser extent, by degree. These discrepancies in reporting family history of cancer imply we need to take more care in collecting accurate family histories and also in the clinical management of individuals in relation to hereditary risk. C1 [Hughes, Kevin S.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Hughes, Kevin S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Avon Breast Evaluat Ctr,Newton Wellesley Hosp, Boston, MA USA. [Hughes, Kevin S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Newton Wellesley Hosp, Boston, MA USA. [Ozanne, Elissa M.] Univ Calif San Francisco, Dept Surg, Inst Hlth Policy Studies, San Francisco, CA USA. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St,YAW 7, Boston, MA 02114 USA. EM elissa.ozanne@ucsfmedctr.org; kshughes@partners.org OI Hughes, Kevin/0000-0003-4084-6484 FU MGH; Sandra Perrin Fund for Women's Imaging Education at Newton Wellesley Hospital; American Cancer Society [MRSG112037] FX Supported by Philanthropic Funds from the MGH and the Sandra Perrin Fund for Women's Imaging Education at Newton Wellesley Hospital. E. Ozanne's work on this project was supported in part by grant number MRSG112037 from the American Cancer Society NR 33 TC 16 Z9 16 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 J9 J GENET COUNS JI J. Genet. Couns. PD AUG PY 2012 VL 21 IS 4 BP 547 EP 556 DI 10.1007/s10897-011-9470-x PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 967MV UT WOS:000305913200008 PM 22237666 ER PT J AU Saadi, A Bond, B Percac-Lima, S AF Saadi, Altaf Bond, Barbara Percac-Lima, Sanja TI Perspectives on Preventive Health Care and Barriers to Breast Cancer Screening Among Iraqi Women Refugees SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Refugees; Immigrants; Arab; Breast cancer screening; Preventive health ID UNITED-STATES; IMMIGRANT WOMEN; AMERICAN WOMEN; BELIEFS; BEHAVIORS; KNOWLEDGE; ATTITUDES; ETHNICITY; SURVIVAL AB Since the Iraq war began in 2003, over 4 million Iraqis have been displaced. Little is known about preventive cancer care in this population, but stark disparities have been documented. The purpose of this study was to assess the perspectives of Iraqi women refugees on preventive care and perceived barriers to breast cancer screening. Interviews were conducted in Arabic with twenty Iraqi refugee women by a bilingual (English/Arabic) medical student, transcribed, translated and coded according to established qualitative content and thematic analysis procedures. Psychosocial barriers, culturally mediated beliefs, and health consequences of war were identified as major themes, ultimately showing what factors, alone and collectively, have impeded Iraqi refugee women's ability and motivation to obtain breast cancer screening. To improve cancer prevention and decrease disparities in care in this most vulnerable population, culturally appropriate health education and outreach programs, as well as further community-level targeted studies, are needed. C1 [Saadi, Altaf] Harvard Univ, Sch Med, Boston, MA 02150 USA. [Bond, Barbara] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bond, Barbara] Bridgewater State Univ, Dept Social Work, Bridgewater, MA 02325 USA. [Percac-Lima, Sanja] MGH, Chelsea HealthCare Ctr, Chelsea, MA 02150 USA. RP Saadi, A (reprint author), Harvard Univ, Sch Med, 260 Longwood Ave, Boston, MA 02150 USA. EM altaf_saadi@hms.harvard.edu; bbond@partners.org; spercaclima@partners.org FU AHRQ HHS [1R18 HS019161-01] NR 32 TC 7 Z9 7 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD AUG PY 2012 VL 14 IS 4 BP 633 EP 639 DI 10.1007/s10903-011-9520-3 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 967MZ UT WOS:000305913600015 PM 21901446 ER PT J AU Percac-Lima, S Milosavljevic, B Oo, SA Marable, D Bond, B AF Percac-Lima, Sanja Milosavljevic, Bosiljka Oo, Sarah Abernethy Marable, Danelle Bond, Barbara TI Patient Navigation to Improve Breast Cancer Screening in Bosnian Refugees and Immigrants SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Refugees; Breast cancer; Mammograms; Patient navigation ID HEALTH AB Refugee women have low breast cancer screening rates. This study highlights the culturally competent implementation and reports the outcomes of a breast cancer screening patient navigation program for refuge/immigrant women from Bosnia. Refugees/immigrant women from Bosnia age 40-79 were contacted by a Serbo-Croatian speaking patient navigator who addressed patient-reported barriers to breast cancer screening and, using individually tailored interventions, helped women obtain screening. The proportion of women up-to-date for mammography was compared at baseline and after 1-year using McNemar's Chi-Square test. 91 Serbo-Croatian speaking women were eligible for mammography screening. At baseline, 44.0% of women had a mammogram within the previous year, with the proportion increasing to 67.0% after 1-year (P = 0.001). A culturally-tailored, language-concordant navigator program designed to overcome specific barriers to breast cancer screening can significantly improve mammography rates in refugees/immigrants. C1 [Percac-Lima, Sanja; Milosavljevic, Bosiljka; Oo, Sarah Abernethy] Massachusetts Gen Hosp, Chelsea HealthCare Ctr, Chelsea, MA 02150 USA. [Percac-Lima, Sanja; Milosavljevic, Bosiljka; Oo, Sarah Abernethy; Marable, Danelle] Massachusetts Gen Hosp, Ctr Community Hlth Improvement, Boston, MA 02114 USA. [Percac-Lima, Sanja] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Percac-Lima, Sanja] Harvard Univ, Sch Med, Boston, MA USA. [Bond, Barbara] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Percac-Lima, S (reprint author), Massachusetts Gen Hosp, Chelsea HealthCare Ctr, 151 Everett Ave, Chelsea, MA 02150 USA. EM spercaclima@partners.org FU AHRQ HHS [1R18 HS019161-01] NR 10 TC 10 Z9 10 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD AUG PY 2012 VL 14 IS 4 BP 727 EP 730 DI 10.1007/s10903-011-9539-5 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 967MZ UT WOS:000305913600027 PM 22009215 ER PT J AU Fields, EC Kuperberg, GR AF Fields, Eric C. Kuperberg, Gina R. TI It's All About You: An ERP Study of Emotion and Self-Relevance in Discourse SO NEUROIMAGE LA English DT Article DE Emotion; Event-related Potentials; Language; Late positive potential; Self-relevance; Perspective ID NEGATIVITY BIAS; NEURAL MECHANISMS; VISUAL-ATTENTION; POSITIVITY BIAS; STROOP TASK; STIMULI; NAME; FACE; VALENCE; BRAIN AB Accurately communicating self-relevant and emotional information is a vital function of language, but we have little idea about how these factors impact normal discourse comprehension. In an event-related potential (ERP) study, we fully crossed self-relevance and emotion in a discourse context. Two-sentence social vignettes were presented either in the third or the second person (previous work has shown that this influences the perspective from which mental models are built). ERPs were time-locked to a critical word toward the end of the second sentence which was pleasant, neutral, or unpleasant (e.g., A man knocks on Sandra's/your hotel room door. She/You see(s) that he has a gift/tray/gun in his hand.). We saw modulation of early components (P1, N1, and P2) by self-relevance, suggesting that a self-relevant context can lead to top-down attentional effects during early stages of visual processing. Unpleasant words evoked a larger late positivity than pleasant words, which evoked a larger positivity than neutral words, indicating that, regardless of self-relevance, emotional words are assessed as motivationally significant, triggering additional or deeper processing at post-lexical stages. Finally, self-relevance and emotion interacted on the late positivity: a larger late positivity was evoked by neutral words in self-relevant, but not in non-self-relevant, contexts. This may reflect prolonged attempts to disambiguate the emotional valence of ambiguous stimuli that are relevant to the self. More broadly, our findings suggest that the assessment of emotion and self-relevance are not independent, but rather that they interactively influence one another during word-by-word language comprehension. (C) 2012 Elsevier Inc. All rights reserved. C1 [Fields, Eric C.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Fields, EC (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM Eric.Fields@tufts.edu FU NIMH [R01 MH071635]; NARSAD; Sidney Baer Trust FX This work was supported was supported by NIMH (R01 MH071635) and NARSAD (with the Sidney Baer Trust) grants to Gina Kuperberg. We extend a big thanks to Wonja Fairbrother for her help with stimuli creation, data collection, and data analysis. We also thank Sorabh Kothari for his help with stimuli norming and analysis and Nate Delaney-Busch for comments on the manuscript and helpful conversations about these topics. NR 82 TC 37 Z9 39 U1 10 U2 40 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 1 PY 2012 VL 62 IS 1 BP 562 EP 574 DI 10.1016/j.neuroimage.2012.05.003 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 966TC UT WOS:000305859300054 PM 22584232 ER PT J AU Castro, NJ Hacking, SA Zhang, LG AF Castro, Nathan J. Hacking, S. Adam Zhang, Lijie Grace TI Recent Progress in Interfacial Tissue Engineering Approaches for Osteochondral Defects SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Tissue engineering; Bone; Cartilage; Osteochondral; Interface; Biomimetic; Nanotechnology ID MESENCHYMAL STEM-CELLS; SCAFFOLD-FREE CARTILAGE; MARROW STROMAL CELLS; BOVINE ARTICULAR-CARTILAGE; MUSCLE-DERIVED CELLS; GAS-FORMING AGENT; SUBCHONDRAL BONE; PROGENITOR CELLS; GROWTH-FACTOR; IN-VITRO AB This review provides a brief synopsis of the anatomy and physiology of the osteochondral interface, scaffold-based and non-scaffold based approaches for engineering both tissues independently as well as recent developments in the manufacture of gradient constructs. Novel manufacturing techniques and nanotechnology will be discussed with potential application in osteochondral interfacial tissue engineering. C1 [Castro, Nathan J.; Zhang, Lijie Grace] George Washington Univ, Inst Biomed Engn, Dept Mech & Aerosp Engn, Washington, DC 20052 USA. [Castro, Nathan J.; Zhang, Lijie Grace] George Washington Univ, Inst Nanotechnol, Washington, DC 20052 USA. [Hacking, S. Adam] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Hacking, S. Adam] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zhang, LG (reprint author), George Washington Univ, Inst Biomed Engn, Dept Mech & Aerosp Engn, 726 Phillips Hall,801 22nd St NW, Washington, DC 20052 USA. EM lgzhang@gwu.edu FU George Washington University Facilitating Fund (UFF); Oak Ridge Associated Universities (ORAU) organization FX The authors would like to thank the financial support from the George Washington University Facilitating Fund (UFF) and Ralph E. Powe Junior Faculty Enhancement Award by the Oak Ridge Associated Universities (ORAU) organization. NR 124 TC 44 Z9 46 U1 3 U2 42 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD AUG PY 2012 VL 40 IS 8 BP 1628 EP 1640 DI 10.1007/s10439-012-0605-5 PG 13 WC Engineering, Biomedical SC Engineering GA 965VK UT WOS:000305795200002 PM 22677924 ER PT J AU Hegedus, C Truta-Feles, K Antalffy, G Varady, G Nemet, K Ozvegy-Laczka, C Keri, G Orfi, L Szakacs, G Settleman, J Varadi, A Sarkadi, B AF Hegedues, Csilla Truta-Feles, Krisztina Antalffy, Geza Varady, Gyoergy Nemet, Katalin Oezvegy-Laczka, Csilla Keri, Gyoergy Orfi, Laszlo Szakacs, Gergely Settleman, Jeffrey Varadi, Andras Sarkadi, Balazs TI Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: Implications for the emergence and reversal of cancer drug resistance SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE ABCG2; Multidrug resistance; Receptor tyrosine kinase; EGFR inhibitor; Cancer stem cell ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; SIDE-POPULATION PHENOTYPE; STEM-CELLS; MONOCLONAL-ANTIBODY; LUNG-CANCER; ACQUIRED-RESISTANCE; EXPRESSION; TUMORS; ZD6474 AB Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side population that is characteristically enriched in normal and cancer stem cells. Numerous tumors depend on unregulated EGFR signaling, thus inhibition of this receptor by small molecular weight inhibitors such as gefitinib, and the novel second generation agents vandetanib, pelitinib and neratinib, is a promising therapeutic option. In the present study, we provide detailed biochemical characterization regarding the interaction of these EGFR inhibitors with ABCG2. We show that ABCG2 confers resistance to gefitinib and pelitinib, whereas the intracellular action of vandetanib and neratinib is unaltered by the presence of the transporter. At higher concentrations, however, all these EGFR inhibitors inhibit ABCG2 function, thereby promoting accumulation of ABCG2 substrate drugs. We also report enhanced expression of ABCG2 in gefitinib-resistant non-small cell lung cancer cells, suggesting potential clinical relevance of ABCG2 in acquired drug resistance. Since ABCG2 has important impact on both the pharmacological properties and anti-cancer efficiencies of drugs, our results regarding the novel EGFR inhibitors should provide useful information about their therapeutic applicability against ABCG2-expressing cancer cells depending on EGFR signaling. In addition, the finding that these EGFR inhibitors efficiently block ABCG2 function may help to design novel drug-combination therapeutic strategies. (C) 2012 Elsevier Inc. All rights reserved. C1 [Hegedues, Csilla; Truta-Feles, Krisztina; Antalffy, Geza; Varady, Gyoergy; Nemet, Katalin; Oezvegy-Laczka, Csilla; Sarkadi, Balazs] Semmelweis Univ, Dept Biophys, Hungarian Acad Sci, Membrane Res Grp, H-1113 Budapest, Hungary. [Keri, Gyoergy] Semmelweis Univ, Dept Med Chem, Hungarian Acad Sci, Pathobiochem Res Grp, H-1113 Budapest, Hungary. [Hegedues, Csilla; Truta-Feles, Krisztina; Antalffy, Geza; Varady, Gyoergy; Nemet, Katalin; Oezvegy-Laczka, Csilla; Sarkadi, Balazs] Natl Blood Ctr, Budapest, Hungary. [Keri, Gyoergy; Orfi, Laszlo] VICHEM Chem Res Ltd, Budapest, Hungary. [Orfi, Laszlo] Semmelweis Univ, Dept Pharmaceut Chem, H-1113 Budapest, Hungary. [Szakacs, Gergely; Varadi, Andras] Hungarian Acad Sci, Inst Enzymol, Res Ctr Nat Sci, Budapest, Hungary. [Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. [Sarkadi, Balazs] Hungarian Acad Sci, Inst Mol Pharmacol, Res Ctr Nat Sci, Budapest, Hungary. RP Sarkadi, B (reprint author), Semmelweis Univ, Dept Biophys, Hungarian Acad Sci, Membrane Res Grp, Dioszegi U 64, H-1113 Budapest, Hungary. EM csilla.hegedus@biomembrane.hu; kristina_feles@yahoo.se; antalffy@biomembrane.hu; varady@biomembrane.hu; nemet@biomembrane.hu; lozvegy@biomembrane.hu; gykeri@vichem.hu; lorfi@vichem.hu; szakacs@biomembrane.hu; settleman.jeffrey@gene.com; varadi@enzim.hu; sarkadi@biomembrane.hu RI Szakacs, Gergely/A-2580-2009; Orfi, Laszlo/A-2116-2008; Sarkadi, Balazs/I-5024-2013 OI Szakacs, Gergely/0000-0002-9311-7827; Orfi, Laszlo/0000-0001-6149-2385; FU OTKA [NK83533, KMOP-1.1.2-07/1-2008-0003]; NKTH-ANR and Stemkill; Hungarian Academy of Sciences FX The technical help of Gyongyi Bezsenyi, Eva Krizsan and Zsuzsanna Andrasi is greatly appreciated. This work has been supported by grants from OTKA NK83533, KMOP-1.1.2-07/1-2008-0003, and NKTH-ANR and Stemkill. Csilla ozvegy-Laczka is a recipient of the Jdnos Bolyai Scholarship of the Hungarian Academy of Sciences. Gergely Szakacs is supported by the Lendtilet grant from the Hungarian Academy of Sciences. NR 48 TC 26 Z9 28 U1 1 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 1 PY 2012 VL 84 IS 3 BP 260 EP 267 DI 10.1016/j.bcp.2012.04.010 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 962LI UT WOS:000305546200003 PM 22548830 ER PT J AU McDermott, PJ Baicu, CF Wahl, SR Van Laer, AO Zile, MR AF McDermott, Paul J. Baicu, Catalin F. Wahl, Shaun R. Van Laer, An O. Zile, Michael R. TI In vivo measurements of the contributions of protein synthesis and protein degradation in regulating cardiac pressure overload hypertrophy in the mouse SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Myocardium; Amino acids; Infusion; Inbred C57BL mice ID MYOSIN HEAVY-CHAIN; VENTRICULAR HYPERTROPHY; VOLUME OVERLOAD; MICE; TURNOVER; CANINE; HEART; DYSFUNCTION; MECHANISMS; PROTEASOME AB Cardiac hypertrophy is generated in response to hemodynamic overload by altering steady-state protein metabolism such that the rate of protein synthesis exceeds the rate of protein degradation. To determine the relative contributions of protein synthesis and degradation in regulating cardiac hypertrophy in mice, a continuous infusion strategy was developed to measure myocardial protein synthesis rates in vivo. Osmotic mini-pumps were implanted in the abdominal cavity to infuse radiolabeled leucine in mice that are conscious and ambulatory. Protein synthesis rates were calculated by measuring incorporation of leucine into myocardial protein over 24 h prior to each time point and dividing by the specific radioactivity of plasma leucine. Compared to sham-operated controls, fractional rates of protein synthesis (K (s)) increased significantly at days 1 and 3 of TAC, but was lower on day 7 and returned to control values by day 14. These changes coincided with the curvilinear increase in LV mass that characterizes the hypertrophic response. Fractional rates of protein degradation (K (d)) were calculated by subtracting the rate of myocardial growth from the corresponding K (s) value. K (d) fell at days 1 and 3 of TAC, increased at day 7 and returned to control on day 14. Thus, the increase in LV mass generated in response to pressure overload is caused by acceleration of K (s) and suppression of K (d). As the growth rate slows, a new steady-state is achieved once the hypertrophic response is completed. C1 [McDermott, Paul J.; Baicu, Catalin F.; Wahl, Shaun R.; Van Laer, An O.; Zile, Michael R.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Charleston, SC 29403 USA. [McDermott, Paul J.; Baicu, Catalin F.; Wahl, Shaun R.; Van Laer, An O.; Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP McDermott, PJ (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Strom Thurmond Biomed Res Bldg,Room 303,114 Dough, Charleston, SC 29403 USA. EM mcdermp@musc.edu FU Department of Veterans Affairs FX We thank Daisy Dominick and Dr. Harinath Kasiganesan for their excellent technical assistance, and Dr. Francis G. Spinale for his help using osmotic mini-pumps. This work was supported by Merit Review Awards (P. J. McDermott and M. R. Zile) from the Health Services Research and Development Program of the Department of Veterans Affairs. NR 24 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD AUG PY 2012 VL 367 IS 1-2 BP 205 EP 213 DI 10.1007/s11010-012-1334-7 PG 9 WC Cell Biology SC Cell Biology GA 964GX UT WOS:000305683100021 PM 22610791 ER PT J AU Grigoriev, Y Lange, J Peterson, SM Takashima, JR Ritchey, ML Ko, D Feusner, JH Shamberger, RC Green, DM Breslow, NE AF Grigoriev, Yevgeny Lange, Jane Peterson, Susan M. Takashima, Janice R. Ritchey, Michael L. Ko, Dicken Feusner, James H. Shamberger, Robert C. Green, Daniel M. Breslow, Norman E. TI Treatments and outcomes for end-stage renal disease following Wilms tumor SO PEDIATRIC NEPHROLOGY LA English DT Article DE Chronic kidney failure; Transplantation; Graft failure ID DENYS-DRASH-SYNDROME; KIDNEY-TRANSPLANTATION; CANCER-RISK; DISPARITIES; RECIPIENTS; SURVIVAL; CHILDREN AB Little is known about treatment outcomes for children who have end-stage renal disease (ESRD) after treatment for Wilms tumor (WT). Time-to-transplant, graft failure, and survival outcomes were examined for 173 children enrolled on the National Wilms Tumor Study who developed ESRD. Fifty-five patients whose ESRD resulted from progressive bilateral WT (PBWT) experienced high early mortality from WT that limited their opportunity for transplant (47% at 5 years) and survival (44% at 10 years) in comparison to population controls. The 118 patients whose ESRD was due to other causes (termed "chronic kidney disease"), many of whom had WT-associated congenital anomalies, had transplant (77% at 5 years) and survival (73% at 10 years) outcomes no worse than those for population controls. Graft failure following transplant was comparable for the two groups. Minority children had twice the median time to transplant as non-Hispanic whites and twice the mortality rates, also reflecting population trends. In view of the continuing high mortality in patients with ESRD, and the dramatic improvement in outlook following kidney transplantation, re-evaluation of current guidelines for a 2-year delay in transplant following WT treatment may be warranted. C1 [Lange, Jane; Breslow, Norman E.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Grigoriev, Yevgeny; Peterson, Susan M.; Takashima, Janice R.; Breslow, Norman E.] Fred Hutchinson Canc Res Ctr, Dept Biostat & Bioinformat, Seattle, WA 98104 USA. [Ritchey, Michael L.] Phoenix Childrens Hosp, Dept Urol, Phoenix, AZ USA. [Ko, Dicken] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ko, Dicken] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Ko, Dicken] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Feusner, James H.] Childrens Hosp, Dept Hematol Oncol, Oakland, CA 94609 USA. [Feusner, James H.] Res Ctr Oakland, Oakland, CA USA. [Shamberger, Robert C.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Green, Daniel M.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. RP Breslow, NE (reprint author), Univ Washington, Dept Biostat, Mail Stop 357232, Seattle, WA 98195 USA. EM norm@u.washington.edu FU United States National Cancer Institute [CA054498] FX This study was supported in part by grant CA054498 from the United States National Cancer Institute. We thank investigators of the Children's Oncology Group and the health professionals who managed the care of children entered in the National Wilms Tumor Study. NR 29 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X EI 1432-198X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD AUG PY 2012 VL 27 IS 8 BP 1325 EP 1333 DI 10.1007/s00467-012-2140-x PG 9 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 964GS UT WOS:000305682600014 PM 22430485 ER PT J AU Jaremko, JL MacMahon, PJ Torriani, M Merker, VL Mautner, VF Plotkin, SR Bredella, MA AF Jaremko, Jacob L. MacMahon, Peter J. Torriani, Martin Merker, Vanessa L. Mautner, Victor F. Plotkin, Scott R. Bredella, Miriam A. TI Whole-body MRI in neurofibromatosis: incidental findings and prevalence of scoliosis SO SKELETAL RADIOLOGY LA English DT Article DE Whole-body MRI (WBMRI); Neurofibromatosis; Incidental findings ID IDIOPATHIC SCOLIOSIS; SPINAL DEFORMITY; TUMOR BURDEN; SCHWANNOMATOSIS AB To demonstrate incidental findings and scoliosis on whole-body MRI (WBMRI) in patients with neurofibromatosis type 1 and 2 (NF1 & NF2, respectively), and schwannomatosis. Institutional review board approval and written informed consent were obtained for this prospective HIPAA-compliant study. A total of 247 subjects (141 with NF1, 55 with NF2, 51 with schwannomatosis; 132 women (53.5%); mean age, 41 years, range, 18-97 years) underwent WBMRI using coronal STIR (TR/TE: 4190/111 ms, TI: 150 ms) and T1-weighted images (TR/TE: 454/10 ms), 10-mm slice thickness, imaging time similar to 40 min. Images were reviewed for the presence of incidental findings, outside of nerve sheath tumors. The presence of scoliosis was recorded and curve morphology was assessed and quantified. Incidental findings other than scoliosis were recorded in 104/247 (42%) patients, most often affecting the musculoskeletal system (65/247 patients, 26%). We found 16/247 (6.5%) significant incidental findings likely to affect clinical management, including avascular necrosis of bone in eight patients (five with NF2), eight insufficiency fractures, and four non-neurogenic neoplasms (Hodgkin's lymphoma, liposarcoma, dermoid cyst, large uterine myoma requiring excision). Scoliosis was seen in 50/247 patients (20%), including 8/55 with NF2 (15%) and 11/51 with schwannomatosis (22%). Incidental findings in the neurofibromatoses frequently involve the skeleton. Given the relatively high incidence of unsuspected osteonecrosis and stress fractures, close attention to the skeleton on WBMRI is advised. In addition, knowledge of common incidental findings can help clinicians prepare patients who undergo WBMRI for potential unexpected findings. C1 [Jaremko, Jacob L.; MacMahon, Peter J.; Torriani, Martin; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Jaremko, Jacob L.; MacMahon, Peter J.; Torriani, Martin; Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mautner, Victor F.] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Hamburg, Germany. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org OI Merker, Vanessa/0000-0002-4542-5227 FU Department of Defense Neurofibromatosis Research Program [NF0502020]; NIH/NINDS [P01NS024279] FX Department of Defense Neurofibromatosis Research Program (NF0502020) and the NIH/NINDS (P01NS024279). NR 22 TC 9 Z9 10 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD AUG PY 2012 VL 41 IS 8 BP 917 EP 923 DI 10.1007/s00256-011-1333-x PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 962HM UT WOS:000305533800004 PM 22146869 ER PT J AU Ramdhian-Wihlm, R Le Minor, JM Schmittbuhl, M Jeantroux, J Mac Mahon, P Veillon, F Dosch, JC Dietemann, JL Bierry, G AF Ramdhian-Wihlm, Reeta Le Minor, Jean-Marie Schmittbuhl, Matthieu Jeantroux, Jeremy Mac Mahon, Peter Veillon, Francis Dosch, Jean-Claude Dietemann, Jean-Louis Bierry, Guillaume TI Cone-beam computed tomography arthrography: an innovative modality for the evaluation of wrist ligament and cartilage injuries SO SKELETAL RADIOLOGY LA English DT Article DE Cone beam computed tomography; Wrist; Ligaments; Cartilage ID TRIANGULAR FIBROCARTILAGE COMPLEX; MR ARTHROGRAPHY; CT ARTHROGRAPHY; IMAGE QUALITY; MULTISLICE; EXPERIENCE; DIAGNOSIS; LANDMARKS; SYSTEM; TEARS AB Cone-beam computed tomography (CBCT) has become an important modality in dento-facial imaging but remains poorly used in the exploration of the musculoskeletal system. The purpose of this study was to prospectively evaluate the performance and radiation exposure of CBCT arthrography in the evaluation of ligament and cartilage injuries in cadaveric wrists, with gross pathology findings as the standard of reference. Conventional arthrography was performed under fluoroscopic guidance on 10 cadaveric wrists, followed by MDCT acquisition and CBCT acquisition. CBCT arthrography and MDCT arthrography images were independently analyzed by two musculoskeletal radiologists working independently and then in consensus. The following items were observed: scapholunate and lunotriquetral ligaments, triangular fibrocartilage complex (TFCC) (tear, integrity), and proximal carpal row cartilage (chondral tears). Wrists were dissected and served as the standard of reference for comparisons. Interobserver agreement, sensitivity, specificity, and accuracy were determined. Radiation dose (CTDI) of both modalities was recorded. CBCT arthrography provides equivalent results to MDCT arthrography in the evaluation of ligaments and cartilage with sensitivity and specificity between 82 and 100%, and interobserver agreement between 0.83 and 0.97. However, radiation dose was significantly lower (p < 0.05) for CBCT arthrography than for MDCT arthrography with a mean CTDI of 2.1 mGy (range 1.7-2.2) versus a mean of 15.1 mGy (range 14.7-16.1). CBCT arthrography appears to be an innovative alternative to MDCT arthrography of the wrist as it allows an accurate and low radiation dose evaluation of ligaments and cartilage. C1 [Jeantroux, Jeremy; Veillon, Francis; Dosch, Jean-Claude; Dietemann, Jean-Louis; Bierry, Guillaume] Univ Hosp Strasbourg, Dept Radiol, F-67098 Strasbourg, France. [Ramdhian-Wihlm, Reeta] Univ Hosp Strasbourg, Dept Orthoped Surg, F-67098 Strasbourg, France. [Le Minor, Jean-Marie] Univ Strasbourg, Inst Anat, Strasbourg, France. [Le Minor, Jean-Marie; Schmittbuhl, Matthieu] Univ Strasbourg, Fac Dent, Strasbourg, France. [Mac Mahon, Peter] Massachusetts Gen Hosp, Dept Musculoskeletal Radiol, Boston, MA 02114 USA. RP Bierry, G (reprint author), Univ Hosp Strasbourg, Dept Radiol, 10 Ave Moliere, F-67098 Strasbourg, France. EM Guillaume.bierry@chru-strasbourg.fr NR 37 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD AUG PY 2012 VL 41 IS 8 BP 963 EP 969 DI 10.1007/s00256-011-1305-1 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 962HM UT WOS:000305533800010 PM 22064983 ER PT J AU Stephan, MT Stephan, SB Bak, P Chen, JZ Irvine, DJ AF Stephan, Matthias T. Stephan, Sirkka B. Bak, Peter Chen, Jianzhu Irvine, Darrell J. TI Synapse-directed delivery of immunomodulators using T-cell-conjugated nanoparticles SO BIOMATERIALS LA English DT Article DE Cell therapy; Nanoparticle; Drug delivery; Immune synapse ID IMMUNOLOGICAL SYNAPSE; CANCER-IMMUNOTHERAPY; TYROSINE PHOSPHATASES; TRANSFERRIN RECEPTOR; TUMOR; LYMPHOCYTE; ACTIVATION; INHIBITOR; SHP-1; TRANSPLANTATION AB Regulating molecular interactions in the T-cell synapse to prevent autoimmunity or, conversely, to boost anti-tumor immunity has long been a goal in immunotherapy. However, delivering therapeutically meaningful doses of immune-modulating compounds into the synapse represents a major challenge. Here, we report that covalent coupling of maleimide-functionlized nanoparticles (NPs) to free thiol groups on T-cell membrane proteins enables efficient delivery of compounds into the T-cell synapse. We demonstrate that surface-linked NPs are rapidly polarized toward the nascent immunological synapse (IS) at the T-cell/APC contact zone during antigen recognition. To translate these findings into a therapeutic application we tested the NP delivery of NSC-87877, a dual inhibitor of Shp1 and Shp2, key phosphatases that downregulate T-cell receptor activation in the synapse, in the context of adoptive T cell therapy of cancer. Conjugating NSC-87877-loaded NPs to the surface of tumor-specific T cells just prior to adoptive transfer into mice with advanced prostate cancer promoted a much greater T-cell expansion at the tumor site, relative to co-infusing the same drug dose systemically, leading to enhanced survival of treated animals. In summary, our studies support the application of T-cell-linked synthetic NPs as efficient drug delivery vehicles into the IS, as well as the broad applicability of this new paradigm for therapeutically modulating signaling events at the T-cell/APC interface. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Stephan, Matthias T.; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Stephan, Matthias T.; Stephan, Sirkka B.; Bak, Peter; Chen, Jianzhu; Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Irvine, Darrell J.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. [Irvine, Darrell J.] Harvard Univ, Boston, MA 02115 USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Irvine, DJ (reprint author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. EM djirvine@mit.edu FU NIH [CA140476, EB123622]; Dept. of Defense Prostate Cancer Research Program [W81XWH-10-1-0290]; Cancer Center from NCI [P30-CA14051] FX This work was supported in part by the NIH (CA140476 to DJI and EB123622 to MTS), the Dept. of Defense Prostate Cancer Research Program (W81XWH-10-1-0290), and a Cancer Center Support (core) grant P30-CA14051 from the NCI. SPB is an American Cancer Society Postdoctoral Fellow (12109-PF-11-025-01-LIB). DJI is an investigator of the Howard Hughes Medical Institute. NR 69 TC 38 Z9 38 U1 2 U2 53 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD AUG PY 2012 VL 33 IS 23 BP 5776 EP 5787 DI 10.1016/j.biomaterials.2012.04.029 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 963CG UT WOS:000305597100012 PM 22594972 ER PT J AU Khocht, A Yaskell, T Janal, M Turner, BF Rams, TE Haffajee, AD Socransky, SS AF Khocht, A. Yaskell, T. Janal, M. Turner, B. F. Rams, T. E. Haffajee, A. D. Socransky, S. S. TI Subgingival microbiota in adult Down syndrome periodontitis SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE Down syndrome; periodontal; periodontitis; subgingival microbiota ID DNA-DNA HYBRIDIZATION; PORPHYROMONAS-GINGIVALIS; REFRACTORY PERIODONTITIS; MICROBIOLOGICAL PARAMETERS; PERIODONTOPATHIC BACTERIA; DISEASE; PLAQUE; FIBROBLASTS; MICROFLORA; HEALTH AB Khocht A, Yaskell T, Janal M, Turner BF, Rams TE, Haffajee AD, Socransky SS. Subgingival microbiota in adult Down syndrome periodontitis. J Periodont Res 2012; 47: 500507. (c) 2012 John Wiley & Sons A/S Background and Objective: The subgingival microbiota in Down syndrome and non-Down syndrome adults receiving periodic dental care was examined for 40 bacterial species using checkerboard DNADNA hybridization and the results were related to clinical periodontal attachment loss. Material and Methods: A total of 44 Down syndrome, 66 non-Down syndrome mentally retarded and 83 mentally normal adults were clinically evaluated. This involved, for each subject, the removal of subgingival specimens from three interproximal sites on different teeth; all subgingival samples per subject were then pooled and assessed for the presence and levels of 40 bacterial species using species-specific whole-genomic DNA probes and checkerboard DNADNA hybridization. Significant group differences in species proportions averaged across subjects were evaluated using the KruskalWallis test, and associations between subgingival species and mean subject attachment loss within Down syndrome and non-Down syndrome subject groups were quantified using Pearson correlation and multiple linear regression analysis. Results: Down syndrome subjects exhibited greater attachment loss than non-Down syndrome subjects (p = 0.05). Most microbial species were present in Down syndrome subjects at levels similar to non-Down syndrome subjects, except for higher proportions of Selenomonas noxia, Propionibacterium acnes, Streptococcus gordonii, Streptococcus mitis and Streptococcus oralis in Down syndrome subjects compared with non-Down syndrome study subjects, higher proportions of Treponema socranskii in Down syndrome subjects compared with non-Down syndrome mentally retarded subjects, and higher proportions of Streptococcus constellatus in Down syndrome subjects compared with mentally normal subjects. Down syndrome adults classified with periodontitis revealed higher subgingival levels of T. socranskii than Down syndrome subjects with no periodontitis (p = 0.02). Higher subgingival proportions of S. constellatus, Fusobacterium nucleatum ssp. nucleatum, S. noxia and Prevotella nigrescens showed significant positive correlations (r = 0.350.42) and higher proportions of Actinomyces naeslundii II and Actinomyces odontolyticus showed negative correlations (r = -0.36 to -0.40), with increasing mean subject attachment loss in Down syndrome adults. Conclusion: Individuals with Down syndrome show higher levels of some subgingival bacterial species and specific associations between certain subgingival bacterial species and loss of periodontal attachment. These findings are consistent with the notion that certain subgingival bacteria may contribute to the increased level of periodontal disease seen in Down syndrome individuals and raise the question as to the reason for increased colonization in Down syndrome. C1 [Khocht, A.] Temple Univ, Sch Dent, Dept Periodontol & Oral Implantol, Philadelphia, PA 19140 USA. [Yaskell, T.; Haffajee, A. D.; Socransky, S. S.] Forsyth Inst, Cambridge, MA USA. [Janal, M.] NYU, Coll Dent, New York, NY USA. [Turner, B. F.] E Cent Reg Hosp, Gracewood, GA USA. RP Khocht, A (reprint author), Temple Univ, Sch Dent, Dept Periodontol & Oral Implantol, 3223 N Broad St, Philadelphia, PA 19140 USA. EM akhocht@temple.edu FU National Institute of Dental and Craniofacial Research, Bethesda, Maryland [R21 DE015012-02] FX This study was supported by grant R21 DE015012-02 from the National Institute of Dental and Craniofacial Research, Bethesda, Maryland. NR 40 TC 8 Z9 10 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD AUG PY 2012 VL 47 IS 4 BP 500 EP 507 DI 10.1111/j.1600-0765.2011.01459.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 962VN UT WOS:000305575600012 PM 22221039 ER PT J AU Soria, JC Mok, TS Cappuzzo, F Janne, PA AF Soria, Jean-Charles Mok, Tony S. Cappuzzo, Federico Jaenne, Pasi A. TI EGFR-mutated oncogene-addicted non-small cell lung cancer: Current trends and future prospects SO CANCER TREATMENT REVIEWS LA English DT Review DE Biological markers; Carcinoma; Non-small cell lung; Receptor; Epidermal growth factor; Erlotinib; Gefitinib; Mutation; Oncogenes ID GROWTH-FACTOR-RECEPTOR; PHASE-III TRIAL; TYROSINE KINASE INHIBITORS; GENE COPY NUMBER; IN-SITU HYBRIDIZATION; CLINICAL-PRACTICE GUIDELINES; HARBORING BRAF MUTATIONS; EML4-ALK FUSION GENE; GROUP-STUDY BR.21; ACQUIRED-RESISTANCE AB Non-small cell lung cancer (NSCLC) tumours with certain mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase have been termed 'oncogene addicted' to reflect their dependence on EGFR-mediated pro-survival signalling and their high susceptibility to apoptosis induced by EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g. gefitinib and erlotinib). The most common mutations (L858R and exon 19 deletions) predict an improved clinical response to first-line oral EGFR-TKIs compared with standard platinum-based chemotherapy in patients with advanced NSCLC. Moreover, these mutations are also prognostic of a relatively indolent course of disease, regardless of treatment, as compared with classical NSCLC. Treatment strategies for oncogene-addicted NSCLC are therefore distinct from those for non-oncogene addicted NSCLC, and will depend on the specific genetic mutation present. (C) 2011 Published by Elsevier Ltd. C1 [Soria, Jean-Charles] Inst Gustave Roussy, INSERM, Serv Innovat Therapeut Precoces, U981, F-94805 Villejuif, France. [Soria, Jean-Charles] Univ Paris 11, F-94805 Villejuif, France. [Mok, Tony S.] Chinese Univ Hong Kong, State Key Lab Oncol S China, Sir YK Pao Ctr Canc, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. [Cappuzzo, Federico] Osped Civile Livorno, Ist Toscano Tumori, I-57100 Livorno, Italy. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Soria, JC (reprint author), Inst Gustave Roussy, INSERM, Serv Innovat Therapeut Precoces, U981, F-94805 Villejuif, France. EM jean-charles.soria@igr.fr; tony@clo.cuhk.edu.hk; f.cappuzzo@googlemail.com; Pasi_Janne@dfci.harvard.edu RI Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; Cappuzzo, Federico/0000-0002-6295-6767 FU Astrazeneca; Dana-Farber Cancer Institute; Boehringer-Ingelheim FX J.C.S. has acted as a consultant for Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, glaxosmithkiline, Lilly, Merck-Serono, Merck Sharp & Dohme, Pfizer, Roche-Genentech, Servier and sanofi-aventis. T.S.M. has acted as a consultant for AstraZeneca, Roche, Eli Lilly, Pfizer, Taiho, BMS, Merck Serono and Boellinger Ingelheim, has received honoraria from AstraZeneca, Roche, Eli Lilly, Pfizer, Merck Serono, Boehringer-Ingelheim, and has received research funding from Astrazeneca. F.C. has acted as a consultant for Roche and holds a patent for EGFR FISH testing. P.A.J. has acted as a consultant for Boehringer-Ingelheim, Roche, Genentech, Abbott, AstraZeneca and Pfizer. He owns stocks in Gatekeeper Pharmaceuticals and has received royalties from intellectual property related to EGFR mutation tests owned by the Dana-Farber Cancer Institute and licensed to Genzyme.; Editorial assistance in the development of this paper, furnished by Prism Ideas Ltd. (Nantwich, Cheshire, UK) was supported by an unrestricted grant from Boehringer-Ingelheim. NR 176 TC 67 Z9 72 U1 1 U2 27 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 EI 1532-1967 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD AUG PY 2012 VL 38 IS 5 BP 416 EP 430 DI 10.1016/j.ctrv.2011.10.003 PG 15 WC Oncology SC Oncology GA 956SN UT WOS:000305109500011 PM 22119437 ER EF