FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Seah, DS Gelber, S Ruddy, KJ Tamimi, RM Schapira, L Come, SE Meyer, ME Larsen, BG Winer, EP Partridge, A AF Seah, Davinia Shien Gelber, Shari Ruddy, Kathryn Jean Tamimi, Rulla M. Schapira, Lidia Come, Steven E. Meyer, Meghan E. Larsen, Bryce G. Winer, Eric P. Partridge, Ann TI Quality of life and psychosocial distress in young women with advanced breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA e20508 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419604780 ER PT J AU Sequist, LV Soria, JC Gadgeel, SM Wakelee, HA Camidge, DR Varga, A Fidias, P Wozniak, AJ Neal, JW Doebele, RC Garon, EB Jaw-Tsai, SS Stern, JC Allen, AR Goldman, JW AF Sequist, Lecia V. Soria, Jean-Charles Gadgeel, Shirish M. Wakelee, Heather A. Camidge, D. Ross Varga, Andrea Fidias, Panos Wozniak, Antoinette J. Neal, Joel W. Doebele, Robert Charles Garon, Edward B. Jaw-Tsai, Sarah S. Stern, Jennifer C. Allen, Andrew R. Goldman, Jonathan Wade TI First-in-human evaluation of CO-1686, an irreversible, selective, and potent tyrosine kinase inhibitor of EGFR T790M. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Gustave Roussy, Villejuif, France. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Stanford Canc Inst, Stanford, CA USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Univ Calif Los Angeles, Santa Monica, CA USA. Clovis Oncol Inc, San Francisco, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 5 Z9 5 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 2524 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601042 ER PT J AU Serrano-Garcia, C Heinrich, MC Zhu, MJ Raut, CP Eilers, G Ravegnini, G Demetri, GD Bauer, S Fletcher, JA George, S AF Serrano-Garcia, Cesar Heinrich, Michael C. Zhu, Meijun Raut, Chandrajit P. Eilers, Grant Ravegnini, Gloria Demetri, George D. Bauer, Sebastian Fletcher, Jonathan A. George, Suzanne TI In vitro and in vivo activity of regorafenib (REGO) in drug-resistant gastrointestinal stromal tumors (GIST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Duisburg Essen, Dept Med Oncol, West German Canc Ctr, Univ Hosp Essen, Essen, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 10510 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600282 ER PT J AU Sethi, RV Shih, HA Kim, D Yeap, BY Mouw, K Marcus, KC Grabowski, E Yock, TI Tarbell, N Mukai, S MacDonald, SM AF Sethi, Rosin V. Shih, Helen Alice Kim, David Yeap, Beow Y. Mouw, Kent Marcus, Karen Chayt Grabowski, Eric Yock, Torunn I. Tarbell, Nancy Mukai, Shizuo MacDonald, Shannon M. TI Second non-ocular tumors among survivors of retinoblastom treated with proton therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Hematol & Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 10018 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600172 ER PT J AU Seymour, JF Davids, MS Pagel, JM Kahl, BS Wierda, WG Miller, TP Gerecitano, JF Kipps, TJ Anderson, MA Huang, DCS Darden, DE Gressick, LA Nolan, CE Yang, JN Busman, TA Graham, AM Cerri, E Enschede, SH Humerickhouse, RA Roberts, AW AF Seymour, John Francis Davids, Matthew Steven Pagel, John M. Kahl, Brad S. Wierda, William G. Miller, Thomas P. Gerecitano, John F. Kipps, Thomas J. Anderson, Mary Ann Huang, David C. S. Darden, David E. Gressick, Lori A. Nolan, Cathy E. Yang, Jianning Busman, Todd A. Graham, Alison M. Cerri, Elisa Enschede, Sari H. Humerickhouse, Rod A. Roberts, Andrew Warwick TI Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Arizona, Ctr Canc, Tucson, AZ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. UC San Diego Moores Canc Ctr, La Jolla, CA USA. Royal Melbourne Hosp, Melbourne, Vic, Australia. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. AbbVie Inc, N Chicago, IL USA. Royal Melbourne Hosp, Melbourne, Vic, Australia. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 7018 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602376 ER PT J AU Shah, A Motiwala, S Brose, MS O'Dwyer, PJ Flaherty, K Keefe, SM AF Shah, Amishi Motiwala, Shweta Brose, Marcia S. O'Dwyer, Peter J. Flaherty, Keith Keefe, Stephen Michael TI Increase in blood pressure with sorafenib exposure: Renal cell carcinoma (RCC) versus other solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA e15564 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419604137 ER PT J AU Shaheen, S Upadhyay, S Marak, CP Kumar, G Guddati, AK AF Shaheen, Shagufta Upadhyay, Shivanck Marak, Creticus Petrov Kumar, Gagan Guddati, Achuta Kumar TI Outcomes of invasive fungal infections in hematopoietic stem cell transplant patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, Harlem Hosp Ctr, New York, NY USA. Montefiore Hosp, Albert Einstein Coll Med, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA e18008 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419604475 ER PT J AU Shaik, M Korant, AK Saha, SK Johnston, G Dhar, VK Abadeer, B Wiese, D Arora, ML Stewart, A Saha, S AF Shaik, Mohammed Korant, Alpesh K. Saha, Supriya Kumar Johnston, Gregory Dhar, Vikrom K. Abadeer, Benjamin Wiese, David Arora, Madan L. Stewart, Andrew Saha, Sukamal TI Impact of nodal metastasis on survival of stage IV colon cancer: Analysis of National Cancer Data Base (NCDB) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Michigan State Univ, Hurley Med Ctr, Flint, MI USA. Michigan State Univ, McLaren Reg Med Ctr, Flint, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. McLaren Macomb Med Ctr, Mt Clemens, MI USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Amer Coll Surg, Commiss Canc, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 3582 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601317 ER PT J AU Shapiro, G Supko, JG Cho, DC Hilton, JF Hadfield, M Pruitt-Thompson, S Bordoli-Trachsela, E Zvereva, N Wolanski, A Sato-DiLorenzo, A Gotthardt, S Fox, EA Verselis, SJ Kumar, A Holden, SA Ram, S Chafai-Fadela, K Harding, K Menon, KE AF Shapiro, Geoffrey Supko, Jeffrey G. Cho, Daniel C. Hilton, John Frederick Hadfield, Matthew Pruitt-Thompson, Salida Bordoli-Trachsela, Eveline Zvereva, Nela Wolanski, Andrew Sato-DiLorenzo, Aya Gotthardt, Susan Fox, Edward A. Verselis, Sigitas Jonas Kumar, Ashok Holden, Sylvia A. Ram, Siya Chafai-Fadela, Karima Harding, Kimberly Menon, Krishna E. TI A phase I, dose-escalation, safety, pharmacokinetic, pharmacodynamic study of thioureidobutyronitrile, a novel p53 targeted therapy, in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. KARD Sci, Beverly, MA USA. Cellceutix, Beverly, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA TPS2627 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419605398 ER PT J AU Shapiro, G Rosen, LS Tolcher, AW Goldman, JW Gandhi, L Papadopoulos, KP Tolaney, SM Beeram, M Rasco, DW Kulanthaivel, P Li, Q Hu, TL Cronier, D Chan, EM Flaherty, K Wen, PY Patnaik, A AF Shapiro, Geoffrey Rosen, Lee S. Tolcher, Anthony W. Goldman, Jonathan Wade Gandhi, Leena Papadopoulos, Kyriakos P. Tolaney, Sara M. Beeram, Muralidhar Rasco, Drew Warren Kulanthaivel, Palaniappan Li, Qian Hu, Tianle Cronier, Damien Chan, Edward M. Flaherty, Keith Wen, Patrick Y. Patnaik, Amita TI A first-in-human phase I study of the CDK4/6 inhibitor, LY2835219, for patients with advanced cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Santa Monica, CA USA. START Ctr Canc Care, San Antonio, TX USA. START, San Antonio, TX USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. PharmaNet I3, Indianapolis, IN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. NR 0 TC 3 Z9 3 U1 6 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 2500 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601018 ER PT J AU Shaw, AT Mok, T Spigel, DR Nishio, M Felip, E Tan, DSW Garcia-Campelo, MR Gruen, HJM Dakhil, SR Schaefer, ES Farrell, NJ Blakesley, RE Weir, A Ristic, M Selvaggi, G Scagliotti, G AF Shaw, Alice Tsang Mok, Tony Spigel, David R. Nishio, Makoto Felip, Enriqueta Tan, Daniel Shao-Weng Garcia-Campelo, M. Rosario Gruen, Harry J. M. Dakhil, Shaker R. Schaefer, Eric Scott Farrell, Nicholas John Blakesley, Rick E. Weir, Alexander Ristic, Mirta Selvaggi, Giovanni Scagliotti, Giorgio TI A phase II single-arm study of LDK378 in patients with ALK-activated (ALK plus ) non-small cell lung cancer (NSCLC) previously treated with chemotherapy and crizotinib (CRZ). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Sarah Cannon Res Inst, Tennessee Oncol, Nashville, TN USA. Japanese Fdn Canc Res, Canc Inst Hosp, Dept Thorac Med Oncol, Tokyo, Japan. Vall dHebron Inst Oncol, Thorac Tumors Grp, Barcelona, Spain. Natl Canc Ctr Singapore, Singapore, Singapore. Complexo Hosp A Coruna, La Coruna, Spain. Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. Canc Ctr Kansas, Wichita, KS USA. Highlands Oncol Grp, Fayetteville, AZ USA. Associates Oncol & Hematol, Rockville, MD USA. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Pharma AG, Basel, Switzerland. Univ Turin, Orbassano, Italy. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA TPS8119 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419605508 ER PT J AU Shaw, AT Mehra, R Kim, DW Felip, E Chow, LQM Camidge, DR Tan, DSW Vansteenkiste, JF Sharma, S De Pas, T Wolf, J Katayama, R Lau, YYY Goldwasser, M Boral, A Engelman, JA AF Shaw, Alice Tsang Mehra, Ranee Kim, Dong-Wan Felip, Enriqueta Chow, Laura Quan Man Camidge, D. Ross Tan, Daniel Shao-Weng Vansteenkiste, Johan F. Sharma, Sunil De Pas, Tommaso Wolf, Juergen Katayama, Ryohei Lau, Yi-Yang Yvonne Goldwasser, Meredith Boral, Anthony Engelman, Jeffrey A. TI Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Vall dHebron Inst Oncol, Thorac Tumors Grp, Barcelona, Spain. Univ Washington, Seattle Canc Care, Seattle, WA 98195 USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Natl Canc Ctr Singapore, Singapore, Singapore. Univ Hosp KU Leuven, Louvain, Belgium. Huntsman Canc Inst, Salt Lake City, UT USA. European Inst Oncol, Milan, Italy. Univ Hosp Cologne, Lung Canc Grp Cologne, Ctr Integrated Oncol, Cologne, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Inst BioMed Res Inc, Cambridge, MA USA. NR 0 TC 27 Z9 28 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 8010 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602492 ER PT J AU Shedlock, K Porock, D Brown, JK Burton, H Horvath, P Berry, DL AF Shedlock, Kathleen Porock, Davina Brown, Jean K. Burton, Harold Horvath, Peter Berry, Donna Lynn TI Effects of physical activity on symptoms in prostate cancer survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 SUNY, Univ Buffalo, Sch Nursing, Boston, MA USA. Univ Nottingham, Sch Nursing, Buffalo, NY USA. SUNY Buffalo, Sch Nursing, Buffalo, NY 14260 USA. SUNY Buffalo, Dept Exercise & Nutr Sci, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA e20540 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419604810 ER PT J AU Sherman, SI Cohen, EEW Schoffski, P Elisei, R Schlumberger, M Wirth, LJ Mangeshkar, M Aftab, DT Clary, DO Brose, MS AF Sherman, Steven I. Cohen, Ezra E. W. Schoffski, Patrick Elisei, Rossella Schlumberger, Martin Wirth, Lori J. Mangeshkar, Milan Aftab, Dana T. Clary, Douglas O. Brose, Marcia S. TI Efficacy of cabozantinib (Cabo) in medullary thyroid cancer (MTC) patients with RAS or RET mutations: Results from a phase III study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Katholieke Univ Leuven, Univ Hosp Leuven, Dept Gen Med Oncol, Louvain, Belgium. Univ Pisa, Pisa, Italy. Inst Gustave Roussy, Villejuit, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Exelixis Inc, San Francisco, CA USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. NR 0 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 6000 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602125 ER PT J AU Shi, Q De Gramont, A Buyse, ME Grothey, A Schmoll, HJ Seymour, MT Adams, RA Saltz, L Goldberg, RM Punt, CJA Douillard, JY Hecht, JR Hurwitz, H Diaz-Rubio, E Porschen, R Tebbutt, NC Fuchs, CS Souglakos, J Falcone, A Sargent, DJ AF Shi, Qian De Gramont, Aimery Buyse, Marc E. Grothey, Axel Schmoll, Hans-Joachim Seymour, Matthew T. Adams, Richard A. Saltz, Leonard Goldberg, Richard M. Punt, Cornelis J. A. Douillard, Jean-Yves Hecht, J. Randolph Hurwitz, Herbert Diaz-Rubio, Eduardo Porschen, Rainer Tebbutt, Niall C. Fuchs, Charles S. Souglakos, John Falcone, Alfredo Sargent, Daniel J. CA ARCAD Grp TI Individual patient data (IPD) analysis of progression-free survival (PFS) versus overall survival (OS) as an endpoint for metastatic colorectal cancer (mCRC) in modern trials: Findings from the 16,700 patients (pts) ARCAD database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Hosp St Antoine, Paris, France. Int Inst Drug Dev, Louvain, Belgium. Univ Halle Wittenberg, D-06108 Halle, Germany. Canc Res UK Clin Ctr, Leeds, W Yorkshire, England. Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. ICO Ctr Rene Gauducheau, St Herblain, France. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Duke Univ, Med Ctr, Durham, NC USA. Hosp Clin San Carlos, Madrid, Spain. Klinikum Bremen Ost, Bremen, Germany. Austin Hlth, Heidelberg, Vic, Australia. Univ Melbourne, Heidelberg, Vic, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Crete, Sch Med, Iraklion, Greece. Santa Chiara Hosp, Pisa, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 3533 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601269 ER PT J AU Shulman, LN Berry, DA Cirrincione, CT Becker, H Perez, EA O'Regan, R Martino, S Shapiro, CL Atkins, J Schneider, C Kimmick, GG Burstein, HJ Norton, L Musa, HB Hudis, C Winer, EP AF Shulman, Lawrence N. Berry, Donald A. Cirrincione, Constance T. Becker, Heather Perez, Edith A. O'Regan, Ruth Martino, Silvana Shapiro, Charles L. Atkins, James Schneider, Charles Kimmick, Gretchen Genevieve Burstein, Harold J. Norton, Larry Musa, Hyman Bernard Hudis, Clifford Winer, Eric P. CA Canc Leukemia Grp B TI Comparison of doxorubicin and cyclophosphamide (AC) versus single-agent paclitaxel (T) as adjuvant therapy for breast cancer in women with 0-3 positive axillary nodes: CALGB 40101 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Canc Inst Biostat, Durham, NC USA. Univ Chicago, Chicago, IL 60637 USA. Mayo Clin, Jacksonville, FL 32224 USA. Grady Mem Hosp, Georgia Canc Ctr Excellence, Atlanta, GA USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Ohio State Univ, Columbus, OH 43210 USA. Southeastern Med Oncol Ctr, Goldsboro, NC USA. Christiana Care Hlth Syst, Newark, DE USA. Duke Canc Inst, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 1007 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600229 ER PT J AU Siegel, DSD Richardson, PGG Vij, R Hofmeister, CC Baz, RC Jagannath, S Chen, C Lonial, S Jakubowiak, AJ Bahlis, NJ Song, KW Belch, A Raje, NS Shustik, C Lentzsch, S Chen, M Zaki, MH Anderson, KC AF Siegel, David Samuel DiCapua Richardson, Paul Gerard Guy Vij, Ravi Hofmeister, Craig C. Baz, Rachid C. Jagannath, Sundar Chen, Christine Lonial, Sagar Jakubowiak, Andrzej J. Bahlis, Nizar J. Song, Kevin W. Belch, Andrew Raje, Noopur S. Shustik, Chaim Lentzsch, Suzanne Chen, Min Zaki, Mohamed H. Anderson, Kenneth Carl TI Long-term safety and efficacy of pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in relapsed and refractory multiple myeloma (RRMM) patients enrolled in the MM-002 phase II trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, St Louis, MO USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Emory Univ, Sch Med, Atlanta, GA USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ Calgary, Calgary, AB, Canada. Vancouver Gen Hosp, Vancouver, BC, Canada. Univ Alberta, Edmonton, AB, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Celgene Corp, Summit, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 8588 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602683 ER PT J AU Smith, MR Borre, M Rathenborg, P Werbrouck, P Van Poppel, H Heidenreich, A Iversen, P Baskin-Bey, E Perabo, F Phung, D Tombal, B AF Smith, Matthew Raymond Borre, Michael Rathenborg, Per Werbrouck, Patrick Van Poppel, Hendrik Heidenreich, Axel Iversen, Peter Baskin-Bey, Edwina Perabo, Frank De Phung Tombal, Bertrand TI Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Ctr Canc, Dept Hematol, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Dept Oncol, Boston, MA USA. Arhus Univ Hosp, Dept Urol, Skejby, Denmark. Herlev Hosp, Dept Urol, DK-2730 Herlev, Denmark. AZ Groeninge Kortrijk, Dept Urol, Kortrijk, Belgium. Univ Hosp Leuven, Dept Urol, Louvain, Belgium. RWTH Univ, Dept Urol, Aachen, Germany. Univ Copenhagen, Rigshosp, Dept Urologuy, DK-2100 Copenhagen, Denmark. Astellas Pharma Global Dev Inc, Staines, England. Astellas Pharma Global Dev Inc, Leiderdorp, Netherlands. Clin Univ St Luc, Dept Urol, B-1200 Brussels, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 5001 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601602 ER PT J AU Sonpavde, G Pond, GR Agarwal, N Choueiri, TK Qu, AQ Fougeray, R Salhi, Y Vaughn, DJ James, ND Niegisch, G Albers, P Galsky, MD Wong, YN Stadler, WM O'Donnell, PH Vogelzang, NJ Sridhar, SS Ko, YJ Sternberg, CN Bellmunt, J AF Sonpavde, Guru Pond, Gregory Russell Agarwal, Neeraj Choueiri, Toni K. Qu, Angela Q. Fougeray, Ronan Salhi, Yacine Vaughn, David J. James, Nicholas David Niegisch, Guenter Albers, Peter Galsky, Matt D. Wong, Yu-Ning Stadler, Walter Michael O'Donnell, Peter H. Vogelzang, Nicholas J. Sridhar, Srikala S. Ko, Yoo-Joung Sternberg, Cora N. Bellmunt, Joaquim TI Nomogram to estimate the activity of second-line therapy for advanced urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA. McMaster Univ, Hamilton, ON, Canada. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Rech Pierre Fabre, Boulogne, France. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Birmingham, Birmingham, W Midlands, England. Univ Dusseldorf, Dept Urol, Dusseldorf, Germany. Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Chicago, Chicago, IL 60637 USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. Princess Margaret Canc Ctr, Div Med Oncol & Hematol, Toronto, ON, Canada. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. San Camillo Forlanini Hosp, Rome, Italy. Univ Hosp del Mar, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 4524 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601538 ER PT J AU Soriano, G Landrum, MB Weeks, JC Arora, NK Malin, J Ganz, PA van Ryn, M Keating, NL AF Soriano, Gabriela Landrum, Mary Beth Weeks, Jane C. Arora, Neeraj K. Malin, Jennifer Ganz, Patricia A. van Ryn, Michelle Keating, Nancy Lynn TI The role of families in decisions about cancer treatments SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, Brookline, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NSABP, Los Angeles, CA USA. Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. Univ Minnesota, Minneapolis, MN USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 6528 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602247 ER PT J AU Sosman, JA Martin-Algarra, S Wolchok, JD Sharfman, WH Bhatia, S Hodi, FS Hwu, WJ Gajewski, T Slingluff, CL Kaufman, H Gupta, M McGirr, A Horak, CE Ahlers, CM Wigginton, JM Urba, WJ AF Sosman, Jeffrey Alan Martin-Algarra, Salvador Wolchok, Jedd D. Sharfman, William Howard Bhatia, Shailender Hodi, F. Stephen Hwu, Wen-Jen Gajewski, Thomas Slingluff, Craig L. Kaufman, Howard Gupta, Manish McGirr, Analia Horak, Christine E. Ahlers, Christoph Matthias Wigginton, Jon M. Urba, Walter John TI An exploratory study of the biologic effects of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) treatment in patients (pts) with advanced (unresectable or metastatic) melanoma (MEL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Navarra, E-31080 Pamplona, Spain. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Earle A Chiles Res Inst, Portland, OR USA. Providence Canc Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA TPS3114 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419605408 ER PT J AU Sosman, JA Daud, A Weber, JS Kim, K Kefford, R Flaherty, K Infante, JR Hamid, O Cebon, JS Schuchter, LM McWilliams, RR Sznol, M Sharfman, WH Algazi, AP Lewis, KD Little, SM Sun, P Long, G Patel, K Gonzalez, R AF Sosman, Jeffrey Alan Daud, Adil Weber, Jeffrey S. Kim, Kevin Kefford, Richard Flaherty, Keith Infante, Jeffrey R. Hamid, Omid Cebon, Jonathan S. Schuchter, Lynn Mara McWilliams, Robert R. Sznol, Mario Sharfman, William Howard Algazi, Alain Patrick Lewis, Karl D. Little, Shonda M. Sun, Peng Long, Georgina Patel, Kiran Gonzalez, Rene TI BRAF inhibitor (BRAFi) dabrafenib in combination with the MEK1/2 inhibitor (MEKi) trametinib in BRAFi-naive and BRAFi-resistant patients (pts) with BRAF mutation-positive metastatic melanoma (MM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. H Lee Moffitt Canc Ctr & Res Inst, Comprehens Melanoma Res Ctr, Tampa, FL USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Westmead Hosp, Westmead, NSW 2145, Australia. Melanoma Inst Australia, Westmead, NSW, Australia. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. Angeles Clin & Res Inst, Los Angeles, CA USA. Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Mayo Clin, Rochester, MN USA. Yale Univ, New Haven, CT USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Colorado, Ctr Canc, Aurora, CO USA. GlaxoSmithKline, Collegeville, PA USA. Univ Sydney, Sydney, NSW 2006, Australia. UCHSC, Aurora, CO USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 9005 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602709 ER PT J AU Spigel, DR Gettinger, SN Horn, L Herbst, RS Gandhi, L Gordon, MS Cruz, C Conkling, P Cassier, PA Antonia, SJ Burris, HA Fine, GD Mokatrin, A Kowanetz, M Shen, XD Chen, DS Soria, JC AF Spigel, David R. Gettinger, Scott N. Horn, Leora Herbst, Roy S. Gandhi, Leena Gordon, Michael S. Cruz, Cristina Conkling, Paul Cassier, Philippe Alexandre Antonia, Scott J. Burris, Howard A. Fine, Gregg Daniel Mokatrin, Ahmad Kowanetz, Marcin Shen, Xiaodong Chen, Daniel S. Soria, Jean-Charles TI Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Sarah Cannon Res Inst, Nashville, TN USA. Yale Univ, Sch Med, New Haven, CT USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Yale Univ, New Haven, CT USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Pinnacle Oncol Hematol, Scottsdale, AZ USA. Vall dHebron Univ Hosp, Barcelona, Spain. Virginia Oncol Associates US Oncol, Norfolk, VA USA. Ctr Leon Berard, F-69373 Lyon, France. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Genentech Inc, San Francisco, CA 94080 USA. Inst Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 8008 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602490 ER PT J AU Spurgeon, SEF Wagner-Johnston, ND Furman, RR Flinn, I Coutre, SE Brown, JR Benson, DM Byrd, JC Leonard, J Peterman, S Johnson, DM Gu, J Dansey, RD Godfrey, WR Kahl, BS AF Spurgeon, Stephen Edward Forbes Wagner-Johnston, Nina D. Furman, Richard R. Flinn, Ian Coutre, Steven E. Brown, Jennifer R. Benson, Don M. Byrd, John C. Leonard, John Peterman, Sissy Johnson, David Michael Gu, Jessie Dansey, Roger D. Godfrey, Wayne R. Kahl, Brad S. TI Final results of a phase I study of idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase P110 delta (PI3K delta), in patients with relapsed or refractory mantle cell lymphoma (MCL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Washington Univ, Sch Med, St Louis, MO USA. Weill Cornell Med Coll, New York, NY USA. Sarah Cannon Res Inst, Nashville, TN USA. Stanford Canc Inst, Stanford, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. Gilead Sci Inc, Seattle, WA USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 8519 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602615 ER PT J AU Stinchcombe, T Sholl, LM Wang, XFF Gu, L Socinski, MA Rodig, SJ Capelletti, M Crawford, J Edelman, MJ Villalona-Calero, MA Kratzke, RA Vokes, EE Miller, VA Janne, PA AF Stinchcombe, Tom Sholl, Lynette M. Wang, Xiaofei F. Gu, Lin Socinski, Mark A. Rodig, Scott J. Capelletti, Marzia Crawford, Jeffrey Edelman, Martin J. Villalona-Calero, Miguel Angel Kratzke, Robert Arthur Vokes, Everett E. Miller, Vincent A. Janne, Pasi Antero TI An analysis of the prevalence of HER2 and KRAS mutations, and ALK rearrangements and clinical outcomes in Cancer and Leukemia Group B [CALGB (Alliance)] trial 30406 in advanced non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ N Carolina, Chapel Hill, NC USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Div Hematopathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. Univ Minnesota, Minneapolis, MN USA. Univ Chicago Med & Biol Sci, Chicago, IL USA. Fdn Med Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 8039 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602520 ER PT J AU Strosberg, JR Bobiak, S Zornosa, CC Choti, MA Bergsland, EK Benson, A Bloomston, M Kulke, M Shah, MH Yao, JC AF Strosberg, Jonathan R. Bobiak, Sarah Zornosa, Carrie C. Choti, Michael A. Bergsland, Emily K. Benson, Al Bowen Bloomston, Mark Kulke, Matthew Shah, Manisha H. Yao, James C. TI Dosing patterns for octreotide LAR in neuroendocrine tumor (NET) patients: NCCN NET outcomes database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Natl Comprehens Canc Network, Ft Washington, PA USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Ohio State Univ, Ctr Comprehens Canc, Arthur G James Canc Hosp, Columbus, OH 43210 USA. Richard J Solove Res Inst, Columbus, OH USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Bloomston, Mark/E-2767-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 4142 PG 2 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601515 ER PT J AU Stuckey, A Robison, K Dizon, DS Rogers, M Ott, M Miller, S Politi, M Clark, M AF Stuckey, Ashley Robison, Katina Dizon, Don S. Rogers, Michelle Ott, Miles Miller, Susan Politi, Mary Clark, Melissa TI The role of oncologic health care providers in end of life discussions for women with recurrent gynecologic or breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. Brown Univ, Publ Hlth Program, Providence, RI 02912 USA. Washington Univ, Div Publ Hlth Sci, Sch Med St Louis, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA e20543 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419604812 ER PT J AU Stupp, R Hegi, ME Goriia, T Erridge, S Grujicic, D Steinbach, JP Wick, W Tarnawski, R Nam, DH Weyerbrock, A Hau, P Taphoorn, MJB Nabors, LB Reardon, DA Van den Bent, MJ Perry, JR Hong, YK Hicking, C Picard, M Weller, M AF Stupp, Roger Hegi, Monika E. Goriia, Thierry Erridge, Sara Grujicic, Danica Steinbach, Joachim Peter Wick, Wolfgang Tarnawski, Rafal Nam, Do-Hyun Weyerbrock, Astrid Hau, Peter Taphoorn, Martin J. B. Nabors, Louis B. Reardon, David A. Van den Bent, Martin J. Perry, James R. Hong, Yong Kil Hicking, Christine Picard, Martin Weller, Michael CA EORTC Canadian Brain Tumor Consortium CENTRIC Study Team TI Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation: Final results of the multicenter, randomized, open-label, controlled, phase III CENTRIC study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 CHU Vaudois, CH-1011 Lausanne, Switzerland. EORTC Data Ctr, Brussels, Belgium. Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland. Clin Ctr Serbia, Inst Neurosurg, Belgrade, Serbia. Klinikum JW Goethe Univ Frankfurt, Dr Senkenberg Inst Neuroonkol, Frankfurt, Germany. Univ Klinikum Heidelberg, Heidelberg, Germany. Maria Sklodowska Curie Mem Canc Ctr, Gliwice, Poland. Inst Oncol, Gliwice Branch, Radiotherapy & Chemotherapy Clin, Gliwice, Poland. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. Univ Freiburg Klinikum, Freiburg, Germany. Univ Klinikum Regensburg, Neurol & Wilhelm Sander Therapieeinheit NeuroOnko, Regensburg, Germany. Med Ctr Haaglanden, The Hague, Netherlands. Univ Alabama Birmingham, Birmingham, AL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Erasmus MC, Rotterdam, Netherlands. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea. Merck KGaA, Darmstadt, Germany. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. RI Tarnawski, Rafal/N-7526-2016 NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA LBA2009 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419605334 ER PT J AU Sullivan, RJ Ibrahim, N Lawrence, DP Aldridge, J Hodi, FS Flaherty, K Conley, C DeNoble, S Mier, JW Cho, DC Atkins, MB McDermott, DF AF Sullivan, Ryan J. Ibrahim, Nageatte Lawrence, Donald P. Aldridge, Julie Hodi, F. Stephen Flaherty, Keith Conley, Christine DeNoble, Sarah Mier, James Walter Cho, Daniel C. Atkins, Michael B. McDermott, David F. TI A phase I study of the combination of sorafenib (Sor) and bortezomib (Bor) in patients (pts) with metastatic melanoma (MM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Int Beast Canc Study Grp Stat Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 9076 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602777 ER PT J AU Sznol, M Kluger, HM Hodi, FS McDermott, DF Carvajal, RD Lawrence, DP Topalian, SL Atkins, MB Powderly, JD Sharfman, WH Puzanov, I Smith, DC Wigginton, JM Kollia, G Gupta, AK Sosman, JA AF Sznol, Mario Kluger, Harriet M. Hodi, F. Stephen McDermott, David F. Carvajal, Richard D. Lawrence, Donald P. Topalian, Suzanne Louise Atkins, Michael B. Powderly, John D. Sharfman, William Howard Puzanov, Igor Smith, David C. Wigginton, Jon M. Kollia, Georgia Gupta, Ashok Kumar Sosman, Jeffrey Alan TI Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Yale Canc Ctr, New Haven, CT USA. Yale Univ, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Carolina BioOncol Inst, Huntersville, NC USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA CRA9006 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419603136 ER PT J AU Tanaka, S Batchelor, T Iafrate, AJ Dias-Santagata, D Borger, DR Ellisen, LW Yang, D Louis, DN Cahill, DP Chi, AS AF Tanaka, Shota Batchelor, Tracy Iafrate, Anthony John Dias-Santagata, Dora Borger, Darrell R. Ellisen, Leif William Yang, Daniel Louis, David N. Cahill, Daniel P. Chi, Andrew S. TI Association of PIK3CA-activating mutations with more disseminated disease at presentation and earlier recurrence in glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 2029 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600690 ER PT J AU Topalian, SL Sznol, M Brahmer, JR McDermott, DF Smith, DC Gettinger, SN Taube, JM Drake, CG Pardoll, DM Powderly, JD Carvajal, RD Sosman, JA Atkins, MB Antonia, SJ Spigel, DR Lawrence, DP Kollia, G Gupta, AK Wigginton, JM Hodi, FS AF Topalian, Suzanne Louise Sznol, Mario Brahmer, Julie R. McDermott, David F. Smith, David C. Gettinger, Scott N. Taube, Janis M. Drake, Charles G. Pardoll, Drew M. Powderly, John D. Carvajal, Richard D. Sosman, Jeffrey Alan Atkins, Michael B. Antonia, Scott J. Spigel, David R. Lawrence, Donald P. Kollia, Georgia Gupta, Ashok Kumar Wigginton, Jon M. Hodi, F. Stephen TI Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: Survival and long-term safety in a phase I trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Yale Canc Ctr, New Haven, CT USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Yale Univ, New Haven, CT USA. Johns Hopkins Sch Med, Baltimore, MD USA. Carolina BioOncol Inst, Huntersville, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Bristol Myers Squibb Co, Princeton, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 3002 PG 2 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601135 ER PT J AU Touqir, Z Shaheen, S Upadhyay, S Marak, CP Kumar, G Guddati, AK AF Touqir, Zahra Shaheen, Shagufta Upadhyay, Shivanck Marak, Creticus Petrov Kumar, Gagan Guddati, Achuta Kumar TI Outcomes of severe sepsis in very elderly (age > 80 years) patients with metastatic cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, Ctr Hosp, New York, NY USA. Montefiore Hosp, Albert Einstein Coll Med, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 9558 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419603041 ER PT J AU Tsao, CK Gray, KP Nakabayashi, M Evan, C Galsky, MD Kantoff, PW Oh, WK Pomerantz, M AF Tsao, Che-Kai Gray, Kathryn P. Nakabayashi, Mari Evan, Caroline Galsky, Matt D. Kantoff, Philip W. Oh, William K. Pomerantz, Mark TI Association of Gleason 9-10 prostate cancer with worse outcomes compared to Gleason 8 disease. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mt Sinai Med Ctr, New York, NY 10029 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA e16032 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419604223 ER PT J AU Tseng, YD Paciorek, AT Martin, NE D'Amico, AV Cooperberg, MR Nguyen, PL AF Tseng, Yolanda Diana Paciorek, Alan T. Martin, Neil E. D'Amico, Anthony Victor Cooperberg, Matthew R. Nguyen, Paul Linh TI Impact of prostate cancer national guidelines on brachytherapy monotherapy practice patterns SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Harvard Radiat Oncol Program, Boston, MA USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 5024 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601625 ER PT J AU Uno, H Cronin, A Schrag, D Abel, GA AF Uno, Hajime Cronin, Angel Schrag, Deborah Abel, Gregory Alan TI Derivation and validation of the SEER-Medicare MDS risk score (SMMRS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 [Uno, Hajime; Cronin, Angel; Schrag, Deborah; Abel, Gregory Alan] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 7128 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602485 ER PT J AU Urun, Y Gray, KP Signoretti, S McDermott, DF Atkins, MB Lampron, ME Freedman, M Choueiri, TK Pomerantz, MM AF Urun, Yuksel Gray, Kathryn P. Signoretti, Sabina McDermott, David F. Atkins, Michael B. Lampron, Megan E. Freedman, Matthew Choueiri, Toni K. Pomerantz, Mark M. TI Pharmacogenetics as predictor of sunitinib and mTOR inhibitors toxicity in patients with metastatic renal cell carcinoma (mRCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 4570 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601584 ER PT J AU Vakiavas, C Abramson, VG Lin, NU Liu, MC Rugo, HS Nanda, R Storniolo, AM Traina, TA Li, YF Patil, S Hayes, DF Van Poznak, CH Nangia, JR Irvin, WJ Krontiras, H De Los Santos, JF Haluska, P Wolff, AC Forero-Torres, A AF Vakiavas, Christos Abramson, Vandana Gupta Lin, Nancy U. Liu, Minetta C. Rugo, Hope S. Nanda, Rita Storniolo, Anna Maria Traina, Tiffany A. Li, Yufeng Patil, Sujata Hayes, Daniel F. Van Poznak, Catherine H. Nangia, Julie R. Irvin, William Johnson Krontiras, Helen De Los Santos, Jennifer F. Haluska, Paul Wolff, Antonio C. Forero-Torres, Andres CA TBCRC TI TBCRC 019: An open label, randomized, phase II trial of nanoparticle albumin-bound paclitaxel (nab-PAC) with or without the anti-death receptor 5 (DR5) monoclonal antibody tigatuzumab (TIG) in patients with metastatic triple negative breast cancer (TNBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Alabama Birmingham, Birmingham, AL USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Chicago, Chicago, IL 60637 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Rush Univ, Med Ctr, Houston, TX USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Mayo Clin, Rochester, MN USA. Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 1052 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600292 ER PT J AU Van Allen, EM Wagle, N Carter, SL Sucker, A Farlow, DN Hodis, F Taylor-Weiner, A Berking, C Egberts, F Hassel, JC Gogas, H Gutzmer, R Goldinger, SM Loquai, C Ugurel, S Zimmer, L Gabriel, SB Getz, G Garraway, LA Schadendorf, D AF Van Allen, Eliezer Mendel Wagle, Nikhil Carter, Scott L. Sucker, Antje Farlow, Deborah Norman Hodis, Fran Taylor-Weiner, Amara Berking, Carola Egberts, Friederike Hassel, Jessica Cecile Gogas, Helen Gutzmer, Ralf Goldinger, Simone M. Loquai, Carmen Ugurel, Selma Zimmer, Lisa Gabriel, Stacey B. Getz, Gad Garraway, Levi A. Schadendorf, Dirk CA DeCOG TI The genetic landscape of clinical resistance to RAF inhibition in melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. Univ Hosp Essen, Essen, Germany. Univ Munich, Dept Dermatol, Munich, Germany. Univ Kiel, Kiel, Germany. Univ Heidelberg Hosp, Univ Hautklin, Hauttumorzentrum, Heidelberg, Germany. Hellen Cooperat Oncol Grp HeCOG, Athens, Greece. Hannover Med Sch, D-30623 Hannover, Germany. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Johannes Gutenberg Univ Mainz, Univ Med, D-55122 Mainz, Germany. Univ Wurzburg, D-97070 Wurzburg, Germany. Univ Hosp, Dept Dermatol, Essen, Germany. Univ Klinikum Essen, Essen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 11009 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600419 ER PT J AU Van Cutsem, E Fram, RJ Schlichting, M Ryan, DP AF Van Cutsem, Eric Fram, Robert J. Schlichting, Michael Ryan, David P. TI Efficacy and safety of gemcitabine in combination with TH-302 compared with gemcitabine in combination with placebo in previously untreated patients with metastatic or locally advanced unresectable pancreatic adenocarcinoma: The MAESTRO trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Hosp Leuven, Louvain, Belgium. EMD Serono Inc, Rockland, MA USA. Merck KGaA, Darmstadt, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA TPS4148 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419605432 ER PT J AU Van Loon, K Owzar, K Jiang, C Kindler, HL Mulcahy, MF Niedzwiecki, D O'Reilly, EM Fuchs, CS Innocenti, F Venook, AP AF Van Loon, Katherine Owzar, Kouros Jiang, Chen Kindler, Hedy Lee Mulcahy, Mary Frances Niedzwiecki, Donna O'Reilly, Eileen Mary Fuchs, Charles S. Innocenti, Federico Venook, Alan Paul TI 25-hydroxyvitamin D levels and survival in patients with advanced pancreatic cancer (APC): Findings from CALGB 80303 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Duke Univ, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 4022 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601397 ER PT J AU Vergote, I Teneriello, M Powell, MA Miller, DS Garcia, AA Mikheeva, ON Pinter, T Bidzinski, M Cebotaru, CL Fan, J Ren, M Meneses, N Funahashi, Y Kadowaki, T O'Brien, JP Penson, RT AF Vergote, Ignace Teneriello, Michael Powell, Matthew A. Miller, David S. Garcia, Agustin A. Mikheeva, Olga N. Pinter, Tamas Bidzinski, Mariusz Cebotaru, Cristina Ligia Fan, Jean Ren, Min Meneses, Nicole Funahashi, Yasuhiro Kadowaki, Tadashi O'Brien, James P. Penson, Richard T. TI A phase II trial of lenvatinib in patients with advanced or recurrent endometrial cancer: Angiopoietin-2 as a predictive marker for clinical outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 UZ Leuven, Leuven, Belgium. US Oncol, The Woodlands, TX USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ So Calif, Los Angeles, CA USA. Leningrad Reg Oncol Ctr, State Healthcare Inst, St Petersburg, Russia. Aladar Petz Teaching Cty Hosp, Gyor, Hungary. Maria Sklodowska Curie Mem Inst Oncol, Warsaw, Poland. Inst Oncol Prof Dr Ion Chiricuta, Cluj Napoca, Romania. Eisai Inc, Woodcliff Lake, NJ USA. Eisai Inc, Andover, MA USA. Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. RI Miller, David/H-4604-2011 OI Miller, David/0000-0002-8215-5887 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 5520 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602034 ER PT J AU Wagle, N Van Allen, EM Frederick, DT Cooper, ZA Farlow, DN Treacy, D Goetz, EM Johannessen, CM Carter, SL Taylor-Weiner, A Hodis, E Lawrence, DP Sullivan, RJ Getz, G Gabriel, SB Flaherty, K Wargo, JA Garraway, LA AF Wagle, Nikhil Van Allen, Eliezer Mendel Frederick, Dennie T. Cooper, Zachary A. Farlow, Deborah Norman Treacy, Daniel Goetz, Eva M. Johannessen, Cory M. Carter, Scott L. Taylor-Weiner, Amaro Hodis, Eran Lawrence, Donald P. Sullivan, Ryan J. Getz, Gad Gabriel, Stacey B. Flaherty, Keith Wargo, Jennifer Ann Garraway, Levi A. TI Whole exome and whole transcriptome sequencing in melanoma patients to identify mechanisms of resistance to combined RAF/MEK inhibition SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Broad Inst, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 9015 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602716 ER PT J AU Warren, JL Mariotto, A Melbert, D Schrag, D Doria-Rose, P Penson, DF Yabroff, KR AF Warren, Joan L. Mariotto, Angela Melbert, Danielle Schrag, Deborah Doria-Rose, Paul Penson, David F. Yabroff, K. Robin TI Sensitivity of Medicare claims to identify recurrence SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Informat Management Serv Inc, Beltsville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 6522 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602241 ER PT J AU Wattson, DA Shih, HA Niemierko, A Merritt, RM Lawrence, DP Oh, KS Sullivan, RJ Flaherty, K AF Wattson, Daniel A. Shih, Helen Alice Niemierko, Andrzej Merritt, Ryan M. Lawrence, Donald P. Oh, Kevin S. Sullivan, Ryan J. Flaherty, Keith TI Survival patterns following brain metastases for patients with melanoma in the targeted therapy era SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Harvard Radiat Oncol Program, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 9064 PG 2 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602765 ER PT J AU Weidhaas, JB Lee, JW Slebos, R Howard, J Perez, J Gilbert, J Nallur, S Paranjape, T Garcia, JJ Burtness, B Forastiere, AA Chung, CH AF Weidhaas, Joanne B. Lee, Ju-Whei Slebos, Robbert Howard, Jason Perez, Jimena Gilbert, Jill Nallur, Sunitha Paranjape, Trupti Garcia, Joaquin J. Burtness, Barbara Forastiere, Arlene A. Chung, Christine H. TI Association of the 3 '-untranslated region KRAS-variant with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Yale Univ, Sch Med, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Nashville, TN 37235 USA. Johns Hopkins Univ, Baltimore, MD USA. Yale Univ, New Haven, CT USA. Mayo Clin, Rochester, MN USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Eviti Inc, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 6016 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602140 ER PT J AU Weiss, M Gertz, MA Little, RF Rajkumar, V Jacobus, SJ Abonour, R Anderson, KC Barlogie, B Callander, NS Gorak, EJ Matous, J Mills, GM Kane, RC Katz, MS Jensen, L Omel, J Orlowski, RZ Richardson, PGG Munshi, NC AF Weiss, Matthias Gertz, Morie A. Little, Richard F. Rajkumar, Vincent Jacobus, Susanna J. Abonour, Rafat Anderson, Kenneth Carl Barlogie, Bart Callander, Natalie Scott Gorak, Edward J. Matous, Jeffrey Mills, Glenn Morris Kane, Robert C. Katz, Michael S. Jensen, LeeAnn Omel, James Orlowski, Robert Z. Richardson, Paul Gerard Guy Munshi, Nikhil C. TI Strategies to overcome barriers to accrual (BtA) to NCI-sponsored clinical trials: A project of the NCI-Myeloma Steering Committee Accrual Working Group (NCI-MYSC AWG) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Mayo Clin, Rochester, MN USA. NCI, Rockville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Myeloma Inst Res & Therapy, Little Rock, AR USA. Univ Wisconsin, Madison, WI USA. Geisinger Med Ctr, Danville, PA 17822 USA. Rocky Mt Canc Centers, Denver, CO USA. LSU Hlth Sci Ctr, Shreveport, LA USA. US FDA, Silver Spring, MD USA. Int Myeloma Fdn, North Hollywood, CA USA. Patient Advocate, Rockville, MD USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. VA Boston Healthcare Syst, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 8592 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602687 ER PT J AU Wen, PY Yung, WKA Mellinghoff, IK Lamborn, K Ramkissoon, S Cloughesy, TF Rinne, M Omuro, AMP DeAngelis, LM Gilbert, MR Chi, AS Batchelor, T Colman, H Chang, SM Massacesi, C DiTomaso, E Prados, M Reardon, DA Ligon, KL AF Wen, Patrick Y. Yung, W. K. Alfred Mellinghoff, Ingo K. Lamborn, Kathleen Ramkissoon, Shakti Cloughesy, Timothy Francis Rinne, Mikael Omuro, Antonio Marcilio Padula DeAngelis, Lisa Marie Gilbert, Mark R. Chi, Andrew S. Batchelor, Tracy Colman, Howard Chang, Susan Marina Massacesi, Cristian DiTomaso, Emmanuelle Prados, Michael Reardon, David A. Ligon, Keith L. TI Phase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor BKM120 in recurrent glioblastoma (GBM) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Novartis Pharma SAS, Rueil Malmaison, France. Novartis Inst BioMed Res Inc, Cambridge, MA USA. Boston Childrens Hosp, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 2015 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600676 ER PT J AU Wirth, LJ Dakhil, SR Kornek, G Axelrod, R Adkins, D Pant, S O'Brien, PE Debruyne, PR Oliner, KS Dong, J Bach, BA AF Wirth, Lori J. Dakhil, Shaker R. Kornek, Gabriela Axelrod, Rita Adkins, Douglas Pant, Shubham O'Brien, Paul E. Debruyne, Philip R. Oliner, Kelly S. Dong, Jun Bach, Bruce A. TI PARTNER: A randomized phase II study of docetaxel/cisplatin (doc/cis) chemotherapy with or without panitumumab (pmab) as first-line treatment (tx) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Canc Ctr Kansas, Wichita, KS USA. Med Univ Wien, Vienna, Austria. Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Med Oncol, Philadelphia, PA 19107 USA. Washington Univ Sch Med, St Louis, MO USA. Univ Oklahoma Hlth Sci Ctr, Oklahoma City, OK USA. Med Univ S Carolina, Charleston, SC 29425 USA. AZ Groeninge Hosp, Kortrijk, Belgium. Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 6029 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602153 ER PT J AU Wood, ME Qin, R Le-Petross, HT Hwang, ES Ligibel, JA Mayer, IA Marshall, JR Goodwin, PJ AF Wood, Marie E. Qin, Rui Le-Petross, Hthong T. Hwang, E. Shelley Ligibel, Jennife A. Mayer, Ingrid A. Marshall, James Roger Goodwin, Pamela Jean TI Change in mammographic density with metformin use: A companion study to NCIC study MA.32. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Vermont, Coll Med, Burlington, VT USA. Mayo Clin, Rochester, MN USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA TPS1608 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419605381 ER PT J AU Wright, AA Earle, C Keating, NL AF Wright, Alexi A. Earle, Craig Keating, Nancy Lynn TI End-of-life care for Medicare beneficiaries with ovarian cancer: Evaluation of intensity and rate of hospitalizations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Clin Evaluat Sci, Toronto, ON, Canada. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 9523 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419603006 ER PT J AU Xu, CF Johnson, T Choueiri, TK Deen, KC Xue, ZY Spraggs, CF Bartlett-Pandite, AN Carpenter, C Motzer, RJ AF Xu, Chun-Fang Johnson, Toby Choueiri, Toni K. Deen, Keith C. Xue, Zhengyu Spraggs, Colin F. Bartlett-Pandite, Arundathy N. Carpenter, Christopher Motzer, Robert John TI Association of IL8 polymorphisms with overall survival in patients with renal cell carcinoma in COMPARZ (pazopanib versus sunitinib phase III study) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 GlaxoSmithKline, Harlow, Essex, England. GlaxoSmithKline, Uxbridge, Middx, England. Dana Farber Canc Inst, Boston, MA 02115 USA. GlaxoSmithKline, Collegeville, PA USA. GlaxoSmithKline, Res Triangle Pk, NC USA. GlaxoSmithKline Res & Dev Ltd, Collegeville, PA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 4519 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601533 ER PT J AU Yardley, DA Hortobagyi, GN Lebrun, F Beck, JT Neven, P Baselga, J Petrakova, K Dakhil, SR Sabatini, S Komorowski, A Chouinard, EE Young, RR Gnant, M Pritchard, KI Zhang, J Ziemiecki, R Panneerselvam, A Taran, T Sahmoud, T Noguchi, S AF Yardley, Denise Aysel Hortobagyi, Gabriel N. Lebrun, Fabienne Beck, J. Thaddeus Neven, Patrick Baselga, Jose Petrakova, Katarina Dakhil, Shaker R. Sabatini, Silvia Komorowski, Anna Chouinard, Edmond Emilien Young, Robyn R. Gnant, Michael Pritchard, Kathleen I. Zhang, Jie Ziemiecki, Ryan Panneerselvam, Ashok Taran, Tanya Sahmoud, Tarek Noguchi, Shinzaburo TI Patient-reported physical, emotional, and social functioning in advanced breast cancer: Insights from BOLERO-2. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Sarah Cannon Res Inst, Nashville, TN USA. Tennessee Oncol, Nashville, TN USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Highlands Oncol Grp, Fayetteville, AR USA. Hosp Gasthuisberg, Louvain, Belgium. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Masaryk Mem Canc Inst, Brno, Czech Republic. Canc Ctr Kansas, Wichita, KS USA. Hosp Santa Maria, Terni, Italy. Hematol Oncol Associates Rockland, Nyack, NY USA. Cambridge Mem Hosp, Cambridge, ON, Canada. Ctr Canc & Blood Disorders, Ft Worth, TX USA. Med Univ Vienna, Dept Surg, Ctr Comprehens Canc, Vienna, Austria. Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON M4N 3M5, Canada. Univ Toronto, Toronto, ON, Canada. Novartis Pharmaceut, Florham Pk, NJ USA. RTI Hlth Solut, Res Triangle Pk, NC USA. Novartis Pharmaceut, Florham Pk, NJ USA. Novartis Pharmaceut, Global Oncol Dev, Florham Pk, NJ USA. Osaka Univ, Osaka, Japan. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 553 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600058 ER PT J AU Yoo, SM Werner, L Nakabayashi, M Sweeney, C Hirsch, MS Kantoff, PW Pomerantz, MM AF Yoo, Sun Mi Werner, Lillian Nakabayashi, Mari Sweeney, Christopher Hirsch, Michelle S. Kantoff, Philip W. Pomerantz, Mark M. TI Clinicopathologic features and clinical outcomes associated with Gleason upgrading from biopsy to radical prostatectomy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 5056 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601654 ER PT J AU Youn, T Jacene, HA Dipiro, P Tanaka, Y Bellon, JR Nakhlis, F Hirshfield-Bartek, J Yeh, E Overmoyer, B AF Youn, Trisha Jacene, Heather A. Dipiro, Pamela Tanaka, Yoko Bellon, Jennifer Ruth Nakhlis, Faina Hirshfield-Bartek, Judith Yeh, Eren Overmoyer, Beth TI Metabolic characterization of inflammatory breast cancer (IBC) with baseline FDG-PET/CT: Relationship with histopathology, hormone receptor status, and pathologic response after neoadjuvant chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 1105 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600463 ER PT J AU Yu, EY Duan, FH Muzi, M Gorelick, J Chin, B Alumkal, JJ Taplin, ME Herman, B Higano, CS Doot, RK Hartfeil, DM Febbo, PG Mankoff, DA AF Yu, Evan Y. Duan, Fenghai Muzi, Mark Gorelick, Jeremy Chin, Bennett Alumkal, Joshi J. Taplin, Mary-Ellen Herman, Ben Higano, Celestia S. Doot, Robert K. Hartfeil, Donna M. Febbo, Phillip G. Mankoff, David A. CA Dept Def Prostate Canc Clinical Amer Coll Radiology Imaging TI Correlation of F-18-fluoride PET response to dasatinib in castration-resistant prostate cancer bone metastases with progression-free survival: Preliminary results from ACRIN 6687 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. Brown Univ, Providence, RI 02912 USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Durham, NC USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Amer Coll Radiol Imaging Network, Philadelphia, PA USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Univ Penn, Philadelphia, PA 19104 USA. RI Duan, Fenghai/J-3709-2014 OI Duan, Fenghai/0000-0002-5084-0070 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 5003 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601604 ER PT J AU Zafar, Y Abernethy, AP Tulsky, JA Ubel, PA Schrag, D Rushing, C Chino, F Nicolla, J Altomare, I Samsa, G Peppercorn, JM AF Zafar, Yousuf Abernethy, Amy Pickar Tulsky, James A. Ubel, Peter A. Schrag, Deborah Rushing, Christel Chino, Fumiko Nicolla, Jonathan Altomare, Ivy Samsa, Greg Peppercorn, Jeffrey M. TI Financial distress, communication, and cancer treatment decision making: Does cost matter? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Duke Univ, Med Ctr, Durham, NC USA. Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC USA. Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Sch Med, Durham, NC USA. Duke Univ, Med Ctr, Dept Biostat & Informat, Durham, NC USA. Duke Canc Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 6506 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602226 ER PT J AU Zeghibe, CA Luis, IMVD Frank, ES Sohl, J Washington, KE Silverman, SG Fonte, JM Mayer, EL Overmoyer, B Richardson, AL Krop, IE Winer, EP Lin, NU AF Zeghibe, Catherine A. Luis, Ines Maria Vaz Duarte Frank, Elizabeth S. Sohl, Jessica Washington, Kimberly E. Silverman, Stuart G. Fonte, Joseph M. Mayer, Erica L. Overmoyer, Beth Richardson, Andrea L. Krop, Ian E. Winer, Eric P. Lin, Nancy U. TI Prospective clinical experience with research biopsies in breast cancer patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Faulkner Hosp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA e17574 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419604443 ER PT J AU Zeidan, A Sun, ZX Prebet, T Greenberg, P Juckett, M Smith, MR Paietta, E Gabrilove, JL Erba, HP Gore, S Tallman, MS AF Zeidan, Amer Sun, Zhuoxin Prebet, Thomas Greenberg, Peter Juckett, Mark Smith, Mitchell Reed Paietta, Elisabeth Gabrilove, Janice Lynn Erba, Harry P. Gore, Steven Tallman, Martin S. CA Eastern Cooperative Oncology Grp TI Application of the French prognostic score (FPS) to assess overall survival (OS) in a US-based cohort of patients (pts) treated with azacitidine (Aza). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Aix Marseille Univ, Marseille, France. Stanford Univ, Stanford, CA 94305 USA. Univ Wisconsin, Madison, WI USA. Cleveland Clin, Cleveland, OH 44106 USA. Montefiore Med Ctr, North Div, New York, NY USA. Icahn Sch Med Mt Sinai, New York, NY USA. Univ Alabama Birmingham, Birmingham, AL USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 7126 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602483 ER PT J AU Zhang, Y Schnabel, CA Schroeder, B Jerevall, PL Jankowitz, RC Stal, O Brufsky, A Sgroi, D Erlander, MG AF Zhang, Yi Schnabel, Catherine A. Schroeder, Brock Jerevall, Piiha-Lotta Jankowitz, Rachel Catherine Stal, Olle Brufsky, Adam Sgroi, Dennis Erlander, Mark G. TI Prediction of early and late distant recurrence in early-stage breast cancer with Breast Cancer Index SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 BioTheranost Inc, San Diego, CA USA. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Pittsburgh, Med Ctr, Magee Womens Canc Program, Pittsburgh, PA USA. Linkoping Univ, Linkoping, Sweden. Univ Pittsburgh, Sch Med, Div Hematol & Oncol, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 594 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419600099 ER PT J AU Zuo, ZX Keck, MK Khattri, A Patel, RD Walter, K Lingen, MW White, KP Hammerman, PS Cohen, EEW Stenson, K Blair, EA Shames, DS Vokes, EE Seiwert, TY AF Zuo, Zhixiang Keck, Michaela K. Khattri, Arun Patel, Rajesh D. Walter, Kim Lingen, Mark W. White, Kevin P. Hammerman, Peter S. Cohen, Ezra E. W. Stenson, Kerstin Blair, Elizabeth A. Shames, David S. Vokes, Everett E. Seiwert, Tanguy Y. TI Multimodality determination of HPV status in head and neck cancers (HNC) and development of an HPV signature SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ Chicago, Chicago, IL 60637 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Chicago Med & Biol Sci, Chicago, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Zuo, Zhixiang/M-4441-2016 OI Zuo, Zhixiang/0000-0002-2492-2689 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 6008 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602133 ER PT J AU De Waal, EM Liang, HY Pierce, A Hamilton, RT Buffenstein, R Chaudhuri, AR AF De Waal, Eric M. Liang, Hanyu Pierce, Anson Hamilton, Ryan T. Buffenstein, Rochelle Chaudhuri, Asish R. TI Elevated protein carbonylation and oxidative stress do not affect protein structure and function in the long-living naked-mole rat: A proteomic approach SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Naked-mole rat; Peroxiredoxin 1; Triosephosphate isomerase; Protein carbonylation; Oxidative stress ID AGE-RELATED-CHANGES; 2-CYS PEROXIREDOXIN; TRIOSEPHOSPHATE ISOMERASE; CRYSTAL-STRUCTURE; LONGEVITY; RODENT; ERYTHROCYTES; DISEASE AB The 'oxidative stress theory of aging' predicts that aging is primarily regulated by progressive accumulation of oxidized macromolecules that cause deleterious effects to cellular homeostasis and induces a decline in physiological function. However, our reports on the detection of higher level of oxidized protein carbonyls in the soluble cellular fractions of long-living rodent naked-mole rats (NMRs, lifespan similar to 30 yrs) compared to short-lived mice (lifespan similar to 3.5 yrs) apparently contradicts a key tenet of the oxidative theory. As oxidation often inactivates enzyme function and induces higher-order soluble oligomers, we performed a comprehensive study to measure global protein carbonyl level in different tissues of age-matched NMRs and mice to determine if the traditional concept of oxidation mediated impairment of function and induction of higher-order structures of proteins are upheld in the NMRs. We made three intriguing observations with NMRs proteins: (1) protein carbonyl is significantly elevated across different tissues despite of its exceptional longevity, (2) enzyme function is restored despite of experiencing higher level of protein carbonylation, and (3) enzymes show lesser sensitivity to form higher-order non-reducible oligomers compared to short-living mouse proteins in response to oxidative stress. These observations were made based on the global analysis of protein carbonyl and identification of two heavily carbonylated proteins in the kidney, triosephosphate isomerase (TPI) and cytosolic peroxiredoxin (Prdx1). These un-expected intriguing observations thus strongly suggest that oxidative modification may not be the only criteria for impairment of protein and enzyme function; cellular environment is likely be the critical determining factor in this process and may be the underlying mechanism for exceptional longevity of NMR. (C) 2013 Elsevier Inc. All rights reserved. C1 [De Waal, Eric M.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Liang, Hanyu] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, San Antonio, TX 78229 USA. [Pierce, Anson] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. [Buffenstein, Rochelle; Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Hamilton, Ryan T.; Buffenstein, Rochelle] South Texas Vet Hlth Care Syst, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Chaudhuri, Asish R.] South Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. [Hamilton, Ryan T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Chaudhuri, AR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Texas Res Pk Campus,15355 Lambda Dr, San Antonio, TX 78245 USA. EM chaudhuria@uthscsa.edu FU National Institutes of Health/National Institute on Aging [K07 AG025063 04]; NIH/NIA [RO1AG-022891] FX This work was supported by the National Institutes of Health/National Institute on Aging pilot Grants K07 AG025063 04 (to A.C.) and from an NIH/NIA RO1AG-022891 (to R.B.). The following funding sources had no involvement in the interpretation, representation or publication of the work other providing the funding necessary. NR 20 TC 8 Z9 8 U1 1 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 17 PY 2013 VL 434 IS 4 BP 815 EP 819 DI 10.1016/j.bbrc.2013.04.019 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 161SI UT WOS:000320213200020 PM 23618867 ER PT J AU Slopen, N Goodman, E Koenen, KC Kubzansky, LD AF Slopen, Natalie Goodman, Elizabeth Koenen, Karestan C. Kubzansky, Laura D. TI Socioeconomic and Other Social Stressors and Biomarkers of Cardiometabolic Risk in Youth: A Systematic Review of Less Studied Risk Factors SO PLOS ONE LA English DT Review ID CARDIOVASCULAR-DISEASE RISK; ADVERSE CHILDHOOD EXPERIENCES; BODY-MASS INDEX; INSULIN-RESISTANCE; HEART-DISEASE; METABOLIC SYNDROME; ALLOSTATIC LOAD; YOUNG-PEOPLE; WAIST CIRCUMFERENCE; PHYSICAL-ACTIVITY AB Background: Socioeconomic disadvantage and other social stressors in childhood have been linked with cardiometabolic diseases in adulthood; however the mechanisms underlying these observed associations and the timing of their emergence are unclear. The aim of this review was to evaluate research that examined relationships between socioeconomic disadvantage and other social stressors in relation to less-studied cardiometabolic risk factors among youth, including carbohydrate metabolism-related factors, lipids, and central adiposity. Methods: We searched PubMed and ISI Web of Science to identify relevant publications between 2001 and 2013. Studies were selected based on 4 criteria: (1) the study examined an association between at least one social or economic stressor and one relevant outcome prior to age 21; (2) the sample originated from a high-income country; (3) the sample was not selected based on a health condition; and (4) a central aim was to evaluate the effect of the social or economic stressor on at least one relevant outcome. Abstracts were screened and relevant publications were obtained and evaluated for inclusion criteria. We abstracted data from selected articles, summarized them by exposures and outcomes, and assigned an evidence grade. Results: Our search identified 37 publications from 31 studies. Socioeconomic disadvantage was consistently associated with greater central adiposity. Research to date does not provide clear evidence of an association between childhood stressors and lipids or carbohydrate metabolism-related factors. Conclusions: This review demonstrates a paucity of research on the relationship of socioeconomic disadvantage and other social stressors to lipid and carbohydrate metabolism-related factors in youth. Accordingly, it is not possible to form strong conclusions, particularly with regard to stressors other than socioeconomic disadvantage. Findings are used to inform priorities for future research. An improved understanding of these pathways is critical for identifying novel prevention targets and intervention opportunities to protect the long-term health of children and adolescents. C1 [Slopen, Natalie] Harvard Univ, Ctr Developing Child, Cambridge, MA 02138 USA. [Slopen, Natalie; Kubzansky, Laura D.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Goodman, Elizabeth] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Goodman, Elizabeth] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Koenen, Karestan C.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. RP Slopen, N (reprint author), Harvard Univ, Ctr Developing Child, Cambridge, MA 02138 USA. EM nslopen@hsph.harvard.edu RI Koenen, Karestan/K-5402-2014 OI Koenen, Karestan/0000-0003-3293-4281 FU NIH [DL46200]; Robert Wood Johnson Foundation FX This research was supported in part by NIH grant DL46200, and funding from the Robert Wood Johnson Foundation to support the research related to the Early Childhood Innovation Project at the Center on the Developing Child. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 4 Z9 5 U1 7 U2 25 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 MAY 17 PY 2013 VL 8 IS 5 AR e64418 DI 10.1371/journal.pone.0064418 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RJ UT WOS:000319107900098 PM 23691213 ER PT J AU Rosen, LS Lipton, L Price, TJ Belman, ND Boccia, RV Hurwitz, HI Stephenson, JJ Wirth, LJ Mccoy, S Hei, Y Hsu, CP Tebbutt, NC AF Rosen, Lee S. Lipton, Lara Price, Timothy J. Belman, Neil D. Boccia, Ralph V. Hurwitz, Herbert I. Stephenson, Joe J., Jr. Wirth, Lori J. Mccoy, Sheryl Hei, Yong-jiang Hsu, Cheng-Pang Tebbutt, Niall C. TI The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors SO BMC CANCER LA English DT Article ID RENAL-CELL CARCINOMA; GASTROINTESTINAL STROMAL TUMORS; ORAL ANGIOGENESIS INHIBITOR; IMATINIB MESYLATE; LUNG-CANCER; CONTROLLED-TRIALS; CLINICAL-TRIALS; THYROID-CANCER; SAFETY; COMBINATION AB Background: Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function. Methods: Patients with advanced metastatic solid tumors ineligible for or progressing on standard-of-care therapies with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14-days-on/7-days-off (Arm B); or 75 mg BID, 5-days-on/2-days-off (Arm C). Primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound; independent review) and function (ejection fraction by CCK-HIDA; investigator assessment). Results: Forty-nine patients received >= 1 dose of motesanib (Arms A/B/C, n = 25/12/12). Across all patients, gallbladder volume increased by a mean 22.2 cc (from 38.6 cc at baseline) and ejection fraction decreased by a mean 19.2% (from 61.3% at baseline) during treatment. Changes were similar across arms and appeared reversible after treatment discontinuation. Three patients had cholecystitis (grades 1, 2, 3, n = 1 each) that resolved after treatment discontinuation, one patient developed grade 3 acute cholecystitis requiring cholecystectomy, and two patients had other notable grade 1 gallbladder disorders (gallbladder wall thickening, gallbladder dysfunction) (all in Arm A). Two patients developed de novo gallstones during treatment. Twelve patients had right upper quadrant pain (Arms A/B/C, n = 8/1/3). The incidence of biliary "sludge" in Arms A/B/C was 39%/36%/27%. Conclusions: Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis. C1 [Rosen, Lee S.] Univ Calif Los Angeles, Dept Med, Santa Monica, CA USA. [Lipton, Lara] Western Hosp, Footscray, Vic, Australia. [Lipton, Lara] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Price, Timothy J.] Univ Adelaide, Queen Elizabeth Hosp, Sch Med, Woodville, SA 5011, Australia. [Belman, Neil D.] Oncol Hematol Lehigh Valley, Bethlehem, PA USA. [Boccia, Ralph V.] Ctr Canc & Blood Disorders, Bethesda, MD USA. [Hurwitz, Herbert I.] Duke Univ, Med Ctr, Durham, NC USA. [Stephenson, Joe J., Jr.] Canc Ctr Carolinas, Greenville, SC USA. [Wirth, Lori J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wirth, Lori J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mccoy, Sheryl] Amgen Inc, Dept Biostat, San Francisco, CA USA. [Hei, Yong-jiang] Amgen Inc, Dept Oncol, Thousand Oaks, CA 91320 USA. [Hsu, Cheng-Pang] Amgen Inc, Dept Pharmacokinet & Drug Metab, Thousand Oaks, CA 91320 USA. [Tebbutt, Niall C.] Austin Hosp, Ludwig Oncol Unit, Heidelberg, Vic 3084, Australia. RP Rosen, LS (reprint author), Univ Calif Los Angeles, Dept Med, Santa Monica, CA USA. EM LRosen@mednet.ucla.edu RI Price, Timothy/G-1404-2012 OI Price, Timothy/0000-0002-3922-2693 FU Amgen Inc.; GSK FX LSR, LL, NDB, and JJS have no competing interests to declare. TJP and LJW have been consultants to Amgen Inc. RVB has received honoraria from and holds stock in Amgen Inc. HIH has received research funding from GSK. NCT has received research funding from Amgen Inc. and has provided expert testimony on behalf of Amgen Inc. SM, Y-JH, and C-PH are employees of and shareholders in Amgen Inc. The authors thank Rebeca Melara (Amgen Inc.) for pharmacokinetic analysis; Benjamin Scott (Complete Healthcare Communications, Inc., Chadds Ford, PA, USA), whose work was funded by Amgen Inc., and Beate Quednau (Amgen Inc.) for assistance in manuscript writing. NR 41 TC 3 Z9 3 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAY 16 PY 2013 VL 13 AR 242 DI 10.1186/1471-2407-13-242 PG 11 WC Oncology SC Oncology GA 170XH UT WOS:000320888000001 PM 23679351 ER PT J AU Bohr, S Patel, SJ Vasko, R Shen, KY Huang, GF Yarmush, ML Berthiaume, F AF Bohr, Stefan Patel, Suraj J. Vasko, Radovan Shen, Keyue Huang, Guofeng Yarmush, Martin L. Berthiaume, Francois TI Highly Upregulated Lhx2 in the Foxn1(-/-) Nude Mouse Phenotype Reflects a Dysregulated and Expanded Epidermal Stem Cell Niche SO PLOS ONE LA English DT Article ID HAIR FOLLICLE DEVELOPMENT; SKIN EPITHELIAL-CELLS; IMMUNOHISTOCHEMICAL EXPRESSION; PROMOTES DIFFERENTIATION; BETA-CATENIN; IN-VITRO; KERATINOCYTES; CD34; SHH; CD200 AB Hair cycling is a prime example of stem cell dependent tissue regeneration and replenishment, and its regulatory mechanisms remain poorly understood. In the present study, we evaluated the effect of a blockage in terminal keratinocytic lineage differentiation in the Foxn1(-/-) nude phenotype on the epithelial progeny. Most notably we found a constitutive upregulation of LIM homeobox protein 2 (Lhx2), a marker gene of epithelial stem cellness indispensible for hair cycle progression. However, histological evidence along with an erratic, acyclic rise of otherwise suppressed CyclinD1 levels along with several key markers of keratinocyte lineage differentiation indicate a frustrated expansion of epithelial stem cell niches in skin. In addition, CD49f/CD34/CD200-based profiling demonstrated highly significant shifts in subpopulations of epithelial progeny. Intriguingly this appeared to include the expansion of Oct4+ stem cells in dermal fractions of skin isolates in the Foxn1 knock-out opposed to wild type. Overall our findings indicate that the Foxn1(-/-) phenotype has a strong impact on epithelial progeny and thus offers a promising model to study maintenance and regulation of stem cell niches within skin not feasible in other in vitro or in vivo models. C1 [Bohr, Stefan; Patel, Suraj J.; Shen, Keyue; Huang, Guofeng; Yarmush, Martin L.] Harvard Univ, Shriners Hosp Children, Sch Med, Ctr Engn Med, Boston, MA 02115 USA. [Bohr, Stefan; Patel, Suraj J.; Shen, Keyue; Huang, Guofeng; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Vasko, Radovan] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Yarmush, Martin L.; Berthiaume, Francois] Rutgers State Univ, Dept Biomed Engn, New Brunswick, NJ 08903 USA. RP Bohr, S (reprint author), Harvard Univ, Shriners Hosp Children, Sch Med, Ctr Engn Med, Boston, MA 02115 USA. EM bohrs@partners.org FU Shriners Hospitals for Children; Deutsche Forschungs Gemeinschaft (DFG, Germany) [GZ:BO3468/2-1] FX This work was funded by the Shriners Hospitals for Children. S. Bohr is a recipient of a Deutsche Forschungs Gemeinschaft (DFG, Germany) postdoctoral fellowship award (GZ:BO3468/2-1). S. J. Patel was supported by a Shriners Hospital for Children postdoctoral fellowship award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 2 Z9 2 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 16 PY 2013 VL 8 IS 5 AR e64223 DI 10.1371/journal.pone.0064223 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146HW UT WOS:000319081900074 PM 23696871 ER PT J AU Prabhakar, S Goto, J Zuang, X Sena-Esteves, M Bronson, R Brockmann, J Gianni, D Wojtkiewicz, GR Chen, JW Stemmer-Rachamimov, A Kwiatkowski, DJ Breakefield, XO AF Prabhakar, Shilpa Goto, June Zuang, Xuan Sena-Esteves, Miguel Bronson, Roderick Brockmann, Jillian Gianni, Davide Wojtkiewicz, Gregory R. Chen, John W. Stemmer-Rachamimov, Anat Kwiatkowski, David J. Breakefield, Xandra O. TI Stochastic Model of Tsc1 Lesions in Mouse Brain SO PLOS ONE LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; MTOR PATHWAY; GIANT-CELLS; RAPAMYCIN; ACTIVATION; MANAGEMENT; SURVIVAL; DEFICITS; MICE AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC comprise a high frequency of mental retardation and developmental disorders including autism, as well as epilepsy. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple brain cell types in a stochastic pattern. Injection of an adeno-associated virus vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a Tsc1 conditional allele on the day of birth led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. The severity of clinical and pathologic findings as well as survival was shown to be dependent upon the dose and serotype of Cre virus injected. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated lesions involving different numbers and types of cells. This model provides a valuable and unique addition for therapeutic assessment. C1 [Prabhakar, Shilpa; Zuang, Xuan; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Prabhakar, Shilpa; Zuang, Xuan; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Prabhakar, Shilpa; Zuang, Xuan; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Goto, June; Kwiatkowski, David J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Translat Med Div,Dept Med, Boston, MA 02115 USA. [Sena-Esteves, Miguel; Gianni, Davide] Univ Massachusetts, Sch Med, Dept Neurol, Gene Therapy Ctr, Worcester, MA USA. [Bronson, Roderick] Harvard Univ, Sch Med, Rodent Histopathol Core Facil, Boston, MA USA. [Brockmann, Jillian; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wojtkiewicz, Gregory R.; Chen, John W.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Wojtkiewicz, Gregory R.; Chen, John W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu FU NIH/NINDS [NS24279-23, R01NS070835, R01NS072167]; DOD Army Grant [W81XWH-13-1-0076] FX NIH/NINDS NS24279-23, R01NS070835, R01NS072167 and DOD Army Grant W81XWH-13-1-0076 for the Award Mechanism: Exploration - Hypothesis Development Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 6 Z9 6 U1 1 U2 5 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 MAY 16 PY 2013 VL 8 IS 5 AR e64224 DI 10.1371/journal.pone.0064224 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146HW UT WOS:000319081900075 PM 23696872 ER PT J AU Heo, K Kim, JS Kim, K Kim, H Choi, J Yang, K An, W AF Heo, K. Kim, J-S Kim, K. Kim, H. Choi, J. Yang, K. An, W. TI Cell-penetrating H4 tail peptides potentiate p53-mediated transactivation via inhibition of G9a and HDAC1 SO ONCOGENE LA English DT Article DE p53; histone; transcription; acetylation; methylation ID TUMOR-SUPPRESSOR P53; TRANSCRIPTIONAL REGULATION; CANCER-CELLS; COMPLEX; PROTEIN; RECRUITMENT; TRANSDUCTION; ACTIVATION; REPRESSION; PHYSIOLOGY AB Histone acetylation has a central role in establishing an active chromatin environment. The functional contribution of histone acetylation to chromatin transcription is accomplished by a dominant action of histone acetyltransferases over repressive histone-modifying activities at gene promoters; misregulation of these dynamic events can lead to various diseases. Here, we describe the synthesis and characterization of transducible peptides derived from histone H4 N-terminal tail as a molecular tool to establish and maintain the active state of p53 target genes. Cellular experiments demonstrate a distinct increase in p53 transactivation by acetylated H4 tail peptides, but only a modest change by unmodified H4 tail peptides. The molecular basis underlying the observed effects involves the selective interaction of the tail peptides with G9a histone methyltransferase and histone deacetylase 1 (HDAC1) and the disruption of their occupancy at p53 target promoters. Furthermore, treatment of xenograft models and cancer cell lines with the tail peptides sharply decline tumor cell growth and enhances apoptosis in response to DNA damage. These results indicate that H4 tail peptide mimics upregulate p53 transcription pathway and may be used as a novel strategy for anticancer therapy. C1 [Heo, K.; Kim, K.; Kim, H.; Choi, J.; An, W.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. [Heo, K.; Kim, J-S; Yang, K.] Dongnam Inst Radiol & Med Sci DIRAMS, Res Ctr, Pusan, South Korea. [Kim, H.] Harvard Univ, Sch Med, Dept Pediat,Dana Farber Canc Inst,Childrens Hosp, Dept Pediat Oncol,Div Hematol Oncol, Boston, MA 02115 USA. RP An, W (reprint author), Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biochem & Mol Biol, 1450 Biggy St NRT6507, Los Angeles, CA 90089 USA. EM woojinan@usc.edu OI Heo, Kyu/0000-0001-8833-4731 FU National Institutes of Health [R01GM84209]; American Cancer Society [RSG DMC1005001]; DIRAMS from the Ministry of Education, Science and Technology [50595-2012] FX We thank Dr Michael Stallcup and Mr Dan Gerke for the gift of pSG5-FLAG-G9a and G9a shRNA constructs. The technical assistance of Drs Balachandra Hegde and Ralph Langen in circular dichroism analysis is greatly acknowledged. We also thank Dr Jing Huang for p53K373me2 antibody. This work was supported by R01GM84209 to WA from the National Institutes of Health, RSG DMC1005001 to WA from the American Cancer Society and DIRAMS (50595-2012) to KH from the Ministry of Education, Science and Technology. NR 33 TC 7 Z9 8 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 16 PY 2013 VL 32 IS 20 BP 2510 EP 2520 DI 10.1038/onc.2012.273 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 148UY UT WOS:000319274300002 PM 22751130 ER PT J AU Donelan, K DesRoches, CM Dittus, RS Buerhaus, P AF Donelan, Karen DesRoches, Catherine M. Dittus, Robert S. Buerhaus, Peter TI Perspectives of Physicians and Nurse Practitioners on Primary Care Practice SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DIRECTIONS AB BACKGROUND The U.S. health care system is at a critical juncture in health care workforce planning. The nation has a shortage of primary care physicians. Policy analysts have proposed expanding the supply and scope of practice of nurse practitioners to address increased demand for primary care providers. These proposals are controversial. METHODS From November 23, 2011, to April 9, 2012, we conducted a national postal-mail survey of 972 clinicians (505 physicians and 467 nurse practitioners) in primary care practice. Questionnaire domains included scope of work, practice characteristics, and attitudes about the effect of expanding the role of nurse practitioners in primary care. The response rate was 61.2%. RESULTS Physicians reported working longer hours, seeing more patients, and earning higher incomes than did nurse practitioners. A total of 80.9% of nurse practitioners reported working in a practice with a physician, as compared with 41.4% of physicians who reported working with a nurse practitioner. Nurse practitioners were more likely than physicians to believe that they should lead medical homes, be allowed hospital admitting privileges, and be paid equally for the same clinical services. When asked whether they agreed with the statement that physicians provide a higher-quality examination and consultation than do nurse practitioners during the same type of primary care visit, 66.1% of physicians agreed and 75.3% of nurse practitioners disagreed. CONCLUSIONS Current policy recommendations that are aimed at expanding the supply and scope of practice of primary care nurse practitioners are controversial. Physicians and nurse practitioners do not agree about their respective roles in the delivery of primary care. (Funded by the Gordon and Betty Moore Foundation and others.) C1 [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Donelan, Karen] Harvard Univ, Sch Med, Boston, MA USA. [DesRoches, Catherine M.] Math Policy Res, Cambridge, MA USA. [Dittus, Robert S.] Vanderbilt Univ, Dept Med, Inst Med & Publ Hlth, Nashville, TN USA. [Dittus, Robert S.] VA Tennessee Valley Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Buerhaus, Peter] Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Nashville, TN USA. RP Donelan, K (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM kdonelan@partners.org FU Gordon and Betty Moore Foundation; Johnson & Johnson Campaign for Nursing's Future; Robert Wood Johnson Foundation FX Funded by the Gordon and Betty Moore Foundation and others.; Supported by the Gordon and Betty Moore Foundation, the Johnson & Johnson Campaign for Nursing's Future, and the Robert Wood Johnson Foundation. NR 14 TC 50 Z9 50 U1 3 U2 30 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 2013 VL 368 IS 20 BP 1898 EP 1906 DI 10.1056/NEJMsa1212938 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 143VK UT WOS:000318896200009 PM 23675658 ER PT J AU Vyas, JM Gonzalez, RG Pierce, VM AF Vyas, Jatin M. Gonzalez, R. Gilberto Pierce, Virginia M. TI Case 15-2013: A 76-Year-Old Man with Fever, Worsening Renal Function, and Altered Mental Status SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID WEST-NILE-VIRUS; INFECTIONS C1 [Vyas, Jatin M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Pierce, Virginia M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Vyas, Jatin M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Pierce, Virginia M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Vyas, JM (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 NR 17 TC 3 Z9 3 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 2013 VL 368 IS 20 BP 1919 EP 1927 DI 10.1056/NEJMcpc1302330 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 143VK UT WOS:000318896200012 PM 23675661 ER PT J AU Drazen, JM Solomon, CG Greene, MF AF Drazen, Jeffrey M. Solomon, Caren G. Greene, Michael F. TI Informed Consent and SUPPORT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EXTREMELY PRETERM INFANTS; OXYGEN-SATURATION; TARGET C1 [Greene, Michael F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Drazen, Jeffrey/0000-0003-2715-9890 NR 5 TC 45 Z9 45 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 2013 VL 368 IS 20 BP 1929 EP 1931 DI 10.1056/NEJMe1304996 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 143VK UT WOS:000318896200013 PM 23593944 ER PT J AU Mantel, PY Hoang, AN Goldowitz, I Potashnikova, D Hamza, B Vorobjev, I Ghiran, I Toner, M Irimia, D Ivanov, AR Barteneva, N Marti, M AF Mantel, Pierre-Yves Hoang, Anh N. Goldowitz, Ilana Potashnikova, Daria Hamza, Bashar Vorobjev, Ivan Ghiran, Ionita Toner, Mehmet Irimia, Daniel Ivanov, Alexander R. Barteneva, Natasha Marti, Matthias TI Malaria-Infected Erythrocyte-Derived Microvesicles Mediate Cellular Communication within the Parasite Population and with the Host Immune System SO CELL HOST & MICROBE LA English DT Article ID PLASMODIUM-FALCIPARUM GAMETOCYTES; IN-VITRO; MICROPARTICLES; CELLS; VESICLES; GROWTH AB Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBCs), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have proinflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system. C1 [Mantel, Pierre-Yves; Goldowitz, Ilana; Marti, Matthias] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Hoang, Anh N.; Hamza, Bashar; Toner, Mehmet; Irimia, Daniel] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. [Potashnikova, Daria; Vorobjev, Ivan; Barteneva, Natasha] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Potashnikova, Daria] Moscow MV Lomonosov State Univ, Dept Cell Biol & Histol, Moscow 119991, Russia. [Vorobjev, Ivan] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119991, Russia. [Ghiran, Ionita] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Ivanov, Alexander R.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. RP Marti, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM mmarti@hsph.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082; Potashnikova, Daria/0000-0002-0098-827X FU Harvard Catalyst; Becton Dickinson Bioscience Immunology Award; Grand Challenges Exploration grant from the Bill and Melinda Gates Foundation [OPP1069401]; Novartis Foundation FX We acknowledge Maria Ericsson for expert technical support with electron microscopy, Dr. Xandra Breakefield for access to the NanoSight platform, and Drs. Barbara Burleigh and Barry Bloom for critical reading of the manuscript. Drs. Klaus Lingelbach (anti-Exp-1), Brian Cooke (anti-SBP1), Diane Taylor (anti-KAHRP), Robin Anders (anti-RESA and anti-AMA1), and Alan Cowman (anti-ATS 6H1, anti-EBA-175, and anti-EBA-181) are gratefully acknowledged for providing specific antisera to P. falciparum proteins. Anti-BIP has been provided by MR4 as MRA19. Thanks to Drs. Sarah Volkman for parasite strains Sen.T135.09 and Sen.T151.09, Joe Smith for parasite strains Pf2004 and Pf2006, and Manoj Duraisingh for the CDPK5-DD transgenic parasite line. We also acknowledge Dr. Pardis Sabeti for providing us with aliquots of serum samples derived from the Millennium Village Project and Dr. Barry Karger for his instrumental support. This work has been supported through a collaborative seed grant from Harvard Catalyst to M. M., N.A.B., and A. R. I., a Becton Dickinson Bioscience Immunology Award (M. M. and N.B.), Grand Challenges Exploration grant OPP1069401 from the Bill and Melinda Gates Foundation (D. I.), and a Novartis Foundation research fellowship to P.-Y.M. NR 28 TC 94 Z9 94 U1 2 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD MAY 15 PY 2013 VL 13 IS 5 BP 521 EP 534 DI 10.1016/j.chom.2013.04.009 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AA1IW UT WOS:000330850800006 PM 23684304 ER PT J AU Grant, SS Hung, DT AF Grant, Sarah Schmidt Hung, Deborah T. TI Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response SO VIRULENCE LA English DT Review DE persistent bacterial infections; antibiotic tolerance; persisters; oxidative stress; small colony variants; biofilms ID SMALL-COLONY VARIANTS; UROPATHOGENIC ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS PERSISTENCE; PNEUMONIAE BIOFILM RESISTANCE; URINARY-TRACT INFECTION; STAPHYLOCOCCUS-AUREUS; CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; STATIONARY-PHASE; INTRACELLULAR PERSISTENCE AB Certain bacterial pathogens are able to evade the host immune system and persist within the human host. The consequences of persistent bacterial infections potentially include increased morbidity and mortality from the infection itself as well as an increased risk of dissemination of disease. Eradication of persistent infections is difficult, often requiring prolonged or repeated courses of antibiotics. During persistent infections, a population or subpopulation of bacteria exists that is refractory to traditional antibiotics, possibly in a non-replicating or metabolically altered state. This review highlights the clinical significance of persistent infections and discusses different in vitro models used to investigate the altered physiology of bacteria during persistent infections. We specifically focus on recent work establishing increased protection against oxidative stress as a key element of the altered physiologic state across different in vitro models and pathogens. C1 [Grant, Sarah Schmidt; Hung, Deborah T.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Grant, Sarah Schmidt; Hung, Deborah T.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Grant, Sarah Schmidt; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Grant, SS (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM sgrant@broadinstitute.org; hung@molbio.mgh.harvard.edu FU NIAID NIH HHS [K08 AI085033] NR 120 TC 31 Z9 33 U1 4 U2 65 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD MAY 15 PY 2013 VL 4 IS 4 BP 273 EP 283 DI 10.4161/viru.23987 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 198BQ UT WOS:000322897100002 PM 23563389 ER PT J AU Le Grand, JN Bon, K Fraichard, A Zhang, JH Jouvenot, M Risold, PY Boyer-Guittaut, M Delage-Mourroux, R AF Le Grand, Jaclyn Nicole Bon, Karine Fraichard, Annick Zhang, Jianhua Jouvenot, Michele Risold, Pierre-Yves Boyer-Guittaut, Michael Delage-Mourroux, Regis TI Specific Distribution of the Autophagic Protein GABARAPL1/GEC1 in the Developing and Adult Mouse Brain and Identification of Neuronal Populations Expressing GABARAPL1/GEC1 SO PLOS ONE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GABA(A) RECEPTOR; MESSENGER-RNAS; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; IN-VIVO; GEC1; MICE; DEGRADATION; INTERACTS AB Macroautophagy is a highly conserved cellular degradation process, regulated by autophagy-related (atg) factors, in which a double membrane autophagosome engulfs cytoplasmic components to target them for degradation. In yeast, the Atg8 protein is indispensable for autophagosome formation. In mammals, this is complicated by the presence of six Atg8 homologues grouped into the GABARAP and MAP1LC3 subfamilies. Although these proteins share a high similarity, their transcript expression, regulation and protein interactions differ, suggesting they may display individual properties and specific functions. GABARAPL1/GEC1 is a member of the GABARAP subfamily and its mRNA is the most highly expressed Atg8 homologue in the central nervous system. Consequently, we performed an in depth study of GABARAPL1 distribution in the developing and adult murine brain. Our results show that GABARAPL1 brain expression is visible as early as embryonic day 11 and progressively increases to a maximum level in the adult. Immunohistochemical staining was detected in both fibers and immature neurons in embryos but was restrained to neurons in adult tissue. By E17, intense punctate-like structures were visible and these accumulated in cortical primary neurons treated with the autophagosome/lysosome fusion inhibitor Bafilomycin A1 (Baf A1), suggesting that they represent autophagosomes. Finally, GABARAPL1 expression was particularly intense in motoneurons in the embryo and in neurons involved in somatomotor and neuroendocrine functions in the adult, particularly in the substantia nigra pars compacta, a region affected in Parkinson's disease. Our study of cerebral GABARAPL1 protein expression provides insight into its role in the development and homeostasis of the mouse brain. C1 [Le Grand, Jaclyn Nicole; Bon, Karine; Fraichard, Annick; Jouvenot, Michele; Risold, Pierre-Yves; Boyer-Guittaut, Michael; Delage-Mourroux, Regis] Univ Franche Comte, UFR Sci & Tech, Estrogenes Express Gen & Pathol Syst Nerveux Cent, Lab Biochim,SFR IBCT FED 4234, F-25030 Besancon, Doubs, France. [Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35294 USA. RP Delage-Mourroux, R (reprint author), Univ Franche Comte, UFR Sci & Tech, Estrogenes Express Gen & Pathol Syst Nerveux Cent, Lab Biochim,SFR IBCT FED 4234, F-25030 Besancon, Doubs, France. EM regis.delage-mourroux@univ-fcomte.fr FU Ministere de l'Enseignement Superieur et de la Recherche (MESR); VA merit award; [NIHR01-NS064090] FX JNLG is supported by a fellowship from the Ministere de l'Enseignement Superieur et de la Recherche (MESR) and Dr. JZ was supported by NIHR01-NS064090 and a VA merit award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 7 Z9 8 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 15 PY 2013 VL 8 IS 5 AR e63133 DI 10.1371/journal.pone.0063133 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 145XK UT WOS:000319052700021 PM 23690988 ER PT J AU Seay, K Qi, XH Zheng, JH Zhang, C Chen, K Dutta, M Deneroff, K Ochsenbauer, C Kappes, JC Littman, DR Goldstein, H AF Seay, Kieran Qi, Xiaohua Zheng, Jian Hua Zhang, Cong Chen, Ken Dutta, Monica Deneroff, Kathryn Ochsenbauer, Christina Kappes, John C. Littman, Dan R. Goldstein, Harris TI Mice Transgenic for CD4-Specific Human CD4, CCR5 and Cyclin T1 Expression: A New Model for Investigating HIV-1 Transmission and Treatment Efficacy SO PLOS ONE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; LENTIVIRAL-VECTORS; MOUSE MODEL; RAG2(-/-)GAMMA(-/-)(C) MICE; GENE-TRANSFER; INFECTION; REPLICATION; ANTIBODY; VIVO; LYMPHOCYTES AB Mice cannot be used to evaluate HIV-1 therapeutics and vaccines because they are not infectible by HIV-1 due to structural differences between several human and mouse proteins required for HIV-1 entry and replication including CD4, CCR5 and cyclin T1. We overcame this limitation by constructing mice with CD4 enhancer/promoter-regulated human CD4, CCR5 and cyclin T1 genes integrated as tightly linked transgenes (hCD4/R5/cT1 mice) promoting their efficient co-transmission and enabling the murine CD4-expressing cells to support HIV-1 entry and Tat-mediated LTR transcription. All of the hCD4/R5/ cT1 mice developed disseminated infection of tissues that included the spleen, small intestine, lymph nodes and lungs after intravenous injection with an HIV-1 infectious molecular clone (HIV-IMC) expressing Renilla reniformis luciferase (LucR). Furthermore, localized infection of cervical-vaginal mucosal leukocytes developed after intravaginal inoculation of hCD4/R5/ cT1 mice with the LucR-expressing HIV-IMC. hCD4/R5/cT1 mice reproducibly developed in vivo infection after inoculation with LucR-expressing HIV-IMC which could be bioluminescently quantified and visualized with a high sensitivity and specificity which enabled them to be used to evaluate the efficacy of HIV-1 therapeutics. Treatment with highly active anti-retroviral therapy or one dose of VRC01, a broadly neutralizing anti-HIV-1 antibody, almost completed inhibited acute systemic HIV-1 infection of the hCD4/R5/cT1 mice. hCD4/R5/cT1 mice could also be used to evaluate the capacity of therapies delivered by gene therapy to inhibit in vivo HIV infection. VRC01 secreted in vivo by primary B cells transduced with a VRC01-encoding lentivirus transplanted into hCD4/R5/cT1 mice markedly inhibited infection after intravenous challenge with LucR-expressing HIV-IMC. The reproducible infection of CD4/R5/cT1 mice with LucR-expressing HIV-IMC after intravenous or mucosal inoculation combined with the availability of LucR-expressing HIV-IMC expressing transmitted/ founder and clade A/E and C Envs will provide researchers with a highly accessible pre-clinical in vivo HIV-1-infection model to study HIV-1 acquisition, treatment, and prevention. C1 [Seay, Kieran; Goldstein, Harris] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Qi, Xiaohua; Zheng, Jian Hua; Zhang, Cong; Dutta, Monica; Deneroff, Kathryn; Goldstein, Harris] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Chen, Ken] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA. [Ochsenbauer, Christina; Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. [Littman, Dan R.] NYU, Sch Med, Skirball Inst Biomol Med, Mol Pathogenesis Program, New York, NY USA. [Littman, Dan R.] NYU, Sch Med, Skirball Inst Biomol Med, Howard Hughes Med Inst, New York, NY USA. RP Goldstein, H (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. EM harris.goldstein@einstein.yu.edu FU National Institutes of Health (National Institute of Drug Abuse) [R01-DA-033788]; National Institutes of Health (National Institute of Allergy and Infectious Diseases) [R01-AI065309]; National Institutes of Health (Einstein-Montefiore Center for AIDS Research) [AI51519]; Charles Michael Chair in Autoimmune Diseases; NIH-funded AIDS training grant [T32-AI007501]; VHA Merit Review Award; NIH Center for HIV-1/AIDS Vaccine Immunology (CHAVI) [UO1-AI067854]; UAB Center for AIDS Research [P30-AI-27767]; [U01-GM-094665]; [U54-GM-094662]; [P30-CA-013330] FX The construct expressing VRC01 was a kind gift of Dr. John Mascola (VRC/NIAID/NIH) which was used to generate VRC01 antibody in the Einstein Macromolecular Therapeutics Facility (supported by U01-GM-094665, U54-GM-094662 and P30-CA-013330) by Man K. Chan. The following reagents were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: TZM-bl cells, pT4B and pCCR-5.; This work was supported by the National Institutes of Health (National Institute of Drug Abuse R01-DA-033788, National Institute of Allergy and Infectious Diseases R01-AI065309 and the Einstein-Montefiore Center for AIDS Research AI51519). HG was supported by the Charles Michael Chair in Autoimmune Diseases, KS by an NIH-funded AIDS training grant, T32-AI007501 and JCK by a VHA Merit Review Award. Work by JCK and CO was supported by the NIH Center for HIV-1/AIDS Vaccine Immunology (CHAVI), UO1-AI067854; and the UAB Center for AIDS Research (P30-AI-27767). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 14 Z9 14 U1 1 U2 12 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 MAY 15 PY 2013 VL 8 IS 5 AR e63537 DI 10.1371/journal.pone.0063537 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 145XK UT WOS:000319052700042 PM 23691059 ER PT J AU Rogers, IS Massaro, JM Truong, QA Mahabadi, AA Kriegel, MF Fox, CS Thanassoulis, G Isselbacher, EM Hoffmann, U O'Donnell, CJ AF Rogers, Ian S. Massaro, Joseph M. Truong, Quynh A. Mahabadi, Amir A. Kriegel, Matthias F. Fox, Caroline S. Thanassoulis, George Isselbacher, Eric M. Hoffmann, Udo O'Donnell, Christopher J. TI Distribution, Determinants, and Normal Reference Values of Thoracic and Abdominal Aortic Diameters by Computed Tomography (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DIMENSIONS; DISEASE; CHILDREN; ADULTS; WOMEN; AREA; MEN; AGE AB Current screening and detection of asymptomatic aortic aneurysms is based largely on uniform cut-point diameters. The aims of this study were to define normal aortic diameters in asymptomatic men and women in a community-based cohort and to determine the association between aortic diameters and traditional risk factors for cardiovascular disease. Measurements of the diameters of the ascending thoracic aorta (AA), descending thoracic aorta (DTA), infrarenal abdominal aorta (IRA), and lower abdominal aorta (LAA) were acquired from 3,431 Framingham Heart Study (FHS) participants. Mean diameters were stratified by gender, age, and body surface area. Univariate associations with risk factor levels were examined, and multivariate linear regression analysis was used to assess the significance of covariate-adjusted relations with aortic diameters. For men, the average diameters were 34.1 mm for the AA, 25.8 mm for the DTA, 19.3 mm for the IRA, and 18.7 mm for the LAA. For women, the average diameters were 31.9 mm for the AA, 23.1 mm for the DTA, 16.7 mm for the IRA, and 16.0 mm for the LAA. The mean aortic diameters were strongly correlated (p<0.0001) with age and body surface area in age-adjusted analyses, and these relations remained significant in multivariate regression analyses. Positive associations of diastolic blood pressure with AA and DTA diameters in both genders and pack-years of cigarette smoking with DTA diameter in women and IRA diameter in men and women were observed. In conclusion, average diameters of the thoracic and abdominal aorta by computed tomography are larger in men compared with women, vary significantly with age and body surface area, and are associated with modifiable cardiovascular disease risk factors, including diastolic blood pressure and cigarette smoking. Published by Elsevier Inc. (Am J Cardiol 2013;111:1510-1516) C1 [Rogers, Ian S.; Truong, Quynh A.; Mahabadi, Amir A.; Kriegel, Matthias F.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Rogers, Ian S.; Truong, Quynh A.; Isselbacher, Eric M.; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Rogers, Ian S.] Stanford Univ, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Massaro, Joseph M.; Fox, Caroline S.; Thanassoulis, George; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Mahabadi, Amir A.] Univ Duisburg Essen, Dept Cardiol, West German Heart Ctr, Essen, Germany. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Thanassoulis, George] McGill Univ, Div Cardiol, Ctr Hlth, Montreal, PQ, Canada. [Thanassoulis, George] McGill Univ, Div Clin Epidemiol, Ctr Hlth, Montreal, PQ, Canada. RP O'Donnell, CJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM odonnellc@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute's FHS [N01-HC-25195]; National Institutes of Health [1T32 HL076136, K23 HL098370, L30 HL093806]; American Heart Association [12CRP12060237] FX From the Framingham Heart Study (FHS) of the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland, and Boston University School of Medicine, Boston, Massachusetts. This work was supported by the National Heart, Lung, and Blood Institute's FHS (Contract N01-HC-25195). Drs. Rogers and Truong received salary support from Grant 1T32 HL076136 from the National Institutes of Health. Dr. Rogers also received salary support from Grant 12CRP12060237 from the American Heart Association. Dr. Truong also received salary support from Grants K23 HL098370 and L30 HL093806 from the National Institutes of Health. NR 19 TC 32 Z9 33 U1 0 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2013 VL 111 IS 10 BP 1510 EP 1516 DI 10.1016/j.amjcard.2013.01.306 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 150EB UT WOS:000319371900023 PM 23497775 ER PT J AU Sun, HF Qin, B Liu, T Wang, QX Liu, J Wang, J Lin, XQ Yang, YL Taing, L Rao, PK Brown, M Zhang, Y Long, HW Liu, XS AF Sun, Hanfei Qin, Bo Liu, Tao Wang, Qixuan Liu, Jing Wang, Juan Lin, Xueqiu Yang, Yulin Taing, Len Rao, Prakash K. Brown, Myles Zhang, Yong Long, Henry W. Liu, X. Shirley TI CistromeFinder for ChIP-seq and DNase-seq data reuse SO BIOINFORMATICS LA English DT Article ID HUMAN GENOME AB Chromatin immunoprecipitation and DNase I hypersensitivity assays with high-throughput sequencing have greatly accelerated the understanding of transcriptional and epigenetic regulation, although data reuse for the community of experimental biologists has been challenging. We created a data portal CistromeFinder that can help query, evaluate and visualize publicly available Chromatin immunoprecipitation and DNase I hypersensitivity assays with high-throughput sequencing data in human and mouse. The database currently contains 6378 samples over 4391 datasets, 313 factors and 102 cell lines or cell populations. Each dataset has gone through a consistent analysis and quality control pipeline; therefore, users could evaluate the overall quality of each dataset before examining binding sites near their genes of interest. CistromeFinder is integrated with UCSC genome browser for visualization, Primer3Plus for ChIP-qPCR primer design and CistromeMap for submitting newly available datasets. It also allows users to leave comments to facilitate data evaluation and update. C1 [Sun, Hanfei; Qin, Bo; Wang, Qixuan; Liu, Jing; Wang, Juan; Lin, Xueqiu; Yang, Yulin; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 20092, Peoples R China. [Liu, Tao; Taing, Len; Rao, Prakash K.; Long, Henry W.; Liu, X. Shirley] Dana Faber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Liu, Tao; Liu, X. Shirley] Dana Faber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Liu, Tao; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA USA. [Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USA. [Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Liu, XS (reprint author), Dana Faber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. EM henry_long@dfci.harvard.edu; xsliu@jimmy.harvard.edu RI Zhang, Yong/B-4838-2011; Liu, Tao/G-3585-2010; OI Liu, Tao/0000-0003-0446-9001; Zhang, Yong/0000-0001-6316-2734; Liu, Tao/0000-0002-8818-8313; Brown, Myles/0000-0002-8213-1658 FU National Basic Research (973) Program of China [2010CB944904]; National Natural Science Foundation of China [31028011]; National Institutes of Health [HG4069] FX National Basic Research (973) Program of China [2010CB944904]; National Natural Science Foundation of China [31028011]; and National Institutes of Health [HG4069]. NR 12 TC 10 Z9 10 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD MAY 15 PY 2013 VL 29 IS 10 BP 1352 EP 1354 DI 10.1093/bioinformatics/btt135 PG 3 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 150YR UT WOS:000319428200018 PM 23508969 ER PT J AU Pucci, F Pittet, MJ AF Pucci, Ferdinando Pittet, Mikael J. TI Molecular Pathways: Tumor-Derived Microvesicles and Their Interactions with Immune Cells In Vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID PLACENTAL GROWTH-FACTOR; REGULATORY T-CELLS; DENDRITIC CELLS; PLASMA-MEMBRANE; DIAGNOSTIC BIOMARKERS; PROTEOMIC ANALYSIS; SUPPRESSOR-CELLS; PROGENITOR CELLS; MESSENGER-RNA; MYELOID CELLS AB Cancer is not merely a cell-intrinsic genetic disease but also the result of complex cell-extrinsic interactions with host components, including immune cells. For example, effector T lymphocytes and natural killer cells are thought to participate in an immunosurveillance process, which eliminates neoplastic cells, whereas regulatory T lymphocytes and some myeloid cells, including macrophages, can create a milieu that prevents antitumor activity, supports tumor growth, and reduces survival of the host. Increasing evidence supports the notion that carcinoma cells communicate with immune cells directly, both within and away from the tumor stroma, and that this process fosters suppression of immunosurveillance and promotes tumor outgrowth. An important mode of communication between carcinoma cells and immune cells may involve tumor-derived microvesicles (tMV), also known as exosomes, ectosomes, or microparticles. These microvesicles carry lipids, proteins, mRNAs and microRNAs and travel short or long distances to deliver undegraded and undiluted material to other cells. Here, we consider the capacity of tMVs to control tumor-associated immune responses and highlight the known and unknown actions of tMVs in vivo. We also discuss why microvesicles may play a role in cancer diagnostics and prognostics and how they could be harnessed for anticancer therapy. (C) 2013 AACR. C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu FU U.S. NIH [R01-AI084880, P50-CA086355]; EMBO FX This work was supported in part by U.S. NIH grants R01-AI084880 and P50-CA086355 (to M.J. Pittet) and by the EMBO long-term fellowship program (to F. Pucci). NR 87 TC 20 Z9 20 U1 4 U2 28 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2013 VL 19 IS 10 BP 2598 EP 2604 DI 10.1158/1078-0432.CCR-12-0962 PG 7 WC Oncology SC Oncology GA 144AO UT WOS:000318911600002 PM 23426276 ER PT J AU Coffee, EM Faber, AC Roper, J Sinnamon, MJ Goel, G Keung, L Wang, WV Vecchione, L de Vriendt, V Weinstein, BJ Bronson, RT Tejpar, S Xavier, RJ Engelman, JA Martin, ES Hung, KE AF Coffee, Erin M. Faber, Anthony C. Roper, Jatin Sinnamon, Mark J. Goel, Gautam Keung, Lily Wang, Wei Vivian Vecchione, Loredana de Vriendt, Veerle Weinstein, Barbara J. Bronson, Roderick T. Tejpar, Sabine Xavier, Ramnik J. Engelman, Jeffrey A. Martin, Eric S. Hung, Kenneth E. TI Concomitant BRAF and PI3K/mTOR Blockade Is Required for Effective Treatment of BRAF(V600E) Colorectal Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID COLON-CANCER; MOUSE MODEL; B-RAF; MICROSATELLITE INSTABILITY; PATHWAY ACTIVATION; ANTITUMOR-ACTIVITY; V600E MUTATION; MAPK PATHWAY; INHIBITION; RESISTANCE AB Purpose: BRAF(V600E) mutations are associated with poor clinical prognosis in colorectal cancer (CRC). Although selective BRAF inhibitors are effective for treatment of melanoma, comparable efforts in CRC have been disappointing. Here, we investigated potential mechanisms underlying this resistance to BRAF inhibitors in BRAF(V600E) CRC. Experimental Design: We examined phosphoinositide 3-kinase (PI3K)/mTOR signaling in BRAF(V600E) CRC cell lines after BRAF inhibition and cell viability and apoptosis after combined BRAF and PI3K/mTOR inhibition. We assessed the efficacy of in vivo combination treatment using a novel genetically engineered mouse model (GEMM) for BRAF(V600E) CRC. Results: Western blot analysis revealed sustained PI3K/mTOR signaling upon BRAF inhibition. Our BRAF(V600E) GEMM presented with sessile serrated adenomas/polyps, as seen in humans. Combination treatment in vivo resulted in induction of apoptosis and tumor regression. Conclusions: We have established a novel GEMM to interrogate BRAF(V600E) CRC biology and identify more efficacious treatment strategies. Combination BRAF and PI3K/mTOR inhibitor treatment should be explored in clinical trials. (C) 2013 AACR. C1 [Coffee, Erin M.; Roper, Jatin; Sinnamon, Mark J.; Keung, Lily; Wang, Wei Vivian; Hung, Kenneth E.] Tufts Med Ctr, Div Gastroenterol, Boston, MA 02111 USA. [Weinstein, Barbara J.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA. [Faber, Anthony C.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Bronson, Roderick T.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Martin, Eric S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vecchione, Loredana; de Vriendt, Veerle; Tejpar, Sabine] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium. RP Hung, KE (reprint author), Tufts Med Ctr, 750 Washington St,Box 233, Boston, MA 02111 USA. EM kenneth.hung@tufts.edu RI Waha, Andreas/J-2950-2014; OI Roper, Jatin/0000-0002-8851-1352 FU Novartis; Sanofi-Aventis; National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK) [K08-DK078033]; National Cancer Institute (NCI) [U01-CA084301] FX J.A. Engelman has commercial research grants from Novartis and Sanofi-Aventis and is a consultant/advisory board member of Novartis, Genentech, Sanofi-Aventis, and GSK. No potential conflicts of interest were disclosed by the other authors.; This research was supported by grants from the National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK; K08-DK078033) and National Cancer Institute (NCI; U01-CA084301). NR 48 TC 42 Z9 43 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2013 VL 19 IS 10 BP 2688 EP 2698 DI 10.1158/1078-0432.CCR-12-2556 PG 11 WC Oncology SC Oncology GA 144AO UT WOS:000318911600013 PM 23549875 ER PT J AU Zheng, BH DeRan, M Li, XY Liao, XB Fukata, M Wu, X AF Zheng, Baohui DeRan, Michael Li, Xinyan Liao, Xuebin Fukata, Masaki Wu, Xu TI 2-Bromopalmitate Analogues as Activity-Based Probes To Explore Palmitoyl Acyltransferases SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEIN S-ACYLTRANSFERASES; FATTY-ACIDS; INHIBITORS; CANCER; IDENTIFICATION; TRAFFICKING; STABILITY; DISCOVERY; ENZYMES; 5P15.33 AB Reversible S-palmitoylation is an important post-translational modification that regulates the trafficking, localization, and activity of proteins. Cysteine-rich Asp-His-His-Cys (DHHC) domain-containing enzymes are evolutionarily conserved protein palmitoyl acyltransferases (PATs). The human genome encodes 23 DHHC-PATs that regulate diverse cellular functions. Although chemical probes and proteomic methods to detect palmitoylated protein substrates have been reported, no probes for direct detection of the activity of PATs are available. Here we report the synthesis and characterization of 2-bromohexadec-15-ynoic acid and 2-bromooctadec-17-ynoic acid, which are analogues of 2-bromopalmitate (2-BP), as activity-based probes for PATs as well as other palmitoylating and 2-BP-binding enzymes. These probes will serve as new chemical tools for activity-based protein profiling to explore PATs, to dissect the functions of PATs in cell signaling and diseases, and to facilitate the identification of their inhibitors. C1 [Zheng, Baohui; DeRan, Michael; Li, Xinyan; Wu, Xu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Liao, Xuebin] Tsinghua Univ, Dept Pharmacol & Pharmaceut Sci, Beijing 100084, Peoples R China. [Fukata, Masaki] Natl Inst Physiol Sci, Dept Cell Physiol, Div Membrane Physiol, Okazaki, Aichi 4448787, Japan. RP Wu, X (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM xwu@cbrc2.mgh.harvard.edu RI zheng, baohui/O-6828-2014 OI zheng, baohui/0000-0002-3272-843X FU Massachusetts General Hospital (MGH) Institutional Fund; Stewart Rahr-MRA Young Investigator Award FX We thank Ross Tomaino at the Taplin Mass Spectrometry Facility of Harvard Medical School for proteomics studies and Drs. Matthew Tremblay and Jianming Zhang for critical comments on the manuscript. This work was supported by the Massachusetts General Hospital (MGH) Institutional Fund and the Stewart Rahr-MRA Young Investigator Award (X.W.). NR 33 TC 26 Z9 26 U1 1 U2 61 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 15 PY 2013 VL 135 IS 19 BP 7082 EP 7085 DI 10.1021/ja311416v PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 148NB UT WOS:000319250200001 PM 23631516 ER PT J AU Deyo, RA Smith, DHM Johnson, ES Tillotson, CJ Donovan, M Yang, XH Petrik, A Morasco, BJ Dobscha, SK AF Deyo, Richard A. Smith, David H. M. Johnson, Eric S. Tillotson, Carrie J. Donovan, Marilee Yang, Xiuhai Petrik, Amanda Morasco, Benjamin J. Dobscha, Steven K. TI Prescription Opioids for Back Pain and Use of Medications for Erectile Dysfunction SO SPINE LA English DT Article DE opioids; low back pain; erectile dysfunction; sexual dysfunction ID CHRONIC NONCANCER PAIN; UNITED-STATES; ORAL OPIOIDS; ASSOCIATION; HYPOGONADISM; TRENDS; MEN; EPIDEMIOLOGY; METAANALYSIS; PREVALENCE AB Study Design. Cross-sectional analysis of electronic medical and pharmacy records. Objective. To examine associations between use of medication for erectile dysfunction or testosterone replacement and use of opioid therapy, patient age, depression, and smoking status. Summary of Background Data. Males with chronic pain may experience erectile dysfunction related to depression, smoking, age, or opioid-related hypogonadism. The prevalence of this problem in back pain populations and the relative importance of several risk factors are unknown. Methods. We examined electronic pharmacy and medical records for males with back pain in a large group model health maintenance organization during 2004. Relevant prescriptions were considered for 6 months before and after the index visit. Results. There were 11,327 males with a diagnosis of back pain. Males who received medications for erectile dysfunction or testosterone replacement (n = 909) were significantly older than those who did not and had greater comorbidity, depression, smoking, and use of sedative-hypnotics. In logistic regressions, the long-term use of opioids was associated with greater use of medications for erectile dysfunction or testosterone replacement compared with no opioid use (odds ratio, 1.45; 95% confidence interval, 1.12-1.87, P < 0.01). Age, comorbidity, depression, and use of sedative-hypnotics were also independently associated with the use of medications for erectile dysfunction or testosterone replacement. Patients prescribed daily opioid doses of 120 mg of morphine-equivalents or more had greater use of medication for erectile dysfunction or testosterone replacement than patients without opioid use (odds ratio, 1.58; 95% confidence interval, 1.03-2.43), even with adjustment for the duration of opioid therapy. Conclusion. Dose and duration of opioid use, as well as age, comorbidity, depression, and use of sedative-hypnotics, were associated with evidence of erectile dysfunction. These findings may be important in the process of decision making for the long-term use of opioids. C1 [Deyo, Richard A.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Dept Family Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Dept Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Dept Publ Hlth, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Dept Prevent Med, Portland, OR 97201 USA. [Deyo, Richard A.] Kaiser Ctr Hlth Res, Portland, OR USA. [Smith, David H. M.; Johnson, Eric S.; Donovan, Marilee; Yang, Xiuhai; Petrik, Amanda] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Portland, OR USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, Dept Family Med, Mail Code FM, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM deyor@ohsu.edu FU NIH/NCRR FX NIH/NCRR grant funds were received to support this work. NR 38 TC 13 Z9 13 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 15 PY 2013 VL 38 IS 11 BP 909 EP 915 DI 10.1097/BRS.0b013e3182830482 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 144CD UT WOS:000318916300015 PM 23459134 ER PT J AU Harlow, BL MacLehose, RF Smolenski, DJ Soares, CN Otto, MW Joffe, H Cohen, LS AF Harlow, Bernard L. MacLehose, Richard F. Smolenski, Derek J. Soares, Claudio N. Otto, Michael W. Joffe, Hadine Cohen, Lee S. TI Disparate Rates of New-Onset Depression During the Menopausal Transition in 2 Community-based Populations: Real, or Really Wrong? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bias; depression; prospective studies ID DIRECTED ACYCLIC GRAPHS; BIAS; HEALTH; SENSITIVITY; PREVALENCE; HARVARD; CYCLES; MOODS; WOMEN; TWIN AB This study took place in eastern Massachusetts and included respondents from the Harvard Study of Moods and Cycles Cohort 1, enrolled between 1995 and 1997, and the Harvard Study of Moods and Cycles Cohort 2, enrolled between 2005 and 2009. In prospectively assessing rates of new-onset depression in 2 populations of late-reproductive-aged women with no Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) lifetime history of depression, we were surprised to find far lower rates of depression in the population with greater racial diversity and lower socioeconomic status, contrary to what had been reported in the scientific literature. To better understand why these disparate results occurred, we assessed confounding and outcome misclassification as potential explanations for the discrepancy. After determining that these were unlikely explanations for the findings, we explored 2 potential sources of selection bias: one induced by self-referral of healthy participants into the study and the other induced by the design of the study itself. We concluded that both types of selection bias were likely to have occurred in this study and could account for the observed difference in rates. C1 [Harlow, Bernard L.; MacLehose, Richard F.; Smolenski, Derek J.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA. [MacLehose, Richard F.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55454 USA. [Soares, Claudio N.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Soares, Claudio N.] McMaster Univ, Dept Obstet & Gynecol, Hamilton, ON, Canada. [Otto, Michael W.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Joffe, Hadine; Cohen, Lee S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth, Boston, MA USA. RP Harlow, BL (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 South 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM harlow@umn.edu FU National Institute of Mental Health, National Institutes of Health [R01-MH-50013, R01-MH-69732] FX This research was supported by grants R01-MH-50013 and R01-MH-69732 from the National Institute of Mental Health, National Institutes of Health. NR 19 TC 1 Z9 1 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 2013 VL 177 IS 10 BP 1148 EP 1156 DI 10.1093/aje/kws365 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 142MJ UT WOS:000318801200014 PM 23589585 ER PT J AU Huang, YH Goel, S Duda, DG Fukumura, D Jain, RK AF Huang, Yuhui Goel, Shom Duda, Dan G. Fukumura, Dai Jain, Rakesh K. TI Vascular Normalization as an Emerging Strategy to Enhance Cancer Immunotherapy SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; REGULATORY T-CELLS; TUMOR MICROENVIRONMENT; ANTIANGIOGENIC THERAPY; INHIBITOR; BLOCKADE; SURVIVAL; HYPOXIA; ANGIOGENESIS; PROGRESSION AB The recent approval of Provenge has brought new hope for anticancer vaccine therapies. However, the immunosuppressive tumor microenvironment seems to impair the efficacy of vaccine therapies. The abnormal tumor vasculature creates a hypoxic microenvironment that polarizes inflammatory cells toward immune suppression. Moreover, tumors systemically alter immune cells' proliferation, differentiation, and function via secretion of growth factors and cytokines. For example, VEGF, a major proangiogenic cytokine induced by hypoxia, plays a critical role in immunosuppression via these mechanisms. Hence, antiangiogenic treatment may be an effective modality to potentiate immunotherapy. Here, we discuss the local and systemic effects of VEGF on tumor immunity and propose a potentially translatable strategy to re-engineer the tumor-immune microenvironment and improve cancer immunotherapy by using lower "vascular normalizing" doses of antiangiogenic agents. Cancer Res; 73(10); 2943-8. (C) 2013 AACR. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab, Cox 734, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Huang, Yuhui/0000-0003-1985-3575 FU Medimmune; Roche; NIH [P01-CA080124, R01-CA115767, R01-CA085140, R01-CA126642, R21-CA139168, R01-CA159258, R01-CA096915]; Federal Share/NCI Proton Beam Program; Department of Defense [W81XWH-10-1-0016]; Postdoctoral Research Fellowship [W81XWH-11-1-0619]; American Cancer Society [RSG-11-073-01-TBG]; National Foundation for Cancer Research; Australian-American Fulbright Commission; American Society of Clinical Oncology FX R.K. Jain has commercial research grants from Medimmune and Roche; has ownership interest (including patents) in XTuit Pharmaceuticals, Syn-DevRx, and Enlight Biosciences; and is a consultant/advisory board member of Noxxon Pharmaceuticals, Zyngenia, SynDevRx, XTuit Pharmaceuticals, Enlight, Hambrecht & Quist Healthcare Investors, and Hambrecht & Quist Life Sciences Investors. No potential conflicts of interest were disclosed by the other authors.; The study was supported by NIH grants P01-CA080124 (R.K. Jain, D.G. Duda, D. Fukumura); R01-CA115767, R01-CA085140, and R01-CA126642 (R. K. Jain); R21-CA139168 and R01-CA159258 (D.G. Duda); R01-CA096915 (D. Fukumura); Federal Share/NCI Proton Beam Program Income Grants (R.K. Jain, D.G. Duda, D. Fukumura); Department of Defense Innovator Award W81XWH-10-1-0016 (R.K. Jain); Postdoctoral Research Fellowship W81XWH-11-1-0619 (Y. Huang); American Cancer Society Grant RSG-11-073-01-TBG (D.G. Duda); National Foundation for Cancer Research Grant (R.K. Jain); and Australian-American Fulbright Commission and an American Society of Clinical Oncology Young Investigator Award (S. Goel). NR 35 TC 100 Z9 105 U1 6 U2 45 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2013 VL 73 IS 10 BP 2943 EP 2948 DI 10.1158/0008-5472.CAN-12-4354 PG 6 WC Oncology SC Oncology GA 143XY UT WOS:000318903700003 PM 23440426 ER PT J AU Katayama, R Aoyama, A Yamori, T Qi, J Oh-hara, T Song, Y Engelman, JA Fujita, N AF Katayama, Ryohei Aoyama, Aki Yamori, Takao Qi, Jie Oh-hara, Tomoko Song, Youngchul Engelman, Jeffrey A. Fujita, Naoya TI Cytotoxic Activity of Tivantinib (ARQ 197) Is Not Due Solely to c-MET Inhibition SO CANCER RESEARCH LA English DT Article ID RECEPTOR TYROSINE KINASE; CELL LUNG-CANCER; ANTICANCER DRUG SCREEN; ANTITUMOR-ACTIVITY; GEFITINIB RESISTANCE; SELECTIVE INHIBITOR; ACQUIRED-RESISTANCE; DOSE-ESCALATION; PLUS ERLOTINIB; IN-VITRO AB The receptor tyrosine kinase c-MET is the high-affinity receptor for the hepatocyte growth factor (HGF). The HGF/c-MET axis is often dysregulated in tumors. c-MET activation can be caused by MET gene amplification, activating mutations, and auto-or paracrine mechanisms. Thus, c-MET inhibitors are under development as anticancer drugs. Tivantinib (ARQ 197) was reported as a small-molecule c-MET inhibitor and early clinical studies suggest antitumor activity. To assess whether the antitumor activity of tivantinib was due to inhibition of c-MET, we compared the activity of tivantinib with other c-MET inhibitors in both c-MET-addicted and nonaddicted cancer cells. As expected, other c-MET inhibitors, crizotinib and PHA-665752, suppressed the growth of c-MET-addicted cancers, but not the growth of cancers that are not addicted to c-MET. In contrast, tivantinib inhibited cell viability with similar potency in both c-MET-addicted and nonaddicted cells. These results suggest that tivantinib exhibits its antitumor activity in a manner independent of c-MET status. Tivantinib treatment induced a G2-M cell-cycle arrest in EBC1 cells similarly to vincristine treatment, whereas PHA-665752 or crizotinib treatment markedly induced G(0)-G(1) cell-cycle arrest. To identify the additional molecular target of tivantinib, we conducted COMPARE analysis, an in silico screening of a database of drug sensitivities across 39 cancer cell lines (JFCR39), and identified microtubule as a target of tivantinib. Tivantinib-treated cells showed typical microtubule disruption similar to vincristine and inhibited microtubule assembly in vitro. These results suggest that tivantinib inhibits microtubule polymerization in addition to inhibiting c-MET. Cancer Res; 73(10); 3087-96. (C) 2013 AACR. C1 [Katayama, Ryohei; Qi, Jie; Song, Youngchul; Engelman, Jeffrey A.; Fujita, Naoya] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Katayama, Ryohei; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Katayama, Ryohei; Aoyama, Aki; Oh-hara, Tomoko; Fujita, Naoya] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Div Expt Chemotherapy, Tokyo 170, Japan. [Yamori, Takao] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Div Mol Pharmacol, Tokyo 170, Japan. [Aoyama, Aki] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Tokyo, Japan. [Yamori, Takao] PMDA, Tokyo, Japan. RP Engelman, JA (reprint author), Bldg149,13th St, Charlestown, MA 02129 USA. EM jengelman@partners.org; naoya.fujita@jfcr.or.jp FU National Cancer Institute Lung SPORE [R01CA137008, R01CA140594]; JSPS [24300344, 22112008] FX The study was supported in part by R01CA137008, R01CA140594, National Cancer Institute Lung SPORE (J.A. Engelman), and JSPS KAKENHI grant number, 24300344 and 22112008 (N. Fujita). NR 40 TC 81 Z9 83 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2013 VL 73 IS 10 BP 3087 EP 3096 DI 10.1158/0008-5472.CAN-12-3256 PG 10 WC Oncology SC Oncology GA 143XY UT WOS:000318903700017 PM 23598276 ER PT J AU Womack, JA Goulet, JL Gibert, C Brandt, CA Skanderson, M Gulanski, B Rimland, D Rodriguez-Barradas, MC Tate, J Yin, MT Justice, AC AF Womack, Julie A. Goulet, Joseph L. Gibert, Cynthia Brandt, Cynthia A. Skanderson, Melissa Gulanski, Barbara Rimland, David Rodriguez-Barradas, Maria C. Tate, Janet Yin, Michael T. Justice, Amy C. CA Vet Aging Cohort Study Project TI Physiologic Frailty and Fragility Fracture in HIV-Infected Male Veterans SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; frailty; fragility fractures; Veterans ID BONE-MINERAL DENSITY; ALCOHOL INTAKE; OLDER-ADULTS; RISK-FACTORS; ELDERLY-MEN; FALLS; WOMEN; INFLAMMATION; MORTALITY; INDEX AB Background. The Veterans Aging Cohort Study (VACS) Index is associated with all-cause mortality in individuals infected with human immunodeficiency virus (HIV). It is also associated with markers of inflammation and may thus reflect physiologic frailty. This analysis explores the association between physiologic frailty, as assessed by the VACS Index, and fragility fracture. Methods. HIV-infected men from VACS were included. We identified hip, vertebral, and upper arm fractures using ICD-9-CM codes. We used Cox regression models to assess fragility fracture risk factors including the VACS Index, its components (age, hepatitis C status, FIB-4 score, estimated glomerular filtration rate, hemoglobin, HIV RNA, CD4 count), and previously identified risk factors for fragility fractures. Results. We included 40 115 HIV-infected male Veterans. They experienced 588 first fragility fractures over 6.0 +/- 3.9 years. The VACS Index score (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.11-1.19), white race (HR, 1.92; 95% CI, 1.63-2.28), body mass index (HR, 0.94; 95% CI, .92-.96), alcohol-related diagnoses (HR, 1.65; 95% CI, 1.26-2.17), cerebrovascular disease (HR, 1.95; 95% CI, 1.14-3.33), proton pump inhibitor use (HR, 1.87; 95% CI, 1.54-2.27), and protease inhibitor use (HR, 1.25; 95% CI, 1.04-1.50) were associated with fracture risk. Components of the VACS Index score most strongly associated with fracture risk were age (HR, 1.40; 95% CI, 1.27-1.54), log HIV RNA (HR, 0.91; 95% CI, .88-.94), and hemoglobin level (HR, 0.82; 95% CI, .78-.86). Conclusions. Frailty, as measured by the VACS Index, is an important predictor of fragility fractures among HIV-infected male Veterans. C1 [Womack, Julie A.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Goulet, Joseph L.; Brandt, Cynthia A.; Skanderson, Melissa; Gulanski, Barbara; Tate, Janet; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Goulet, Joseph L.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06536 USA. [Gibert, Cynthia] George Washington Univ, Vet Affairs Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Dept Med, Washington, DC USA. [Brandt, Cynthia A.] Yale Univ, Yale Ctr Med Informat, New Haven, CT 06536 USA. [Gulanski, Barbara; Justice, Amy C.] Yale Univ, Dept Internal Med, Sect Gen Internal Med, New Haven, CT 06536 USA. [Rimland, David] Vet Affairs Med Ctr, Atlanta, GA 30033 USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Med Serv, Michael E De Bakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Yin, Michael T.] Columbia Univ, Dept Med, Med Ctr, Div Infect Dis, New York, NY USA. RP Womack, JA (reprint author), Yale Univ, Sch Nursing, 100 Church St South, New Haven, CT 06536 USA. EM julie.womack@yale.edu OI Goulet, Joseph/0000-0002-0842-804X FU Veterans Administration Office, Academic Affiliations, Information Research and Development Medical Informatics Fellowship Program; National Institute of Nursing Research of the National Institutes of Health [1K01NR013437-01]; CTSA Grant from the National Center for Research Resources, component of the National Institutes of Health [UL1 RR024139]; National Center for Advancing Translational Science, component of the National Institutes of Health; National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566]; VHA Public Health Strategic Health Core Group; NIH roadmap for Medical Research FX This work was supported by the Veterans Administration Office, Academic Affiliations, Information Research and Development Medical Informatics Fellowship Program; the National Institute of Nursing Research of the National Institutes of Health (grant number 1K01NR013437-01); CTSA Grant Number UL1 RR024139 from the National Center for Research Resources and the National Center for Advancing Translational Science, components of the National Institutes of Health, and NIH roadmap for Medical Research; the Veterans Aging Cohort Study funded by the National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566) and VHA Public Health Strategic Health Core Group. NR 40 TC 42 Z9 42 U1 3 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2013 VL 56 IS 10 BP 1498 EP 1504 DI 10.1093/cid/cit056 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 140EF UT WOS:000318636500024 PM 23378285 ER PT J AU Schultheis, PJ Fleming, SM Clippinger, AK Lewis, J Tsunemi, T Giasson, B Dickson, DW Mazzulli, JR Bardgett, ME Haik, KL Ekhator, O Chava, AK Howard, J Gannon, M Hoffman, E Chen, YH Prasad, V Linn, SC Tamargo, RJ Westbroek, W Sidransky, E Krainc, D Shull, GE AF Schultheis, Patrick J. Fleming, Sheila M. Clippinger, Amy K. Lewis, Jada Tsunemi, Taiji Giasson, Benoit Dickson, Dennis W. Mazzulli, Joseph R. Bardgett, Mark E. Haik, Kristi L. Ekhator, Osunde Chava, Anil Kumar Howard, John Gannon, Matt Hoffman, Elizabeth Chen, Yinhuai Prasad, Vikram Linn, Stephen C. Tamargo, Rafael J. Westbroek, Wendy Sidransky, Ellen Krainc, Dimitri Shull, Gary E. TI Atp13a2-deficient mice exhibit neuronal ceroid lipofuscinosis, limited -synuclein accumulation and age-dependent sensorimotor deficits SO HUMAN MOLECULAR GENETICS LA English DT Article ID P-TYPE ATPASE; KUFOR-RAKEB-SYNDROME; PALLIDO-PYRAMIDAL DEGENERATION; SUPRANUCLEAR UPGAZE PARESIS; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; ATP13A2 MUTATIONS; TRANSGENIC MICE; DOPAMINERGIC-NEURONS; CEREBROSPINAL-FLUID AB Mutations in ATP13A2 (PARK9), encoding a lysosomal P-type ATPase, are associated with both KuforRakeb syndrome (KRS) and neuronal ceroid lipofuscinosis (NCL). KRS has recently been classified as a rare genetic form of Parkinsons disease (PD), whereas NCL is a lysosomal storage disorder. Although the transport activity of ATP13A2 has not been defined, in vitro studies show that its loss compromises lysosomal function, which in turn is thought to cause neuronal degeneration. To understand the role of ATP13A2 dysfunction in disease, we disrupted its gene in mice. Atp13a2(/) and Atp13a2(/) mice were tested behaviorally to assess sensorimotor and cognitive function at multiple ages. In the brain, lipofuscin accumulation, -synuclein aggregation and dopaminergic pathology were measured. Behaviorally, Atp13a2(/) mice displayed late-onset sensorimotor deficits. Accelerated deposition of autofluorescent storage material (lipofuscin) was observed in the cerebellum and in neurons of the hippocampus and the cortex of Atp13a2(/) mice. Immunoblot analysis showed increased insoluble -synuclein in the hippocampus, but not in the cortex or cerebellum. There was no change in the number of dopaminergic neurons in the substantia nigra or in striatal dopamine levels in aged Atp13a2(/) mice. These results show that the loss of Atp13a2 causes sensorimotor impairments, -synuclein accumulation as occurs in PD and related synucleinopathies, and accumulation of lipofuscin deposits characteristic of NCL, thus providing the first direct demonstration that null mutations in Atp13a2 can cause pathological features of both diseases in the same organism. C1 [Schultheis, Patrick J.; Clippinger, Amy K.; Haik, Kristi L.; Chava, Anil Kumar; Linn, Stephen C.] No Kentucky Univ, Dept Biol Sci, Highland Hts, KY 41099 USA. [Bardgett, Mark E.; Gannon, Matt; Hoffman, Elizabeth] No Kentucky Univ, Dept Psychol Sci, Highland Hts, KY 41099 USA. [Fleming, Sheila M.; Ekhator, Osunde] Univ Cincinnati, Dept Psychol & Neurol, Cincinnati, OH 45267 USA. [Chen, Yinhuai; Prasad, Vikram; Shull, Gary E.] Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Lewis, Jada; Giasson, Benoit; Howard, John] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. [Lewis, Jada; Giasson, Benoit; Howard, John] Univ Florida, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. [Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Tsunemi, Taiji; Mazzulli, Joseph R.; Krainc, Dimitri] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Tsunemi, Taiji; Mazzulli, Joseph R.; Krainc, Dimitri] Mass Gen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Tamargo, Rafael J.; Westbroek, Wendy; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Schultheis, PJ (reprint author), No Kentucky Univ, Dept Biol Sci, Highland Hts, KY 41099 USA. EM schultheisp@nku.edu FU National Institutes of Health [NS070268, GM103436, DK050594, HL061974, NS077022, MH094955, NS076054]; UF CTRND; Department of Neuroscience; UC Gardner Family Center for Parkinson's Disease and Movement Disorders; Intramural Research program of the National Human Genome Research Institute at the National Institutes of Health, Bethesda, MD, USA FX This work was supported by the National Institutes of Health (NS070268 to P.J.S., GM103436 to P.J.S. and M. E. B., DK050594 and HL061974 to G. E. S., NS077022 to S. M. F., MH094955 to M. E. B., NS076054 to D. K.); the UF CTRND and Department of Neuroscience; the UC Gardner Family Center for Parkinson's Disease and Movement Disorders and the Intramural Research program of the National Human Genome Research Institute at the National Institutes of Health, Bethesda, MD, USA. NR 84 TC 36 Z9 38 U1 1 U2 12 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 MAY 15 PY 2013 VL 22 IS 10 BP 2067 EP 2082 DI 10.1093/hmg/ddt057 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 139CL UT WOS:000318559000013 PM 23393156 ER PT J AU Crosslin, DR McDavid, A Weston, N Zheng, XW Hart, E Andrade, M Kullo, IJ McCarty, CA Doheny, KF Pugh, E Kho, A Hayes, MG Ritchie, MD Saip, A Crawford, DC Crane, PK Newton, K Carrell, DS Gallego, CJ Nalls, MA Li, R Mirel, DB Crenshaw, A Couper, DJ Tanaka, T van Rooij, FJA Chen, MH Smith, AV Zakai, NA Yango, Q Garcia, M Liu, YM Lumley, T Folsom, AR Reiner, AP Felix, JF Dehghan, A Wilson, JG Bis, JC Fox, CS Glazer, NL Cupples, A Coresh, J Eiriksdottir, G Gudnason, V Bandinelli, S Frayling, TM Chakravarti, A van Duijn, CM Melzer, D Levy, D Boerwinkle, E Singleton, AB Hernandez, DG Longo, DL Witteman, JCM Psaty, BM Ferrucci, L Harris, TB O'Donnell, CJ Ganesh, SK Larson, EB Carlson, CS Jarvik, GP AF Crosslin, David R. McDavid, Andrew Weston, Noah Zheng, Xiuwen Hart, Eugene de Andrade, Mariza Kullo, Iftikhar J. McCarty, Catherine A. Doheny, Kimberly F. Pugh, Elizabeth Kho, Abel Hayes, M. Geoffrey Ritchie, Marylyn D. Saip, Alexander Crawford, Dana C. Crane, Paul K. Newton, Katherine Carrell, David S. Gallego, Carlos J. Nalls, Michael A. Li, Rongling Mirel, Daniel B. Crenshaw, Andrew Couper, David J. Tanaka, Toshiko van Rooij, Frank J. A. Chen, Ming-Huei Smith, Albert V. Zakai, Neil A. Yango, Qiong Garcia, Melissa Liu, Yongmei Lumley, Thomas Folsom, Aaron R. Reiner, Alex P. Felix, Janine F. Dehghan, Abbas Wilson, James G. Bis, Joshua C. Fox, Caroline S. Glazer, Nicole L. Cupples, Adrienne Coresh, Josef Eiriksdottir, Gudny Gudnason, Vilmundur Bandinelli, Stefania Frayling, Timothy M. Chakravarti, Aravinda van Duijn, Cornelia M. Melzer, David Levy, Daniel Boerwinkle, Eric Singleton, Andrew B. Hernandez, Dena G. Longo, Dan L. Witteman, Jacqueline C. M. Psaty, Bruce M. Ferrucci, Luigi Harris, Tamara B. O'Donnell, Christopher J. Ganesh, Santhi K. Larson, Eric B. Carlson, Chris S. Jarvik, Gail P. CA CHARGE Hematology Working Grp Elect Med Records Genomics eMERGE TI Genetic variation associated with circulating monocyte count in the eMERGE Network SO HUMAN MOLECULAR GENETICS LA English DT Article ID BLOOD-CELL COUNT AB With white blood cell count emerging as an important risk factor for chronic inflammatory diseases, genetic associations of differential leukocyte types, specifically monocyte count, are providing novel candidate genes and pathways to further investigate. Circulating monocytes play a critical role in vascular diseases such as in the formation of atherosclerotic plaque. We performed a joint and ancestry-stratified genome-wide association analyses to identify variants specifically associated with monocyte count in 11 014 subjects in the electronic Medical Records and Genomics Network. In the joint and European ancestry samples, we identified novel associations in the chromosome 16 interferon regulatory factor 8 (IRF8) gene (P-value 2.7810(16), 0.22). Other monocyte associations include novel missense variants in the chemokine-binding protein 2 (CCBP2) gene (P-value 1.8810(7), 0.30) and a region of replication found in ribophorin I (RPN1) (P-value 2.6310(16), 0.23) on chromosome 3. The CCBP2 and RPN1 region is located near GATA binding protein2 gene that has been previously shown to be associated with coronary heart disease. On chromosome 9, we found a novel association in the prostaglandin reductase 1 gene (P-value 2.2910(7), 0.16), which is downstream from lysophosphatidic acid receptor 1. This region has previously been shown to be associated with monocyte count. We also replicated monocyte associations of genome-wide significance (P-value 5.6810(17), 0.23) at the integrin, alpha 4 gene on chromosome 2. The novel IRF8 results and further replications provide supporting evidence of genetic regions associated with monocyte count. C1 [Crosslin, David R.; Gallego, Carlos J.; Jarvik, Gail P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Zheng, Xiuwen; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Crane, Paul K.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Reiner, Alex P.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Bis, Joshua C.; Glazer, Nicole L.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bis, Joshua C.; Glazer, Nicole L.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [McDavid, Andrew; Carlson, Chris S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Weston, Noah; Hart, Eugene; Newton, Katherine; Carrell, David S.; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [de Andrade, Mariza] Div Biomed Stat & Informat, Rochester, MN USA. [Kullo, Iftikhar J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN USA. [McCarty, Catherine A.] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI 54449 USA. [Doheny, Kimberly F.; Pugh, Elizabeth] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA. [Coresh, Josef] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Chakravarti, Aravinda] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Kho, Abel] Northwestern Univ, Div Gen Internal Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Kho, Abel] Northwestern Univ, Div Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Hayes, M. Geoffrey] Northwestern Univ, Div Endocrinol Metab & Mol Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, Ctr Syst Genom, University Pk, PA 16802 USA. [Saip, Alexander] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN USA. [Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA. [Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Li, Rongling] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA. [Mirel, Daniel B.; Crenshaw, Andrew; Singleton, Andrew B.; Hernandez, Dena G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [van Rooij, Frank J. A.; Felix, Janine F.; Dehghan, Abbas; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [van Rooij, Frank J. A.; Felix, Janine F.; Dehghan, Abbas; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Netherlands Consortium Healthy Aging NGI NCHA, Netherlands Genom Initiat, Leiden, Netherlands. [Chen, Ming-Huei; Yango, Qiong; Fox, Caroline S.; Cupples, Adrienne; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Smith, Albert V.; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Zakai, Neil A.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Zakai, Neil A.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Yango, Qiong; Cupples, Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Liu, Yongmei] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Bandinelli, Stefania] Geriatr Unit ASF, Florence, Italy. [Frayling, Timothy M.; Melzer, David] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England. [Melzer, David] PCMD, European Ctr Environm & Human Hlth, Truro, England. [Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Hernandez, Dena G.] UCL, Dept Mol Neurosci, London, England. [Hernandez, Dena G.] UCL, Inst Neurol, Reta Lila Labs, London, England. [Longo, Dan L.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Dept Grp Hlth, Seattle, WA USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. [Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Crosslin, DR (reprint author), Univ Washington, Dept Genome Sci, S213,Campus Mail Box 355065, Seattle, WA 98195 USA. EM davidcr@u.washington.edu RI Crane, Paul/C-8623-2014; Singleton, Andrew/C-3010-2009; Jarvik, Gail/N-6476-2014; Gudnason, Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015; OI Cupples, L. Adrienne/0000-0003-0273-7965; Felix, Janine/0000-0002-9801-5774; Crane, Paul/0000-0003-4278-7465; McDavid, Andrew/0000-0002-6581-1213; Zheng, Xiuwen/0000-0002-1390-0708; Jarvik, Gail/0000-0002-6710-8708; Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Melzer, David/0000-0002-0170-3838; Dehghan, Abbas/0000-0001-6403-016X FU National Human Genome Research Institute (NHGRI), a component of the National Institutes of Health (NIH), Bethesda, MD, USA [HG004610, AG06781, HG04599, HG004608, HG004609, HG004438, HG004424, HG004603]; State of Washington Life Sciences Discovery Fund award; NIA/NIH [AG000932-02]; NIH [N01-AG-12100, HHSN268200625226C, UL1RR025005, HHSN268200782096C]; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, R01 HL-071862]; National Human Genome Research Institute [U01HG004402]; Intramural Research Program of the NIH, National Institute on Aging; MedStar Research Institute; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix for genotyping services [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; Intramural Research Program of the NIH, National Institute on Aging, NIA [N01AG62101, N01AG62103, N01AG62106]; NIA [1R01AG032098-01A1]; Italian Ministry of Health [ICS 110.1RS97.71]; U.S. National Institute on Aging [N01-AG-916413, N01-AG-821336, 263 MD 9164 13, 263 MD 821336]; Intramural Research Program, National Institute on Aging, National Institutes of Health, USA; Netherlands Organization of Scientific Research NWO [175.010.2005.011, 911.03.012]; Research Institute for Diseases in the Elderly (RIDE); Netherlands Genomics Initiative (NGI)/NWO [050 060 810]; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Netherlands Heart Foundation; Ministry of Education, Culture, and Science; Ministry of Health, Welfare, and Sports; European Commission (DG XII); Municipality of Rotterdam; Netherlands Organization for Scientific Research (NWO, VICI) [918-76-619]; Netherlands Organization for Scientific Research (NWO) FX eMERGE: This study was supported by the following U01 grants from the National Human Genome Research Institute (NHGRI), a component of the National Institutes of Health (NIH), Bethesda, MD, USA: (i) HG004610, AG06781 (Group Health Cooperative), (ii) HG04599 (Mayo Clinic), (iii) HG004608 (Marshfield Clinic), (iv) HG004609 (Northwestern University), (v) HG004438 (CIDR), (vi) HG004424 (BROAD) and (vii) HG004603 (Vanderbilt University). Additional support was provided by a State of Washington Life Sciences Discovery Fund award to the Northwest Institute of Genetic Medicine (GPJ). CHARGE: This research was made possible by NIA/NIH contract AG000932-02 (2009) Characterization of Normal Genomic Variability. This study utilized the high-performance computational capabilities of the BiowulfLinux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). The Age, Gene/Environment Susceptibility Reykjavik Study was funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022 and grants R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The BLSA was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. A portion of that support was through a R&D contract with MedStar Research Institute. The National Heart, Lung, and Blood Institute's Framingham Heart Study is a joint project of the National Institutes of Health and Boston University School of Medicine and was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195) and its contract with Affymetrix for genotyping services (contract No. N02-HL-6-4278). Analyses reflect the efforts and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The Health ABC Study was supported in part by the Intramural Research Program of the NIH, National Institute on Aging, NIA contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences, and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. The InChianti Study was supported as a 'targeted project' (ICS 110.1RS97.71) by the Italian Ministry of Health, by the U.S. National Institute on Aging (Contracts N01-AG-916413, N01-AG-821336, 263 MD 9164 13 and 263 MD 821336), and in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health, USA.; The GWAS database of the Rotterdam Study was funded through the Netherlands Organization of Scientific Research NWO (nr. 175.010.2005.011, 911.03.012) and the Research Institute for Diseases in the Elderly (RIDE). This study was supported by the Netherlands Genomics Initiative (NGI)/NWO project number 050 060 810 (Netherlands Consortium for Healthy Ageing). The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands organization for scientific research (NWO), the Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Heart Foundation, the Ministry of Education, Culture, and Science, the Ministry of Health, Welfare, and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. J.F.F. and A. D. were supported by the Netherlands Organization for Scientific Research (NWO, VICI no. 918-76-619). The participation of A. P. R. was supported by National Heart, Lung, and Blood Institute grant R01 HL-071862. NR 17 TC 27 Z9 28 U1 0 U2 8 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 MAY 15 PY 2013 VL 22 IS 10 BP 2119 EP 2127 DI 10.1093/hmg/ddt010 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 139CL UT WOS:000318559000017 PM 23314186 ER PT J AU Sun, HY Munoz, P Torre-Cisneros, J Aguado, JM Lattes, R Montejo, M Garcia-Reyne, A Bouza, E Valerio, M Lara, R John, GT Bruno, D Singh, N AF Sun, Hsin-Yun Munoz, Patricia Torre-Cisneros, Julian Aguado, Jose M. Lattes, Roberta Montejo, Miguel Garcia-Reyne, Ana Bouza, Emilio Valerio, Maricela Lara, Rosario John, George T. Bruno, Didier Singh, Nina TI Mycobacterium Tuberculosis-Associated Immune Reconstitution Syndrome in Solid-Organ Transplant Recipients SO TRANSPLANTATION LA English DT Article DE Immune reconstitution syndrome; Mycobacterium tuberculosis; Solid-organ transplant recipients ID CRYPTOCOCCUS-NEOFORMANS INFECTION; T-CELL RESPONSES; CLINICAL CHARACTERISTICS; PULMONARY TUBERCULOSIS; INFLAMMATORY SYNDROME; RISK-FACTORS; THERAPY; DISEASE AB Background. Incidence, characteristics, and risk factors for tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRS) in solid-organ transplant (SOT) recipients are not known. Methods. Patients are composed of 64 consecutive SOT recipients with TB followed for 12 months. IRS was defined based on previously proposed criteria. Results. IRS developed in 14% (9/64) of the patients, a median of 47 days after the use of anti-TB therapy. Liver versus other types of organ transplant recipients (adjusted odds ratio [OR], 6.11; 95% confidence interval [CI], 1.08-34.86), prior cytomegalovirus infection (adjusted OR, 5.65; 95% CI, 0.93-34.47), and rifampin use (adjusted OR, 4.56; 95% CI, 0.74-27) were associated with a higher risk of IRS. The presence of more than one factor (liver transplantation, cytomegalovirus infection, and rifampin use) when compared with none of these factors conferred a 19-fold increase in the risk of IRS (P=0.01). Mortality at 1 year after diagnosis was 33.3% in patients with IRS and 17.2% in those without IRS (P=0.31). Conclusions. IRS was documented in 14% of the SOT recipients with TB. We determined clinically identifiable factors that may be useful in assessing the risk of tuberculosis-associated posttransplantation IRS. C1 [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 100, Taiwan. [Munoz, Patricia; Bouza, Emilio; Valerio, Maricela] Univ Complutense Madrid, Hosp Gen Univ Gregorio Maranon, Dept Med, Madrid, Spain. [Torre-Cisneros, Julian; Lara, Rosario] Univ Cordoba, Hosp Univ Reina Sofia, Inst Maimonides Invest Biomed Cordoba, Cordoba, Spain. [Aguado, Jose M.; Garcia-Reyne, Ana] Hosp 12 Octubre, E-28041 Madrid, Spain. [Lattes, Roberta] Inst Nefrol, Infect Dis Sect, Dept Transplantat, Buenos Aires, DF, Argentina. [Montejo, Miguel] Hosp Univ Cruces, Bilbao, Spain. [John, George T.] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Bruno, Didier] Hosp Univ Fdn Favaloro, Dept Internal Med, Buenos Aires, DF, Argentina. [Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. RP Sun, HY (reprint author), Natl Taiwan Univ Hosp, Dept Internal Med, 7 Chung Shan South Rd, Taipei 100, Taiwan. EM hy.jamie.sun@gmail.com RI Montejo, Jose Miguel/E-1755-2012; OI Bruno, Didier/0000-0002-9540-2269; Munoz Garcia, Patricia Carmen/0000-0001-5706-5583; bouza, emilio/0000-0001-6967-9267; SUN, HSIN-YUN/0000-0003-0074-7721 FU Ministerio de Economia y Competitividad, Instituto de Salud Carlos III; European Development Regional Fund "A way to achieve Europe," Spanish Network for the Research in Infectious Diseases [REIPI RD06/0008, RD12/0015]; Instituto de Salud Carlos III (Rio Hortega) [CN09130] FX The Spanish investigators are supported by Ministerio de Economia y Competitividad, Instituto de Salud Carlos III-cofinanced by the European Development Regional Fund "A way to achieve Europe," Spanish Network for the Research in Infectious Diseases (REIPI RD06/0008 and RD12/0015). A.G.-R. was supported by a grant from Instituto de Salud Carlos III (Rio Hortega grant no. CN09130). NR 33 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 2013 VL 95 IS 9 BP 1173 EP 1181 DI 10.1097/TP.0b013e31828719c8 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 141ZF UT WOS:000318764500018 PM 23435454 ER PT J AU Beverly, LJ Howell, LA Hernandez-Corbacho, M Casson, L Chipuk, JE Siskind, LJ AF Beverly, Levi J. Howell, Lauren A. Hernandez-Corbacho, Maria Casson, Lavona Chipuk, Jerry E. Siskind, Leah J. TI BAK activation is necessary and sufficient to drive ceramide synthase-dependent ceramide accumulation following inhibition of BCL2-like proteins SO BIOCHEMICAL JOURNAL LA English DT Article DE ABT-263; ABT-737; apoptosis; BCL2; ceramide; haematology; leukaemia; sphingolipid ID BCL-2 FAMILY INHIBITOR; CELL LUNG-CANCER; SPHINGOLIPID METABOLISM; ANTIAPOPTOTIC BCL-2; INDUCED APOPTOSIS; DRUG-RESISTANCE; BH3 DOMAINS; ABT-737; MCL-1; CHANNELS AB Determining mechanistic details about how drugs kill cancer cells is critical for predicting which cancers will respond to given therapeutic regimens and for identifying effective combinations of drugs that more potently kill cancer cells while sparing normal cells. The BCL2 family of proteins and bioactive sphingolipids are intricately linked during apoptotic cell death. In fact, many chemotherapeutic drugs are known to cause accumulation of the pro-apoptotic sphingolipid ceramide; however, the mechanism by which this occurs is not completely understood. In the present study we demonstrate that direct inhibition of antiapoptotic BCL2 proteins with ABT-263 is sufficient to induce C-16-ceramide synthesis in multiple cell lines, including human leukaemia and myeloma cells. ABT-263 activates CerS (ceramide synthase) activity only in cells expressing BAK or in cells capable of activating BAK. Importantly, recombinant BAK is sufficient to increase in vitro CerS activity in microsomes purified from Bak-KO (knockout) cells and activated BAK more potently activates CerS than inactive BAK. Likewise, ABT-263 addition to wild-type, but not Bak-deficient, microsomes increases CerS in vitro activity. Furthermore, we present a feed-forward model by which BAK activation of CerS by chemotherapeutic drugs leads to elevated ceramide levels that result in synergistic channel formation by ceramide (or one of its metabolites) and BAX/BAK. C1 [Beverly, Levi J.; Casson, Lavona] Univ Louisville, James Graham Brown Canc Ctr, Dept Med, Div Hematol & Oncol, Louisville, KY 40202 USA. [Howell, Lauren A.; Siskind, Leah J.] South Carolina Coll Pharm, Med Sch South Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Hernandez-Corbacho, Maria] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Chipuk, Jerry E.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Siskind, Leah J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Beverly, LJ (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Dept Med, Div Hematol & Oncol, Louisville, KY 40202 USA. EM levi.beverly@louisville.edu; siskind@musc.edu OI Chipuk, Jerry Edward/0000-0002-1337-842X FU National Institute of Diabetes and Digestive and Kidney Diseases of the NIH (National Institutes of Health) [R01DK093462]; Cancer Center Support Grant [P30 CA138313]; NIH/NCRR (National Center for Research Resources) COBRE (Centers of Biomedical Research Excellence) in Lipidomics and Pathobiology [P20 RR17677]; NIH, Molecular Targets COBRE [8P20GM103482-10]; Wendy Will Case Cancer Fund [GB220413]; Kosair Pediatric Cancer Research Program award; James Graham Brown Cancer Center, NIH [CA157740]; March of Dimes Foundation [5-FY11-74] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH (National Institutes of Health) [grant number R01DK093462 (to L.J.S.)], the Lipidomics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina supported by a Cancer Center Support Grant [grant number P30 CA138313], pilot project from the NIH/NCRR (National Center for Research Resources) COBRE (Centers of Biomedical Research Excellence) in Lipidomics and Pathobiology [grant number P20 RR17677 (to L.J.S)]; NIH, Molecular Targets COBRE [grant number 8P20GM103482-10 (to L.J.B.)], the Wendy Will Case Cancer Fund [grant number GB220413 (to L.J.B.)], a Kosair Pediatric Cancer Research Program award (to L.J.B.) the James Graham Brown Cancer Center, NIH R01 [grant number CA157740 (to J.E.C.)] and the March of Dimes Foundation [grant number 5-FY11-74 (to J.E.C.)]. NR 49 TC 26 Z9 26 U1 0 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 15 PY 2013 VL 452 BP 111 EP 119 DI 10.1042/BJ20130147 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 137RS UT WOS:000318455700011 PM 23480852 ER PT J AU Manoach, DS Lee, AKC Hamalainen, MS Dyckman, KA Friedman, JS Vangel, M Goff, DC Barton, JJS AF Manoach, Dara S. Lee, Adrian K. C. Hamalainen, Matti S. Dyckman, Kara A. Friedman, Jesse S. Vangel, Mark Goff, Donald C. Barton, Jason J. S. TI Anomalous Use of Context During Task Preparation in Schizophrenia: A Magnetoencephalography Study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anterior cingulate cortex; antisaccade; cognitive control; frontal eye field; lateral prefrontal cortex; schizophrenia ID FRONTAL EYE-FIELD; ANTERIOR CINGULATE CORTEX; DORSOLATERAL PREFRONTAL CORTEX; VISUALLY GUIDED SACCADES; SIGNAL SPACE SEPARATION; FUNCTIONAL CONNECTIVITY; VOLITIONAL SACCADES; COGNITIVE CONTROL; CORTICAL ACTIVITY; BRAIN ACTIVATION AB Background: Impaired ability to use contextual information to optimally prepare for tasks contributes to performance deficits in schizophrenia. We used magnetoencephalography and an antisaccade task to investigate the neural basis of this deficit. Methods: In schizophrenia patients and healthy control participants, we examined the difference in preparatory activation to cues indicating an impending antisaccade or prosaccade. We analyzed activation for correct trials only and focused on the network for volitional ocular motor control-frontal eye field (FEF), dorsal anterior cingulate cortex (dACC), and the ventrolateral and dorsolateral prefrontal cortex (VLPFC, DLPFC). Results: Compared with control subjects, patients made more antisaccade errors and showed reduced differential preparatory activation in the dACC and increased differential preparatory activation in the VLPFC. In patients only, antisaccade error rates correlated with preparatory activation in the FEF, DLPFC, and VLPFC. Conclusions: In schizophrenia, reduced differential preparatory activation of the dACC may reflect reduced signaling of the need for control. Greater preparatory activation in the VLPFC and the correlations of error rate with FEF, DLPFC, and VLPFC activation may reflect that patients who are more error prone require stronger activation in these regions for correct performance. These findings provide the first evidence of abnormal task preparation, distinct from response generation, during volitional saccades in schizophrenia. We conclude that schizophrenia patients are impaired in using task cues to modulate cognitive control and that this contributes to deficits inhibiting prepotent but contextually inappropriate responses and to behavior that is stimulus bound and error prone rather than flexibly guided by context. C1 [Manoach, Dara S.; Lee, Adrian K. C.; Dyckman, Kara A.; Friedman, Jesse S.; Goff, Donald C.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA USA. [Hamalainen, Matti S.; Vangel, Mark] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA USA. [Manoach, Dara S.; Lee, Adrian K. C.; Hamalainen, Matti S.; Vangel, Mark] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Lee, Adrian K. C.] Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. [Barton, Jason J. S.] Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 1M9, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Ophthalmol, Vancouver, BC, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Visual Sci, Vancouver, BC V5Z 1M9, Canada. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, Charlestown Navy Yard, 149 13th St Room 1-111, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012; Hamalainen, Matti/C-8507-2013; OI Lee, Adrian KC/0000-0002-7611-0500 FU National Institute for Mental Health [R01 MH67720, F32 MH082514]; National Alliance for Research on Schizophrenia and Depression; Mental Illness and Neuroscience Discovery (MIND) Institute; Postdoctoral Fellowship Award, MGH-ECOR Fund for Medical Discovery; Advanced Multimodal Neuroimaging Training Program [1-R90 DA023427-02]; National Center for Research Resources [P41RR14075]; CIHR [MOP-81270]; Sepracor, Inc.; Pfizer; Janssen; Novartis; GlaxoSmithKline FX Support: National Institute for Mental Health (R01 MH67720, F32 MH082514); National Alliance for Research on Schizophrenia and Depression; Mental Illness and Neuroscience Discovery (MIND) Institute; Postdoctoral Fellowship Award, MGH-ECOR Fund for Medical Discovery (AKCL); Advanced Multimodal Neuroimaging Training Program (1-R90 DA023427-02 - AKCL); National Center for Research Resources P41RR14075; Canada Research Chair and CIHR grant MOP-81270.; Dr. Manoach reports having received research funding from Sepracor, Inc. and an honorarium from Lilly, Inc. Dr. Goff reports having served as a consultant or advisor to Xytis, Forest Labs, Pfizer, Indevus Pharmaceuticals, H. Lundbeck, Schering-Plough, Eli Lilly, Takeda, Biovail, Solvay, Hoffman-La Roche, Cypress, and Dianippon Sumitomo. He served on a Data and Safety Monitoring Board for Otsuka and Wyeth. He received research funding from Pfizer, Janssen, Novartis, and GlaxoSmithKline. Drs. Lee, Dyckman, Hamalainen, Van gel, and Barton and Mr. Freidman reported: no biomedical financial interests or potential conflicts of interest. NR 70 TC 3 Z9 3 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 2013 VL 73 IS 10 BP 967 EP 975 DI 10.1016/j.biopsych.2012.12.018 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 137SV UT WOS:000318458600006 PM 23380717 ER PT J AU Calkins, ME Ray, A Gur, RC Freedman, R Green, MF Greenwood, TA Light, GA Nuechterlein, KH Olincy, A Radant, AD Seidman, LJ Siever, LJ Silverman, JM Stone, WS Sugar, C Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL Lazzeroni, LC Gur, RE AF Calkins, Monica E. Ray, Amrita Gur, Ruben C. Freedman, Robert Green, Michael F. Greenwood, Tiffany A. Light, Gregory A. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Sugar, Catherine Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. Lazzeroni, Laura C. Gur, Raquel E. TI Sex Differences in Familiality Effects on Neurocognitive Performance in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Endophenotype; genetics; heritability; neurocognition; schizophrenia; sex differences ID 1ST-DEGREE RELATIVES; COGNITIVE DEFICITS; HERITABILITY; ENDOPHENOTYPES; CONSORTIUM; GENETICS; IMPAIRMENTS; VALIDATION; SIBLINGS; FAMILIES AB Background: Numerous studies have documented that patients with schizophrenia show neurocognitive impairments, which are also heritable in schizophrenia families. In view of these findings, the current investigation tested the hypothesis that neurocognitive performance of schizophrenia probands can predict the neurocognitive performance of their unaffected family members. Methods: Participants (n = 1967; schizophrenia = 369; first-degree relatives = 1072; community comparison subjects = 526) in the Consortium on the Genetics of Schizophrenia were administered the Penn Computerized Neurocognitive Battery. Results: Consistent with prior work, probands showed significant neurocognitive impairment, and neurocognitive ability was significantly heritable across domains. On average, unaffected relatives did not differ from community comparison subjects in their neurocognitive performance. However, in six of seven domains, proband scores predicted the performance of their unaffected siblings. Male, but not female, proband performance was predictive of their unaffected relatives' (siblings and mothers) performance, most consistently in face memory and spatial processing. Conclusions: Using a novel approach in which individual probands are paired with their respective unaffected relatives within each family, we found that male proband performance predicted both sister and brother performance, an effect that was most powerfully observed for face memory and spatial processing. Results suggest that the familial transmission of sexually dimorphic neurocognitive domains, in which a particular sex tends to show a performance advantage over the other, may not itself be sex specific in schizophrenia families. C1 [Calkins, Monica E.; Gur, Ruben C.; Turetsky, Bruce I.; Gur, Raquel E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Ray, Amrita; Tsuang, Debby W.; Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA. [Ray, Amrita; Tsuang, Debby W.; Lazzeroni, Laura C.] Stanford Univ, Dept Behav Sci, Stanford, CA 94305 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA. [Greenwood, Tiffany A.; Light, Gregory A.; Swerdlow, Neal R.; Tsuang, Ming T.; Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Vet Affairs San Diego Healthcare Syst, Vet Integrated Serv Network Mental Illness Res Ed, San Diego, CA USA. [Radant, Allen D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.] US Dept Vet Affairs, Vet Integrated Serv Network Mental Illness Res Ed, Seattle, WA USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Dept Psychiat,Sch Med, Boston, MA 02115 USA. [Siever, Larry J.; Silverman, Jeremy M.] SUNY Upstate Med Univ, Med Genet Res Program, Syracuse, NY 13210 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.] James J Peters Vet Affairs, Bronx, NY USA. [Siever, Larry J.] Vet Integrated Serv Network Mental Illness Res Ed, Bronx, NY USA. [Green, Michael F.; Sugar, Catherine] US Dept Vet Affairs, Vet Integrated Serv Network Mental Illness Res Ed, Los Angeles, CA USA. RP Calkins, ME (reprint author), Univ Penn, Sch Med, Dept Psychiat, Schizophrenia Res Ctr, 3600 Spruce St, Philadelphia, PA 19104 USA. EM mcalkins@upenn.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016; OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920 FU National Institute of Mental Health [R01 MH086735, R01 MH65571, R01 MH42228, R01 MH65588, R01 MH65562, R01 MH65707, R01 MH65554, R01 MH65578, R01 MH65558, K08 MH79364]; Neuropsychiatry Postdoctoral traineeship [MH19112]; Scottish Rite Schizophrenia Research Fellowship; Abbott Laboratories; Amgen; Cypress; Lundbeck; Teva; Otsuka; Sunovion; Janssen Scientific Affairs; Genentech; AstraZeneca; Pfizer Pharmaceuticals; La Roche; Bristol-Myers FX This study was supported by National Institute of Mental Health Grants R01 MH086735, R01 MH65571, R01 MH42228, R01 MH65588, R01 MH65562, R01 MH65707, R01 MH65554, R01 MH65578, R01 MH65558, and K08 MH79364; a Neuropsychiatry Postdoctoral traineeship (MH19112); and a Scottish Rite Schizophrenia Research Fellowship.; Dr. Michael F. Green reports having received consulting fees from Abbott Laboratories, Amgen, Cypress, Lundbeck, and Teva. He has received speaking fees from Otsuka and Sunovion. Dr. Gregory A. Light has received compensation for one-time participation in a scientific advisory board meeting for Astellas Inc. Dr. Keith H. Nuechterlein reports research grant funding from Janssen Scientific Affairs and Genentech and consulting fees from Genentech and Otsuka. Dr. Neal R. Swerdlow was a consultant to Neurocrine, Inc. Dr. Bruce I. Turetsky reports unrelated research grant support from AstraZeneca and Pfizer Pharmaceuticals and consulting fees from La Roche and Bristol-Myers. Dr. Laura C Lazzeroni is named as an inventor on a pharmacogenetic patent application that is being pursued by Stanford University. All other authors report no biomedical financial interests or potential conflicts of interest. NR 33 TC 11 Z9 11 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 2013 VL 73 IS 10 BP 976 EP 984 DI 10.1016/j.biopsych.2012.12.021 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 137SV UT WOS:000318458600007 PM 23395246 ER PT J AU Lester-Coll, NH Goldhaber, SZ Sher, DJ D'Amico, AV AF Lester-Coll, Nataniel H. Goldhaber, Samuel Z. Sher, David J. D'Amico, Anthony V. TI Death from high-risk prostate cancer versus cardiovascular mortality with hormonal therapy A Decision Analysis SO CANCER LA English DT Article DE prostate cancer; cardiovascular disease; hormonal therapy; radiation therapy; decision analysis ID ANDROGEN DEPRIVATION THERAPY; PHASE-III TRIAL; CONGESTIVE-HEART-FAILURE; RADIATION-THERAPY; RANDOMIZED-TRIAL; MYOCARDIAL-INFARCTION; RADIOTHERAPY; DISEASE; MEN; SUPPRESSION AB BACKGROUND: Randomized trials have demonstrated improved survival when hormonal therapy (HT) is added to radiation therapy (RT) for high-risk prostate cancer. However, it is still unknown whether men who have a history of myocardial infarction (MI) or MI risk factors achieve a superior outcome from HT. METHODS: A Markov decision analysis model was used to compare quality-adjusted life expectancy (QALE) in men aged 50, 60, and 70 years who received RT and no HT, 6 months of HT (short-term), or 3 years of HT (long-term) for high-risk prostate cancer stratified by cardiac risk group. RESULTS: In men with a history of MI, there was a decrease of 0.1 to 0.2 quality-adjusted life years and 0.5 to 0.6 quality-adjusted life years across all ages with short-term HT and long-term HT, respectively, compared with no HT. In men without MI, receipt of short-term or long-term HT was associated with a QALE benefit versus no HT in all cohorts. Among men without MI, the optimal duration of HT was a function of age and the number of MI risk factors. Long-term HT improved QALE (range, 1.4-5.4 years) for men aged 50 or 60 years except those with MI; whereas, for men aged 70 years with 4 cardiac risk factors, short-term and long-term HT yielded identical QALE. CONCLUSIONS: Men who received RT for high-risk prostate cancer and had a history of MI experienced net harm when they received HT. Men without MI gained a QALE benefit from HT, even if they had up to 4 cardiac risk factors. The optimal duration of HT is a function of patient age and the number of cardiac risk factors. Cancer 2013. (c) 2013 American Cancer Society. C1 [Lester-Coll, Nataniel H.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Goldhaber, Samuel Z.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Sher, David J.] Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Lester-Coll, NH (reprint author), 15 York St,101 FMP, New Haven, CT 06510 USA. EM nataniel.lester-coll@yale.edu OI Lester-Coll, Nataniel/0000-0002-1012-1477 FU Daiichi Sankyo; Eisai; EKOS; Johnson Johnson; Sanofi Aventis; Baxter; Boehringer Ingelheim; Bristol-Myers Squibb; Medscape; Merck; Portola FX Samuel Z. Goldhaber has received research grants from Daiichi Sankyo, Eisai, EKOS, Johnson & Johnson, and Sanofi Aventis and is a paid consultant for Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Medscape, Merck, Portola, and Sanofi Aventis. NR 31 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2013 VL 119 IS 10 BP 1808 EP 1815 DI 10.1002/cncr.27980 PG 8 WC Oncology SC Oncology GA 138JT UT WOS:000318505500009 PM 23400678 ER PT J AU Iasonos, A Keung, EZ Zivanovic, O Mancari, R Peiretti, M Nucci, M George, S Colombo, N Carinelli, S Hensley, ML Raut, CP AF Iasonos, Alexia Keung, Emily Z. Zivanovic, Oliver Mancari, Rosanna Peiretti, Michele Nucci, Marisa George, Suzanne Colombo, Nicoletta Carinelli, Silvestro Hensley, Martee L. Raut, Chandrajit P. TI External validation of a prognostic nomogram for overall survival in women with uterine leiomyosarcoma SO CANCER LA English DT Article DE nomogram; uterine leiomyosarcoma; International Federation of Gynecology and Obstetrics and American Joint Committee on Cancer; cancer; staging; validation ID PROSTATE-CANCER; STAGE-I; SARCOMAS; RADIOTHERAPY; RECURRENCE; THERAPY; SYSTEMS; 5-YEAR AB BACKGROUND: There is no validated system to identify prognostically distinct cohorts of women with uterine leiomyosarcoma (ULMS). By using an independent, pooled, multi-institutional, international patient cohort, the authors validated a recently proposed ULMS nomogram. METHODS: The ULMS nomogram incorporated 7 clinical characteristics (age, tumor size, tumor grade, cervical involvement, locoregional metastases, distant metastases, and mitotic index (per 10 high-power fields) to predict overall survival (OS) after primary surgery. Independent cohorts from 2 sarcoma centers were included. Eligible women, at minimum, underwent a hysterectomy for primary, locally advanced, or metastatic ULMS and received part of their care at 1 of the centers between 1994 and 2010. RESULTS: In total, 187 women with ULMS were identified who met the above criteria described above (median age, 51 years; median tumor size, 9 cm; median mitotic index, 20 per 10 high-power fields). Tumors generally were high grade (88%), FIGO stage I or II (61%) without cervical involvement (93%) and without locoregional metastases (77%) or distant metastases (83%). The median OS and the 5-year OS rate were 4.5 years (95% confidence interval, 3.2-5.3 years) and 46%, respectively; and 65 women (35%) remained alive at last follow-up. The nomogram concordance index was 0.67(standard error, 0.02), which was as high as the concordance index from the initial cohort used for nomogram development. The concordance between actual OS and nomogram predictions suggests excellent calibration because predictions were within 1% of actual 5-year OS rates for patients with a predicted 5-year OS of less than 0.68. CONCLUSIONS: The ULMS nomogram was externally validated using independent cohorts. These findings support the international use of the ULMS nomogram prognostic of OS in ULMS. Cancer 2013. (c) 2012 American Cancer Society. C1 [Iasonos, Alexia] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10065 USA. [Keung, Emily Z.; Raut, Chandrajit P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. [Zivanovic, Oliver] Univ Hosp Bonn, Dept Obstet & Gynecol, Bonn, Germany. [Mancari, Rosanna; Peiretti, Michele] European Inst Oncol, Div Gynecol, Gynecol Med Oncol Unit, Milan, Italy. [Nucci, Marisa] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA. [George, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Colombo, Nicoletta] Univ Milano Bicocca, Dept Surg Sci, Milan, Italy. [Colombo, Nicoletta] European Inst Oncol, Milan, Italy. [Carinelli, Silvestro] European Inst Oncol, Div Pathol & Lab Med, Milan, Italy. [Hensley, Martee L.] Mem Sloan Kettering Canc Ctr, Dept Med, Gynecol Med Oncol Serv, New York, NY 10021 USA. [Hensley, Martee L.] Weill Cornell Med Coll, New York, NY USA. RP Iasonos, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, 407 East 63rd St, New York, NY 10065 USA. EM iasonosa@mskcc.org FU NCI NIH HHS [P30 CA008748] NR 24 TC 15 Z9 17 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2013 VL 119 IS 10 BP 1816 EP 1822 DI 10.1002/cncr.27971 PG 7 WC Oncology SC Oncology GA 138JT UT WOS:000318505500010 PM 23456762 ER PT J AU Sharma, A Schwartz, SM Mendez, E AF Sharma, Arun Schwartz, Stephen M. Mendez, Eduardo TI Hospital volume is associated with survival but not multimodality therapy in Medicare patients with advanced head and neck cancer SO CANCER LA English DT Article DE head and neck neoplasms; survival; radiotherapy; chemoradiotherapy; cisplatin ID LOCALLY ADVANCED HEAD; SQUAMOUS-CELL CARCINOMA; STAGE LARYNGEAL-CANCER; COMORBIDITY INDEX; CHEMOTHERAPY; RADIOTHERAPY; IMPACT; FACILITIES; MORTALITY; RESECTION AB BACKGROUND: Given the complexity of management of advanced head and neck squamous cell carcinoma (HNSCC), this study hypothesized that high hospital volume would be associated with receiving National Comprehensive Cancer Network (NCCN) guideline therapy and improved survival in patients with advanced HNSCC. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify patients with advanced HNSCC. Treatment modalities and survival were determined using Medicare data. Hospital volume was determined by the number of patients with HNSCC treated at each hospital. RESULTS: There were 1195 patients with advanced HNSCC who met inclusion criteria. In multivariable analyses, high hospital volume was not associated with receiving multimodality therapy per NCCN guidelines (odds ratio = 1.02, 95% confidence interval = 0.66-1.60), but showed a nearly significant inverse association with survival in a model adjusted for National Cancer Institutedesignated cancer center status, age, sex, race, socioeconomic status, marital status, comorbidity, year of diagnosis, tumor site, and tumor stage (hazard ratio = 0.85, 95% confidence interval = 0.69-1.04). CONCLUSIONS: Medicare patients with advanced HNSCC treated at high-volume hospitals were not more likely to receive NCCN guideline therapy, but had nearly statistically significant better survival, when compared with patients treated at low-volume hospitals. These results suggest that features of high-volume hospitals other than delivery of NCCN guideline therapy influence survival. Cancer 2013. (c) 2013 American Cancer Society. C1 [Sharma, Arun; Mendez, Eduardo] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. [Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. [Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. RP Mendez, E (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave,North Mailstop D4-100, Seattle, WA 98109 USA. EM edmendez@u.washington.edu OI Schwartz, Stephen/0000-0001-7499-8502 FU National Institute on Deafness and Other Communication Disorders Grant [2T32DC000018]; National Cancer Institute [N01-PC-35142]; National Center for Research Resources Grant [5KL2RR025015]; Intuitive Surgical, Inc. FX This work was funded by National Institute on Deafness and Other Communication Disorders Grant 2T32DC000018; National Cancer Institute Contract N01-PC-35142; and National Center for Research Resources Grant 5KL2RR025015.; Dr. Mendez has received speaking fees/honoraria from Intuitive Surgical, Inc. All other authors made no disclosures. NR 29 TC 14 Z9 14 U1 0 U2 6 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 MAY 15 PY 2013 VL 119 IS 10 BP 1845 EP 1852 DI 10.1002/cncr.27976 PG 8 WC Oncology SC Oncology GA 138JT UT WOS:000318505500014 PM 23456789 ER PT J AU Kolpa, HJ Peal, DS Lynch, SN Giokas, AC Ghatak, S Misra, S Norris, RA MacRae, CA Markwald, RR Ellinor, P Bischoff, J Milan, DJ AF Kolpa, Heather J. Peal, David S. Lynch, Stacey N. Giokas, Andrea C. Ghatak, Shibnath Misra, Suniti Norris, Russell A. MacRae, Calum A. Markwald, Roger R. Ellinor, Patrick Bischoff, Joyce Milan, David J. TI miR-21 represses Pdcd4 during cardiac valvulogenesis SO DEVELOPMENT LA English DT Article DE Cardiac valves; microRNA; Endothelium ID EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR GENE; VALVE FORMATION; BREAST-CANCER; MICRORNA EXPRESSION; ZEBRAFISH; OSTEOPONTIN; CELLS; GROWTH; MORPHOGENESIS AB The discovery of small non-coding microRNAs has revealed novel mechanisms of post-translational regulation of gene expression, the implications of which are still incompletely understood. We focused on microRNA 21 (miR-21), which is expressed in cardiac valve endothelium during development, in order to better understand its mechanistic role in cardiac valve development. Using a combination of in vivo gene knockdown in zebrafish and in vitro assays in human cells, we show that miR-21 is necessary for proper development of the atrioventricular valve (AV). We identify pdcd4b as a relevant in vivo target of miR-21 and show that protection of pdcd4b from miR-21 binding results in failure of AV development. In vitro experiments using human pulmonic valve endothelial cells demonstrate that miR-21 overexpression augments endothelial cell migration. PDCD4 knockdown alone was sufficient to enhance endothelial cell migration. These results demonstrate that miR-21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4. C1 [Kolpa, Heather J.; Peal, David S.; Lynch, Stacey N.; Giokas, Andrea C.; MacRae, Calum A.; Ellinor, Patrick; Milan, David J.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ghatak, Shibnath; Misra, Suniti; Norris, Russell A.; Markwald, Roger R.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Bischoff, Joyce] Harvard Univ, Sch Med, Dept Surg, Vasc Biol Program,Childrens Hosp Boston, Boston, MA 02115 USA. RP Milan, DJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, 55 Fruit St, Boston, MA 02114 USA. EM dmilan@partners.org OI Bischoff, Joyce/0000-0002-6367-1974 FU Fondation Leducq, Paris, France for the Transatlantic MITRAL Network of Excellence [07CVD04]; American Heart Association [2261354, 11SDG5270006]; National Institutes of Health [HL33756] FX This work was supported in part by the Fondation Leducq, Paris, France for the Transatlantic MITRAL Network of Excellence to D. S. P, J.B., R.A.N, R. R. M. and D.J.M. [07CVD04]; by the American Heart Association [2261354 to D.J.M. and 11SDG5270006 to R.A.N.]; and by the National Institutes of Health [HL33756 to R. R. M.]. Deposited in PMC for release after 12 months. NR 53 TC 8 Z9 8 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY 15 PY 2013 VL 140 IS 10 BP 2172 EP 2180 DI 10.1242/dev.084475 PG 9 WC Developmental Biology SC Developmental Biology GA 135FO UT WOS:000318273900012 PM 23578931 ER PT J AU Parekh, VV Wu, L Boyd, KL Williams, JA Gaddy, JA Olivares-Villagomez, D Cover, TL Zong, WX Zhang, JH Van Kaer, L AF Parekh, Vrajesh V. Wu, Lan Boyd, Kelli L. Williams, Janice A. Gaddy, Jennifer A. Olivares-Villagomez, Danyvid Cover, Timothy L. Zong, Wei-Xing Zhang, Jianhua Van Kaer, Luc TI Impaired Autophagy, Defective T Cell Homeostasis, and a Wasting Syndrome in Mice with a T Cell-Specific Deletion of Vps34 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NKT CELLS; MAMMALIAN-CELLS; KINASE VPS34; DEATH; EXPRESSION; ANTIGEN; PROLIFERATION; INFLAMMATION; LYMPHOCYTES; METABOLISM AB Autophagy plays a critical role in multiple aspects of the immune system, including the development and function of T lymphocytes. In mammalian cells, the class III PI3K vacuolar protein sorting (Vps) 34 is thought to play a critical role in autophagy. However, recent studies have cast doubt on the role of Vps34 in autophagy, at least in certain cell types. To study the effects of Vps34 on autophagy in T lymphocytes, we generated mice that selectively lack Vps34 in the T cell lineage. Vps34 ablation in T cells caused profound defects in autophagic flux, resulting in accumulation of cellular organelles and apoptosis. These animals exhibited normal intrathymic development of conventional T cells, but they were profoundly impaired in the intrathymic development of invariant NKT cells. In peripheral organs, T cell-specific ablation of Vps34 had a profound impact on T cell homeostasis and function. Furthermore, aged animals developed an inflammatory wasting syndrome characterized by weight loss, intestinal inflammation, and anemia. Consistent with this phenotype, Vps34 was required for the peripheral maintenance and function of CD4(+)Foxp3(+) regulatory T cells. Collectively, our study reveals a critical role for Vps34 in autophagy and for the peripheral homeostasis and function of T lymphocytes. C1 [Parekh, Vrajesh V.; Wu, Lan; Boyd, Kelli L.; Olivares-Villagomez, Danyvid; Cover, Timothy L.; Van Kaer, Luc] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Williams, Janice A.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Gaddy, Jennifer A.; Cover, Timothy L.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Cover, Timothy L.] Vet Affairs Tennessee Valley Healthcare Sys, Nashville, TN 37232 USA. [Zong, Wei-Xing] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. [Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Parekh, VV (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Med Ctr North, 21st Ave South Garland Ave,Room AA 5206, Nashville, TN 37232 USA. EM vrajesh.v.parekh@vanderbilt.edu; luc.van.kaer@vanderbilt.edu RI Van Kaer, Luc/H-1033-2015; Cover, Timothy/I-3814-2015; OI Van Kaer, Luc/0000-0001-5275-2309; Cover, Timothy/0000-0001-8503-002X; Zhang, Jianhua/0000-0002-2128-9574 FU National Institutes of Health [AI070305, HL089667, DK081536, CA129536, GM97355, NS064090, P30DK058404]; Veterans Affairs merit award; Vanderbilt Digestive Diseases Research Center; National Multiple Sclerosis Society of America FX This work was supported by National Institutes of Health Grants AI070305 (to L. V. K.), HL089667 (to L. V. K.), DK081536 (to L. W. and L. V. K.), CA129536 (to W.-X.Z), GM97355 (to W.-X.Z.), and NS064090 (to J.Z.), a Veterans Affairs merit award (to J.Z.), the Vanderbilt Digestive Diseases Research Center (supported by National Institutes of Health Grant P30DK058404), and a postdoctoral fellowship from the National Multiple Sclerosis Society of America (to V.V.P.). NR 53 TC 36 Z9 37 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 MAY 15 PY 2013 VL 190 IS 10 BP 5086 EP 5101 DI 10.4049/jimmunol.1202071 PG 16 WC Immunology SC Immunology GA 138YB UT WOS:000318546700020 PM 23596309 ER PT J AU Xu, P Wen, Z Shi, X Li, Y Fan, L Xiang, M Li, A Scott, MJ Xiao, G Li, S Billiar, TR Wilson, MA Fan, J AF Xu, Peng Wen, Zongmei Shi, Xueyin Li, Yuehua Fan, Liyan Xiang, Meng Li, Aijun Scott, Melanie J. Xiao, Guozhi Li, Song Billiar, Timothy R. Wilson, Mark A. Fan, Jie TI Hemorrhagic Shock Augments Nlrp3 Inflammasome Activation in the Lung through Impaired Pyrin Induction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; RESPIRATORY-DISTRESS-SYNDROME; MULTIPLE ORGAN FAILURE; SEVERE BLUNT TRAUMA; PULMONARY INFLAMMATION; GENE-EXPRESSION; INTERLEUKIN-10; CYTOKINE; INJURY; MEDIATORS AB Hemorrhagic shock (HS) promotes the development of systemic inflammatory response syndrome and organ injury by activating and priming the innate immune system for an exaggerated inflammatory response through, as of yet, unclear mechanisms. IL-1 beta also plays an important role in the development of post-HS systemic inflammatory response syndrome and active IL-1 beta production is tightly controlled by the inflammasome. Pyrin, a protein of 781 aa with pyrin domain at the N-terminal, negatively regulates inflammasome activation through interaction with nucleotide-binding oligomerization domain-like receptor protein (NLRP). Expression of pyrin can be induced by LPS and cytokines, and IL-10 is a known potent inducer of pyrin expression in macrophages. In the current study, we tested the hypothesis that HS downregulates IL-10 and therefore decreases pyrin expression to promote inflammasome activation and subsequent IL-1 beta processing and secretion in the lungs. Our results show that LPS, while activating Nlrp3 inflammasome in the lungs, also induced pyrin expression, which in turn suppressed inflammasome activation. More importantly, LPS-mediated upregulation of IL-10 enhanced pyrin expression, which serves, particularly in later phases, as a potent negative-feedback mechanism regulating inflammasome activation. However, HS-mediated suppression of IL-10 expression in alveolar macrophages attenuated the upregulation of pyrin in alveolar macrophages and lung endothelial cells and thereby significantly enhanced inflammasome activation and IL-1 beta secretion in the lungs. This study demonstrates a novel mechanism by which HS suppresses negative-feedback regulation of Nlrp3 inflammasome to enhance IL-1 beta secretion in response to subsequent LPS challenge and so primes for inflammation. C1 [Xu, Peng; Wen, Zongmei; Li, Yuehua; Xiang, Meng; Scott, Melanie J.; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie] Univ Pittsburgh, Dept Surg, Sch Med, Pittsburgh, PA 15213 USA. [Xu, Peng; Wen, Zongmei; Shi, Xueyin] Second Mil Med Univ, Changzheng Hosp, Dept Anesthesiol, Shanghai 200003, Peoples R China. [Fan, Liyan] Univ Pittsburgh, Sch Arts & Sci, Pittsburgh, PA 15213 USA. [Xiang, Meng] Fudan Univ, Dept Physiol & Pathophysiol, Shanghai Med Coll, Shanghai 200032, Peoples R China. [Li, Aijun] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai 200003, Peoples R China. [Xiao, Guozhi] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Li, Song] Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Billiar, Timothy R.; Fan, Jie] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15219 USA. [Wilson, Mark A.; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA 15240 USA. RP Fan, J (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Bldg 1,2W109 151L U,Univ Dr C, Pittsburgh, PA 15240 USA. EM shixueyin1128@yahoo.com.cn; jif7@pitt.edu FU National Institutes of Health [R01-HL-079669]; National Institutes of Health Center Grant [P50-GM-53789]; Veterans Affairs Merit Award; 12th five-year key project grant of the People's Liberation Army [BWS12J027] FX This work was supported by the National Institutes of Health Grant R01-HL-079669 (to M. A. W. and J.F.), National Institutes of Health Center Grant P50-GM-53789 (to T. R. B. and J.F.), a Veterans Affairs Merit Award (to J.F.), and the 12th five-year key project grant of the People's Liberation Army BWS12J027 (to X.S.). NR 48 TC 17 Z9 19 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2013 VL 190 IS 10 BP 5247 EP 5255 DI 10.4049/jimmunol.1203182 PG 9 WC Immunology SC Immunology GA 138YB UT WOS:000318546700036 PM 23585683 ER PT J AU Zanni, MV Abbara, S Lo, J Wai, B Hark, D Marmarelis, E Grinspoon, SK AF Zanni, Markella V. Abbara, Suhny Lo, Janet Wai, Bryan Hark, David Marmarelis, Eleni Grinspoon, Steven K. TI Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men SO AIDS LA English DT Article DE atherosclerosis; cardiovascular disease; HIV; myocardial infarction; plaque ID ACTIVE ANTIRETROVIRAL THERAPY; ACUTE MYOCARDIAL-INFARCTION; INTRAVASCULAR ULTRASOUND; RISK-FACTORS; DISEASE; DEATH; LESIONS; INFLAMMATION; MORPHOLOGY; MORTALITY AB Objective: Among HIV-infected patients, high rates of myocardial infarction (MI) and sudden cardiac death have been observed. Exploring potential underlying mechanisms, we used multidetector spiral coronary computed tomography angiography (coronary CTA) to compare atherosclerotic plaque morphology in HIV-infected patients and non-HIV-infected controls. Methods: Coronary atherosclerotic plaques visualized by CTA in HIV-infected (101) and non-HIV-infected (41) men without clinically apparent heart disease matched on cardiovascular risk factors were analyzed for three vulnerability features: low attenuation, positive remodeling, and spotty calcification. Results: Ninety-five percent of HIV-infected patients were receiving ART (median duration 7.9 years) and had well controlled disease (median CD4 cell count, 473 cells/mu l; median HIV RNA <50 copies/ml). Age and traditional cardiovascular risk factors were similar in HIV-infected patients and controls. Among the HIV-infected (versus control) group, there was a higher prevalence of patients with at least one: low attenuation plaque (22.8 versus 7.3%, P = 0.02), positively remodeled plaque (49.5 versus 31.7%, P = 0.05) and high-risk 3-feature plaque (7.9 versus 0%, P = 0.02). Moreover, patients in the HIV-infected (versus control) group demonstrated a higher number of low attenuation plaques (P = 0.01) and positively remodeled plaques (P = 0.03) per patient. Conclusion: Our data demonstrate an increased prevalence of vulnerable plaque features among relatively young HIV-infected patients. Differences in coronary atherosclerotic plaque morphology - namely, increased vulnerable plaque among HIV-infected patients - are here for the first time reported and may contribute to increased rates of MI and sudden cardiac death in this population. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:1263-1272 C1 [Zanni, Markella V.; Lo, Janet; Hark, David; Marmarelis, Eleni; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Zanni, Markella V.; Abbara, Suhny; Lo, Janet; Wai, Bryan; Hark, David; Marmarelis, Eleni; Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA USA. [Abbara, Suhny; Wai, Bryan] Massachusetts Gen Hosp, Cardiovasc Imaging Sect, Dept Radiol, Boston, MA 02114 USA. RP Zanni, MV (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM mzanni@partners.org FU Medical Research Investigator Training (MeRIT) award from Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences) [8KL2TR000168-05]; Bristol Myers Squibb; National Institutes of Health [K23 HL092792, K24 DK064545, RO1HL095123, M01-RR-01066, 1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center; National Center for Research Resources; NIH [P30DK040561] FX This work was conducted with the support of a Medical Research Investigator Training (MeRIT) award from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8KL2TR000168-05. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. This work was also conducted with research funding from Bristol Myers Squibb to S. K. G. and with the support of National Institutes of Health Grants K23 HL092792 to J.L., K24 DK064545 and RO1HL095123 to S. K. G., and M01-RR-01066 and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. Finally, this work was supported in part by the NIH grant P30DK040561 to the Nutrition Obesity Research Center at Harvard. NR 37 TC 38 Z9 38 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 15 PY 2013 VL 27 IS 8 BP 1263 EP 1272 DI 10.1097/QAD.0b013e32835eca9b PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 133RG UT WOS:000318156400009 PM 23324657 ER PT J AU Lang, JS Scherzer, R Weekley, CC Tien, PC Grunfeld, C Shlipak, MG AF Lang, Joshua Scherzer, Rebecca Weekley, Cristin C. Tien, Phyllis C. Grunfeld, Carl Shlipak, Michael G. TI Serum albumin and short-term risk for mortality and cardiovascular disease among HIV-infected veterans SO AIDS LA English DT Article DE albumin; cardiovascular disease; end-stage renal disease; glomerular filtration rate; kidney ID INFLAMMATION; PROGRESSION; SURVIVAL; MARKERS; ASSOCIATION; PREDICTOR; VIRUS; WOMEN AB Objective: We examined the short-term and long-term associations of serum albumin with mortality and cardiovascular disease among HIV-infected veterans. Design: Retrospective cohort analysis using a national database of US veterans with HIV infection. Methods: This analysis evaluated all HIV-infected veterans in the Department of Veterans Affairs HIV Clinical Case Registry (CCR), a national database consisting of demographic, clinical, laboratory, pharmaceutical, and viral status data. There were 25 522 patients enrolled between 1986 and 2007. We evaluated the associations of baseline and time-updated serum albumin levels with all-cause mortality, atherosclerotic cardiovascular disease, and heart failure by multivariate proportional hazards models. Results: Over 21 years, there were 10 869 deaths; the cumulative mortality was 73.2 per 1000 person-years. After multivariate adjustment for covariates measured at baseline, the lowest category of serum albumin (<2.5 g/dl) was associated with a higher mortality risk compared with the highest category (>4 g/dl; hazard ratio 3.00; 2.67-3.37). When analyzed as a time-dependent model, the association strengthened substantially (15.1; 14.0-16.4). Findings were similar for atherosclerotic cardiovascular disease and heart failure. We stratified the baseline mortality model by year of follow-up and found that albumin was more strongly associated with deaths that occurred within 1 year of baseline (9.29; 7.85-11.0) than in the second (1.66; 1.18-2.33) or third (1.22; 0.77-1.96) year after measurement. Conclusion: Among ambulatory HIV-infected patients, lower serum albumin levels are strongly predictive of mortality risk, particularly within 1 year. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:1339-1343 C1 [Lang, Joshua] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Scherzer, Rebecca; Tien, Phyllis C.; Grunfeld, Carl; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA USA. [Scherzer, Rebecca; Tien, Phyllis C.; Grunfeld, Carl; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Weekley, Cristin C.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU [1R03AG034871-01] FX 1R03AG034871-01: 'Kidney Disease, Antiretroviral Therapy and Cardiovascular Events in HIV-Infection' (principal investigator, M. G. S.), which was administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, CA, USA. NR 16 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 15 PY 2013 VL 27 IS 8 BP 1339 EP 1343 DI 10.1097/QAD.0b013e32835f1dd6 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 133RG UT WOS:000318156400017 PM 23343914 ER PT J AU Thomas, B Matson, S Chopra, V Sun, LP Sharma, S Hersch, S Rosas, HD Scherzer, C Ferrante, R Matson, W AF Thomas, Beena Matson, Samantha Chopra, Vanita Sun, Liping Sharma, Swati Hersch, Steven Rosas, H. Diana Scherzer, Clemens Ferrante, Robert Matson, Wayne TI A novel method for detecting 7-methyl guanine reveals aberrant methylation levels in Huntington disease SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE 7-Methyl guanine (7-MG); Guanine (G); Huntington disease (HD); Electrochemical detection (ECD) ID TANDEM MASS-SPECTROMETRY; NF-KAPPA-B; LIQUID-CHROMATOGRAPHY; ELECTROCHEMICAL DETECTION; DNA; ADDUCTS; BRAIN; CANCER; SENSITIVITY; EPIGENETICS AB Guanine methylation is a ubiquitous process affecting DNA and various RNA species. N-7 guanine methylation (7-MG), although relatively less studied, could have a significant role in normal transcriptional regulation as well as in the onset and development of pathological conditions. The lack of a sensitive method to accurately quantify trace amounts of altered bases such as 7-MG has been a major deterrent in delineating its biological function(s). Here we report the development of methods to detect trace amounts of 7-MG in biological samples using electrochemical detection combined with high-performance liquid chromatography (HPLC) separation of compounds. We further sought to assess global alterations in DNA methylation in Huntington disease (HD), where transcriptional dysregulation is a major factor in pathogenesis. The developed method was used to study guanine methylation in cytoplasmic and nuclear nucleic acids from human and transgenic mouse HD brain and controls. Significant differences were observed in the guanine methylation levels in mouse and human samples, consistent with the known transcriptional pathology of HD. The sensitivity of the method makes it capable of detecting subtle aberrations. Identification of changes in methylation pattern will provide insights into the molecular mechanism changes that translate into onset and/or development of symptoms in diseases such as HD. (C) 2013 Elsevier Inc. All rights reserved. C1 [Thomas, Beena; Sun, Liping; Sharma, Swati; Matson, Wayne] Bedford VA Med Ctr, Dept Syst Biochem, Bedford, MA 01730 USA. [Matson, Samantha; Chopra, Vanita; Hersch, Steven] Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Boston, MA 02115 USA. [Chopra, Vanita; Hersch, Steven; Rosas, H. Diana] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rosas, H. Diana] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scherzer, Clemens] Harvard Univ, Sch Med, Biomarker Program, Harvard NeuroDiscovery Ctr, Cambridge, MA 02139 USA. [Scherzer, Clemens] Brigham & Womens Hosp, Ctr Neurol Dis, Cambridge, MA 02139 USA. [Ferrante, Robert] Vet Adm Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Ferrante, Robert] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA. [Ferrante, Robert] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Ferrante, Robert] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA. RP Matson, W (reprint author), Bedford VA Med Ctr, Dept Syst Biochem, Bedford, MA 01730 USA. EM wayne.matson@va.gov FU National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) [PO1NS058793] FX This research was supported by a National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) grant (PO1NS058793). We also acknowledge the VA Medical Center (Bedford, MA, USA). NR 37 TC 17 Z9 17 U1 0 U2 39 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 15 PY 2013 VL 436 IS 2 BP 112 EP 120 DI 10.1016/j.ab.2013.01.035 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 128US UT WOS:000317795800010 PM 23416183 ER PT J AU Hsiao, FJ Cheng, CH Chen, WT Lin, YY AF Hsiao, Fu-Jung Cheng, Chia-Hsiung Chen, Wei-Ta Lin, Yung-Yang TI Neural correlates of somatosensory paired-pulse suppression: A MEG study using distributed source modeling and dynamic spectral power analysis SO NEUROIMAGE LA English DT Article DE Paired-pulse suppression; Somatosensory; Minimum norm estimates; Spectral power; Magnetoencephalography ID MEDIAN NERVE-STIMULATION; MAGNETIC-FIELDS; HUMAN BRAIN; OSCILLATORY CHARACTERISTICS; ALPHA OSCILLATIONS; CORTICAL NETWORK; CORTEX; SCHIZOPHRENIA; ACTIVATION; RESPONSES AB Paired-pulse stimulation has been used previously to evaluate cortical excitability and sensory gating. To help elucidate the neural network involved in paired-pulse suppression of somatosensoly cortical processing, magnetoencephalographic (MEG) responses to paired-pulse electrical stimulation of the left median nerve of the wrists of 13 healthy males were recorded using an intra-pair interstimulus interval (ISI) of 500 ms and an inter-pair ISI of 8 s. Minimum norm estimates showed the presence of cortical activation in the bilateral primary somatosensmy cortex, the post-central sulcus and the supplementary motor areas. Compared with the responses to the first stimulation, the responses to the second stimulation were attenuated in these areas with gating ratios (the amplitude ratios of the second response to the first response) of 0.54-0.69. By spectral power dynamic analysis, beta frequency oscillations were found to be associated with an early-latency (30-36 ms) gating process in the contralateral primary somatosensory cortex and post-central sulcus, whereas theta and alpha oscillations were correlated with paired-pulse suppression of activations at 98-136 ms in the ipsilateral primary somatosensory cortex, the bilateral post-central sulcus and the supplementary motor areas. In summary, it can be concluded that differential oscillatory activities are involved in the pair-pulse suppression in various somatosensoty regions in response to repetitive external stimulations. (C) 2013 Elsevier Inc. All rights reserved. C1 [Hsiao, Fu-Jung; Cheng, Chia-Hsiung; Lin, Yung-Yang] Natl Yang Ming Univ, Inst Brain Sci, Sch Med, Taipei 112, Taiwan. [Chen, Wei-Ta; Lin, Yung-Yang] Natl Yang Ming Univ, Dept Neurol, Sch Med, Taipei 112, Taiwan. [Lin, Yung-Yang] Natl Yang Ming Univ, Inst Clin Med, Sch Med, Taipei 112, Taiwan. [Lin, Yung-Yang] Natl Yang Ming Univ, Inst Physiol, Sch Med, Taipei 112, Taiwan. [Hsiao, Fu-Jung] Taipei City Hosp, Dept Educ & Res, Taipei, Taiwan. [Hsiao, Fu-Jung; Cheng, Chia-Hsiung; Lin, Yung-Yang] Taipei Vet Gen Hosp, Neurophysiol Lab, Taipei, Taiwan. [Hsiao, Fu-Jung; Cheng, Chia-Hsiung; Lin, Yung-Yang] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan. [Chen, Wei-Ta; Lin, Yung-Yang] Taipei Vet Gen Hosp, Dept Neurol, Taipei, Taiwan. [Chen, Wei-Ta] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Lin, YY (reprint author), Natl Yang Ming Univ, Inst Brain Sci, 155,Sec 2,Linong St, Taipei 112, Taiwan. EM yylin@vghtpe.gov.tw OI Cheng, Chia-Hsiung/0000-0001-6654-9387 FU Taipei Veterans General Hospital [VGH-ER3-99-006, V99C1-156, V100C-146, V101C-023, V102C-101]; National Science Council [NSC-98-2321-B-010-007, NSC-99-2321-B-010-004-, NSC-99-2628-B-010-011-MY3, NSC 100-2218-E-010-002, 101-2314-B-010-068-MY3]; Taipei City Hospital [99TPECH04]; Ministry of Education (Aim for the Top University Plan), Taipei, Taiwan FX The study was supported in part by research grants from Taipei Veterans General Hospital (VGH-ER3-99-006; V99C1-156; V100C-146; V101C-023; V102C-101) and from the National Science Council (NSC-98-2321-B-010-007; NSC-99-2321-B-010-004-; NSC-99-2628-B-010-011-MY3; NSC 100-2218-E-010-002; 101-2314-B-010-068-MY3), Taipei City Hospital (99TPECH04), and the grant from Ministry of Education (Aim for the Top University Plan), Taipei, Taiwan. NR 64 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2013 VL 72 BP 133 EP 142 DI 10.1016/j.neuroimage.2013.01.041 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 120JO UT WOS:000317166800013 PM 23370054 ER PT J AU Huang, SL Du, F Shih, YYI Shen, Q Gonzalez-Lima, F Duong, TQ AF Huang, Shiliang Du, Fang Shih, Yen-Yu I. Shen, Qiang Gonzalez-Lima, F. Duong, Timothy Q. TI Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia SO NEUROIMAGE LA English DT Article DE fMRI; BOLD; CBF; Perfusion; Oxidative metabolism; Arterial spin labeling; Cerebral metabolic rate of oxygen; Forepaw stimulation ID RAT FOREPAW STIMULATION; FUNCTIONAL MRI; BLOOD-FLOW; QUANTITATIVE PERFUSION; ANESTHETIZED RATS; DIFFUSION; BOLD; NEUROPROTECTION; MEMORY; CBF AB Methylene blue USP (MB) at low doses has metabolic-enhancing and antioxidant properties and exhibits experimental neurotherapeutic benefits, but little is known about its in vivo effects on cerebral blood flow (CBF), functional evoked responses, and the associated changes in cerebral metabolic rate of oxygen (CMRO2). This study used magnetic resonance imaging (MRI) to evaluate the in vivo effects of a single intravenous MB therapeutic dose (0.5 mg/kg) on basal CBF, blood oxygenation level-dependent (BOLD) and CBF responses to hypercapnic (5% CO2 in air) inhalation, as well as changes in BOLD, CBF, and CMRO2 during forepaw stimulation in the rat brain. MB did not have significant effects on arterial oxygen saturation, heart rate and fMRI responses to hypercapnia. However, MB significantly potentiated forepaw-evoked BOLD and CBF changes under normoxia. To further evaluate in vivo effects of MB under metabolic stress conditions, MRI measurements were also made under mild hypoxia (15% O-2). Hypoxia per se increased evoked functional MRI responses. MB under hypoxia further potentiated forepaw-evoked BOLD, CBF and oxygen consumption responses relative to normoxia. These findings provide insights into MB's effects on cerebral hemodynamics in vivo and could help to optimize treatments in neurological diseases with mitochondrial dysfunction and oxidative stress. (C) 2013 Elsevier Inc. All rights reserved. C1 [Huang, Shiliang; Du, Fang; Shih, Yen-Yu I.; Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Gonzalez-Lima, F.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Gonzalez-Lima, F.] Univ Texas Austin, Dept Pharmacol & Toxicol, Austin, TX 78712 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Shen, Qiang/B-8784-2008; OI Shen, Qiang/0000-0002-4287-3403; Shih, Yen-Yu Ian/0000-0001-6529-911X; Gonzalez-Lima, Francisco/0000-0001-9856-0775 FU Translational Technology Resource grant via the Clinical Translational Science Award (CTSA) [NIH 8UL1TR000149]; NIH/NEI [R01 EY014211, EY018855]; NIH/NINDS [R01-NS45879] FX This work was supported in part by a Translational Technology Resource grant via the Clinical Translational Science Award (CTSA, parent grant NIH 8UL1TR000149), the NIH/NEI (R01 EY014211 and EY018855), NIH/NINDS (R01-NS45879). TQD holds the Stanley I Glickman, MD, Endowed Chair in Ophthalmic Research. We thank Dr. Shaohau Yang and Dr. Ailing Lin for the helpful discussion in various phases of the project NR 46 TC 13 Z9 13 U1 1 U2 19 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 MAY 15 PY 2013 VL 72 BP 237 EP 242 DI 10.1016/j.neuroimage.2013.01.027 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 120JO UT WOS:000317166800023 PM 23357077 ER PT J AU Ramos, RA Zapata, J Condat, CA Deisboeck, TS AF Ramos, R. A. Zapata, Jair Condat, C. A. Deisboeck, Thomas S. TI Modeling cancer immunotherapy: Assessing the effects of lymphocytes on cancer cell growth and motility SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE Tumor model; Cancer growth; Immunotherapy; Lymphocytes; Cell blockade ID IMMUNE SYSTEM COMPETITION; MATHEMATICAL-MODEL; THERAPY; TUMORS; INTERLEUKIN-2; CHEMOTHERAPY; TRIAL AB A mesoscopic model is used to describe the effects of lymphocyte activity on a growing tumor. The model yields novel insights into the tumor immune system interaction. In particular, we found that the presence of a putative chemotactic messenger that helps guide the lymphocytes towards the tumor is not critical to elicit the anti-tumor effects of the immune system, while lymphocytes that block tumor cell migration contribute to limit cancer expansion and thus have a more significant therapeutic impact. (C) 2013 Elsevier B.V. All rights reserved. C1 [Ramos, R. A.; Zapata, Jair] Univ Puerto Rico, Dept Phys, Mayaguez, PR 00681 USA. [Condat, C. A.] Univ Nacl Cordoba, IFEG CONICET, RA-5000 Cordoba, Argentina. [Condat, C. A.] Univ Nacl Cordoba, FAMAF, RA-5000 Cordoba, Argentina. [Deisboeck, Thomas S.] Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. RP Condat, CA (reprint author), Univ Nacl Cordoba, IFEG CONICET, RA-5000 Cordoba, Argentina. EM condat@famaf.unc.edu.ar FU SECyT-UNC; ANPCyT [PICT 2205/33675]; CONICET (Argentina) [PIP 6311/05] FX This work was supported by SECyT-UNC, ANPCyT (PICT 2205/33675), and CONICET (Argentina) through grant PIP 6311/05. CAC thanks the University of Puerto Rico for its hospitality. NR 43 TC 3 Z9 3 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 EI 1873-2119 J9 PHYSICA A JI Physica A PD MAY 15 PY 2013 VL 392 IS 10 BP 2415 EP 2425 DI 10.1016/j.physa.2013.01.047 PG 11 WC Physics, Multidisciplinary SC Physics GA 121OV UT WOS:000317255000011 ER PT J AU Pignon, JC Grisanzio, C Geng, Y Song, JX Shivdasani, RA Signoretti, S AF Pignon, Jean-Christophe Grisanzio, Chiara Geng, Yan Song, Jiaxi Shivdasani, Ramesh A. Signoretti, Sabina TI p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE large intestine; hindgut; genitourinary tract ID MOUSE PROSTATE; SELF-RENEWAL; REGENERATIVE PROLIFERATION; UROTHELIAL DEVELOPMENT; EXPRESSION PROFILES; P53 HOMOLOG; P63; CANCER; BASAL; DIFFERENTIATION AB The tumor protein p63 (p63), and more specifically the NH2-terminal truncated (Delta N) p63 isoform, is a marker of basal epithelial cells and is required for normal development of several epithelial tissues, including the bladder and prostate glands. Although p63-expressing cells are proposed to be the stem cells of the developing prostate epithelium and bladder urothelium, cell lineages in these endoderm-derived epithelia remain highly controversial, and rigorous lineage tracing studies are warranted. Here, we generated knock-in mice expressing Cre recombinase (Cre) under the control of the endogenous Delta Np63 promoter. Heterozygote Delta Np63(+/Cre) mice were phenotypically normal and fertile. Cre-mediated recombination in Delta Np63(+/Cre); ROSA26(EYFP) reporter mice faithfully recapitulated the pattern of Delta Np63 expression and were useful for genetic lineage tracing of Delta Np63-expressing cells of the caudal endoderm in vivo. We found that Delta Np63-positive cells of the urogenital sinus generated all epithelial lineages of the prostate and bladder, indicating that these cells represent the stem/progenitor cells of those epithelia during development. We also observed Delta Np63 expression in caudal gut endoderm and the contribution of Delta Np63-positive cells to the stem/progenitor compartment of adult colorectal epithelium. Because p63 is a master regulator of stratified epithelial development, this finding provides a unique developmental insight into the cell of origin of squamous cell metaplasia and squamous cell carcinoma of the colon. C1 [Pignon, Jean-Christophe; Grisanzio, Chiara; Song, Jiaxi; Signoretti, Sabina] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Grisanzio, Chiara; Geng, Yan; Shivdasani, Ramesh A.; Signoretti, Sabina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Signoretti, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM ssignoretti@partners.org FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [1R21DK72152, 1R01DK089975]; Harvard Stem Cell Institute FX We thank L. Ding and D. Tom (Enhanced Neuroimaging Core, Harvard Neurodiscovery Center) for help with acquisition of the confocal images. This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grants 1R21DK72152 and 1R01DK089975 and the Harvard Stem Cell Institute (S.S.). NR 42 TC 70 Z9 71 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 2013 VL 110 IS 20 BP 8105 EP 8110 DI 10.1073/pnas.1221216110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156EH UT WOS:000319803500035 PM 23620512 ER PT J AU Ramkissoon, LA Horowitz, PM Craig, JM Ramkissoon, SH Rich, BE Schumacher, SE McKenna, A Lawrence, MS Bergthold, G Brastianos, PK Tabak, B Ducar, MD Van Hummelen, P MacConaill, LE Pouissant-Young, T Cho, YJ Taha, H Mahmoud, M Bowers, DC Margraf, L Tabori, U Hawkins, C Packer, RJ Hill, DA Pomeroy, SL Eberhart, CG Dunn, IF Goumnerova, L Getz, G Chan, JA Santagata, S Hahn, WC Stiles, CD Ligon, AH Kieran, MW Beroukhim, R Ligon, KL AF Ramkissoon, Lori A. Horowitz, Peleg M. Craig, Justin M. Ramkissoon, Shakti H. Rich, Benjamin E. Schumacher, Steven E. McKenna, Aaron Lawrence, Michael S. Bergthold, Guillaume Brastianos, Priscilla K. Tabak, Barbara Ducar, Matthew D. Van Hummelen, Paul MacConaill, Laura E. Pouissant-Young, Tina Cho, Yoon-Jae Taha, Hala Mahmoud, Madeha Bowers, Daniel C. Margraf, Linda Tabori, Uri Hawkins, Cynthia Packer, Roger J. Hill, D. Ashley Pomeroy, Scott L. Eberhart, Charles G. Dunn, Ian F. Goumnerova, Liliana Getz, Gad Chan, Jennifer A. Santagata, Sandro Hahn, William C. Stiles, Charles D. Ligon, Azra H. Kieran, Mark W. Beroukhim, Rameen Ligon, Keith L. TI Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; aCGH; A-myb ID MAPK PATHWAY ACTIVATION; CENTRAL-NERVOUS-SYSTEM; COPY-NUMBER ALTERATION; DNA-SEQUENCING DATA; BRAF FUSION GENE; ASTROCYTOMAS; DUPLICATION; MUTATIONS; CANCER; GLIOBLASTOMA AB Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. C1 [Ramkissoon, Lori A.; Horowitz, Peleg M.; Craig, Justin M.; Ramkissoon, Shakti H.; Rich, Benjamin E.; Schumacher, Steven E.; Bergthold, Guillaume; Brastianos, Priscilla K.; Tabak, Barbara; Hahn, William C.; Beroukhim, Rameen; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stiles, Charles D.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ducar, Matthew D.; Van Hummelen, Paul; MacConaill, Laura E.; Hahn, William C.; Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Ligon, Azra H.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Horowitz, Peleg M.; Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Ramkissoon, Shakti H.; MacConaill, Laura E.; Packer, Roger J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Horowitz, Peleg M.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Tabak, Barbara; Pomeroy, Scott L.; Getz, Gad; Hahn, William C.; Beroukhim, Rameen] MIT, Broad Inst, Cambridge, MA 02142 USA. [Horowitz, Peleg M.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Tabak, Barbara; Pomeroy, Scott L.; Getz, Gad; Hahn, William C.; Beroukhim, Rameen] Harvard Univ, Cambridge, MA 02142 USA. [Horowitz, Peleg M.; Goumnerova, Liliana] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Ramkissoon, Shakti H.; Santagata, Sandro; Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Pouissant-Young, Tina] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Pomeroy, Scott L.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Kieran, Mark W.] Boston Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. [Cho, Yoon-Jae] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. [Cho, Yoon-Jae] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. [Taha, Hala; Mahmoud, Madeha] Childrens Canc Hosp, Dept Pediat Oncol & Pathol, Cairo 57357, Egypt. [Bowers, Daniel C.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Margraf, Linda] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Tabori, Uri] Hosp Sick Children, Dept Hematol & Oncol, Toronto, ON M5G 1X8, Canada. [Hawkins, Cynthia] Hosp Sick Children, Dept Pathol, Toronto, ON M5G 1X8, Canada. [Packer, Roger J.] Childrens Natl Med Ctr, Ctr Neurosci & Behav Med, Washington, DC 20010 USA. [Packer, Roger J.] Childrens Natl Med Ctr, Brain Tumor Inst, Washington, DC 20010 USA. [Hill, D. Ashley] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA. [Chan, Jennifer A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 1N4, Canada. [Santagata, Sandro; Ligon, Azra H.; Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Hahn, William C.; Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Beroukhim, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM rameen_beroukhim@dfci.harvard.edu; keith_ligon@dfci.harvard.edu RI Schumacher, Steven/E-9821-2013; OI Schumacher, Steven/0000-0002-6819-5647; Tabori, Uri/0000-0002-5019-2683; Brastianos, Priscilla/0000-0003-4470-8425; Kieran, Mark/0000-0003-2184-7692; Horowitz, Peleg/0000-0002-5177-1783 FU Pediatric Low Grade Astrocytoma Foundation; Sontag Foundation; Goldhirsh Foundation; Boston Children's Hospital Team Path to Cure; American Brain Tumor Association; Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine; Nuovo-Soldati Foundation; Philippe Foundation, Inc.; National Institutes of Health [R01 CA109467, P30 HD018655, U54CA143789, K08CA122833, P01CA142536] FX The authors thank Denise Garcia and Heather Homer for technical help with FISH experiments; Yotam Drier and Cheng-Zhong Zhang for assistance with analytical algorithms; and Anna Pisarek-Horowitz and Sophie Horowitz for critical reading of the manuscript. This work was supported by the Pediatric Low Grade Astrocytoma Foundation; The Sontag Foundation (K. L. L., R. B.); Goldhirsh Foundation (K. L. L.); Boston Children's Hospital Team Path to Cure (K. L. L.); American Brain Tumor Association Basic Research Fellowship in Honor of Joel A. Gingras, Jr. (to L. A. R.); the Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine (to A. H. L.); Nuovo-Soldati Foundation and Philippe Foundation, Inc. (to G. B.); and National Institutes of Health Grants R01 CA109467 and P30 HD018655 (to S. L. P.), U54CA143789 and K08CA122833 (to R. B.), and P01CA142536 (to K. L. L., W. C. H., S. S., C. D. S., L. E. M., and M.W.K.). NR 35 TC 64 Z9 66 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 2013 VL 110 IS 20 BP 8188 EP 8193 DI 10.1073/pnas.1300252110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156EH UT WOS:000319803500049 PM 23633565 ER PT J AU Khandelwal, P Blanco-Mezquita, T Emami, P Lee, HS Reyes, NJ Mathew, R Huang, R Saban, DR AF Khandelwal, Payal Blanco-Mezquita, Tomas Emami, Parisa Lee, Hyun Soo Reyes, Nancy J. Mathew, Rose Huang, Randy Saban, Daniel R. TI Ocular Mucosal CD11b+and CD103+Mouse Dendritic Cells under Normal Conditions and in Allergic Immune Responses SO PLOS ONE LA English DT Article ID CROSS-PRESENTATION; IN-VIVO; ANTIGEN; CONJUNCTIVITIS; SUBSETS AB Steady state dendritic cells (DC) found in non-lymphoid tissue sites under normal physiologic conditions play a pivotal role in triggering T cell responses upon immune provocation. CD11b+ and CD103+ DC have received considerable attention in this regard. However, still unknown is whether such CD11b+ and CD103+ DC even exist in the ocular mucosa, and if so, what functions they have in shaping immune responses. We herein identified in the ocular mucosa of normal wild-type (WT) and Flt3-/- mice the presence of a CD11b+ DC (i.e., CD11c+ MHCII+ CD11b+ CD103-F4/80+ Sirp-a+). CD103+ DC (i.e. CD11c+ MHCII+ CD11b low CD103+ CD8a+ DEC205+ Langerin+) were also present in WT, but not in Flt3-/- mice. These CD103+ DC expressed high levels of Id2 and Flt3 mRNA; whereas CD11b+ DC expressed high Irf4, Csfr, and Cx3cr1 mRNA. Additionally, the functions of these DC differed in response to allergic immune provocation. This was assessed utilizing a previously validated model, which includes transferring specific populations of exogenous DC into the ocular mucosa of ovalbumin (OVA)/alum-primed mice. Interestingly, in such mice, topical OVA instillation following engraftment of exogenous CD11b+ DC led to dominant allergic T cell responses and clinical signs of ocular allergy relative to those engrafted with CD103+ DC. Thus, although CD11b+ and CD103+ DC are both present in the normal ocular mucosa, the CD11b+ DC subset plays a dominant role in a mouse model of ocular allergy. C1 [Khandelwal, Payal; Emami, Parisa; Lee, Hyun Soo; Huang, Randy] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02114 USA. [Blanco-Mezquita, Tomas; Reyes, Nancy J.; Mathew, Rose; Saban, Daniel R.] Duke Univ, Sch Med, Duke Eye Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Saban, Daniel R.] Duke Univ, Sch Med, Dept Immunol, Durham, NC USA. RP Saban, DR (reprint author), Duke Univ, Sch Med, Duke Eye Ctr, Dept Ophthalmol, Durham, NC 27710 USA. EM daniel.saban@duke.edu FU NIH [R01EY021798] FX Funding for this work came exclusively from NIH grant R01EY021798 awarded to DRS, the PI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 15 Z9 15 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 14 PY 2013 VL 8 IS 5 AR e64193 DI 10.1371/journal.pone.0064193 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RE UT WOS:000319107400104 PM 23691170 ER PT J AU Song, M Wu, K Ogino, S Fuchs, CS Giovannucci, EL Chan, AT AF Song, M. Wu, K. Ogino, S. Fuchs, C. S. Giovannucci, E. L. Chan, A. T. TI A prospective study of plasma inflammatory markers and risk of colorectal cancer in men SO BRITISH JOURNAL OF CANCER LA English DT Article DE C-reactive protein; interleukin-6; soluble tumour necrosis factor receptor 2; colorectal cancer; body mass index ID C-REACTIVE PROTEIN; PHYSICAL-ACTIVITY; COLON-CANCER; OBESITY; WOMEN; DISEASE; ASSOCIATIONS; MECHANISMS; DIAGNOSIS; INSULIN AB Background: Chronic inflammation may mediate risk of colorectal cancer (CRC); however, the association between circulating inflammatory markers and risk of CRC has been inconsistent. Methods: We prospectively evaluated the association of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and the soluble tumour necrosis factor receptor 2 (sTNFR-2) with incident CRC among 274 cases and 532 matched controls nested in the Health Professionals Follow-up Study. Results: Multivariate relative risk (RR) of CRC comparing the extreme quartiles of plasma IL-6 was 1.54 (95% confidence interval (CI), 0.99-2.40; P-trend = 0.02). However, after excluding cases diagnosed within 2 years of blood draw, this association was not statistically significant (RR = 1.26, 95% CI, 0.78-2.05; P-trend = 0.21). In analyses restricted to cases diagnosed at least 2 years after blood draw, the association of IL-6 with CRC appeared to differ by body mass index such that the significantly positive association was only present among lean individuals (P-interaction = 0.03). We did not observe any significant association between CRP or sTNFR-2 and CRC. Conclusion: Plasma inflammatory markers are not generally associated with risk of CRC among men. However, the possibility that plasma IL-6 is associated with increased risk of CRC among lean men requires further investigation. C1 [Song, M.; Wu, K.; Giovannucci, E. L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ogino, S.; Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, S.; Fuchs, C. S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ogino, S.; Fuchs, C. S.; Giovannucci, E. L.; Chan, A. T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Div Network Med, Boston, MA 02115 USA. [Ogino, S.; Giovannucci, E. L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chan, A. T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, A. T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chan, AT (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Div Network Med, Boston, MA 02115 USA. EM achan@partners.org RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU US National Institute of Health [P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA151993, R01 CA137178, K24 DK 098311] FX We thank the participants and staff of the Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. We also thank Xuehong Zhang, ScD, for assistance in programming; and Gary Bradwin and Nader Rifai, PhD, for measurements of the inflammatory analytes. This work was supported by US National Institute of Health Grants, P01 CA55075 (to WC Willett), UM1 CA167552 (to WC Willett), P50 CA127003 (to CSF), R01 CA151993 (to SO), and R01 CA137178 and K24 DK 098311 (to ATC). Dr Andrew T Chan is a Damon Runyon Cancer Foundation Clinical Investigator. NR 48 TC 31 Z9 32 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY 14 PY 2013 VL 108 IS 9 BP 1891 EP 1898 DI 10.1038/bjc.2013.172 PG 8 WC Oncology SC Oncology GA 146WI UT WOS:000319125300019 PM 23591192 ER PT J AU van der Meer, P Postmus, D Ponikowski, P Cleland, JG O'Connor, CM Cotter, G Metra, M Davison, BA Givertz, MM Mansoor, GA Teerlink, JR Massie, BM Hillege, HL Voors, AA AF van der Meer, Peter Postmus, Douwe Ponikowski, Piotr Cleland, John G. O'Connor, Christopher M. Cotter, Gad Metra, Marco Davison, Beth A. Givertz, Michael M. Mansoor, George A. Teerlink, John R. Massie, Barry M. Hillege, Hans L. Voors, Adriaan A. TI The Predictive Value of Short-Term Changes in Hemoglobin Concentration in Patients Presenting With Acute Decompensated Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute heart failure; hemoglobin; outcome ID RENAL DYSFUNCTION; ENDOGENOUS ERYTHROPOIETIN; ANEMIA; MORTALITY; ROLOFYLLINE; PREVALENCE; SURVIVAL; ASSOCIATION; ANTAGONIST; REGISTRY AB Objectives The study sought to investigate the clinical correlates and prognostic role of anemia and changes in hemoglobin in patients hospitalized for acute decompensated heart failure (AHF). Background Anemia is related to a poor outcome in patients with heart failure. In addition, an increase in hemoglobin during hospitalization might be a sign of effective decongestion and therefore related to improved outcome. Methods This is a post hoc analysis of the PROTECT (Placebo-Controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) study in 1,969 patients with AHF and mild to moderate impaired renal function. Hemoglobin levels were measured daily for the first 4 days and at day 7. The endpoint was 180-day all-cause mortality. Results Anemia at baseline was observed in 50.3% of the patients. During follow-up, 359 patients (18.2%) died. Hemoglobin increased in 69.1% and was associated with a better renal function at baseline and more weight loss, but was associated with a deterioration of renal function (p = 0.01), whereas total dose diuretics was lower in patients with hemoconcentration (p < 0.01). Interaction analysis showed that greater weight loss and better baseline renal function were associated with a more rapid increase in hemoglobin concentration (p < 0.01 for both). The absolute change in hemoglobin (g/dl) independently predicted outcome (hazard ratio: 0.66; 95% confidence interval: 0.51 to 0.86; p = 0.002), whereas baseline hemoglobin levels did not. Conclusions Patients with AHF and preserved renal function are decongested better, as shown by an increase in hemoglobin. A rapid increase in hemoglobin during the first week is independently associated with a favorable outcome, despite a slight decrease in renal function. (C) 2013 by the American College of Cardiology Foundation C1 [van der Meer, Peter; Postmus, Douwe; Hillege, Hans L.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 GZ Groningen, Netherlands. [Ponikowski, Piotr] Kardiol Klin, Wroclaw, Poland. [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Voors, AA (reprint author), Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Postmus, Douwe/0000-0002-9458-7038; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016 FU Vifor Pharma; Amgen, Inc.; Merck; Abbott; Amgen; Biogen Idec; Corthera; Cytokinetics; Johnson Johnson/Scios; Novartis; Relypsa; Solvay FX Dr. Ponikowski has received honoraria from Merck; consulting fees from Vifor Pharma and Amgen, Inc., honoraria from Vifor Pharma; and travel/accommodation expenses covered by Vifor Pharma and Amgen, Inc. Dr. Cleland was on the Steering Committee for the study; served on the advisory board for MSD; and received payments for both. Dr. O'Connor is a consultant to Merck and Amgen. Dr. Davison and Dr. Cotter are employees of Momentum Research Inc, which was contracted to perform work on the project by Merck. Drs. Metra and Massie have received honoraria and reimbursements from NovaCardia, sponsors of the study, and from Merck, which purchased the rights to rolofylline after completion of the PROTECT pilot study. Dr. Givertz has received institutional research support and served on a scientific Advisory Board for Merck. Dr. Mansoor is an employee of Merck. Dr. Teerlink has received research funds and consulting fees from Merck, the makers of rolofylline for the conduct of this study and has also received research funds and consulting fees from Abbott, Amgen, Biogen Idec, Corthera, Cytokinetics, Johnson & Johnson/Scios, Novartis, Relypsa, and Solvay for research in related areas. Dr. Voors has received speaker and consultancy fees from Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to report. NR 23 TC 56 Z9 57 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 14 PY 2013 VL 61 IS 19 BP 1973 EP 1981 DI 10.1016/j.jacc.2012.12.050 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 144AB UT WOS:000318910300007 PM 23500313 ER PT J AU Piccini, JP Stevens, SR Lokhnygina, Y Patel, MR Halperin, JL Singer, DE Hankey, GJ Hacke, W Becker, RC Nessel, CC Mahaffey, KW Fox, KAA Califf, RM Breithardt, G AF Piccini, Jonathan P. Stevens, Susanna R. Lokhnygina, Yuliya Patel, Manesh R. Halperin, Jonathan L. Singer, Daniel E. Hankey, Graeme J. Hacke, Werner Becker, Richard C. Nessel, Christopher C. Mahaffey, Kenneth W. Fox, Keith A. A. Califf, Robert M. Breithardt, Guenter CA ROCKET AF Steering Comm Investigat TI Outcomes After Cardioversion and Atrial Fibrillation Ablation in Patients Treated With Rivaroxaban and Warfarin in the ROCKET AF Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atrial fibrillation; cardioversion; catheter ablation; stroke; rivaroxaban; warfarin ID PREDICTING STROKE; ASSOCIATION; MANAGEMENT; RISK; THROMBOEMBOLISM; ANTICOAGULATION AB Objectives This study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban. Background There are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors. Methods We compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial. Results Over a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 [n = 161] in the warfarin arm, 1.46 [n = 160] in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups. Conclusions Despite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation [ROCKET AF]; NCT00403767) (C) 2013 by the American College of Cardiology Foundation C1 [Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Becker, Richard C.; Mahaffey, Kenneth W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC 27710 USA. [Breithardt, Guenter] Hosp Univ Munster, Dept Cardiovasc Med, Munster, Germany. RP Piccini, JP (reprint author), Duke Univ, Med Ctr, Electrophysiol Sect, Duke Clin Res Inst, POB 17969, Durham, NC 27710 USA. EM jonathan.piccini@duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson & Johnson Pharmaceutical Research and Development; Bayer HealthCare AG; Johnson Johnson; Bayer; Ortho McNeil Janssen; Bayer HealthCare; Eliot B. and Edith C. Shoolman fund of Massachusetts General Hospital; Boehringer-Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; Pfizer; Sanofi; Bristol Myers-Squibb; AstraZeneca; Eli Lilly; GlaxoSmithKline; Merck; Momenta Pharmaceuticals; Novartis; Portola; Pozen; Regado Biotechnologies; Sanofi-Aventis; Medicines Company; Ortho/McNeill; Polymedix; Lilly FX The ROCKET AF trial was sponsored by Johnson & Johnson Pharmaceutical Research and Development and Bayer HealthCare AG. Dr. Piccini has received research grants from Johnson & Johnson and is a consultant/advisory board member for Medtronic, Forest Laboratories, Sanofi Aventis, and Johnson & Johnson. Dr. Lokhnygina receives consulting fees from Johnson & Johnson and Bayer. Dr. Patel has received honoraria from Johnson & Johnson and Bayer; and consultancy fees from Ortho McNeil Janssen, Bayer HealthCare, and is an advisory board member with Genzyme. Dr. Singer is supported, in part, by the Eliot B. and Edith C. Shoolman fund of Massachusetts General Hospital; and has received consulting fees from Bayer HealthCare, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Pfizer, and Sanofi. Dr. Halperin has received honoraria from Johnson & Johnson and Bayer; and advisory fees from Boehringer-Ingelheim, Bristol Myers-Squibb, and Pfizer. Dr. Hankey has received honoraria from Johnson & Johnson, Bayer, and Sanofi-Aventis and is a member of the trial adjudication committee and advisory board for Boehringer-Ingelheim. Dr. Hacke has received honoraria from Johnson & Johnson and Bayer and advisory board fees from Boehringer-Ingelheim. Dr. Becker has received research support from Bayer and Johnson & Johnson. Dr. Nessel is an employee of Johnson & Johnson Mahaffey; received grant support from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Momenta Pharmaceuticals, Novartis, Portola, Pozen, Regado Biotechnologies, Sanofi-Aventis, Schering-Plough (now Merck), and The Medicines Company; and has received consulting fees from AstraZeneca and Johnson & Johnson, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Glaxo SmithKline, Merck, Novartis, Ortho/McNeill, Pfizer, Polymedix, Sanofi-Aventis, and Schering-Plough (now Merck). Dr. Fox has received research grants and honoraria from Bayer, Lilly, Boehringer-Ingelheim, Sanofi-Aventis, and GlaxoSmith Kline. Dr. Califf has received consulting fees and research funding from Johnson & Johnson and all other industry interactions are listed at the Duke Clinical Research Institute website. Dr. Breithardt has received honoraria from Johnson & Johnson and Bayer; and advisory board fees from Boehringer-Ingelheim, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. NR 17 TC 96 Z9 103 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 14 PY 2013 VL 61 IS 19 BP 1998 EP 2006 DI 10.1016/j.jacc.2013.02.025 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 144AB UT WOS:000318910300011 PM 23500298 ER PT J AU Allison, TA Sudore, RL AF Allison, Theresa A. Sudore, Rebecca L. TI Disregard of Patients' Preferences Is a Medical Error SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID ADVANCE CARE C1 [Allison, Theresa A.; Sudore, Rebecca L.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Allison, Theresa A.; Sudore, Rebecca L.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94143 USA. [Allison, Theresa A.] Univ Calif San Francisco, Div Geriatr, Dept Family & Community Med, San Francisco, CA 94143 USA. RP Allison, TA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,POB 181-G, San Francisco, CA 94941 USA. EM Theresa.Allison@UCSF.edu NR 9 TC 11 Z9 11 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY 13 PY 2013 VL 173 IS 9 BP 787 EP 788 DI 10.1001/jamainternmed.2013.203 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 159JN UT WOS:000320041800018 PM 23545699 ER PT J AU Kerlikowske, K Zhu, WW Hubbard, RA Geller, B Dittus, K Braithwaite, D Wernli, KJ Miglioretti, DL O'Meara, ES AF Kerlikowske, Karla Zhu, Weiwei Hubbard, Rebecca A. Geller, Berta Dittus, Kim Braithwaite, Dejana Wernli, Karen J. Miglioretti, Diana L. O'Meara, Ellen S. CA Breast Canc Surveillance Consorti TI Outcomes of Screening Mammography by Frequency, Breast Density, and Postmenopausal Hormone Therapy SO JAMA INTERNAL MEDICINE LA English DT Article ID FALSE-POSITIVE RECALL; SERVICES TASK-FORCE; REPLACEMENT THERAPY; CANCER RISK; TUMOR CHARACTERISTICS; WOMEN; ASSOCIATION; BENEFITS; COHORT; REPRODUCIBILITY AB Importance: Controversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age. Objective: To compare the benefits and harms of screening mammography frequencies according to age, breast density, and postmenopausal hormone therapy (HT) use. Design: Prospective cohort. Setting: Data collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries. Participants: Data were collected prospectively on 11 474 women with breast cancer and 922 624 without breast cancer who underwent mammography at facilities that participate in the BCSC. Main Outcomes and Measures: We used logistic regression to calculate the odds of advanced stage (IIb, III, or IV) and large tumors (> 20 mm in diameter) and 10-year cumulative probability of a false-positive mammography result by screening frequency, age, breast density, and HT use. The main predictor was screening mammography interval. Results: Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of women's breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively). Conclusions and Relevance: Women aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. Whendeciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advancedstage disease but the cumulative risk of false-positive results is high. C1 [Kerlikowske, Karla; Braithwaite, Dejana] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kerlikowske, Karla] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. [Zhu, Weiwei; Hubbard, Rebecca A.; Wernli, Karen J.; Miglioretti, Diana L.; O'Meara, Ellen S.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [O'Meara, Ellen S.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Geller, Berta] Univ Vermont, Coll Med, Dept Family Med, Burlington, VT 05405 USA. [Geller, Berta] Univ Vermont, Coll Med, Dept Radiol, Burlington, VT 05405 USA. [Dittus, Kim] Univ Vermont, Coll Med, Dept Med Oncol, Burlington, VT 05405 USA. [Miglioretti, Diana L.] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 4150 Clement St,Mailing Code 111A1, San Francisco, CA 94121 USA. EM Karla.Kerlikowske@ucsf.edu FU National Cancer Institute-funded Breast Cancer Surveillance Consortium cooperative agreement [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040]; National Cancer Institute [RC2CA148577, R03CA150007, P01 CA107584] FX This work was supported by the National Cancer Institute-funded Breast Cancer Surveillance Consortium cooperative agreement (grants U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040) and the National Cancer Institute-funded grants RC2CA148577, R03CA150007, and P01 CA107584. The collection of cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States For a full description of these sources, please see http://breastscreening.cancer.gov/work/acknowledgement.html. NR 38 TC 58 Z9 59 U1 1 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY 13 PY 2013 VL 173 IS 9 BP 807 EP 816 DI 10.1001/jamainternmed.2013.307 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 159JN UT WOS:000320041800023 PM 23552817 ER PT J AU Chen, XH Yang, GX Song, JH Xu, H Li, D Goldsmith, J Zeng, HY Parsons-Wingerter, PA Reinecker, HC Kelly, CP AF Chen, Xinhua Yang, Guoxun Song, Joo-Hye Xu, Hua Li, Dan Goldsmith, Jeffrey Zeng, Huiyan Parsons-Wingerter, Patricia A. Reinecker, Hans-Christian Kelly, Ciaran P. TI Probiotic Yeast Inhibits VEGFR Signaling and Angiogenesis in Intestinal Inflammation SO PLOS ONE LA English DT Article ID CLOSTRIDIUM-DIFFICILE DISEASE; ANTIBIOTIC-ASSOCIATED DIARRHEA; ENDOTHELIAL GROWTH-FACTOR; SACCHAROMYCES-BOULARDII; BOWEL-DISEASE; EXPERIMENTAL COLITIS; ULCERATIVE-COLITIS; TOXIN-A; GNOTOBIOTIC MICE; CROHNS-DISEASE AB Background and Aims: Saccharomyces boulardii (Sb) can protect against intestinal injury and tumor formation, but how this probiotic yeast controls protective mucosal host responses is unclear. Angiogenesis is an integral process of inflammatory responses in inflammatory bowel diseases (IBD) and required for mucosal remodeling during restitution. The aim of this study was to determine whether Sb alters VEGFR (vascular endothelial growth factor receptor) signaling, a central regulator of angiogenesis. Methods: HUVEC were used to examine the effects of Sb on signaling and on capillary tube formation (using the ECMatrix (TM) system). The effects of Sb on VEGF-mediated angiogenesis were examined in vivo using an adenovirus expressing VEGF-A(164) in the ears of adult nude mice (NuNu). The effects of Sb on blood vessel volume branching and density in DSS-induced colitis was quantified using VESsel GENeration (VESGEN) software. Results: 1) Sb treatment attenuated weight-loss (p<0.01) and histological damage (p<0.01) in DSS colitis. VESGEN analysis of angiogenesis showed significantly increased blood vessel density and volume in DSS-treated mice compared to control. Sb treatment significantly reduced the neo-vascularization associated with acute DSS colitis and accelerated mucosal recovery restoration of the lamina propria capillary network to a normal morphology. 2) Sb inhibited VEGF-induced angiogenesis in vivo in the mouse ear model. 3) Sb also significantly inhibited angiogenesis in vitro in the capillary tube assay in a dose-dependent manner (p<0.01). 4) In HUVEC, Sb reduced basal VEGFR-2 phosphorylation, VEGFR-2 phosphorylation in response to VEGF as well as activation of the downstream kinases PLC gamma and Erk1/2. Conclusions: Our findings indicate that the probiotic yeast S boulardii can modulate angiogenesis to limit intestinal inflammation and promote mucosal tissue repair by regulating VEGFR signaling. C1 [Chen, Xinhua; Yang, Guoxun; Xu, Hua; Li, Dan; Kelly, Ciaran P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. [Song, Joo-Hye; Reinecker, Hans-Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Goldsmith, Jeffrey] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol & Lab Med, Boston, MA 02215 USA. [Zeng, Huiyan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Mol & Vasc Med, Boston, MA 02215 USA. [Parsons-Wingerter, Patricia A.] John Glenn NASA Res Ctr, Cleveland, OH USA. RP Chen, XH (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. EM xchen1@bidmc.harvard.edu FU NIH [PO1 DK 33506, DK-068181, DK-043351, AI-093588]; Crohn's & Colitis Foundation of America; Global Probiotic Council FX This work was supported by NIH grants PO1 DK 33506 (CPK, HCR), DK-068181, DK-043351 and AI-093588 (HCR), Crohn's & Colitis Foundation of America (Research Fellowship and Career Development Award, XC) and Global Probiotic Council (Young Investigator Award, XC). NASA and PPW have filed a United States patent application for the VESGEN software. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 7 Z9 7 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2013 VL 8 IS 5 AR e64227 DI 10.1371/journal.pone.0064227 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 145RZ UT WOS:000319036100060 PM 23675530 ER PT J AU Lai, PS Hofmann, O Baron, RM Cernadas, M Meng, QR Bresler, HS Brass, DM Yang, IV Schwartz, DA Christiani, DC Hide, W AF Lai, Peggy S. Hofmann, Oliver Baron, Rebecca M. Cernadas, Manuela Meng, Quanxin Ryan Bresler, Herbert S. Brass, David M. Yang, Ivana V. Schwartz, David A. Christiani, David C. Hide, Winston TI Integrating Murine Gene Expression Studies to Understand Obstructive Lung Disease Due to Chronic Inhaled Endotoxin SO PLOS ONE LA English DT Article ID CIGARETTE-SMOKE; PULMONARY-DISEASE; BACTERIAL-ENDOTOXIN; FOLLOW-UP; COPD; INHALATION; ASTHMA; LIPOPOLYSACCHARIDE; MICE; RISK AB Rationale: Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD). These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease. Methods: We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke. Results: A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature. Conclusions: Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene expression were observed. The endotoxin component of tobacco smoke may play an important role in disease development. C1 [Lai, Peggy S.; Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lai, Peggy S.; Hofmann, Oliver; Christiani, David C.; Hide, Winston] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Baron, Rebecca M.; Cernadas, Manuela] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Meng, Quanxin Ryan; Bresler, Herbert S.] Battelle Mem Inst, Columbus, OH USA. [Brass, David M.] Duke Univ, Med Ctr, Dept Pediat Neonatol, Durham, NC USA. [Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA. [Yang, Ivana V.; Schwartz, David A.] Univ Colorado, Dept Med, Aurora, CO USA. RP Lai, PS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM plai@partners.org RI Hide, Winston Hide/C-7217-2009; OI Hide, Winston Hide/0000-0002-8621-3271; Lai, Peggy/0000-0001-9501-8606; Hofmann, Oliver/0000-0002-7738-1513 FU National Institute of Environmental Health Sciences [ES00002, P30 ES00002, P01 ES18181, F32 ES020082]; Battelle Memorial Institute FX Support was provided by ES00002, P30 ES00002, and P01 ES18181 from the National Institute of Environmental Health Sciences for generation of primary microarray data for the Lai and Brass et al studies, Battelle Memorial Institute's Corporate Science & Technology Program for generation of microarray data for the Meng et al study, and F32 ES020082 from the National Institute of Environmental Health Sciences to PL as a career development award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Environmental Health Sciences 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 52 TC 1 Z9 1 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2013 VL 8 IS 5 AR e62910 DI 10.1371/journal.pone.0062910 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 145RZ UT WOS:000319036100020 PM 23675439 ER PT J AU Beguelin, W Popovic, R Teater, M Jiang, YW Bunting, KL Rosen, M Shen, H Yang, SN Wang, L Ezponda, T Martinez-Garcia, E Zhang, HK Zheng, YP Verma, SK McCabe, MT Ott, HM Van Aller, GS Kruger, RG Liu, Y McHugh, CF Scott, DW Chung, YR Kelleher, N Shaknovich, R Creasy, CL Gascoyne, RD Wong, KK Cerchietti, L Levine, RL Abdel-Wahab, O Licht, JD Elemento, O Melnick, AM AF Beguelin, Wendy Popovic, Relja Teater, Matt Jiang, Yanwen Bunting, Karen L. Rosen, Monica Shen, Hao Yang, Shao Ning Wang, Ling Ezponda, Teresa Martinez-Garcia, Eva Zhang, Haikuo Zheng, Yupeng Verma, Sharad K. McCabe, Michael T. Ott, Heidi M. Van Aller, Glenn S. Kruger, Ryan G. Liu, Yan McHugh, Charles F. Scott, David W. Chung, Young Rock Kelleher, Neil Shaknovich, Rita Creasy, Caretha L. Gascoyne, Randy D. Wong, Kwok-Kin Cerchietti, Leandro Levine, Ross L. Abdel-Wahab, Omar Licht, Jonathan D. Elemento, Olivier Melnick, Ari M. TI EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation SO CANCER CELL LA English DT Article ID B-CELL LYMPHOMA; HISTONE METHYLTRANSFERASE EZH2; EMBRYONIC STEM-CELLS; NON-HODGKIN-LYMPHOMA; EXPRESSION PATTERNS; TRANSGENIC MICE; GROUP PROTEINS; LYSINE 27; RNA-SEQ; POLYCOMB AB The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B cells and targeted by somatic mutations in B cell lymphomas. Here, we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GC B cell (GCB)-type diffuse large B cell lymphomas (DLBCLs) are mostly addicted to EZH2 but not the more differentiated activated B cell (ABC)-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting. C1 [Beguelin, Wendy; Teater, Matt; Jiang, Yanwen; Bunting, Karen L.; Rosen, Monica; Shen, Hao; Yang, Shao Ning; Wang, Ling; Shaknovich, Rita; Cerchietti, Leandro; Melnick, Ari M.] Weill Cornell Med Coll, Div Hematol Oncol, Dept Med, New York, NY 10021 USA. [Teater, Matt; Jiang, Yanwen; Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10021 USA. [Cerchietti, Leandro; Melnick, Ari M.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10021 USA. [Popovic, Relja; Ezponda, Teresa; Martinez-Garcia, Eva; Licht, Jonathan D.] Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Zhang, Haikuo; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Zheng, Yupeng; Kelleher, Neil] Northwestern Univ, Chem Life Proc Inst, Dept Chem, Evanston, IL 60208 USA. [Zheng, Yupeng; Kelleher, Neil] Northwestern Univ, Chem Life Proc Inst, Dept Mol Biosci, Evanston, IL 60208 USA. [Verma, Sharad K.; McCabe, Michael T.; Ott, Heidi M.; Van Aller, Glenn S.; Kruger, Ryan G.; Liu, Yan; McHugh, Charles F.; Creasy, Caretha L.] GlaxoSmithKline, Oncol R&D, Canc Res, Canc Epigenet Discovery Performance Unit, Collegeville, PA 19426 USA. [Scott, David W.; Gascoyne, Randy D.] British Columbia Canc Res Ctr, British Columbia Canc Agcy, Ctr Lymphoid Canc, Dept Pathol, Vancouver, BC V5Z 1L3, Canada. [Scott, David W.; Gascoyne, Randy D.] British Columbia Canc Res Ctr, British Columbia Canc Agcy, Ctr Lymphoid Canc, Dept Expt Therapeut, Vancouver, BC V5Z 1L3, Canada. [Chung, Young Rock; Levine, Ross L.; Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Chung, Young Rock; Levine, Ross L.; Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10065 USA. RP Licht, JD (reprint author), Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. EM j-licht@northwestern.edu; ole2001@med.cornell.edu; amm2014@med.cornell.edu RI Zheng, Yupeng/B-3782-2014; OI Abdel-Wahab, Omar/0000-0002-3907-6171; Zheng, Yupeng/0000-0002-3351-5161; Cerchietti, Leandro/0000-0003-0608-1350; wong, kwok kin/0000-0001-6323-235X FU Burroughs Wellcome Foundation; Chemotherapy Foundation; Samuel Waxman Cancer Research Foundation; National Cancer Institute Physical Sciences in Oncology Center program [U54 CA143869, CA143879]; Leukemia and Lymphoma Society Specialized Center of Research Excellence; T & C Schwartz Family Foundation; NIH K08 Clinical Investigator Award [1K08CA160647-01]; CIHR; New Frontiers in Cancer Terry Fox Program project [019001]; NCI [R01 CA104348]; NSF CAREER; Starr Cancer Consortium FX We thank Dr. Alexander Tarakhovsky (Rockefeller University) for sharing the EZH2 conditional knockout mouse strain. A.M.M. is supported by the Burroughs Wellcome Foundation and Chemotherapy Foundation. A.M.M., R.L.L., and J.D.L. are supported by the Samuel Waxman Cancer Research Foundation and a collaborative transnetwork grant from the National Cancer Institute Physical Sciences in Oncology Center program (U54 CA143869 and CA143879). J.D.L., A.M.M., and O.E. are supported by a Leukemia and Lymphoma Society Specialized Center of Research Excellence, and A.M.M. and J.D.L. are supported by the T & C Schwartz Family Foundation. O.A.-W. is an American Society of Hematology Basic Research Fellow and is supported by a grant from the NIH K08 Clinical Investigator Award (1K08CA160647-01). L.C. is a Raymond and Beverly Sackler Scholar and Scholar of the American Society of Hematology. D.W.S. is supported by a CIHR postdoctoral fellowship award, and R.D.G. is supported by a New Frontiers in Cancer Terry Fox Program project grant (No. 019001). O.E. and A.M.M. are supported by NCI R01 CA104348. O.E. is supported by the NSF CAREER grant and grants from the Starr Cancer Consortium. This work was enabled by the Beverly and Raymond Sackler Center for Physical and Biomedical Sciences as well as the Weill Cornell Epigenomics Core Facility. S.K.V., M.T.M., H.M.O., G.S.V.A., R.G.K., Y.L., C.F.M., and C.L.C. are employees of GlaxoSmithKline. NR 39 TC 193 Z9 196 U1 4 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY 13 PY 2013 VL 23 IS 5 BP 677 EP 692 DI 10.1016/j.ccr.2013.04.011 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 146PQ UT WOS:000319103400015 PM 23680150 ER PT J AU Cho, HS Hashimoto, T Wong, E Hori, Y Wood, LB Zhao, LZ Haigis, KM Hyman, BT Irimia, D AF Cho, Hansang Hashimoto, Tadafumi Wong, Elisabeth Hori, Yukiko Wood, Levi B. Zhao, Lingzhi Haigis, Kevin M. Hyman, Bradley T. Irimia, Daniel TI Microfluidic Chemotaxis Platform for Differentiating the Roles of Soluble and Bound Amyloid-beta on Microglial Accumulation SO SCIENTIFIC REPORTS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; MOUSE MODEL; PLAQUES; ACTIVATION; BRAIN; MAINTENANCE; EXPRESSION; CLEARANCE; CELLS AB Progressive microglial accumulation at amyloid-beta (A beta) plaques is a well-established signature of the pathology of Alzheimer's disease, but how and why microglia accumulate in the vicinity of A beta plaques is unknown. To understand the distinct roles of A beta on microglial accumulation, we quantified microglial responses to week-long lasting gradients of soluble A beta and patterns of surface-bound A beta in microfluidic chemotaxis platforms. We found that human microglia chemotaxis in gradients of soluble A beta(42) was most effective at two distinct concentrations of 23 pg.mL(-1) and 23 ng.mL(-1) A beta(42) in monomers and oligomers. We uncovered that while the chemotaxis at higher A beta concentrations was exclusively due to A beta gradients, chemotaxis at lower concentrations was enhanced by A beta-induced microglial production of MCP-1. Microglial migration was inhibited by surface-bound A beta(42) in oligomers and fibrils above 45 pg.mm(-2). Better understanding of microglial migration can provide insights into the pathophysiology of senile plaques in AD. C1 [Cho, Hansang; Wong, Elisabeth; Irimia, Daniel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Cambridge, MA 02138 USA. [Hashimoto, Tadafumi; Hori, Yukiko; Zhao, Lingzhi; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Cambridge, MA 02138 USA. [Wood, Levi B.; Haigis, Kevin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Pathol Unit, Cambridge, MA 02138 USA. [Zhao, Lingzhi] Weill Cornell Med Coll, Dept Neurol & Neurosci, Appel Alzheimers Dis Res Inst, New York, NY USA. RP Irimia, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Cambridge, MA 02138 USA. EM dirimia@hms.harvard.edu FU National Institutes of Health [AG005134, 27.3, GM092804, EB002503] FX This work was supported in part by funding from the National Institutes of Health, grants AG005134 - pilot project 27.3, GM092804 and EB002503. We thank the BioMEMS RC for the use of fabrication facilities, Dr. Salil Desai for advise on microscale patterning techniques, and Dr. Ken Arai for discussion of A beta stability. NR 30 TC 13 Z9 13 U1 4 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD MAY 10 PY 2013 VL 3 AR 1823 DI 10.1038/srep01823 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AC0KF UT WOS:000332182500001 PM 23665843 ER PT J AU Mwimanzi, P Markle, TJ Ogata, Y Martin, E Tokunaga, M Mahiti, M Kuang, XT Walker, BD Brockman, MA Brumme, ZL Ueno, T AF Mwimanzi, Philip Markle, Tristan J. Ogata, Yoko Martin, Eric Tokunaga, Michiyo Mahiti, Macdonald Kuang, Xiaomei T. Walker, Bruce D. Brockman, Mark A. Brumme, Zabrina L. Ueno, Takamasa TI Dynamic range of Nef functions in chronic HIV-1 infection SO VIROLOGY LA English DT Article DE HIV-1; Nef; Chronic infection; CD4; HLA class I; CD74; Infectivity; Replication ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 DOWN-REGULATION; COMPLEX CLASS-II; LONG-TERM-NONPROGRESSOR; INVARIANT CHAIN; VIRAL INFECTIVITY; ELITE CONTROLLERS; T-LYMPHOCYTES; UP-REGULATION; GENETIC-CHARACTERIZATION AB HIV-1 Nef is required for efficient viral replication and pathogenesis. However, the extent to which Nefs functions are maintained in natural sequences during chronic infection, and their clinical relevance, remains incompletely characterized. Relative to a control Nef from HIV-1 strain SF2, HLA class I and CD4 down-regulation activities of 46 plasma RNA Nef sequences derived from unique chronic infected individuals were generally high and displayed narrow dynamic ranges, whereas Nef-mediated virion infectivity, PBMC replication and CD74 up-regulation exhibited broader dynamic ranges. 80% of patient-derived Nets were active for at least three functions examined. Functional co-dependencies were identified, including positive correlations between CD4 down-regulation and virion infectivity, replication, and CD74 up-regulation, and between CD74 upregulation and PBMC replication. Net-mediated virion infectivity inversely correlated with patient CD +/- T-cell count. Strong functional co-dependencies and the polyfunctional nature of patient-derived Net sequences suggest a phenotypic requirement to maintain multiple Nef functions during chronic infection. (C) 2013 Elsevier Inc. All rights reserved. C1 [Mwimanzi, Philip; Ogata, Yoko; Tokunaga, Michiyo; Mahiti, Macdonald; Ueno, Takamasa] Kumamoto Univ, Ctr AIDS Res, Kumamoto 8600811, Japan. [Mwimanzi, Philip; Markle, Tristan J.; Martin, Eric; Kuang, Xiaomei T.; Brockman, Mark A.; Brumme, Zabrina L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Walker, Bruce D.] Harvard Univ, Boston, MA 02115 USA. [Brockman, Mark A.; Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada. RP Ueno, T (reprint author), Kumamoto Univ, Ctr AIDS Res, 2-2-1 Honjo, Kumamoto 8600811, Japan. EM zbrumme@sfu.ca; uenotaka@kumamoto-u.ac.jp RI Kumamoto University, CAIDS/G-8446-2013; Ueno, Takamasa/F-5788-2013; OI Ueno, Takamasa/0000-0003-4852-4236; Brockman, Mark/0000-0001-6432-1426 FU Ministry of Education, Science, Sports, and Culture (MEXT) of Japan; Global COE Program (Global Education and Research Center Aiming at the control of AIDS), MEXT, Japan; Ministry of Health, Labor, and Welfare of Japan; Canadian Institutes for Health Research [MOP-93536]; Microsoft Research; Japan AIDS Foundation; Global Health Research Initiative (GHRI); CIHR; Canadian International Development Agency; International Development Research Centre; Canadian Association of HIV Research; Abbott Virology; Canadian Institutes of Health Research; Michael Smith Foundation for Health Research FX This research was supported by a grant-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture (MEXT) of Japan, by a Global COE Program (Global Education and Research Center Aiming at the control of AIDS), MEXT, Japan, and by a grant-in-aid for AIDS research from the Ministry of Health, Labor, and Welfare of Japan (to TU). It was also supported in part by an operating grant from the Canadian Institutes for Health Research (MOP-93536) and a Jim Gray seed grant from Microsoft Research (to ZLB/MAB). PM is a postdoctoral fellow who received support from the Japan AIDS Foundation and the Global Health Research Initiative (GHRI), a collaborative research funding partnership of the CIHR, the Canadian International Development Agency, and the International Development Research Centre. EM was supported by a Master's Scholarship from the Canadian Association of HIV Research and Abbott Virology. MAB holds a Canada Research Chair, Tier 2, in Viral Pathogenesis and Immunity. ZLB is the recipient of a New Investigator Award from the Canadian Institutes of Health Research and a Scholar Award from the Michael Smith Foundation for Health Research. NR 57 TC 15 Z9 16 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 10 PY 2013 VL 439 IS 2 BP 74 EP 80 DI 10.1016/j.virol.2013.02.005 PG 7 WC Virology SC Virology GA 168EC UT WOS:000320687500002 PM 23490051 ER PT J AU Russo, SB Tidhar, R Futerman, AH Cowart, LA AF Russo, Sarah Brice Tidhar, Rotem Futerman, Anthony H. Cowart, L. Ashley TI Myristate-derived d16:0 Sphingolipids Constitute a Cardiac Sphingolipid Pool with Distinct Synthetic Routes and Functional Properties SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMALIAN SERINE-PALMITOYLTRANSFERASE; TANDEM MASS-SPECTROMETRY; CERAMIDE SYNTHASES; CELL-DEATH; ACYL-CHAIN; SPHINGOSINE 1-PHOSPHATE; DIABETIC CARDIOMYOPATHY; HEART-FAILURE; LONG-CHAIN; RAT-BRAIN AB The enzyme serine palmitoyltransferase (SPT) catalyzes the formation of the sphingoid base "backbone" from which all sphingolipids are derived. Previous studies have shown that inhibition of SPT ameliorates pathological cardiac outcomes in models of lipid overload, but the metabolites responsible for these phenotypes remain unidentified. Recent in vitro studies have shown that incorporation of the novel subunit SPTLC3 broadens the substrate specificity of SPT, allowing utilization of myristoyl-coenzyme A (CoA) in addition to its canonical substrate palmitoyl-CoA. However, the relevance of these findings in vivo has yet to be determined. The present study sought to determine whether myristate-derived d16 sphingolipids are represented among myocardial sphingolipids and, if so, whether their function and metabolic routes were distinct from those of palmitate-derived d18 sphingolipids. Data showed that d16: 0 sphingoid bases occurred in more than one-third of total dihydrosphingosine and dihydroceramides in myocardium, and a diet high in saturated fat promoted their de novo production. Intriguingly, d16-ceramides demonstrated highly limited N-acyl chain diversity, and in vitro enzyme activity assays showed that these bases were utilized preferentially to canonical bases by CerS1. Functional differences between myristate- and palmitate-derived sphingolipids were observed in that, unlike d18 sphingolipids and SPTLC2, d16 sphingolipids and SPTLC3 did not appear to contribute to myristate-induced autophagy, whereas only d16 sphingolipids promoted cell death and cleavage of poly(ADPribose) polymerase in cardiomyocytes. Thus, these results reveal a previously unappreciated component of cardiac sphingolipids with functional differences from canonical sphingolipids. C1 [Russo, Sarah Brice; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29403 USA. [Tidhar, Rotem; Futerman, Anthony H.] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. RP Cowart, LA (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Biochem & Mol Biol, 173 Ashley Ave,MSC509, Charleston, SC 29403 USA. EM cowartl@musc.edu OI Futerman, Anthony/0000-0003-0013-0115 FU National Institutes of Health (NIH), NIDDK [F30DK092125]; NIH [P30 CA138313, P20 RR017677]; NIH COBRE in Lipidomics and Pathobiology at MUSC; Department of Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health (NIH), NIDDK, Grant F30DK092125 (to S. B. R.); NIH Grant P30 CA138313 (Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (MUSC)); NIH Grant P20 RR017677 (Lipidomics Core in the South Carolina Lipidomics and Pathobiology Centers of Biomedical Research Excellence (COBRE), Department of Biochemistry, MUSC); and the NIH COBRE in Lipidomics and Pathobiology at MUSC (to L. A. C.). This work was also supported by a Merit Award from the Department of Veterans Affairs (to L. A. C.). NR 63 TC 16 Z9 16 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 2013 VL 288 IS 19 BP 13397 EP 13409 DI 10.1074/jbc.M112.428185 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 143EV UT WOS:000318850300025 PM 23530041 ER PT J AU Qin, WP Sun, L Cao, J Peng, YZ Collier, L Wu, Y Creasey, G Li, JH Qin, YW Jarvis, J Bauman, WA Zaidi, M Cardozo, C AF Qin, Weiping Sun, Li Cao, Jay Peng, Yuanzhen Collier, Lauren Wu, Yong Creasey, Graham Li, Jianhua Qin, Yiwen Jarvis, Jonathan Bauman, William A. Zaidi, Mone Cardozo, Christopher TI The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINAL-CORD-INJURY; GENE-EXPRESSION; C-FOS; CELLS; DIFFERENTIATION; IMMOBILIZATION; DISEASE; OSTEOCLASTOGENESIS; STIMULATION; NANDROLONE AB Muscle and bone work as a functional unit. Cellular and molecular mechanisms underlying effects of muscle activity on bone mass are largely unknown. Spinal cord injury (SCI) causes muscle paralysis and extensive sublesional bone loss and disrupts neural connections between the central nervous system (CNS) and bone. Muscle contraction elicited by electrical stimulation (ES) of nerves partially protects against SCI-related bone loss. Thus, application of ES after SCI provides an opportunity to study the effects of muscle activity on bone and roles of the CNS in this interaction, as well as the underlying mechanisms. Using a rat model of SCI, the effects on bone of ES-induced muscle contraction were characterized. The SCI-mediated increase in serum C-terminal telopeptide of type I collagen (CTX) was completely reversed by ES. In ex vivo bone marrow cell cultures, SCI increased the number of osteoclasts and their expression of mRNA for several osteoclast differentiation markers, whereas ES significantly reduced these changes; SCI decreased osteoblast numbers, but increased expression in these cells of receptor activator of NF-kappa B ligand (RANKL) mRNA, whereas ES increased expression of osteoprotegerin (OPG) and the OPG/RANKL ratio. A microarray analysis revealed that ES partially reversed SCI-induced alterations in expression of genes involved in signaling through Wnt, FSH, parathyroid hormone (PTH), oxytocin, and calcineurin/nuclear factor of activated T-cells (NFAT) pathways. ES mitigated SCI-mediated increases in mRNA levels for the Wnt inhibitors DKK1, sFRP2, and sclerostin in ex vivo cultured osteoblasts. Our results demonstrate an anti-bone-resorptive activity of muscle contraction by ES that develops rapidly and is independent of the CNS. The pathways involved, particularly Wnt signaling, suggest future strategies to minimize bone loss after immobilization. C1 [Qin, Weiping; Sun, Li; Peng, Yuanzhen; Li, Jianhua; Bauman, William A.; Zaidi, Mone; Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. [Sun, Li; Li, Jianhua; Zaidi, Mone] Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10029 USA. [Qin, Weiping; Peng, Yuanzhen; Collier, Lauren; Wu, Yong; Bauman, William A.; Cardozo, Christopher] James J Peters Vet Affairs Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY 10468 USA. [Cao, Jay] Res Serv, USDA, Human Nutr Res Ctr, Grand Forks, ND 58201 USA. [Creasey, Graham] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Creasey, Graham] Stanford Univ, Palo Alto, CA 94304 USA. [Qin, Yiwen] Chapin Sch, New York, NY 10028 USA. [Jarvis, Jonathan] Liverpool John Moores Univ, Sch Sport & Exercise Sci, Liverpool L3 3AF, Merseyside, England. RP Qin, WP (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences SCI, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM weiping.qin@mssm.edu; Chris.cardozo@mssm.edu FU United States Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, B4055X, B3347K]; United States Department of Defense [SC090504]; National Institutes of Health [AG23176, DK80459]; European Commission [QLG5-CT-2001-02191] FX This work was supported by the United States Veterans Health Administration, Rehabilitation Research and Development Service Grants B4162C (to W. A. B.) and B4055X and B3347K (to C. C.), the United States Department of Defense Grant SC090504 (to W. Q.), National Institutes of Health Grants AG23176 and DK80459 (to M. Z.), and European Commission Project RISE Grant QLG5-CT-2001-02191 (to J. J.). NR 62 TC 21 Z9 21 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 2013 VL 288 IS 19 BP 13511 EP 13521 DI 10.1074/jbc.M113.454892 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 143EV UT WOS:000318850300035 PM 23530032 ER PT J AU Raymond, VM Mukherjee, B Wang, F Huang, SC Stoffel, EM Kastrinos, F Syngal, S Cooney, KA Gruber, SB AF Raymond, Victoria M. Mukherjee, Bhramar Wang, Fei Huang, Shu-Chen Stoffel, Elena M. Kastrinos, Fay Syngal, Sapna Cooney, Kathleen A. Gruber, Stephen B. TI Elevated Risk of Prostate Cancer Among Men With Lynch Syndrome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; DNA-MISMATCH-REPAIR; MSH2 MUTATION CARRIERS; MICROSATELLITE INSTABILITY; EXTRACOLONIC CANCERS; GERMLINE MUTATIONS; FAMILIES; GENES; BRCA1; MLH1 AB Purpose Prostate cancer has been described as a component tumor of Lynch syndrome (LS), with tumors obtained from mutation carriers demonstrating the DNA mismatch repair deficiency phenotype. Previous studies quantifying prostate cancer risk in LS have provided conflicting results. Methods We examined cancer histories of probands and their first-through fourth-degree relatives for 198 independent mutation-positive LS families enrolled in two US familial cancer registries. Modified segregation analysis was used to calculate age-specific cumulative risk or penetrance estimates, with accompanying Wald-type CIs. Cumulative lifetime risks and hazard ratio (HR) estimates for prostate cancer were calculated and compared with those of the general population. Results Ninety-seven cases of prostate cancer were observed in 4,127 men. Median age at prostate cancer diagnosis was 65 years (range, 38 to 89 years), with 11.53% of affected individuals diagnosed before age 50 years. The cumulative risk of prostate cancer at ages 60 and 80 years was 6.30% (95% CI, 2.47 to 9.96) and 30.0% (95% CI, 16.54 to 41.30), as compared with the population risk of 2.59% and 17.84%, respectively. The overall prostate cancer HR among carriers was 1.99 (95% CI, 1.31 to 3.03). Conclusion The cumulative lifetime risk of prostate cancer in individuals with LS is two-fold higher than in the general population and is slightly higher in carriers diagnosed before age 60 years (HR, 2.48; 95% CI, 1.34 to 4.59). These estimates are clinically valuable to quantify risk for both patients and providers. J Clin Oncol 31:1713-1718. (C) 2013 by American Society of Clinical Oncology C1 [Raymond, Victoria M.; Mukherjee, Bhramar; Wang, Fei; Huang, Shu-Chen; Stoffel, Elena M.; Cooney, Kathleen A.; Gruber, Stephen B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Cooney, Kathleen A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Stoffel, Elena M.; Kastrinos, Fay; Syngal, Sapna] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Stoffel, Elena M.; Kastrinos, Fay; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Kastrinos, Fay] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Gruber, Stephen B.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Raymond, VM (reprint author), Univ Michigan, 300 North Ingalls, Ann Arbor, MI 48109 USA. EM vraymond@umich.edu FU NIH/NCI [K24 113433, P30 CA014089, P30 CA046592]; NCI [R01 CA136621, P50 CA69568] FX Supported by Grants No. K24 113433 from NIH/NCI (S. S.), R01 CA136621 and P50 CA69568 from NCI (K. A. C.), and P30 CA014089 and P30 CA046592 from NIH/NCI (S.B.G.). NR 33 TC 34 Z9 34 U1 0 U2 6 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 MAY 10 PY 2013 VL 31 IS 14 BP 1713 EP + DI 10.1200/JCO.2012.44.1238 PG 8 WC Oncology SC Oncology GA 141ZW UT WOS:000318766300008 PM 23530095 ER PT J AU Trunzer, K Pavlick, AC Schuchter, L Gonzalez, R McArthur, GA Hutson, TE Moschos, SJ Flaherty, KT Kim, KB Weber, JS Hersey, P Long, GV Lawrence, D Ott, PA Amaravadi, RK Lewis, KD Puzanov, I Lo, RS Koehler, A Kockx, M Spleiss, O Schell-Steven, A Gilbert, HN Cockey, L Bollag, G Lee, RJ Joe, AK Sosman, JA Ribas, A AF Trunzer, Kerstin Pavlick, Anna C. Schuchter, Lynn Gonzalez, Rene McArthur, Grant A. Hutson, Thomas E. Moschos, Stergios J. Flaherty, Keith T. Kim, Kevin B. Weber, Jeffrey S. Hersey, Peter Long, Georgina V. Lawrence, Donald Ott, Patrick A. Amaravadi, Ravi K. Lewis, Karl D. Puzanov, Igor Lo, Roger S. Koehler, Astrid Kockx, Mark Spleiss, Olivia Schell-Steven, Annette Gilbert, Houston N. Cockey, Louise Bollag, Gideon Lee, Richard J. Joe, Andrew K. Sosman, Jeffrey A. Ribas, Antoni TI Pharmacodynamic Effects and Mechanisms of Resistance to Vemurafenib in Patients With Metastatic Melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RAF INHIBITOR RESISTANCE; B-RAF; BRAF; MUTATIONS; CELLS; BRAF(V600E); SURVIVAL; OVERCOME; PATHWAY; CANCER AB Purpose To assess pharmacodynamic effects and intrinsic and acquired resistance mechanisms of the BRAF inhibitor vemurafenib in BRAF(V600)-mutant melanoma, leading to an understanding of the mechanism of action of vemurafenib and ultimately to optimization of metastatic melanoma therapy. Methods In the phase II clinical study NP22657 (BRIM-2), patients received oral doses of vemurafenib (960 mg twice per day). Serial biopsies were collected to study changes in mitogen-activated protein kinase (MAPK) signaling, cell-cycle progression, and factors causing intrinsic or acquired resistance by immunohistochemistry, DNA sequencing, or somatic mutation profiling. Results Vemurafenib inhibited MAPK signaling and cell-cycle progression. An association between the decrease in extracellular signal-related kinase (ERK) phosphorylation and objective response was observed in paired biopsies (n = 22; P = .013). Low expression of phosphatase and tensin homolog showed a modest association with lower response. Baseline mutations in MEK1(P124) coexisting with BRAF(V600) were noted in seven of 92 samples; their presence did not preclude objective tumor responses. Acquired resistance to vemurafenib associated with reactivation of MAPK signaling as observed by elevated ERK1/2 phosphorylation levels in progressive lesions and the appearance of secondary NRAS(Q61) mutations or MEK1(Q56P) or MEK1(E203K) mutations. These two activating MEK1 mutations had not previously been observed in vivo in biopsies of progressive melanoma tumors. Conclusion Vemurafenib inhibits tumor proliferation and oncogenic BRAF signaling through the MAPK pathway. Acquired resistance results primarily from MAPK reactivation driven by the appearance of secondary mutations in NRAS and MEK1 in subsets of patients. The data suggest that inhibition downstream of BRAF should help to overcome acquired resistance. (C) 2013 by American Society of Clinical Oncology C1 [Trunzer, Kerstin; Spleiss, Olivia; Schell-Steven, Annette; Cockey, Louise] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Pavlick, Anna C.; Ott, Patrick A.] NYU, Med Ctr, New York, NY 10016 USA. [Schuchter, Lynn; Amaravadi, Ravi K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Moschos, Stergios J.] Univ Pittsburgh, Pittsburgh, PA USA. [Gonzalez, Rene; Lewis, Karl D.] Univ Colorado, Denver, CO 80202 USA. [McArthur, Grant A.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Hersey, Peter] Univ Newcastle, Newcastle, NSW 2300, Australia. [Long, Georgina V.] Univ Sydney, Westmead Inst Canc Res, Sydney, NSW 2006, Australia. [Long, Georgina V.] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. [Hutson, Thomas E.] Texas Oncol Baylor Sammons Canc Ctr, Dallas, TX USA. [Kim, Kevin B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Flaherty, Keith T.; Lawrence, Donald] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Weber, Jeffrey S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Puzanov, Igor; Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Lo, Roger S.; Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Gilbert, Houston N.] Genentech Inc, San Francisco, CA 94080 USA. [Bollag, Gideon] Plexxikon, Berkeley, CA USA. [Koehler, Astrid] Roche Diagnost, Penzberg, Germany. [Kockx, Mark] HistoGeneX, Antwerp, Belgium. [Lee, Richard J.; Joe, Andrew K.] F Hoffmann La Roche & Co Ltd, Nutley, NJ USA. RP Sosman, JA (reprint author), Vanderbilt Ingram Canc Ctr, 777 Preston Res Bldg, Nashville, TN 37232 USA. EM jeff.sosman@vanderbilt.edu FU Genentech; Roche Genentech; F. Hoffmann-La Roche FX Anna C. Pavlick, Genentech; Rene Gonzalez, Roche Genentech; Keith Flaherty, Roche Genentech; Kevin B. Kim, Roche Genentech; Jeffrey S. Weber, Roche Genentech; Georgina V. Long, Roche Genentech; Karl D. Lewis, Roche Genentech; Houston N. Gilbert, Roche Genentech; Supported by F. Hoffmann-La Roche. NR 30 TC 140 Z9 142 U1 1 U2 33 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2013 VL 31 IS 14 BP 1767 EP 1774 DI 10.1200/JCO.2012.44.7888 PG 8 WC Oncology SC Oncology GA 141ZW UT WOS:000318766300015 PM 23569304 ER PT J AU Steensma, DP Sekeres, MA AF Steensma, David P. Sekeres, Mikkael A. TI Decitabine in Older Adults With Acute Myeloid Leukemia: Why Was the Dream Broken? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. [Sekeres, Mikkael A.] Cleveland Clin, Leukemia Program, Taussig Canc Inst, Cleveland, OH 44106 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [P30 CA016672] NR 5 TC 0 Z9 0 U1 0 U2 0 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 MAY 10 PY 2013 VL 31 IS 14 BP 1796 EP 1797 DI 10.1200/JCO.2013.48.7140 PG 3 WC Oncology SC Oncology GA 141ZW UT WOS:000318766300021 PM 23802242 ER PT J AU Chi, AS Batchelor, TT Yang, D Dias-Santagata, D Borger, DR Ellisen, LW Iafrate, AJ Louis, DN AF Chi, Andrew S. Batchelor, Tracy T. Yang, Daniel Dias-Santagata, Dora Borger, Darrell R. Ellisen, Leif W. Iafrate, A. John Louis, David N. TI BRAF V600E Mutation Identifies a Subset of Low-Grade Diffusely Infiltrating Gliomas in Adults SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IDH2 MUTATIONS; GENE; TEMOZOLOMIDE; GLIOBLASTOMA C1 [Chi, Andrew S.; Batchelor, Tracy T.; Yang, Daniel] Harvard Univ, Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Canc Ctr,Med Sch, Boston, MA 02114 USA. [Dias-Santagata, Dora; Borger, Darrell R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Translat Res Lab,Med Sch, Boston, MA 02114 USA. [Ellisen, Leif W.; Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Iafrate, A. John] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Translat Res Lab,Med Sch, Boston, MA 02114 USA. [Iafrate, A. John; Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Pathol Serv,Med Sch, Boston, MA 02114 USA. RP Chi, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Canc Ctr,Med Sch, Boston, MA 02114 USA. NR 14 TC 19 Z9 19 U1 0 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 MAY 10 PY 2013 VL 31 IS 14 BP E233 EP E236 DI 10.1200/JCO.2012.46.0220 PG 4 WC Oncology SC Oncology GA 141ZW UT WOS:000318766300001 PM 23547069 ER PT J AU Rajabali, A Caton, H AF Rajabali, Alefiyah Caton, Harmony TI BOSTON MARATHON BOMBING A tale of two physicians: reflections on the Boston Marathon bombing SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 [Rajabali, Alefiyah; Caton, Harmony] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Rajabali, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM arajabali@partners.org NR 0 TC 1 Z9 1 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD MAY 10 PY 2013 VL 346 AR f2993 DI 10.1136/bmj.f2993 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 144BV UT WOS:000318915300006 PM 23667127 ER PT J AU Baxt, LA Garza-Mayers, AC Goldberg, MB AF Baxt, Leigh A. Garza-Mayers, Anna Cristina Goldberg, Marcia B. TI Subversion of Host Innate Immune Pathways SO SCIENCE LA English DT Review ID NF-KAPPA-B; PHOSPHOTHREONINE LYASE ACTIVITY; LEGIONELLA-PNEUMOPHILA; EFFECTOR FAMILY; AUTOPHAGY; KINASE; GTPASE; INACTIVATION; CONTRIBUTES; DYSFUNCTION AB The pathogenesis of infection is a continuously evolving battle between the human host and the infecting microbe. The past decade has brought a burst of insights into the molecular mechanisms of innate immune responses to bacterial pathogens. In parallel, multiple specific mechanisms by which microorganisms subvert these host responses have been uncovered. This Review highlights recently characterized mechanisms by which bacterial pathogens avoid killing by innate host responses, including autophagy pathways and a proinflammatory cytokine transcriptional response, and by the manipulation of vesicular trafficking to avoid the toxicity of lysosomal enzymes. C1 [Baxt, Leigh A.; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. [Garza-Mayers, Anna Cristina; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [R01 AI081724]; NIGMS NIH HHS [T32 GM007753] NR 50 TC 66 Z9 67 U1 2 U2 56 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 10 PY 2013 VL 340 IS 6133 BP 697 EP 701 DI 10.1126/science.1235771 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139XR UT WOS:000318619000027 PM 23661751 ER PT J AU Jardine, J Julien, JP Menis, S Ota, T Kalyuzhniy, O McGuire, A Sok, D Huang, PS MacPherson, S Jones, M Nieusma, T Mathison, J Baker, D Ward, AB Burton, DR Stamatatos, L Nemazee, D Wilson, IA Schief, WR AF Jardine, Joseph Julien, Jean-Philippe Menis, Sergey Ota, Takayuki Kalyuzhniy, Oleksandr McGuire, Andrew Sok, Devin Huang, Po-Ssu MacPherson, Skye Jones, Meaghan Nieusma, Travis Mathison, John Baker, David Ward, Andrew B. Burton, Dennis R. Stamatatos, Leonidas Nemazee, David Wilson, Ian A. Schief, William R. TI Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors SO SCIENCE LA English DT Article ID STRUCTURAL BASIS; ANTIBODIES; POTENT; BROAD; NEUTRALIZATION; VIRUSES; ENV AB Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens. C1 [Jardine, Joseph; Menis, Sergey; Ota, Takayuki; Kalyuzhniy, Oleksandr; Sok, Devin; MacPherson, Skye; Jones, Meaghan; Mathison, John; Burton, Dennis R.; Nemazee, David; Schief, William R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Jardine, Joseph; Julien, Jean-Philippe; Menis, Sergey; Kalyuzhniy, Oleksandr; Sok, Devin; MacPherson, Skye; Jones, Meaghan; Nieusma, Travis; Ward, Andrew B.; Burton, Dennis R.; Wilson, Ian A.; Schief, William R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Jardine, Joseph; Julien, Jean-Philippe; Menis, Sergey; Kalyuzhniy, Oleksandr; Sok, Devin; MacPherson, Skye; Nieusma, Travis; Ward, Andrew B.; Burton, Dennis R.; Wilson, Ian A.; Schief, William R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Jardine, Joseph; Menis, Sergey; Kalyuzhniy, Oleksandr; Huang, Po-Ssu; MacPherson, Skye; Jones, Meaghan; Baker, David; Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Julien, Jean-Philippe; Nieusma, Travis; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [McGuire, Andrew; Stamatatos, Leonidas] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Burton, Dennis R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02129 USA. [Stamatatos, Leonidas] Univ Washington, Dept Global Hlth, Seattle, WA 98109 USA. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Schief, WR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM schief@scripps.edu RI Cheng, Yushao/E-6256-2011; Ward, Andrew/F-9203-2014; Baker, David/K-8941-2012; OI Ward, Andrew/0000-0001-7153-3769; Baker, David/0000-0001-7896-6217; Spencer, Skye/0000-0001-9570-9634 FU IAVI Neutralizing Antibody Center, CHAVI-ID [UM1 AI100663]; NIH [AI84817, AI081625, AI33292]; NIH National Research Service Award [T32CA080416]; Canadian Institutes of Health Research; Creative and Novel Ideas in HIV Research grant [P30 AI027767-24]; NIH Interdisciplinary Training Program in Immunology [5T32AI007606-10]; Ragon Institute; DOE Office of Biological and Environmental Research; NIH's National Center for Research Resources, Biomedical Technology Program [P41RR001209]; National Institute of General Medical Sciences (NIGMS); DOE, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; National Cancer Institute [Y1-CO-1020]; NIGMS [Y1-GM-1104] FX We thank J. Mascola and X. Wu for providing sequences of mature PGV19 and PGV20; R. Wyatt for providing the YU2 gp140 trimer; C. Sundling and G. Karlsson Hedestam for the sequence of the Rhe1 VH gene; A. Bradley, R. L. Stanfield, and D. C. Diwanji for technical assistance and insightful discussions; and M. Azoitei, R. Jacak, and D. Kulp for comments on the manuscript. The data presented in this manuscript are tabulated in the main paper and the supplementary materials. Coordinates and structure factors for GL-VRC01 Fab, eOD-GT6, and GL-VRC01+eODGT6 structures have been deposited with the PDB under accession codes 4JPI, 4JPJ, and 4JPK, respectively. The International AIDS Vaccine Initiative (IAVI) has filed a patent relating to immunogens in this manuscript: PCT Application PCT/US12/60062, titled "Engineered Outer Domain (EOD) of HIV GP120 and Mutants Thereof," with inventors W. R. S., J. J., S. M., and P.-S.H. Materials and information will be provided under a material transfer agreement. This work was supported by IAVI Neutralizing Antibody Center, CHAVI-ID (UM1 AI100663); NIH grants AI84817 (I. A. W.), AI081625 (L. S.), and AI33292 (D. R. B.); NIH National Research Service Award Training Grant fellowship T32CA080416 (J. J.); Canadian Institutes of Health Research fellowship (J.-P.J.); Creative and Novel Ideas in HIV Research grant P30 AI027767-24 (T.O.); NIH Interdisciplinary Training Program in Immunology 5T32AI007606-10 (D. S.); and the Ragon Institute. Portions of this research were carried out at the Stanford Synchrotron Radiation Lightsource (SSRL), a directorate of the SLAC National Accelerator Laboratory and an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research; NIH's National Center for Research Resources, Biomedical Technology Program (P41RR001209); and the National Institute of General Medical Sciences (NIGMS). Use of the Advanced Photon Source was supported by the DOE, Basic Energy Sciences, Office of Science, under contract DE-AC02-06CH11357. GM/CA CAT has been funded in whole or in part with federal funds from the National Cancer Institute (grant Y1-CO-1020) and NIGMS (grant Y1-GM-1104). This is manuscript 23050 from The Scripps Research Institute. NR 29 TC 203 Z9 207 U1 12 U2 85 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 10 PY 2013 VL 340 IS 6133 BP 711 EP 716 DI 10.1126/science.1234150 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139XR UT WOS:000318619000030 PM 23539181 ER PT J AU van Balkom, BWM de Jong, OG Smits, M Brummelman, J den Ouden, K de Bree, PM van Eijndhoven, MAJ Pegtel, DM Stoorvogel, W Wurdinger, T Verhaar, MC AF van Balkom, Bas W. M. de Jong, Olivier G. Smits, Michiel Brummelman, Jolanda den Ouden, Krista de Bree, Petra M. van Eijndhoven, Monique A. J. Pegtel, D. Michiel Stoorvogel, Willem Wuerdinger, Thomas Verhaar, Marianne C. TI Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells SO BLOOD LA English DT Article ID PROMOTE TUMOR-GROWTH; PROGENITOR CELLS; DIAGNOSTIC BIOMARKERS; OXIDATIVE STRESS; LUNG-CANCER; IN-VITRO; T-CELLS; MECHANISM; MICRORNA; EXPRESSION AB Signaling between endothelial cells, endothelial progenitor cells, and stromal cells is crucial for the establishment and maintenance of vascular integrity and involves exosomes, among other signaling pathways. Exosomes are important mediators of intercellular communication in immune signaling, tumor survival, stress responses, and angiogenesis. The ability of exosomes to incorporate and transfer messenger RNAs (mRNAs) encoding for "acquired" proteins or micro RNAs (miRNAs) repressing "resident" mRNA translation suggests that they can influence the physiological behavior of recipient cells. We demonstrate that miR-214, an miRNA that controls endothelial cell function and angiogenesis, plays a dominant role in exosome-mediated signaling between endothelial cells. Endothelial cell-derived exosomes stimulated migration and angiogenesis in recipient cells, whereas exosomes from miR-214-depleted endothelial cells failed to stimulate these processes. Exosomes containing miR-214 repressed the expression of ataxia telangiectasia mutated in recipient cells, thereby preventing senescence and allowing blood vessel formation. Concordantly, specific reduction of miR-214 content in exosome-producing endothelial cells abolishes the angiogenesis stimulatory function of the resulting exosomes. Collectively, our data indicate that endothelial cells release miR-214-containing exosomes to stimulate angiogenesis through the silencing of ataxia telangiectasia mutated in neighboring target cells. C1 [van Balkom, Bas W. M.; de Jong, Olivier G.; Brummelman, Jolanda; den Ouden, Krista; de Bree, Petra M.; Verhaar, Marianne C.] Univ Med Ctr Utrecht, Dept Hypertens & Nephrol, Utrecht, Netherlands. [Smits, Michiel; Wuerdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [van Eijndhoven, Monique A. J.; Pegtel, D. Michiel] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Stoorvogel, Willem] Univ Utrecht, Fac Vet Med, Dept Biochem & Cell Biol, Utrecht, Netherlands. [Wuerdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Wuerdinger, Thomas] Harvard Univ, Sch Med, Boston, MA USA. RP van Balkom, BWM (reprint author), Dept Hypertens & Nephrol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM b.w.m.vanbalkom@umcutrecht.nl RI Pegtel, Dirk/M-8393-2015; OI Pegtel, Dirk/0000-0002-7357-4406; Verhaar, Marianne/0000-0002-3276-6428 FU Netherlands Organization for Scientific Research (NGI/ZonMW) [935190280]; UMC Utrecht Focus and Massa [DIGD-DGK-DHL]; Netherlands Organization for Scientific Research (NWO-VIDI) FX This work was supported by The Netherlands Organization for Scientific Research (NGI/ZonMW Horizon project 935190280) (B. W. M. v. B.) and UMC Utrecht Focus and Massa (grant DIGD-DGK-DHL) (M. C. V.). T. W. and M. C. V. are both supported by The Netherlands Organization for Scientific Research (NWO-VIDI). NR 50 TC 92 Z9 96 U1 4 U2 37 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 9 PY 2013 VL 121 IS 19 BP 3997 EP 4006 DI 10.1182/blood-2013-02-478925 PG 10 WC Hematology SC Hematology GA 184EO UT WOS:000321870900031 PM 23532734 ER PT J AU Loffredo, FS Steinhauser, ML Jay, SM Gannon, J Pancoast, JR Yalamanchi, P Sinha, M Dall'Osso, C Khong, D Shadrach, JL Miller, CM Singer, BS Stewart, A Psychogios, N Gerszten, RE Hartigan, AJ Kim, MJ Serwold, T Wagers, AJ Lee, RT AF Loffredo, Francesco S. Steinhauser, Matthew L. Jay, Steven M. Gannon, Joseph Pancoast, James R. Yalamanchi, Pratyusha Sinha, Manisha Dall'Osso, Claudia Khong, Danika Shadrach, Jennifer L. Miller, Christine M. Singer, Britta S. Stewart, Alex Psychogios, Nikolaos Gerszten, Robert E. Hartigan, Adam J. Kim, Mi-Jeong Serwold, Thomas Wagers, Amy J. Lee, Richard T. TI Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy SO CELL LA English DT Article ID DIASTOLIC HEART-FAILURE; HEMATOPOIETIC STEM-CELLS; SKELETAL-MUSCLE; BLOOD-PRESSURE; MYOSTATIN; PROTEIN; MICE; REJUVENATION; EPIDEMIOLOGY; CARDIOLOGY AB The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGF-beta superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging. C1 [Loffredo, Francesco S.; Jay, Steven M.; Sinha, Manisha; Dall'Osso, Claudia; Khong, Danika; Shadrach, Jennifer L.; Miller, Christine M.; Hartigan, Adam J.; Kim, Mi-Jeong; Serwold, Thomas; Wagers, Amy J.; Lee, Richard T.] Brigham & Womens Hosp, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Loffredo, Francesco S.; Steinhauser, Matthew L.; Jay, Steven M.; Gannon, Joseph; Pancoast, James R.; Yalamanchi, Pratyusha; Lee, Richard T.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Sinha, Manisha; Dall'Osso, Claudia; Khong, Danika; Shadrach, Jennifer L.; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Sinha, Manisha; Dall'Osso, Claudia; Khong, Danika; Shadrach, Jennifer L.; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Miller, Christine M.; Hartigan, Adam J.; Kim, Mi-Jeong; Serwold, Thomas; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Singer, Britta S.; Stewart, Alex] SomaLogic Inc, Boulder, CO 80301 USA. [Psychogios, Nikolaos; Gerszten, Robert E.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Charlestown, MA 02129 USA. RP Wagers, AJ (reprint author), Brigham & Womens Hosp, Harvard Stem Cell Inst, 75 Francis St, Boston, MA 02115 USA. EM amy_wagers@harvard.edu; rlee@partners.org RI Loffredo, Francesco/F-6638-2014; OI Loffredo, Francesco/0000-0001-5911-780X; Psychogios, Nikolaos/0000-0002-2747-6012; Jay, Steven/0000-0002-3827-5988 FU NIH [P30DK036836, 1RO1 AG033053, 1DP2 OD004345, 5U01 HL100402, R01 AG032977 1R01 AG040019, KO8 DK090147]; American Heart Association; Glenn Foundation; Watkins Cardiovascular Leadership Award FX The authors gratefully acknowledge the HSCI and DRC (NIH Award Number P30DK036836) Flow Cytometry Cores for excellent cytometry support. This work was funded in part by grants from the American Heart Association to F.S.L. (postdoctoral fellowship) and M.L.S. (AHA FTF), Glenn Foundation and NIH (1RO1 AG033053, 1DP2 OD004345, and 5U01 HL100402) to A.J.W., NIH (R01 AG032977 1R01 AG040019) to R.T.L., and NIH (KO8 DK090147) to M.L.S. M.L.S. is supported by the Watkins Cardiovascular Leadership Award. A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies. SOMAscan and SOMAmers are trademarks of Soma Logic, Inc. NR 38 TC 224 Z9 235 U1 13 U2 151 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 9 PY 2013 VL 153 IS 4 BP 828 EP 839 DI 10.1016/j.cell.2013.04.015 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 143CN UT WOS:000318844000012 PM 23663781 ER PT J AU Horman, SR Janas, MM Litterst, C Wang, B MacRae, IJ Sever, MJ Morrissey, DV Graves, P Luo, B Umesalma, S Qi, HH Miraglia, LJ Novina, CD Orth, AP AF Horman, Shane R. Janas, Maja M. Litterst, Claudia Wang, Bingbing MacRae, Ian J. Sever, Mary J. Morrissey, David V. Graves, Paul Luo, Biao Umesalma, Shaikamjad Qi, Hank H. Miraglia, Loren J. Novina, Carl D. Orth, Anthony P. TI Akt-Mediated Phosphorylation of Argonaute 2 Downregulates Cleavage and Upregulates Translational Repression of MicroRNA Targets SO MOLECULAR CELL LA English DT Article ID MESSENGER-RNA DEGRADATION; P-BODIES; ENDONUCLEOLYTIC CLEAVAGE; DEPENDENT LOCALIZATION; QUANTITATIVE-ANALYSIS; CELL-PROLIFERATION; GENE; EXPRESSION; PROTEINS; DECAY AB A high-throughput RNA interference (RNAi) screen targeting 542 genes of the human kinome was used to discover regulators of RNAi. Here we report that the proto-oncogene Akt-3/PKB gamma (Akt3) phosphorylates Argonaute 2 (Ago2) at S387, which down-regulates cleavage and upregulates translational repression of endogenous microRNA (miRNA)targeted messenger RNAs (mRNAs). We further demonstrate that Akt3 coimmunoprecipitates with Ago2 and phosphorylation of Ago2 at S387 facilitates its interaction with GW182 and localization to cytoplasmic processing bodies (P bodies), where miRNA-targeted nnRNAs are thought to be stored and degraded. Therefore, Akt3-mediated phosphorylation of Ago2 is a molecular switch between target mRNA cleavage and translational repression activities of Ago2. C1 [Horman, Shane R.; Litterst, Claudia; Miraglia, Loren J.; Orth, Anthony P.] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. [Janas, Maja M.; Wang, Bingbing; Novina, Carl D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Janas, Maja M.; Wang, Bingbing; Novina, Carl D.] Harvard Univ, Sch Med, Dept Microbiol & lmmunobiol, Boston, MA 02215 USA. [Janas, Maja M.; Wang, Bingbing; Luo, Biao; Novina, Carl D.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Janas, Maja M.; Wang, Bingbing; Luo, Biao; Novina, Carl D.] MIT, Cambridge, MA 02142 USA. [MacRae, Ian J.; Sever, Mary J.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Morrissey, David V.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Graves, Paul] New York Methodist Hosp, Dept Radiat Oncol, Brooklyn, NY 11215 USA. [Umesalma, Shaikamjad; Qi, Hank H.] Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. RP Orth, AP (reprint author), Novartis Res Fdn, Genom Inst, 10675 John Jay Hopkins Dr, San Diego, CA 92121 USA. EM aorth@gnf.org FU W.M. Keck Foundation FX We wish to thank Richard G. Brusch for assistance with confocal microscopy, Angelica Romero for synthesis of viruses, Genevieve Welch for running the human kinome siRNA screen, Anthony Marelli for assistance with cloning Ago2 cDNAs, Myleen N. Medina for synthesis of AKT shRNA plasmids, Daniel E. Mason for performing LC-MS, and Lauren C. Fox for generation of Figure 6. This work was supported by a Distinguished Young Scholars Award from the W.M. Keck Foundation to C.D.N. NR 47 TC 41 Z9 41 U1 2 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 9 PY 2013 VL 50 IS 3 BP 356 EP 367 DI 10.1016/j.molce1.2013.03.015 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 147RA UT WOS:000319183500007 PM 23603119 ER PT J AU Sullivan, RJ Flaherty, K AF Sullivan, R. J. Flaherty, K. TI MAP kinase signaling and inhibition in melanoma SO ONCOGENE LA English DT Review DE melanoma; targeted therapy; BRAF ID RANDOMIZED DISCONTINUATION TRIAL; UNTREATED METASTATIC MELANOMA; CHRONIC MYELOID-LEUKEMIA; B-RAF INHIBITOR; NF-KAPPA-B; BRAF INHIBITION; WILD-TYPE; MULTIKINASE INHIBITOR; AZD6244 ARRY-142886; ACQUIRED-RESISTANCE AB The mitogen-activated protein kinase (MAPK) pathway is critical to oncogenic signaling in the majority of patients with malignant melanoma. Driver mutations in both NRAS and BRAF have important implications for prognosis and treatment. The development of inhibitors to mediators of the MAPK pathway, including those to CRAF, BRAF, and MEK, has led to major advances in the treatment of patients with melanoma. In particular, the selective BRAF inhibitor vemurafenib has been shown to improve overall survival in patients with tumors harboring BRAF mutations. However, the duration of benefit is limited in many patients and highlights the need for understanding the limitations of therapy in order to devise more effective strategies. MEK inhibitors have proven to particularly active in BRAF mutant melanomas also. Emerging knowledge about mechanisms of resistance as well as a more complete understanding of the biology of MAPK pathway signaling provides insight into rational combination regimens and sequences of molecularly targeted therapies. C1 [Sullivan, R. J.; Flaherty, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Flaherty, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM kflaherty@partners.org NR 96 TC 55 Z9 58 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 9 PY 2013 VL 32 IS 19 BP 2373 EP 2379 DI 10.1038/onc.2012.345 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 140ZL UT WOS:000318694900001 PM 22945644 ER PT J AU Gabuzda, D Yankner, BA AF Gabuzda, Dana Yankner, Bruce A. TI PHYSIOLOGY Inflammation links ageing to the brain SO NATURE LA English DT Editorial Material ID C-ELEGANS; NEURONS; LONGEVITY; PERSPECTIVE C1 [Gabuzda, Dana] Dana Farber Canc Inst, Dept Neurol, Boston, MA 02115 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yankner, Bruce A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Neurol, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu; bruce_yankner@hms.harvard.edu FU NIA NIH HHS [DP1 AG044161, P01 AG027916]; NIDA NIH HHS [DP1 DA028994]; NIH HHS [DP1 OD006849]; NIMH NIH HHS [R01 MH097659] NR 15 TC 15 Z9 17 U1 0 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 9 PY 2013 VL 497 IS 7448 BP 197 EP 198 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139CD UT WOS:000318558200027 PM 23636321 ER PT J AU Penson, RT Goodman, A Growdon, WB Borger, DR Lee, SI Oliva, E AF Penson, Richard T. Goodman, Annekathryn Growdon, Whitfield B. Borger, Darrell R. Lee, Susanna I. Oliva, Esther TI Case 14-2013: A 70-Year-Old Woman with Vaginal Bleeding SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; ENDOMETRIAL CANCER; UTERINE SARCOMAS; UTERUS; CARCINOSARCOMA; TUMORS; PACLITAXEL; CARCINOMAS; MUTATIONS C1 [Penson, Richard T.; Borger, Darrell R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Goodman, Annekathryn; Growdon, Whitfield B.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Lee, Susanna I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Penson, Richard T.; Borger, Darrell R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goodman, Annekathryn; Growdon, Whitfield B.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Lee, Susanna I.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Oliva, Esther] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. FU Apotex; Genentech; AstraZeneca; Lifecore Biomedical; BioMarin Pharmaceuticals; Clovis Oncology; Seattle Genetics; ImClone Systems; Endocyte; Eisai Pharmaceuticals; Amgen; Leerink Swann Laboratory; Prous Science Laboratory; Bio-Reference Laboratory FX Dr. Penson reports receiving payment from Apotex for providing expert testimony in a case of Aventis Pharma S. A. v. Apotex Inc.; payment for serving on scientific advisory boards from Genentech, AstraZeneca, Lifecore Biomedical, BioMarin Pharmaceuticals, Clovis Oncology, and Seattle Genetics; and grant support through his institution from ImClone Systems, Endocyte, AstraZeneca, Eisai Pharmaceuticals, and Amgen. Dr. Borger reports receiving consulting fees from Leerink Swann, Prous Science, and Bio-Reference Laboratories. Dr. Oliva reports providing expert opinions in legal cases on behalf of patients or physicians. No other potential conflict of interest relevant to this article was reported. NR 44 TC 1 Z9 1 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 9 PY 2013 VL 368 IS 19 BP 1827 EP 1835 DI 10.1056/NEJMcpc1209276 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 138WA UT WOS:000318540000014 PM 23656649 ER PT J AU Kawai, T Sachs, DH Sykes, M Cosimi, AB AF Kawai, Tatsuo Sachs, David H. Sykes, Megan Cosimi, A. Benedict TI HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID KIDNEY C1 [Kawai, Tatsuo; Sachs, David H.; Cosimi, A. Benedict] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sykes, Megan] Columbia Univ, New York, NY USA. RP Kawai, T (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM tkawai@partners.org FU NHLBI NIH HHS [P01 HL018646]; NIAID NIH HHS [N01 AI015416, R01 AI037692, R21 AI037692, U19 AI102405] NR 5 TC 49 Z9 52 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 9 PY 2013 VL 368 IS 19 BP 1850 EP 1852 DI 10.1056/NEJMc1213779 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 138WA UT WOS:000318540000030 PM 23656665 ER PT J AU Bogart, LM Chetty, S Giddy, J Sypek, A Sticklor, L Walensky, RP Losina, E Katz, JN Bassett, IV AF Bogart, Laura M. Chetty, Senica Giddy, Janet Sypek, Alexis Sticklor, Laurel Walensky, Rochelle P. Losina, Elena Katz, Jeffrey N. Bassett, Ingrid V. TI Barriers to care among people living with HIV in South Africa: Contrasts between patient and healthcare provider perspectives SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE linkage to care; HIV; AIDS; qualitative methods; South Africa; stigma ID ANTIRETROVIRAL THERAPY; INTERVENTION; ADHERENCE; DISEASE; ADULTS; CHINA AB We collected qualitative data (semi-structured interviews with 11 healthcare providers and 10 patients; 8 focus groups with 41 patients) to identify barriers to linkage to care among people living with HIV in South Africa who were not yet taking antiretroviral treatment. Patients and providers identified HIV stigma as a sizable barrier. Patients felt that stigma-related issues were largely beyond their control, fearing discrimination if they disclosed to employers or were seen visiting clinics in their community. Providers believed that patients should take responsibility for overcoming internal stigma and disclosing serostatus. Patients had considerable concerns about inconvenient clinic hours, long queues, difficulty in appointment scheduling, and disrespect from staff. Providers seemed to minimize the effects of such barriers and not recognize the extent of patient dissatisfaction. Better communication and understanding between patients and providers are needed to facilitate greater patient satisfaction and retention in HIV care. C1 [Bogart, Laura M.; Sticklor, Laurel] Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA USA. [Bogart, Laura M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Chetty, Senica; Giddy, Janet] McCord Hosp, Durban, South Africa. [Sypek, Alexis; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Losina, Elena; Bassett, Ingrid V.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Katz, Jeffrey N.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Bogart, LM (reprint author), Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA USA. EM laura.bogart@childrens.harvard.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU NCRR NIH HHS [UL1 RR025758, UL1 RR 025758]; NIAID NIH HHS [P30 AI060354]; NIAMS NIH HHS [K24 AR057827, K24AR057827]; NIMH NIH HHS [R01 MH090326, R01 MH073445] NR 25 TC 30 Z9 30 U1 0 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD MAY 8 PY 2013 VL 25 IS 7 BP 843 EP 853 DI 10.1080/09540121.2012.729808 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 166RI UT WOS:000320574400007 PM 23061894 ER PT J AU Bhargava, R Janssen, W Altmann, C Andres-Hernando, A Okamura, K Vandivier, RW Ahuja, N Faubel, S AF Bhargava, Rhea Janssen, William Altmann, Christopher Andres-Hernando, Ana Okamura, Kayo Vandivier, R. William Ahuja, Nilesh Faubel, Sarah TI Intratracheal IL-6 Protects against Lung Inflammation in Direct, but Not Indirect, Causes of Acute Lung Injury in Mice SO PLOS ONE LA English DT Article ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; ISCHEMIA-REPERFUSION INJURY; CRITICALLY-ILL PATIENTS; RESPIRATORY-DISTRESS-SYNDROME; BILATERAL-NEPHRECTOMY; ALVEOLAR MACROPHAGES; MECHANICAL VENTILATION; PERSISTENT ELEVATION; CARDIAC-SURGERY AB Introduction: Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS) and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury), intraperitoneal (IP) endotoxin administration (indirect lung injury) and, for comparison, intratracheal (IT) endotoxin administration (direct lung injury) with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation. Methods: Bronchoalveolar cytokines (IL-6, CXCL1, TNF-alpha, IL-1 beta, and IL-10), BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [ a biochemical marker of neutrophil infiltration]), and serum cytokines were determined in adult male C57Bl/ 6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping), IP endotoxin (10 mu g), or IT endotoxin (80 mu g) with and without intratracheal (IT) IL-6 (25 ng or 200 ng) treatment. Results: Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin. Conclusion: IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of ARDS. C1 [Bhargava, Rhea; Altmann, Christopher; Andres-Hernando, Ana; Okamura, Kayo; Ahuja, Nilesh] Univ Colorado Denver, Div Renal Dis & Hypertens, Dept Med, Aurora, CO USA. [Janssen, William] Natl Jewish Hlth, Dept Med, Div Pulm Med, Denver, CO USA. [Vandivier, R. William] Univ Colorado Denver, Div Pulm Med, Dept Med, Aurora, CO USA. [Faubel, Sarah] Univ Colorado Denver, Div Renal Dis & Hypertens, Dept Med, Aurora, CO USA. [Faubel, Sarah] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. RP Faubel, S (reprint author), Univ Colorado Denver, Div Renal Dis & Hypertens, Dept Med, Aurora, CO USA. EM Sarah.Faubel@ucdenver.edu FU United States National Institutes of Health (NIH); NHLBI [R01 HL095363]; NIH [HL109517]; AHA Postdoctoral Fellowship FX This work was supported by United States National Institutes of Health (NIH) funding from NHLBI: R01 HL095363 to S.F., NIH HL109517, and AHA Postdoctoral Fellowship to A.A.-H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 15 Z9 19 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 8 PY 2013 VL 8 IS 5 AR e61405 DI 10.1371/journal.pone.0061405 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 145YI UT WOS:000319055600011 PM 23667439 ER PT J AU Lewis, KB Hughes, RJ Epstein, MS Josephson, NC Kempton, CL Kessler, CM Key, NS Howard, TE Kruse-Jarres, R Lusher, JM Walsh, CE Watts, RG Ettinger, RA Pratt, KP AF Lewis, Kenneth B. Hughes, Richard J. Epstein, Melinda S. Josephson, Neil C. Kempton, Christine L. Kessler, Craig M. Key, Nigel S. Howard, Tom E. Kruse-Jarres, Rebecca Lusher, Jeanne M. Walsh, Christopher E. Watts, Raymond G. Ettinger, Ruth A. Pratt, Kathleen P. CA PATH Personalized Alternative TI Phenotypes of Allo- and Autoimmune Antibody Responses to FVIII Characterized by Surface Plasmon Resonance SO PLOS ONE LA English DT Article ID FACTOR-VIII ANTIBODIES; HUMAN/PORCINE FACTOR-VIII; VON-WILLEBRAND-FACTOR; FAB-ARM EXCHANGE; HEMOPHILIA-A; BETHESDA ASSAY; IGG4 ANTIBODIES; B-CELL; MONOCLONAL-ANTIBODIES; INHIBITOR ANTIBODIES AB Evidence of antibody isotype/ subtype switching may provide prognostic value regarding the state of immune responses to therapeutic proteins, e.g. anti-factor VIII (FVIII) antibodies that develop in many hemophilia A patients, clinically termed "inhibitors''. A sensitive, high-information-content surface plasmon resonance (SPR) assay has been developed to quantify IgG subtype distributions and the domain specificity of anti-drug antibodies. Plasma samples from 22 subjects with an alloor auto-immune reaction to FVIII were analyzed. Pre-analytical treatment protocols were developed to minimize nonspecific binding and specific matrix interference due to von Willebrand factor-FVIII interactions. The dynamic range for IgG quantification was 0.2-5 mu g/ml (similar to 1-33 nM), allowing characterization of inhibitor-positive samples. Subtype-specific monoclonal antibodies were used to quantify the IgG subtype distribution of FVIII-specific antibodies. Most samples obtained from multiply-infused inhibitor subjects contained IgG(4) antibodies. Several distinct phenotypes were assigned based on the IgG subtype distribution: IgG(1), IgG(4), IgG(1) & IgG(4), and IgG(1), IgG(2) & IgG(4). An IgG(1)-only response was found in mild/moderate HA subjects during early FVIII infusions, and analysis of serial samples followed antibody class switching as several subjects' immune responses developed. Competition studies utilizing a recombinant FVIII-C2 domain indicated 40-80% of FVIII-specific antibodies in most samples were directed against this domain. C1 [Lewis, Kenneth B.; Josephson, Neil C.; Ettinger, Ruth A.; Pratt, Kathleen P.] Puget Sound Blood Ctr, Res Inst, Seattle, WA 98104 USA. [Hughes, Richard J.; Epstein, Melinda S.; Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Josephson, Neil C.; Pratt, Kathleen P.] Univ Washington, Div Hematol, Seattle, WA 98195 USA. [Kempton, Christine L.] Emory Univ, Atlanta, GA 30322 USA. [Kessler, Craig M.] Georgetown Univ, Washington, DC USA. [Key, Nigel S.] Univ N Carolina, Chapel Hill, NC USA. [Howard, Tom E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Howard, Tom E.] USC, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA USA. [Kruse-Jarres, Rebecca] Tulane Univ, New Orleans, LA 70118 USA. [Lusher, Jeanne M.] Wayne State Univ, Detroit, MI USA. [Walsh, Christopher E.] Mt Sinai Sch Med, New York, NY USA. [Watts, Raymond G.] Univ Alabama Birmingham, Birmingham, AL USA. RP Pratt, KP (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. EM KathleenP@psbc.org FU NHLBI [1RC2 HL101851]; Bayer HealthCare LLC FX Major support for this work was from NHLBI 1RC2 HL101851: "Mechanisms of Race-Based Differences in Factor VIII Immunogenicity in Hemophilia A" (PIs TE Howard and KP Pratt). Minor support for this work was from: 1. Unrestricted research support was received under a CSL Behring Foundation Hemophilia grant: "Do Non-Synonymous Single Nucleotide Polymorphisms in Factor VIII Lead to T-Cell Responses and Subsequent Inhibitor Development in Black Hemophilia A Patients?" (PI: KP Pratt), funder: CSL Behring Foundation for Research and Advancement of Patient Health, http://www.cslbehringfoundation.com/.2. Unrestricted research support was received from a Bayer Healthcare LLC grant: "Repository for Human HLA-restricted T-Cell Clones" (PI: KP Pratt), funder: Bayer HealthCare LLC, http://grants-contributions.bayerweb.com/en/home/index. php, 800 Dwight Way, Berkeley, California 94710. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The authors have the following interests. Dr's. Pratt and Lewis are inventors on a patent describing the SPR methodology described in this study. Dr. Pratt received travel support from GE Health Sciences to present preliminary SPR studies at the 2011 DiPia meeting in Boston, Massachusetts. This study was partly funded by Bayer HealthCare LLC. The authors thank Dr. Jason Schuman (GE Health Sciences) for technical advice and Bill Church (Green Mountain Antibodies, Burlington, Vermont) for donations of monoclonal antibodies. Drs. Lewis and Pratt are inventors on the following patent: International Patent Application No. PCT/US2012/61/553, 660, Title: Antibody Response Phenotyping, Filed: October 31, 2012, Inventors: Kathleen Pratt, PhD; Kenneth Lewis, PhD. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. NR 43 TC 6 Z9 6 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 8 PY 2013 VL 8 IS 5 AR e61120 DI 10.1371/journal.pone.0061120 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 145YI UT WOS:000319055600009 PM 23667433 ER PT J AU Lobsien, D Dreyer, AY Stroh, A Boltze, J Hoffmann, KT AF Lobsien, Donald Dreyer, Antje Y. Stroh, Albrecht Boltze, Johannes Hoffmann, Karl-Titus TI Imaging of VSOP Labeled Stem Cells in Agarose Phantoms with Susceptibility Weighted and T2*Weighted MR Imaging SO PLOS ONE LA English DT Article ID IRON-OXIDE PARTICLES; IN-VIVO; CLINICAL-APPLICATIONS; ISCHEMIC-STROKE; BRAIN; TRACKING; NANOPARTICLES; RAT; GUIDELINES; MANAGEMENT AB Objective: This study aimed to evaluate the detectability of stem cells labeled with very small iron oxide particles (VSOP) at 3T with susceptibility weighted (SWI) and T2* weighted imaging as a methodological basis for subsequent examinations in a large animal stroke model (sheep). Materials and Methods: We examined ovine mesenchymal stem cells labeled with VSOP in agarose layer phantoms. The experiments were performed in 2 different groups, with quantities of 0-100,000 labeled cells per layer. 15 different SWI-and T2*-weighted sequences and 3 RF coils were used. All measurements were carried out on a clinical 3T MRI. Images of Group A were analyzed by four radiologists blinded for the number of cells, and rated for detectability according to a four-step scale. Images of Group B were subject to a ROI-based analysis of signal intensities. Signal deviations of more than the 0.95 confidence interval in cell containing layers as compared to the mean of the signal intensity of non cell bearing layers were considered significant. Results: Group A: 500 or more labeled cells were judged as confidently visible when examined with a SWI-sequence with 0.15 mm slice thickness. Group B: 500 or more labeled cells showed a significant signal reduction in SWI sequences with a slice thickness of 0.25 mm. Slice thickness and cell number per layer had a significant influence on the amount of detected signal reduction. Conclusion: 500 VSOP labeled stem cells could be detected with SWI imaging at 3 Tesla using an experimental design suitable for large animal models. C1 [Lobsien, Donald; Hoffmann, Karl-Titus] Univ Hosp Leipzig, Dept Neuroradiol, Leipzig, Germany. [Dreyer, Antje Y.; Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol, Leipzig, Germany. [Dreyer, Antje Y.; Boltze, Johannes] Univ Leipzig, Translat Ctr Regenerat Med, D-04109 Leipzig, Germany. [Stroh, Albrecht] Johannes Gutenberg Univ Mainz, Res Grp Mol Imaging & Optogenet, Inst Microscop Anat & Neurobiol, Focus Program Translat Neurosci, D-55122 Mainz, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Charlestown, MA USA. [Boltze, Johannes] Harvard Univ, Sch Med, Ctr Neurosci, Charlestown, MA USA. RP Lobsien, D (reprint author), Univ Hosp Leipzig, Dept Neuroradiol, Leipzig, Germany. EM donald.lobsien@medizin.uni-leipzig.de NR 40 TC 3 Z9 3 U1 0 U2 17 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 MAY 8 PY 2013 VL 8 IS 5 AR e62644 DI 10.1371/journal.pone.0062644 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 145YI UT WOS:000319055600037 PM 23667503 ER PT J AU Nizar, K Uhlirova, H Tian, PF Saisan, PA Cheng, Q Reznichenko, L Weldy, KL Steed, TC Sridhar, VB MacDonald, CL Cui, JX Gratiy, SL Sakadzic, S Boas, DA Beka, TI Einevoll, GT Chen, J Masliah, E Dale, AM Silva, GA Devor, A AF Nizar, Krystal Uhlirova, Hana Tian, Peifang Saisan, Payam A. Cheng, Qun Reznichenko, Lidia Weldy, Kimberly L. Steed, Tyler C. Sridhar, Vishnu B. MacDonald, Christopher L. Cui, Jianxia Gratiy, Sergey L. Sakadzic, Sava Boas, David A. Beka, Thomas I. Einevoll, Gaute T. Chen, Ju Masliah, Eliezer Dale, Anders M. Silva, Gabriel A. Devor, Anna TI In vivo Stimulus-Induced Vasodilation Occurs without IP3 Receptor Activation and May Precede Astrocytic Calcium Increase SO JOURNAL OF NEUROSCIENCE LA English DT Article ID TRANSGENIC MOUSE MODEL; CEREBRAL-BLOOD-FLOW; HEMODYNAMIC-RESPONSE; NEURONAL-ACTIVITY; NEURAL ACTIVITY; HIPPOCAMPAL ASTROCYTES; SOMATOSENSORY CORTEX; NETWORK ACTIVITY; RAT NEOCORTEX; BRAIN AB Calcium-dependent release of vasoactive gliotransmitters is widely assumed to trigger vasodilation associated with rapid increases in neuronal activity. Inconsistent with this hypothesis, intact stimulus-induced vasodilation was observed in inositol 1,4,5-triphosphate (IP3) type-2 receptor (R2) knock-out (KO) mice, in which the primary mechanism of astrocytic calcium increase-the release of calcium from intracellular stores following activation of an IP3-dependent pathway-is lacking. Further, our results in wild-type (WT) mice indicate that in vivo onset of astrocytic calcium increase in response to sensory stimulus could be considerably delayed relative to the simultaneously measured onset of arteriolar dilation. Delayed calcium increases in WT mice were observed in both astrocytic cell bodies and perivascular endfeet. Thus, astrocytes may not play a role in the initiation of blood flow response, at least not via calcium-dependent mechanisms. Moreover, an increase in astrocytic intracellular calcium was not required for normal vasodilation in the IP3R2-KO animals. C1 [Nizar, Krystal; Steed, Tyler C.] Univ Calif San Diego, Grad Program Neurosci, La Jolla, CA 92093 USA. [Uhlirova, Hana; Gratiy, Sergey L.; Dale, Anders M.; Devor, Anna] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Tian, Peifang; Saisan, Payam A.; Cheng, Qun; Reznichenko, Lidia; Weldy, Kimberly L.; Beka, Thomas I.; Masliah, Eliezer; Dale, Anders M.; Devor, Anna] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Sridhar, Vishnu B.; MacDonald, Christopher L.; Cui, Jianxia; Silva, Gabriel A.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Chen, Ju] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Silva, Gabriel A.] Univ Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USA. [Tian, Peifang] John Carroll Univ, Dept Phys, University Hts, OH 44118 USA. [Sakadzic, Sava; Boas, David A.; Devor, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Beka, Thomas I.; Einevoll, Gaute T.] Norwegian Univ Life Sci, Dept Math Sci & Technol, CIGENE, N-1432 As, Norway. RP Devor, A (reprint author), 9500 Gilman Dr,MC 0624, La Jolla, CA 92093 USA. EM adevor@ucsd.edu RI Uhlirova, Hana/E-2702-2012; Chen, Ju/E-5579-2011 FU National Institute of Neurological Disorders and Stroke [NS051188, NS057198, NS057476, NS055104, NS054736]; National Institute of Biomedical Imaging and Bioengineering [EB00790, EB009118]; American Heart Association [11SDG7600037]; European Regional Development Fund [Centre for Integrative Genetics] [CZ.1.05/1.1.00/02.0068]; John Carroll University (JCU) Monville's fund grant; JCU Summer Research Fellowship FX We gratefully acknowledge support from the National Institute of Neurological Disorders and Stroke (Grants NS051188 and NS057198 to A.D., NS057476 and NS055104 to D.A.B., and NS054736 to G.A.S.), National Institute of Biomedical Imaging and Bioengineering (Grant EB00790 to A.M.D. and Grant EB009118 to A.D.), American Heart Association (Grant 11SDG7600037 to S.S.), European Regional Development Fund [Centre for Integrative Genetics (CZ.1.05/1.1.00/02.0068) to H.U.], John Carroll University (JCU) Monville's fund grant, and JCU Summer Research Fellowship to P.T. NR 72 TC 73 Z9 74 U1 1 U2 17 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 MAY 8 PY 2013 VL 33 IS 19 BP 8411 EP 8422 DI 10.1523/JNEUROSCI.3285-12.2013 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 142CZ UT WOS:000318775200029 PM 23658179 ER PT J AU Hasegawa, K Hiraide, A Brown, DFM AF Hasegawa, Kohei Hiraide, Atsushi Brown, David F. M. TI Prehospital Airway Management for Out-of-Hospital Cardiac Arrest Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ENDOTRACHEAL INTUBATION C1 [Hasegawa, Kohei; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hiraide, Atsushi] Kinki Univ, Fac Med, Dept Acute Med, Osaka, Japan. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM khasegawa1@partners.org NR 4 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 8 PY 2013 VL 309 IS 18 BP 1889 EP 1890 DI 10.1001/jama.2013.3107 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 138AZ UT WOS:000318481900016 PM 23652515 ER PT J AU Ecker, J AF Ecker, Jeffrey TI Elective Cesarean Delivery on Maternal Request SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PLANNED VAGINAL BIRTH; TERM BREECH TRIAL; PREGNANT-WOMEN; SECTION; OUTCOMES; MODE; STILLBIRTH; CLINICIAN; MORBIDITY AB Importance Some pregnant women prefer cesarean delivery and request it without maternal or fetal indication rather than proceeding with a plan for vaginal delivery. Objective To review approaches for counseling women who ask for cesarean delivery without maternal or fetal indication (known as cesarean delivery on maternal request [CDMR]). Evidence Review An Agency for Healthcare Research and Quality evidence report of studies published after 1990, a 2006 National Institutes of Health state-of-the-science conference report, and published literature were examined. Findings The prevalence of CDMR in the United States is not precisely known but probably occurs in less than 3% of all deliveries. Most practicing obstetricians have received requests for CDMR from patients. Compared with a plan for vaginal delivery, CDMR may be associated with lower rates of hemorrhage, maternal incontinence, and rare but serious neonatal outcomes. However, CDMR is associated with a higher risk of neonatal respiratory morbidity. Adverse consequences of CDMR may be manifested only in future pregnancies. Repeated cesarean deliveries have higher rates of operative complications, placental abnormalities such as placenta previa and accreta, and consequent gravid hysterectomy. Conclusions and Relevance There is no immediate expectation for CDMR to reduce the health risks of mothers or infants. Accordingly, counseling and decisions regarding CDMR should be made after considering a woman's full reproductive plans. JAMA. 2013;309(18):1930-1936 www.jama.com C1 [Ecker, Jeffrey] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Ecker, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Founders 420A, Boston, MA 02114 USA. EM jecker@partners.org NR 35 TC 24 Z9 25 U1 2 U2 15 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 MAY 8 PY 2013 VL 309 IS 18 BP 1930 EP 1936 DI 10.1001/jama.2013.3982 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 138AZ UT WOS:000318481900028 PM 23652524 ER PT J AU Raitt, MH AF Raitt, Merritt H. TI Reducing Shocks and Improving Outcomes With Implantable Defibrillators SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CARDIOVERTER-DEFIBRILLATORS; HEART-FAILURE; THERAPY; MORTALITY C1 [Raitt, Merritt H.] Portland VA Med Ctr, Portland, OR USA. [Raitt, Merritt H.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. RP Raitt, MH (reprint author), Portland VA Med Ctr, P-3 CARD,3710 SW US Vet Rd, Portland, OR 97239 USA. EM merritt.raitt@va.gov OI Raitt, Merritt/0000-0001-5638-7732 NR 13 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 8 PY 2013 VL 309 IS 18 BP 1937 EP 1938 DI 10.1001/jama.2013.5561 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 138AZ UT WOS:000318481900029 PM 23652525 ER PT J AU Tchkonia, T Thomou, T Zhu, Y Karagiannides, I Pothoulakis, C Jensen, MD Kirkland, JL AF Tchkonia, Tamara Thomou, Thomas Zhu, Yi Karagiannides, Iordanes Pothoulakis, Charalabos Jensen, Michael D. Kirkland, James L. TI Mechanisms and Metabolic Implications of Regional Differences among Fat Depots SO CELL METABOLISM LA English DT Review ID HUMAN ADIPOSE-TISSUE; INDUCED INSULIN-RESISTANCE; ACTIVATED RECEPTOR-GAMMA; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; BODY-FAT; CELLULAR SENESCENCE; HUMAN PREADIPOCYTES; ACID-METABOLISM; VISCERAL FAT AB Fat distribution is closely linked to metabolic disease risk. Distribution varies with sex, genetic background, disease state, certain drugs and hormones, development, and aging. Preadipocyte replication and differentiation, developmental gene expression, susceptibility to apoptosis and cellular senescence, vascularity, inflammatory cell infiltration, and adipokine secretion vary among depots, as do fatty-acid handling and mechanisms of enlargement with positive-energy and loss with negative-energy balance. How interdepot differences in these molecular, cellular, and pathophysiological properties are related is incompletely understood. Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question. C1 [Tchkonia, Tamara; Zhu, Yi; Kirkland, James L.] Mayo Clin, Robert & Arlene Kogod Ctr Aging, Rochester, MN 55905 USA. [Jensen, Michael D.] Mayo Clin, Endocrine Res Unit, Rochester, MN 55905 USA. [Thomou, Thomas] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Karagiannides, Iordanes; Pothoulakis, Charalabos] Univ Calif Los Angeles, Inflammatory Bowel Dis Ctr, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. RP Jensen, MD (reprint author), Mayo Clin, Endocrine Res Unit, Rochester, MN 55905 USA. EM jensen@mayo.edu; kirkland.james@mayo.edu RI Kirkland, James/F-9159-2016 FU NIH [AG41122, AG13925, AG31736, DK50456, DK40484, DK45343, DK47343, DK60729, DK86150]; Noaber Medical Foundation; Ellison Medical Foundation; Broad Medical Foundation; Crohn's and Colitis Foundation of America FX The authors are grateful for the administrative support of L. Wadum and J. Armstrong. This work was funded by NIH grants AG41122 (J. K.), AG13925 (J. K.), AG31736 (J. K.), DK50456 (J. K. and M. D. J.), DK40484 (M. D. J.), DK45343 (M. D. J.), DK47343 (C. P.), DK60729 (C. P.), and DK86150 (C. P.); the Noaber, Ellison, and Broad Medical Foundations; and the Crohn's and Colitis Foundation of America. NR 132 TC 110 Z9 114 U1 3 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD MAY 7 PY 2013 VL 17 IS 5 BP 644 EP 656 DI 10.1016/j.cmet.2013.03.008 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 242TU UT WOS:000326266000007 PM 23583168 ER PT J AU Xie, H Hou, S Jiang, J Sekutowicz, M Kelly, J Bacskai, BJ AF Xie, Hong Hou, Steven Jiang, Jun Sekutowicz, Maria Kelly, Jonathan Bacskai, Brian J. TI Rapid cell death is preceded by amyloid plaque-mediated oxidative stress SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE in vivo imaging; reduction-oxidation sensitive GFP ID GREEN FLUORESCENT PROTEIN; ANTIOXIDANT ENZYME-ACTIVITY; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; IN-VIVO; TRANSGENIC MICE; MULTIPHOTON MICROSCOPY; INCREASED PEROXIDATION; MITOCHONDRIAL-DNA; BETA-PLAQUES AB Neuronal loss is the ultimate outcome in a variety of neurodegenerative diseases and central nerve system disorders. Understanding the sequelae of events that leads to cell death would provide insight into neuroprotective approaches. We imaged neurons in the living brain of a mouse model of Alzheimer's disease that overexpresses mutant human amyloid precursor protein and presenilin 1 and followed the death of individual neurons in real time. This mouse model exhibited limited neurodegeneration and atrophy, but we were able to identify a small fraction of vulnerable cells that would not have been detectable by using standard approaches. By exploiting a genetically encoded reporter of oxidative stress, we identified susceptible neurons by their increased redox potential. The oxidative stress was most dramatic in neurites near plaques, propagated to cell bodies, and preceded activation of caspases that led to cell death within 24 h. Thus, local oxidative stress surrounding plaques contributes to long-range toxicity and selective neuronal death in Alzheimer's disease. C1 [Xie, Hong; Hou, Steven; Sekutowicz, Maria; Kelly, Jonathan; Bacskai, Brian J.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Xie, Hong; Jiang, Jun] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM bbacskai@partners.org FU National Institutes of Health [AG024688, EB000768, NCSF31100776] FX We thank James Remington (University of Oregon) for providing the roGFP construct (proGFP-N1). This study was supported by National Institutes of Health Grants AG024688 (to B.J.B.), EB000768 (to B.J.B.), and NCSF31100776 (to H.X.). NR 29 TC 37 Z9 37 U1 2 U2 30 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 7 PY 2013 VL 110 IS 19 BP 7904 EP 7909 DI 10.1073/pnas.1217938110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 149NP UT WOS:000319327700082 PM 23610434 ER PT J AU Desai, SP Bhatia, SN Toner, M Irimia, D AF Desai, Salil P. Bhatia, Sangeeta N. Toner, Mehmet Irimia, Daniel TI Mitochondrial Localization and the Persistent Migration of Epithelial Cancer cells SO BIOPHYSICAL JOURNAL LA English DT Article ID AXONAL-TRANSPORT; BREAST-CANCER; METASTASIS; INVASION; TUMORS; HETEROGENEITY; REORIENTATION; MICROTUBULES; TRAFFICKING; MACROPHAGES AB During cancer cell invasion, faster moving cancer cells play a dominant role by invading further and metastasizing earlier. Despite the importance of these outlier cells, the source of heterogeneity in their migratory behavior remains poorly understood. Here, we show that anterior localization of mitochondria, in between the nucleus and the leading edge of migrating epithelial cancer cells, correlates with faster migration velocities and increased directional persistence. The asymmetry of mitochondrial localization along the axis of migration is absent during spontaneous cell migration on two-dimensional surfaces and only occurs in the presence of chemical attractant cues or in conditions of mechanical confinement. Moreover, perturbing the asymmetric distribution of mitochondria within migrating cells by interfering with mitochondria! fusion (opa-1) or fission (drp-1) proteins, significantly reduces the number of cells with anterior localization of mitochondria and significantly decreases the velocity and directional persistence of the fastest moving cells. We also observed similar changes after perturbing the linkage between mitochondria and microtubules by the knockdown of mitochondrial rhoGTPase-1 (miro-1). Taken together, the changes in migration velocity and directional persistence in cells with anterior-localized mitochondria could account for an order of magnitude differences in invasive abilities between cells from otherwise homogenous cell populations. C1 [Desai, Salil P.; Bhatia, Sangeeta N.; Toner, Mehmet] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Desai, Salil P.; Toner, Mehmet; Irimia, Daniel] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bhatia, Sangeeta N.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Irimia, D (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM dirimia@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU ECOR MGH-MIT Fellowship in Translational Medicine; National Institutes of Health [CA135601, GM092840, EB002503] FX This work was supported by the ECOR MGH-MIT Fellowship in Translational Medicine and National Institutes of Health grants CA135601, GM092840, and EB002503. S.N.B. is a Howard Hughes Investigator. NR 36 TC 40 Z9 41 U1 5 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY 7 PY 2013 VL 104 IS 9 BP 2077 EP 2088 DI 10.1016/j.bpj.2013.03.025 PG 12 WC Biophysics SC Biophysics GA 141VJ UT WOS:000318754300029 PM 23663851 ER PT J AU Mayr, M Watkins, MT AF Mayr, Manuel Watkins, Michael T. TI Endothelial Seeding for Abdominal Aortic Aneurysms Lessons Learned From the Past and Present SO CIRCULATION LA English DT Editorial Material DE Editorials; aortic aneurysm, abdominal; endothelium; extracellular matrix; growth factor; inflammation ID FIBROBLAST-GROWTH-FACTOR; EXTRACELLULAR-MATRIX; ARTERIAL PROSTHESES; PROTEOMIC ANALYSIS; PROGENITOR-CELL; GRAFTS; PROGRESSION; SURFACES; HEPARIN; MARKERS C1 [Mayr, Manuel] Kings Coll London, British Heart Fdn Ctr, Div Cardiovasc, London WC2R 2LS, England. [Watkins, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Ste 440, Boston, MA 02114 USA. EM mtwatkins@partners.org OI Mayr, Manuel/0000-0002-0597-829X FU British Heart Foundation [FS/13/2/29892, PG/10/61/28498] NR 29 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 7 PY 2013 VL 127 IS 18 BP 1847 EP 1849 DI 10.1161/CIRCULATIONAHA.113.002573 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140VU UT WOS:000318685200007 PM 23572501 ER PT J AU Mega, JL Braunwald, E Murphy, SA Plotnikov, AN Burton, P Kiss, RG Parkhomenko, A Tendera, M Widimsky, P Gibson, CM AF Mega, Jessica L. Braunwald, Eugene Murphy, Sabina A. Plotnikov, Alexei N. Burton, Paul Kiss, Robert Gabor Parkhomenko, Alexander Tendera, Michal Widimsky, Petr Gibson, C. Michael TI Rivaroxaban in Patients Stabilized After a ST-Segment Elevation Myocardial Infarction Results From the ATLAS ACS-2-TIMI-51 Trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction-51) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DOUBLE-BLIND; INTERVENTION; CLOPIDOGREL; DISEASE AB Objectives The present analysis reports on the pre-specified subgroup of ST-elevation myocardial infarction (STEMI) patients, in whom anticoagulant therapy has been of particular interest. Background In ATLAS ACS-2-TIMI-51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction-51), rivaroxaban reduced cardiovascular events across the spectrum of acute coronary syndrome (ACS). Methods Seven thousand eight hundred seventeen patients in ATLAS ACS-2-TIMI 51 presented with a STEMI. After being stabilized (1 to 7 days), they underwent randomization to twice daily rivaroxaban 2.5 mg, rivaroxaban 5 mg, or placebo. Data are presented as 2-year Kaplan-Meier rates, and for intention-to-treat (ITT) and modified ITT (mITT) analyses. Results Among STEMI patients, rivaroxaban reduced the primary efficacy endpoint of cardiovascular death, myocardial infarction, or stroke, compared with placebo (ITT: 8.4% vs. 10.6%, hazards ratio [HR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.97, p = 0.019; mITT: 8.3% vs. 9.7%, HR: 0.85, 95% CI: 0.70 to 1.03, p = 0.09). This reduction emerged by 30 days (ITT and mITT: 1.7% vs. 2.3%, p = 0.042) and was evident in analyses that included events while patients received background dual antiplatelet therapies (ITT: 7.9% vs. 11.9%, p = 0.010; mITT: 7.7% vs. 10.1%, p = 0.061). In terms of the individual doses, rivaroxaban 2.5 mg reduced cardiovascular death (ITT: 2.5% vs. 4.2%, p = 0.006; mITT: 2.2% vs. 3.9%, p = 0.006), which was not seen with 5 mg of rivaroxaban. Rivaroxaban versus placebo increased non-coronary artery bypass grafting Thrombolysis In Myocardial Infarction major bleeding (2.2% vs. 0.6%, p < 0.001) and intracranial hemorrhage (0.6% vs. 0.1%, p = 0.015) without a significant increase in fatal bleeding (0.2% vs. 0.1%, p = 0.51). Conclusions In patients with a recent STEMI, rivaroxaban reduced cardiovascular events. This benefit emerged early and persisted during continued treatment with background antiplatelet therapies. Rivaroxaban compared with placebo increased the rate of major bleeding, but there was no significant increase in fatal bleeding. (An Efficacy and Safety Study for Rivaroxaban in Patients With Acute Coronary Syndrome; NCT00809965) 2013 by the American College of Cardiology Foundation C1 [Mega, Jessica L.; Braunwald, Eugene; Murphy, Sabina A.; Gibson, C. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Plotnikov, Alexei N.; Burton, Paul] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Kiss, Robert Gabor] Mil Hosp, Dept Cardiol, Budapest, Hungary. [Parkhomenko, Alexander] Natl Sci Ctr, Inst Cardiol, Kiev, Ukraine. [Tendera, Michal] Med Univ Silesia, Katowice, Poland. [Widimsky, Petr] Charles Univ Prague, Prague, Czech Republic. [Gibson, C. Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02215 USA. RP Mega, JL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jmega@partners.org RI Widimsky, Petr/P-8088-2016 OI Widimsky, Petr/0000-0001-5686-7752 FU Johnson Johnson; Johnson & Johnson Pharmaceutical Research and Development; Bayer Healthcare; Bristol-Myers Squibb/sanofi-aventis; Daiichi Sankyo; Eli Lilly; Abbott; AstraZeneca; Amgen; GlaxoSmithKline; Merck (SPRI); Pfizer; Roche (Diagnostics); sanofi-aventis FX From the *TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; dagger Johnson & Johnson Pharmaceutical Research and Development, Raritan, New Jersey; double dagger Department of Cardiology, Military Hospital, Budapest, Hungary; National Scientific Center Institute of Cardiology, Kiev, Ukraine; parallel to Medical University of Silesia, Katowice, Poland; Charles University, Prague, Czech Republic; and the #Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. This study was supported by research grants from Johnson & Johnson Pharmaceutical Research and Development and Bayer Healthcare. Dr. Mega has received research grant support from Johnson & Johnson, Bayer Healthcare, Bristol-Myers Squibb/sanofi-aventis, Daiichi Sankyo, Eli Lilly; research supplies from Accumetrics and Nanosphere; and honoraria for consulting from American Genomics, Boehringer Ingelheim, Janssen, and Merck. Dr. Braunwald has received research grant support from Abbott, AstraZeneca, Amgen, Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck (SPRI), Pfizer, Roche (Diagnostics), sanofi-aventis, Johnson & Johnson; and has been a consultant for Merck (no compensation), Amorcyte, Daiichi Sankyo, The Medicines Co., Ikaria, CardioRentis, sanofi-aventis, and CVRx (no compensation). Ms. Murphy has received research grant support from Bayer Healthcare, Johnson & Johnson; and honoraria for consulting from Amarin Pharmaceuticals, and Eli Lilly and Company. Drs. Kiss, Parkhomenko, Tendera, and Widimsky have received research grant support from Johnson & Johnson and Bayer Healthcare. Drs. Burton and Plotnikov are employed by and own stock in Johnson & Johnson. Dr. Gibson has received research grant support from Johnson & Johnson, Bayer Healthcare, Bristol-Myers Squibb; honoraria for consulting from Portola Pharmaceuticals, sanofi-aventis, The Medicines Co., Daiichi Sankyo Company, Eli Lilly and Company, Biogen IDEC, Bristol-Myers Squibb, Ischemix, Inc., Johnson & Johnson, Bayer Healthcare, GlaxoSmithKline, Merck Schering Plough, Ortho McNeil, Medicure, Inc., Archemix, Inc., Genentech, Inc., and Boeringer Ingelheim; payment for lectures from Daiichi Sankyo Company, Eli Lilly and Company, Medicines Co.; and payment for development of educational presentations from Daiichi Sankyo Company and Eli Lilly and Company. NR 8 TC 41 Z9 41 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 7 PY 2013 VL 61 IS 18 BP 1853 EP 1859 DI 10.1016/j.jacc.2013.01.066 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 139TL UT WOS:000318607400004 PM 23500262 ER PT J AU Boutchko, R Sitek, A Gullberg, GT AF Boutchko, R. Sitek, A. Gullberg, G. T. TI Practical implementation of tetrahedral mesh reconstruction in emission tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID CARDIAC SPECT; POINT CLOUD; PHANTOM; MODEL AB This paper presents a practical implementation of image reconstruction on tetrahedral meshes optimized for emission computed tomography with parallel beam geometry. Tetrahedral mesh built on a point cloud is a convenient image representation method, intrinsically three-dimensional and with a multi-level resolution property. Image intensities are defined at the mesh nodes and linearly interpolated inside each tetrahedron. For the given mesh geometry, the intensities can be computed directly from tomographic projections using iterative reconstruction algorithms with a system matrix calculated using an exact analytical formula. The mesh geometry is optimized for a specific patient using a two stage process. First, a noisy image is reconstructed on a finely-spaced uniform cloud. Then, the geometry of the representation is adaptively transformed through boundary-preserving node motion and elimination. Nodes are removed in constant intensity regions, merged along the boundaries, and moved in the direction of the mean local intensity gradient in order to provide higher node density in the boundary regions. Attenuation correction and detector geometric response are included in the system matrix. Once the mesh geometry is optimized, it is used to generate the final system matrix for ML-EM reconstruction of node intensities and for visualization of the reconstructed images. In dynamic PET or SPECT imaging, the system matrix generation procedure is performed using a quasi-static sinogram, generated by summing projection data from multiple time frames. This system matrix is then used to reconstruct the individual time frame projections. Performance of the new method is evaluated by reconstructing simulated projections of the NCAT phantom and the method is then applied to dynamic SPECT phantom and patient studies and to a dynamic microPET rat study. Tetrahedral mesh-based images are compared to the standard voxel-based reconstruction for both high and low signal-to-noise ratio projection datasets. The results demonstrate that the reconstructed images represented as tetrahedral meshes based on point clouds offer image quality comparable to that achievable using a standard voxel grid while allowing substantial reduction in the number of unknown intensities to be reconstructed and reducing the noise. C1 [Boutchko, R.; Gullberg, G. T.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Sitek, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Boutchko, R (reprint author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, 1 Cyclotron Rd,MS 55R0121, Berkeley, CA 94720 USA. EM rbuchko@lbl.gov OI Sitek, Arkadiusz/0000-0002-0677-4002 FU National Institutes of Health [R01-EB07219, R01-HL50663, R01-EB00121]; Office of Science, Office of Biological and Environmental Research of the US Department of Energy [DE-AC02-05CH11231] FX The work presented in this paper has been funded in part by National Institutes of Health grants R01-EB07219, R01-HL50663 and R01-EB00121 and by the Director, Office of Science, Office of Biological and Environmental Research of the US Department of Energy under contract no. DE-AC02-05CH11231. The authors would like to thank Dr Bryan Reutter (formerly LBNL), Dr Youngho Seo (UCSF) and Mr Andrew Hernandez (formerly UCSF) for their help in acquiring and preparing the experimental data and Dr W Paul Segars, Department of Bioengineering, Duke University for providing the digital NCAT phantom. NR 18 TC 5 Z9 5 U1 0 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2013 VL 58 IS 9 BP 3001 EP 3022 DI 10.1088/0031-9155/58/9/3001 PG 22 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 125ZD UT WOS:000317579900017 PM 23588373 ER PT J AU Krishnan, K Duncan, MJ AF Krishnan, Karthik Duncan, Margaret J. TI Role of Sodium in the RprY-Dependent Stress Response in Porphyromonas gingivalis SO PLOS ONE LA English DT Article ID BACTEROIDES-FRAGILIS; ESCHERICHIA-COLI; EPITHELIAL-CELLS; OXIDATIVE STRESS; GENE-EXPRESSION; POLYHYDROXYALKANOATES; IDENTIFICATION; PERIODONTITIS; PROTEIN; OPERON AB Porphyromonas gingivalis is a Gram-negative oral anaerobe which is strongly associated with periodontal disease. Environmental changes in the gingival sulcus trigger the growth of P. gingivalis and a concurrent shift from periodontal health to disease. Bacteria adjust their physiology in response to environmental changes and gene regulation by two-component phospho-relay systems is one mechanism by which such adjustments are effected. In P. gingivalis RprY is an orphan response regulator and previously we showed that the RprY regulon included genes associated with oxidative stress and sodium metabolism. The goals of the present study were to identify environmental signals that induce rprY and clarify the role of the regulator in the stress response. In Escherichia coli an RprY-LacZ fusion protein was induced in sodium-depleted medium and a P. gingivalis rprY mutant was unable to grow in similar medium. By several approaches we established that sodium depletion induced up-regulation of genes involved in oxidative stress. In addition, we demonstrated that RprY interacted directly with the promoters of several molecular chaperones. Further, both genetic and transcription data suggest that the regulator acts as a repressor. We conclude that RprY is one of the regulators that controls stress responses in P. gingivalis, possibly by acting as a repressor since an rprY mutant showed a superstress reponse in sodium-depleted medium which we propose inhibited growth. C1 [Krishnan, Karthik; Duncan, Margaret J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Krishnan, Karthik] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Microbiol, Cambridge, MA USA. EM mduncan@forsyth.org FU National Institutes of Health [R01-DE015931] FX This work was supported by National Institutes of Health grant R01-DE015931 (MJD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 2 Z9 2 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 6 PY 2013 VL 8 IS 5 AR e63180 DI 10.1371/journal.pone.0063180 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177QL UT WOS:000321390200045 PM 23671672 ER PT J AU Kiviranta, R Yamana, K Saito, H Ho, DK Laine, J Tarkkonen, K Nieminen-Pihala, V Hesse, E Correa, D Maatta, J Tessarollo, L Rosen, ED Horne, WC Jenkins, NA Copeland, NG Warming, S Baron, R AF Kiviranta, Riku Yamana, Kei Saito, Hiroaki Ho, Daniel K. Laine, Julius Tarkkonen, Kati Nieminen-Pihala, Vappu Hesse, Eric Correa, Diego Maatta, Jorma Tessarollo, Lino Rosen, Evan D. Horne, William C. Jenkins, Nancy A. Copeland, Neal G. Warming, Soren Baron, Roland TI Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ZINC-FINGER PROTEIN; KAPPA-B LIGAND; OSTEOBLAST DIFFERENTIATION; OSTEOCLAST DIFFERENTIATION; RECEPTOR ACTIVATOR; CELL-FACTOR; GENE-EXPRESSION; BETA-CATENIN; IN-VITRO; PROGENITORS AB Bone homeostasis is maintained by the coupled actions of hematopoietic bone-resorbing osteoclasts (OCs) and mesenchymal bone-forming osteoblasts (OBs). Here we identify early B cell factor 1 (Ebf1) and the transcriptional coregulator Zfp521 as components of the machinery that regulates bone homeostasis through coordinated effects in both lineages. Deletion of Zfp521 in OBs led to impaired bone formation and increased OB-dependent osteoclastogenesis (OC-genesis), and deletion in hematopoietic cells revealed a strong cell-autonomous role for Zfp521 in OC progenitors. In adult mice, the effects of Zfp521 were largely caused by repression of Ebf1, and the bone phenotype of Zfp521(+/-) mice was rescued in Zfp521(+/-):Ebf1(+/-) mice. Zfp521 interacted with Ebf1 and repressed its transcriptional activity. Accordingly, deletion of Zfp521 led to increased Ebf1 activity in OBs and OCs. In vivo, Ebf1 overexpression in OBs resulted in suppressed bone formation, similar to the phenotype seen after OB-targeted deletion of Zfp521. Conversely, Ebf1 deletion led to cell-autonomous defects in both OB-dependent and cell-intrinsic OC-genesis, a phenotype opposite to that of the Zfp521 knockout. Thus, we have identified the interplay between Zfp521 and Ebf1 as a novel rheostat for bone homeostasis. C1 [Kiviranta, Riku; Yamana, Kei; Saito, Hiroaki; Ho, Daniel K.; Hesse, Eric; Correa, Diego; Horne, William C.; Baron, Roland] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Kiviranta, Riku; Yamana, Kei; Saito, Hiroaki; Ho, Daniel K.; Hesse, Eric; Correa, Diego; Horne, William C.; Baron, Roland] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. [Rosen, Evan D.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Kiviranta, Riku; Yamana, Kei; Saito, Hiroaki; Ho, Daniel K.; Hesse, Eric; Correa, Diego; Horne, William C.; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Kiviranta, Riku; Laine, Julius; Tarkkonen, Kati; Nieminen-Pihala, Vappu] Univ Turku, Turku Univ Hosp, Dept Med Biochem & Genet, FI-20520 Turku, Finland. [Kiviranta, Riku; Laine, Julius; Tarkkonen, Kati; Nieminen-Pihala, Vappu] Univ Turku, Turku Univ Hosp, Dept Med, FI-20520 Turku, Finland. [Maatta, Jorma] Univ Turku, Turku Univ Hosp, Turku Ctr Dis Modeling, FI-20520 Turku, Finland. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, Ft Detrick, MD 21702 USA. [Jenkins, Nancy A.; Copeland, Neal G.] Methodist Hosp, Res Inst, Houston, TX 77030 USA. [Warming, Soren] Genentech Inc, San Francisco, CA 94080 USA. RP Baron, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. EM roland_baron@hsdm.harvard.edu OI Maatta, Jorma/0000-0001-8752-6862 FU National Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR048218, AR57769]; Academy of Finland [10945, 120116]; Gideon and Sevgi Rodan Fellowship from the International Bone and Mineral Society; Finnish Cultural Foundation; Emil Aaltonen Foundation; Sigrid Juselius Foundation FX This work was supported in part by National Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin Diseases grants to R. Baron (AR048218 and AR57769). Additional support was provided by the Academy of Finland (Projects 10945 and 120116 to R. Kiviranta), the Gideon and Sevgi Rodan Fellowship from the International Bone and Mineral Society (to R. Kiviranta and E. Hesse), the Finnish Cultural Foundation (to R. Kiviranta), the Emil Aaltonen Foundation (to R. Kiviranta), and the Sigrid Juselius Foundation (R. Kiviranta). NR 48 TC 16 Z9 16 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 6 PY 2013 VL 210 IS 5 BP 969 EP 985 DI 10.1084/jem.20121187 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 139UG UT WOS:000318609700008 PM 23569325 ER PT J AU Harrison, WJ Retell, JD Remington, RW Mattingley, JB AF Harrison, William J. Retell, James D. Remington, Roger W. Mattingley, Jason B. TI Visual Crowding at a Distance during Predictive Remapping SO CURRENT BIOLOGY LA English DT Article ID SACCADIC EYE-MOVEMENTS; OBJECT RECOGNITION; FRONTAL-CORTEX; ATTENTION; REPRESENTATION; SIGNALS; VISION; MOTION; FIELD AB When we move our eyes, images of objects are displaced on the retina, yet the visual world appears stable. Oculomotor activity just prior to an eye movement contributes to perceptual stability by providing information about the predicted location of a relevant object on the retina following a saccade [1, 2]. It remains unclear, however, whether an object's features are represented at the remapped location. Here, we exploited the phenomenon of visual crowding [3] to show that presaccadic remapping preserves the elementary features of objects at their predicted postsaccadic locations. Observers executed an eye movement and identified a letter probe flashed just before the saccade. Flanking stimuli were flashed around the location that would be occupied by the probe immediately following the saccade. Despite being positioned in the opposite visual field to the probe, these flankers disrupted observers' ability to identify the probe. Crucially, this "remapped crowding" interference was stronger when the flankers were visually similar to the probe than when the flanker and probe stimuli were distinct. Our findings suggest that visual processing at remapped locations is featurally dependent, providing a mechanism for achieving perceptual continuity of objects across saccades. C1 [Harrison, William J.; Retell, James D.; Remington, Roger W.; Mattingley, Jason B.] Univ Queensland, Sch Psychol, St Lucia, Qld 4072, Australia. [Mattingley, Jason B.] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia. RP Harrison, WJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. EM willjharri@gmail.com RI Mattingley, Jason/J-1537-2014; OI Mattingley, Jason/0000-0003-0929-9216; Harrison, William/0000-0002-6408-0359 FU Australian Research Council [DP0666772, FL110100103]; ARC [DP120103721] FX The authors thank Dustin Venini for his help with data collection. This research was supported by an Australian Professorial Fellowship to R.W.R. (DP0666772), an Australian Laureate Fellowship from the Australian Research Council to J.B.M. (FL110100103), and an ARC Discovery Grant to R.W.R. and J.B.M. (DP120103721). The study was approved by The University of Queensland's School of Psychology Ethical Review Committee. NR 37 TC 18 Z9 19 U1 4 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 6 PY 2013 VL 23 IS 9 BP 793 EP 798 DI 10.1016/j.cub.2013.03.050 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 141UB UT WOS:000318750900031 PM 23562269 ER PT J AU Hai, HL Shen, CA Chai, JK Li, HT Yu, YM Li, DW AF Hai Heng-lin Shen Chuan-an Chai Jia-ke Li Hua-tao Yu Yong-ming Li Da-wei TI Quadrilobed superior gluteal artery perforator nap for sacrococcygeal defects SO CHINESE MEDICAL JOURNAL LA English DT Article DE quadrilobed superior gluteal artery perforator flap; sacrococcygeal region; pressure sore; soft tissue defect ID SACRAL PRESSURE SORES; FLAP; RECONSTRUCTION; COVERAGE; REPAIR AB Background Perforator flaps are used extensively in repairing soft tissue defects. Superior gluteal artery perforator flaps are used for repairing sacral defects, but the tension required for direct closure of the donor area after harvesting of relatively large flaps carries a risk of postoperative dehiscence. This research was to investigate a modified superior gluteal artery perforator flap for repairing sacrococcygeal soft tissue defects. Methods From June 2003 to April 2010, we used our newly designed superior gluteal artery perforator flap for repair of sacrococcygeal soft tissue defects in 10 patients (study group). The wound and donor areas were measured, and the flaps were designed accordingly. Wound healing was assessed over a follow-up period of 6-38 months. From January 1998 to February 2003, twelve patients with sacrococcygeal pressure sores were treated with traditional methods, VY advancement flaps or oblong flaps, as control group. Results After debridement, the soft tissue defects ranged from 12 cm x 10 cm to 26 cm x 22 cm (mean 16.3 cm x 13.5 cm). Four patients were treated using right-sided flaps ranging from 15 cm x 11 cm to 25 cm x 20 cm (mean 18.2 cm x 14 cm). Four patients were treated using left-sided flaps, and two were treated using both right- and left-sided flaps. Suction drains were removed on postoperative Days 3-21 (mean 5.9) and sutures were removed on postoperative Days 12-14. Each flap included 1-2 perforators for each of the donor and recipient sites. Donor sites were closed directly. All flaps survived. In eight patients, the wounds healed after single-stage surgery. After further debridement, the wounds of the remaining two patients were considered healed on postoperative Days 26 and 33, respectively. The rate of first intention in the study group (80%, 8/10) significantly increased than that of control group ((25%, 3/12), chi(2)=4.583, P=0.032). Follow-up examinations found that the flaps had a soft texture without ulceration. In the two patients without paraplegia, the range of motion of the hip joints was not affected. Conclusion The use of the quadrilobed superior gluteal artery perforator flap can overcome the disadvantages of traditional perforator flaps and represents an improved approach for repairing soft tissue defects in the sacrococcygeal region. C1 [Hai Heng-lin; Shen Chuan-an; Chai Jia-ke; Li Da-wei] Peoples Liberat Army, Affiliated Hosp 1, Peoples Liberat Army Burn Ctr, Gen Hosp, Beijing 100048, Peoples R China. [Hai Heng-lin; Li Hua-tao] Peoples Liberat Army, Hosp 98, Dept Burns & Plast Surg, Huzhou 313000, Zhejiang, Peoples R China. [Yu Yong-ming] Massachusetts Gen Hosp, Burn Unit, Dept Surg, Boston, MA 02114 USA. [Yu Yong-ming] Shriners Burns Hosp Boston, Boston, MA 02114 USA. RP Shen, CA (reprint author), Peoples Liberat Army, Affiliated Hosp 1, Peoples Liberat Army Burn Ctr, Gen Hosp, Beijing 100048, Peoples R China. EM shenchuanan@yahoo.com FU National Natural Science Foundation of China [30971128] FX This work was supported by a grant from the National Natural Science Foundation of China (No. 30971128). NR 23 TC 0 Z9 0 U1 3 U2 6 PU CHINESE MEDICAL ASSOC PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD MAY 5 PY 2013 VL 126 IS 9 BP 1743 EP 1749 DI 10.3760/cma.j.issn.0366-6999.20130002 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 152JX UT WOS:000319529100026 PM 23652061 ER PT J AU Cassol, E Misra, V Holman, A Kamat, A Morgello, S Gabuzda, D AF Cassol, Edana Misra, Vikas Holman, Alexander Kamat, Anupa Morgello, Susan Gabuzda, Dana TI Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors SO BMC INFECTIOUS DISEASES LA English DT Article DE HIV; HCV; Antiretroviral therapy; Protease inhibitors; Dyslipidemia; Metabolomics; Hepatic dysfunction; Inflammation ID NONALCOHOLIC FATTY LIVER; HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL; SIMPLE NONINVASIVE INDEX; HCV COINFECTED PATIENTS; SERUM FIBROSIS MARKERS; C-VIRUS; INFECTED PATIENTS; BILE-ACIDS; ANTIRETROVIRAL THERAPY AB Background: Metabolic abnormalities are common in HIV-infected individuals on antiretroviral therapy (ART), but the biochemical details and underlying mechanisms of these disorders have not been defined. Methods: Untargeted metabolomic profiling of plasma was performed for 32 HIV patients with low nadir CD4 counts (< 300 cells/ul) on protease inhibitor (PI)-based ART and 20 healthy controls using liquid or gas chromatography and mass spectrometry. Effects of Hepatitis C (HCV) co-infection and relationships between altered lipid metabolites and markers of inflammation, microbial translocation, and hepatic function were examined. Unsupervised hierarchical clustering, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), Random forest, pathway mapping, and metabolite set enrichment analysis (MSEA) were performed using dChip, Metaboanalyst, and MSEA software. Results: A 35-metabolite signature mapping to lipid, amino acid, and nucleotide metabolism distinguished HIV patients with advanced disease on PI-based ART from controls regardless of HCV serostatus (p<0.05, false discovery rate (FDR)<0.1). Many altered lipids, including bile acids, sulfated steroids, polyunsaturated fatty acids, and eicosanoids, were ligands of nuclear receptors that regulate metabolism and inflammation. Distinct clusters of altered lipids correlated with markers of inflammation (interferon-a and interleukin-6), microbial translocation (lipopolysaccharide (LPS) and LPS-binding protein), and hepatic function (bilirubin) (p<0.05). Lipid alterations showed substantial overlap with those reported in non-alcoholic fatty liver disease (NALFD). Increased bile acids were associated with noninvasive markers of hepatic fibrosis (FIB-4, APRI, and YKL-40) and correlated with acylcarnitines, a marker of mitochondrial dysfunction. Conclusions: Lipid alterations in HIV patients receiving PI-based ART are linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that therapeutic strategies attenuating dysregulated innate immune activation and hepatic dysfunction may be beneficial for prevention and treatment of metabolic disorders in HIV patients. C1 [Cassol, Edana; Misra, Vikas; Holman, Alexander; Kamat, Anupa; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Cassol, Edana; Kamat, Anupa; Gabuzda, Dana] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Morgello, Susan] Mt Sinai Med Ctr, Dept Neurol Neurosci & Pathol, New York, NY 10029 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM dana_gabuzda@dfci.harvard.edu FU National Institute on Drug Abuse (NIDA) grant [DP1 DA028994]; Canadian Institutes of Health Research (CIHR); National Institute of Mental Health (NIMH); National Institute of Neurological Disorders and Stroke (NINDS) [U01MH083501, R24MH59724, U01MH083507, R24NS45491, U01MH083500, R24NS38841, U01MH083506, R24MH59745, U01MH083545, N01MH32002, N01MH22005]; Harvard Center for AIDS Research grant [P30 AI060354]; Dana-Farber Cancer Institute/Harvard Center for Cancer Research grant [P30 CA065/6] FX This work was supported by the National Institute on Drug Abuse (NIDA) grant DP1 DA028994 to D.G. E.C. was supported by a fellowship from Canadian Institutes of Health Research (CIHR). NNTC and CHARTER sites were supported by National Institute of Mental Health (NIMH) and National Institute of Neurological Disorders and Stroke (NINDS) (grants U01MH083501, R24MH59724, U01MH083507, R24NS45491, U01MH083500, R24NS38841, U01MH083506, R24MH59745, U01MH083545, N01MH32002, and N01MH22005). Core facilities were supported by the Harvard Center for AIDS Research grant (P30 AI060354) and Dana-Farber Cancer Institute/Harvard Center for Cancer Research grant (P30 CA065/6). NR 97 TC 31 Z9 33 U1 3 U2 41 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD MAY 4 PY 2013 VL 13 AR 203 DI 10.1186/1471-2334-13-203 PG 17 WC Infectious Diseases SC Infectious Diseases GA 147CG UT WOS:000319142300001 PM 23641933 ER PT J AU Corey, KE Misdraji, J Zheng, H Malecki, KM Kneeman, J Gelrud, L Chung, RT AF Corey, Kathleen E. Misdraji, Joseph Zheng, Hui Malecki, Kyle M. Kneeman, Jacob Gelrud, Louis Chung, Raymond T. TI The Absence of Obstructive Sleep Apnea May Protect against Non-Alcoholic Fatty Liver in Patients Undergoing Bariatric Surgery SO PLOS ONE LA English DT Article ID CHRONIC INTERMITTENT HYPOXIA; DISEASE; OBESE; STEATOHEPATITIS; RISK AB Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and its progressive form, steatohepatitis, will be the leading indication for liver transplant by 2020. While risk factors for steatohepatitis have been identified, little work has been performed to identify factors protective against NAFLD development. Aim: This study sought to identify factors predictive of normal liver histology in a bariatric cohort. Methods: Patients undergoing weight loss surgery with liver biopsies at the time of surgery were included. Patients with other causes of chronic liver disease were excluded. Results: One hundred fifty-nine patients were included. Forty-nine patients had normal liver histology and 110 patients had NAFLD. Several previously identified factors associated with normal liver histology were found. Black race was the strongest predictor of the absence of NAFLD with an odds ratio (OR) of 6.8, 95% confidence interval (CI) 2.4-18.9. Low HOMA-IR was also associated with normal histology (OR 1.4, 95% CI 1.03-1.9). In contrast, low HDL was associated with a decreased chance of normal histology (OR 0.38, 95% CI 0.05-0.83). Interestingly, a novel protective factor, the absence of obstructive sleep apnea (OSA) was strongly associated with normal histology (OR 5.6, 95% CI 2.0-16.1). In multivariate regression controlling for BMI, black race, absence of OSA, low HOMA-IR and low ALT independently predicted normal liver histology with an area under the ROC curve of 0.85. Conclusions: Our study confirmed several factors associated with normal liver histology, including black race and identified a novel factor, absence of OSA. Further evaluation of these factors will allow for improved understanding of the pathogenesis of NAFLD. C1 [Corey, Kathleen E.; Malecki, Kyle M.; Kneeman, Jacob; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Corey, Kathleen E.; Zheng, Hui; Gelrud, Louis; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Gelrud, Louis] Bon Secours Richmond Hlth Syst, Dept Internal Med, Richmond, VA USA. RP Corey, KE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM kcorey@partners.org; rtchung@partners.org FU American Association for the Study of Liver Disease Clinical and Translational Research Award; NIH [2T32DK0007191-37, DK078772] FX KEC receives support from the American Association for the Study of Liver Disease Clinical and Translational Research Award. JK receives support from the NIH 2T32DK0007191-37. RTC receives support from NIH DK078772. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 13 TC 6 Z9 6 U1 0 U2 5 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 MAY 3 PY 2013 VL 8 IS 5 AR e62504 DI 10.1371/journal.pone.0062504 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175AS UT WOS:000321202100011 PM 23658732 ER PT J AU Yomogida, K Wu, SL Baravati, B Avendano, C Caldwell, T Maniaci, B Zhu, Y Chu, CQ AF Yomogida, Kentaro Wu, Shili Baravati, Bobby Avendano, Camilo Caldwell, Tom Maniaci, Brian Zhu, Yong Chu, Cong-Qiu TI Cell penetrating recombinant Foxp3 protein enhances Treg function and ameliorates arthritis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Foxp3; T regulatory cells; Arthritis ID REGULATORY T-CELLS; TRANSCRIPTION FACTOR FOXP3; AUTOIMMUNITY; ACTIVATION; GENERATION; EXPRESSION; TOLERANCE; ALLERGY; CD25 AB Foxp3 is the master transcription factor for T regulatory (Treg) cell differentiation and function. This study aimed to test the therapeutic potential of cell penetrating recombinant Foxp3 protein in arthritis. Recombinant Foxp3 protein was fused to a cell penetrating polyarginine (Foxp3-11R) tag to facilitate intracellular transduction. In vitro Foxp3-11R treated CD4(+) T cells showed a 50% increase in suppressive function compared with control protein treated cells. Severity of arthritis in Foxp3-11R treated mice was significantly reduced compared with those treated with a control protein. CD4(+) T cells of lymph nodes and spleen from Foxp3-11R treated mice showed increased levels of Foxp3 expression compared with those of a control protein treated. These results demonstrated that Foxp3-11R can enhance T cell suppressive function and ameliorate experimental arthritis and suggest that cell penetrating recombinant Foxp3 is a potentially useful agent in therapy of arthritis. Published by Elsevier Inc. C1 [Yomogida, Kentaro; Chu, Cong-Qiu] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Yomogida, Kentaro; Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR 97239 USA. [Wu, Shili; Baravati, Bobby; Avendano, Camilo; Caldwell, Tom; Maniaci, Brian; Zhu, Yong] VivoScript Inc, Costa Mesa, CA 92626 USA. RP Chu, CQ (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,OP09, Portland, OR 97239 USA. EM chuc@ohsu.edu FU NIH [AR055254]; Portland VA Medical Center FX This work was supported by a grant from NIH to CQC (AR055254) and Portland VA Medical Center to CQC. NR 24 TC 3 Z9 3 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 3 PY 2013 VL 434 IS 2 BP 263 EP 267 DI 10.1016/j.bbrc.2013.02.114 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 146NW UT WOS:000319098800014 PM 23541572 ER PT J AU Bajunirwe, F Bangsberg, DR Sethi, AK AF Bajunirwe, Francis Bangsberg, David R. Sethi, Ajay K. TI Alcohol use and HIV serostatus of partner predict high-risk sexual behavior among patients receiving antiretroviral therapy in South Western Uganda SO BMC PUBLIC HEALTH LA English DT Article DE High-risk sexual behavior; Antiretroviral treatment; Rural and urban; Uganda ID QUALITY-OF-LIFE; FISHING COMMUNITIES; HOMOSEXUAL-MEN; LAKE VICTORIA; RURAL UGANDA; TRANSMISSION; IMPACT; COHORT; ADULTS; KENYA AB Background: Antiretroviral treatment restores the physical and immunological function for patients with HIV/AIDS and the return of sexual desire. The frequency and correlates of sexual activity among patients receiving ART have not been widely studied. There is concern that widespread availability of ART may result in sexual disinhibition including practice of high-risk sexual behavior. We determined the correlates of sexual activity and high-risk sexual behavior in an ART-treated population in rural and urban Uganda. Methods: We conducted a cross-sectional study among 329 ART-treated adult patients at two hospitals, one located in rural and another in urban western Uganda. We collected data on sexual activity, frequency of condom use, pregnancy, viral load (VL) and CD4. Patients were considered sexually active if they had had sexual intercourse in the last 6 months. Any unprotected sex was considered high-risk sex. A two-stage logistic regression was performed to determine factors associated with sexual activity and high-risk sex among those sexually active. Results: Overall, 222 (67%) patients were women, 138 (41.2%) had been on ART for at least one year, and 168 (51.4%) were sexually active of whom 127 (75.6%) used condoms at the last intercourse. Younger age (<=30 years) (Odds ratio; OR=2.3, 95% CI 1.2, 4.2), higher monthly income (OR=4.1, 95% CI 2.4, 7.4), and being married (OR=22.7, 95% CI 8.2, 62.9) were associated with being sexually active. Undetectable VL, CD4 count and treatment duration were not significantly associated with sexual activity. Among the sexually active, alcohol consumption (OR=3.3, 95% CI 1.2, 9.1) and unknown serostatus of partner (OR=5.8, 95% CI 1.5, 21.4) were significant predictors of high-risk sexual behavior. The frequency of unprotected sex at the last intercourse was 25.9% and 22.1% among the men and women respectively and was not significantly different (p value for chi square test =0.59). Conclusion: Younger persons receiving ART are more likely to be sexually active. ART clients are more likely to engage in unprotected sex when sero-status of partner is unknown or report use of alcohol. Counseling on alcohol use and disclosure of sero-status may be useful in reducing high risk sexual behavior. C1 [Bajunirwe, Francis] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Sethi, Ajay K.] Univ Wisconsin Madison, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. RP Bajunirwe, F (reprint author), Mbarara Univ Sci & Technol, Dept Community Hlth, POB 1410, Mbarara, Uganda. EM fbaj@yahoo.com FU AIDS International Training and Research Program (AITRP) at Case Western Reserve University through the Fogarty International Center (FIC) at the National Institutes of Health [TW00011]; Harvard Global Scholars program FX This study was funded by the AIDS International Training and Research Program (AITRP) at Case Western Reserve University through the Fogarty International Center (FIC) at the National Institutes of Health (TW00011). FB receives support from the Harvard Global Scholars program. NR 38 TC 10 Z9 10 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD MAY 3 PY 2013 VL 13 AR 430 DI 10.1186/1471-2458-13-430 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 140FQ UT WOS:000318640200001 PM 23641795 ER PT J AU Joseph, K Kulik, L Coughlin, B Kunchithapautham, K Bandyopadhyay, M Thiel, S Thielens, NM Holers, VM Rohrer, B AF Joseph, Kusumam Kulik, Liudmila Coughlin, Beth Kunchithapautham, Kannan Bandyopadhyay, Mausumi Thiel, Steffen Thielens, Nicole M. Holers, V. Michael Rohrer, Baerbel TI Oxidative Stress Sensitizes Retinal Pigmented Epithelial (RPE) Cells to Complement-mediated Injury in a Natural Antibody-, Lectin Pathway-, and Phospholipid Epitope-dependent Manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED CHOROIDAL NEOVASCULARIZATION; LIPID-PEROXIDATION PRODUCTS; MACULAR DEGENERATION AMD; MEMBRANE-ATTACK-COMPLEX; MANNOSE-BINDING LECTIN; FACTOR-H; ISCHEMIA/REPERFUSION INJURY; SERINE-PROTEASE; ALTERNATIVE PATHWAY; REPERFUSION INJURY AB Uncontrolled activation of the alternative complement pathway (AP) is thought to be associated with age-related macular degeneration. Previously, we have shown that in retinal pigmented epithelial (RPE) monolayers, oxidative stress reduced complement inhibition on the cell surface, resulting in sublytic complement activation and loss of transepithelial resistance (TER), but the potential ligand and pathway involved are unknown. ARPE-19 cells were grown as monolayers on transwell plates, and sublytic complement activation was induced with H2O2 and normal human serum. TER deteriorated rapidly in H2O2-exposed monolayers upon adding normal human serum. Although the effect required AP activation, AP was not sufficient, because elimination of MASP, but not C1q, prevented TER reduction. Reconstitution experiments to unravel essential components of the lectin pathway (LP) showed that both ficolin and mannan-binding lectin can activate the LP through natural IgM antibodies (IgM-C2) that recognize phospholipid cell surface modifications on oxidatively stressed RPE cells. The same epitopes were found on human primary embryonic RPE monolayers. Likewise, mouse laser-induced choroidal neovascularization, an injury that involves LP activation, could be increased in antibody-deficient rag1(-/-) mice using the phospholipid-specific IgM-C2. In summary, using a combination of depletion and reconstitution strategies, we have shown that the LP is required to initiate the complement cascade following natural antibody recognition of neoepitopes, which is then further amplified by the AP. LP activation is triggered by IgM bound to phospholipids. Taken together, we have defined novel mechanisms of complement activation in oxidatively stressed RPE, linking molecular events involved in age-related macular degeneration, including the presence of natural antibodies and neoepitopes. C1 [Joseph, Kusumam; Coughlin, Beth; Kunchithapautham, Kannan; Bandyopadhyay, Mausumi; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Kulik, Liudmila; Holers, V. Michael] Univ Colorado, Hlth Sci Ctr, Dept Med, Aurora, CO 80045 USA. [Thiel, Steffen] Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark. [Thielens, Nicole M.] Univ Grenoble 1, CNRS, Inst Biol Struct, UMR 5075 CEA, F-38027 Grenoble 1, France. [Rohrer, Baerbel] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave,SEI 511, Charleston, SC 29425 USA. EM rohrer@musc.edu FU National Institutes of Health Grant [R01EY019320, C06 RR015455]; Department of Veterans Affairs Grant [I01 RX000444]; Foundation Fighting Blindness; Research to Prevent Blindness, Inc. (New York) FX This work was supported, in whole or in part, by National Institutes of Health Grant R01EY019320. This work was also supported by Department of Veterans Affairs Grant I01 RX000444, Foundation Fighting Blindness, and an unrestricted grant to the Medical University of South Carolina from Research to Prevent Blindness, Inc. (New York). Animal studies were conducted in a facility constructed with support from National Institutes of Health Grant C06 RR015455. NR 69 TC 19 Z9 20 U1 5 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 2013 VL 288 IS 18 BP 12753 EP 12765 DI 10.1074/jbc.M112.421891 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139AZ UT WOS:000318555100032 PM 23493397 ER PT J AU Gameiro, PA Laviolette, LA Kelleher, JK Iliopoulos, O Stephanopoulos, G AF Gameiro, Paulo A. Laviolette, Laura A. Kelleher, Joanne K. Iliopoulos, Othon Stephanopoulos, Gregory TI Cofactor Balance by Nicotinamide Nucleotide Transhydrogenase (NNT) Coordinates Reductive Carboxylation and Glucose Catabolism in the Tricarboxylic Acid (TCA) Cycle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENINE DINUCLEOTIDE PHOSPHATE; MALATE-ASPARTATE SHUTTLE; ISOCITRATE DEHYDROGENASE; CELL-GROWTH; GLUTAMINE-METABOLISM; INSULIN-SECRETION; MALIC ENZYME; TUMOR-CELLS; REDOX STATE; RAT LIVER AB Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of alpha-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)(+) cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P) H/NAD(P)+ ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle. C1 [Gameiro, Paulo A.; Kelleher, Joanne K.; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Gameiro, Paulo A.; Laviolette, Laura A.; Iliopoulos, Othon] Massachusetts Gen Hosp Canc Ctr, Ctr Canc Res, Charlestown, MA 02129 USA. [Gameiro, Paulo A.; Laviolette, Laura A.; Iliopoulos, Othon] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Laviolette, Laura A.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02139 USA. [Gameiro, Paulo A.] Univ Coimbra, Dept Life Sci, P-3004517 Coimbra, Portugal. RP Stephanopoulos, G (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM gregstep@mit.edu FU Massachusetts General Hospital (MGH) ProtonBeam Federal Share Project; National Institutes of Health [R01 DK075850, R01 CA122591]; Astra-Zeneca; Foundation for Science and Technology (FCT), Portugal FX We thank Ana M. Metelo for insights on the xenograft experiments, Eric L. Bell for help with the NNT cDNA plasmid, Taylor Murphy for help on extracellular flux analyses, Thomas Wasylenko for feedback on cofactor measurements, and Christian M. Metallo for scientific discussions. This work was also supported by the Massachusetts General Hospital (MGH) ProtonBeam Federal Share Project.; This work was supported, in whole or in part, by National Institutes of Health Grants R01 DK075850 (to G.S.) and R01 CA122591 (to O.I.). This work was also supported by an Award from Astra-Zeneca (to O.I.) and the Foundation for Science and Technology (FCT), Portugal (to P.A.G.). NR 46 TC 30 Z9 30 U1 5 U2 28 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 2013 VL 288 IS 18 BP 12967 EP 12977 DI 10.1074/jbc.M112.396796 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139AZ UT WOS:000318555100050 PM 23504317 ER PT J AU Donnelly, BF Needham, PG Snyder, AC Roy, A Khadem, S Brodsky, JL Subramanya, AR AF Donnelly, Bridget F. Needham, Patrick G. Snyder, Avin C. Roy, Ankita Khadem, Shaheen Brodsky, Jeffrey L. Subramanya, Arohan R. TI Hsp70 and Hsp90 Multichaperone Complexes Sequentially Regulate Thiazide-sensitive Cotransporter Endoplasmic Reticulum-associated Degradation and Biogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; NA-CL COTRANSPORTER; HEAT-SHOCK PROTEINS; CHAPERONE MACHINERY; QUALITY-CONTROL; MOLECULAR CHAPERONES; GITELMANS-SYNDROME; MUTATIONS; CHIP; CFTR AB The thiazide-sensitive NaCl cotransporter (NCC) is the primary mediator of salt reabsorption in the distal convoluted tubule and is a key determinant of the blood pressure set point. Given its complex topology, NCC is inefficiently processed and prone to endoplasmic reticulum (ER)-associated degradation (ERAD), although the mechanisms governing this process remain obscure. Here, we identify factors that impact the ER quality control of NCC. Analyses of NCC immunoprecipitates revealed that the cotransporter formed complexes with the core chaperones Hsp90, Hsp70, and Hsp40. Disruption of Hsp90 function accelerated NCC degradation, suggesting that Hsp90 promotes NCC folding. In addition, two cochaperones, the C terminus of Hsp70-interacting protein (CHIP) and the Hsp70/Hsp90 organizer protein, were associated with NCC. Although CHIP, an E3 ubiquitin ligase, promoted NCC ubiquitination and ERAD, the Hsp70/Hsp90 organizer protein stabilized NCC turnover, indicating that these two proteins differentially remodel the core chaperone systems to favor cotransporter degradation and biogenesis, respectively. Adjusting the folding environment in mammalian cells via reduced temperature enhanced NCC biosynthetic trafficking, increased Hsp90-NCC interaction, and diminished binding to Hsp70. In contrast, cotransporters harboring disease-causing mutations that impair NCC biogenesis failed to escape ERAD as efficiently as the wild type protein when cells were incubated at a lower temperature. Instead, these mutants interacted more strongly with Hsp70, Hsp40, and CHIP, consistent with a role for the Hsp70/Hsp40 system in selecting misfolded NCC for ERAD. Collectively, these observations indicate that Hsp70 and Hsp90 comprise two functionally distinct ER quality control checkpoints that sequentially monitor NCC biogenesis. C1 [Needham, Patrick G.; Brodsky, Jeffrey L.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15261 USA. [Donnelly, Bridget F.; Snyder, Avin C.; Roy, Ankita; Khadem, Shaheen; Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. [Khadem, Shaheen; Subramanya, Arohan R.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. RP Subramanya, AR (reprint author), 3550 Terrace St,S832 Scaife Hall, Pittsburgh, PA 15261 USA. EM ars129@pitt.edu FU National Institutes of Health [DK79307, GM75061]; U.S. Dept. of Veterans Affairs; James A. Shaver Fund of the American Heart Association [10BGIA3890010] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK79307 (to the Pittsburgh Center for Kidney Research, Model Organisms Core) and GM75061 (to J. L. B.). This work was also supported by a Mid-Level Career Development Award from the U.S. Dept. of Veterans Affairs (to A. R. S.) and Grant 10BGIA3890010 from the James A. Shaver Fund of the American Heart Association (to A. R. S.). NR 52 TC 14 Z9 14 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 2013 VL 288 IS 18 BP 13124 EP 13135 DI 10.1074/jbc.M113.455394 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139AZ UT WOS:000318555100062 PM 23482560 ER PT J AU Ramos, AD Diaz, A Nellore, A Delgado, RN Park, KY Gonzales-Roybal, G Oldham, MC Song, JS Lim, DA AF Ramos, Alexander D. Diaz, Aaron Nellore, Abhinav Delgado, Ryan N. Park, Ki-Youb Gonzales-Roybal, Gabriel Oldham, Michael C. Song, Jun S. Lim, Daniel A. TI Integration of Genome-wide Approaches Identifies lncRNAs of Adult Neural Stem Cells and Their Progeny In Vivo SO CELL STEM CELL LA English DT Article ID LONG NONCODING RNAS; RETINAL DEVELOPMENT; GENE-EXPRESSION; MOUSE-BRAIN; CHROMATIN; DIFFERENTIATION; REVEALS; NEUROGENESIS; LINCRNAS; LINEAGE AB Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease. C1 [Ramos, Alexander D.; Delgado, Ryan N.; Park, Ki-Youb; Gonzales-Roybal, Gabriel; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Ramos, Alexander D.; Delgado, Ryan N.; Park, Ki-Youb; Gonzales-Roybal, Gabriel; Oldham, Michael C.; Song, Jun S.; Lim, Daniel A.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Ramos, Alexander D.; Delgado, Ryan N.] Univ Calif San Francisco, Med Scientist Training Program, Biomed Sci Grad Program, San Francisco, CA 94143 USA. [Diaz, Aaron; Nellore, Abhinav; Song, Jun S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Oldham, Michael C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Song, Jun S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Lim, Daniel A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Lim, DA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. EM limd@neurosurg.ucsf.edu OI Lim, Daniel/0000-0001-7221-3425 FU NIH [DP2-OD006505-01, R01CA163336]; VA [1I01 BX000252-01]; Sontag Foundation; Sandler Foundation; NIH GMS [K12-GM081266]; California Institute for Regenerative Medicine (CIRM); UCSF Program for Breakthrough Biomedical Research; MSTP [2T32GM007618-34] FX This project was supported by NIH DP2-OD006505-01, VA 1I01 BX000252-01, and the Sontag Foundation to D.A.L., NIH R01CA163336 and the Sontag Foundation to J.S.S., the UCSF Program for Breakthrough Biomedical Research, which is funded in part by the Sandler Foundation, to M.C.O., NIH GMS K12-GM081266 to G.G.-R., a training grant from the California Institute for Regenerative Medicine (CIRM) to A.D.R., MSTP training grant 2T32GM007618-34 to A.D.R. and R.N.D, and facilities and resources provided by the San Francisco Veterans Affairs Medical Center. NR 55 TC 85 Z9 92 U1 2 U2 37 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 2 PY 2013 VL 12 IS 5 BP 616 EP 628 DI 10.1016/j.stem.2013.03.003 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VE UT WOS:000329569600016 PM 23583100 ER PT J AU Kanakry, JA Li, HL Gellert, LL Lemas, MV Hsieh, WS Hong, FX Tan, KL Gascoyne, RD Gordon, LI Fisher, RI Bartlett, NL Stiff, P Cheson, BD Advani, R Miller, TP Kahl, BS Horning, SJ Ambinder, RF AF Kanakry, Jennifer A. Li, Hailun Gellert, Lan L. Lemas, M. Victor Hsieh, Wen-son Hong, Fangxin Tan, King L. Gascoyne, Randy D. Gordon, Leo I. Fisher, Richard I. Bartlett, Nancy L. Stiff, Patrick Cheson, Bruce D. Advani, Ranjana Miller, Thomas P. Kahl, Brad S. Horning, Sandra J. Ambinder, Richard F. TI Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial SO BLOOD LA English DT Article ID TUMOR-ASSOCIATED MACROPHAGES; EBV-DNA; NASOPHARYNGEAL CARCINOMA; PERIPHERAL-BLOOD; DISEASE; CELL; QUANTITATION; PROGNOSTICATION; INTERGROUP; IMPACT AB Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH. A cutoff of >60 viral copies/100 mu L plasma yielded 96% concordance with EBER-ISH. Pretreatment and month 6 plasma specimens were designated EBV(-) or EBV(1) by this cutoff. Patients with pretreatment EBV(1) plasma (n = 54) had inferior failure-free survival (FFS) compared with those with pretreatment EBV(-) plasma (n = 274), log-rank P = .009. By contrast, no difference in FFS was observed when patients were stratified by EBER-ISH. Pretreatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses. At month 6, plasma EBV(1) patients (n = 7) had inferior FFS compared with plasma EBV(-) patients (n = 125), log-rank P = .007. These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility both at baseline and after therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003389. C1 [Kanakry, Jennifer A.; Lemas, M. Victor; Ambinder, Richard F.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. [Li, Hailun; Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gellert, Lan L.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Hsieh, Wen-son] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Tan, King L.; Gascoyne, Randy D.] Univ British Columbia, Ctr Lymphoid Canc, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. [Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Fisher, Richard I.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Bartlett, Nancy L.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Stiff, Patrick] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Cheson, Bruce D.] Georgetown Univ, Ctr Hosp, Washington, DC USA. [Advani, Ranjana] Stanford Univ, Stanford, CA 94305 USA. [Miller, Thomas P.] Univ Arizona, Arizona Canc Ctr, Div Hematol & Med Oncol, Tucson, AZ USA. [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA. RP Ambinder, RF (reprint author), Johns Hopkins Univ, Dept Hematol Malignancies, 1650 Orleans St,CRB1,Room 389, Baltimore, MD 21287 USA. EM ambinder@jhu.edu OI Gordon, Leo/0000-0003-1666-7064 FU National Cancer Institute, National Institutes of Health; Department of Health and Human Services [CA96888, CA95423, CA21115, CA23318, CA66636, CA16116, CA17145, CA21076] FX This work was supported by National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services (grants CA96888, CA95423, CA21115, CA23318, CA66636, CA16116, CA17145, and CA21076). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 26 TC 38 Z9 39 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 2 PY 2013 VL 121 IS 18 BP 3547 EP 3553 DI 10.1182/blood-2012-09-454694 PG 7 WC Hematology SC Hematology GA 184EG UT WOS:000321870000005 PM 23386127 ER PT J AU Mullally, A Bruedigam, C Poveromo, L Heidel, FH Purdon, A Vu, T Austin, R Heckl, D Breyfogle, LJ Kuhn, CP Kalaitzidis, D Armstrong, SA Williams, DA Hill, GR Ebert, BL Lane, SW AF Mullally, Ann Bruedigam, Claudia Poveromo, Luke Heidel, Florian H. Purdon, Amy Vu, Therese Austin, Rebecca Heckl, Dirk Breyfogle, Lawrence J. Kuhn, Catherine Paine Kalaitzidis, Demetrios Armstrong, Scott A. Williams, David A. Hill, Geoff R. Ebert, Benjamin L. Lane, Steven W. TI Depletion of Jak2V617F myeloproliferative neoplasm-propagating stem cells by interferon-alpha in a murine model of polycythemia vera SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; V617F MUTATION OCCURS; TYROSINE KINASE JAK2; LONG-TERM TREATMENT; HEMATOPOIETIC STEM; ESSENTIAL THROMBOCYTHEMIA; BONE-MARROW; PEGYLATED INTERFERON-ALPHA-2A; ACTIVATING MUTATION; SELF-RENEWAL AB Interferon-alpha (IFN alpha) is an effective treatment of patients with myeloproliferative neoplasms (MPNs). In addition to inducing hematological responses in most MPN patients, IFN alpha reduces the JAK2V617F allelic burden and can render the JAK2V617F mutant clone undetectable in some patients. The precise mechanism underlying these responses is incompletely understood and whether the molecular responses that are seen occur due to the effects of IFN alpha on JAK2V617F mutant stem cells is debated. Using a murine model of Jak2V617F MPN, we investigated the effects of IFN alpha on Jak2V617F MPN-propagating stem cells in vivo. We report that IFN alpha treatment induces hematological responses in the model and causes depletion of Jak2V617F MPN-propagating cells over time, impairing disease transplantation. We demonstrate that IFN alpha treatment induces cell cycle activation of Jak2V617F mutant long-term hematopoietic stem cells and promotes a predetermined erythroid-lineage differentiation program. These findings provide insights into the differential effects of IFN alpha on Jak2V617F mutant and normal hematopoiesis and suggest that IFN alpha achieves molecular remissions in MPN patients through its effects on MPN stem cells. Furthermore, these results support combinatorial therapeutic approaches in MPN by concurrently depleting dormant JAK2V617F MPN propagating stem cells with IFN alpha and targeting the proliferating downstream progeny with JAK2 inhibitors or cytotoxic chemotherapy. C1 [Mullally, Ann; Poveromo, Luke; Heckl, Dirk; Breyfogle, Lawrence J.; Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA. [Bruedigam, Claudia; Purdon, Amy; Vu, Therese; Austin, Rebecca; Kuhn, Catherine Paine; Hill, Geoff R.; Lane, Steven W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Heidel, Florian H.] Otto Von Guericke Univ, Klin Hamatol & Onkol, Magdeburg, Germany. [Kalaitzidis, Demetrios; Armstrong, Scott A.; Williams, David A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Kalaitzidis, Demetrios; Armstrong, Scott A.; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Lane, Steven W.] Univ Queensland, Brisbane, Qld, Australia. RP Lane, SW (reprint author), Queensland Inst Med Res, 300 Herston Rd, Brisbane, Qld 4006, Australia. EM amullally@partners.org; steven.lane@qimr.edu.au RI Lane, Steven/C-3215-2012; Hill, Geoffrey/O-2630-2016 OI Lane, Steven/0000-0002-8050-6209; Hill, Geoffrey/0000-0003-2994-0429 FU MPN Foundation; National Institutes of Health, National Cancer Institute [P01 CA108631, P01 CA066996]; National Institutes of Health, National Heart, Lung, and Blood Institute [K08 HL109734]; German Cancer Aid (Deutsche Krebshilfe) [DKH D/08/00661]; German Cancer Foundation, Mildred-Scheel Fellowship; National Institute of Diabetes and Digestive and Kidney Diseases [K01DK092300]; Jeanne D. Housman Fund for Research on Myeloproliferative Disorders; Leukaemia Foundation of Australia; National Health and Medical Research Council [1026594]; J.J. Richards/In Vitro Technologies Rhys Pengelly Fellowship in Leukaemia Research FX This work was supported by the MPN Foundation (B. L. E.) and the National Institutes of Health, National Cancer Institute (P01 CA108631 and P01 CA066996 to B. L. E.) and the National Institutes of Health, National Heart, Lung, and Blood Institute (K08 HL109734 to A. M.). G. R. H. is a NHMRC Australia Fellow and Queensland Health Senior Clinical Research Fellow. F. H. H. was supported by a Mildred-Scheel grant of the German Cancer Aid (DKH D/08/00661, Deutsche Krebshilfe). D. H. was supported by the German Cancer Foundation, Mildred-Scheel Fellowship. D.K. was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K01DK092300. A. M. has received support from the Jeanne D. Housman Fund for Research on Myeloproliferative Disorders and is an ASH Scholar recipient. S. W. L. has received funding from the Leukaemia Foundation of Australia, National Health and Medical Research Council project grant 1026594, J.J. Richards/In Vitro Technologies Rhys Pengelly Fellowship in Leukaemia Research and private philanthropic donations. NR 56 TC 35 Z9 36 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 2 PY 2013 VL 121 IS 18 BP 3692 EP 3702 DI 10.1182/blood-2012-05-432989 PG 11 WC Hematology SC Hematology GA 184EG UT WOS:000321870000022 PM 23487027 ER PT J AU Van Daele, CM De Meyer, T De Buyzere, ML Gillebert, TC Denil, SLIJ Bekaert, S Chirinos, JA Segers, P De Backer, GG De Bacquer, D Rietzschel, ER AF Van Daele, Caroline M. De Meyer, Tim De Buyzere, Marc L. Gillebert, Thierry C. Denil, Simon L. I. J. Bekaert, Sofie Chirinos, Julio A. Segers, Patrick De Backer, Guy G. De Bacquer, Dirk Rietzschel, Ernst R. CA Asklepios Investigators TI Addition of a Novel, Protective Family History Category Allows Better Profiling of Cardiovascular Risk and Atherosclerotic Burden in the General Population. The Asklepios Study SO PLOS ONE LA English DT Article ID CORONARY-HEART-DISEASE; MIDDLE-AGED ADULTS; LOW-DENSITY-LIPOPROTEIN; INTIMA-MEDIA THICKNESS; MYOCARDIAL-INFARCTION; PARENTAL-HISTORY; STROKE; HEALTH; STATEMENT; MEDICINE AB Objectives: Whereas the importance of family history (FH) is widely recognized in cardiovascular risk assessment, its full potential could be underutilized, when applied with its current simple guidelines-based definition (cFH): presence of premature cardiovascular disease (CVD) in a first-degree relative. We tested the added value of a new, extended family history definition (eFH), also taking into account later onset of disease, second-degree relatives and number of affected relatives, on profiling cardiovascular risk and atherosclerotic burden in the general population. Design: longitudinal population study. Setting: random, representative population sample from Erpe-Mere and Nieuwerkerken (Belgium, primary care). Subjects: 2524 male/female volunteers, aged 35-55 years, free from overt CVD. Main outcome measures: Subjects were extensively phenotyped including presence of atherosclerosis (ultrasound) and a newly developed FH questionnaire (4 generations). Results: Compared to cFH, eFH was superior in predicting an adverse risk profile (glycemic state, elevated blood pressure, lipid abnormalities, presence of metabolic syndrome components) and presence of atherosclerosis (all age & sex-adjusted p<0.05). Unlike cFH, eFH remained a significant predictor of subclinical atherosclerosis after adjusting for confounders. Most relations with eFH were not graded but showed clear informational breakpoints, with absence of CVD (including late onset) in any first-degree relative being a negative predictor of atherosclerosis, and a particularly interesting phenotype for further study. Conclusions: A novel, extended FH definition is superior to the conventional definition in profiling cardiovascular risk and atherosclerotic burden in the general population. There remain clear opportunities to refine and increase the performance and informational content of this simple, readily-available inexpensive tool. C1 [Van Daele, Caroline M.; De Buyzere, Marc L.; Gillebert, Thierry C.; Rietzschel, Ernst R.] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium. [De Meyer, Tim; Denil, Simon L. I. J.] Univ Ghent, Fac Biosci Engn, Dept Math Modelling Stat & Bioinformat, B-9000 Ghent, Belgium. [Bekaert, Sofie] Ghent Univ Hosp, Clin Res Ctr Ghent, Bimetra, Ghent, Belgium. [Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19104 USA. [Segers, Patrick] Univ Ghent, Inst Biomed Technol IbiTech, B-9000 Ghent, Belgium. [De Backer, Guy G.; De Bacquer, Dirk; Rietzschel, Ernst R.] Univ Ghent, Fac Med & Hlth Sci, Dept Publ Hlth, B-9000 Ghent, Belgium. RP Van Daele, CM (reprint author), Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium. EM Caroline.Vandaele@UGent.be OI Gillebert, Thierry/0000-0002-3832-919X FU Fund for Scientific Research - Flanders (FWO) [G042703, G083810N] FX The Asklepios Study is supported by the Fund for Scientific Research - Flanders (FWO research grants G042703 and G083810N). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 2 Z9 2 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 2 PY 2013 VL 8 IS 5 AR e63185 DI 10.1371/journal.pone.0063185 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175AF UT WOS:000321200500058 PM 23658806 ER PT J AU Tirumani, SH Jagannathan, JP Regan, KO Kim, KW Shinagare, AB Krajewski, KM Ramaiya, NH AF Tirumani, Sree Harsha Jagannathan, Jyothi P. Regan, Kevin O. Kim, Kyung Won Shinagare, Atul B. Krajewski, Katherine M. Ramaiya, Nikhil H. TI Molecular targeted therapies in non-GIST soft tissue sarcomas: what the radiologist needs to know SO CANCER IMAGING LA English DT Review DE Soft tissue sarcomas; molecular targeted therapies; CT; MRI; PET/CT; drug toxicities ID RENAL-CELL CARCINOMA; TUMOR RESPONSE ASSESSMENT; GASTROINTESTINAL STROMAL TUMOR; POSITRON-EMISSION-TOMOGRAPHY; PHASE-II TRIAL; SINGLE-INSTITUTION; IMATINIB MESYLATE; PART SARCOMA; DERMATOFIBROSARCOMA PROTUBERANS; VILLONODULAR SYNOVITIS AB Non-gastrointestinal stromal soft tissue sarcomas are uncommon neoplasms that have a dismal prognosis due to a high incidence of metastases and a poor response to conventional chemotherapy. The identification of characteristic genetic alterations in several of these tumors has opened the window for molecular targeted therapies in patients who have failed conventional chemotherapy. Imaging plays a critical role in assessing the response to these novel therapeutic agents. Just like the response of gastrointestinal stromal tumors to imatinib, the response of non-gastrointestinal stromal soft tissue sarcomas to molecular targeted drugs is better evaluated on imaging by alternate tumor response criteria such as the Choi criteria. In addition, these drugs are associated with distinct class-specific drug toxicities that can come to attention for the first time on imaging. The purpose of this article is to provide a primer for the radiologist on the various molecular targeted therapies in advanced/metastatic non-gastrointestinal stromal soft tissue sarcomas with emphasis on the role of imaging in assessing treatment response and complications. C1 [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Kim, Kyung Won; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Kim, Kyung Won; Shinagare, Atul B.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02115 USA. [Regan, Kevin O.] Cork Univ Hosp, Dept Radiol, Cork, Ireland. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 65 TC 7 Z9 7 U1 0 U2 7 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 J9 CANCER IMAGING JI Cancer Imaging PD MAY 2 PY 2013 VL 13 IS 2 BP 197 EP 211 DI 10.1102/1470-7330.2013.0022 PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 173EA UT WOS:000321059700001 PM 23649384 ER PT J AU Getz, G Gabriel, SB Cibulskis, K Lander, E Sivachenko, A Sougnez, C Lawrence, M Kandoth, C Dooling, D Fulton, R Fulton, L Kalicki-Veizer, J McLellan, MD O'Laughlin, M Schmidt, H Wilson, RK Ye, K Ding, L Mardis, ER Ally, A Balasundaram, M Birol, I Butterfield, YSN Carlsen, R Carter, C Chu, A Chuah, E Chun, HJE Dhalla, N Guin, R Hirst, C Holt, RA Jones, SJM Lee, D Li, HI Marra, MA Mayo, M Moore, RA Mungall, AJ Plettner, P Schein, JE Sipahimalani, P Tam, A Varhol, RJ Robertson, AG Pashtan, I Saksena, G Onofrio, RC Schumacher, SE Tabak, B Carter, SL Hernandez, B Gentry, J Salvesen, HB Ardlie, K Getz, G Winckler, W Beroukhim, R Gabriel, SB Meyerson, M Hadjipanayis, A Lee, S Mahadeshwar, HS Park, P Protopopov, A Ren, XJ Seth, S Song, XZ Tang, JB Xi, RB Yang, LX Zeng, D Kucherlapati, R Chin, L Zhang, JH Auman, JT Balu, S Bodenheimer, T Buda, E Hayes, DN Hoyle, AP Jefferys, SR Jones, CD Meng, SW Mieczkowski, PA Mose, LE Parker, JS Perou, CM Roach, J Shi, Y Simons, JV Soloway, MG Tan, DH Topal, MD Waring, S Wu, JY Hoadley, KA Baylin, SB Bootwalla, MS Lai, PH Triche, TJ Van Den Berg, D Weisenberger, DJ Laird, PW Shen, H Chin, L Zhang, JH Getz, G Cho, J DiCara, D Frazer, S Heiman, D Jing, R Lin, P Mallard, W Stojanov, P Voet, D Zhang, HL Zou, LH Noble, M Lawrence, M Reynolds, SM Shmulevich, I Aksoy, BA Antipin, Y Ciriello, G Dresdner, G Gao, JJ Gross, B Jacobsen, A Ladanyi, M Reva, B Sander, C Sinha, R Sumer, SO Taylor, BS Cerami, E Weinhold, N Schultz, N Shen, RL Benz, S Goldstein, T Haussler, D Ng, S Szeto, C Stuart, J Benz, CC Yau, C Zhang, W Annala, M Broom, BM Casasent, TD Ju, ZL Liang, H Liu, GY Lu, YL Unruh, AK Wakefield, C Weinstein, JN Zhang, NX Liu, YX Broaddus, R Akbani, R Mills, GB Adams, C Barr, T Black, AD Bowen, J Deardurff, J Frick, J Gastier-Foster, JM Grossman, T Harper, HA Hart-Kothari, M Helsel, C Hobensack, A Kuck, H Kneile, K Leraas, K Lichtenberg, TM McAllister, C Pyatt, RE Ramirez, NC Tabler, TR Vanhoose, N White, P Wise, L Zmuda, E Barnabas, N Berry-Green, C Blanc, V Boice, L Button, M Farkas, A Green, A MacKenzie, J Nicholson, D Kalloger, SE Gilks, CB Karlan, BY Lester, J Orsulic, S Borowsky, M Cadungog, M Czerwinski, C Huelsenbeck-Dill, L Iacocca, M Petrelli, N Petrelli, N Witkin, G Nemirovich-Danchenko, E Potapova, O Rotin, D Berchuck, A Birrer, M DiSaia, P Monovich, L Curley, E Gardner, J Mallery, D Penny, R Dowdy, SC Winterhoff, B Dao, L Gostout, B Meuter, A Teoman, A Dao, F Olvera, N Bogomolniy, F Garg, K Soslow, RA Levine, DA Abramov, M Bartlett, JMS Kodeeswaran, S Parfitt, J Moiseenko, F Clarke, BA Goodman, MT Carney, ME Matsuno, RK Fisher, J Huang, M Rathmell, WK Thorne, L Van Le, L Dhir, R Edwards, R Elishaev, E Zorn, K Broaddus, R Goodfellow, PJ Mutch, D Schultz, N Liu, YX Akbani, R Cherniack, AD Cerami, E Weinhold, N Shen, H Hoadley, KA Kahn, AB Bell, DW Pollock, PM Wang, C Wheeler, DA Shinbrot, E Karlan, BY Berchuck, A Dowdy, SC Winterhoff, B Goodman, MT Robertson, AG Beroukhim, R Pashtan, I Salvesen, HB Laird, PW Noble, M Stuart, J Ding, L Kandoth, C Gilks, CB Soslow, RA Goodfellow, PJ Mutch, D Broaddus, R Zhang, W Mills, GB Kucherlapati, R Mardis, ER Levine, DA Ayala, B Chu, AL Jensen, MA Kothiyal, P Pihl, TD Pontius, J Pot, DA Snyder, EE Srinivasan, D Kahn, AB Shaw, KRM Sheth, M Davidsen, T Eley, G Ferguson, ML Demchok, JA Yang, LM Guyer, MS Ozenberger, BA Sofia, HJ Kandoth, C Schultz, N Cherniack, AD Akbani, R Liu, YX Shen, H Robertson, AG Pashtan, I Shen, R Benz, CC Yau, C Laird, PW Ding, L Zhang, W Mills, GB Kucherlapati, R Mardis, ER Levine, DA AF Getz, Gad Gabriel, Stacey B. Cibulskis, Kristian Lander, Eric Sivachenko, Andrey Sougnez, Carrie Lawrence, Mike Kandoth, Cyriac Dooling, David Fulton, Robert Fulton, Lucinda Kalicki-Veizer, Joelle McLellan, Michael D. O'Laughlin, Michelle Schmidt, Heather Wilson, Richard K. Ye, Kai Ding, Li Mardis, Elaine R. Ally, Adrian Balasundaram, Miruna Birol, Inanc Butterfield, Yaron S. N. Carlsen, Rebecca Carter, Candace Chu, Andy Chuah, Eric Chun, Hye-Jung E. Dhalla, Noreen Guin, Ranabir Hirst, Carrie Holt, Robert A. Jones, Steven J. M. Lee, Darlene Li, Haiyan I. Marra, Marco A. Mayo, Michael Moore, Richard A. Mungall, Andrew J. Plettner, Patrick Schein, Jacqueline E. Sipahimalani, Payal Tam, Angela Varhol, Richard J. Robertson, A. Gordon Pashtan, Itai Saksena, Gordon Onofrio, Robert C. Schumacher, Steven E. Tabak, Barbara Carter, Scott L. Hernandez, Bryan Gentry, Jeff Salvesen, Helga B. Ardlie, Kristin Getz, Gad Winckler, Wendy Beroukhim, Rameen Gabriel, Stacey B. Meyerson, Matthew Hadjipanayis, Angela Lee, Semin Mahadeshwar, Harshad S. Park, Peter Protopopov, Alexei Ren, Xiaojia Seth, Sahil Song, Xingzhi Tang, Jiabin Xi, Ruibin Yang, Lixing Zeng, Dong Kucherlapati, Raju Chin, Lynda Zhang, Jianhua Auman, J. Todd Balu, Saianand Bodenheimer, Tom Buda, Elizabeth Hayes, D. Neil Hoyle, Alan P. Jefferys, Stuart R. Jones, Corbin D. Meng, Shaowu Mieczkowski, Piotr A. Mose, Lisle E. Parker, Joel S. Perou, Charles M. Roach, Jeff Shi, Yan Simons, Janae V. Soloway, Mathew G. Tan, Donghui Topal, Michael D. Waring, Scot Wu, Junyuan Hoadley, Katherine A. Baylin, Stephen B. Bootwalla, Moiz S. Lai, Phillip H. Triche, Timothy J., Jr. Van Den Berg, DavidJ. Weisenberger, Daniel J. Laird, Peter W. Shen, Hui Chin, Lynda Zhang, Jianhua Getz, Gad Cho, Juok DiCara, Daniel Frazer, Scott Heiman, David Jing, Rui Lin, Pei Mallard, Will Stojanov, Petar Voet, Doug Zhang, Hailei Zou, Lihua Noble, Michael Lawrence, Mike Reynolds, Sheila M. Shmulevich, Ilya Aksoy, B. Arman Antipin, Yevgeniy Ciriello, Giovanni Dresdner, Gideon Gao, Jianjiong Gross, Benjamin Jacobsen, Anders Ladanyi, Marc Reva, Boris Sander, Chris Sinha, Rileen Sumer, S. Onur Taylor, Barry S. Cerami, Ethan Weinhold, Nils Schultz, Nikolaus Shen, Ronglai Benz, Stephen Goldstein, Ted Haussler, David Sam Ng Szeto, Christopher Stuart, Joshua Benz, Christopher C. Yau, Christina Zhang, Wei Annala, Matti Broom, Bradley M. Casasent, Tod D. Ju, Zhenlin Liang, Han Liu, Guoyan Lu, Yiling Unruh, Anna K. Wakefield, Chris Weinstein, John N. Zhang, Nianxiang Liu, Yuexin Broaddus, Russell Akbani, Rehan Mills, Gordon B. Adams, Christopher Barr, Thomas Black, Aaron D. Bowen, Jay Deardurff, John Frick, Jessica Gastier-Foster, Julie M. Grossman, Thomas Harper, Hollie A. Hart-Kothari, Melissa Helsel, Carmen Hobensack, Aaron Kuck, Harkness Kneile, Kelley Leraas, KristenM. Lichtenberg, Tara M. McAllister, Cynthia Pyatt, Robert E. Ramirez, Nilsa C. Tabler, Teresa R. Vanhoose, Nathan White, Peter Wise, Lisa Zmuda, Erik Barnabas, Nandita Berry-Green, Charlenia Blanc, Victoria Boice, Lori Button, Michael Farkas, Adam Green, Alex MacKenzie, Jean Nicholson, Dana Kalloger, Steve E. Gilks, C. Blake Karlan, Beth Y. Lester, Jenny Orsulic, Sandra Borowsky, Mark Cadungog, Mark Czerwinski, Christine Huelsenbeck-Dill, Lori Iacocca, Mary Petrelli, Nicholas Petrelli, Nicholas Witkin, Gary Nemirovich-Danchenko, Elena Potapova, Olga Rotin, Daniil Berchuck, Andrew Birrer, Michael DiSaia, Phillip Monovich, Laura Curley, Erin Gardner, Johanna Mallery, David Penny, Robert Dowdy, Sean C. Winterhoff, Boris Dao, Linda Gostout, Bobbie Meuter, Alexandra Teoman, Attila Dao, Fanny Olvera, Narciso Bogomolniy, Faina Garg, Karuna Soslow, Robert A. Levine, Douglas A. Abramov, Mikhail Bartlett, John M. S. Kodeeswaran, Sugy Parfitt, Jeremy Moiseenko, Fedor Clarke, Blaise A. Goodman, Marc T. Carney, Michael E. Matsuno, Rayna K. Fisher, Jennifer Huang, Mei Rathmell, W. Kimryn Thorne, Leigh Van Le, Linda Dhir, Rajiv Edwards, Robert Elishaev, Esther Zorn, Kristin Broaddus, Russell Goodfellow, Paul J. Mutch, David Schultz, Nikolaus Liu, Yuexin Akbani, Rehan Cherniack, Andrew D. Cerami, Ethan Weinhold, Nils Shen, Hui Hoadley, Katherine A. Kahn, Ari B. Bell, Daphne W. Pollock, Pamela M. Wang, Chen Wheeler, David A. Shinbrot, Eve Karlan, Beth Y. Berchuck, Andrew Dowdy, Sean C. Winterhoff, Boris Goodman, Marc T. Robertson, A. Gordon Beroukhim, Rameen Pashtan, Itai Salvesen, Helga B. Laird, Peter W. Noble, Michael Stuart, Joshua Ding, Li Kandoth, Cyriac Gilks, C. Blake Soslow, Robert A. Goodfellow, Paul J. Mutch, David Broaddus, Russell Zhang, Wei Mills, Gordon B. Kucherlapati, Raju Mardis, Elaine R. Levine, Douglas A. Ayala, Brenda Chu, Anna L. Jensen, Mark A. Kothiyal, Prachi Pihl, Todd D. Pontius, Joan Pot, David A. Snyder, Eric E. Srinivasan, Deepak Kahn, Ari B. Shaw, Kenna R. Mills Sheth, Margi Davidsen, Tanja Eley, Greg Ferguson, Martin L. Demchok, John A. Yang, Liming Guyer, Mark S. Ozenberger, Bradley A. Sofia, Heidi J. Kandoth, Cyriac Schultz, Nikolaus Cherniack, Andrew D. Akbani, Rehan Liu, Yuexin Shen, Hui Robertson, A. Gordon Pashtan, Itai Shen, Ronglai Benz, Christopher C. Yau, Christina Laird, Peter W. Ding, Li Zhang, Wei Mills, Gordon B. Kucherlapati, Raju Mardis, Elaine R. Levine, Douglas A. CA Canc Genome Atlas Res Network TI Integrated genomic characterization of endometrial carcinoma SO NATURE LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; MICROSATELLITE INSTABILITY; MATRIX FACTORIZATION; SOMATIC MUTATIONS; HIGH-FREQUENCY; LUNG-CANCER; TUMORS; COLON; DOXORUBICIN; PROTEIN AB We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine seroustumours and similar to 25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. C1 [Getz, Gad; Gabriel, Stacey B.; Cibulskis, Kristian; Lander, Eric; Sivachenko, Andrey; Sougnez, Carrie; Lawrence, Mike; Pashtan, Itai; Saksena, Gordon; Onofrio, Robert C.; Schumacher, Steven E.; Tabak, Barbara; Carter, Scott L.; Hernandez, Bryan; Gentry, Jeff; Salvesen, Helga B.; Ardlie, Kristin; Winckler, Wendy; Beroukhim, Rameen; Meyerson, Matthew; Chin, Lynda; Cho, Juok; DiCara, Daniel; Frazer, Scott; Heiman, David; Jing, Rui; Lin, Pei; Mallard, Will; Stojanov, Petar; Voet, Doug; Zhang, Hailei; Zou, Lihua; Noble, Michael; Cherniack, Andrew D.] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA. [Kandoth, Cyriac; Dooling, David; Fulton, Robert; Fulton, Lucinda; Kalicki-Veizer, Joelle; McLellan, Michael D.; O'Laughlin, Michelle; Schmidt, Heather; Wilson, Richard K.; Ye, Kai; Ding, Li; Mardis, Elaine R.] Washington Univ, Genome Inst, St Louis, MO 63108 USA. [Mardis, Elaine R.; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Plettner, Patrick; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Varhol, Richard J.; Robertson, A. Gordon] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hadjipanayis, Angela; Ren, Xiaojia; Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lee, Semin; Park, Peter; Xi, Ruibin; Yang, Lixing] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Mahadeshwar, Harshad S.; Protopopov, Alexei; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Zeng, Dong; Zhang, Jianhua] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77054 USA. [Park, Peter] Boston Childrens Hosp, Informat Program, Boston, MA 02115 USA. [Auman, J. Todd] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Auman, J. Todd] Univ N Carolina, Inst Pharmacogenet & Individualized Therapy, Chapel Hill, NC 27599 USA. [Balu, Saianand; Bodenheimer, Tom; Buda, Elizabeth; Hayes, D. Neil; Hoyle, Alan P.; Jefferys, Stuart R.; Meng, Shaowu; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Shi, Yan; Simons, Janae V.; Soloway, Mathew G.; Tan, Donghui; Topal, Michael D.; Waring, Scot; Wu, Junyuan; Rathmell, W. Kimryn] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Hayes, D. Neil] Univ N Carolina, Div Med Oncol, Dept Internal Med, Chapel Hill, NC 27599 USA. [Jones, Corbin D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Mieczkowski, Piotr A.; Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Perou, Charles M.; Topal, Michael D.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Roach, Jeff] Univ N Carolina, Res Comp Ctr, Chapel Hill, NC 27599 USA. [Baylin, Stephen B.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Canc Biol Div, Baltimore, MD 21231 USA. [Bootwalla, Moiz S.; Lai, Phillip H.; Triche, Timothy J., Jr.; Van Den Berg, DavidJ.; Weisenberger, Daniel J.; Laird, Peter W.; Shen, Hui] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90089 USA. [Reynolds, Sheila M.; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98109 USA. [Aksoy, B. Arman; Antipin, Yevgeniy; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Sander, Chris; Sinha, Rileen; Sumer, S. Onur; Cerami, Ethan; Weinhold, Nils; Schultz, Nikolaus] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA. [Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Taylor, Barry S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. [Shen, Ronglai] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Benz, Stephen; Goldstein, Ted; Haussler, David; Sam Ng; Szeto, Christopher; Stuart, Joshua] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Benz, Stephen; Goldstein, Ted; Sam Ng; Szeto, Christopher; Stuart, Joshua] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Benz, Christopher C.; Yau, Christina] Buck Inst Age Res, Novato, CA 94945 USA. [Zhang, Wei; Annala, Matti; Liu, Guoyan; Liu, Yuexin] Univ Texas MD Anderson Canc Ctr, Canc Genom Core Lab, Houston, TX 77054 USA. [Liu, Guoyan; Liu, Yuexin; Broaddus, Russell] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Tampere Univ Technol, FI-33720 Tampere, Finland. [Bootwalla, Moiz S.; Van Den Berg, DavidJ.; Weisenberger, Daniel J.; Broom, Bradley M.; Ju, Zhenlin; Liang, Han; Unruh, Anna K.; Wakefield, Chris; Akbani, Rehan] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Lu, Yiling; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Adams, Christopher; Barr, Thomas; Black, Aaron D.; Bowen, Jay; Deardurff, John; Frick, Jessica; Gastier-Foster, Julie M.; Grossman, Thomas; Harper, Hollie A.; Hart-Kothari, Melissa; Helsel, Carmen; Hobensack, Aaron; Kuck, Harkness; Kneile, Kelley; Leraas, KristenM.; Lichtenberg, Tara M.; McAllister, Cynthia; Pyatt, Robert E.; Ramirez, Nilsa C.; Tabler, Teresa R.; Vanhoose, Nathan; White, Peter; Wise, Lisa; Zmuda, Erik] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA. [Gastier-Foster, Julie M.; Ramirez, Nilsa C.; Goodfellow, Paul J.] Ohio State Univ, Columbus, OH 43210 USA. [Barnabas, Nandita; Berry-Green, Charlenia; Blanc, Victoria; Button, Michael; Farkas, Adam; Green, Alex; MacKenzie, Jean; Nicholson, Dana] Asterand, Detroit, MI 48202 USA. [Boice, Lori; Fisher, Jennifer; Huang, Mei; Thorne, Leigh; Van Le, Linda] Univ N Carolina, Chapel Hill, NC 27599 USA. [Kalloger, Steve E.; Gilks, C. Blake] British Columbia Canc Agcy, OvCaRe British Columbia, Vancouver, BC V5Z 4E6, Canada. [Kalloger, Steve E.; Gilks, C. Blake] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada. [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Borowsky, Mark; Cadungog, Mark; Czerwinski, Christine; Huelsenbeck-Dill, Lori; Iacocca, Mary; Petrelli, Nicholas; Witkin, Gary] Helen F Graham Canc Ctr Christiana Care, Newark, DC 19713 USA. [Nemirovich-Danchenko, Elena; Potapova, Olga; Rotin, Daniil] Cureline Inc, San Francisco, CA 94080 USA. [Berchuck, Andrew] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC 27710 USA. [Birrer, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [DiSaia, Phillip] Univ Calif Irvine, Med Ctr, Orange, CA 92868 USA. [Monovich, Laura] Nationwide Childrens Hosp, Res Inst, GOG Tissue Bank, Columbus, OH 43205 USA. [Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA. [Dowdy, Sean C.; Winterhoff, Boris; Gostout, Bobbie; Meuter, Alexandra; Teoman, Attila] Mayo Clin, Div Gynecol Oncol, Dept OB Gyn, Rochester, MN 55905 USA. [Dao, Linda] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA. [Dao, Fanny; Olvera, Narciso; Bogomolniy, Faina; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA. [Garg, Karuna; Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Abramov, Mikhail] NN Blokhin Russian Canc Res Ctr RAMS, Moscow 115478, Russia. [Bartlett, John M. S.; Kodeeswaran, Sugy] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada. [Parfitt, Jeremy] London Hlth Sci Ctr, Ontario Tumour Bank, London, ON N6A 5A5, Canada. [Moiseenko, Fedor] St Petersburg Acad Univ, St Petersburg 199034, Russia. [Clarke, Blaise A.; Demchok, John A.; Yang, Liming] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada. [Goodman, Marc T.; Carney, Michael E.; Matsuno, Rayna K.; Eley, Greg] Univ Hawaii, Honolulu, HI 96813 USA. [Goodman, Marc T.] Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA. [Dhir, Rajiv; Edwards, Robert; Elishaev, Esther; Zorn, Kristin] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Goodfellow, Paul J.; Mutch, David] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Kahn, Ari B.; Ayala, Brenda; Chu, Anna L.; Jensen, Mark A.; Kothiyal, Prachi; Pihl, Todd D.; Pontius, Joan; Pot, David A.; Snyder, Eric E.; Srinivasan, Deepak] SRA Int, Fairfax, VA 22033 USA. [Bell, Daphne W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Pollock, Pamela M.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia. [Wang, Chen] Mayo Clin, Dept Biomed Stat & Informat, Rochester, MN 55905 USA. [Wheeler, David A.; Shinbrot, Eve] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Shaw, Kenna R. Mills; Sheth, Margi; Davidsen, Tanja] NCI, Canc Genome Atlas Program Off, NIH, Bethesda, MD 20892 USA. Scimentis LLC, Atlanta, GA 30666 USA. [Ferguson, Martin L.] MLF Consulting, Arlington, MD 02474 USA. [Guyer, Mark S.; Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Getz, G (reprint author), MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA. RI Lee, Semin/S-2629-2016; Marra, Marco/B-5987-2008; Birol, Inanc/G-5440-2011; salvesen, Helga/C-1187-2017; Jones, Steven/C-3621-2009; Jacobsen, Anders/K-1081-2013; Schumacher, Steven/E-9821-2013; Reva, Boris/B-6436-2014; Tang, Macy/B-9798-2014; White, Peter/E-4301-2011; Moiseenko, Fedor/E-1775-2014; Holt, Robert/C-3303-2009; Ye, Kai/B-3640-2012; Laird, Peter/G-8683-2012; Schein, Jacquie/G-3674-2015; Gao, Jianjiong/B-5673-2016; Wang, Chen/B-3244-2011 OI Seth, Sahil/0000-0003-4579-3959; Pot, David/0000-0002-1480-9826; Sinha, Rileen/0000-0001-5497-5055; Casasent, Anna/0000-0002-7857-179X; Perou, Charles/0000-0001-9827-2247; Lee, Semin/0000-0002-9015-6046; Birol, Inanc/0000-0003-0950-7839; salvesen, Helga/0000-0002-4438-8831; Liang, Han/0000-0001-7633-286X; Schultz, Nikolaus/0000-0002-0131-4904; Benz, Stephen/0000-0002-4067-0602; Kandoth, Cyriac/0000-0002-1345-3573; Triche, Tim/0000-0001-5665-946X; Soslow, Robert/0000-0002-7269-5898; Jacobsen, Anders/0000-0001-6847-4980; Schumacher, Steven/0000-0002-6819-5647; Reva, Boris/0000-0002-8805-389X; White, Peter/0000-0002-5218-5903; Moiseenko, Fedor/0000-0003-2544-9042; Gao, Jianjiong/0000-0002-5739-1781; Wang, Chen/0000-0003-2638-3081 FU US National Institutes of Health [5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067-11, U54HG003079-10, U54HG003273-10] FX We wish to thank all patients and families who contributed to this study. We thank M. Sheth and L. Lund for administrative coordination of TCGA activities, G. Monemvasitis for editing the manuscript, and C. Gunter for critical reading of the manuscript. This work was supported by the following grants from the US National Institutes of Health: 5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067-11, U54HG003079-10 and U54HG003273-10. NR 40 TC 642 Z9 646 U1 15 U2 160 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAY 2 PY 2013 VL 497 IS 7447 BP 67 EP 73 DI 10.1038/nature12113 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134OK UT WOS:000318221500035 ER PT J AU Ko, M An, J Bandukwala, HS Chavez, L Aijo, T Pastor, WA Segal, MF Li, HM Koh, KP Lahdesmaki, H Hogan, PG Aravind, L Rao, A AF Ko, Myunggon An, Jungeun Bandukwala, Hozefa S. Chavez, Lukas Aijo, Tarmo Pastor, William A. Segal, Matthew F. Li, Huiming Koh, Kian Peng Lahdesmaki, Harri Hogan, Patrick G. Aravind, L. Rao, Anjana TI Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX SO NATURE LA English DT Article ID WNT SIGNALING PATHWAY; EMBRYONIC STEM-CELLS; CPG ISLANDS; 5-HYDROXYMETHYLCYTOSINE CONTENT; DNA METHYLATION; BINDING PROTEIN; MAMMALIAN DNA; DIFFERENTIATION; COMPLEX; 5-CARBOXYLCYTOSINE AB TET (ten-eleven-translocation) proteins are Fe(II)- and alpha-ketogluta-rate-dependent dioxygenases(1-3) that modify the methylation status of DNA by successively oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine(1,3-5), potential intermediates in the active erasure of DNA-methylation marks(5,6). Here we show that IDAX (also known as CXXC4), a reported inhibitor of Wnt signalling(7) that has been implicated in malignant renal cell carcinoma(8) and colonic villous adenoma(9), regulates TET2 protein expression. IDAX was originally encoded within an ancestral TET2 gene that underwent a chromosomal gene inversion during evolution, thus separating the TET2 CXXC domain from the catalytic domain. The IDAX CXXC domain binds DNA sequences containing unmethylated CpG dinucleotides, localizes to promoters and CpG islands in genomic DNA and interacts directly with the catalytic domain of TET2. Unexpectedly, IDAX expression results in caspase activation and TET2 protein downregulation, in a manner that depends on DNA binding through the IDAX CXXC domain, suggesting that IDAX recruits TET2 to DNA before degradation. IDAX depletion prevents TET2 downregulation in differentiating mouse embryonic stem cells, and short hairpin RNA against IDAX increases TET2 protein expression in the human monocytic cell line U937. Notably, we find that the expression and activity of TET3 is also regulated through its CXXC domain. Taken together, these results establish the separate and linked CXXC domains of TET2 and TET3, respectively, as previously unknown regulators of caspase activation and TET enzymatic activity. C1 [Ko, Myunggon; An, Jungeun; Bandukwala, Hozefa S.; Chavez, Lukas; Aijo, Tarmo; Pastor, William A.; Segal, Matthew F.; Hogan, Patrick G.; Rao, Anjana] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA. [Aijo, Tarmo; Lahdesmaki, Harri] Aalto Univ, Sch Sci, Dept Informat & Comp Sci, FI-00076 Aalto, Finland. [Li, Huiming; Koh, Kian Peng; Rao, Anjana] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Li, Huiming; Koh, Kian Peng; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Rao, Anjana] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA. RP Rao, A (reprint author), La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA. EM arao@liai.org OI Chavez, Lukas/0000-0002-8718-8848 FU National Institutes of Health (NIH) [HD065812, CA151535]; California Institute of Regenerative Medicine and Translational Research [RM-01729]; Leukemia and Lymphoma Society [TRP 6187-12]; NIH [AI40127]; Leukemia and Lymphoma Society; Lady Tata Memorial Trust; GlaxoSmithKline-Immune Disease Institute Alliance; National Science Foundation FX We thank G. Seumois, M. Ku and J. Day for help with library preparation, B. Ren for use of his Illumina Hi-Seq 2000, J. A. Zepeda-Martinez for the recombinant Flag-TET2CD, and members of the Rao laboratory for discussions. This work was supported by National Institutes of Health (NIH) R01 grants HD065812 and CA151535, grant RM-01729 from the California Institute of Regenerative Medicine and Translational Research, grant TRP 6187-12 from the Leukemia and Lymphoma Society (to A. R.) and NIH R01 grant AI40127 (to P. G. H. and A. R). We also gratefully acknowledge a Special Fellow Award from the Leukemia and Lymphoma Society (to M. K.), postdoctoral fellowships from the Lady Tata Memorial Trust and from the GlaxoSmithKline-Immune Disease Institute Alliance (to H. S. B.) and a predoctoral graduate research fellowship from the National Science Foundation (to W.A.P.). NR 40 TC 86 Z9 90 U1 4 U2 55 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAY 2 PY 2013 VL 497 IS 7447 BP 122 EP + DI 10.1038/nature12052 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134OK UT WOS:000318221500046 PM 23563267 ER PT J AU Miraoui, H Dwyer, AA Sykiotis, GP Plummer, L Chung, W Feng, BH Beenken, A Clarke, J Pers, TH Dworzynski, P Keefe, K Niedziela, M Raivio, T Crowley, WF Seminara, SB Quinton, R Hughes, VA Kumanov, P Young, J Yialamas, MA Hall, JE Van Vliet, G Chanoine, JP Rubenstein, J Mohammadi, M Tsai, PS Sidis, Y Lage, K Pitteloud, N AF Miraoui, Hichem Dwyer, Andrew A. Sykiotis, Gerasimos P. Plummer, Lacey Chung, Wilson Feng, Bihua Beenken, Andrew Clarke, Jeff Pers, Tune H. Dworzynski, Piotr Keefe, Kimberley Niedziela, Marek Raivio, Taneli Crowley, William F., Jr. Seminara, Stephanie B. Quinton, Richard Hughes, Virginia A. Kumanov, Philip Young, Jacques Yialamas, Maria A. Hall, Janet E. Van Vliet, Guy Chanoine, Jean-Pierre Rubenstein, John Mohammadi, Moosa Tsai, Pei-San Sidis, Yisrael Lage, Kasper Pitteloud, Nelly TI Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 Are Identified in Individuals with Congenital Hypogonadotropic Hypogonadism SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; AUDITORY SENSORY EPITHELIUM; KALLMANN-SYNDROME; MOUSE EMBRYOS; CELL-PROLIFERATION; DIGENIC MUTATIONS; EXPRESSION; GROWTH; SEF; GENE AB Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for similar to 12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH. C1 [Miraoui, Hichem; Dwyer, Andrew A.; Hughes, Virginia A.; Sidis, Yisrael; Pitteloud, Nelly] Univ Lausanne, Serv Endocrinol Diabetol & Metab, CHU Vaudois, Fac Biol & Med, CH-1005 Lausanne, Switzerland. [Miraoui, Hichem; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Plummer, Lacey; Feng, Bihua; Keefe, Kimberley; Crowley, William F., Jr.; Seminara, Stephanie B.; Hughes, Virginia A.; Hall, Janet E.; Sidis, Yisrael; Pitteloud, Nelly] Harvard Univ, Sch Med, Ctr Excellence Reprod Endocrinol, Reprod Endocrine Unit,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sykiotis, Gerasimos P.] Univ Patras, Sch Med, Dept Internal Med, Div Endocrinol & Metab, Patras 26500, Greece. [Chung, Wilson; Tsai, Pei-San] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Chung, Wilson; Tsai, Pei-San] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA. [Beenken, Andrew; Mohammadi, Moosa] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA. [Clarke, Jeff] Univ Calif San Francisco, Dept Psychiat, Ctr Neurobiol & Psychiat, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA. [Pers, Tune H.; Dworzynski, Piotr; Lage, Kasper] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Pers, Tune H.; Lage, Kasper] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Pers, Tune H.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02114 USA. [Pers, Tune H.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02114 USA. [Niedziela, Marek] Poznan Univ Med Sci, Dept Pediat Endocrinol & Rheumatol, PL-60572 Poznan, Poland. [Raivio, Taneli] Helsinki Univ Cent Hosp, Univ Helsinki Childrens Hosp, Inst Biomed Physiol, Helsinki 00029, Finland. [Quinton, Richard] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Kumanov, Philip] Med Univ Sofia, Clin Ctr Endocrinol, Sofia 1431, Bulgaria. [Young, Jacques] Hop Bicetre, Serv Endocrinol & Malad Reprod, F-94275 Le Kremlin Bicetre, France. [Yialamas, Maria A.] Brigham & Womens Hosp, Dept Med, Div Endocrine, Boston, MA 02114 USA. [Van Vliet, Guy] Univ Montreal, Ctr Hosp St Justine, Fac Med, Serv Endocrinol, Montreal, PQ H3T 1C5, Canada. [Van Vliet, Guy] Univ Montreal, Ctr Hosp St Justine, Fac Med, Res Ctr, Montreal, PQ H3T 1C5, Canada. [Chanoine, Jean-Pierre] Univ British Columbia, British Columbia Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC V6H 3V4, Canada. [Lage, Kasper] Massachusetts Gen Hosp, Pediat Surg Res Labs, Dept Mol Biol, Boston, MA 02114 USA. [Lage, Kasper] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA. [Lage, Kasper] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark. RP Pitteloud, N (reprint author), Univ Lausanne, Serv Endocrinol Diabetol & Metab, CHU Vaudois, Fac Biol & Med, Rue Bugnon 7, CH-1005 Lausanne, Switzerland. EM nelly.pitteloud@chuv.ch RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Chung, Wilson/0000-0003-0550-7567; Tsai, Pei-San/0000-0002-8650-647X; Mohammadi, Moosa/0000-0003-2434-9437; Hall, Janet/0000-0003-4644-3061; Sykiotis, Gerasimos/0000-0002-9565-4941 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health [R01HD056264, R01HD15788, U54HD028138, 2R01DE013686-11]; NINDS [R01 NS34661]; Swiss National Science Foundation; COST Action [BM1105] FX We thank the individuals and their families for their invaluable and enthusiastic participation. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health R01HD056264 (N.P.), R01HD15788 (W.C.), through Cooperative Agreement U54HD028138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, 2R01DE013686-11 (MM), NINDS R01 NS34661 (J.R.), the Swiss National Science Foundation (N.P.), and COST Action BM1105. NR 78 TC 54 Z9 73 U1 5 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 2 PY 2013 VL 92 IS 5 BP 725 EP 743 DI 10.1016/j.ajhg.2013.04.008 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 139KY UT WOS:000318582800008 PM 23643382 ER PT J AU Hatoum, IJ Greenawalt, DM Cotsapas, C Daly, MJ Reitman, ML Kaplan, LM AF Hatoum, Ida J. Greenawalt, Danielle M. Cotsapas, Chris Daly, Mark J. Reitman, Marc L. Kaplan, Lee M. TI Weight Loss after Gastric Bypass Is Associated with a Variant at 15q26.1 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; ENERGY-EXPENDITURE; BARIATRIC SURGERY; RISK-FACTORS; AQUAPORIN-11; OBESITY; BILE; INDIVIDUALS; OVERWEIGHT AB The amount of weight loss attained after Roux-en-Y gastric bypass (RYGB) surgery follows a wide and normal distribution, and recent evidence indicates that this weight loss is due to physiological, rather than mechanical, mechanisms. To identify potential genetic factors associated with weight loss after RYGB, we performed a genome-wide association study (GWAS) of 693 individuals undergoing RYGB and then replicated this analysis in an independent population of 327 individuals undergoing RYGB. We found that a 15q26.1 locus near ST8SIA2 and SLCO3A1 was significantly associated with weight loss after RYGB. Expression of ST8SIA2 in omental fat of these individuals at baseline was significantly associated with weight loss after RYGB. Gene expression analysis in RYGB and weight-matched, sham-operated (WMS) mice revealed that expression of St8sia2 and Slco3a1 was significantly altered in metabolically active tissues in RYGB-treated compared to WMS mice. These findings provide strong evidence for specific genetic influences on weight loss after RYGB and underscore the biological nature of the response to RYGB. C1 [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hatoum, Ida J.; Cotsapas, Chris; Daly, Mark J.; Kaplan, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Greenawalt, Danielle M.] Merck Res Labs, Dept Genet, Boston, MA 02115 USA. [Cotsapas, Chris; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Cotsapas, Chris; Daly, Mark J.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02141 USA. [Reitman, Marc L.] Merck Res Labs, Clin Pharmacol, Rahway, NJ 07065 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. EM lmkaplan@partners.org RI Reitman, Marc/B-4448-2013 OI Cotsapas, Chris/0000-0002-7772-5910; Reitman, Marc/0000-0002-0426-9475 FU National Institutes of Health [DK093257, DK088661, DK090956]; Merck Research Laboratories; Ethicon Endo-Surgery FX The authors thank Shubhra Kashyap and Melissa Paziuk for their expert technical assistance, Harveen Dhillon Natarajan and Nadia Ahmad for their help with the animal studies, and Rahul Deo for his invaluable statistical expertise. This work was supported by National Institutes of Health grants DK093257 (I.J.H.), DK088661 (L.M.K.), and DK090956 (L.M.K.) and by research grants from Merck Research Laboratories (L.M.K.) and Ethicon Endo-Surgery (L.M.K.). D.M.G. reports employment by Merck Research Laboratories. M.L.R. reports former employment by Merck Research Laboratories. NR 35 TC 20 Z9 20 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 2 PY 2013 VL 92 IS 5 BP 827 EP 834 DI 10.1016/j.ajhg.2013.04.009 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 139KY UT WOS:000318582800018 PM 23643386 ER PT J AU Lieberman, J Sarnow, P AF Lieberman, Judy Sarnow, Peter TI Micromanaging Hepatitis C Virus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MICRORNA; LIVER; PRIMATES; MIR-122; GENOME C1 [Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Sarnow, Peter] Stanford Univ, Dept Microbiol & Immunol, Palo Alto, CA 94304 USA. RP Lieberman, J (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. RI Lieberman, Judy/A-2717-2015 NR 15 TC 9 Z9 9 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 2 PY 2013 VL 368 IS 18 BP 1741 EP 1743 DI 10.1056/NEJMe1301348 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 134MN UT WOS:000318214400011 PM 23534545 ER PT J AU Kahle, KT Duhaime, AC AF Kahle, Kristopher T. Duhaime, Ann-Christine TI Intracranial-Pressure Monitoring in Traumatic Brain Injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Kahle, Kristopher T.; Duhaime, Ann-Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Duhaime, AC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM aduhaime@partners.org NR 3 TC 2 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 2 PY 2013 VL 368 IS 18 BP 1750 EP 1750 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 134MN UT WOS:000318214400021 PM 23635062 ER PT J AU Nohria, A AF Nohria, Anju TI beta-Adrenergic Blockade for Anthracycline- and Trastuzumab-Induced Cardiotoxicity Is Prevention Better Than Cure? SO CIRCULATION-HEART FAILURE LA English DT Editorial Material DE Editorials; anthracyclines; trastuzumab ID BREAST-CANCER; ADJUVANT TRASTUZUMAB; HEART-FAILURE; INDUCED CARDIOMYOPATHY; RETROSPECTIVE ANALYSIS; VENTRICULAR MYOCYTES; DOXORUBICIN; CARVEDILOL; THERAPY; CHEMOTHERAPY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiooncol Program,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nohria, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiooncol Program,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM anohria@partners.org NR 34 TC 7 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2013 VL 6 IS 3 BP 358 EP 361 DI 10.1161/CIRCHEARTFAILURE.113.000267 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA8ZM UT WOS:000331383500007 PM 23694770 ER PT J AU Chatterjee, NA Murphy, RM Malhotra, R Dhakal, BP Baggish, AL Pappagianopoulos, PP Hough, SS Semigran, MJ Lewis, GD AF Chatterjee, Neal A. Murphy, Ryan M. Malhotra, Rajeev Dhakal, Bishnu P. Baggish, Aaron L. Pappagianopoulos, Paul P. Hough, Stacyann S. Semigran, Marc J. Lewis, Gregory D. TI Prolonged Mean VO2 Response Time in Systolic Heart Failure An Indicator of Impaired Right Ventricular-Pulmonary Vascular Function SO CIRCULATION-HEART FAILURE LA English DT Article DE exercise physiology; exercise testing; heart failure ID OXYGEN-UPTAKE KINETICS; LOW-LEVEL EXERCISE; LOW-INTENSITY EXERCISE; O-2 UPTAKE KINETICS; SUBMAXIMAL EXERCISE; SKELETAL-MUSCLE; GAS-EXCHANGE; AMBULATORY PATIENTS; HEAVY EXERCISE; PEAK EXERCISE AB Background-In patients with left ventricular systolic dysfunction (LVSD), the rate at which oxygen uptake (Vo(2)) increases on initiation of exercise is inadequate to match metabolic demands. To gain mechanistic insights into delayed Vo(2) kinetics in LVSD, we simultaneously assessed hemodynamic measurements, ventilatory parameters, and peripheral oxygen usage during exercise. Methods and Results-Forty-two patients with symptomatic LVSD (age, 59 +/- 2 years [mean +/- SEM]; LV ejection fraction, 30 +/- 1%) and 17 controls (LV ejection fraction, 68 +/- 1%) underwent maximum upright cycle ergometry cardiopulmonary exercise testing. Hemodynamic monitoring and first-pass radionuclide ventriculography were performed at rest and during exercise. Vo(2) kinetics were quantified by mean response time (MRT), which was significantly longer in patients with LVSD compared with controls (64 +/- 3 versus 45 +/- 5 s; P=0.004). In LVSD patients, MRT was associated with higher biventricular filling pressures and reduced cardiac output during early exercise. LVSD patients with MRT >= 60 s, compared with LVSD subjects with MRT < 60 s, demonstrated greater impairment in right ventricular-pulmonary vascular function during exercise as evidenced by lower right ventricular ejection fraction (35 +/- 2 versus 45 +/- 2%; P=0.03), steeper increment in transpulmonary gradient relative to cardiac output (3.7 versus 2.2 mm Hg/L; P<0.001), and increased ventilatory dead-space fraction (17 +/- 1 versus 12 +/- 2%; P=0.03). In contrast, MRT was not associated with LV ejection fraction (rest, exercise), Pao(2), hemoglobin, or resting pulmonary function test results. Conclusions-Delayed oxygen uptake on initiation of exercise (ie, MRT >= 60 s) in LVSD is closely related to impaired right ventricular-pulmonary vascular function and may represent an important surrogate for inability to augment RV performance during physical activity in patients with heart failure. C1 [Chatterjee, Neal A.; Murphy, Ryan M.; Malhotra, Rajeev; Dhakal, Bishnu P.; Baggish, Aaron L.; Semigran, Marc J.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. [Baggish, Aaron L.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Performance Program,Dept Med, Boston, MA USA. [Pappagianopoulos, Paul P.; Hough, Stacyann S.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM glewis@partners.org OI Malhotra, Rajeev/0000-0003-0120-4630 FU American Heart Association [11FTF7290032]; National Heart Lung and Blood Institute Heart Failure Network training grant; Heart Failure Research Innovation Fund; Massachusetts General Hospital Cardiac Performance Program FX We gratefully acknowledge support from the American Heart Association (11FTF7290032 Dr Malhotra), the National Heart Lung and Blood Institute Heart Failure Network training grant (Dr Lewis), the Heart Failure Research Innovation Fund (Dr Lewis, R. M. Murphy, Dr Chatterjee, and Dr Dhakal), and The Massachusetts General Hospital Cardiac Performance Program (Drs Baggish and Lewis). NR 47 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2013 VL 6 IS 3 BP 499 EP + DI 10.1161/CIRCHEARTFAILURE.112.000157 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA8ZM UT WOS:000331383500025 PM 23572493 ER PT J AU Colt, HG Murgu, SD Korst, RJ Slatore, CG Unger, M Quadrelli, S AF Colt, Henri G. Murgu, Septimiu D. Korst, Robert J. Slatore, Christopher G. Unger, Michael Quadrelli, Silvia TI Follow-up and Surveillance of the Patient With Lung Cancer After Curative-Intent Therapy Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines SO CHEST LA English DT Article ID QUALITY-OF-LIFE; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; BRONCHIAL CARCINOID-TUMORS; SQUAMOUS-CELL CARCINOMA; BRONCHOSCOPIC TREATMENT; NEUROENDOCRINE TUMORS; COMPLETE RESECTION; PROGNOSTIC-FACTORS; RADIATION-THERAPY AB Background: These guidelines are an update of the evidence-based recommendations for follow-up and surveillance of patients after curative-intent therapy for lung cancer. Particular updates pertain to whether imaging studies, health-related quality-of-life (HRQOL) measures, tumor markers, and bronchoscopy improve outcomes after curative-intent therapy. Methods: Meta-analysis of Observational Studies in Epidemiology guidelines were followed for this systematic review, including published studies on posttreatment outcomes in patients who received curative-intent therapy since the previous American College of Chest Physicians subject review. Four population, intervention, comparison, and outcome questions were formulated to guide the review. The MEDLINE and CINAHL databases were searched from June 1, 2005, to July 8, 2011, to ensure overlap with the search strategies used previously. Results: A total of 3,412 citations from MEDLINE and 431 from CINAHL were identified. Only 303 were relevant. Seventy-six of the 303 articles were deemed eligible on the basis of predefined inclusion criteria after full-text review, but only 34 provided data pertaining directly to the subject of the questions formulated to guide this review. In patients undergoing curative-intent surgical resection of non-small cell lung cancer, chest CT imaging performed at designated time intervals after resection is suggested for detecting recurrence. It is recommended that treating physicians who are able to incorporate the patient's clinical findings into decision-making processes be included in follow-up and surveillance strategies. The use of validated HRQOL instruments at baseline and during follow-up is recommended. Biomarker testing during surveillance outside clinical trials is not suggested. Surveillance bronchoscopy is suggested for patients with early central airway squamous cell carcinoma treated by curative-intent photodynamic therapy and for patients with intraluminal bronchial carcinoid tumor who have undergone curative-intent bronchoscopic treatment with Nd:YAG laser or electrocautery. Conclusions: There is a paucity of well-designed prospective studies specifically targeting follow-up and surveillance modalities aimed at improving survival or QOL after curative-intent therapy. Additional research is warranted to clarify which curative-intent treatment modalities affect HRQOL the most and to identify patients who are at the most risk for recurrence or impaired QOL after treatment. Further evidence is needed to determine how the frequency and duration of surveillance programs that include imaging studies, QOL measurements, tumor markers, or bronchoscopy affect patient morbidity, survival, HRQOL, and health-care costs. C1 [Colt, Henri G.] Univ Calif Irvine, Div Pulm & Crit Care Med, Irvine, CA USA. [Murgu, Septimiu D.] Univ Chicago, Div Pulm & Crit Care Med, Chicago, IL 60637 USA. [Korst, Robert J.] Valley Hosp, Valley Hlth Syst, Daniel & Gloria Blumenthal Canc Ctr, Paramus, NJ USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR 97201 USA. [Unger, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Quadrelli, Silvia] Buenos Aires British Hosp, Buenos Aires, DF, Argentina. RP Colt, HG (reprint author), 422 Glenneyre, Laguna Beach, CA 92651 USA. EM hcolt@uci.edu OI Slatore, Christopher/0000-0003-0958-8122 FU Lung Cancer Research Foundation; Boehringer Ingelheim Pharmaceuticals, Inc. FX The overall process for the development of these guidelines, including matters pertaining to funding and conflicts of interest, are described in the methodology article. 1 The development of this guideline was supported primarily by the American College of Chest Physicians. The lung cancer guidelines conference was supported in part by a grant from the Lung Cancer Research Foundation. The publication and dissemination of the guidelines was supported in part by a 2009 independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. COI grids reflecting the conflicts of interest that were current as of the date of the conference and voting are posted in the online supplementary materials. NR 94 TC 23 Z9 23 U1 1 U2 10 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2013 VL 143 IS 5 SU S BP E437 EP E454 DI 10.1378/chest.12-2365 PG 18 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AB1HL UT WOS:000331542000020 PM 23649451 ER PT J AU Socinski, MA Evans, T Gettinger, S Hensing, TA Sequist, LV Ireland, B Stinchcombe, TE AF Socinski, Mark A. Evans, Tracey Gettinger, Scott Hensing, Thomas A. Sequist, Lecia VanDam Ireland, Belinda Stinchcombe, Thomas E. TI Treatment of Stage IV Non-small Cell Lung Cancer Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines SO CHEST LA English DT Article ID PHASE-III TRIAL; PLATINUM-BASED CHEMOTHERAPY; FACTOR-RECEPTOR MUTATIONS; QUALITY-OF-LIFE; COMPARING PACLITAXEL POLIGLUMEX; RANDOMIZED CONTROLLED-TRIAL; CISPLATIN PLUS GEMCITABINE; COOPERATIVE-ONCOLOGY-GROUP; POOR PERFORMANCE STATUS; PS 2 PATIENTS AB Background: Stage IV non-small cell lung cancer (NSCLC) is a treatable, but not curable, clinical entity in patients given the diagnosis at a time when their performance status (PS) remains good. Methods: A systematic literature review was performed to update the previous edition of the American College of Chest Physicians Lung Cancer Guidelines. Results: The use of pemetrexed should be restricted to patients with nonsquamous histology. Similarly, bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1; however, the data now suggest it is safe to use in those patients with treated and controlled brain metastases. Data at this time are insufficient regarding the safety of bevacizumab in patients receiving therapeutic anticoagulation who have an ECOG PS of 2. The role of cetuximab added to chemotherapy remains uncertain and its routine use cannot be recommended. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line therapy are the recommended treatment of those patients identified as having an EGFR mutation. The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression. The use of second-and third-line therapy in stage IV NSCLC is recommended in those patients retaining a good PS; however, the benefit of therapy beyond the third-line setting has not been demonstrated. In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred. Palliative care should be initiated early in the course of therapy for stage IV NSCLC. Conclusions: Significant advances continue to be made, and the treatment of stage IV NSCLC has become nuanced and specific for particular histologic subtypes and clinical patient characteristics and according to the presence of specific genetic mutations. C1 [Socinski, Mark A.] Univ Pittsburgh, Div Hematol Oncol, Pittsburgh, PA USA. [Evans, Tracey] Perelman Ctr Adv Med, Philadelphia, PA USA. [Gettinger, Scott] Yale Canc Ctr, New Haven, CT USA. [Hensing, Thomas A.] NorthShore Univ HealthSyst, Evanston Hosp, Evanston, IL USA. [Sequist, Lecia VanDam] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ireland, Belinda] TheEvidenceDoc LLC, St Louis, MO USA. [Stinchcombe, Thomas E.] Univ N Carolina, Chapel Hill, NC USA. RP Socinski, MA (reprint author), Div Hematol Oncol, Lung Canc Sect, UPMC Canc Pavilion,5150 Ctr Ave,Fifth Floor, Pittsburgh, PA 15232 USA. EM socinskima@upmc.edu FU Lung Cancer Research Foundation; Boehringer Ingelheim Pharmaceuticals, Inc. FX The overall process for the development of these guidelines, including matters pertaining to funding and conflicts of interest, are described in the methodology article. 1 The development of this guideline was supported primarily by the American College of Chest Physicians. The lung cancer guidelines conference was supported in part by a grant from the Lung Cancer Research Foundation. The publication and dissemination of the guidelines was supported in part by a 2009 independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. COI Grids reflecting the conflicts of interest that were current as of the date of the conference and voting are posted in the online supplementary materials. NR 133 TC 37 Z9 39 U1 3 U2 10 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2013 VL 143 IS 5 SU S BP E341 EP E368 DI 10.1378/chest.12-2361 PG 28 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AB1HL UT WOS:000331542000016 PM 23649446 ER PT J AU Frank, JW Hong, CS Subramanian, SV Wang, EA AF Frank, Joseph W. Hong, Clemens S. Subramanian, S. V. Wang, Emily A. TI Neighborhood Incarceration Rate and Asthma Prevalence in New York City: A Multilevel Approach SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CHILDHOOD ASTHMA; HEALTH DISPARITIES; RACIAL DISPARITIES; RISK-FACTORS; PRISONERS; CARE; MORBIDITY; FAMILIES; VIOLENCE; RELEASE AB Objectives. We examined the association between neighborhood incarceration rate and asthma prevalence and morbidity among New York City adults. Methods. We used multilevel modeling techniques and data from the New York City Community Health Survey (2004) to analyze the association between neighborhood incarceration rate and asthma prevalence, adjusting for individual-level sociodemographic, behavioral, and environmental characteristics. We examined interactions between neighborhood incarceration rate, respondent incarceration history, and race/ethnicity. Results. The mean neighborhood rate of incarceration was 5.4% (range = 2.1%-12.8%). Neighborhood incarceration rate was associated with individual-level asthma prevalence (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.03, 1.10) in unadjusted models but not after adjustment for sociodemographic characteristics (OR = 1.01; 95% CI = 0.98, 1.04). This association did not differ according to respondent race/ethnicity. Conclusions. Among New York City adults, the association between neighborhood incarceration rate and asthma prevalence is explained by the sociodemographic composition of neighborhoods and disparities in asthma prevalence at the individual level. Public health practitioners should further engage with criminal justice professionals and correctional health care providers to target asthma outreach efforts toward both correctional facilities and neighborhoods with high rates of incarceration. C1 [Frank, Joseph W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Hong, Clemens S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Cambridge, MA 02138 USA. [Wang, Emily A.] Yale Univ, Sch Med, Gen Internal Med Sect, New Haven, CT USA. RP Frank, JW (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM josephwfrank@gmail.com FU National Research Service Award [T32HP10251, T32HP12706]; Division of General Medicine and Primary Care at Brigham and Women's Hospital; General Medicine Division at Massachusetts General Hospital; National Heart, Lung and Blood Institute [K23 HL103720] FX J. W. Frank is supported by an institutional National Research Service Award (T32HP10251) and by the Division of General Medicine and Primary Care at Brigham and Women's Hospital. C. S. Hong was supported by an institutional National Research Service Award (T32HP12706) and by the General Medicine Division at Massachusetts General Hospital. E. A. Wang is supported by the National Heart, Lung and Blood Institute (K23 HL103720). NR 38 TC 4 Z9 4 U1 2 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2013 VL 103 IS 5 BP E38 EP E44 DI 10.2105/AJPH.2013.301255 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA2UJ UT WOS:000330949300014 PM 23488496 ER PT J AU Abukawa, H Oriel, BS Leaf, J Vacanti, JP Kaban, LB Troulis, MJ Hartnick, CJ AF Abukawa, Harutsugi Oriel, Brad S. Leaf, Jeremy Vacanti, Joseph P. Kaban, Leonard B. Troulis, Maria J. Hartnick, Christopher J. TI Growth Factor Directed Chondrogenic Differentiation of Porcine Bone Marrow-Derived Progenitor Cells SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Bone marrow; cartilage; chondrocytes; chondrogenic differentiation; mandibular condyle; stem cells; tissue engineering ID MESENCHYMAL STEM-CELLS; CARTILAGE; CULTURE; PROTEIN; MATRIX AB Background: Despite advances in surgical technique, reconstruction of a mandibular condyle still causes significant donor-site morbidity. The purpose of this study was to compare the effect of 3 different growth factors and define optimal cell culture conditions for bone marrow-derived progenitor cells to differentiate into chondrocytes for mandibular condyle reconstruction. Methods: Porcine bone marrow-derived progenitor cells (pBMPCs) were cultured as a pellet for 2, 3, and 4 weeks under the following conditions: group 1, TGF-beta 3 + standard medium; group 2, TGF-beta 3 + BMP-2 + standard medium; group 3, TGF-beta 3 + IGF-1 + standard medium; and group 4, TGF-beta 3 + BMP-2 + IGF-1 + standard medium. Chondrogenic differentiation was evaluated using 3 lineage differentiation markers. Results: The mean type II collagen positive area increased over weeks 2, 3, and 4 in group 4 compared to all the other groups (ANOVA; P = 0.005). At week 4, there was significantly greater type II collagen production in group 4 compared to all the other groups (ANOVA; P = 0.003). The medium in group 4 produces the greatest amount of cartilage when compared to groups 1, 2, and 3, and that 4 weeks produces the greatest amount of type II collagen. Conclusions: The results of this study indicate that the most efficacious medium for chondrogenic differentiation of pBMPCs was group 4 medium and the most type II collagen was produced at 4 weeks. C1 [Abukawa, Harutsugi; Leaf, Jeremy; Kaban, Leonard B.; Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Abukawa, Harutsugi; Leaf, Jeremy; Kaban, Leonard B.; Troulis, Maria J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Abukawa, Harutsugi] Tokyo Med Univ, Dept Oral & Maxillofacial Surg, Tokyo 1600023, Japan. [Oriel, Brad S.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, Boston, MA 02114 USA. [Oriel, Brad S.; Vacanti, Joseph P.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. [Oriel, Brad S.] Tufts Med Ctr, Dept Gen Surg, Boston, MA USA. [Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Tissue Engn & Organ Fabricat Lab, Boston, MA 02114 USA. RP Abukawa, H (reprint author), Tokyo Med Univ, Dept Oral & Maxillofacial Surg, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan. EM habukawa@tokyo-med.ac.jp FU Center for Integration of Medicine and Innovative Technology (Boston, MA); Massachusetts General Hospital's Department of Oral and Maxillofacial Surgery Education and Research Fund FX Funded in part by the Center for Integration of Medicine and Innovative Technology (Boston, MA), and the Massachusetts General Hospital's Department of Oral and Maxillofacial Surgery Education and Research Fund. NR 22 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 EI 1536-3732 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAY PY 2013 VL 24 IS 3 BP 1026 EP 1030 DI 10.1097/SCS.0b013e31827ff323 PG 5 WC Surgery SC Surgery GA 294WI UT WOS:000330078200118 PM 23714939 ER PT J AU Wen, LS Baca, JT O'Malley, P Bhatia, K Peak, D Takayesu, JK AF Wen, Leana S. Baca, Justin T. O'Malley, Patricia Bhatia, Kriti Peak, David Takayesu, J. Kimo TI Implementation of small-group reflection rounds at an emergency medicine residency program SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE burnout; humanism; reflection; residency training AB Few residency curricular interventions have focused on improving well-being and promoting humanism. We describe the implementation of a novel curriculum based on small-group reflection rounds-the Emergency Medicine Reflection Rounds (EMRR)-at a 4-year US emergency medicine (EM) residency. During the inaugural year (2010-2011), nine residents volunteered to take part in 1-hour monthly sessions with faculty facilitators. Residents were provided with a confidential environment to discuss difficult ethical and interpersonal encounters from their clinical experiences. Ongoing feedback from participants was solicited, culminating with a four-question survey in which all respondents remarked that the EMRR contributed to improving their own well-being and agreed that it provided an important forum for residents to discuss difficult issues in a safe environment. In this article, we describe our innovation as an example of a wellness initiative that has promoted reflective practice and fostered cooperative learning around the communication, professional, and ethical challenges inherent in EM practice. Our EMRR model may be useful to other EM residences looking to supplement their wellness curriculum. C1 [Wen, Leana S.; Baca, Justin T.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA 02116 USA. [O'Malley, Patricia; Peak, David; Takayesu, J. Kimo] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02116 USA. [Bhatia, Kriti] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Wen, LS (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, 178 Marlborough St,5, Boston, MA 02116 USA. EM Wen.Leana@gmail.com NR 10 TC 1 Z9 1 U1 1 U2 2 PU DECKER PUBL INC PI HAMILTON PA 69 JOHN ST S, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1481-8035 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD MAY PY 2013 VL 15 IS 3 BP 175 EP 177 DI 10.2310/8000.2013.130935 PG 3 WC Emergency Medicine SC Emergency Medicine GA AA5MT UT WOS:000331144300009 PM 23663465 ER PT J AU Buchanan, GL Chieffo, A Meliga, E Mehran, R Park, SJ Onuma, Y Capranzano, P Valgimigli, M Jegere, S Makkar, R Palacios, IF Kim, YH Buszman, P Charavarty, T Sheiban, I Naber, C Margey, R Agnihotri, A Marra, S Davide, D Leon, M Fajadet, J Lefevre, T Morice, MC Erglis, A Tamburino, C Alfieri, O Serruys, PW Colombo, A AF Buchanan, G. L. Chieffo, A. Meliga, E. Mehran, R. Park, S. J. Onuma, Y. Capranzano, P. Valgimigli, M. Jegere, S. Makkar, R. Palacios, I. F. Kim, Y. H. Buszman, P. Charavarty, T. Sheiban, I. Naber, C. Margey, R. Agnihotri, A. Marra, S. Davide, D. Leon, M. Fajadet, J. Lefevre, T. Morice, M. C. Erglis, A. Tamburino, C. Alfieri, O. Serruys, P. W. Colombo, A. TI THE ROLE OF FEMALE SEX IN THE CONTEMPORARY TREATMENT OF THE LEFT MAIN CORONARY ARTERY INSIGHTS FROM THE W-DELTA (WOMEN-DRUG ELUTING STENT FOR LEFT MAIN CORONARY ARTERY DISEASE) REGISTRY SO HEART LA English DT Meeting Abstract CT Annual Conference of the British-Cardiovascular-Society (BCS) CY JUN 03-05, 2013 CL London, ENGLAND SP British Cardiovascular Soc C1 [Buchanan, G. L.; Chieffo, A.; Alfieri, O.; Colombo, A.] Ist Sci San Raffaele, Milan, Italy. [Meliga, E.] AO Ordine Mauriziano Umberto I, Turin, Italy. [Mehran, R.] Mt Sinai Med Ctr, New York, NY USA. [Park, S. J.; Kim, Y. H.] Asan Med Ctr, Seoul, South Korea. [Onuma, Y.; Serruys, P. W.] Erasmus MC, Rotterdam, Netherlands. [Capranzano, P.; Davide, D.; Tamburino, C.] Ferrarotto Hosp, Catania, Italy. [Valgimigli, M.] St Anna Hosp, Catanzaro, Italy. [Jegere, S.; Erglis, A.] Univ Latvia, Riga, Latvia. [Makkar, R.; Charavarty, T.; Margey, R.] Cedars Sinai Med Ctr, Los Angeles, CA USA. [Palacios, I. F.; Agnihotri, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Palacios, I. F.; Agnihotri, A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Buszman, P.] Amer Heart Poland Inc, Katowice, Poland. [Sheiban, I.] Giovanni Battista Hosp, Turin, Italy. [Naber, C.] Contilia Heart & Vasc Ctr, Essen, Germany. [Marra, S.] S Giovanni Battista Hosp, Turin, Italy. [Leon, M.] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Fajadet, J.] Clin Pasteur, Toulouse, France. [Lefevre, T.; Morice, M. C.] Inst Hosp Jacques Cartier, Massy, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD MAY PY 2013 VL 99 SU 2 DI 10.1136/heartjnl-2013-304019.58 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA6NJ UT WOS:000331214700070 ER PT J AU Fadi, GH Meaghan, B Xing, DQ Akash, K Chen, YF Alexander, S Suzanne, O AF Fadi, Hage G. Meaghan, Bowling Xing Dongqi Akash, Kapadia Chen Yu-Fai Alexander, Szalai Suzanne, Oparil TI Estrogen Ameliorates Vascular Inflammation in Young but not Aged Mice SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Meeting Abstract DE vascular injury; vascular inflammation; estrogen; aging C1 [Fadi, Hage G.; Meaghan, Bowling; Xing Dongqi; Akash, Kapadia; Chen Yu-Fai; Alexander, Szalai; Suzanne, Oparil] Univ Alabama Birmingham, Birmingham, AL USA. [Fadi, Hage G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD MAY PY 2013 VL 15 SU 1 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AA0EX UT WOS:000330769400102 ER PT J AU Fadi, GH Maricica, P Xing, DQ Rob, H Guo, YY Chen, YF AF Fadi, Hage G. Maricica, Pacurari Xing Dongqi Rob, Hilgers Guo YuanYuan Chen Yiu-Fai TI Endothelial Cell Transfusion in Nephrectomized Rats Ameliorates Endothelial Dysfunction by Increasing eNOS Activity SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Meeting Abstract DE Endothelial Cells; Endothelial Dysfunction; Chronic Kidney Disease; Nitric Oxide Synthase C1 [Fadi, Hage G.; Maricica, Pacurari; Xing Dongqi; Rob, Hilgers; Guo YuanYuan; Chen Yiu-Fai] Univ Alabama Birmingham, Birmingham, AL USA. [Fadi, Hage G.; Guo YuanYuan] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD MAY PY 2013 VL 15 SU 1 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AA0EX UT WOS:000330769400094 ER PT J AU Oscar, R Rene, AO Joan, HF Shuko, L Robert, JC AF Oscar, Rivera Rene, Oliveros A. Joan, Finch H. Shuko, Lee Robert, Chilton J. TI Central Aortic Pulse Pressure, a Better Predictor of Vascular Aging SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Meeting Abstract DE Central Pulse Pressure; Aging C1 [Oscar, Rivera; Rene, Oliveros A.; Shuko, Lee; Robert, Chilton J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Rene, Oliveros A.; Joan, Finch H.; Shuko, Lee; Robert, Chilton J.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 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 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD MAY PY 2013 VL 15 SU 1 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AA0EX UT WOS:000330769400047 ER PT J AU Lawson, EA Holsen, LM Santin, M DeSanti, R Meenaghan, E Eddy, KT Herzog, DB Goldstein, JM Klibanski, A AF Lawson, Elizabeth A. Holsen, Laura M. Santin, McKale DeSanti, Rebecca Meenaghan, Erinne Eddy, Kamryn T. Herzog, David B. Goldstein, Jill M. Klibanski, Anne TI Postprandial Oxytocin Secretion Is Associated With Severity of Anxiety and Depressive Symptoms in Anorexia Nervosa SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIENT MICE; STRESS; HYPOACTIVATION; RESPONSES; BEHAVIOR; MODELS; WOMEN; RATS; FAT AB Objective: Anorexia nervosa, a psychiatric disorder characterized by self-induced starvation, is associated with endocrine dysfunction and comorbid anxiety and depression. Animal data suggest that oxytocin may have anxiolytic and antidepressant effects. We have reported increased postprandial oxytocin levels in women with active anorexia nervosa and decreased levels in weight-recovered women with anorexia nervosa compared to healthy controls. A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between postprandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa. Method: We performed a cross-sectional study of 35 women (13 women with active anorexia nervosa, 9 with weight-recovered anorexia nervosa, and 13 healthy controls). Anorexia nervosa was diagnosed according to DSM-IV-TR criteria. Serum oxytocin and cortisol and plasma leptin levels were measured fasting and 30, 60, and 120 minutes after a standardized mixed meal. The area under the curve (AUC) and, for oxytocin, postprandial nadir and peak levels were determined. Anxiety and depressive symptoms were assessed using the Spielberger State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II). The study was conducted from January 2009 to March 2011. Results: In women with anorexia nervosa, oxytocin AUC and postprandial nadir and peak levels were positively associated with STAI trait and STAI premeal and postmeal state scores. Oxytocin AUC and nadir levels were positively associated with BDI-II scores. After controlling for cortisol AUC, all of the relationships remained significant. After controlling for leptin AUC, most of the relationships remained significant. Oxytocin secretion explained up to 51% of the variance in STAI trait and 24% of the variance in BDI-II scores. Conclusions: Abnormal postprandial oxytocin secretion in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. This link may represent an adaptive response of oxytocin secretion to food-related symptoms of anxiety and depression. (C) Copyright 2013 Physicians Postgraduate Press, Inc. C1 [Lawson, Elizabeth A.; Santin, McKale; DeSanti, Rebecca; Meenaghan, Erinne; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Eddy, Kamryn T.; Herzog, David B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Holsen, Laura M.; Goldstein, Jill M.] Harvard Univ, Sch Med, Boston, MA USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Lawson, EA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457-D, Boston, MA 02114 USA. EM ealawson@partners.org FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Institutes of Health [NIH] Award [UL1 RR025758]; NIH Office of Research in Women's Health [K12 HD051959]; NIH [K23 MH092560] FX Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Institutes of Health [NIH] Award #UL1 RR025758); Harvard K12 HD051959 Building Interdisciplinary Research Careers in Women's Health Program supported by NIH Office of Research in Women's Health; and NIH K23 MH092560. NR 27 TC 15 Z9 16 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2013 VL 74 IS 5 BP E451 EP E457 DI 10.4088/JCP.12m08154 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AA5AI UT WOS:000331107500007 PM 23759466 ER PT J AU Giannino, K Berry, L McCarthy, MW Campbell, M AF Giannino, Kerri Berry, Laura McCarthy, Maureen W. Campbell, Melissa TI THE POUCH HALF FULL: PROMOTING POSITIVITY THROUGH CREATIVE RESOURCES SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [Giannino, Kerri; Berry, Laura; McCarthy, Maureen W.; Campbell, Melissa] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM KmGiannino@partners.org; lberry1@partners.org; mmccarthy29@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 EI 1528-3976 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2013 VL 40 SU 3 MA 1608 BP S64 EP S65 PG 2 WC Nursing SC Nursing GA 300KD UT WOS:000330461900179 ER PT J AU Giannino, K McCarthy, MW Berry, L Campbell, M AF Giannino, Kerri McCarthy, Maureen W. Berry, Laura Campbell, Melissa TI "LET'S TRY A BABY NIPPLE": CREATIVE MANAGEMENT OF A COMPLEX ABDOMINAL WOUND SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [Giannino, Kerri; McCarthy, Maureen W.; Berry, Laura; Campbell, Melissa] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM KmGiannino@partners.org; mmccarthy29@partners.org; lberry1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 EI 1528-3976 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2013 VL 40 SU 3 MA 1449 BP S24 EP S24 PG 1 WC Nursing SC Nursing GA 300KD UT WOS:000330461900065 ER PT J AU Hyder, JA Kor, DJ Cima, R Subramanian, A AF Hyder, J. A. Kor, D. J. Cima, R. Subramanian, A. TI SAMPLING STRATEGY FOR VITAL SIGNS AFFECTS PERFORMANCE OF INTRAOPERATIVE RISK MODELS: THE EXAMPLE OF THE SURGICAL APGAR SCORE SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 04-07, 2013 CL San Diego, CA SP Int Anesthesia Res Soc C1 [Hyder, J. A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cima, R.] Mayo Clin, Dept Surg, Rochester, MN USA. [Kor, D. J.; Subramanian, A.] Mayo Clin, Dept Anesthesioloy, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 SU 1 MA S271 BP 216 EP 216 PG 1 WC Anesthesiology SC Anesthesiology GA 300CJ UT WOS:000330441700186 ER PT J AU Campana, LM George, E Freeman, J Ladd, D MacNabb, C Lee, JC Voscopoulos, C AF Campana, L. M. George, E. Freeman, J. Ladd, D. MacNabb, C. Lee, J. C. Voscopoulos, C. TI THE USE OF NONINVASIVE RESPIRATORY VOLUME MONITORING TO ASSESS OBSTRUCTIVE SLEEP APNEA IN THE POST-ANESTHESIA CARE UNIT SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 04-07, 2013 CL San Diego, CA SP Int Anesthesia Res Soc C1 [Campana, L. M.; Freeman, J.; MacNabb, C.; Lee, J. C.] Resp Mot Inc, Waltham, MA USA. [George, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ladd, D.] W Virginia Univ, Morgantown, WV 26506 USA. [Voscopoulos, C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 SU 1 MA S286 BP 230 EP 230 PG 1 WC Anesthesiology SC Anesthesiology GA 300CJ UT WOS:000330441700201 ER PT J AU Voscopoulos, C Freeman, J Ladd, D Brayanov, JB MacNabb, C George, E AF Voscopoulos, C. Freeman, J. Ladd, D. Brayanov, J. B. MacNabb, C. George, E. TI USE OF A NON-INVASIVE RESPIRATORY VOLUME MONITOR TO IDENTIFY OPIOID INDUCED RESPIRATORY DEPRESSION IN THE POST-ANESTHESIA CARE UNIT SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 04-07, 2013 CL San Diego, CA SP Int Anesthesia Res Soc C1 [Voscopoulos, C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Freeman, J.; Brayanov, J. B.; MacNabb, C.] Resp Mot Inc, Waltham, MA USA. [Ladd, D.] W Virginia Univ, Morgantown, WV 26506 USA. [George, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 SU 1 MA S287 BP 231 EP 232 PG 2 WC Anesthesiology SC Anesthesiology GA 300CJ UT WOS:000330441700202 ER PT J AU Wanderer, JP Anderson-Dam, J Levine, W Bittner, EA AF Wanderer, J. P. Anderson-Dam, J. Levine, W. Bittner, E. A. TI DEVELOPMENT AND VALIDATION OF AN INTRA-OPERATIVE PREDICTIVE MODEL FOR UNPLANNED POST-OPERATIVE INTENSIVE CARE SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 04-07, 2013 CL San Diego, CA SP Int Anesthesia Res Soc C1 [Wanderer, J. P.] Vanderbilt Univ, Dept Anesthesiol, Nashville, TN 37235 USA. [Anderson-Dam, J.; Levine, W.; Bittner, E. A.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 SU 1 MA S364 BP 287 EP 287 PG 1 WC Anesthesiology SC Anesthesiology GA 300CJ UT WOS:000330441700244 ER PT J AU Preiss, D AF Preiss, D. TI THE NOISE BECOMES THE SIGNAL: VARIATIONS IN TIDAL VOLUME AND EXHALED CO2 CAN BE USED TO CALCULATE PULMONARY BLOOD FLOW SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 04-07, 2013 CL San Diego, CA SP Int Anesthesia Res Soc ID CARDIAC-OUTPUT C1 [Preiss, D.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 SU 1 MA S379 BP 304 EP 304 PG 1 WC Anesthesiology SC Anesthesiology GA 300CJ UT WOS:000330441700259 ER PT J AU Chen, HH Mekkaoui, C Cho, H Ngoy, S Marinelli, B Waterman, P Nahrendorf, M Liao, R Josephson, L Sosnovik, DE AF Chen, Howard H. Mekkaoui, Choukri Cho, Hoonsung Ngoy, Soeun Marinelli, Brett Waterman, Peter Nahrendorf, Matthias Liao, Ronglih Josephson, Lee Sosnovik, David E. TI Fluorescence Tomography of Rapamycin-Induced Autophagy and Cardioprotection In Vivo SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE apoptosis; autophagy; molecular imaging; myocardium; rapamycin ID ISCHEMIC-MYOCARDIUM; ISCHEMIA/REPERFUSION INJURY; INFARCTED MYOCARDIUM; REPERFUSION INJURY; CARDIAC MYOCYTES; CELL-DEATH; APOPTOSIS; HEART; MICE; CARDIOMYOCYTES AB Background-Autophagy is a biological process during which cells digest organelles in their cytoplasm and recycle the constituents. The impact of autophagy in the heart, however, remains unclear in part because of the inability to noninvasively image this process in living animals. Methods and Results-Here, we report the use of fluorescence molecular tomography and a cathepsin-activatable fluorochrome to image autophagy in the heart in vivo after ischemia/reperfusion and rapamycin (RAP) therapy. We show that cathepsin-B activity in the lysosome is upregulated by RAP and that this allows the expanded lysosomal compartment in autophagy to be imaged in vivo with fluorescence molecular tomography. We further demonstrate that the delivery of diagnostic nanoparticles to the lysosome by endocytosis is enhanced during autophagy. The upregulation of autophagy by RAP was associated with a 23% reduction (P<0.05) of apoptosis in the area at risk and a 45% reduction in final infarct size (19.6 +/- 5.6% of area at risk with RAP versus 35.9 +/- 9.1% of area at risk without RAP; P<0.05). Conclusions-The ability to perform noninvasive tomographic imaging of autophagy in the heart has the potential to provide valuable insights into the pathophysiology of autophagy, particularly its role in cardiomyocyte salvage. Although additional data are needed, our study supports the investigation of RAP therapy in patients with acute coronary syndromes. C1 [Chen, Howard H.; Mekkaoui, Choukri; Josephson, Lee; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Chen, Howard H.; Marinelli, Brett; Waterman, Peter; Nahrendorf, Matthias; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Chen, Howard H.; Mekkaoui, Choukri; Cho, Hoonsung; Josephson, Lee; Sosnovik, David E.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cho, Hoonsung; Josephson, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Translat Nucl Med & Mol Imaging, Boston, MA USA. [Marinelli, Brett; Waterman, Peter; Nahrendorf, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Ngoy, Soeun; Liao, Ronglih] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Ngoy, Soeun; Liao, Ronglih] Harvard Univ, Sch Med, Boston, MA USA. RP Sosnovik, DE (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu FU National Institutes of Health [R01 HL093038, R01 EB011996, P41RR14075] FX This work was funded in part by the following grants from the National Institutes of Health: R01 HL093038 (Dr Sosnovik), R01 EB011996 (Dr Josephson), and P41RR14075 (Martinos Center). NR 31 TC 14 Z9 14 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2013 VL 6 IS 3 BP 441 EP + DI 10.1161/CIRCIMAGING.112.000074 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 298YI UT WOS:000330360300019 PM 23537953 ER PT J AU Kato, K Yonetsu, T Jia, HB Abtahian, F Vergallo, R Hu, SN Tian, JW Kim, SJ Lee, H McNulty, I Lee, S Uemura, S Jang, Y Park, SJ Mizuno, K Yu, B Jang, IK AF Kato, Koji Yonetsu, Taishi Jia, Haibo Abtahian, Farhad Vergallo, Rocco Hu, Sining Tian, Jinwei Kim, Soo-Joong Lee, Hang McNulty, Iris Lee, Stephen Uemura, Shiro Jang, Yangsoo Park, Seung-Jung Mizuno, Kyoichi Yu, Bo Jang, Ik-Kyung TI Nonculprit Coronary Plaque Characteristics of Chronic Kidney Disease SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE cholesterol crystal; chronic kidney disease; optical coherence tomography; plaque ID OPTICAL COHERENCE TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; GLOMERULAR-FILTRATION-RATE; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; CARDIOVASCULAR-DISEASE; ARTERY-DISEASE; RISK-FACTOR; MORPHOLOGY; DEATH AB Background-Chronic kidney disease (CKD) promotes the development of atherosclerosis and increases the risk of cardiovascular disease. The aim of the present study was to compare the coronary plaque characteristics of patients with and without CKD using optical coherence tomography. Methods and Results-We identified 463 nonculprit plaques from 287 patients from the Massachusetts General Hospital (MGH) optical coherence tomography registry. CKD was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m(2). A total of 402 plaques (250 patients) were in the non-CKD group and 61 plaques (37 patients) were in the CKD group. Compared with non-CKD plaques, plaques with CKD had a larger lipid index (mean lipid arcxlipid length, 1248.4 +/- 782.8 mm degrees [non-CKD] versus 1716.1 +/- 1116.2 mm degrees [CKD]; P=0.003). Fibrous cap thickness was not significantly different between the groups. Calcification (34.8% [non-CKD] versus 50.8% [CKD]; P=0.041), cholesterol crystals (11.2% [non-CKD] versus 23.0% [CKD]; P=0.048), and plaque disruption (5.5% [non-CKD] versus 13.1% [CKD]; P=0.049) were more frequently observed in the CKD group. In the multivariate linear regression model, a lower estimated glomerular filtration rate and diabetes mellitus were independent risk factors for a larger lipid index. Conclusions-Compared with non-CKD patients, the patients with CKD had a larger lipid index with a higher prevalence of calcium, cholesterol crystals, and plaque disruption. The multivariate linear regression model demonstrated that a lower estimated glomerular filtration rate was an independent risk factor for a larger lipid index. C1 [Kato, Koji; Yonetsu, Taishi; Jia, Haibo; Abtahian, Farhad; Vergallo, Rocco; Hu, Sining; Tian, Jinwei; Kim, Soo-Joong; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Jia, Haibo; Hu, Sining; Tian, Jinwei; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Key Lab Myocardial Ischemia,Chinese Minist Educ, Harbin 150086, Peoples R China. [Kim, Soo-Joong] Kyung Hee Univ, Dept Cardiol, Coll Med, Seoul, South Korea. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA USA. [Lee, Stephen] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Peoples R China. [Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [Jang, Yangsoo] Yonsei Univ, Severance Cardiovasc Hosp, Seoul 120749, South Korea. [Park, Seung-Jung] Asan Med Ctr, Seoul, South Korea. [Mizuno, Kyoichi] Nippon Med Sch, Dept Cardiovasc Med, Tokyo 113, Japan. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Key Lab Myocardial Ischemia,Chinese Minist Educ, Harbin 246 Xuefu Rd, Harbin 150086, Peoples R China. EM yubodr@163.com FU St. Jude Medical, the Cardiology Division of Massachusetts General Hospital; Dr John Nam fellowship grant FX This study was supported by research grants from St. Jude Medical, the Cardiology Division of Massachusetts General Hospital, and the Dr John Nam fellowship grant. NR 42 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2013 VL 6 IS 3 BP 448 EP + DI 10.1161/CIRCIMAGING.112.000165 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 298YI UT WOS:000330360300020 PM 23536265 ER PT J AU Parker, BA Zaleski, AL Capizzi, JA Lorson, L Ballard, KD Troyanos, CS Baggish, AL D'Hemecourt, PA Thompson, PD AF Parker, Beth A. Zaleski, Amanda L. Capizzi, Jeffrey A. Lorson, Lindsay Ballard, Kevin D. Troyanos, Christopher S. Baggish, Aaron L. D'Hemecourt, Pierre A. Thompson, Paul D. TI Chronic Exercise Does Not Mitigate The Effects Of Age And Cardiovascular Risk On Coronary Atherosclerosis SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [Parker, Beth A.; Zaleski, Amanda L.; Capizzi, Jeffrey A.; Lorson, Lindsay; Ballard, Kevin D.; Thompson, Paul D.] Hartford Hosp, Hartford, CT 06115 USA. [Troyanos, Christopher S.; D'Hemecourt, Pierre A.] Childrens Hosp, Boston, MA 02115 USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 112 BP 10 EP 10 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469700032 ER PT J AU La Fountaine, MF Bauman, WA AF La Fountaine, Michael F. Bauman, William A. TI Use of Phase-rectified Signal Averaging to Examine Autonomic Dysfunction After Concussive Head Trauma SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [La Fountaine, Michael F.] Seton Hall Univ, S Orange, NJ 07079 USA. [Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 217 BP 40 EP 40 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469700119 ER PT J AU Contursi, ME Baggish, AL Lewis, GD AF Contursi, Miranda E. Baggish, Aaron L. Lewis, Gregory D. TI Exercise Induced Hemoptysis: A Hemodynamic Intervention Case Report SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [Contursi, Miranda E.; Baggish, Aaron L.; Lewis, Gregory D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 1034 BP 224 EP 224 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469701380 ER PT J AU Zilinski, JL Contursi, ME Lowry, PA O'Callaghan, CH Fifer, MA Lewis, GD Baggish, AL AF Zilinski, Jodi L. Contursi, Miranda E. Lowry, Patricia A. O'Callaghan, Caitlin H. Fifer, Michael A. Lewis, Gregory D. Baggish, Aaron L. TI Syncope and Abnormal Electrocardiogram in an Adolescent Basketball Player SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [Zilinski, Jodi L.; Contursi, Miranda E.; Lowry, Patricia A.; O'Callaghan, Caitlin H.; Fifer, Michael A.; Lewis, Gregory D.; Baggish, Aaron L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 1772 BP 408 EP 409 PG 2 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469703180 ER PT J AU Scarborough, DM Driscoll, S Salzler, M Berkson, EM AF Scarborough, Donna M. Driscoll, Sean Salzler, Mathew Berkson, Eric M. TI Comparison Of The Biomechanics Of Running In Barefoot And Minimalist Shoe Conditions SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [Scarborough, Donna M.; Driscoll, Sean; Berkson, Eric M.] Massachusetts Gen Hosp, Foxboro, MA USA. [Salzler, Mathew] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 5 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 1877 BP 425 EP 425 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469703221 ER PT J AU Ingram, KH Thalacker-Mercer, A Garvey, WT AF Ingram, Katherine H. Thalacker-Mercer, Anna Garvey, W. Timothy TI Amino Acids and Insulin Sensitivity in Non-Obese, Obese, and Type 2 Diabetic Patients SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [Ingram, Katherine H.] Kennesaw State Univ, Kennesaw, GA USA. [Thalacker-Mercer, Anna] Cornell Univ, Ithaca, NY USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Birmingham, AL USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 1886 BP 427 EP 428 PG 2 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469703229 ER PT J AU Ackerman, KE Nazem, TG Patel, KT Ouellette, M Huguenel, B Shimodaira, K Pierce, L Guereca, G Hubbard, J Holmes, TM Anderson, EJ Misra, M AF Ackerman, Kathryn Elizabeth Nazem, Taraneh G. Patel, Kamal T. Ouellette, Miranda Huguenel, Brynn Shimodaira, Kenji Pierce, Lisa Guereca, Gabriela Hubbard, Jane Holmes, Tara M. Anderson, Ellen J. Misra, Madhusmita TI Macro- and Micronutrient Intake Is Associated With Bone Density In Young Athletes And Non-athletes SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [Ackerman, Kathryn Elizabeth] Boston Childrens Hosp, Boston, MA USA. [Nazem, Taraneh G.; Patel, Kamal T.; Ouellette, Miranda; Huguenel, Brynn; Shimodaira, Kenji; Pierce, Lisa; Guereca, Gabriela; Hubbard, Jane; Holmes, Tara M.; Anderson, Ellen J.; Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 2246 BP 521 EP 521 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469704146 ER PT J AU McConnell, TR Trevino, KM AF McConnell, Timothy R. Trevino, Kelly M. TI A Longitudinal Evaluation Of Religiosity, Spirituality, And Religious Coping Following A First Time Cardiac Event SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [McConnell, Timothy R.] Bloomsburg Univ Penn, Bloomsburg, PA 17815 USA. [Trevino, Kelly M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 2367 BP 556 EP 556 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469704259 ER PT J AU DiPasquale, DM Strangman, GE Muza, SR AF DiPasquale, Dana M. Strangman, Gary E. Muza, Stephen R. TI Altitude Vs. Hypoxia: Comparing The Effects Of Exercise In Hypobaric And Normobaric Hypoxia On Resting Heart Rate SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [DiPasquale, Dana M.; Strangman, Gary E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Muza, Stephen R.] US Army Res Inst Environm Med, Natick, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 2706 BP 632 EP 632 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469705068 ER PT J AU DiPiro, ND Bowden, MG Embry, AE Perry, LA Morgan, PJ Gregory, CM AF DiPiro, Nicole D. Bowden, Mark G. Embry, Aaron E. Perry, Lindsay A. Morgan, Patrick J. Gregory, Chris M. TI A Short-term, High-intensity Multimodal Exercise Program Improves Strength and Function After Incomplete SCI SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [DiPiro, Nicole D.; Embry, Aaron E.; Perry, Lindsay A.; Morgan, Patrick J.] MUSC, Charleston, SC USA. [Bowden, Mark G.; Gregory, Chris M.] MUSC, Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 2767 BP 652 EP 652 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469705129 ER PT J AU Killoran, A Biglan, KM Jankovic, J Eberly, S Kayson, E Oakes, D Young, AB Shoulson, I AF Killoran, Annie Biglan, Kevin M. Jankovic, Joseph Eberly, Shirley Kayson, Elise Oakes, David Young, Anne B. Shoulson, Ira TI Characterization of the Huntington intermediate CAG repeat expansion phenotype in PHAROS SO NEUROLOGY LA English DT Article ID FRAGILE-X PREMUTATION; AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; DISEASE CHROMOSOMES; GENE; CARRIERS; ALLELES; LENGTH; HD AB Objectives: We aimed to describe the clinical phenotype conferred by the intermediate-length huntingtin allele CAG repeat expansion in a population-based study. Methods: The Prospective Huntington At Risk Observational Study (PHAROS) enrolled adults at risk for Huntington disease (HD). They were assessed approximately every 9 months with the Unified Huntington's Disease Rating Scale (UHDRS) by investigators unaware of participants' gene status. UHDRS scores were compared according to the Huntingtin gene CAG repeat number: expanded >36, intermediate 27-35, and nonexpanded controls <26. Results: Fifty (5.1%) of the 983 participants had an intermediate allele (IA). They were similar to controls on UHDRS motor, cognitive, and functional measures, but significantly worse behaviorally on apathy and suicidal ideation. On 5 of the 9 other behavioral items and on total behavior, the IA group's scores were worse than those of controls and expanded participants, who themselves scored significantly worse than controls on 6 behavioral measures. Retention rates at 4 years were 48% for the IA group compared to 58% and 60% for the expanded and control groups. Conclusions: In a cohort at risk for HD, the IA was associated with significant behavioral abnormalities but normal motor and cognition. This behavioral phenotype may represent a prodromal stage of HD, with the potential for subsequent clinical manifestations, or be part of a distinct phenotype conferred by pathology independent of the CAG expansion length. C1 [Killoran, Annie; Biglan, Kevin M.] Univ Rochester, Rochester, NY 14627 USA. [Killoran, Annie] W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Morgantown, WV 26506 USA. [Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA. [Eberly, Shirley; Kayson, Elise; Oakes, David] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Young, Anne B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shoulson, Ira] Georgetown Univ, Washington, DC USA. RP Killoran, A (reprint author), Univ Rochester, Rochester, NY 14627 USA. EM ankilloran@hsc.wvu.edu FU NIH/NHGRI/National Institute of Neurological Disorders and Stroke [R01HG02449] FX Supported by NIH/NHGRI/National Institute of Neurological Disorders and Stroke R01HG02449. NR 27 TC 27 Z9 27 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY PY 2013 VL 80 IS 22 BP 2022 EP 2027 DI 10.1212/WNL.0b013e318294b304 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 300LX UT WOS:000330466500013 PM 23624566 ER PT J AU Cooper, ZA Frederick, DT Ahmed, Z Wargo, JA AF Cooper, Zachary A. Frederick, Dennie T. Ahmed, Zain Wargo, Jennifer A. TI Combining checkpoint inhibitors and BRAF-targeted agents against metastatic melanoma SO ONCOIMMUNOLOGY LA English DT Editorial Material DE BRAF; checkpoint blockade; immunotherapy; melanoma; PDL1 ID INFILTRATION; ANTIBODY; CANCER; SAFETY AB The combination of BRAF-targeted agents with immune checkpoint inhibitors represents a recent advance in the treatment of melanoma, even though each of these therapeutic approaches alone has specific limitations. Increasing evidence suggests indeed the existence of a synergistic interaction between these therapeutic modalities. C1 [Cooper, Zachary A.; Frederick, Dennie T.; Ahmed, Zain; Wargo, Jennifer A.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Wargo, JA (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM jwargo@partners.org OI Cooper, Zachary/0000-0003-1059-0940 NR 10 TC 19 Z9 19 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD MAY PY 2013 VL 2 IS 5 AR e24320 DI 10.4161/onci.24320 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 301HQ UT WOS:000330523800029 ER PT J AU Cortez-Retamozo, V Engblom, C Pittet, MJ AF Cortez-Retamozo, Virna Engblom, Camilla Pittet, Mikael J. TI Remote control of macrophage production by cancer SO ONCOIMMUNOLOGY LA English DT Editorial Material DE hematopoietic stem cell; monocyte; macrophage; cancer; NSCLC; lung adenocarcinoma; Angiotensin II ID TUMOR; MONOCYTES AB The communication between tumor and host cells involves signals that act across extended distances in the body. recent evidence indicates that the hormone angiotensin II is overproduced by lung adenocarcinoma to remotely expand bone marrow-derived hematopoietic stem cells. this process amplifies the supply of tumor-associated macrophages, which promote disease progression. C1 [Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu FU NIAID NIH HHS [R01 AI084880] NR 10 TC 5 Z9 6 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD MAY PY 2013 VL 2 IS 5 AR e24183 DI 10.4161/onci.24183 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 301HQ UT WOS:000330523800025 PM 23762799 ER PT J AU Black, EM Antoci, V Lee, JT Weaver, MJ Johnson, AH Susarla, SM Kwon, JY AF Black, Eric M. Antoci, Valentin Lee, Jared T. Weaver, Michael J. Johnson, A. Holly Susarla, Seenu M. Kwon, John Y. TI Role of Preoperative Computed Tomography Scans in Operative Planning for Malleolar Ankle Fractures SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE trauma; CT scan; advanced imaging; malleolar ankle fracture; operative planning ID PILON FRACTURES; ANATOMY AB Background: There remains no consensus regarding the role of computed tomography (CT) scans in preoperative planning for malleolar ankle fractures. The aim of this study was to determine the role of preoperative CT scans on operative planning in these fractures. Methods: A retrospective analysis was performed on 100 consecutive patients treated at our institution for malleolar ankle fractures (AO type 44) with both preoperative radiographs and CT scans. Six study participants reviewed available radiographs and formulated an operative (or nonoperative) plan including positioning, operative approach, and fixation. Participants then analyzed CT scans of the same fractures, deciding whether (and how) they would alter operative strategy. Characteristics of fractures and radiographs were correlated with changes in operative strategy. Results: Operative strategy was notably changed in 24% of cases after CT review, with strong intraclass correlation (0.733). Common changes included alterations in medial malleolar (21%) or posterior malleolar (15%) fixation and fixation of an occult anterolateral plafond fracture (9%). Notable predictors of changes in operative strategy included trimalleolar over unimalleolar fractures (29% vs 10% rate of change), preoperative dislocation over no dislocation (31% vs 20%), the presence of only radiographs with overlying plaster versus fractures with at least 1 set of radiographs without plaster (25% vs 14%), and suprasyndesmotic versus trans- and infra-syndesmotic fractures (40% vs 20% and 4%, respectively). Conclusions: CT scans may be useful adjuncts in preoperative planning for malleolar ankle fractures, most notably in fracture dislocations, cases in which all available radiographs are obscured by plaster, trimalleolar fractures, and suprasyndesmotic fractures. C1 [Black, Eric M.; Antoci, Valentin; Johnson, A. Holly; Susarla, Seenu M.; Kwon, John Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Jared T.] Steadman Clin, Vail, CO USA. [Weaver, Michael J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kwon, JY (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM Jkwon@Partners.Org OI Susarla, Srinivas/0000-0003-0155-8260 NR 12 TC 9 Z9 9 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAY PY 2013 VL 34 IS 5 BP 697 EP 704 DI 10.1177/1071100713475355 PG 8 WC Orthopedics SC Orthopedics GA 298FE UT WOS:000330308700010 PM 23637238 ER PT J AU Riegel, B Hanlon, AL Zhang, XM Fleck, D Sayers, SL Goldberg, LR Weintraub, WS AF Riegel, Barbara Hanlon, Alexandra L. Zhang, Xuemei Fleck, Desiree Sayers, Steven L. Goldberg, Lee R. Weintraub, William S. TI What is the best measure of daytime sleepiness in adults with heart failure? SO JOURNAL OF THE AMERICAN ASSOCIATION OF NURSE PRACTITIONERS LA English DT Article DE Heart failure; screening; sleep disorders; outcomes ID APNEA PATIENTS; SCALE; QUALITY; POPULATION; CONSEQUENCES; DEPRIVATION; SENSITIVITY; PERFORMANCE; PREVALENCE; VIGILANCE AB Purpose: To identify the best screening measure of daytime sleepiness in adults with heart failure (HF). Data sources: A total of 280 adults with HF completed the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, and a single Likert item measuring daytime sleepiness. The sensitivity and specificity of these self-report measures were assessed in relation to a measure of daytime dysfunction from poor sleep quality. Conclusions: Only 16% of the sample reported significant daytime dysfunction because of poor sleep quality. Those reporting daytime dysfunction were likely to be younger (p < .001), to be unmarried (p = .002), to have New York Heart Association (NYHA) functional class IV HF (p = .015), and to report low income (p = .006) and fewer hours of sleep (p = .015). The measure of daytime sleepiness that was most sensitive to daytime dysfunction was a single Likert item measured on a 10-point (1-10) scale. Patients with a score >= 4 were 2.4 times more likely to have daytime dysfunction than those with a score <4. Implications for practice: Complaints of daytime dysfunction because of poor sleep are not common in adults with HF. Routine use of a single question about daytime sleepiness can help nurse practitioners to identify those HF patients with significant sleep issues that may require further screening. C1 [Riegel, Barbara; Hanlon, Alexandra L.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Zhang, Xuemei] Childrens Hosp Philadelphia Westat BDMC, Philadelphia, PA USA. [Fleck, Desiree] Univ Penn, Sch Nursing, Childrens Hosp Penn, Philadelphia, PA 19104 USA. [Sayers, Steven L.; Goldberg, Lee R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Sayers, Steven L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Weintraub, William S.] Christiana Care Ctr Outcomes Res Christiana Care, Newark, DE USA. RP Riegel, B (reprint author), Univ Penn, Sch Nursing, 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 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 47 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2327-6886 EI 2327-6924 J9 J AM ASSOC NURSE PRA JI J. Am. Assoc. Nurs. Pract. PD MAY PY 2013 VL 25 IS 5 BP 272 EP 279 DI 10.1111/j.1745-7599.2012.00784.x PG 8 WC Health Care Sciences & Services; Nursing SC Health Care Sciences & Services; Nursing GA 296GM UT WOS:000330173200006 PM 24170569 ER PT J AU Quinn, AM Farraye, FA Naini, BV Cerda, S Coukos, J Li, Y Khor, T Odze, RD AF Quinn, Andrew M. Farraye, Francis A. Naini, Bita V. Cerda, Sandra Coukos, Jennifer Li, Yuan Khor, Tze Odze, Robert D. TI Polypectomy is Adequate Treatment for Adenoma-like Dysplastic Lesions (DALMs) in Crohn's Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE adenoma-like DALM; Crohn's disease; dysplasia; adenocarcinoma; polyp ID INFLAMMATORY-BOWEL-DISEASE; CHRONIC ULCERATIVE-COLITIS; CANCER-RISK; COLORECTAL-CANCER; POLYPOID DYSPLASIA; SPORADIC ADENOMAS; ENDOSCOPIC RESECTION; FOLLOW-UP; CARCINOMA; SURVEILLANCE AB Background:The purpose of this study was to reevaluate the clinical and pathologic features and outcomes in patients with Crohn's disease with an adenoma-like dysplasia-associated lesion or mass (DALMs) to determine if polypectomy is adequate treatment.Methods:The clinical, endoscopic and pathologic features, and outcomes of 50 patients with Crohn's disease, each with 1 adenoma-like DALM were evaluated. The median length of follow-up was 39 months (range: 0.5-156 months).Results:Of the 50 patients with Crohn's disease (male to female ratio, 30:20; median age: 53 years; median duration of disease: 83 months), 11 had ileal disease, 26 had colonic disease, and 13 had both ileal and colonic disease. Approximately 43% of polyps occurred within areas of previous or concurrent colitis, whereas 57% occurred in areas not previously involved by colitis. Most polyps had tubular architecture and contained low-grade dysplasia. Of the patients who had polypectomy followed by surveillance, 45% developed new adenoma-like DALMs, but none developed flat dysplasia and only 1 had adenocarcinoma at the time of resection, which was within 3 months of polypectomy. There were no differences in the clinical or pathologic features or outcomes in patients who had adenoma-like DALMs within versus outside areas of previous or concurrent colitis, except that the former showed a higher risk of developing new polyps within areas of colitis and near the site of the original polyp compared with the latter.Conclusions:Patients with Crohn's disease who develop an adenoma-like DALM, regardless of its location in relationship to previous or concurrent colitis, may be treated safely with polypectomy and continued surveillance. C1 [Quinn, Andrew M.; Odze, Robert D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Farraye, Francis A.; Cerda, Sandra; Coukos, Jennifer] Boston Med Ctr, Boston, MA USA. [Naini, Bita V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Li, Yuan; Khor, Tze] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Odze, RD (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM rodze@partners.org OI Farraye, Francis/0000-0001-6371-2441; Cerda, Sandra/0000-0002-7779-6110 NR 33 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2013 VL 19 IS 6 BP 1186 EP 1193 DI 10.1097/MIB.0b013e318280e749 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284WT UT WOS:000329353200014 PM 23567776 ER PT J AU Klimesova, K Kverka, M Zakostelska, Z Hudcovic, T Hrncir, T Stepankova, R Rossmann, P Ridl, J Kostovcik, M Mrazek, J Kopecny, J Kobayashi, KS Tlaskalova-Hogenova, H AF Klimesova, Klara Kverka, Miloslav Zakostelska, Zuzana Hudcovic, Tomas Hrncir, Tomas Stepankova, Renata Rossmann, Pavel Ridl, Jakub Kostovcik, Martin Mrazek, Jakub Kopecny, Jan Kobayashi, Koichi S. Tlaskalova-Hogenova, Helena TI Altered Gut Microbiota Promotes Colitis-Associated Cancer in IL-1 Receptor-Associated Kinase M-Deficient Mice SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE cancer in IBD; mucosal immunity; colorectal cancer; microbiota; germ-free ID INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; COLORECTAL-CANCER; IRAK-M; GERM-FREE; ANTIBIOTIC-TREATMENT; NEGATIVE REGULATOR; SYSTEMIC IMMUNITY; TUMOR-GROWTH; TGF-BETA AB Background:Microbial sensing by Toll-like receptors (TLR) and its negative regulation have an important role in the pathogenesis of inflammation-related cancer. In this study, we investigated the role of negative regulation of Toll-like receptors signaling and gut microbiota in the development of colitis-associated cancer in mouse model.Methods:Colitis-associated cancer was induced by azoxymethane and dextran sodium sulfate in wild-type and in interleukin-1 receptor-associated kinase M (IRAK-M)-deficient mice with or without antibiotic (ATB) treatment. Local cytokine production was analyzed by multiplex cytokine assay or enzyme-linked immunosorbent assay, and regulatory T cells were analyzed by flow cytometry. Changes in microbiota composition during tumorigenesis were analyzed by pyrosequencing, and -glucuronidase activity was measured in intestinal content by fluorescence assay.Results:ATB treatment of wild-type mice reduced the incidence and severity of tumors. Compared with nontreated mice, ATB-treated mice had significantly lower numbers of regulatory T cells in colon, altered gut microbiota composition, and decreased -glucuronidase activity. However, the -glucuronidase activity was not as low as in germ-free mice. IRAK-M-deficient mice not only developed invasive tumors, but ATB-induced decrease in -glucuronidase activity did not rescue them from severe carcinogenesis phenotype. Furthermore, IRAK-M-deficient mice had significantly increased levels of proinflammatory cytokines in the tumor tissue.Conclusions:We conclude that gut microbiota promotes tumorigenesis by increasing the exposure of gut epithelium to carcinogens and that IRAK-M-negative regulation is essential for colon cancer resistance even in conditions of altered microbiota. Therefore, gut microbiota and its metabolic activity could be potential targets for colitis-associated cancer therapy. C1 [Klimesova, Klara; Kverka, Miloslav; Zakostelska, Zuzana; Hudcovic, Tomas; Hrncir, Tomas; Stepankova, Renata; Rossmann, Pavel; Tlaskalova-Hogenova, Helena] Acad Sci Czech Republic, Inst Microbiol, Dept Immunol & Gnotobiol, Vvi, CR-14220 Prague, Czech Republic. [Klimesova, Klara; Kverka, Miloslav; Zakostelska, Zuzana; Hudcovic, Tomas; Hrncir, Tomas; Stepankova, Renata; Rossmann, Pavel; Tlaskalova-Hogenova, Helena] Acad Sci Czech Republic, Inst Microbiol, Dept Immunol & Gnotobiol, Vvi, Novy Hradek, Czech Republic. [Ridl, Jakub] Acad Sci Czech Republic, Inst Mol Genet, Lab Genom & Bioinformat, Vvi, CR-14220 Prague, Czech Republic. [Kostovcik, Martin] Acad Sci Czech Republic, Inst Microbiol, Dept Biogenesis & Biotechnol Nat Cpds, Vvi, CR-14220 Prague, Czech Republic. [Mrazek, Jakub; Kopecny, Jan] Acad Sci Czech Republic, Lab Anaerob Microbiol, Inst Anim Physiol & Genet, Vvi, CR-14220 Prague, Czech Republic. [Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Klimesova, K (reprint author), Acad Sci Czech Republic, Inst Microbiol, Dept Immunol & Gnotobiol, Vvi, Videnska 1083, CR-14220 Prague, Czech Republic. EM klimesov@biomed.cas.cz RI Kopecny, Jan/C-3899-2011; Kverka, Miloslav/H-2507-2014; Mrazek, Jakub/G-7198-2014; Hrncir, Tomas/H-6733-2014; Kostovcik, Martin/H-2663-2014; Klimesova, Klara/J-6851-2014; Tlaskalova-Hogenova, Helena/J-8008-2014; stepankova, renata/J-9735-2014; Hudcovic, Tomas/H-7917-2014; Zakostelska, Zuzana/D-6518-2012 OI Kopecny, Jan/0000-0002-2428-2511; Kverka, Miloslav/0000-0002-1335-5252; Mrazek, Jakub/0000-0003-1907-3333; Klimesova, Klara/0000-0003-1821-398X; stepankova, renata/0000-0001-7504-6300; Hudcovic, Tomas/0000-0002-4761-5040; FU Czech Science Foundation [P304/11/1252, P303/08/0367, P303/12/0535]; Academy of Sciences of the Czech Republic [M200201207]; NIH [R01DK074738, R03TW006833]; Institutional Research Concept [RVO: 61388971] FX Supported by grants from the Czech Science Foundation (P304/11/1252, P303/08/0367, and P303/12/0535), the Academy of Sciences of the Czech Republic (No. M200201207), NIH (R01DK074738 and R03TW006833), and Institutional Research Concept (RVO: 61388971). NR 44 TC 27 Z9 27 U1 3 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2013 VL 19 IS 6 BP 1266 EP 1277 DI 10.1097/MIB.0b013e318281330a PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284WT UT WOS:000329353200025 PM 23567778 ER PT J AU Linder, JA Rigotti, NA Brawarsky, P Kontos, EZ Park, ER Klinger, EV Marinacci, L Li, WJ Haas, JS AF Linder, Jeffrey A. Rigotti, Nancy A. Brawarsky, Phyllis Kontos, Emily Z. Park, Elyse R. Klinger, Elissa V. Marinacci, Lucas Li, Wenjun Haas, Jennifer S. TI Use of Practice-Based Research Network Data to Measure Neighborhood Smoking Prevalence SO PREVENTING CHRONIC DISEASE LA English DT Article ID ELECTRONIC MEDICAL-RECORDS; SMALL-AREA ESTIMATION; PRIMARY-CARE; PRIORITIZING COMMUNITIES; TOBACCO DEPENDENCE; MASSACHUSETTS AB Introduction Practice-Based Research Networks (PBRNs) and health systems may provide timely, reliable data to guide the development and distribution of public health resources to promote healthy behaviors, such as quitting smoking. The objective of this study was to determine if PBRN data could be used to make neighborhood-level estimates of smoking prevalence. Methods We estimated the smoking prevalence in 32 greater Boston neighborhoods (population = 877,943 adults) by using the electronic health record data of adults who in 2009 visited one of 26 Partners Primary Care PBRN practices (n = 77,529). We compared PBRN-derived estimates to population-based estimates derived from 1999-2009 Behavioral Risk Factor Surveillance System (BRFSS) data (n = 20,475). Results The PBRN estimates of neighborhood smoking status ranged from 5% to 22% and averaged 11%. The 2009 neighborhood-level smoking prevalence estimates derived from the BRFSS ranged from 5% to 26% and averaged 13%. The difference in smoking prevalence between the PBRN and the BRFSS averaged -2 percentage points (standard deviation, 3 percentage points). Conclusion Health behavior data collected during routine clinical care by PBRNs and health systems could supplement or be an alternative to using traditional sources of public health data. C1 [Linder, Jeffrey A.; Brawarsky, Phyllis; Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA. [Linder, Jeffrey A.; Rigotti, Nancy A.; Park, Elyse R.; Haas, Jennifer S.] Harvard Univ, Sch Med, Boston, MA USA. [Rigotti, Nancy A.; Park, Elyse R.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.; Park, Elyse R.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Kontos, Emily Z.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Li, Wenjun] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Boston, MA 02125 USA. RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St, Boston, MA 02120 USA. EM jhaas@partners.org RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 FU Lung Cancer Disparities Center at the Harvard School of Public Health (National Cancer Institute) [P50 CA148596]; Harvard Catalyst, the Harvard Clinical and Translational Science Center (NIH) [1 UL1 RR 025758-01] FX This work was conducted with support from The Lung Cancer Disparities Center at the Harvard School of Public Health (National Cancer Institute Award no. P50 CA148596) and the Harvard Catalyst, the Harvard Clinical and Translational Science Center (NIH Grant no. 1 UL1 RR 025758-01 and financial contributions from participating institutions). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard University and its affiliated academic health care centers or the National Institutes of Health. NR 23 TC 1 Z9 1 U1 0 U2 1 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD MAY PY 2013 VL 10 AR UNSP 120132 DI 10.5888/pcd10.120132 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 285JX UT WOS:000329391200018 ER PT J AU Wyte-Lake, T Tran, K Bowman, CC Needleman, J Dobalian, A AF Wyte-Lake, Tamar Tran, Kim Bowman, Candice C. Needleman, Jack Dobalian, Aram TI A Systematic Review of Strategies to Address the Clinical Nursing Faculty Shortage SO JOURNAL OF NURSING EDUCATION LA English DT Review ID EDUCATION; PARTNERSHIP; WORKFORCE AB This systematic review provides a comprehensive assessment of models used to expand the ranks of clinical nursing faculty. Nursing faculty shortages constrict the pipeline for educating nurses and make addressing the projected nursing shortage more difficult. Schools of nursing have denied admission to qualified applicants, citing insufficient numbers of nursing faculty as one major reason. Using key search terms in PubMed (R) and CINAHL (R), we identified 14 peer-reviewed articles published between 1980 and 2010 about models for expanding clinical faculty. Partnership models (n = 11) and expanded use of faculty resources (n = 9) were the most common strategies. Few (n = 8) studies assessed program efficacy. A need was identified for studies to assess the effect of alternative models on educational capacity and student performance and to examine the sub-components of academic-practice partnerships and other innovative approaches to understand the essential factors necessary to implement successful programs. C1 [Wyte-Lake, Tamar; Tran, Kim; Bowman, Candice C.] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Study Healthcare Provider, Sepulveda, CA 91343 USA. [Needleman, Jack] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Dobalian, Aram] Vet Emergency Management Evaluat Ctr, North Hills, CA USA. RP Wyte-Lake, T (reprint author), VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Study Healthcare Provider, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM Tamar.wyte@va.gov RI Needleman, Jack/I-5461-2013 OI Needleman, Jack/0000-0002-2875-0589 FU Robert Wood Johnson Foundation [64104]; Department of Veterans Affairs, Veterans Health Administration, Office of Academic Affiliations [XVA 65-010]; Veterans Health Administration Health Service Research Postdoctoral Fellowship program FX This article is based on work supported by the Robert Wood Johnson Foundation (Project 64104) and the Department of Veterans Affairs, Veterans Health Administration, Office of Academic Affiliations (Project XVA 65-010). Dr. Tran receives support from the Veterans Health Administration Health Service Research Postdoctoral Fellowship program. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Robert Wood Johnson Foundation, the Department of Veterans Affairs, or the United States government. NR 26 TC 9 Z9 9 U1 0 U2 6 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 EI 1938-2421 J9 J NURS EDUC JI J. Nurs. Educ. PD MAY PY 2013 VL 52 IS 5 BP 245 EP U15 DI 10.3928/01484834-20130213-02 PG 12 WC Nursing SC Nursing GA 273RJ UT WOS:000328553700002 PM 23402282 ER PT J AU Chan, BT Hohmann, E Barshak, MB Pukkila-Worley, R AF Chan, Brian T. Hohmann, Elizabeth Barshak, Miriam Baron Pukkila-Worley, Read TI Treatment of Listeriosis in First Trimester of Pregnancy SO EMERGING INFECTIOUS DISEASES LA English DT Letter C1 [Chan, Brian T.; Hohmann, Elizabeth; Barshak, Miriam Baron; Pukkila-Worley, Read] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chan, Brian T.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Pukkila-Worley, R (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM rpukkilaworley@partners.org FU NIAID NIH HHS [T32 AI007433, K08 AI081747] NR 10 TC 2 Z9 5 U1 0 U2 5 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2013 VL 19 IS 5 BP 839 EP 841 DI 10.3201/eid1905.121397 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268LX UT WOS:000328173400038 PM 23697599 ER PT J AU Birgfeld, CB Saltzman, BS Luquetti, DV Latham, K Starr, JR Heike, CL AF Birgfeld, Craig B. Saltzman, Babette S. Luquetti, Daniela V. Latham, Kerry Starr, Jackie R. Heike, Carrie L. TI Comparison of Two-Dimensional and Three-Dimensional Images for Phenotypic Assessment of Craniofacial Microsomia SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article DE hemifacial microsomia; photography; 3D photography ID HEMIFACIAL MICROSOMIA; HIGH AGREEMENT; LOW KAPPA; PHOTOGRAPHY; ACQUISITION; PARADOXES; SYSTEM AB Background and Purpose: Three-dimensional surface imaging is used in many craniofacial centers. However, few data exist to indicate whether such systems justify their cost. Craniofacial microsomia is associated with wide phenotypic variability and can affect most facial features. The purpose of this study is to compare three-dimensional versus two-dimensional images for classification of facial features in individuals with craniofacial microsomia. Methods: We obtained a series of two-dimensional and three-dimensional images of 50 participants, aged 0-20 years, diagnosed with craniofacial microsomia, microtia, or Goldenhar syndrome. Three clinicians classified the craniofacial features on each image, and ratings were compared by calculating kappa statistics. We also evaluated image quality using a 5-point Likert scale. Results: Reliability estimates were high for most features using both two-dimensional and three-dimensional image data. Our three-dimensional protocol did not allow for scoring of facial animation, occlusal cant, or tongue anomalies. Image quality scores for the mandible and soft tissue assessment were higher for three-dimensional images. Raters preferred two-dimensional photographs for assessment of the ear, ear canal, and eyes. Conclusions: Both three-dimensional and two-dimensional images provide useful data for objective characterization of the craniofacial features affected in craniofacial microsomia. A series of two-dimensional images has relative advantages for assessment of some specific features, such as the ear, though three-dimensional images may have advantages for quantitative analysis and qualitative assessment of deformities of the jaw and soft tissue. These results should apply to any assessment of these features with or without a craniofacial microsomia diagnosis. C1 [Birgfeld, Craig B.] Univ Washington, Dept Surg, Div Plast Surg, Seattle, WA 98195 USA. [Birgfeld, Craig B.; Heike, Carrie L.] Seattle Childrens Hosp, Seattle, WA 98105 USA. [Saltzman, Babette S.] Seattle Childrens Hosp, Craniofacial Ctr, Seattle, WA 98105 USA. [Luquetti, Daniela V.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Latham, Kerry] Mil Med Ctr, Walter Reed Hosp, Bethesda, MD USA. [Starr, Jackie R.] Forsyth Inst, Cambridge, MA USA. [Heike, Carrie L.] Univ Washington, Dept Pediat, Div Craniofacial Med, Seattle, WA 98195 USA. RP Birgfeld, CB (reprint author), Seattle Childrens Hosp, M-S 7847,4800 Sand Point Way, Seattle, WA 98105 USA. OI Starr, Jacqueline/0000-0002-3039-2311 NR 26 TC 3 Z9 3 U1 1 U2 3 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1545-1569 EI 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD MAY PY 2013 VL 50 IS 3 BP 305 EP 314 DI 10.1597/11-173 PG 10 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 259OA UT WOS:000327535000008 PM 22849636 ER PT J AU Bolkan, CR Bonner, LM Campbell, DG Lanto, A Zivin, K Chaney, E Rubenstein, LV AF Bolkan, Cory R. Bonner, Laura M. Campbell, Duncan G. Lanto, Andy Zivin, Kara Chaney, Edmund Rubenstein, Lisa V. TI Family Involvement, Medication Adherence, and Depression Outcomes Among Patients in Veterans Affairs Primary Care SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SERIOUS MENTAL-ILLNESS; SOCIAL SUPPORT; QUALITY IMPROVEMENT; HEALTH; SCHIZOPHRENIA; METAANALYSIS; INDIVIDUALS; HEART; TRIAL AB Objective: Family involvement and social support are associated with recovery from mental disorders. This project explored how family involvement in health care and social support among depressed veterans in primary care related to medication adherence and depression outcomes. Methods: During a longitudinal telephone survey, 761 Veterans Affairs (VA) primary care patients (mean age=60 years) with probable major depression were asked about depression symptoms, self-reported health, medication adherence, social support, family involvement with care, and satisfaction with clinicians' efforts to involve the patients' families in their care. Follow-up interviews at seven and 18 months assessed depression severity and medication adherence. Results: Most participants lived with others (71%) and reported moderately high social support. Most participants (62%) reported being very likely to discuss treatment of a major medical condition with family, but 64% reported that VA providers had not involved the participants' family in their care within the prior six months. In multivariate regression analyses, lower depression severity and better medication adherence over time were significantly linked to higher satisfaction with limited efforts by clinicians to involve families in care. Neither social support nor the extent of family involvement by itself was associated with outcomes. Conclusions: The results suggested a link between patient satisfaction with family involvement by clinicians and clinical outcomes among depressed veterans. In addition, clinician responsiveness to patient wishes may be more important than the amount of family involvement per se. Further research is needed to clarify when and how clinicians should involve a patient's family in depression treatment in primary care. C1 [Bolkan, Cory R.] Washington State Univ, Dept Human Dev, Vancouver, WA 98686 USA. [Bonner, Laura M.] Vet Affairs VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Bonner, Laura M.] Hlth Serv Res & Dev Northwest Ctr Excellence, Seattle, WA USA. [Campbell, Duncan G.] Univ Montana, Dept Psychol, Missoula, MT 59812 USA. [Lanto, Andy; Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, VA Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Rubenstein, Lisa V.] RAND Hlth Program, Santa Monica, CA USA. [Zivin, Kara] US Dept Vet Affairs, Natl Serious Mental Illness Treatment Res & Evalu, Ann Arbor, MI USA. [Zivin, Kara] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Chaney, Edmund] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Bolkan, CR (reprint author), Washington State Univ, Dept Human Dev, 14204 Salmon Creek Ave, Vancouver, WA 98686 USA. EM bolkan@vancouver.wsu.edu FU Veterans Affairs (VA) Health Services Research and Development Service; VA Mental Health Quality Enhancement Research Initiative [MHI 99-375, MNT 01-027, MHQ 10-06] FX Funding was provided by the Veterans Affairs (VA) Health Services Research and Development Service and the VA Mental Health Quality Enhancement Research Initiative (MHI 99-375, MNT 01-027, and MHQ 10-06). The authors acknowledge the contributions of the many study participants, without whom this work would not have been possible. The views expressed herein are those of the authors and do not necessarily represent the views of the VA and other affiliated institutions. NR 34 TC 11 Z9 12 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2013 VL 64 IS 5 BP 472 EP 478 DI 10.1176/appi.ps.201200160 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255WI UT WOS:000327270400019 PM 23370463 ER PT J AU Olumi, AF Kaufman, DS Zietman, A Harisinghani, MG Wu, CL AF Olumi, Aria F. Kaufman, Donald S. Zietman, Anthony Harisinghani, Mukesh G. Wu, Chin-Lee TI Case 25-2013: A 71-Year-Old Man with Hematuria and a Mass in the Bladder SO GLOBAL PUBLIC HEALTH LA English DT Article ID PROSTATIC DUCT ADENOCARCINOMA; RADICAL PROSTATECTOMY; ENDOMETRIOID FEATURES; CARCINOMA; UTRICLE AB A 71-year-old man with gross hematuria and a mass in the bladder was seen in the cancer center. Six weeks earlier, painless hematuria had developed, with passage of clots. CT and cystoscopy showed a lobulated mass at the bladder neck. A diagnostic test was performed. Presentation of CaseDr. Donald S. Kaufman: A 71-year-old man was seen in the outpatient cancer center of this hospital because of gross hematuria and a mass in the bladder. The patient had been well until 6 weeks earlier, when painless hematuria had developed, with passage of clots, while he was traveling in a wilderness area. After 2 days, he saw a nurse practitioner at a local facility. Attempts at passing a catheter into his bladder were unsuccessful, and he was referred to a hospital in a larger city. Computed tomography (CT) performed without the administration of contrast material reportedly ... C1 [Olumi, Aria F.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Kaufman, Donald S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zietman, Anthony] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Olumi, Aria F.] Harvard Univ, Sch Med, Dept Urol, Boston, MA USA. [Kaufman, Donald S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zietman, Anthony] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Olumi, AF (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1744-1692 EI 1744-1706 J9 GLOB PUBLIC HEALTH JI Glob. Public Health PD MAY 1 PY 2013 VL 8 IS 5 BP 660 EP 667 DI 10.1056/NEJMcpc1209278 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 243XE UT WOS:000326350900009 ER PT J AU Garcia-Godoy, F Trusbkowsky, RD AF Garcia-Godoy, Franklin Trusbkowsky, Richard D. TI A diagnostic device to record dentin hypersensitivity SO AMERICAN JOURNAL OF DENTISTRY LA English DT Editorial Material ID DENTIFRICE; FLUORIDE; ETIOLOGY; 8-WEEK C1 [Garcia-Godoy, Franklin] Univ Tennessee, Coll Dent, Biosci Res Ctr, Memphis, TN 38168 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Cambridge, MA USA. [Trusbkowsky, Richard D.] NYU, Coll Dent, Adv Programs Int Dentists Esthet Dent, New York, NY USA. RP Garcia-Godoy, F (reprint author), Univ Tennessee, Hlth Sci Ctr, Coll Dent, 875 Union Ave, Memphis, TN 38168 USA. EM fgarciagodoy@gmail.com NR 24 TC 0 Z9 0 U1 0 U2 0 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD MAY PY 2013 VL 26 SI B BP 3B EP 4B PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 233UZ UT WOS:000325596300002 PM 24156202 ER PT J AU Custodio, JCD Martins, CW Lugon, MDV Fregni, F Nakamura-Palacios, EM AF de Souza Custodio, Juliana Cardoso Martins, Cleciane Waldetario Valladao Lugon, Marcelo Di Marcello Fregni, Felipe Nakamura-Palacios, Ester Miyuki TI Epidural Direct Current Stimulation Over the Left Medial Prefrontal Cortex Facilitates Spatial Working Memory Performance in Rats SO BRAIN STIMULATION LA English DT Article DE Epidural direct current stimulation; Medial prefrontal cortex; Delayed task; Spatial working memory; Radial maze ID DEEP BRAIN-STIMULATION; RADIAL-ARM MAZE; CORTICAL SPREADING DEPRESSION; ELECTRICAL-STIMULATION; MOTOR CORTEX; POLARIZING CURRENTS; SYNAPTIC PLASTICITY; DOPAMINE MODULATION; CLINICAL-TRIAL; DOUBLE-BLIND AB Background: Extensive evidence supports the notion that modulation of PFC excitability using low-intensity electrical stimulation is a promising modality for treating neuropsychiatric diseases and improving cognitive function. Objective: This study examined the effects of epidural direct current stimulation (eDCS), a method providing smaller shunting of current and more focal stimulation, on spatial working memory. Methods: Male Wistar rats that were well trained in an 8-arm radial maze and in which 5-mm round electrodes were implanted over the left medial prefrontal cortex (mPFC) received anodal eDCS (400 mu A during 11 min) (n = 9) or sham procedure (n = 9) five minutes before delayed tests in the radial maze. Results: Animals that received eDCS over the left mPFC had significantly fewer errors in the post-delay performance on the 1-h (P < 0.01), 4-h (P < 0.001), and 10-h (P < 0.001) delayed tests compared with sham-treated animals. General locomotor activity was unaffected because time spent in each visited arm did not change significantly by eDCS. There was no evidence of neuronal lesions in the mPFC underneath the eDCS. Conclusions: Our results suggest that epidural direct current stimulation over the mPFC facilitates spatial working memory in rats, an effect that persisted over the long term. (c) 2013 Elsevier Inc. All rights reserved. C1 [de Souza Custodio, Juliana Cardoso; Martins, Cleciane Waldetario; Valladao Lugon, Marcelo Di Marcello; Nakamura-Palacios, Ester Miyuki] Univ Fed Espirito Santo, Program Postgrad Physiol Sci, Lab Cognit Sci, BR-29047105 Vitoria, ES, Brazil. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Lab Neuromodulat, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spauding Rehabil Hosp, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat,Beth I, Boston, MA 02115 USA. RP Nakamura-Palacios, EM (reprint author), Univ Fed Espirito Santo, Programa Posgrad Ciencias Fisiol, Ctr Ciencias Saude, Av Marechal Campos 1468, BR-29047105 Vitoria, ES, Brazil. EM emnpalacios@gmail.com FU NIH [1R21DK81773-1A1] FX FF is partially supported by a NIH grant (1R21DK81773-1A1) investigating the mechanisms of DC stimulation. NR 74 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY PY 2013 VL 6 IS 3 BP 261 EP 269 DI 10.1016/j.brs.2012.07.004 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 234VF UT WOS:000325671700006 ER PT J AU Nahas, Z Short, B Burns, C Archer, M Schmidt, M Prudic, J Nobler, MS Devanand, DP Fitzsimons, L Lisanby, SH Payne, N Perera, T George, MS Sackeim, HA AF Nahas, Ziad Short, Baron Burns, Carol Archer, Melanie Schmidt, Matthew Prudic, Joan Nobler, Mitchell S. Devanand, D. P. Fitzsimons, Linda Lisanby, Sarah H. Payne, Nancy Perera, Tarique George, Mark S. Sackeim, Harold A. TI A Feasibility Study of a New Method for Electrically Producing Seizures in Man: Focal Electrically Administered Seizure Therapy [FEAST] SO BRAIN STIMULATION LA English DT Article DE ECT; FEAST; Depression; Seizure ID TRANSCRANIAL MAGNETIC STIMULATION; ELECTROCONVULSIVE-THERAPY; ELECTRODE PLACEMENT; PERIPHERAL-NERVE; MOTOR CORTEX; STIMULUS-INTENSITY; COIL STIMULATION; ECT; EFFICACY; MECHANISMS AB Background: Electroconvulsive therapy (ECT) remains the most effective acute treatment for severe major depression, but with significant risk of adverse cognitive effects. Unidirectional electrical stimulation with a novel electrode placement and geometry (Focal Electrically Administered Seizure Therapy (FEAST)) has been proposed as a means to initiate seizures in prefrontal cortex prior to secondary generalization. As such, it may have fewer cognitive side effects than traditional ECT. We report on its first human clinical application. Method: Seventeen unmedicated depressed adults (5 men; 3 bipolar disorder; age 53 +/- 16 years) were recruited after being referred for ECT. Open-label FEAST was administered with a modified spECTrum 5000Q device and a traditional ECT dosing regimen until patients clinically responded. Clinical and cognitive assessments were obtained at baseline, and end of course. Time to orientation recovery, a predictor of long-term amnestic effects, was assessed at each treatment. Nonresponders to FEAST were transitioned to conventional ECT. Results: One patient withdrew from the study after a single titration session. After the course of FEAST (median 10 sessions), there was a 46.1 +/- 35.5% improvement in Hamilton Rating Scale for Depression (HRSD24) scores compared to baseline (33.1 +/- 6.8, 16.8 +/- 10.9; P < 0.0001). Eight of 16 patients met response criteria (50% decrease in HRSD24) and 5/16 met remission criteria (HRSD24 < 10). Patients achieved full re-orientation (4 of 5 items) in 5.5 +/- 6.4 min (median = 3.6), timed from when their eyes first opened after treatment. Conclusion: In this feasibility study, FEAST produced clinically meaningful antidepressant improvement, with relatively short time to reorientation. Our preliminary work first in primates and now depressed adults demonstrates that FEAST is feasible, safe, well-tolerated and, if efficacy can be optimized, has potential to replace traditional Ea. (C) 2013 Elsevier Inc. All rights reserved. C1 [Nahas, Ziad] Amer Univ Beirut, Dept Psychiat, Beirut, Lebanon. [Nahas, Ziad; Short, Baron; Burns, Carol; Archer, Melanie; Schmidt, Matthew; George, Mark S.] Med Univ S Carolina, Charleston, SC USA. [Prudic, Joan; Devanand, D. P.; Fitzsimons, Linda; Perera, Tarique; Sackeim, Harold A.] Columbia Univ, Dept Psychiat, New York, NY 10027 USA. [Nobler, Mitchell S.] New York Med Coll, Dept Psychiat & Behav Sci, Valhalla, NY 10595 USA. [Lisanby, Sarah H.] Duke Univ Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA. [Payne, Nancy] NYU, New York, NY 10003 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Nahas, Z (reprint author), Amer Univ Beirut, Beirut, Lebanon. EM zn17@aub.edu.lb NR 46 TC 23 Z9 23 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY PY 2013 VL 6 IS 3 BP 403 EP 408 DI 10.1016/j.brs.2013.03.004 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 234VF UT WOS:000325671700026 PM 23518262 ER PT J AU Neuss, MN Polovich, M McNiff, K Esper, P Gilmore, TR LeFebvre, KB Schulmeister, L Jacobson, JO AF Neuss, Michael N. Polovich, Martha McNiff, Kristen Esper, Peg Gilmore, Terry R. LeFebvre, Kristine B. Schulmeister, Lisa Jacobson, Joseph O. TI 2013 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards Including Standards for the Safe Administration and Management of Oral Chemotherapy SO ONCOLOGY NURSING FORUM LA English DT Article ID CANCER; ADHERENCE; LEUKEMIA; ERRORS AB In 2009; the American Society-of Oncology (ASCO) and the Oncology Nursing Society (ONS) published standards for the safe use of parenteral, chemotherapy in the outpatient setting, including issues of practitioner orders, preparation, and administration of medication. In 2011, these were updated to include inpatient facilities. In December 2011; a multistakeholder workgroup met to address the issues associated with orally administered antineoplastics, under the leadership of ASCO and ONS. The workgroup participants developed,recommended Standards, which were presented for public comment Public comments informed final edits; and the final standards were reviewed and approved by the ASCO and ONS Boards of Directors. Significant newly identified recommendations include those associated with drug prescription and the necessity of ascertaining that prescriptions are filled. In addition; the importance of patient and family education regarding administration schedules, exception procedures, disposal of unused Oral medication, and aspects of continuity of care across settings were identified. This article presents the newly developed standards. C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Duke Oncol Network, Durham, NC USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [McNiff, Kristen] Amer Soc Clin Oncol, Alexandria, VA USA. Oncol Nursing Soc, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP McNiff, K (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Ste 800, Alexandria, VA USA. EM Kristen.mcniff@asco.org NR 18 TC 25 Z9 25 U1 1 U2 5 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2013 VL 40 IS 3 BP 225 EP 233 DI 10.1188/13.ONF.40-03AP2 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 220EL UT WOS:000324564800006 PM 23619103 ER PT J AU Wang, M Maragani, S Huang, LY Jeon, S Canteenwala, T Hamblin, MR Chiang, LY AF Wang, Min Maragani, Satyanarayana Huang, Liyi Jeon, Seaho Canteenwala, Taizoon Hamblin, Michael R. Chiang, Long Y. TI Synthesis of decacationic [60]fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Decacationic C-60 monoadducts; Photoinduced radicals; Transesterification; Di(N,N ',N,N,N,N-hexapropyl-hexa(aminoethyl)amido)malonate arm; Photosensitizer; Antimicrobial photodynamic therapy ID GRAM-POSITIVE BACTERIA; PHOTODYNAMIC THERAPY; FULLERENE DERIVATIVES; NEGATIVE BACTERIA; SURFACE-PROTEINS; INACTIVATION; C-60; OXYGEN; INFECTIONS; WATER AB We report a novel class of highly water-soluble decacationic methano[60]fullerene decaiodides C-60[>M(C3N6+C3)(2)]-(I-)(10) [1-(I-)(10)] capable of co-producing singlet oxygen (Type-II) and highly reactive hydroxyl radicals, formed from superoxide radicals in Type-I photosensitizing reactions, upon illumination at both UVA and white light wavelengths. The O-2(-)center dot-production efficiency of 1-(I-)(10) was confirmed by using an O-2(-)center dot-reactive bis(2,4-dinitrobenzenesulfonyl)tetrafluorofluorescein probe and correlated to the photoinduced electron-transfer event going from iodide anions to C-3(60)*[>M(C3N6+C3)(2)] leading to C-60(-)center dot[>M(C3N6+C3)(2)]. Incorporation of a defined number (ten) of quaternary ammonium cationic charges per C60 in 1 was aimed to enhance its ability to target pathogenic Gram-positive and Gram-negative bacterial cells. We used the well-characterized malonato[60]fullerene diester monoadduct C-60[>M(t-Bu)(2)] as the starting fullerene derivative to provide a better synthetic route to C-60[>M(C3N6+C3)(2)] via transesterification reaction under trifluoroacetic acid catalyzed conditions. These compounds may be used as effective photosensitizers and nano-PDT drugs for photoinactivation of pathogens. (C) 2013 Elsevier Masson SAS. All rights reserved. C1 [Wang, Min; Maragani, Satyanarayana; Jeon, Seaho; Canteenwala, Taizoon; Chiang, Long Y.] Univ Massachusetts, Inst Nanosci & Engn Technol, Dept Chem, Lowell, MA 01854 USA. [Huang, Liyi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Liyi; 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. [Chiang, Long Y.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. RP Chiang, LY (reprint author), Univ Massachusetts, Inst Nanosci & Engn Technol, Dept Chem, Lowell, MA 01854 USA. EM hamblin@helix.mgh.harvard.edu; long_chiang@uml.edu OI Hamblin, Michael/0000-0001-6431-4605 FU National Institute of Health (NIH) [R01 CA137108] FX We thank the financial support of National Institute of Health (NIH) under the grant number R01 CA137108. We thank Jin Xu of UML for the collection of ESI-MS spectroscopic data. NR 40 TC 12 Z9 12 U1 5 U2 45 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 EI 1768-3254 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD MAY PY 2013 VL 63 BP 170 EP 184 DI 10.1016/j.ejmech.2013.01.052 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 197MN UT WOS:000322855400018 PM 23474903 ER PT J AU Karlin, BE Agarwal, M AF Karlin, Bradley E. Agarwal, Madhulika TI Achieving the Promise of Evidence-Based Psychotherapies for Posttraumatic Stress Disorder and Other Mental Health Conditions for Veterans SO PSYCHOLOGICAL SCIENCE IN THE PUBLIC INTEREST LA English DT Editorial Material ID COGNITIVE-BEHAVIORAL THERAPY; PROCESSING THERAPY; DISSEMINATION; OUTCOMES C1 [Karlin, Bradley E.; Agarwal, Madhulika] US Dept Vet Affairs, Cent Off, Washington, DC 20420 USA. RP Karlin, BE (reprint author), US Dept Vet Affairs, Cent Off, 810 Vermont Ave, Washington, DC 20420 USA. EM bradley.karlin2@va.gov NR 16 TC 9 Z9 9 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1529-1006 J9 PSYCHOL SCI PUBL INT JI Psychol. Sci. Public Interest PD MAY PY 2013 VL 14 IS 2 BP 62 EP 64 DI 10.1177/1529100613484706 PG 3 WC Psychology, Multidisciplinary SC Psychology GA 217ZQ UT WOS:000324402500001 PM 26173291 ER PT J AU Meeker, JD Cooper, EM Stapleton, HM Hauser, R AF Meeker, John D. Cooper, Ellen M. Stapleton, Heather M. Hauser, Russ TI Urinary Metabolites of Organophosphate Flame Retardants: Temporal Variability and Correlations with House Dust Concentrations SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarker; epidemiology; exposure; human; TDCPP; triphenyl phosphate ID SAN-ANTONIO STATEMENT; TRIS(1,3-DICHLORO-2-PROPYL) PHOSPHATE; HORMONE-LEVELS; MEN; SERUM; RAT; DISPOSITION; WOMEN AB BACKGROUND: A reduction in the use of polybrominated diphenyl ethers (PBDEs) because of human health concerns may result in an increased use of and human exposure to organophosphate flame retardants (OPFRs). Human exposure and health studies of OPFRs are lacking. OBJECTIVES: We sought to define the degree of temporal variability in urinary OPFR metabolites in order to inform epidemiologic study design, and to explore a potential primary source of exposure by examining the relationship between OPFRs in house dust and their metabolites in urine. METHODS: Nine repeated urine samples were collected from 7 men over the course of 3 months and analyzed for bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP), metabolites of the OPFRs tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), respectively. Intraclass correlation coefficients (ICCs) were calculated to characterize temporal reliability. Paired house dust and urine samples were collected from 45 men. RESULTS: BDCPP was detected in 91% of urine samples, and DPP in 96%. Urinary BDCPP showed moderate-to-strong temporal reliability (ICC range, 0.55-0.72). ICCs for DPP were lower, but moderately reliable (range, 0.35-0.51). There was a weak [Spearman r (r(S)) = 0.31] but significant (p = 0.03) correlation between urinary BDCPP and TDCPP concentrations in house dust that strengthened when nondetects (r(S) = 0.47) were excluded. There was no correlation between uncorrected DPP and TPP measured in house dust (r(S) < 0.1). CONCLUSIONS: Household dust may be an important source of exposure to TDCPP but not TPP. Urinary concentrations of BDCPP and DPP were moderately to highly reliable within individuals over 3 months. C1 [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Cooper, Ellen M.; Stapleton, Heather M.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, M6017 SPH II,1415 Washington Hts, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu OI Meeker, John/0000-0001-8357-5085 FU National Institute of Environmental Health Sciences, National Institutes of Health [R01 ES009718, R01 ES016099] FX This work was supported by grants R01 ES009718 and R01 ES016099 from the National Institute of Environmental Health Sciences, National Institutes of Health. NR 26 TC 58 Z9 59 U1 11 U2 134 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2013 VL 121 IS 5 BP 580 EP 585 DI 10.1289/ehp.1205907 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 208UX UT WOS:000323707300021 PM 23461877 ER PT J AU Ali, O Doherty, E Dranoff, G Mooney, D AF Ali, Omar Doherty, Ed Dranoff, Glenn Mooney, David TI Infection-mimicking materials to regulate dendritic cell subsets and T cell in situ for cancer vaccination SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Ali, Omar; Doherty, Ed; Dranoff, Glenn; Mooney, David] Harvard Univ, Sch Med, Wyss Inst Biol Inspired Engn, Boston, MA USA. [Ali, Omar; Mooney, David] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4324 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105139 ER PT J AU Bencherif, S Draganov, D Lewin, S Li, A Sands, R Verbeke, C Dranoff, G Mooney, D AF Bencherif, Sidi Draganov, Dobrin Lewin, Sarah Li, Aileen Sands, Roger Verbeke, Catia Dranoff, Glenn Mooney, David TI Immunologically active cryogels for breast cancer therapy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Bencherif, Sidi; Li, Aileen; Sands, Roger; Verbeke, Catia; Mooney, David] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Bencherif, Sidi; Lewin, Sarah; Mooney, David] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Draganov, Dobrin; Dranoff, Glenn] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Draganov, Dobrin; Dranoff, Glenn] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 MAY 1 PY 2013 VL 190 MA P4329 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105144 ER PT J AU Bodhankar, S Offner, H AF Bodhankar, Sheetal Offner, Halina TI PD-1 interaction with PD-L1 but not PD-L2 on B cells mediates protective effects of estrogen against EAE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Bodhankar, Sheetal; Offner, Halina] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bodhankar, Sheetal; Offner, Halina] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P5176 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987107037 ER PT J AU Bodhankar, S Chen, YX Murphy, S Offner, H AF Bodhankar, Sheetal Chen, Yingxin Murphy, Stephanie Offner, Halina TI Opposing roles of PD-1 and PD-L in modulating CNS inflammation and infarct volume following experimental stroke in mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Bodhankar, Sheetal; Chen, Yingxin; Murphy, Stephanie; Offner, Halina] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bodhankar, Sheetal; Offner, Halina] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1012 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100014 ER PT J AU Boucau, J Madouasse, J Carlin, C Zhu, T Xu, Y Shimada, M Le Gall, S AF Boucau, Julie Madouasse, Julien Carlin, Christopher Zhu, Tom Xu, Yang Shimada, Mariko Le Gall, Sylvie TI Effect of cellular activation on the antigen processing machinery of primary CD4 T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Boucau, Julie; Madouasse, Julien; Carlin, Christopher; Zhu, Tom; Xu, Yang; Shimada, Mariko; Le Gall, Sylvie] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P5029 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987106141 ER PT J AU Brandon, D Williams, S Zhang, X AF Brandon, Danielle Williams, Sarah Zhang, Xian TI Fli-1 transcription factor is involved in cytokine production in spleen cells upon Toll-like receptor stimulation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Brandon, Danielle; Zhang, Xian] Med Univ S Carolina, Charleston, SC 29425 USA. [Williams, Sarah; Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1218 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100217 ER PT J AU Bryce, S Luster, A Graham, G Nibbs, R AF Bryce, Steven Luster, Andrew Graham, Gerry Nibbs, Rob TI The 'atypical' chemokine receptor CCRL1 aids dendritic cell migration from inflamed skin SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Bryce, Steven; Graham, Gerry; Nibbs, Rob] Univ Glasgow, Glasgow, Lanark, Scotland. [Luster, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P6352 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987108188 ER PT J AU Chang, JJ Woods, M Lindsay, R Doyle, E Griesbeck, M Chan, E Robbins, G Bosch, R Altfeld, M AF Chang, J. Judy Woods, Matt Lindsay, Robert Doyle, Erin Griesbeck, Morgane Chan, Ellen Robbins, Gregory Bosch, Ronald Altfeld, Marcus TI Higher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Chang, J. Judy; Woods, Matt; Lindsay, Robert; Doyle, Erin; Griesbeck, Morgane; Altfeld, Marcus] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Chan, Ellen; Bosch, Ronald] Ctr Biostat AIDS Res, Boston, MA USA. [Robbins, Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P3039 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987102216 ER PT J AU Choudhuri, K Beilin, C Bouma, G Llodra, J Malinova, D Stokes, D Springer, T Shimaoka, M Dustin, M Thrasher, A Burns, S AF Choudhuri, Kaushik Beilin, Chiara Bouma, Gerben Llodra, Jaime Malinova, Dessislava Stokes, David Springer, Timothy Shimaoka, Motomu Dustin, Michael Thrasher, Adrain Burns, Siobhan TI Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the immunological synapse SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Choudhuri, Kaushik; Llodra, Jaime; Stokes, David; Dustin, Michael] NYU Sch Med, Skirball Inst Biomol Med, New York, NY USA. [Beilin, Chiara; Bouma, Gerben; Malinova, Dessislava; Thrasher, Adrain; Burns, Siobhan] UCL, Inst Child Hlth, London, England. [Springer, Timothy; Shimaoka, Motomu] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P6286 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987108123 ER PT J AU Choudhuri, K Llodra, J Tsai, J Roth, E Gordo, S Wucherpfennig, K Kam, L Stokes, D Dustin, M AF Choudhuri, Kaushik Llodra, Jaime Tsai, Jones Roth, Eric Gordo, Susana Wucherpfennig, Kai Kam, Lance Stokes, David Dustin, Michael TI Polarized release and retroviral subversion of TCR-enriched microvesicles at the T cell immunological synapse SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Choudhuri, Kaushik; Llodra, Jaime; Stokes, David; Dustin, Michael] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY USA. [Tsai, Jones; Kam, Lance] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Gordo, Susana; Wucherpfennig, Kai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Roth, Eric] Northwestern Univ, NUANCE Ctr, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P6155 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987107246 ER PT J AU Ding, YN Hsu, HC Li, J Yang, P Zajac, A Mountz, J AF Ding, Yanna Hsu, Hui-Chen Li, Jun Yang, PingAr Zajac, Allan Mountz, John TI IL-21 promotes autoreactive germinal center development in BXD2 mice partially by regulating T-FR SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Ding, Yanna; Hsu, Hui-Chen; Li, Jun; Yang, PingAr; Zajac, Allan; Mountz, John] Univ Alabama Birmingham, Birmingham, AL USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4116 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104185 ER PT J AU Dugan, J Griffiths, E Snow, P Rosenzweig, H Carr, D Rosenbaum, J Davey, M AF Dugan, Jae Griffiths, Eric Snow, Paige Rosenzweig, Holly Carr, Daniel Rosenbaum, Jim Davey, Michael TI Nucleotide-binding and oligomerization domain 2 (NOD2) knock-in mice carrying a mutation associated with Blau syndrome show reduced amounts of NOD2 protein and decreased muramyl dipeptide (MDP)-induced inflammatory responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Dugan, Jae; Griffiths, Eric; Snow, Paige; Carr, Daniel; Davey, Michael] Portland VA Med Ctr, Portland, OR USA. [Dugan, Jae; Rosenzweig, Holly; Carr, Daniel; Rosenbaum, Jim; Davey, Michael] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Rosenzweig, Holly; Davey, Michael] Oregon Hlth & Sci Univ, MMI, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 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 MAY 1 PY 2013 VL 190 MA P1254 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987101003 ER PT J AU Fletcher, A Elman, J Knoblich, K Armant, M Parekkadan, B Boyd, R Turley, S AF Fletcher, Anne Elman, Jessica Knoblich, Konstantin Armant, Myriam Parekkadan, Biju Boyd, Richard Turley, Shannon TI Identification of a new cell therapy candidate reveals immunological specialization and robust therapeutic efficacy against high-mortality sepsis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Fletcher, Anne; Knoblich, Konstantin; Turley, Shannon] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fletcher, Anne; Elman, Jessica; Armant, Myriam; Parekkadan, Biju; Turley, Shannon] Harvard Univ, Sch Med, Boston, MA USA. [Fletcher, Anne; Boyd, Richard] Monash Univ, Immunol & Stem Cell Labs, Clayton, Vic, Australia. [Elman, Jessica; Parekkadan, Biju] Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Elman, Jessica; Parekkadan, Biju] Shriners Hosp Children, Boston, MA USA. [Knoblich, Konstantin] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. [Armant, Myriam] Boston Childrens Hosp, Ctr Human Cell Therapy, Boston, MA USA. RI Knoblich, Konstantin/B-5980-2009 OI Knoblich, Konstantin/0000-0002-5646-837X NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4212 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105029 ER PT J AU Gagnon, E Wucherpfennig, K AF Gagnon, Etienne Wucherpfennig, Kai TI Local changes in lipid environment of T cell receptor microclusters regulate membrane binding by the CD3epsilon cytoplasmic domain (P1103) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Gagnon, Etienne; Wucherpfennig, Kai] Univ Montreal, IRIC, Montreal, PQ, Canada. [Gagnon, Etienne] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100104 ER PT J AU Hansbro, P Beckett, E Stevens, R Jarnicki, A Kim, R Hanish, I Hansbro, N Deane, A Keely, S Horvat, J Yang, M Oliver, B van Rooijen, N Inman, M Adachi, R Soberman, R Hamadi, S Wark, P Foster, P AF Hansbro, Philip Beckett, Emma Stevens, Richard Jarnicki, Andrew Kim, Richard Hanish, Irwan Hansbro, Nicole Deane, Andrew Keely, Simon Horvat, Jay Yang, Ming Oliver, Brian van Rooijen, Nico Inman, Mark Adachi, Roberto Soberman, Roy Hamadi, Sahar Wark, Peter Foster, Paul TI A short-term model of COPD identifies a role for mast cell tryptase SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Hansbro, Philip; Beckett, Emma; Jarnicki, Andrew; Kim, Richard; Hanish, Irwan; Hansbro, Nicole; Deane, Andrew; Keely, Simon; Horvat, Jay; Yang, Ming; Wark, Peter; Foster, Paul] Univ Newcastle, Prior Res Ctr Asthma & Resp Dis, Callaghan, NSW 2308, Australia. [Hansbro, Philip; Jarnicki, Andrew; Kim, Richard; Hanish, Irwan; Hansbro, Nicole; Deane, Andrew; Keely, Simon; Horvat, Jay; Yang, Ming; Wark, Peter; Foster, Paul] Hunter Med Res Inst, VIVA, New Lambton Hts, NSW, Australia. [Stevens, Richard; Soberman, Roy; Hamadi, Sahar] Harvard Univ, Sch Med, Boston, MA USA. [Stevens, Richard] Brigham & Womens Hosp, Boston, MA 02115 USA. [Oliver, Brian] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Oliver, Brian] Woolcock Inst Med Res, Sydney, NSW, Australia. [van Rooijen, Nico] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Inman, Mark] St Josephs Healthcare, Firestone Inst Resp Hlth, Med, Hamilton, ON, Canada. [Adachi, Roberto] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Soberman, Roy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wark, Peter] John Hunter Hosp, New Lambton Hts, NSW, Australia. RI Oliver, Brian/E-7939-2010 OI Oliver, Brian/0000-0002-7122-9262 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P3242 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987103168 ER PT J AU Hu, Z Xia, JX Wargo, J Yang, YG AF Hu, Zheng Xia, Jinxing Wargo, Jennifer Yang, Yong-Guang TI Generation of human T cells expressing only the engineered tumor antigen specific TCR in humanized mice for preclinical research and anticancer therapy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Hu, Zheng; Xia, Jinxing; Yang, Yong-Guang] Columbia Univ Coll Phys & Surg, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Wargo, Jennifer] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RI Xia, Jinxing/E-5658-2015 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4364 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105178 ER PT J AU Jost, S Chang, J Rands, K Tomezsko, P Doyle, E Daillere, R Dudek, T Vrbanac, V Allen, T Tager, A Altfeld, M AF Jost, Stephanie Chang, Judy Rands, Keith Tomezsko, Phillip Doyle, Erin Daillere, Romain Dudek, Timothy Vrbanac, Vladimir Allen, Todd Tager, Andrew Altfeld, Marcus TI Impact of NK cells on control of HIV infection in humanized BLT mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Jost, Stephanie; Chang, Judy; Rands, Keith; Tomezsko, Phillip; Doyle, Erin; Daillere, Romain; Dudek, Timothy; Allen, Todd; Tager, Andrew; Altfeld, Marcus] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Vrbanac, Vladimir; Tager, Andrew] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA 11827 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987108044 ER PT J AU Kang, YJ Chang, HC AF Kang, Yoon-Joong Chang, Hsiu-Ching TI Transgenic mice expressing functional CD8 alpha beta without an active CD8aa implies the contribution of CD8 alpha alpha in the biological function of CD8 alpha alpha plus TCR alpha beta plus iIELs SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Kang, Yoon-Joong] Jungwon Univ, Dept Biomed Sci, Chungcheongbuk Do, South Korea. [Kang, Yoon-Joong; Chang, Hsiu-Ching] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kang, Yoon-Joong; Chang, Hsiu-Ching] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chang, Hsiu-Ching] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1466 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987101188 ER PT J AU Karam, E Williams, S Zhang, J AF Karam, Eva Williams, Sarah Zhang, John TI Fli-1 transcription factor regulates inflammatory mediators in endothelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Karam, Eva; Zhang, John] Med Univ S Carolina, Charleston, SC 29425 USA. [Williams, Sarah; Zhang, John] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA 11516 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987108077 ER PT J AU Lee, KM Kim, J Yeh, H Stott, R Shi, S Deng, SP Markmann, J AF Lee, Kang Mi Kim, James Yeh, Heidi Stott, Ryan Shi, Shuai Deng, Shaoping Markmann, James TI Transplant tolerance depends on regulatory T cells induced by TGF-beta-producing regulatory B cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Lee, Kang Mi; Kim, James; Yeh, Heidi; Stott, Ryan; Shi, Shuai; Deng, Shaoping; Markmann, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deng, Shaoping] Sichuan Prov Peoples Hosp, Chengdu, Peoples R China. [Deng, Shaoping] Sichuan Acad Med Sci, Chengdu, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P2168 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987102117 ER PT J AU Li, H Hsu, HC Wu, Q Yang, PA Cua, D Mountz, J AF Li, Hao Hsu, Hui-Chen Wu, Qi Yang, PingAr Cua, Daniel Mountz, John TI IL-23 controls autoimmunity by maintaining the integrity of marginal zone barrier that clears apoptotic bodies SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Li, Hao; Mountz, John] Univ Alabama Birmingham, Birmingham, AL USA. [Li, Hao; Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Mountz, John] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Cua, Daniel] Merck Res Labs, Palo Alto, CA USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4178 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104246 ER PT J AU Li, H Wu, Q Yang, PA Li, J Fu, YX Mountz, J Hsu, HC AF Li, Hao Wu, Qi Yang, PingAr Li, Jun Fu, YangXin Mountz, John Hsu, Hui-Chen TI Increased type I interferon disrupts marginal zone barrier integrity via dissociation of lymphotoxin-expressing B cells and marginal zone macrophages in systemic autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Li, Hao; Mountz, John] Univ Alabama Birmingham, Birmingham, AL USA. [Li, Hao; Wu, Qi; Yang, PingAr; Li, Jun; Mountz, John; Hsu, Hui-Chen] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Fu, YangXin] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4160 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104228 ER PT J AU Li, J Hsu, HC Yang, PA Wu, Q Spalding, D Mountz, J AF Li, Jun Hsu, Hui-Chen Yang, PingAr Wu, Qi Spalding, David Mountz, John TI Fucosylation is a hallmark of inflammatory macrophages and a novel therapeutic target in rheumatoid arthritis (P5137) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Spalding, David; Mountz, John] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Hsu, Hui-Chen; Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA 13710 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987106248 ER PT J AU Liao, GX van Driel, B Magelky, E O'Keeffe, M Herzog, R Mizoguchi, E Bhan, A Terhorst, C AF Liao, Gongxian van Driel, Boaz Magelky, Erica O'Keeffe, Michael Herzog, Roland Mizoguchi, Emiko Bhan, Atul Terhorst, Cox TI Glucocorticoid-induced TNF receptor family related protein ligand regulates the egress of monocytes from the spleen SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Liao, Gongxian; van Driel, Boaz; Magelky, Erica; O'Keeffe, Michael; Terhorst, Cox] Harvard Univ, Sch Med, Div Immunol, BIDMC, Boston, MA USA. [Herzog, Roland] Univ Florida, Gainesville, FL USA. [Mizoguchi, Emiko; Bhan, Atul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P3288 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987103213 ER PT J AU Lv, HJ Smith, R Shankar, J Lipes, M AF Lv, HuiJuan Smith, Ross Shankar, Jyotsna Lipes, Myra TI Shared and distinct immunogenetic pathways in myocarditis and type 1 diabetes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Lv, HuiJuan; Smith, Ross; Shankar, Jyotsna; Lipes, Myra] Joslin Diabet Ctr, Boston, MA 02215 USA. [Lv, HuiJuan; Smith, Ross; Shankar, Jyotsna; Lipes, Myra] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4108 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104177 ER PT J AU Martin-Gayo, E Hickman, T Pimenova, D Pereyra, F Rosenberg, E Lichterfeld, M Yu, X AF Martin-Gayo, Enrique Hickman, Taylor Pimenova, Dina Pereyra, Florencia Rosenberg, Eric Lichterfeld, Mathias Yu, Xu TI Cell-intrinsic HIV-1 immune responses in conventional dendritic cells from HIV-1 elite controllers SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Martin-Gayo, Enrique; Hickman, Taylor; Pimenova, Dina; Pereyra, Florencia; Yu, Xu] Ragon Inst MGH MIT & Harvard, AIDS Res, Boston, MA USA. [Rosenberg, Eric; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P6171 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987108009 ER PT J AU Matsui, A Rittling, S AF Matsui, Aritsune Rittling, Susan TI Osteopontin supports neutrophil survival and function in polymicrobial infection. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Matsui, Aritsune; Rittling, Susan] Forsyth Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1281 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987101030 ER PT J AU Mikucki, M Skitzki, J Fisher, D Curry, K Frelinger, J Luster, A Evans, S AF Mikucki, Maryann Skitzki, Joseph Fisher, Daniel Curry, Kathryn Frelinger, John Luster, Andrew Evans, Sharon TI Non-redundant requirement for CXCR3 chemokine receptor in T cell trafficking across tumor vascular gateways SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Mikucki, Maryann; Skitzki, Joseph; Fisher, Daniel; Curry, Kathryn; Evans, Sharon] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Frelinger, John] Univ Rochester, Med Ctr, Microbiol & Immunol & Canc Ctr, Rochester, NY 14642 USA. [Luster, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P2137 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987102086 ER PT J AU Mora, JR AF Mora, J. Rodrigo TI Bone marrow precursors require beta 7 integrins to give rise to intestinal mononuclear phagocytes with tolerogenic potential SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Mora, J. Rodrigo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mora, J. Rodrigo] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P3290 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987103215 ER PT J AU Murshid, A Gong, JL Calderwood, S AF Murshid, Ayesha Gong, Jianlin Calderwood, Stuart TI Scavenger receptor SRECI can bind to Toll like receptor 4 and activate LPS-mediated signaling SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Murshid, Ayesha; Calderwood, Stuart] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Gong, Jianlin] Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1362 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987101111 ER PT J AU Nowling, T Richard, E Zhang, J Siskind, L AF Nowling, Tamara Richard, Erin Zhang, John Siskind, Leah TI Reducing Fli1 levels in the MRL/lpr lupus prone mouse model impacts T cell activation and cytokine production SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Nowling, Tamara; Zhang, John; Siskind, Leah] Ralph H Johnson VAMC, Charleston, SC USA. [Nowling, Tamara; Richard, Erin; Zhang, John; Siskind, Leah] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4115 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104184 ER PT J AU Offner, H Chen, YX Murphy, S Bodhankar, S AF Offner, Halina Chen, Yingxin Murphy, Stephanie Bodhankar, Sheetal TI IL-10-producing B cells limit CNS inflammation and infarct volume after experimental stroke in mice (P1090) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Offner, Halina; Chen, Yingxin; Murphy, Stephanie; Bodhankar, Sheetal] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Offner, Halina; Bodhankar, Sheetal] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100090 ER PT J AU Penaloza-MacMaster, P Barouch, D AF Penaloza-MacMaster, Pablo Barouch, Dan TI Severely exhausted CD8 T cells are refractory to rescue by PD-1 blockade, but re-invigorate following concomitant CD4 T cell depletion in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Penaloza-MacMaster, Pablo; Barouch, Dan] Harvard Univ, BIDMC, Boston, MA 02115 USA. [Barouch, Dan] Ragon Inst MGH MIT & Harvard, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P6097 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987107189 ER PT J AU Penaranda, C Hung, D AF Penaranda, Cristina Hung, Deborah TI Identification of factors required for intracellular survival of Pseudomonas aeruginosa SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Penaranda, Cristina; Hung, Deborah] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P3146 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987103072 ER PT J AU Pepper, M Hondowicz, B Garza, E Moon, J AF Pepper, Marion Hondowicz, Brian Garza, Esteban Moon, James TI Th2 differentiation during atopic asthma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Pepper, Marion; Hondowicz, Brian; Garza, Esteban] Univ Washington, Seattle, WA 98195 USA. [Moon, James] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1167 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100167 ER PT J AU Porichis, F Hart, M Barblu, L Zupkosky, J Kavanagh, D Kaufmann, D AF Porichis, Filippos Hart, Meghan Barblu, Lucie Zupkosky, Jennifer Kavanagh, Daniel Kaufmann, Daniel TI Impact of IFN gamma on HIV-specific CD4 T cell and antigen presenting cell function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Porichis, Filippos; Hart, Meghan; Barblu, Lucie; Zupkosky, Jennifer; Kavanagh, Daniel; Kaufmann, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Barblu, Lucie; Kaufmann, Daniel] Univ Montreal, Ctr Rech, Ctr Hosp Univ Montreal, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P6163 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987108002 ER PT J AU Prasad, A Ramirez-Ortiz, Z Means, T AF Prasad, Amit Ramirez-Ortiz, Zaida Means, Terry TI Mechanisms of AIM2 inflammasome regulation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Prasad, Amit; Ramirez-Ortiz, Zaida; Means, Terry] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4093 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104162 ER PT J AU Qiao, F Zhang, LX Yang, XF Hua, YP Narang, A Holers, M Kulik, L Song, HB Tomlinson, S AF Qiao, Fei Zhang, Lixia Yang, Xiaofeng Hua, Yunpeng Narang, Aarti Holers, Michael Kulik, Liudmila Song, Hongbin Tomlinson, Stephen TI Role of pathogenic natural antibodies and complement in a murine model of spinal cord injury SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Qiao, Fei; Zhang, Lixia; Yang, Xiaofeng; Hua, Yunpeng; Narang, Aarti; Tomlinson, Stephen] Med Univ S Carolina, Charleston, SC 29425 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Holers, Michael; Kulik, Liudmila] Univ Colorado, Dept Med & Immunol, Denver, CO 80202 USA. [Song, Hongbin] Acad Mil Med Sci, Inst Dis Control & Prevent, Beijing, Peoples R China. NR 0 TC 0 Z9 0 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 MAY 1 PY 2013 VL 190 MA P4051 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104120 ER PT J AU Richard, ML Nowling, T Zhang, X AF Richard, Mara Lennard Nowling, Tamara Zhang, Xian TI Fli-1 drives transcription from the MCP-1 gene promoter, which may provide a novel mechanism for cytokine and chemokine activation. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Richard, Mara Lennard; Nowling, Tamara; Zhang, Xian] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Nowling, Tamara; Zhang, Xian] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA 11514 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987108073 ER PT J AU Salinthone, S Wilkinson, A Carr, D AF Salinthone, Sonemany Wilkinson, Amelia Carr, Daniel TI Dimethyl fumarate stimulates cyclic AMP production and suppresses production of pro-inflammatory mediators in immune cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Salinthone, Sonemany; Wilkinson, Amelia; Carr, Daniel] Portland VA Med Ctr, Portland, OR USA. [Salinthone, Sonemany; Carr, Daniel] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P5143 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987107004 ER PT J AU Sato, S Williams, S Zhang, X AF Sato, Shuzo Williams, Sarah Zhang, Xian TI Fli-1 transcription factor affects inflammatory cell infiltration into the kidneys independent of autoantibodies SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Sato, Shuzo; Zhang, Xian] Med Univ S Carolina, Charleston, SC 29425 USA. [Williams, Sarah] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4150 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104218 ER PT J AU Sztokman, N Zhang, X AF Sztokman, Nicole Zhang, Xian TI Transcription factor Fli-1 is involved in regulation of inflammatory mediator production and ECM remodeling in primary dermal fibroblasts SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Sztokman, Nicole; Zhang, Xian] Med Univ S Carolina, Charleston, SC 29425 USA. [Zhang, Xian] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P5088 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987106200 ER PT J AU Van Dyke, T Herrera, B Hasturk, H Kantarci, A AF Van Dyke, Thomas Herrera, Bruno Hasturk, Hatice Kantarci, Alpdogan TI RvE1 and phagocytosis of Porphyromonas gingivalis by PMN in type 2 diabetes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Van Dyke, Thomas; Herrera, Bruno; Hasturk, Hatice; Kantarci, Alpdogan] Forsyth Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4227 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105044 ER PT J AU Winstead, C Way, SS Moon, J Weaver, C AF Winstead, Colleen Way, Sing Sing Moon, James Weaver, Casey TI Using reporter mouse models to track CD4 T cell differentiation and fate based on IL-2 expression SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Winstead, Colleen; Weaver, Casey] Univ Alabama Birmingham, Birmingham, AL USA. [Way, Sing Sing] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Moon, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 MAY 1 PY 2013 VL 190 MA P1199 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100198 ER PT J AU Yates, C Rodrigues, M Wells, A AF Yates, Cecelia Rodrigues, Melanie Wells, Alan TI Co-transplantation of mesenchymal stem cell and fibroblast reduces inflammation and corrects defective dermal remodeling SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Yates, Cecelia] Univ Pittsburgh SON, Pittsburgh, PA USA. [Yates, Cecelia; Rodrigues, Melanie; Wells, Alan] Univ Pittsburgh SOM, Pittsburgh, PA USA. [Yates, Cecelia; Wells, Alan] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Yates, Cecelia; Wells, Alan] VA Pittsburgh Healthcare Syst, Pathol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P5062 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987106174 ER PT J AU Yuki, K Sen, M Springer, T AF Yuki, Koichi Sen, Mehmet Springer, Timothy TI Common activation mechanism of beta 2 integrins SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Yuki, Koichi] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Yuki, Koichi; Sen, Mehmet; Springer, Timothy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P5073 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987106185 ER PT J AU Choy, G Kropil, P Scherer, A El-Sherief, AH Chung, J Rojas, CA Abbara, S AF Choy, Garry Kroepil, Patric Scherer, Axel El-Sherief, Ahmed H. Chung, Jonathan Rojas, Carlos A. Abbara, Suhny TI Pertinent reportable incidental cardiac findings on chest CT without electrocardiography gating: review of 268 consecutive cases SO ACTA RADIOLOGICA LA English DT Review DE Computed tomography; incidental cardiac findings; chest CT without ECG gating; coronary artery disease ID AORTIC-STENOSIS; COMPUTED-TOMOGRAPHY; PULMONARY-EMBOLISM; MULTIDETECTOR CT; MYOCARDIAL-INFARCTION; PATHOLOGICAL FINDINGS; ATRIAL-MYXOMA; NONGATED CT; GATED CT; CALCIFICATION AB Background: Pertinent reportable cardiac findings on non-electrocardiography (ECG)-gated chest CT examinations have become easier to detect given recent advancements in multidetector CT technology. However, those findings are easily overlooked on routine chest CT without ECG gating given residual inherent cardiac motion artifact and non-cardiac indications. Purpose: To describe and quantify the types of pertinent reportable cardiac findings that can be detected on chest CT examinations without ECG gating and evaluate how often they were reported. Material and Methods: Two radiologists retrospectively reviewed (blinded to the original interpretation) 268 consecutive routine adult chest CT examinations without ECG gating for the presence of pertinent reportable cardiac findings. Retrospective interpretations were then compared with the original radiological reports. Results: One hundred and sixty-three patients (61%) had pertinent reportable cardiac findings. The findings encountered included: coronary artery disease (n = 131; 80.0%), coronary artery bypass grafts (n = 10; 6.1%), left ventricular aneurysm (n = 1; 0.6%), valve calcification (n 131; 80.0%), valve repair/replacement (n = 5; 3.1%), pericardial effusion (n = 33; 20.2%), left atrial appendage thrombus (n = 1; 0.6%), cardiac mass (n = 1; 0.6%), and cardiac chamber enlargement (n = 29; 17.8%). On the original radiological reports 22.3% of the pertinent reportable cardiac findings, detected by the two radiologists retrospectively, were not reported. Conclusion: Detection of pertinent reportable cardiac findings on routine chest CT examinations without ECG gating is possible. The high volume of chest CT examinations without ECG gating represents an opportunity for radiologists to comment on the presence or absence of cardiac disease which may influence future clinical decisions. C1 [Choy, Garry; El-Sherief, Ahmed H.; Chung, Jonathan; Rojas, Carlos A.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Cardiac Imaging Sect, Boston, MA 02114 USA. [Kroepil, Patric; Scherer, Axel] Univ Dusseldorf, Fac Med, Dept Diagnost & Intervent Radiol, D-40225 Dusseldorf, Germany. RP Kropil, P (reprint author), Univ Dusseldorf, Fac Med, Dept Diagnost & Intervent Radiol, D-40225 Dusseldorf, Germany. EM patric.kroepil@med.uni-duesseldorf.de NR 28 TC 4 Z9 4 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD MAY PY 2013 VL 54 IS 4 BP 396 EP 400 DI 10.1177/0284185113475918 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 190ER UT WOS:000322322500007 PM 23436832 ER PT J AU Rosen, PL Palmer, JN O'Malley, BW Cohen, NA AF Rosen, Philip L. Palmer, James N. O'Malley, Bert W., Jr. Cohen, Noam A. TI Surfactants in the management of rhinopathologies SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID ENDOSCOPIC SINUS SURGERY; CITRIC ACID/ZWITTERIONIC SURFACTANT; BACTERIAL BIOFILMS; CHRONIC RHINOSINUSITIS; STAPHYLOCOCCUS-AUREUS; TOPICAL TOBRAMYCIN; IRRIGATION BOTTLE; ANIMAL-MODEL; SHEEP MODEL; IN-VITRO AB Background: Surfactants are a class of amphiphilic surface active compounds that show several unique physical properties at liquid-liquid or liquid-solid surface interfaces including the ability to increase the solubility of substances, lower the surface tension of a liquid, and decrease friction between two mediums. Because of these unique physical properties several in vitro, ex vivo, and human trials have examined the role of surfactants as stand-alone or adjunct therapy in recalcitrant chronic rhinosinusitis (CRS). Methods: A review of the literature was performed. Results: The data from three different surfactants have been examined in this review: citric acid zwitterionic surfactant (CAZS; Medtronic ENT, Jacksonville FL), Johnson's Baby Shampoo (Johnson & Johnson, New Brunswick NJ), and SinuSurf (NeilMed Pharmaceuticals, Santa Rosa, CA). Dilute surfactant therapy shows in vitro antimicrobial effects with modest inhibition of bacterial biofilm formation. In patients with CRS, surfactants may improve symptoms, most likely through its mucolytic effects. In addition, surfactants have several distinct potential benefits including their ability to improve an irrigant's penetration of the nonoperated sinus and their synergistic effects with antibiotics. However, surfactants potential for nasal irritation and possible transient ciliotoxicity may limit their use. Conclusion: Recent data suggest a possible therapeutic role of surfactants in treating rhinopathologies associated with mucostasis. Further investigation, including a standardization of surfactant formulations, is warranted to further elucidate the potential benefits and drawbacks of this therapy. C1 [Rosen, Philip L.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Palmer, James N.; O'Malley, Bert W., Jr.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Dept Otolaryngol, 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 noam.cohen@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 NR 25 TC 6 Z9 8 U1 2 U2 7 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAY-JUN PY 2013 VL 27 IS 3 BP 177 EP 180 DI 10.2500/ajra.2013.27.3873 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 193HF UT WOS:000322549000007 PM 23710951 ER PT J AU Walensky, LD AF Walensky, Loren D. TI Playing FullBAK SO CELL CYCLE LA English DT Editorial Material ID BH3 DOMAIN; APOPTOSIS; BAX; OLIGOMERIZATION C1 [Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02114 USA. [Walensky, Loren D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dana Farber Canc Inst,Linde Program Canc Chem Bio, Boston, MA USA. RP Walensky, LD (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02114 USA. EM Loren_Walensky@dfci.harvard.edu FU NIGMS NIH HHS [R01 GM090299] NR 8 TC 1 Z9 1 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2013 VL 12 IS 9 BP 1333 EP 1334 DI 10.4161/cc.24607 PG 2 WC Cell Biology SC Cell Biology GA 196FJ UT WOS:000322758600004 PM 23588072 ER PT J AU Rowe, GC Patten, IS Zsengeller, ZK El-Khoury, R Okutsu, M Bampoh, S Koulisis, N Farrell, C Hirshman, MF Yan, Z Goodyear, LJ Rustin, P Arany, Z AF Rowe, Glenn C. Patten, Ian S. Zsengeller, Zsuzsanna K. El-Khoury, Riyad Okutsu, Mitsuharu Bampoh, Sophia Koulisis, Nicole Farrell, Caitlin Hirshman, Michael F. Yan, Zhen Goodyear, Laurie J. Rustin, Pierre Arany, Zolt TI Disconnecting Mitochondrial Content from Respiratory Chain Capacity in PGC-1-Deficient Skeletal Muscle SO CELL REPORTS LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; FIBER-TYPE DETERMINATION; PGC-1 COACTIVATORS; ENERGY-METABOLISM; ADAPTIVE THERMOGENESIS; ATP SYNTHASE; ANGIOGENESIS; BIOGENESIS; DISEASE; MICE AB The transcriptional coactivators PGC-1 alpha and PGC-1 beta are widely thought to be required for mitochondrial biogenesis and fiber typing in skeletal muscle. Here, we show that mice lacking both PGC-1s in myocytes do indeed have profoundly deficient mitochondrial respiration but, surprisingly, have preserved mitochondrial content, isolated muscle contraction capacity, fiber-type composition, in-cage ambulation, and voluntary running capacity. Most of these findings are recapitulated in cell culture and, thus, are cell autonomous. Functional electron microscopy reveals normal cristae density with decreased cytochrome oxidase activity. These data lead to the following surprising conclusions: (1) PGC-1s are in fact dispensable for baseline muscle function, mitochondrial content, and fiber typing, (2) endurance fatigue at low workloads is not limited by muscle mitochondrial capacity, and (3) mitochondrial content and cristae density can be dissociated from respiratory capacity. C1 [Rowe, Glenn C.; Patten, Ian S.; Bampoh, Sophia; Koulisis, Nicole; Farrell, Caitlin; Arany, Zolt] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Rowe, Glenn C.; Patten, Ian S.; Bampoh, Sophia; Koulisis, Nicole; Farrell, Caitlin; Arany, Zolt] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Zsengeller, Zsuzsanna K.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Zsengeller, Zsuzsanna K.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [El-Khoury, Riyad; Rustin, Pierre] Hop Robert Debre, INSERM, UMR 676, F-75019 Paris, France. [El-Khoury, Riyad; Rustin, Pierre] Univ Paris 07, Fac Med Denis Diderot, F-75005 Paris, France. [Okutsu, Mitsuharu; Yan, Zhen] Univ Virginia, Sch Med, Robert M Berne Cardiovasc Res Ctr, Ctr Skeletal Muscle Res, Charlottesville, VA 22908 USA. [Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Arany, Z (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. EM zarany@bidmc.harvard.edu FU National Institutes of Health [NIAMS AR062128, AR42238, NHLBI HL094499] FX This work was supported by grants from the National Institutes of Health (NIAMS AR062128 to G.C.R. and AR42238 L.J.G., and NHLBI HL094499 to Z.A.). G.C.R. and Z.A. designed the research; G.C.R., I.S.P., N.K., Z.K.Z., R.E., M.O., C.F., S.B., and M.F.H. performed research; G.C.R., Z.Y., L.J.G., P.R., and Z.A. analyzed data; and G.C.R. and Z.A. wrote the paper. NR 44 TC 41 Z9 41 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2013 VL 3 IS 5 BP 1449 EP 1456 DI 10.1016/j.celrep.2013.04.023 PG 8 WC Cell Biology SC Cell Biology GA 184NY UT WOS:000321899300016 PM 23707060 ER PT J AU Rheinbay, E Suva, ML Gillespie, SM Wakimoto, H Patel, AP Shahid, M Oksuz, O Rabkin, SD Martuza, RL Rivera, MN Louis, DN Kasif, S Chi, AS Bernstein, BE AF Rheinbay, Esther Suva, Mario L. Gillespie, Shawn M. Wakimoto, Hiroaki Patel, Anoop P. Shahid, Mohammad Oksuz, Ozgur Rabkin, Samuel D. Martuza, Robert L. Rivera, Miguel N. Louis, David N. Kasif, Simon Chi, Andrew S. Bernstein, Bradley E. TI An Aberrant Transcription Factor Network Essential for Wnt Signaling and Stem Cell Maintenance in Glioblastoma SO CELL REPORTS LA English DT Article ID TUMOR-INITIATING CELLS; INTEGRATIVE GENOMICS VIEWER; CHROMATIN STATE; SELF-RENEWAL; DNA METHYLATION; CANCER; GLIOMA; EXPRESSION; BRAIN; DIFFERENTIATION AB Glioblastoma (GBM) is thought to be driven by a sub-population of cancer stem cells (CSCs) that self-renew and recapitulate tumor heterogeneity yet remain poorly understood. Here, we present a comparative analysis of chromatin state in GBM CSCs that reveals widespread activation of genes normally held in check by Polycomb repressors. These activated targets include a large set of developmental transcription factors (TFs) whose coordinated activation is unique to the CSCs. We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1. We show that ASCL1 is essential for the maintenance and in vivo tumorigenicity of GBM CSCs. Genome-wide binding profiles for ASCL1 and the Wnt effector LEF-1 provide mechanistic insight and suggest widespread interactions between the TF module and the signaling pathway. Our findings demonstrate regulatory connections among ASCL1, Wnt signaling, and collaborating TFs that are essential for the maintenance and tumorigenicity of GBM CSCs. C1 [Rheinbay, Esther; Suva, Mario L.; Gillespie, Shawn M.; Chi, Andrew S.; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Rheinbay, Esther; Suva, Mario L.; Gillespie, Shawn M.; Oksuz, Ozgur; Rivera, Miguel N.; Louis, David N.; Chi, Andrew S.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rheinbay, Esther; Suva, Mario L.; Gillespie, Shawn M.; Oksuz, Ozgur; Rivera, Miguel N.; Louis, David N.; Chi, Andrew S.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Wakimoto, Hiroaki; Patel, Anoop P.; Rabkin, Samuel D.; Martuza, Robert L.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Div Neurooncol, Boston, MA 02114 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Chi, Andrew S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rheinbay, Esther; Suva, Mario L.; Gillespie, Shawn M.; Rivera, Miguel N.; Chi, Andrew S.; Bernstein, Bradley E.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Rheinbay, Esther; Kasif, Simon] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Kasif, Simon] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Shahid, Mohammad] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Chi, AS (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. EM chi.andrew@mgh.harvard.edu; bernstein.bradley@mgh.harvard.edu OI rabkin, samuel/0000-0003-2344-2795; Shahid, Mohammad/0000-0003-2615-9848 FU Joan Ambriz American Brain Tumor Association basic research fellowship; Ben and Catherine Ivy Foundation; Oncosuisse grant [BIL-KFS-02590-02-2010]; Medic Foundation grant; Burroughs Wellcome Fund; Howard Hughes Medical Institute; NIH [RO1 CA160762]; Starr Cancer Consortium; Harvard Stem Cell Institute; Affymetrix FX We thank Tarjei Mikkelsen, Timothy Durham, and Noam Shoresh for computational assistance and Chuck Epstein, Robbyn Issner, and the Broad Institute Genome Sequencing Platform for help with data production. We thank David Dombkowski for help with FACS analysis and Lauren Solomon and Leslie Gaffney for assistance with graphics. A.S.C. is supported by a Joan Ambriz American Brain Tumor Association basic research fellowship and early career research award from the Ben and Catherine Ivy Foundation. M.L.S. is supported by Oncosuisse grant BIL-KFS-02590-02-2010 and a Medic Foundation grant. M.N.R. is supported by awards from the Burroughs Wellcome Fund and the Howard Hughes Medical Institute. S.D.R. supported in part by NIH (RO1 CA160762). This research was supported by funds from the Starr Cancer Consortium (B.E.B.), the Harvard Stem Cell Institute, the Burroughs Wellcome Fund (B.E.B.), and the Howard Hughes Medical Institute (B.E.B.). M.N.R. and M.S. receive research funding from Affymetrix. NR 56 TC 66 Z9 67 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2013 VL 3 IS 5 BP 1567 EP 1579 DI 10.1016/j.celrep.2013.04.021 PG 13 WC Cell Biology SC Cell Biology GA 184NY UT WOS:000321899300027 PM 23707066 ER PT J AU Shiotani, B Nguyen, HD Hakansson, P Marechal, A Tse, A Tahara, H Zou, L AF Shiotani, Bunsyo Hai Dang Nguyen Hakansson, Pelle Marechal, Alexandre Tse, Alice Tahara, Hidetoshi Zou, Lee TI Two Distinct Modes of ATR Activation Orchestrated by Rad17 and Nbs1 SO CELL REPORTS LA English DT Article ID REPLICATION PROTEIN-A; DNA-DAMAGE RESPONSE; STRAND BREAK REPAIR; S-PHASE CHECKPOINT; MRE11 COMPLEX; RPA2 PHOSPHORYLATION; CHK1 ACTIVATION; END RESECTION; MRN COMPLEX; TOPBP1 AB The ATM- and Rad3-related (ATR) kinase is a master regulator of the DNA damage response, yet how ATR is activated toward different substrates is still poorly understood. Here, we show that ATR phosphorylates Chk1 and RPA32 through distinct mechanisms at replication-associated DNA double-stranded breaks (DSBs). In contrast to the rapid phosphorylation of Chk1, RPA32 is progressively phosphorylated by ATR at Ser33 during DSB resection prior to the phosphorylation of Ser4/Ser8 by DNA-PKcs. Surprisingly, despite its reliance on ATR and TopBP1, substantial RPA32 Ser33 phosphorylation occurs in a Rad17-independent but Nbs1-dependent manner in vivo and in vitro. Importantly, the role of Nbs1 in RPA32 phosphorylation can be separated from ATM activation and DSB resection, and it is dependent upon the interaction of Nbs1 with RPA. An Nbs1 mutant that is unable to bind RPA fails to support proper recovery of collapsed replication forks, suggesting that the Nbs1-mediated mode of ATR activation is important for the repair of replication-associated DSBs. C1 [Shiotani, Bunsyo; Hai Dang Nguyen; Hakansson, Pelle; Marechal, Alexandre; Tse, Alice; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. [Zou, Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zou, Lee] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Shiotani, Bunsyo; Tahara, Hidetoshi] Hiroshima Univ, Dept Cellular & Mol Biol, Hiroshima 7348553, Japan. RP Shiotani, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. EM bshiotan@hiroshima-u.ac.jp; zou.lee@mgh.harvard.edu OI Hakansson, Pelle/0000-0003-0421-2433 FU Swedish Research Council; FRSQ fellowship; Japanese Ministry of Education, Culture, Sports, Science and Technology [KAKENHI 24800044, KAKENHI 23300363]; NIH [GM076388]; ACS [RSG-08-297]; Federal Share of MGH Proton Program FX We thank Dr. K. Cimprich for communicating previously unpublished results (Duursma et al., 2013); Drs. S. Elledge, A. Nussenzweig, T. Paull, X. Wu, B. Chen, R. Baer, P. Concannon, and K. Komatsu for reagents; and members of the Zou lab for helpful discussions. P.H. was supported by a postdoctoral fellowship from the Swedish Research Council. A.M. is supported by an FRSQ fellowship. L.Z. is a Jim and Ann Orr Massachusetts General Hospital Research Scholar. This work was supported by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology to B.S. (KAKENHI 24800044) and H.T. (KAKENHI 23300363), and grants from the NIH (GM076388), the ACS (RSG-08-297), and the Federal Share of MGH Proton Program to L.Z. NR 70 TC 48 Z9 48 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2013 VL 3 IS 5 BP 1651 EP 1662 DI 10.1016/j.celrep.2013.04.018 PG 12 WC Cell Biology SC Cell Biology GA 184NY UT WOS:000321899300034 PM 23684611 ER PT J AU Wu, HT Xiao, YB Zhang, SH Ji, SY Wei, LY Fan, FQ Geng, J Tian, J Sun, XF Qin, FN Jin, CN Lin, JJ Yin, ZY Zhang, T Luo, LZ Li, Y Song, SY Lin, SC Deng, XM Camargo, F Avruch, J Chen, LF Zhou, DW AF Wu, Hongtan Xiao, Yubo Zhang, Shihao Ji, Suyuan Wei, Luyao Fan, Fuqin Geng, Jing Tian, Jing Sun, Xiufeng Qin, Funiu Jin, Changnan Lin, Jianjun Yin, Zhen-Yu Zhang, Ting Luo, Lianzhong Li, Yang Song, Siyang Lin, Sheng-Cai Deng, Xianming Camargo, Fernando Avruch, Joseph Chen, Lanfen Zhou, Dawang TI The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense SO CELL REPORTS LA English DT Article ID YES-ASSOCIATED PROTEIN; BINDING-PROTEIN; SIGNALING PATHWAY; DNA-BINDING; CELL-PROLIFERATION; OXIDATIVE-STRESS; E4TF1 SUBUNITS; T-LYMPHOCYTES; TISSUE-GROWTH; SELF-RENEWAL AB The transcriptional coactivator Yes-associated protein (YAP) plays an important role in organ-size control and tumorigenesis. However, how Yap gene expression is regulated remains unknown. This study shows that the Ets family member GABP binds to the Yap promoter and activates YAP transcription. The depletion of GABP downregulates YAP, resulting in a G1/S cell-cycle block and increased cell death, both of which are substantially rescued by reconstituting YAP. GABP can be inactivated by oxidative mechanisms, and acetaminophen-induced glutathione depletion inhibits GABP transcriptional activity and depletes YAP. In contrast, activating YAP by deleting Mst1/Mst2 strongly protects against acetaminophen-induced liver injury. Similar to its effects on YAP, Hippo signaling inhibits GABP transcriptional activity through several mechanisms. In human liver cancers, enhanced YAP expression is correlated with increased nuclear expression of GABP. Therefore, we conclude that GABP is an activator of Yap gene expression and a potential therapeutic target for cancers driven by YAP. C1 [Wu, Hongtan; Xiao, Yubo; Zhang, Shihao; Ji, Suyuan; Wei, Luyao; Fan, Fuqin; Geng, Jing; Tian, Jing; Sun, Xiufeng; Qin, Funiu; Li, Yang; Song, Siyang; Lin, Sheng-Cai; Deng, Xianming; Chen, Lanfen; Zhou, Dawang] Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen 361102, Jiangsu, Peoples R China. [Jin, Changnan; Lin, Jianjun; Zhang, Ting] Xiamen Hosp Tradit Chinese Med, Dept Hepatol, Xiamen 361001, Fujian, Peoples R China. [Yin, Zhen-Yu] Xiamen Univ, Dept Hepatobiliary Surg, Zhongshan Hosp, Xiamen 361004, Fujian, Peoples R China. [Luo, Lianzhong] Xiamen Med Coll, Dept Pharm, Xiamen 361008, Fujian, Peoples R China. [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Med Serv, Boston, MA 02114 USA. [Avruch, Joseph] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Camargo, Fernando] Harvard Univ, Boston Childrens Hosp, Sch Med, Stem Cell Program, Boston, MA 02115 USA. [Camargo, Fernando] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Chen, LF (reprint author), Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen 361102, Jiangsu, Peoples R China. EM chenlanfen@xmu.edu.cn; dwzhou@xmu.edu.cn RI Chen, Lanfen/B-7975-2016; OI Chen, Lanfen/0000-0002-9413-1284; Zhou, Dawang/0000-0002-9053-5249 FU China's 1000 Young Talents Program; 111 Project of the Ministration of Education of China [B06016]; Fundamental Research Funds for the Central Universities of China [2010111079]; National Natural Science Foundation of China [81101503/H1602, 31270918/C080101, 81222030/H1602]; Natural Science Foundation of Fujian [2011J05096]; Program of Introducing Talents of Discipline to Universities [B12001]; ROI awards [CA136567, DK17776]; DOD award [W81XWH-09-NFRP-NIA]; Stand Up to Cancer FX D.Z. was supported by grants from the China's 1000 Young Talents Program, the 111 Project of the Ministration of Education of China (B06016), the Fundamental Research Funds for the Central Universities of China (2010111079), the National Natural Science Foundation of China (81101503/H1602, 31270918/C080101, and 81222030/H1602), the Natural Science Foundation of Fujian (2011J05096), and the Program of Introducing Talents of Discipline to Universities (B12001). J.A. was supported in part by ROI awards CA136567 and DK17776, and institutional funds. F.C. was supported in part by DOD award W81XWH-09-NFRP-NIA and Stand Up to Cancer. NR 49 TC 36 Z9 38 U1 3 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2013 VL 3 IS 5 BP 1663 EP 1677 DI 10.1016/j.celrep.2013.04.020 PG 15 WC Cell Biology SC Cell Biology GA 184NY UT WOS:000321899300035 PM 23684612 ER PT J AU Roffman, JL Lamberti, JS Achtyes, E Macklin, EA Galendez, GC Raeke, LH Silverstein, NJ Smoller, JW Hill, M Goff, DC AF Roffman, Joshua L. Lamberti, J. Steven Achtyes, Eric Macklin, Eric A. Galendez, Gail C. Raeke, Lisa H. Silverstein, Noah J. Smoller, Jordan W. Hill, Michele Goff, Donald C. TI Randomized Multicenter Investigation of Folate Plus Vitamin B-12 Supplementation in Schizophrenia SO JAMA PSYCHIATRY LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; FOLIC-ACID FORTIFICATION; HOMOCYSTEINE LEVELS; NEGATIVE SYMPTOMS; RISK-FACTOR; MYOCARDIAL-INFARCTION; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; CONTROLLED-TRIAL; METHYLENETETRAHYDROFOLATE REDUCTASE AB Importance: More effective treatments are needed for negative symptoms of schizophrenia, which are typically chronic, disabling, and costly. Negative symptoms have previously been associated with reduced blood folate levels, especially among patients with low-functioning variants in genes that regulate folate metabolism, suggesting the potential utility of folate supplementation. Objectives: To determine whether folic acid plus vitamin B-12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response. Design: Parallel-group, randomized, double-blind, placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 mu g of vitamin B-12. Setting: Three community mental health centers affiliated with academic medical centers in the United States. Participants: Outpatients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment. Eligible patients were 18 to 68 years old, were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more, and scored 60 or more on the Positive and Negative Syndrome Scale. Intervention: One hundred forty subjects were randomized to receive daily oral folic acid plus vitamin B-12 or placebo. Main Outcome Measures: Change in negative symptoms (Scale for the Assessment of Negative Symptoms [SANS]), as well as positive and total symptoms (Positive and Negative Syndrome Scale). Results: Folate plus vitamin B-12 improved negative symptoms significantly compared with placebo (group difference, -0.33 change in SANS score per week; 95% CI, -0.62 to -0.05) when genotype was taken into account but not when genotype was excluded. An interaction of the 484C>T variant of FOLH1 (rs202676) with treatment was observed (P=.02), where only patients homozygous for the 484T allele demonstrated significantly greater benefit with active treatment (-0.59 change in SANS score per week; 95% CI, -0.99 to -0.18). In parallel, we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load (P=.03), which persisted until 8 weeks of treatment. Change in positive and total symptoms did not differ between treatment groups. Conclusions: Folate plus vitamin B-12 supplementation can improve negative symptoms of schizophrenia, but treatment response is influenced by genetic variation in folate absorption. These findings support a personalized medicine approach for the treatment of negative symptoms. C1 [Roffman, Joshua L.; Galendez, Gail C.; Raeke, Lisa H.; Silverstein, Noah J.; Smoller, Jordan W.; Hill, Michele; Goff, Donald C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Roffman, Joshua L.; Macklin, Eric A.; Galendez, Gail C.; Raeke, Lisa H.; Silverstein, Noah J.; Smoller, Jordan W.; Hill, Michele; Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Lamberti, J. Steven] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Achtyes, Eric] Michigan State Univ, Coll Human Med, Cherry St Hlth Serv, Grand Rapids, MI USA. [Achtyes, Eric] Michigan State Univ, Coll Human Med, Dept Psychiat, Grand Rapids, MI USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 2606, Charlestown, MA 02129 USA. EM jroffman@partners.org OI Macklin, Eric/0000-0003-1618-3502; Achtyes, Eric/0000-0001-8939-1535 FU National Institute of Mental Health [R01MH070831]; Howard Hughes Medical Institute Early Career Physician-Scientist Award; Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 RR 025758]; Harvard University FX This work was supported by National Institute of Mental Health grant R01MH070831 (Dr Goff) and the Howard Hughes Medical Institute Early Career Physician-Scientist Award (Dr Roffman). This work was conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award UL1 RR 025758, and financial contributions from Harvard University and its affiliated academic health care centers). NR 47 TC 26 Z9 28 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-622X J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAY PY 2013 VL 70 IS 5 BP 481 EP 489 DI 10.1001/jamapsychiatry.2013.900 PG 9 WC Psychiatry SC Psychiatry GA 188PF UT WOS:000322204200004 PM 23467813 ER PT J AU Kim, JK Choi, JW Yun, SH AF Kim, Jun Ki Choi, Jin Woo Yun, Seok Hyun TI 350-mu m side-view optical probe for imaging the murine brain in vivo from the cortex to the hypothalamus SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE miniature endoscope; side-view probe; deep brain imaging; neuronal imaging ID MICROSCOPY; NEOCORTEX; TISSUE AB Miniature endoscopic probes offer a solution for deep brain imaging by overcoming the limited depth of intravital microscopy. We describe a small-diameter (350 mu m) graded-index optical probe with a side-view design for in vivo cellular imaging of the mammalian brain. The side-view probe provides a unique view of the vertical network of neurons and penetrating blood vessels. At a given insertion site, the translational and rotational scanning of the probe provides access to a large tissue area (> 1 mm(2)) across the cortex, hippocampus, thalamus, and hypothalamus. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Kim, Jun Ki; Choi, Jin Woo; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Jun Ki; Choi, Jin Woo; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kim, Jun Ki; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, WCU Grad Sch Nanosci & Technol, Taejon 305701, South Korea. [Choi, Jin Woo] Wonkwang Univ, Sch Dent, Dept Dent Pharmacol, Iksan 570749, Chonbuk, South Korea. [Choi, Jin Woo] Wonkwang Univ, Inst Biomat Implant, Iksan 570749, Chonbuk, South Korea. [Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA 02140 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM syun@hms.harvard.edu FU Department of Defense [FA9550-10-1-0537]; National Research Foundation of Korea [R31-2008-000-10071-0] FX This work was supported by grants from the Department of Defense (Grant No. FA9550-10-1-0537) and from the National Research Foundation of Korea (Grant No. R31-2008-000-10071-0). NR 14 TC 2 Z9 2 U1 0 U2 2 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY PY 2013 VL 18 IS 5 AR 050502 DI 10.1117/1.JBO.18.5.050502 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 190KW UT WOS:000322339900002 PM 23629547 ER PT J AU Gillis, JL Selth, LA Centenera, MM Townley, SL Sun, SH Plymate, SR Tilley, WD Butler, LM AF Gillis, Joanna L. Selth, Luke A. Centenera, Margaret M. Townley, Scott L. Sun, Shihua Plymate, Stephen R. Tilley, Wayne D. Butler, Lisa M. TI Constitutively-active androgen receptor variants function independently of the HSP90 chaperone but do not confer resistance to HSP90 inhibitors SO ONCOTARGET LA English DT Article DE Androgen receptor; variant; HSP90; HSP90 inhibitor; prostate cancer ID HEAT-SHOCK-PROTEIN; REFRACTORY PROSTATE-CANCER; SPLICE VARIANTS; NUCLEAR-LOCALIZATION; BINDING DOMAIN; PROGRESSION; MUTATIONS; GROWTH; THERAPY; COMPLEX AB The development of lethal, castration resistant prostate cancer is associated with adaptive changes to the androgen receptor (AR), including the emergence of mutant receptors and truncated, constitutively active AR variants. AR relies on the molecular chaperone HSP90 for its function in both normal and malignant prostate cells, but the requirement for HSP90 in environments with aberrant AR expression is largely unknown. Here, we investigated the efficacy of three HSP90 inhibitors, 17-AAG, HSP990 and AUY922, against clinically-relevant AR missense mutants and truncated variants. HSP90 inhibition effectively suppressed the signaling of wild-type AR and all AR missense mutants tested. By contrast, two truncated AR variants, AR-V7 and ARv567es, exhibited marked resistance to HSP90 inhibitors. Supporting this observation, nuclear localization of the truncated AR variants was not affected by HSP90 inhibition and AR variant: HSP90 complexes could not be detected in prostate cancer cells. Interestingly, HSP90 inhibition resulted in accumulation of AR-V7 and ARv567es in both cell lines and human tumor explants. Despite the apparent independence of AR variants from HSP90 and their treatment-associated induction, the growth of cell lines with endogenous or enforced expression of AR-V7 or ARv567es remained highly sensitive to AUY922. This study demonstrates that functional AR variant signaling does not confer resistance to HSP90 inhibition, yields insight into the interaction between AR and HSP90 and provides further impetus for the clinical application of HSP90 inhibitors in advanced prostate cancer. C1 [Gillis, Joanna L.; Selth, Luke A.; Centenera, Margaret M.; Townley, Scott L.; Tilley, Wayne D.; Butler, Lisa M.] Univ Adelaide, Dame Roma Mitchell Canc Res Labs, Adelaide, SA, Australia. [Gillis, Joanna L.; Selth, Luke A.; Centenera, Margaret M.; Townley, Scott L.; Tilley, Wayne D.; Butler, Lisa M.] Univ Adelaide, Adelaide Prostate Canc Res Ctr, Adelaide, SA, Australia. [Gillis, Joanna L.; Selth, Luke A.; Centenera, Margaret M.; Townley, Scott L.; Tilley, Wayne D.; Butler, Lisa M.] Hanson Inst, Adelaide, SA, Australia. [Sun, Shihua; Plymate, Stephen R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Plymate, Stephen R.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. [Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Educ & Clin Ctr, Seattle, WA USA. RP Butler, LM (reprint author), Univ Adelaide, Dame Roma Mitchell Canc Res Labs, Adelaide, SA, Australia. EM lisa.butler@adelaide.edu.au FU Prostate Cancer Foundation; Prostate Cancer Foundation of Australia/Cancer Australia [YI 0810, YI 0412, 627229]; Royal Adelaide Hospital Research Committee; National Health and Medical Research Council of Australia [627185, 290456, 614296]; Pacific NW Prostate Cancer SPORE [P50 CA97186]; Veterans Affairs Research Program; Prostate Cancer Foundation of Australia [2011/0452] FX No potential conflicts of interest were disclosed by the authors. This work was supported by Young Investigator Awards from the Prostate Cancer Foundation (the Foundation 14 award; L. A. S.) and the Prostate Cancer Foundation of Australia/Cancer Australia (L. A. S., YI 0810; M. M. C., YI 0412) and grants from the Prostate Cancer Foundation of Australia/Cancer Australia (ID 627229 to L. M. B. and W. D. T.), the Royal Adelaide Hospital Research Committee (L. M. B. and M. M. C.), the National Health and Medical Research Council of Australia (ID 627185 to W. D. T. and L. M. B.), the Pacific NW Prostate Cancer SPORE (ID P50 CA97186 to S. R. P.) and the Veterans Affairs Research Program (S. R. P.). The Adelaide Prostate Cancer Research Centre is supported by an establishment grant from the Prostate Cancer Foundation of Australia (ID 2011/0452). The Australian Prostate Cancer BioResource is supported by the National Health and Medical Research Council of Australia (enabling grants 290456 and 614296) and Prostate Cancer Foundation of Australia. L. M. B. holds a senior research fellowship from the Cancer Council of South Australia. NR 48 TC 14 Z9 15 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY PY 2013 VL 4 IS 5 BP 691 EP 704 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 193RU UT WOS:000322580000006 PM 23674566 ER PT J AU Kang, SH Cho, JH Park, SH Toothaker, R Cho, SA AF Kang, Sang-Hwan Cho, Jin Hyun Park, Sang-Hun Toothaker, Randall Cho, Sung-Am TI Comparison of Osseointegration Between Laser-Etched and Magnesium-Incorporated Oxidized Implants in the Rabbit Femur SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE histomorphometric analysis; laser-etched; magnesium-incorporated oxided implant; removal torque ID TREATED TITANIUM IMPLANTS; SURFACE-PROPERTIES; REMOVAL TORQUE; BONE RESPONSE; ROUGHNESS; HYDROXYAPATITE; ALLOY AB Purpose: To compare the osseointegration of a laser-etched (LE) implant with a magnesium-incorporated oxidized (MgO) implant, evaluating their ability to enhance the bond strength between a titanium substrate and rabbit femur. Materials and Methods: Two type of dental implants, LE (test, commercially pure [CP] titanium grade 4) and MgO (control, CP titanium grade 4) (length, 8 mm; diameter, 3.3 mm), were evaluated for the surface characteristics using a field emission scanning electron microscope (FE-SEM), an energy dispersive spectrometer (EDS), and an optical three-dimensional profiling system. After that, two types of dental implants were implanted at the right and left distal femoral metaphysis of 10 adult rabbits weighing approximately 3.0 kg. After 6 weeks, histomorphometric analysis, removal torque tests, and surface analysis of the torque-tested implants were performed. Results: After surgery, the LE group showed thick bonelike materials within the pores observed using FE-SEM (magnifications x500 and x900). The mean removal torque was 40.72 +/- 13.3 Ncm for the test (LE) implant and 22.26 +/- 6.4 Ncm for the control (MgO) implant, respectively (P = .041). The mean bone-implant contact in the three best consecutive threads in the cortical region was 63.35% +/- 16.44% in the LE group and 51.63% +/- 5.09% in the MgO. Conclusions: In the beginning stage of cancellous bone healing, biomechanical properties of the LE implant could influence a more favorable bone response than that of MgO. C1 [Toothaker, Randall] Nebraska Western Iowa Hlth Care Syst, Omaha, NE USA. [Toothaker, Randall] Nebraska Western Iowa Hlth Care Syst, Dent Serv NWIHCS, US Dept Vet Affairs, Dent Lab Serv, Omaha, NE USA. EM sungamcho@gmail.com FU Kyungpook National University Research Fund FX This research was supported by Kyungpook National University Research Fund, 2011. The authors reported no conflicts of interest related to this study. NR 21 TC 2 Z9 2 U1 0 U2 5 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD MAY-JUN PY 2013 VL 28 IS 3 BP 775 EP 781 DI 10.11607/jomi.2448 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 186XE UT WOS:000322078500022 PM 23748308 ER PT J AU Maroules, CD Blaha, MJ El-Haddad, MA Ferencik, M Cury, RC AF Maroules, Christopher D. Blaha, Michael J. El-Haddad, Mohamed A. Ferencik, Maros Cury, Ricardo C. TI Establishing a successful coronary CT angiography program in the emergency department: Official writing of the Fellow and Resident Leaders of the Society of Cardiovascular Computed Tomography (FiRST) SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Coronary CT angiography; Acute chest pain triage ID ACUTE CHEST-PAIN; AMERICAN-HEART-ASSOCIATION; CARDIAC CT; RADIATION; TRIAGE; METAANALYSIS; CARDIOLOGY; RADIOLOGY AB Coronary CT angiography is an effective, evidence-based strategy for evaluating acute chest pain in the emergency department for patients at low-to-intermediate risk of acute coronary syndrome. Recent multicenter trials have reported that coronary CT angiography is safe, reduces time to diagnosis, facilitates discharge, and may lower overall cost compared with routine care. Herein, we provide a 10-step approach for establishing a successful coronary CT angiography program in the emergency department. The importance of strategic planning and multidisciplinary collaboration is emphasized. Patient selection and preparation guidelines for coronary CT angiography are reviewed with straightforward protocols that can be adapted and modified to clinical sites, depending on available cardiac imaging capabilities. Technical parameters and patient-specific modifications are also highlighted to maximize the likelihood of diagnostic quality examinations. Practical suggestions for quality control, process monitoring, and standardized reporting are reviewed. Finally, the role of a "triple rule-out" protocol is featured in the context of acute chest pain evaluation in the emergency department. (C) 2013 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Maroules, Christopher D.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. [Blaha, Michael J.] Johns Hopkins Univ Hosp, Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD 21287 USA. [El-Haddad, Mohamed A.] Wayne State Univ, Med Ctr, Dept Internal Med, Detroit, MI 48202 USA. [Ferencik, Maros] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ferencik, Maros] Harvard Univ, Sch Med, Boston, MA USA. [Cury, Ricardo C.] Baptist Hosp Miami, Dept Radiol, Miami, FL USA. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Miami, FL USA. RP Maroules, CD (reprint author), Univ Texas SW Med Ctr Dallas, Dept Radiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM christopher.maroules@phhs.org NR 20 TC 5 Z9 5 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAY-JUN PY 2013 VL 7 IS 3 BP 150 EP 156 DI 10.1016/j.jcct.2013.05.001 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 187DU UT WOS:000322097900002 PM 23809428 ER PT J AU Yuen, EK Herbert, JD Forman, EM Goetter, EM Juarascio, AS Rabin, S Goodwin, C Bouchard, S AF Yuen, Erica K. Herbert, James D. Forman, Evan M. Goetter, Elizabeth M. Juarascio, Adrienne S. Rabin, Stephanie Goodwin, Christina Bouchard, Stephane TI Acceptance based behavior therapy for social anxiety disorder through videoconferencing SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Social anxiety; Telehealth; Telemental health; Telepsychology; Videoconferencing; Skype ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED-CONTROLLED-TRIAL; BECK DEPRESSION INVENTORY; FACE-TO-FACE; WORKING ALLIANCE INVENTORY; NEGATIVE EVALUATION SCALE; SHEEHAN DISABILITY SCALE; PANIC DISORDER; PSYCHOMETRIC PROPERTIES; CONCURRENT VALIDITY AB Most individuals with social anxiety disorder (SAD) do not receive any type of treatment Reasons include logistical barriers (e.g., geographic location, travel time), fear of stigmatization, and fear of the social interactions associated with seeking treatment. Videoconferencing technology holds great promise in the widespread delivery of evidence-based treatments to those who would otherwise not receive treatment. This pilot study assessed the feasibility, acceptability, and initial efficacy of an acceptance-based behavioral intervention using Skype videoconferencing to treat adults with generalized SAD. Twenty-four participants received 12 sessions of weekly therapy and were assessed at pre-treatment, mid-treatment, post-treatment, and 3-month follow-up. Participants and therapists rated the intervention as acceptable and feasible. Analyses revealed significant pre-treatment to follow-up improvements in social anxiety, depression, disability, quality of life, and experiential avoidance, with effect sizes comparable to or larger than previously published results of studies delivering in-person CBT for SAD. Implications and future directions are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Yuen, Erica K.] Univ Tampa, Tampa, FL 33606 USA. [Yuen, Erica K.; Juarascio, Adrienne S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Yuen, Erica K.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Yuen, Erica K.; Herbert, James D.; Forman, Evan M.; Goetter, Elizabeth M.; Juarascio, Adrienne S.; Rabin, Stephanie; Goodwin, Christina] Drexel Univ, Philadelphia, PA 19104 USA. [Goetter, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodwin, Christina] Ohio State Univ, Columbus, OH 43210 USA. [Bouchard, Stephane] Univ Quebec Outaouais, Quebec City, PQ, Canada. RP Herbert, JD (reprint author), Dept Psychol, 119 Stratton,3141 Chestnut St, Philadelphia, PA 19104 USA. EM james.herbert@drexel.edu RI Forman, Evan/I-1042-2012; OI Rabin, Stephanie/0000-0002-8282-0867 NR 68 TC 20 Z9 20 U1 0 U2 14 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 MAY PY 2013 VL 27 IS 4 BP 389 EP 397 DI 10.1016/j.janxdis.2013.03.002 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 184IJ UT WOS:000321883000004 PM 23764124 ER PT J AU Weber, M Killgore, WDS Rosso, IM Britton, JC Schwab, ZJ Weiner, MR Simon, NM Pollack, MH Rauch, SL AF Weber, Mareen Killgore, William D. S. Rosso, Isabelle M. Britton, Jennifer C. Schwab, Zachary J. Weiner, Melissa R. Simon, Naomi M. Pollack, Mark H. Rauch, Scott L. TI Voxel-based morphometric gray matter correlates of posttraumatic stress disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Magnetic resonance imaging; Chronic post-traumatic stress disorder; Prefrontal cortex; Hippocampus; Amygdala ID SMALLER HIPPOCAMPAL VOLUME; STRUCTURAL BRAIN ABNORMALITIES; MEDIAL PREFRONTAL CORTEX; ADMINISTERED PTSD SCALE; ANTERIOR CINGULATE; BASOLATERAL AMYGDALA; ANXIETY DISORDER; HUMAN EMOTION; CHILD-ABUSE; GREY-MATTER AB Posttraumatic stress disorder (PTSD) is associated with functional abnormalities within a neurocircuitry that includes the hippocampus, amygdala, and medial prefrontal cortex. Evidence of structural abnormalities within these regions, and their association with PTSD severity and symptom burden is, however, sparse. The present study evaluated the relation between indices of gray matter volume and PTSD symptom severity using voxel-based morphometry. Fifteen individuals meeting DSM-IV criteria for PTSD completed the Clinician Administered PTSD Scale and underwent structural magnetic resonance imaging. Greater PTSD severity and avoidance/numbing were correlated with increased gray matter volume of the right amygdala-hippocampal complex. Greater hyper-arousal was associated with reduced gray matter volume in the left superior medial frontal gyrus. Findings are consistent with current neurocircuitry models of PTSD, which posit that the disorder is associated with structural and functional variance within this distributed network. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Weber, Mareen; Killgore, William D. S.; Rosso, Isabelle M.; Schwab, Zachary J.; Rauch, Scott L.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02478 USA. [Britton, Jennifer C.] NIMH, Bethesda, MD 20892 USA. [Weiner, Melissa R.] Yale Univ, New Haven, CT USA. [Simon, Naomi M.; Pollack, Mark H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Killgore, WDS (reprint author), Harvard Univ, Social Cognit & Affect Neurosci Lab, McLean Hosp, Sch Med, 115 Mill St, Belmont, MA 02478 USA. EM mweber@mclean.harvard.edu; killgore@mclean.harvard.edu RI Britton, Jennifer/J-4501-2013; OI Killgore, William/0000-0002-5328-0208 FU NIMH NIH HHS [R01 MH70730-01A2, R01 MH070730] NR 65 TC 14 Z9 16 U1 3 U2 9 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 MAY PY 2013 VL 27 IS 4 BP 413 EP 419 DI 10.1016/j.janxdis.2013.04.004 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 184IJ UT WOS:000321883000007 PM 23746489 ER PT J AU Saunders, DR Bex, PJ Woods, RL AF Saunders, Daniel R. Bex, Peter J. Woods, Russell L. TI Crowdsourcing a Normative Natural Language Dataset: A Comparison of Amazon Mechanical Turk and In-Lab Data Collection SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Internet; web; crowdsourcing; free recall ID PSYCHOLOGICAL-RESEARCH; IMPAIRMENT; INTERNET; ONLINE AB Background: Crowdsourcing has become a valuable method for collecting medical research data. This approach, recruiting through open calls on the Web, is particularly useful for assembling large normative datasets. However, it is not known how natural language datasets collected over the Web differ from those collected under controlled laboratory conditions. Objective: To compare the natural language responses obtained from a crowdsourced sample of participants with responses collected in a conventional laboratory setting from participants recruited according to specific age and gender criteria. Methods: We collected natural language descriptions of 200 half-minute movie clips, from Amazon Mechanical Turk workers (crowdsourced) and 60 participants recruited from the community (lab-sourced). Crowdsourced participants responded to as many clips as they wanted and typed their responses, whereas lab-sourced participants gave spoken responses to 40 clips, and their responses were transcribed. The content of the responses was evaluated using a take-one-out procedure, which compared responses to other responses to the same clip and to other clips, with a comparison of the average number of shared words. Results: In contrast to the 13 months of recruiting that was required to collect normative data from 60 lab-sourced participants (with specific demographic characteristics), only 34 days were needed to collect normative data from 99 crowdsourced participants (contributing a median of 22 responses). The majority of crowdsourced workers were female, and the median age was 35 years, lower than the lab-sourced median of 62 years but similar to the median age of the US population. The responses contributed by the crowdsourced participants were longer on average, that is, 33 words compared to 28 words (P<.001), and they used a less varied vocabulary. However, there was strong similarity in the words used to describe a particular clip between the two datasets, as a cross-dataset count of shared words showed (P<.001). Within both datasets, responses contained substantial relevant content, with more words in common with responses to the same clip than to other clips (P<.001). There was evidence that responses from female and older crowdsourced participants had more shared words (P=.004 and .01 respectively), whereas younger participants had higher numbers of shared words in the lab-sourced population (P=.01). Conclusions: Crowdsourcing is an effective approach to quickly and economically collect a large reliable dataset of normative natural language responses. C1 [Saunders, Daniel R.; Woods, Russell L.] Schepens Eye Res Inst, Boston, MA 02114 USA. [Bex, Peter J.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Saunders, DR (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM daniel_saunders@meei.harvard.edu RI Woods, Russell/O-2600-2015 OI Woods, Russell/0000-0002-7193-1211 FU National Eye Institute [R01EY019100] FX Supported by grant R01EY019100 from the National Eye Institute. All research received ethics approval from the Massachusetts Eye and Ear Infirmary Human Subjects Committee. We thank Rachel Berkowitz for preparing the video clips and Dylan Rose for collecting the lab-sourced data. NR 31 TC 10 Z9 10 U1 1 U2 16 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD MAY PY 2013 VL 15 IS 5 AR UNSP e100 DI 10.2196/jmir.2620 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 185IK UT WOS:000321960900005 PM 23689038 ER PT J AU Hung, JW Tan, TC AF Hung, Judy W. Tan, Timothy C. TI Echocardiography in Mitral Valve Disease Preface SO CARDIOLOGY CLINICS LA English DT Editorial Material C1 [Hung, Judy W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Tan, Timothy C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab,Div Cardiol, Boston, MA 02114 USA. RP Hung, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, YAW 5E,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org; TCTan@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2013 VL 31 IS 2 BP IX EP x DI 10.1016/j.ccl.2013.05.001 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 180LQ UT WOS:000321597100001 PM 23743080 ER PT J AU Dal-Bianco, JP Levine, RA AF Dal-Bianco, Jacob P. Levine, Robert A. TI Anatomy of the Mitral Valve Apparatus Role of 2D and 3D Echocardiography SO CARDIOLOGY CLINICS LA English DT Article DE Mitral valve apparatus; Mitral valve; Mitral annulus; Papillary muscles; Chordae tendineae; Mitral regurgitation; Echocardiography ID SYSTOLIC ANTERIOR MOTION; OUTFLOW TRACT OBSTRUCTION; PAPILLARY-MUSCLE DYSFUNCTION; LEFT-VENTRICULAR DYSFUNCTION; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; VALVULAR HEART-DISEASE; HYPERTROPHIC CARDIOMYOPATHY; CHORDAE TENDINEAE; FUNCTIONAL-ANATOMY; ANNULAR SHAPE AB The mitral valve apparatus is a complex 3-dimensional (3D) functional unit that is critical to unidirectional heart pump function. This review details the normal anatomy, histology, and function of the main mitral valve apparatus components: mitral annulus, mitral valve leaflets, chordae tendineae, and papillary muscles. Two-dimensional and 3D echocardiography is ideally suited to examine the mitral valve apparatus and has provided important insights into the mechanism of mitral valve disease. An overview of standardized echocardiography image acquisition and interpretation is provided. Understanding normal mitral valve apparatus function is essential to comprehend alterations in mitral valve disease and the rationale for repair strategies. C1 [Dal-Bianco, Jacob P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA 02114 USA. [Levine, Robert A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Levine, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. EM rlevine@partners.org FU Leducq Foundation, Paris, France [07CVD04]; National Institutes of Health [K24 HL67434, R01 HL72265, HL109506] FX This work is supported in part by grant 07CVD04 of the Leducq Foundation, Paris, France, for the Leducq Transatlantic MITRAL Network, and by National Institutes of Health grants K24 HL67434, R01 HL72265, and HL109506. NR 133 TC 12 Z9 12 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2013 VL 31 IS 2 BP 151 EP + DI 10.1016/j.ccl.2013.03.001 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 180LQ UT WOS:000321597100002 PM 23743068 ER PT J AU Solis, J Piro, V de Prada, JAV Loughlin, G AF Solis, Jorge Piro, Victoria Vazquez de Prada, Jose Antonio Loughlin, Gerard TI Echocardiographic Assessment of Mitral Regurgitation General Considerations SO CARDIOLOGY CLINICS LA English DT Article DE Mitral valve; Mitral regurgitation mitral; Echo Doppler; 3D echocardiography ID ISOVELOCITY SURFACE-AREA; COLOR DOPPLER-ECHOCARDIOGRAPHY; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; VENA CONTRACTA AREA; ORIFICE AREA; FLOW; SEVERITY; CONVERGENCE; RECOMMENDATIONS; QUANTIFICATION AB Echocardiography is undoubtedly one of the main tools used in assessment of mitral regurgitation (MR) because it allows characterization of valvular morphology, assessment of the severity of the regurgitation, and its secondary effects. In this article we present an overview of the echocardiographic assessment of MR. C1 [Solis, Jorge; Loughlin, Gerard] Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Madrid 28007, Spain. [Solis, Jorge] Complutense Med Sch, Madrid 28007, Spain. [Piro, Victoria] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Vazquez de Prada, Jose Antonio] Hosp Univ Marques de Valdecilla, Dept Cardiol, Santander 39008, Spain. [Vazquez de Prada, Jose Antonio] Marques de Valdecilla Res Inst IFIMAV, Santander 39008, Spain. RP Solis, J (reprint author), Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Doctor Esquerdo 46, Madrid 28007, Spain. EM jsolismartin@yahoo.es NR 29 TC 0 Z9 0 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2013 VL 31 IS 2 BP 165 EP + DI 10.1016/j.ccl.2013.04.001 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 180LQ UT WOS:000321597100003 PM 23743069 ER PT J AU Solis, J Piro, V Loughlin, G de Prada, JAV AF Solis, Jorge Piro, Victoria Loughlin, Gerard Vazquez de Prada, Jose Antonio TI How to Grade Mitral Regurgitation An Integrative Approach SO CARDIOLOGY CLINICS LA English DT Article DE Mitral valve regurgitation; Mitral regurgitation quantification; Doppler echocardiography; 3D echocardiography ID VENA CONTRACTA AREA; COLOR DOPPLER-ECHOCARDIOGRAPHY; ISOVELOCITY SURFACE-AREA; QUANTITATIVE ASSESSMENT; VALVULAR REGURGITATION; ORIFICE AREA; IN-VITRO; VALIDATION; SEVERITY; QUANTIFICATION AB Evaluation of mitral regurgitation (MR) severity remains complex and challenging. An integrative approach to grading MR is recommended. The use of multiple Doppler methods should be used to help discriminate between grades of severity. Importantly, MR severity should always be considered in the context of clinical data. The emerging inclusion of 3-dimensional echocardiography may provide complementary data for MR quantification and better anatomic and pathophysiological detail of the mitral valve. This article summarizes recommendations for MR assessment and highlights the importance of an integrated approach, using anatomic information as well as qualitative and quantitative Doppler measures. C1 [Solis, Jorge; Loughlin, Gerard] Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Madrid 28007, Spain. [Solis, Jorge] Complutense Med Sch, Madrid 28007, Spain. [Piro, Victoria] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Vazquez de Prada, Jose Antonio] Hosp Univ Marques de Valdecilla, Dept Cardiol, Santander 39008, Spain. [Vazquez de Prada, Jose Antonio] Marques de Valdecilla Res Inst IFIMAV, Santander 39008, Spain. RP Solis, J (reprint author), Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Doctor Esquerdo 46, Madrid 28007, Spain. EM jsolismartin@yahoo.es NR 17 TC 0 Z9 2 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 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2013 VL 31 IS 2 BP 169 EP + DI 10.1016/j.ccl.2013.04.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 180LQ UT WOS:000321597100004 PM 23743070 ER PT J AU Hung, JW AF Hung, Judy W. TI Ischemic (Functional) Mitral Regurgitation SO CARDIOLOGY CLINICS LA English DT Article DE Mitral regurgitation; Myocardial infarction; Papillary muscle; Echocardiography ID LEFT-VENTRICULAR DYSFUNCTION; LONG-TERM SURVIVAL; MYOCARDIAL-INFARCTION; DILATED CARDIOMYOPATHY; HEART-FAILURE; REPAIR; ANNULOPLASTY; REVASCULARIZATION; ECHOCARDIOGRAPHY; REPLACEMENT AB Mitral regurgitation (MR) is a frequent complication of myocardial infarction and coronary artery disease that is associated with adverse prognosis. The main mechanism of ischemic MR relates to distortion of the spatial relationships between the mitral valve and papillary muscles secondary to ventricular remodeling. The evidence that treatment of ischemic MR improves long-term survival still remains unclear, and further studies are needed to determine whether correcting ischemic MR will improve survival and/or symptoms. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Hung, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org NR 37 TC 3 Z9 4 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 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2013 VL 31 IS 2 BP 231 EP + DI 10.1016/j.ccl.2013.04.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 180LQ UT WOS:000321597100009 PM 23743075 ER PT J AU Andrawes, MN Feinman, JW AF Andrawes, Michael N. Feinman, Jared W. TI 3-Dimensional Echocardiography and Its Role in Preoperative Mitral Valve Evaluation SO CARDIOLOGY CLINICS LA English DT Article DE 3D echocardiography; Mitral valve; Mitral regurgitation; Mitral stenosis; Perioperative echocardiography ID ISOVELOCITY SURFACE-AREA; COLOR DOPPLER-ECHOCARDIOGRAPHY; TIME 3D ECHOCARDIOGRAPHY; VENA CONTRACTA AREA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; EAE/ASE RECOMMENDATIONS; FLOW CONVERGENCE; CHORDAE RUPTURE; REGURGITATION; STENOSIS AB Echocardiography plays a key role in the preoperative evaluation of mitral valve disease. 3-dimensional echocardiography is a relatively new development that is being used more and more frequently in the evaluation of these patients. This article reviews the available literature comparing the use of this new technology to classic techniques in the assessment of mitral valve pathology. The authors also review some of the novel insights learned from 3-dimensional echocardiography and how they may be used in surgical decision making and planning. C1 [Andrawes, Michael N.; Feinman, Jared W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Andrawes, MN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mandrawes@parters.org NR 71 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2013 VL 31 IS 2 BP 271 EP + DI 10.1016/j.ccl.2013.03.005 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 180LQ UT WOS:000321597100011 PM 23743077 ER PT J AU Okeke, EN Keenan, HA Weinger, K Abrahamson, MJ Hsu, WC AF Okeke, Eyiuche N. Keenan, Hillary A. Weinger, Katie Abrahamson, Martin J. Hsu, William C. TI DO ETHNIC DISPARITIES EXTEND TO SUBSPECIALTY DIABETES CARE? SO ENDOCRINE PRACTICE LA English DT Article ID COMMUNITY-HEALTH CENTERS; MEDICARE MANAGED CARE; RACIAL DISPARITIES; GLYCEMIC CONTROL; MEXICAN-AMERICANS; SELF-MANAGEMENT; ASSOCIATION; POPULATION; DISEASE; QUALITY AB Objective: It is unclear if disparities described in diabetes primary care extend to subspecialty diabetes care. This retrospective observational study examined disparities in diabetes outcomes in a subspecialty practice by assessing glycemic improvement in type 2 diabetes patients during the first year of enrollment. Methods: Electronic data were gathered on 3,945 subjects. The outcome was the proportion of white and minority (Asian, black, and Hispanic) subjects achieving a hemoglobin A1C (A1C) level of <= 7% after the first year of care. Logistic regression was used to identify factors associated with odds of achieving A1C <= 7%. Results: Minority patients had greater diabetes duration, more social disadvantages and missed appointments, and worse control at presentation than whites. The proportion of patients reaching target A1C rose from 37 to 52% among white patients and from 28 to 40% among minority patients. Significant differences between whites and minorities in the rates of patients reaching A1C <= 7% were found only among those with higher initial A1C (iA1C) levels (32% vs. 20.9%; P = .002 in third iA1C quartile, and 28.2% vs. 17.9%; P = .0003 in fourth iA1C quartile). The interaction between race/ethnicity and the top two iA1C quartiles remained significant in the fully adjusted model. Conclusion: Reaching an A1C level of = 7% depends strongly upon the glycemic level at initial presentation to specialty care, not race. However, minority patients with the highest baseline A1C levels do not improve to the same degree as white patients, and therefore should be targeted for more intensive diabetes care management. C1 [Okeke, Eyiuche N.; Keenan, Hillary A.; Weinger, Katie; Abrahamson, Martin J.; Hsu, William C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Adult Diabet, Boston, MA 02115 USA. RP Okeke, EN (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Eyiuche.okeke@joslin.harvard.edu FU Herbert Graetz Fund FX This study was funded by a clinical research award from the Herbert Graetz Fund. The results of this study were presented as a poster presentation at the American Diabetes Association's 70th Scientific Sessions, June 25 to 29, 2010, in Orlando, Florida. NR 28 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2013 VL 19 IS 3 BP 431 EP 438 DI 10.4158/EP12254.OR PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175XM UT WOS:000321267000012 PM 23337143 ER PT J AU Danescu, LG Roe, CA Johnson, LW AF Danescu, Liviu G. Roe, Cheryl A. Johnson, Lewis W. TI PHOTOPLETHYSMOGRAPHY: A SIMPLIFIED METHOD FOR THE OFFICE MEASUREMENT OF ANKLE BRACHIAL INDEX IN INDIVIDUALS WITH DIABETES SO ENDOCRINE PRACTICE LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; PREDICT CARDIOVASCULAR EVENTS; PRESSURE INDEX; ARM INDEX; MORTALITY; DOPPLER; ATHEROSCLEROSIS; SPECIFICITY; SENSITIVITY; HEALTH AB Objective: To compare the use of photoplethysmography (PPG) and Doppler techniques to measure the ankle brachial index (ABI) for the evaluation of peripheral arterial disease (PAD) in individuals with diabetes. Methods: Consecutive patients with diabetes (n = 103) referred for PAD evaluation had ABI measured by PPG and Doppler techniques in our diabetes center. Medical records were reviewed, and the results of the Doppler and PPG testing were compared. Results: Mean age was 60 years, 57% were female, and 79% had type 2 diabetes with an average duration of 17 years. PPG readings could not be obtained in 3 individuals. Of 200 limbs evaluated, 17 (8.5%) had noncompressible (NC) vessels by both techniques. In the remaining 183 limbs, the correlation coefficient comparing the two methods was 0.864. Mean ABI values were 1.11 +/- 0.14 for Doppler and 1.12 +/- 0.14 for PPG. The sensitivity of PPG compared to the Doppler technique for detection of an abnormal result was 88.2%, and the specificity was 99.4%. ABI results were classified as discordant if Doppler and PPG varied by more than 0.15, placing them in different diagnostic categories (abnormal low [<= 0.9], borderline [0.91-0.99], normal [1.0-1.4], or abnormal high [>1.4 or NC vessels]). There were only 4 (2%) discordant results. Conclusions: We found excellent concordance between PPG and the gold standard Doppler technique for ABI measurement in individuals with diabetes. PPG requires less training and takes less time to perform, making it highly suitable for use in an office setting. C1 [Danescu, Liviu G.; Johnson, Lewis W.] SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY 13210 USA. [Roe, Cheryl A.] SUNY Upstate Med Univ, Ctr Res & Evaluat, Syracuse, NY 13210 USA. RP Johnson, LW (reprint author), Joslin Diabet Ctr, 3229 East Genesee St, Syracuse, NY 13214 USA. EM johnsole@upstate.edu NR 28 TC 0 Z9 1 U1 0 U2 7 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2013 VL 19 IS 3 BP 439 EP 443 DI 10.4158/EP12172.OR PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175XM UT WOS:000321267000013 PM 23337138 ER PT J AU McManus, SS Levitsky, LL Misra, M AF McManus, Shilpa S. Levitsky, Lynne L. Misra, Madhusmita TI POLYCYSTIC OVARY SYNDROME: CLINICAL PRESENTATION IN NORMAL-WEIGHT COMPARED WITH OVERWEIGHT ADOLESCENTS SO ENDOCRINE PRACTICE LA English DT Article ID INSULIN-RESISTANCE; TOTAL TESTOSTERONE; SYNDROME PCOS; NORMAL WOMEN; ENDOCRINE; PREVALENCE; OBESITY; GIRLS; HYPERANDROGENEMIA; POPULATION AB Objective: To characterize polycystic ovary syndrome (PCOS) in adolescents and determine whether a distinct clinical presentation differentiates normal-weight (NW) from overweight (OW) PCOS. Methods: Retrospective chart review of patients seen in a tertiary care center from 1998-2008 who met the National Institutes of Health and/or Rotterdam criteria for PCOS (N = 211; NW = 43, OW = 168). We collected data on clinical features, biochemical markers, and ultrasound findings. Results: Patient age ranged from 11.3 to 20.3 years (mean, 15.7 +/- 1.7 years), and body mass index (BMI) from 17.4 to 64.2 kg/m(2) (mean, 31.7 +/- 7.7 kg/m(2)). Seventy-one percent of patients were Caucasian, 85% had irregular menses, 69% reported hirsutism, 18% had moderate to severe acne, 91% had a high free androgen index (FAI), and 8% had abnormal thyroid-stimulating hormone (TSH) levels. The BMI-standard deviation (SD) score was 0.1 +/- 0.5 in NW and 3.4 +/- 1.8 in OW girls. NW girls were older at diagnosis (16.4 +/- 1.4 years vs. 15.5 +/- 1.7 years; P = .0006) than OW girls, less likely to have a family history of obesity (22% vs. 65%; P<.0001), and less likely to have acanthosis nigricans (11% vs. 68%; P<.0001). NW girls were more likely to have polycystic ovaries on ultrasound (88% vs. 52%; P = .01) and a lower FAI (7.3 +/- 4.5 vs. 17.4 +/- 12.9; P<.0001). The BMI-SD score was negatively associated with sex hormone binding globulin (r(s) = -0.52; P<.0001) and positively associated with FAI (r(s) = 0.42; P<.0001). Conclusion: NW girls are more likely to be older at diagnosis and have polycystic ovaries. Other differences in presentation between groups were attributable to differences in weight. NW PCOS is likely part of a continuous spectrum of clinical PCOS rather than a distinct entity. C1 MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Pediat Endocrine Unit, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM mmisra@partners.org FU NICHD NIH HHS [K24 HD071843] NR 30 TC 1 Z9 1 U1 3 U2 4 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2013 VL 19 IS 3 BP 471 EP 478 DI 10.4158/EP12235.OR PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175XM UT WOS:000321267000018 PM 23816935 ER PT J AU Daniels, GH Sluss, P AF Daniels, Gilbert H. Sluss, Patrick TI PURE T3-THYROTOXICOSIS FROM A MEXICAN WEIGHT LOSS SUPPLEMENT SO ENDOCRINE PRACTICE LA English DT Letter C1 [Daniels, Gilbert H.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. [Daniels, Gilbert H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Daniels, Gilbert H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thyroid Unit ACC 730, Boston, MA 02114 USA. [Sluss, Patrick] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sluss, Patrick] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. EM gdaniels@partners.org; psluss@partners.org NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2013 VL 19 IS 3 BP 559 EP 560 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175XM UT WOS:000321267000028 PM 23425657 ER PT J AU Bhargava, A Kaur, M AF Bhargava, Amit Kaur, Manmeet TI What is the diagnosis? The patient was diagnosed with subacute thyroiditis and booked for a repeat ultrasound in 10 weeks, with a view to biopsy the solitary nodule in the right lobe of the thyroid SO ENDOCRINE PRACTICE LA English DT Editorial Material C1 [Bhargava, Amit] Univ Connecticut, Ctr Hlth, Div Endocrinol, Farmington, CT 06030 USA. [Kaur, Manmeet] Hosp Cent Connecticut, Joslin Diabet Ctr Affiliate, New Britain, CT USA. RP Bhargava, A (reprint author), Univ Connecticut, Ctr Hlth, Div Endocrinol, 263 Farmington Ave, Farmington, CT 06030 USA. EM abhargava99@yahoo.com NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2013 VL 19 IS 3 BP 562 EP 562 DI 10.4158/EP12406.VV PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175XM UT WOS:000321267000030 PM 23425654 ER PT J AU Oh, DJ Kang, MH Ooi, YH Choi, KR Sage, EH Rhee, DJ AF Oh, Dong-Jin Kang, Min Hyung Ooi, Yen Hoong Choi, Kyu Ryong Sage, E. Helene Rhee, Douglas J. TI Overexpression of SPARC in Human Trabecular Meshwork Increases Intraocular Pressure and Alters Extracellular Matrix SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE SPARC; adenovirus; matrix metalloproteinases; tissue inhibitors of matrix metalloproteinases; extracellular matrix; intraocular pressure; perfused anterior segment system ID OPEN-ANGLE GLAUCOMA; MATRICELLULAR PROTEIN SPARC; AQUEOUS-HUMOR OUTFLOW; OCULAR HYPERTENSION; HUMAN EYES; JUXTACANALICULAR TISSUE; GENE-EXPRESSION; ORGAN-CULTURE; ALPHA-3 CHAIN; CELLS AB PURPOSE. Intraocular pressure (IOP) regulation is largely unknown. SPARC-null mice demonstrate a lower IOP resulting from increased outflow. SPARC is a matricellular protein often associated with fibrosis. We hypothesized that SPARC overexpression would alter IOP by affecting extracellular matrix (ECM) synthesis and/or turnover in the trabecular meshwork (TM). METHODS. An adenoviral vector containing human SPARC was used to increase SPARC expression in human TM endothelial cells and perfused human anterior segments using multiplicities of infection (MOIs) 25 or 50. Total RNA from TM was used for quantitative PCR, while protein from cell lysates and conditioned media were used for immunoblot analyses and zymography. After completion of perfusion, the anterior segments were fixed, sectioned, and examined by light and confocal microscopy. RESULTS. SPARC overexpression increased the IOP of perfused human anterior segments. Fibronectin and collagens IV and I protein levels were elevated in both TM cell cultures and within the juxtacanalicular (JCT) region of perfused anterior segments. Collagen VI and laminin protein levels were increased in TM cell cultures but not in perfused anterior segments. The protein levels of pro-MMP-9 decreased while the kinetic inhibitors of metalloproteinases, TIMP-1 and PAI-1 protein levels, increased at MOI 25. At MOI 50, the protein levels of pro-MMP-1, -3, and -9 also decreased while PAI-1 and TIMP-1 and -3 increased. Only MMP-9 activity was decreased on zymography. mRNA levels of the collagens, fibronectin, and laminin were not affected by SPARC overexpression. CONCLUSIONS. SPARC overexpression increases IOP in perfused cadaveric human anterior segments resulting from a qualitative change the JCT ECM. Selective decrease of MMP-9 activity is likely part of the mechanism. SPARC is a regulatory node for IOP. C1 [Oh, Dong-Jin; Kang, Min Hyung; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Ooi, Yen Hoong] New York Downtown Hosp, Dept Pediat, New York, NY USA. [Choi, Kyu Ryong] Ewha Womans Univ, Sch Med, Dept Ophthalmol, Seoul, South Korea. [Choi, Kyu Ryong] Mokdong Hosp, Med Ctr, Seoul, South Korea. [Sage, E. Helene] Benaroya Res Inst Virginia Mason, Hope Heart Program, Seattle, WA USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM DougRhee@aol.com FU National Eye Institute [EY 019654-01, EY 014104]; Research to Prevent Blindness; Massachusetts Lions Eye Research Foundation; American Glaucoma Society FX Supported by National Eye Institute Grants EY 019654-01 and EY 014104 (MEEI Vision-Core Grant), Research to Prevent Blindness, Massachusetts Lions Eye Research Foundation, and American Glaucoma Society. NR 61 TC 22 Z9 22 U1 1 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2013 VL 54 IS 5 BP 3309 EP 3319 DI 10.1167/iovs.12-11362 PG 11 WC Ophthalmology SC Ophthalmology GA 173YC UT WOS:000321118300026 PM 23599341 ER PT J AU Cherfan, D Verter, EE Melki, S Gisel, TE Doyle, FJ Scarcelli, G Yun, SH Redmond, RW Kochevar, IE AF Cherfan, Daniel Verter, E. Eri Melki, Samir Gisel, Thomas E. Doyle, Francis J., Jr. Scarcelli, Giuliano Yun, Seok Hyun Redmond, Robert W. Kochevar, Irene E. TI Collagen Cross-Linking Using Rose Bengal and Green Light to Increase Corneal Stiffness SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE collagen cross-linking; corneal stiffness; ectatic disorder; keratoconus; photochemistry ID TREATMENT IN-VITRO; RIBOFLAVIN/UVA-TREATMENT; SINGLET OXYGEN; BRILLOUIN MICROSCOPY; OPTICAL MICROSCOPY; RABBIT CORNEA; ULTRAVIOLET-A; TISSUE; KERATOCONUS; MODEL AB PURPOSE. Photochemical cross-linking of corneal collagen is an evolving treatment for keratoconus and other ectatic disorders. We evaluated collagen cross-linking by rose bengal plus green light (RGX) in rabbit eyes and investigated factors important for clinical application. METHODS. Rose bengal (RB, 0.1%) was applied to deepithelialized corneas of enucleated rabbit eyes for 2 minutes. The diffusion distance of RB into the stroma was measured by fluorescence microscopy on frozen sections. RB-stained corneas were exposed to green (532-nm) light for 3.3 to 9.9 minutes (50-150 J/cm(2)). Changes in the absorption spectrum during the irradiation were recorded. Corneal stiffness was measured by uniaxial tensiometry. The spatial distribution of the stromal elastic modulus was assessed by Brillouin microscopy. Viable keratocytes were counted on H&E-stained sections 24 hours posttreatment. RESULTS. RB penetrated approximately 100 mu m into the corneal stroma and absorbed >90% of the incident green light. RGX (150 J/cm(2)) increased stromal stiffness by 3.8-fold. The elastic modulus increased in the anterior approximately 120 mu m of stroma. RB was partially photobleached during the 2-minute irradiation, but reapplication of RB blocked light transmission by >70%. Spectral measurements suggested that RGX initiated cross-linking by an oxygen-dependent mechanism. RGX did not decrease keratocyte viability. CONCLUSIONS. RGX significantly increases cornea stiffness in a rapid treatment (congruent to 12 minutes total time), does not cause toxicity to keratocytes and may be used to stiffen corneas thinner than 400 mu m. Thus, RGX may provide an attractive approach to inhibit progression of keratoconus and other ectatic disorders. C1 [Cherfan, Daniel] Boston Univ, Med Sci Program, Boston, MA 02215 USA. [Verter, E. Eri; Gisel, Thomas E.; Doyle, Francis J., Jr.; Scarcelli, Giuliano; Yun, Seok Hyun; Redmond, Robert W.; Kochevar, Irene E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Melki, Samir] Boston Eye Grp, Boston, MA USA. RP Kochevar, IE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu OI scarcelli, giuliano/0000-0002-1736-077X FU NEI NIH HHS [R21 EY023043] NR 43 TC 31 Z9 31 U1 0 U2 31 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2013 VL 54 IS 5 BP 3426 EP 3433 DI 10.1167/iovs.12-11509 PG 8 WC Ophthalmology SC Ophthalmology GA 173YC UT WOS:000321118300040 PM 23599326 ER PT J AU Rogers, DJ Ojha, S Maurer, R Hartnick, CJ AF Rogers, Derek J. Ojha, Shilpa Maurer, Rie Hartnick, Christopher J. TI Use of Adjuvant Intralesional Bevacizumab for Aggressive Respiratory Papillomatosis in Children SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; HUMAN-PAPILLOMAVIRUS; CLINICAL-COURSE; CIDOFOVIR; INJECTION; AVASTIN; LASER; RISK; TERM AB Importance: Juvenile recurrent respiratory papillomatosis (RRP) can be an aggressive disease process necessitating frequent trips to the operating room with multiple anesthetics for tumor debulking and airway preservation. Adjuvant therapy, such as that which is reported in this article, may help reduce the number of operative procedures affected children need each year and therefore may also affect their overall quality of life (QOL). Objective: To describe our experience with intralesional bevacizumab (Avastin) treatment for children with severe RRP by comparing median number of surgical procedures per year, median duration of time between procedures, Derkay staging, and voice QOL before and after bevacizumab treatment. Design: Prospective, consecutive case series. Setting: Tertiary care aerodigestive center. Participants: Ten children, aged 18 months to 18 years, with severe RRP necessitating more than 4 operative interventions in 1 year whose parents (or legal guardians) consented to intralesional bevacizumab treatment. Interventions: Intralesional bevacizumab administered at concentration of 2.5 mg/mL for 3 consecutive injections (with 532-nm pulsed KTP [potassium titanyl phosphate] laser when necessary) at intervals of 2 to 3 weeks. Main Outcome Measures: Time between surgical procedures, number of procedures per year, Derkay staging, total Pediatric Voice-Related Quality of Life (PVRQOL) score, Emotional PVRQOL score, and Physical PVRQOL score defined by comparing the year leading up to first of 3 bevacizumab injections with the year following the third bevacizumab injection. Results: The median duration of time between surgical procedures increased by 5.9 weeks after bevacizumab (P=.002). The median number of procedures per year decreased by 4 (P=.002). Derkay staging decreased by 6 (P=.03). The median total PVRQOL score increased by 25.5 (P=.02), the median Emotional PVRQOL score increased by 11.3 (P=.047), and the median Physical PVRQOL score increased by 14.3 (P=.047). Conclusions and Relevance: Intralesional bevacizumab treatment may increase duration of time between surgical procedures and decrease number of procedures per year, while improving voice QOL. C1 [Rogers, Derek J.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, Boston, MA 02114 USA. [Ojha, Shilpa] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Maurer, Rie] Brigham & Womens Hosp, Boston, MA 02115 USA. [Maurer, Rie] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 35 TC 6 Z9 6 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD MAY PY 2013 VL 139 IS 5 BP 496 EP 501 DI 10.1001/jamaoto.2013.1810 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 170MN UT WOS:000320855900009 PM 23681032 ER PT J AU Randolph, GW AF Randolph, Gregory W. TI Modern Thyroidectomy and the Tailored Surgical Approach SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material C1 [Randolph, Gregory W.] Harvard Univ, Div Gen Otolaryngol, Dept Otolaryngol, Med Sch,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Randolph, Gregory W.] Harvard Univ, Div Thyroid Parathyroid Surg, Dept Otolaryngol, Med Sch,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Harvard Univ, Div Gen Otolaryngol, Dept Otolaryngol, Med Sch,Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM gregory_randolph@meei.harvard.edu NR 1 TC 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD MAY PY 2013 VL 139 IS 5 BP 517 EP 518 DI 10.1001/jamaoto.2013.301 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 170MN UT WOS:000320855900013 PM 23681036 ER PT J AU Jimenez, RB Goma, C Nyamwanda, J Kooy, HM Halabi, T Napolitano, BN McBride, SM Taghian, AG Lu, HM MacDonald, SM AF Jimenez, Rachel B. Goma, Carles Nyamwanda, Jacqueline Kooy, Hanne M. Halabi, Tarek Napolitano, Brian N. McBride, Sean M. Taghian, Alphonse G. Lu, Hsiao-Ming MacDonald, Shannon M. TI Intensity modulated proton therapy for postmastectomy radiation of bilateral implant reconstructed breasts: A treatment planning study SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE IMPT; Postmastectomy; Implant; Pencil beam; Proton ID CANCER; RADIOTHERAPY; IMMEDIATE; COMPLICATIONS; MASTECTOMY; 3D-CRT; TRENDS AB Background and purpose: Delivery of post-mastectomy radiation (PMRT) in women with bilateral implants represents a technical challenge, particularly when attempting to cover regional lymph nodes. Intensity modulated proton therapy (IMPT) holds the potential to improve dose delivery and spare nontarget tissues. The purpose of this study was to compare IMPT to three-dimensional (3D) conformal radiation following bilateral mastectomy and reconstruction. Materials and methods: Ten IMPT, 3D conformal photon/electron (P/E), and 3D photon (wide tangent) plans were created for 5 patients with breast cancer, all of whom had bilateral breast implants. Using RTOG guidelines, a physician delineated contours for both target volumes and organs-at-risk. Plans were designed to achieve 95% coverage of all targets (chest wall, IMN, SCV, axilla) to a dose of 50.4 Gy or Gy (RBE) while maximally sparing organs-at-risk. Results: IMPT plans conferred similar target volume coverage with enhanced homogeneity. Both mean heart and lung doses using IMPT were significantly decreased compared to both PIE and wide tangent planning. Conclusions: IMPT provides improved homogeneity to the chest wall and regional lymphatics in the post-mastectomy setting with improved sparing of surrounding normal structures for woman with reconstructed breasts. IMPT may enable women with mastectomy to undergo radiation therapy without the need for delay in breast reconstruction. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 107 (2013) 213-217 C1 [Jimenez, Rachel B.; McBride, Sean M.] Harvard Radiat Oncol Program, Boston, MA USA. [Goma, Carles; Nyamwanda, Jacqueline; Kooy, Hanne M.; Halabi, Tarek; Napolitano, Brian N.; Taghian, Alphonse G.; Lu, Hsiao-Ming; MacDonald, Shannon M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jimenez, RB (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02215 USA. EM rbjimenez@partners.org OI Goma, Carles/0000-0003-0336-390X NR 12 TC 12 Z9 12 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAY PY 2013 VL 107 IS 2 BP 213 EP 217 DI 10.1016/j.radonc.2013.03.028 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 183HH UT WOS:000321804600016 PM 23647751 ER PT J AU Koh, HJ Toyoda, T Didesch, MM Lee, MY Sleeman, MW Kulkarni, RN Musi, N Hirshman, MF Goodyear, LJ AF Koh, Ho-Jin Toyoda, Taro Didesch, Michelle M. Lee, Min-Young Sleeman, Mark W. Kulkarni, Rohit N. Musi, Nicolas Hirshman, Michael F. Goodyear, Laurie J. TI Tribbles 3 mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle SO NATURE COMMUNICATIONS LA English DT Article ID UNFOLDED PROTEIN RESPONSE; STIMULATED GLUCOSE-TRANSPORT; PANCREATIC BETA-CELLS; ER STRESS; RECEPTOR SUBSTRATE-1; CHEMICAL CHAPERONES; DOWN-REGULATION; TRB3; EXPRESSION; KINASE AB Endoplasmic reticulum stress has been linked to insulin resistance in multiple tissues but the role of endoplasmic reticulum stress in skeletal muscle has not been explored. Endoplasmic reticulum stress has been reported to increase tribbles 3 expression in multiple cell lines. Here, we report that high-fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases tribbles 3 and endoplasmic reticulum stress markers in skeletal muscle. Overexpression of tribbles 3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signalling. Incubation of C2C12 cells and mouse skeletal muscle with endoplasmic reticulum stressors thapsigargin and tunicamycin increases tribbles 3 and impairs insulin signalling and glucose uptake, effects reversed in cells overexpressing RNAi for tribbles 3 and in muscles from tribbles 3 knockout mice. Furthermore, tribbles 3 knockout mice are protected from high-fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that tribbles 3 mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle. C1 [Koh, Ho-Jin; Toyoda, Taro; Didesch, Michelle M.; Lee, Min-Young; Kulkarni, Rohit N.; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Koh, Ho-Jin; Toyoda, Taro; Didesch, Michelle M.; Lee, Min-Young; Kulkarni, Rohit N.; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Sleeman, Mark W.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Musi, Nicolas] Audie L Murphy VA Med Ctr, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Koh, HJ (reprint author), Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM Ho-Jin.Koh@joslin.harvard.edu FU NIH [5P30DK036836, P30DK040561, R01AR045670, 5R01DK067536, P30DK036836]; ADA FX We thank M. Montminy (Salk Institute) for providing TRB3 antibody and adenoviruses for TRB3 and RNAi for TRB3, E. A. Caniano (Joslin Diabetes Center) for editorial contributions, and all other members of the Goodyear lab for critical discussions. This work was supported by NIH grants to H.-J.K. (5P30DK036836 and P30DK040561), to L.J.G. (R01AR045670), to R.N.K. (5R01DK067536) and to the Joslin DERC (P30DK036836). T. T. and M.-Y.L. were supported by ADA mentor-based fellowships (to L.J.G.). NR 53 TC 23 Z9 24 U1 3 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAY PY 2013 VL 4 AR 1871 DI 10.1038/ncomms2851 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 166WI UT WOS:000320589900067 PM 23695665 ER PT J AU Li, G Diogo, D Wu, D Spoonamore, J Dancik, V Franke, L Kurreeman, F Rossin, EJ Duclos, G Hartland, C Zhou, XZ Li, KJ Liu, J De Jager, PL Siminovitch, KA Zhernakova, A Raychaudhuri, S Bowes, J Eyre, S Padyukov, L Gregersen, PK Worthington, J Gupta, N Clemons, PA Stahl, E Tolliday, N Plenge, RM AF Li, Gang Diogo, Dorothee Wu, Di Spoonamore, Jim Dancik, Vlado Franke, Lude Kurreeman, Fina Rossin, Elizabeth J. Duclos, Grant Hartland, Cathy Zhou, Xuezhong Li, Kejie Liu, Jun De Jager, Philip L. Siminovitch, Katherine A. Zhernakova, Alexandra Raychaudhuri, Soumya Bowes, John Eyre, Steve Padyukov, Leonid Gregersen, Peter K. Worthington, Jane Gupta, Namrata Clemons, Paul A. Stahl, Eli Tolliday, Nicola Plenge, Robert M. CA RACI TI Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway SO PLOS GENETICS LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; COLLAGEN-INDUCED ARTHRITIS; ANTI-CD40 LIGAND ANTIBODY; DENSITY-LIPOPROTEIN CHOLESTEROL; MONOCLONAL-ANTIBODY; FETAL-HEMOGLOBIN; CONTROLLED-TRIAL; DOUBLE-BLIND; B-CELLS AB Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS) and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4 x 10(-9)). Second, we demonstrate that subjects homozygous for the RA risk allele have similar to 33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10(-9)), a finding corroborated by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2) and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65), a subunit of the NF-kappa B transcription factor. Finally, we develop a high-throughput NF-kappa B luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L) and conduct an HTS of 1,982 chemical compounds and FDA-approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-kappa B signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel therapies in complex traits such as RA. C1 [Li, Gang; Diogo, Dorothee; Wu, Di; Kurreeman, Fina; Duclos, Grant; Raychaudhuri, Soumya; Stahl, Eli; Plenge, Robert M.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA. [Li, Gang; Diogo, Dorothee; Wu, Di; Kurreeman, Fina; Duclos, Grant; Raychaudhuri, Soumya; Stahl, Eli; Plenge, Robert M.] Harvard Univ, Brigham & Womens Hosp, Div Genet, Sch Med, Boston, MA 02115 USA. [Diogo, Dorothee; Wu, Di; Kurreeman, Fina; Rossin, Elizabeth J.; De Jager, Philip L.; Raychaudhuri, Soumya; Gupta, Namrata; Stahl, Eli; Plenge, Robert M.] Broad Inst, Chem Biol Program, Med & Populat Genet Program, Cambridge, MA USA. [Wu, Di; Liu, Jun] Harvard Univ, Dept Stat, Boston, MA 02115 USA. [Spoonamore, Jim; Hartland, Cathy; Tolliday, Nicola] Broad Inst, Cambridge, MA USA. [Dancik, Vlado; Li, Kejie; Clemons, Paul A.] Broad Inst, Chem Biol Program, Cambridge, MA USA. [Franke, Lude; Zhernakova, Alexandra] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Franke, Lude; Zhernakova, Alexandra] Univ Groningen, Groningen, Netherlands. [Rossin, Elizabeth J.] Harvard Univ, Biol & Biomed Sci Program, Hlth Sci & Technol Program, Sch Med, Boston, MA 02115 USA. [Rossin, Elizabeth J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Zhou, Xuezhong] Beijing Jiaotong Univ, Sch Comp & Informat Technol, Beijing, Peoples R China. [De Jager, Philip L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci, Dept Neurol, Boston, MA 02115 USA. [Siminovitch, Katherine A.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Siminovitch, Katherine A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Siminovitch, Katherine A.] Toronto Gen Res Inst, Toronto, ON, Canada. [Zhernakova, Alexandra] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. [Bowes, John; Eyre, Steve; Worthington, Jane] Univ Manchester, Arthrit Res UK Epidemiol Unit, Musculoskeletal Res Grp, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Bowes, John; Eyre, Steve; Worthington, Jane] Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, NIHR Manchester Musculoskeletal Biomed Res Unit, Manchester, Lancs, England. [Padyukov, Leonid] Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden. [Padyukov, Leonid] Karolinska Univ Hosp Solna, Stockholm, Sweden. [Gregersen, Peter K.] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. RP Li, G (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA. EM rplenge@partners.org RI Siminovitch, Katherine/K-1475-2013; Worthington, Jane/M-9770-2014; Franke, Lude/P-7036-2016; OI Worthington, Jane/0000-0003-0544-042X; Franke, Lude/0000-0002-5159-8802; Zhernakova, Alexandra/0000-0002-4574-0841; Eyre, Stephen/0000-0002-1251-6974; Padyukov, Leonid/0000-0003-2950-5670 FU NIH [R01-AR057108, R01-AR056768, U01-GM092691, R01-AR059648, U54-LM008748]; Burroughs Wellcome Fund; [RC2-GM093080] FX RMP was supported by grants from the NIH (R01-AR057108, R01-AR056768, U01-GM092691, R01-AR059648) and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. The PhenoGenetic Project of Brigham and Women's Hospital was supported by RC2-GM093080. Immunochip genotype data from the i2b2 dataset was funded in part from NIH grant U54-LM008748. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 20 Z9 21 U1 0 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 MAY PY 2013 VL 9 IS 5 AR UNSP e1003487 DI 10.1371/journal.pgen.1003487 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 159FH UT WOS:000320030000011 PM 23696745 ER PT J AU Lin, FJ Shen, L Jang, CW Falnes, PO Zhang, Y AF Lin, Fu-Jung Shen, Li Jang, Chuan-Wei Falnes, Pal O. Zhang, Yi TI Ikbkap/Elp1 Deficiency Causes Male Infertility by Disrupting Meiotic Progression SO PLOS GENETICS LA English DT Article ID SEX-CHROMOSOME INACTIVATION; TRANSFER-RNA; FAMILIAL DYSAUTONOMIA; MOUSE SPERMATOCYTES; ELONGATOR COMPLEX; MOLECULAR ARCHITECTURE; PSEUDOAUTOSOMAL REGION; MAMMALIAN MEIOSIS; MICE; TRANSCRIPTION AB Mouse Ikbkap gene encodes IKAP-one of the core subunits of Elongator-and is thought to be involved in transcription. However, the biological function of IKAP, particularly within the context of an animal model, remains poorly characterized. We used a loss-of-function approach in mice to demonstrate that Ikbkap is essential for meiosis during spermatogenesis. Absence of Ikbkap results in defects in synapsis and meiotic recombination, both of which result in increased apoptosis and complete arrest of gametogenesis. In Ikbkap-mutant testes, a few meiotic genes are down-regulated, suggesting IKAP's role in transcriptional regulation. In addition, Ikbkap-mutant testes exhibit defects in wobble uridine tRNA modification, supporting a conserved tRNA modification function from yeast to mammals. Thus, our study not only reveals a novel function of IKAP in meiosis, but also suggests that IKAP contributes to this process partly by exerting its effect on transcription and tRNA modification. C1 [Lin, Fu-Jung; Shen, Li; Jang, Chuan-Wei; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Lin, Fu-Jung; Shen, Li; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Lin, Fu-Jung; Shen, Li; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Falnes, Pal O.] Univ Oslo, Dept Biosci, Oslo, Norway. [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Lin, FJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu OI LIN, FU-JUNG/0000-0003-4065-0983 FU NIH [U01DK089565]; UNC Lineberger Comprehensive Cancer Center [T32-CA009156-36] FX This work was supported by grant U01DK089565 from NIH. F-JL was a recipient of the Basic Research Fellowship from the UNC Lineberger Comprehensive Cancer Center (T32-CA009156-36). YZ is an Investigator of the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 21 Z9 21 U1 0 U2 7 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 MAY PY 2013 VL 9 IS 5 AR e1003516 DI 10.1371/journal.pgen.1003516 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 159FH UT WOS:000320030000034 PM 23717213 ER PT J AU Dunphy, CH Ferry, JA AF Dunphy, Cherie H. Ferry, Judith A. TI Introduction to the series of reactive and abnormal lymphoid proliferations mimicking malignant lymphoma SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Editorial Material C1 [Dunphy, Cherie H.] Lab Corp America, Ctr Mol Biol & Pathol, Res Triangle Pk, NC USA. [Dunphy, Cherie H.] Univ N Carolina, Chapel Hill, NC USA. [Ferry, Judith A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ferry, Judith A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dunphy, CH (reprint author), Lab Corp America, Ctr Mol Biol & Pathol, Res Triangle Pk, NC USA. EM cdunphy@unch.unc.edu NR 0 TC 0 Z9 0 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 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD MAY PY 2013 VL 30 IS 2 BP 101 EP 101 DI 10.1053/j.semdp.2012.08.004 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 172AR UT WOS:000320972800001 PM 23541275 ER PT J AU Sogg, S AF Sogg, Stephanie TI Comment on: Pilot evaluation of a substance abuse prevention group intervention for at-risk bariatric surgery candidates SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Weight Ctr, Boston, MA 02114 USA. RP Sogg, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Weight Ctr, Boston, MA 02114 USA. NR 9 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 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAY-JUN PY 2013 VL 9 IS 3 BP 468 EP 469 PG 2 WC Surgery SC Surgery GA 162VA UT WOS:000320292900029 PM 23477955 ER PT J AU Gonzalez, SD Xu, C Ramirez, ME Zavala, JM Armas, R Contreras, SA Contreras, J Dassori, A Leach, RJ Flores, D Jerez, A Raventos, H Ontiveros, A Nicolini, H Escamilla, M AF Gonzalez, S. D. Xu, C. Ramirez, M. E. Zavala, J. M. Armas, R. Contreras, S. A. Contreras, J. Dassori, A. Leach, R. J. Flores, D. Jerez, A. Raventos, H. Ontiveros, A. Nicolini, H. Escamilla, M. TI Family-based association of an ANK3 haplotype with bipolar disorder in Latino populations SO TRANSLATIONAL PSYCHIATRY LA English DT Letter ID GENOME-WIDE ASSOCIATION; VARIANTS; CACNA1C C1 [Gonzalez, S. D.; Xu, C.; Ramirez, M. E.; Zavala, J. M.; Escamilla, M.] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Psychiat, El Paso, TX USA. [Gonzalez, S. D.; Xu, C.; Ramirez, M. E.; Zavala, J. M.; Escamilla, M.] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Ctr Excellence Neurosci, El Paso, TX USA. [Armas, R.] Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA USA. [Contreras, S. A.; Dassori, A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Contreras, J.; Raventos, H.] Univ Costa Rica, Ctr Invest Biol Celular & Mol, San Jose, Costa Rica. [Contreras, J.; Raventos, H.] Univ Costa Rica, Escuela Biol, San Jose, Costa Rica. [Dassori, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Leach, R. J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Flores, D.] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Ctr Harbor, Torrance, CA 90509 USA. [Jerez, A.] Ctr Int Trastornos Afectivos & Conducta Adictiva, Guatemala City, Guatemala. [Ontiveros, A.] Inst Informac & Invest Salud Mental AC, Monterrey, Mexico. [Nicolini, H.] SC, Grp Estudios Med & Familiares Carracci, Mexico City, DF, Mexico. RP Gonzalez, SD (reprint author), Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Psychiat, El Paso, TX USA. EM m.escamilla@ttuhsc.edu OI Raventos, Henriette/0000-0001-9423-8308; Nicolini, Humberto/0000-0003-2494-0067 NR 10 TC 3 Z9 3 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD MAY PY 2013 VL 3 AR e265 DI 10.1038/tp.2013.40 PG 2 WC Psychiatry SC Psychiatry GA 174VJ UT WOS:000321184400011 PM 23715300 ER PT J AU Choy, G Novelline, RA AF Choy, Garry Novelline, Robert A. TI Past, Present, and Future of Emergency Radiology SO CANADIAN ASSOCIATION OF RADIOLOGISTS JOURNAL-JOURNAL DE L ASSOCIATION CANADIENNE DES RADIOLOGISTES LA English DT Editorial Material DE Emergency radiology; Acute radiology; Emergency department radiology ID MEDICAL-SERVICES USE C1 [Choy, Garry; Novelline, Robert A.] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol & Teleradiol, Boston, MA 02114 USA. RP Choy, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol & Teleradiol, 55 Fruit St,Founders House 210, Boston, MA 02114 USA. EM gchoy@partners.org NR 6 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0846-5371 J9 CAN ASSOC RADIOL J JI Can. Assoc. Radiol. J.-J. Assoc. Can. Radiol. PD MAY PY 2013 VL 64 IS 2 SI SI BP 85 EP 89 DI 10.1016/j.carj.2012.10.002 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 167LM UT WOS:000320633500003 PM 23506981 ER PT J AU Yonekawa, Y Miller, JB Turalba, AV Eliott, D AF Yonekawa, Yoshihiro Miller, John B. Turalba, Angela V. Eliott, Dean TI Traumatic Macular Hole From Intentional Basketball Overinflation SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; EYE INJURY REGISTRY; EPIDEMIOLOGY AB We report a new mechanism of ocular trauma. A basketball was intentionally overinflated until it exploded, resulting in corneal edema, hyphema, iritis, vitreous hemorrhage, commotio retinae, and a macular hole. The macular hole did not close after observation and subsequent pars plana vitrectomy with posterior hyaloid removal, but a repeat vitrectomy with internal limiting membrane peeling resulted in hole closure. Basketball overinflation to the point of explosion is a potentially blinding practice of which the public and manufacturers should be made aware. C1 [Yonekawa, Yoshihiro; Miller, John B.; Turalba, Angela V.; Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Eliott, D (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD MAY-JUN PY 2013 VL 44 IS 3 BP 303 EP 305 DI 10.3928/23258160-20130503-20 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 172QV UT WOS:000321020100019 PM 23676239 ER PT J AU Li, JF Chung, HS Niu, YJ Bush, J McCormack, M Sheen, J AF Li, Jian-Feng Chung, Hoo Sun Niu, Yajie Bush, Jenifer McCormack, Matthew Sheen, Jen TI Comprehensive Protein-Based Artificial MicroRNA Screens for Effective Gene Silencing in Plants SO PLANT CELL LA English DT Article ID ARABIDOPSIS MESOPHYLL PROTOPLASTS; TRANSLATIONAL REPRESSION; WEB SERVER; EXPRESSION; TARGETS; BIOSYNTHESIS; RECOGNITION; INHIBITION; THALIANA; MIRNAS AB Artificial microRNA (amiRNA) approaches offer a powerful strategy for targeted gene manipulation in any plant species. However, the current unpredictability of amiRNA efficacy has limited broad application of this promising technology. To address this, we developed epitope-tagged protein-based amiRNA (ETPamir) screens, in which target mRNAs encoding epitope-tagged proteins were constitutively or inducibly coexpressed in protoplasts with amiRNA candidates targeting single or multiple genes. This design allowed parallel quantification of target proteins and mRNAs to define amiRNA efficacy and mechanism of action, circumventing unpredictable amiRNA expression/processing and antibody unavailability. Systematic evaluation of 63 amiRNAs in 79 ETPamir screens for 16 target genes revealed a simple, effective solution for selecting optimal amiRNAs from hundreds of computational predictions, reaching similar to 100% gene silencing in plant cells and null phenotypes in transgenic plants. Optimal amiRNAs predominantly mediated highly specific translational repression at 59 coding regions with limited mRNA decay or cleavage. Our screens were easily applied to diverse plant species, including Arabidopsis thaliana, tobacco (Nicotiana benthamiana), tomato (Solanum lycopersicum), sunflower (Helianthus annuus), Catharanthus roseus, maize (Zea mays) and rice (Oryza sativa), and effectively validated predicted natural miRNA targets. These screens could improve plant research and crop engineering by making amiRNA a more predictable and manageable genetic and functional genomic technology. C1 [Li, Jian-Feng; Chung, Hoo Sun; Niu, Yajie; Bush, Jenifer; McCormack, Matthew; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Li, Jian-Feng; Chung, Hoo Sun; Niu, Yajie; Bush, Jenifer; McCormack, Matthew; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Li, JF (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM jli@molbio.mgh.harvard.edu FU National Science Foundation [IOS-0843244]; National Institutes of Health [R01 GM60493, R01 GM70567]; Massachusetts General Hospital Executive Committee on Research Postdoctoral Fellowship for Medical Discovery FX We thank Frederick Ausubel for critical reading of the article, Detlef Weigel and Rebecca Schwab for the WMD platform, Jin-Gui Chen for the T-DNA insertion rack1 null mutants, Carolyn Lee-Parsons for C. roseus plants, Mark Curtis and Ueli Grossniklaus for the estradiol-inducible binary vector, and the ABRC for the mekk1 and pds3 mutants. We also thank Guillaume Tena for the original miR319a plasmid, Li Li for maize protoplast transfection, and Qi Hall for assistance in floral dip. J.-F.L. is supported by the Massachusetts General Hospital Executive Committee on Research Postdoctoral Fellowship for Medical Discovery. The research is supported by National Science Foundation Grant IOS-0843244 and the National Institutes of Health Grants R01 GM60493 and R01 GM70567 to J.S. NR 49 TC 40 Z9 44 U1 3 U2 52 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD MAY PY 2013 VL 25 IS 5 BP 1507 EP 1522 DI 10.1105/tpc.113.112235 PG 16 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 172WH UT WOS:000321035800007 PM 23645631 ER PT J AU Abeijon, C Campos-Neto, A AF Abeijon, Claudia Campos-Neto, Antonio TI Potential Non-invasive Urine-Based Antigen (Protein) Detection Assay to Diagnose Active Visceral Leishmaniasis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Editorial Material C1 [Abeijon, Claudia] DetectoGen Inc, Grafton, MA USA. [Campos-Neto, Antonio] Forsyth Inst, Cambridge, MA USA. RP Abeijon, C (reprint author), DetectoGen Inc, Grafton, MA USA. EM acampos@forsyth.org FU NIAID NIH HHS [R43AI084259-01] NR 10 TC 8 Z9 8 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2013 VL 7 IS 5 AR e2161 DI 10.1371/journal.pntd.0002161 PG 4 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 158SW UT WOS:000319994400003 PM 23738023 ER PT J AU Jung, M Chung, D AF Jung, Minsoo Chung, Dongjun TI Evidence of Social Contextual Effects on Adolescent Smoking in South Korea SO ASIA-PACIFIC JOURNAL OF PUBLIC HEALTH LA English DT Article DE smoking; adolescent; social environment; school; multilevel analysis; South Korea ID CIGARETTE-SMOKING; SCHOOL DIFFERENCES; RISK-FACTORS; PREDICTORS; MULTILEVEL; PATTERNS; STUDENTS; BELIEFS; CHINA; RATES AB This study explores the effect of psychological and social factors on smoking behavior among male and female adolescents in South Korea. A cross-sectional analysis was carried out via multilevel logistic regression with pupils at the first level and schools at the second level. The data were collected in 2003 using a nationally representative sample of 3449 students from 100 South Korean middle schools. For both genders, adolescents were more likely to smoke if and when they had lower academic grades, had a higher disposable monetary allowance from their parents, had more friends who smoked, and if the smoking rate at their school was higher. Psychological factors, however, were not factors that significantly influenced smoking. Consequently, the principal contextual factors related to adolescent smoking are the smoking rates in schools and among peer groups. Thus, an antismoking campaign incorporating social environmental factors may be useful in reducing the rates of adolescent smoking. C1 [Jung, Minsoo] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Jung, Minsoo] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Chung, Dongjun] Univ Wisconsin, Madison, WI 53706 USA. RP Chung, D (reprint author), Univ Wisconsin, Dept Stat, Med Sci Ctr, 1300 Univ Ave, Madison, WI 53706 USA. EM dongjun.chung@gmail.com OI Jung, Minsoo/0000-0003-3317-6507; Chung, Dongjun/0000-0002-8072-5671 NR 35 TC 6 Z9 6 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1010-5395 J9 ASIA-PAC J PUBLIC HE JI Asia-Pac. J. Public Health PD MAY PY 2013 VL 25 IS 3 BP 260 EP 270 DI 10.1177/1010539512461667 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 161AH UT WOS:000320161700006 PM 23070756 ER PT J AU Cohen, LS Viguera, AC Masnik, S Kwiatkowski, M Murphy, S Lemon, E Hernandez-Diaz, S AF Cohen, L. S. Viguera, A. C. Masnik, S. Kwiatkowski, M. Murphy, S. Lemon, E. Hernandez-Diaz, S. TI The National Pregnancy Registry for Atypical Antipsychotics: Effects of Fetal Exposure on Risk for Congenital Malformations and Maternal/Newborn Outcomes SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Cohen, L. S.; Viguera, A. C.; Masnik, S.; Kwiatkowski, M.; Murphy, S.; Lemon, E.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Viguera, A. C.] Cleveland Clin, Neurol Inst, Cleveland, OH 44106 USA. [Hernandez-Diaz, S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 MAY PY 2013 VL 97 IS 5 SI SI BP 296 EP 296 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100051 ER PT J AU Holmes, LB AF Holmes, L. B. TI Pregnancy Registry Designs for Multiple Drugs for Similar Medications: North American AED (Antiepileptic Drug) Pregnancy Registry SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Holmes, L. B.] MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 296 EP 296 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100050 ER PT J AU Clark, JC Manak, J Darbro, B Kanan, P Holmes, LB Brophy, PD AF Clark, J. C. Manak, J. Darbro, B. Kanan, P. Holmes, L. B. Brophy, P. D. TI The Familial Nature of Renal Agenesis SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Clark, J. C.; Manak, J.; Darbro, B.; Brophy, P. D.] Univ Iowa, Iowa City, IA USA. [Kanan, P.; Holmes, L. B.] MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 309 EP 309 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100074 ER PT J AU Nasri, HN Macklin, EM Holmes, LH AF Nasri, H. N. Macklin, E. M. Holmes, L. H. TI Vascular Disruption Limb Defects: Correlation with Advanced Maternal Age? SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Nasri, H. N.] Simmons Coll, Boston, MA 02115 USA. [Macklin, E. M.] MassGen Hosp Children, Dept Biostat, Boston, MA USA. [Holmes, L. H.] MassGen Hosp Children, Massachusetts Gen Hosp & Med Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 319 EP 319 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100094 ER PT J AU Le, KY Uslan, DZ Baddour, LM Sohail, MR Prutkin, JM Peacock, JE Danik, SB Vikram, HR Miro, JM Blank, E Naber, CK Carrillo, RG Tseng, CH Greenspon, AJ AF Le, K. Y. Uslan, D. Z. Baddour, L. M. Sohail, M. R. Prutkin, J. M. Peacock, J. E., Jr. Danik, S. B. Vikram, H. R. Miro, J. M. Blank, E. Naber, C. K. Carrillo, R. G. Tseng, C. -H. Greenspon, A. J. CA MEDIC TI PROMPT SYSTEM EXTRACTION DECREASES MORTALITY IN PATIENTS WITH CARDIOVASCULAR IMPLANTABLE ELECTROPHYSIOLOGIC DEVICE INFECTION SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Meeting Abstract CT 12th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections CY MAY 19-21, 2013 CL Dubrovnik, CROATIA SP MSD Pharma C1 [Le, K. Y.] Mayo Clin, Dept Med, Div Hosp Internal Med, Rochester, MN USA. [Uslan, D. Z.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA 90095 USA. [Baddour, L. M.; Sohail, M. R.] Mayo Clin, Dept Med, Div Infect Dis, Rochester, MN USA. [Prutkin, J. M.] Univ Washington, Med Ctr, Div Cardiol, Seattle, WA 98195 USA. [Peacock, J. E., Jr.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Div Infect Dis, Winston Salem, NC 27103 USA. [Danik, S. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Vikram, H. R.] Mayo Clin, Dept Med, Div Infect Dis, Scottsdale, AZ USA. [Miro, J. M.] Univ Barcelona, Hosp Clin IDIBAPS, Infect Dis Serv, Barcelona, Spain. [Naber, C. K.] Elisabeth Hosp, Klin Kardiol & Angiol, Essen, Germany. [Carrillo, R. G.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Tseng, C. -H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. [Greenspon, A. J.] Thomas Jefferson Univ Hosp, Div Cardiol, Dept Med, Philadelphia, PA 19107 USA. EM katherine.y.le@gmail.com RI Sohail, Muhammad/K-1803-2016 OI Sohail, Muhammad/0000-0001-6355-0526 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD MAY PY 2013 VL 41 SU 1 BP S33 EP S33 PG 1 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 171KR UT WOS:000320927100111 ER PT J AU Antiel, RM Reed, DA Van Arendonk, KJ Wightman, SC Hall, DE Porterfield, JR Horvath, KD Terhune, KP Tarpley, JL Farley, DR AF Antiel, Ryan M. Reed, Darcy A. Van Arendonk, Kyle J. Wightman, Sean C. Hall, Daniel E. Porterfield, John R. Horvath, Karen D. Terhune, Kyla P. Tarpley, John L. Farley, David R. TI Effects of Duty Hour Restrictions on Core Competencies, Education, Quality of Life, and Burnout Among General Surgery Interns SO JAMA SURGERY LA English DT Article ID HOURS ENHANCING SLEEP; 80-HOUR WORK WEEK; AMERICAN SURGEONS; PROGRAM DIRECTORS; OPERATIVE EXPERIENCE; RESIDENTS; MEDICINE; SUPERVISION; ATTRITION; HEALTH AB Objective: To measure the implications of the new Accreditation Council for Graduate Medical Education duty hour regulations for education, well-being, and burnout. Design: Longitudinal study. Setting: Eleven university-based general surgery residency programs from July 2011 to May 2012. Participants: Two hundred thirteen surgical interns. Main Outcome Measures: Perceptions of the impact of the new duty hours on various aspects of surgical training, including the 6 Accreditation Council for Graduate Medical Education core competencies, were measured on 3-point scales. Quality of life, burnout, balance between personal and professional life, and career satisfaction were measured using validated instruments. Results: Half of all interns felt that the duty hour changes have decreased the coordination of patient care (53%), their ability to achieve continuity with hospitalized patients (70%), and their time spent in the operating room (57%). Less than half (44%) of interns believed that the new standards have decreased resident fatigue. In longitudinal analysis, residents' beliefs had significantly changed in 2 categories: less likely to believe that practice-based learning and improvement had improved and more likely to report no change to resident fatigue (P < .01, chi(2) tests). The majority (82%) of residents reported a neutral or good overall quality of life. Compared with the normal US population, 50 interns (32%) were 0.5 SD less than the mean on the 8-item Short Form Health Survey mental quality of life score. Approximately one-third of interns demonstrated weekly symptoms of emotional exhaustion (28%) or depersonalization (28%) or reported that their personal-professional balance was either "very poor" or "not great" (32%). Although many interns (67%) reported that they daily or weekly reflect on their satisfaction from being a surgeon, 1 in 7 considered giving up their career as a surgeon on at least a weekly basis. Conclusions: The first cohort of surgical interns to train under the new regulations report decreased continuity with patients, coordination of patient care, and time spent in the operating room. Furthermore, suboptimal quality of life, burnout, and thoughts of giving up surgery were common, even under the new paradigm of reduced work hours. C1 [Reed, Darcy A.] Mayo Clin, Div Primary Care Internal Med, Rochester, MN 55905 USA. [Antiel, Ryan M.; Farley, David R.] Mayo Clin, Dept Surg, Rochester, MN 55905 USA. [Van Arendonk, Kyle J.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Wightman, Sean C.] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Porterfield, John R.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL USA. [Horvath, Karen D.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Terhune, Kyla P.; Tarpley, John L.] Vanderbilt Univ, Dept Surg, Nashville, TN 37240 USA. RP Farley, DR (reprint author), Mayo Clin, Dept Surg, 200 1st St SW, Rochester, MN 55905 USA. EM farley.david@mayo.edu OI Hall, Daniel/0000-0001-6382-0522 NR 42 TC 50 Z9 50 U1 0 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 J9 JAMA SURG JI JAMA Surg. PD MAY PY 2013 VL 148 IS 5 BP 448 EP 455 DI 10.1001/jamasurg.2013.1368 PG 8 WC Surgery SC Surgery GA 163IU UT WOS:000320330300013 PM 23325404 ER PT J AU Lenehan, G AF Lenehan, Gail TI Weigh Children in Kilograms Only! Response SO JOURNAL OF EMERGENCY NURSING LA English DT Letter C1 Massachusetts Gen Hosp, Emergency Nurses Assoc, CNS, Emergency Dept, Boston, MA 02114 USA. RP Lenehan, G (reprint author), Massachusetts Gen Hosp, Emergency Nurses Assoc, CNS, Emergency Dept, Boston, MA 02114 USA. EM gail.lenehan@gmail.com 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 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAY PY 2013 VL 39 IS 3 BP E25 EP E25 DI 10.1016/j.jen.2012.07.004 PG 1 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 162ZX UT WOS:000320306200002 PM 23647995 ER PT J AU Bennett, A Bukowski, RM Flaherty, K Muir, JC Turner, CD AF Bennett, Amanda Bukowski, Ronald M. Flaherty, Keith Muir, J. Cameron Turner, Craig D. TI The Cost of Hope: A Candid Roundtable Discussion SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material AB For Amanda Bennett and her husband Terence Foley, a 7-year battle with kidney cancer resulted in a price tag of more than $600,000, most of it spent in the final 2 years of his life. Ms. Bennett's memoir, The Cost of Hope, chronicles the couple's emotional struggle and the financial irrationality she uncovered when navigating the cancer continuum. She shared her experience in her keynote address at the NCCN 18th Annual Conference, which was followed by a roundtable discussion in which panelists discussed the difficulties inherent in dealing with cancer "uncertainties," the balancing act that seeks to maintain hope in the context of a poor prognosis, and the problem of a health care system that spends too much on some aspects of care while ignoring others. C1 [Bukowski, Ronald M.] Bukowski Consulting LLC, Pepper Pike, OH USA. [Bukowski, Ronald M.] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH USA. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Muir, J. Cameron] Capital Caring, Qual & Access, Falls Church, VA USA. [Muir, J. Cameron] Amer Acad Hospice & Palliat Med, Glenview, IL USA. [Turner, Craig D.] Urol Consultants PC, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2013 VL 11 IS 5.5 SI SI BP 633 EP 635 PG 3 WC Oncology SC Oncology GA 159TX UT WOS:000320071300002 PM 23704231 ER PT J AU Ligibel, JA Denlinger, CS AF Ligibel, Jennifer A. Denlinger, Crystal S. TI New NCCN Guidelines (R) for Survivorship Care SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PHYSICAL-ACTIVITY; CANCER SURVIVORS; DIAGNOSIS AB Survivorship is a stage in the cancer journey like diagnosis and treatment, but it tends to be somewhat neglected in the quiet afterthoughts of treatment completion. Although cancer recurrence, second cancers, and late side effects of treatment are major concerns for survivors, survivors also may experience a variety of long-term physical and psychological sequelae of a cancer diagnosis and treatment. Oncology professionals may be ill-prepared to tackle these topics, and they have few guidelines for meeting these patient needs. In this article, Dr. Jennifer A. Ligibel and Dr. Crystal S. Den linger present highlights from the inaugural NCCN Clinical Practice Guidelines in Oncology on survivorship care, focusing on the subtopics of exercise, cognitive function, immunization, and sexual function. They also discuss implementing new recommendations on survivorship assessment in the clinic. C1 [Ligibel, Jennifer A.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Denlinger, Crystal S.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. RP Ligibel, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jligibel@partners.org; crystal.denlinger@fccc.edu FU AstraZeneca Pharmaceuticals LP; MedImmune Inc.; Merrimack Pharmaceuticals FX Dr. Ligibel has disclosed that she has no financial interests, arrangements, or commercial interest conflicts with the manufacturers of any products discussed in this article or their competitors. Dr. Den linger has disclosed that she receives research support from AstraZeneca Pharmaceuticals LP; MedImmune Inc.; and Merrimack Pharmaceuticals. NR 11 TC 18 Z9 19 U1 0 U2 5 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 MAY PY 2013 VL 11 IS 5.5 SI SI BP 640 EP 644 PG 5 WC Oncology SC Oncology GA 159TX UT WOS:000320071300004 PM 23704233 ER PT J AU Kantoff, PW Mohler, JL AF Kantoff, Philip W. Mohler, James L. TI New Developments in the Management of Prostate Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RADICAL PROSTATECTOMY; INCREASED SURVIVAL; CHEMOTHERAPY; ABIRATERONE AB Rapid progress was recently made in the treatment of prostate cancer, especially metastatic castration-resistant prostate cancer. At the NCCN 18th Annual Conference, Dr. Philip W. Kantoff reviewed the data supporting the use of abiraterone acetate, enzalutamide, cabazitaxel, sipuleucel-T, and radium-223 (pending approval), and offered recommendations for their sequential use in different settings. Dr. James L. Mohler described factors that dictate who should receive treatment, when they should receive it, and how to treat in the setting of prostate-specific antigen elevation. He explained how better treatment decisions will result from individualized estimation of threat-to-life posed by prostate cancer, chance of cure by treatment, and treatment risks. C1 [Kantoff, Philip W.] Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kantoff, Philip W.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mohler, James L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Suite D-1230, Boston, MA 02115 USA. EM philip_kantoff@dfci.harvard.edu; james.mohler@roswellpark.org FU Bavarian Nordic Immunotherapy (BN-IT); Androbiosys, Inc. FX Dr. Kantoff has disclosed he receives research support from Bavarian Nordic Immunotherapy (BN-IT); and and serves as a consultant for Bayer Health Care; Dendreon Corporation; Janssen Pharmaceutica Products, LP; and Bavarian Nordic Immunotherapy (BN-IT). Dr. Mohler has disclosed he has a financial relationship with Androbiosys, Inc. NR 11 TC 5 Z9 5 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 MAY PY 2013 VL 11 IS 5.5 SI SI BP 653 EP 657 PG 5 WC Oncology SC Oncology GA 159TX UT WOS:000320071300007 PM 23704236 ER PT J AU Abramson, JS Zelenetz, AD AF Abramson, Jeremy S. Zelenetz, Andrew D. TI Recent Advances in the Treatment of Non-Hodgkin's Lymphomas SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; RITUXIMAB; PHASE-3; BURDEN; TRIAL AB Non-Hodgkin's lymphomas (NHL) represent a diverse set of diseases, with different treatment pathways based on the stage and type of hematologic cancer. In their presentation at the NCCN 18th Annual Conference, Dr. Jeremy Abramson and Dr. Andrew D. Zelenetz discuss 3 specific B-cell NHLs: follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia. They provided an overview of the treatment strategies for patients with these hematologic malignancies, and offered highlights from recent clinical trials supporting these recommendations. C1 [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Lymphoma Program, Boston, MA 02114 USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey Ctr Outpatient Care, Mailstop Yawkey 9A,32 Fruit St, Boston, MA 02114 USA. EM jabramson@partners.org; a-zelenetz@ski.mskcc.org FU Abbott Laboratories; Celgene Corporation; Cephalon, Inc.; Genentech, Inc.; GlaxoSmithKline; Millennium Pharmaceuticals, Inc.; Onyx Pharmaceuticals, Inc.; Allos Pharm; Calistoga, Pharmacyclics; Plexxikon; Roche; Seattle Genetics FX Dr. Abramson has revealed that he has served as a consultant for Seattle Genetics. Dr. Zelenetz has revealed that he receives clinical research support from Abbott Laboratories; Celgene Corporation; Cephalon, Inc.; Genentech, Inc.; GlaxoSmithKline; Millennium Pharmaceuticals, Inc.; Onyx Pharmaceuticals, Inc.; Allos Pharm; Calistoga, Pharmacyclics; Plexxikon; Roche; and Seattle Genetics and serves on an advisory board or as a consultant for Abbott Laboratories; Celgene Corporation; Cell Therapeutics, Inc.; Cephalon, Inc.; Genentech, Inc.; GlaxoSmithKline; Altos; Cancer Genetics; Gilead; Seattle Genetics; Roche Laboratories, Inc.; and sanofi-aventis U.S. NR 12 TC 5 Z9 5 U1 0 U2 3 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 MAY PY 2013 VL 11 IS 5.5 SI SI BP 671 EP 675 PG 5 WC Oncology SC Oncology GA 159TX UT WOS:000320071300011 PM 23704240 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI Therapeutic Advances in Relapsed or Refractory Multiple Myeloma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID BORTEZOMIB; INHIBITOR AB The past decade has been a time of rapid progress in multiple myeloma, but the future therapeutic landscape may be even more promising, as new agents are better tolerated and novel pathways are exploited. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) now include the proteasome inhibitor carfilzomib and immunomodulatory drug pomalidomide, which are more potent than previous generations of these drugs have been. These agents are extending progression free and overall survival of patients with relapsed refractory myeloma, as is maintenance therapy with lenalidomide after initial therapy of patients with newly diagnosed disease At the NCCN 18th Annual Conference, Dr. Kenneth C. Anderson from Dana-Farber Cancer Institute reviewed the data leading to the approval of these exciting agents, discussed the efficacy of current regimens, and described the future landscape and the exciting potential of new agents to further improve and extend the lives of patients with myeloma. C1 [Anderson, Kenneth C.] Harvard Univ, Sch Med, Kraft Family Prof Med, Boston, MA USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02215 USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. [Anderson, Kenneth C.] Brigham & Womens Canc Ctr, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu NR 15 TC 11 Z9 12 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 MAY PY 2013 VL 11 IS 5.5 SI SI BP 676 EP 679 PG 4 WC Oncology SC Oncology GA 159TX UT WOS:000320071300012 PM 23704241 ER PT J AU Choueiri, TK AF Choueiri, Toni K. TI Clinical Treatment Decisions for Advanced Renal Cell Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PROGNOSTIC MODEL; PHASE-3 TRIAL; CARCINOMA; SURVIVAL; AXITINIB AB Seven targeted agents have improved the prognosis of advanced renal cell carcinoma (RCC), but none are effective in the post-nephrectomy adjuvant setting. Among the available first-line options for advanced RCC, sunitinib remains the most commonly used first-line therapy, but several studies suggest pazopanib may be better tolerated. Increasingly, choice of therapy may be driven by toxicity profiles. Cytoreductive nephrectomy remains important, even in the era of targeted therapies in selected patients. C1 [Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Dana Farber Brigham & Womens Canc Ctr, Lank Ctr Genitourinary Oncol, 450 Brookline Ave,Dana 1230, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu NR 14 TC 8 Z9 8 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 MAY PY 2013 VL 11 IS 5.5 SI SI BP 694 EP 697 PG 4 WC Oncology SC Oncology GA 159TX UT WOS:000320071300017 PM 23704246 ER PT J AU Haddad, RI AF Haddad, Robert I. TI New Developments in Thyroid Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article AB Thyroid cancer is common but rarely deadly. Unfortunately, when the disease becomes refractory to radioactive iodine (RAI), few effective treatment options remain. This situation is changing, however, with the availability of multitargeted tyrosine kinase inhibitors. Cabozantanib and vandetanib, both recently FDA-approved for advanced or metastatic disease, have more than doubled progression-free survival in medullary thyroid cancer. New agents in the pipeline may yield even better outcomes, as discussed by Dr. Robert I. Haddad at the NCCN 18th Annual Conference. C1 [Haddad, Robert I.] Harvard Univ, Sch Med, Boston, MA USA. [Haddad, Robert I.] Dana Farber Canc Inst, Head & Neck Oncol Program, Dis Ctr, Boston, MA 02115 USA. [Haddad, Robert I.] Brigham & Womens Canc Ctr, Boston, MA USA. RP Haddad, RI (reprint author), Dana Farber Brigham & Womens Canc Ctr, 44 Binney St,SW430G, Boston, MA 02115 USA. EM robert_haddad@dfci.harvard.edu NR 8 TC 5 Z9 5 U1 0 U2 0 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 MAY PY 2013 VL 11 IS 5.5 SI SI BP 705 EP 707 PG 3 WC Oncology SC Oncology GA 159TX UT WOS:000320071300020 PM 23704249 ER PT J AU de Souza, DAT Parente, DB de Araujo, ALE Mortele, KJ AF de Souza, Daniel Andrade Tinoco Parente, Daniella Braz Eiras de Araujo, Antonio Luis Mortele, Koenraad J. TI Modern Imaging Evaluation of the Liver Emerging MR Imaging Techniques and Indications SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Liver; Hepatic MRI; Diffusion-weighted imaging; Liver fibrosis; Hepatic steatosis; MR elastography; MR spectroscopy; Hepatocellular contrast ID GD-EOB-DTPA; MAGNETIC-RESONANCE ELASTOGRAPHY; FOCAL NODULAR HYPERPLASIA; DIFFUSION-WEIGHTED MRI; CONTRAST-ENHANCED MRI; HYPERVASCULAR HEPATOCELLULAR CARCINOMAS; HEPATIC FAT FRACTION; GADOXETATE DISODIUM; SPIN-ECHO; TRANSIENT ELASTOGRAPHY AB Modern MR imaging evaluation of the liver allows for a comprehensive morphologic and functional assessment of the liver parenchyma, hepatic vessels, and biliary tree, thus aiding in the diagnosis of both focal and diffuse liver diseases. C1 [de Souza, Daniel Andrade Tinoco] Harvard Univ, Sch Med, Dana Farber Canc Inst, PET CT & Nucl Med, Boston, MA 02215 USA. [Parente, Daniella Braz] D Or Inst Res & Educ, Labs DOr Network, Fleury Grp, BR-22470010 Rio De Janeiro, Brazil. [Eiras de Araujo, Antonio Luis] Univ Fed Rio de Janeiro, Dept Radiol, BR-21941913 Rio De Janeiro, RJ, Brazil. [Eiras de Araujo, Antonio Luis] Fleury Grp, Labs DOr Network, BR-22281100 Rio De Janeiro, Brazil. [Mortele, Koenraad J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Clin MRI Abdominal Imaging & Body MRI, Boston, MA 02215 USA. RP de Souza, DAT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, PET CT & Nucl Med, 400 Brookline Ave, Boston, MA 02215 USA. EM daniel.radiology@gmail.com OI Parente, Daniella/0000-0003-0031-5785 NR 149 TC 2 Z9 3 U1 1 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD MAY PY 2013 VL 21 IS 2 BP 337 EP + DI 10.1016/j.mric.2013.01.001 PG 28 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161PC UT WOS:000320204800009 PM 23642557 ER PT J AU Pandey, GS Yanover, C Howard, TE Sauna, ZE AF Pandey, Gouri Shankar Yanover, Chen Howard, Tom E. Sauna, Zuben E. TI Polymorphisms in the F8 Gene and MHC-II Variants as Risk Factors for the Development of Inhibitory AntiFactor VIII Antibodies during the Treatment of Hemophilia A: A Computational Assessment SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID T-CELL RESPONSES; MILD HEMOPHILIA; KINETIC STABILITY; COMPLEXES; BINDING; FVIII; PREVENTION; MOLECULES; MUTATION; EPITOPE AB The development of neutralizing anti-drug-antibodies to the Factor VIII protein-therapeutic is currently the most significant impediment to the effective management of hemophilia A. Common non-synonymous single nucleotide polymorphisms (ns-SNPs) in the F8 gene occur as six haplotypes in the human population (denoted H1 to H6) of which H3 and H4 have been associated with an increased risk of developing anti-drug antibodies. There is evidence that CD4+ T-cell response is essential for the development of anti-drug antibodies and such a response requires the presentation of the peptides by the MHC-class-II (MHC-II) molecules of the patient. We measured the binding and half-life of peptide-MHC-II complexes using synthetic peptides from regions of the Factor VIII protein where ns-SNPs occur and showed that these wild type peptides form stable complexes with six common MHC-II alleles, representing 46.5% of the North American population. Next, we compared the affinities computed by NetMHCIIpan, a neural network-based algorithm for MHC-II peptide binding prediction, to the experimentally measured values and concluded that these are in good agreement (area under the ROC-curve of 0.778 to 0.972 for the six MHC-II variants). Using a computational binding predictor, we were able to expand our analysis to (a) include all wild type peptides spanning each polymorphic position; and (b) consider more MHC-II variants, thus allowing for a better estimation of the risk for clinical manifestation of anti-drug antibodies in the entire population (or a specific sub-population). Analysis of these computational data confirmed that peptides which have the wild type sequence at positions where the polymorphisms associated with haplotypes H3, H4 and H5 occur bind MHC-II proteins significantly more than a negative control. Taken together, the experimental and computational results suggest that wild type peptides from polymorphic regions of FVIII constitute potential T-cell epitopes and thus could explain the increased incidence of anti-drug antibodies in hemophilia A patients with haplotypes H3 and H4. C1 [Pandey, Gouri Shankar; Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Yanover, Chen] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. RP Pandey, GS (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM zuben.sauna@fda.hhs.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 FU Food and Drug Administration's Modernization of Science program; National Heart, Lung and Blood Institute, NIH [1RC2-HL101851, HL-71130, HL-72533]; Bayer Healthcare Corporation, Bayer Haemophilia Awards Program; Baxter Healthcare Corporation; Clinical Translational Science Institute at the University of Southern California's Keck School of Medicine FX This work was supported by the Food and Drug Administration's Modernization of Science program to ZES. Research conducted in the laboratory of TEH is funded by grants from the National Heart, Lung and Blood Institute, NIH (1RC2-HL101851, HL-71130 and HL-72533) as well as from Bayer Healthcare Corporation, Bayer Haemophilia Awards Program, Baxter Healthcare Corporation, and the Clinical Translational Science Institute at the University of Southern California's Keck School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 30 TC 9 Z9 9 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2013 VL 9 IS 5 AR e1003066 DI 10.1371/journal.pcbi.1003066 PG 11 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 159FX UT WOS:000320032100027 PM 23696725 ER PT J AU Donovan, DM Ingalsbe, MH Benbow, J Daley, DC AF Donovan, Dennis M. Ingalsbe, Michelle H. Benbow, James Daley, Dennis C. TI 12-Step Interventions and Mutual Support Programs for Substance Use Disorders: An Overview SO SOCIAL WORK IN PUBLIC HEALTH LA English DT Review DE 12-Step; mutual support; self-help; recovery activities ID SELF-HELP GROUPS; ALCOHOLICS-ANONYMOUS PARTICIPATION; DUALLY DIAGNOSED PERSONS; ONE-YEAR OUTCOMES; GROUP INVOLVEMENT; FACILITATING INVOLVEMENT; ADDICTION TREATMENT; INITIAL VALIDATION; SOCIAL NETWORKS; ABUSE TREATMENT AB Social workers and other behavioral health professionals are likely to encounter individuals with substance use disorders in a variety of practice settings outside of specialty treatment. 12-Step mutual support programs represent readily available, no cost community-based resources for such individuals; however, practitioners are often unfamiliar with such programs. The present article provides a brief overview of 12-Step programs, the positive substance use and psychosocial outcomes associated with active 12-Step involvement, and approaches ranging from ones that can be utilized by social workers in any practice setting to those developed for specialty treatment programs to facilitate engagement in 12-Step meetings and recovery activities. The goal is to familiarize social workers with 12-Step approaches so that they are better able to make informed referrals that match clients to mutual support groups that best meet the individual's needs and maximize the likelihood of engagement and positive outcomes. C1 [Donovan, Dennis M.; Ingalsbe, Michelle H.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98105 USA. [Donovan, Dennis M.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98105 USA. [Benbow, James] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Daley, Dennis C.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Med Ctr, Pittsburgh, PA 15213 USA. RP Donovan, DM (reprint author), Univ Washington, Alcohol & Drug Abuse Inst, 1107 NE 45th St,Suite 120, Seattle, WA 98105 USA. EM ddonovan@u.washington.edu FU NIDA NIH HHS [U10 DA013714, U10 DA020036] NR 122 TC 10 Z9 10 U1 5 U2 28 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1937-1918 J9 SOC WORK PUBLIC HLTH JI Soc. Work Public Health PD MAY 1 PY 2013 VL 28 IS 3-4 SI SI BP 313 EP 332 DI 10.1080/19371918.2013.774663 PG 20 WC Public, Environmental & Occupational Health; Social Work SC Public, Environmental & Occupational Health; Social Work GA 161GI UT WOS:000320180100013 PM 23731422 ER PT J AU Brady, KT Haynes, LF Hartwell, KJ Killeen, TK AF Brady, Kathleen T. Haynes, Louise F. Hartwell, Karen J. Killeen, Therese K. TI Substance Use Disorders and Anxiety: A Treatment Challenge for Social Workers SO SOCIAL WORK IN PUBLIC HEALTH LA English DT Article DE Anxiety; substance use disorders; comorbidity; treatment ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; PLACEBO-CONTROLLED TRIAL; COMORBIDITY SURVEY REPLICATION; COCAINE-DEPENDENT INDIVIDUALS; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH PROBLEMS; DSM-IV DISORDERS; ALCOHOL DEPENDENCE; PANIC DISORDER AB Converging evidence from epidemiologic and treatment studies indicate that anxiety disorders and substance use disorders commonly co-occur, and the interaction is multifaceted and variable. Epidemiological studies and investigations within clinical substance abuse populations have found an association between anxiety disorders and substance use disorders. Specific anxiety disorders including generalized anxiety disorder, panic disorder, and post traumatic stress disorder have all been associated with substance use. The association with obsessive-compulsive disorder is less robust, and some research has found a negative association. The risk of nicotine dependence is significantly higher among individuals with an anxiety disorder, and conversely, smoking has been found to be associated with trait anxiety and anxiety disorders. A review of the current literature and the relationship between specific anxiety disorders and alcohol and substance use disorders is discussed in detail. This article, written for social workers in a variety of practice settings, reviews the prevalence, diagnostic, and treatment issues at the interface of substance use disorders and anxiety disorders. C1 [Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat, Clin Neurosci Div, Charleston, SC 29425 USA. [Brady, Kathleen T.; Hartwell, Karen J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Haynes, Louise F.] Med Univ S Carolina, Div Neurosci, Charleston, SC 29425 USA. [Hartwell, Karen J.; Killeen, Therese K.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Brady, KT (reprint author), Med Univ S Carolina, Dept Psychiat, Clin Neurosci Div, 67 President St, Charleston, SC 29425 USA. EM bradyk@musc.ed FU NIDA NIH HHS [U10 DA013727] NR 94 TC 1 Z9 2 U1 8 U2 18 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1937-1918 EI 1937-190X J9 SOC WORK PUBLIC HLTH JI Soc. Work Public Health PD MAY 1 PY 2013 VL 28 IS 3-4 SI SI BP 407 EP 423 DI 10.1080/19371918.2013.774675 PG 17 WC Public, Environmental & Occupational Health; Social Work SC Public, Environmental & Occupational Health; Social Work GA 161GI UT WOS:000320180100019 PM 23731428 ER PT J AU Roy, N Barkmeier-Kraemer, J Eadie, T Sivasankar, MP Mehta, D Paul, D Hillman, R AF Roy, Nelson Barkmeier-Kraemer, Julie Eadie, Tanya Sivasankar, M. Preeti Mehta, Daryush Paul, Diane Hillman, Robert TI Evidence-Based Clinical Voice Assessment: A Systematic Review SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Review DE voice disorders; assessment; technology; diagnostics ID AUDITORY-PERCEPTUAL EVALUATION; DYSPHONIC VOICE; PATHOLOGY; SPEECH; DISCRIMINATION; PARAMETERS; ACCURACY; MEDICINE; PROTOCOL AB Purpose: To determine what research evidence exists to support the use of voice measures in the clinical assessment of patients with voice disorders. Method: The American Speech-Language-Hearing Association (ASHA) National Center for Evidence-Based Practice in Communication Disorders staff searched 29 databases for peer-reviewed English-language articles between January 1930 and April 2009 that included key words pertaining to objective and subjective voice measures, voice disorders, and diagnostic accuracy. The identified articles were systematically assessed by an ASHA-appointed committee employing a modification of the critical appraisal of diagnostic evidence rating system. Results: One hundred articles met the search criteria. The majority of studies investigated acoustic measures (60%) and focused on how well a test method identified the presence or absence of a voice disorder (78%). Only 17 of the 100 articles were judged to contain adequate evidence for the measures studied to be formally considered for inclusion in clinical voice assessment. Conclusion: Results provide evidence for selected acoustic, laryngeal imaging-based, auditory-perceptual, functional, and aerodynamic measures to be used as effective components in a clinical voice evaluation. However, there is clearly a pressing need for further high-quality research to produce sufficient evidence on which to recommend a comprehensive set of methods for a standard clinical voice evaluation. C1 [Roy, Nelson] Univ Utah, Salt Lake City, UT USA. [Barkmeier-Kraemer, Julie] Univ Calif Davis, Sacramento, CA 95817 USA. [Eadie, Tanya] Univ Washington, Seattle, WA 98195 USA. [Sivasankar, M. Preeti] Purdue Univ, W Lafayette, IN 47907 USA. [Mehta, Daryush; Hillman, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paul, Diane] Amer Speech Language Hearing Assoc, Rockville, MD USA. [Hillman, Robert] Harvard Univ, Sch Med, Boston, MA USA. RP Mehta, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM daryush.mehta@alum.mit.edu OI Eadie, Tanya/0000-0002-7697-1298 FU Special Interest Group 3, Voice and Voice Disorders, of the American Speech-Language-Hearing Association (ASHA) FX This systematic review was developed by the Ad Hoc Working Group for Clinical Voice Assessment under the auspices of Special Interest Group 3, Voice and Voice Disorders, of the American Speech-Language-Hearing Association (ASHA). The authors thank Leigh Deussing of ASHA for her support in developing the CADE-M form and for feedback during the review process. We thank Lauren Pecora and Kristin Slagle for their help with data transcription and transfer. We would also like to thank National Center for Evidence-Based Practice in Communication Disorders' staff members Tracy Schooling, Hillary Leech, and Rebecca Venediktov for their invaluable assistance with the literature review. NR 43 TC 37 Z9 39 U1 1 U2 10 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY 1 PY 2013 VL 22 IS 2 BP 212 EP 226 DI 10.1044/1058-0360(2012/12-0014) PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 156LD UT WOS:000319822600023 PM 23184134 ER PT J AU Mark, EJ Oliva, E Young, RH AF Mark, Eugene J. Oliva, Esther Young, Robert H. TI Robert E. Scully, MD In Memoriam SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Biographical-Item C1 [Mark, Eugene J.; Oliva, Esther; Young, Robert H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mark, EJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2013 VL 137 IS 5 BP 599 EP 600 DI 10.5858/arpa.2012-0724-IM PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 155WF UT WOS:000319778400001 ER PT J AU St Denis, TG Hamblin, MR AF St Denis, Tyler G. Hamblin, Michael R. TI Synthesis, bioanalysis and biodistribution of photosensitizer conjugates for photodynamic therapy SO BIOANALYSIS LA English DT Review ID GROWTH-FACTOR RECEPTOR; OVARIAN-CANCER CELLS; RADIOLABELED MONOCLONAL-ANTIBODIES; IN-VIVO; IMMUNOREACTIVE FRACTION; CARCINOMA-CELLS; SELECTIVE PHOTODESTRUCTION; CARCINOEMBRYONIC ANTIGEN; TARGETED PHOTOLYSIS; PHOTOIMMUNOTHERAPY AB Photodynamic therapy (PDT) was discovered in 1900 by Raab, and has since emerged as a promising tool for treating diseases characterized by unwanted cells or hyperproliferating tissue (e.g., cancer or infectious disease). PDT consists of the light excitation of a photosensitizer (PS) in the presence of O-2 to yield highly reactive oxygen species. In recent years, PDT has been improved by the synthesis of targeted bioconjugates between monoclonal antibodies and PS, and by investigating PS biodistribution and PD. Here, we provide a comprehensive review of major developments in PS-immunoconjugate-based PDT and the bioanalysis of these agents, with a specific emphasis on anticancer and antimicrobial PDT. C1 [St Denis, Tyler G.] Columbia Univ, Dept Chem, New York, NY 10027 USA. [St Denis, Tyler G.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Dept Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Columbia University II Rabi Fellowship; NIH [R01A1050875] FX Research conducted by TG St Denis is supported by the Columbia University II Rabi Fellowship. Research in the Hamblin laboratory is supported by NIH R01A1050875. There was no involvement of the funders in the design or writing of the work. 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 69 TC 14 Z9 14 U1 0 U2 45 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD MAY PY 2013 VL 5 IS 9 BP 1099 EP 1114 DI 10.4155/BIO.13.37 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 158FR UT WOS:000319955400016 PM 23641699 ER PT J AU Singh, H Lane, AA Correll, M Przychodzen, B Sykes, DB Stone, RM Ballen, KK Amrein, PC Maciejewski, J Attar, EC AF Singh, H. Lane, A. A. Correll, M. Przychodzen, B. Sykes, D. B. Stone, R. M. Ballen, K. K. Amrein, P. C. Maciejewski, J. Attar, E. C. TI Putative RNA-splicing gene LUC7L2 on 7q34 represents a candidate gene in pathogenesis of myeloid malignancies SO BLOOD CANCER JOURNAL LA English DT Letter ID MYELODYSPLASTIC SYNDROMES; DNMT3A MUTATIONS; LEUKEMIA GENOME; MACHINERY; PATHWAY C1 [Singh, H.; Ballen, K. K.; Amrein, P. C.; Attar, E. C.] Massachusetts Gen Hosp, Ctr Canc, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Singh, H.; Ballen, K. K.; Amrein, P. C.; Attar, E. C.] Massachusetts Gen Hosp, Ctr Canc, Ctr Leukaemia, Boston, MA 02114 USA. [Lane, A. A.; Stone, R. M.] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. [Correll, M.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Przychodzen, B.; Maciejewski, J.] Cleveland Clin, Dept Hematol, Cleveland, OH 44106 USA. [Sykes, D. B.] Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. RP Singh, H (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bone Marrow Transplant Unit, Boston, MA 02114 USA. EM eattar@partners.org NR 15 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD MAY PY 2013 VL 3 AR UNSP e117 DI 10.1038/bcj.2013.16 PG 3 WC Oncology SC Oncology GA 156FA UT WOS:000319806000004 PM 23708642 ER PT J AU Brennan-Minnella, AM Shen, Y El-Benna, J Swanson, RA AF Brennan-Minnella, A. M. Shen, Y. El-Benna, J. Swanson, R. A. TI Phosphoinositide 3-kinase couples NMDA receptors to superoxide release in excitotoxic neuronal death (vol 4, e580, 2013) SO CELL DEATH & DISEASE LA English DT Correction C1 [Brennan-Minnella, A. M.; Shen, Y.; Swanson, R. A.] Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [El-Benna, J.] Univ Paris Diderot, Fac Med, INSERM U773,CRB3, Lab Excellence Inflamex, Paris, France. RP Brennan-Minnella, AM (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM angela.brennan@ucsf.edu NR 1 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD MAY PY 2013 VL 4 AR e624 DI 10.1038/cddis.2013.164 PG 1 WC Cell Biology SC Cell Biology GA 156LR UT WOS:000319824100013 ER PT J AU Kim, AI Han, SH Tran, DT Sullivan, P Lassman, C Raman, S Zimmerman, P Chin, EE AF Kim, Andrew I. Han, Steven-Huy Doan-Trang Tran Sullivan, Peggy Lassman, Charles Raman, Steve Zimmerman, Peter Chin, Eva E. TI Abdominal imaging can misdiagnose submassive hepatic necrosis as cirrhosis in acute liver failure SO CLINICAL TRANSPLANTATION LA English DT Article DE cirrhosis; computed tomography; fulminant hepatic failure; transplantation; ultrasound ID TOMOGRAPHY; SURVIVAL; DISEASE; CT AB Patients with acute liver failure (ALF) can be listed status I for liver transplantation (LT) whereas patients with cirrhosis must follow the MELD scoring system. Liver imaging can mistakenly diagnose submassive hepatic necrosis in ALF as cirrhosis. The purpose of our study was to assess the accuracy of ultrasound (US) and computed tomography (CT) in distinguishing cirrhosis from ALF. All patients listed for ALF and transplanted during the study period were included. Controls were age- and gender-matched cirrhotic patients who underwent LT during the same period. Abdominal US or CT scans obtained on all patients were independently reviewed by three blinded abdominal radiologists. Explants from all patients were reviewed by two blinded pathologists, and histological diagnosis was correlated with radiological diagnosis. Forty-one patients with ALF and 42 patients with cirrhosis were analyzed. Univariate and multivariate analyses both revealed overall accuracy of 85% for ultrasound and 93% for CT. US and CT scans both provide high levels of accuracy in terms of discriminating ALF from cirrhosis but measures taken to determine whether a patient has ALF vs. cirrhosis needs to approach 100% accuracy. Thus, imaging studies alone should not definitively diagnosis one etiology of liver failure over the other. C1 [Kim, Andrew I.; Doan-Trang Tran] Univ Calif Los Angeles, David Geffen Sch Med, Dept Gastroenterol, Los Angeles, CA 90095 USA. [Kim, Andrew I.; Han, Steven-Huy] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Han, Steven-Huy] Univ Calif Los Angeles, David Geffen Sch Med, Pfleger Liver Inst, Los Angeles, CA 90095 USA. [Sullivan, Peggy; Lassman, Charles] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Raman, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Zimmerman, Peter; Chin, Eva E.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Radiol, Los Angeles, CA 90073 USA. [Zimmerman, Peter] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Chin, EE (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eva.chin@va.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD MAY-JUN PY 2013 VL 27 IS 3 BP E339 EP E345 DI 10.1111/ctr.12123 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 156OT UT WOS:000319832700023 PM 23647426 ER PT J AU Hayes, D Baker, PB Astor, TL Preston, TJ Kirkby, S Galantowicz, M Hoffman, TM AF Hayes, Don, Jr. Baker, Peter B. Astor, Todd L. Preston, Thomas J. Kirkby, Stephen Galantowicz, Mark Hoffman, Timothy M. TI Aggressive Coronary Artery Vasculopathy after Combined Heart-Lung Transplantation SO CONGENITAL HEART DISEASE LA English DT Article DE Allograft Rejection; Bronchiolitis Obliterans Syndrome; Combined Heart and Lung Transplantation; Coronary Artery Vasculopathy AB Combined heart-lung transplantation remains as a treatment option for patients with cardiopulmonary failure. There is speculation that lung grafts protect the heart from developing graft vasculopathy after combined heart-lung transplantation. This protective mechanism is more likely, at best, a delay in the onset of coronary artery vasculopathy. We present our experiences in two cases of an aggressive form of cardiac allograft vasculopathy after combined heart-lung transplantation that resulted in the death of both patients. C1 [Hayes, Don, Jr.; Baker, Peter B.; Kirkby, Stephen; Galantowicz, Mark; Hoffman, Timothy M.] Nationwide Childrens Hosp, Columbus, OH USA. [Hayes, Don, Jr.; Baker, Peter B.; Preston, Thomas J.; Kirkby, Stephen; Galantowicz, Mark; Hoffman, Timothy M.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Astor, Todd L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hayes, D (reprint author), Ohio State Univ, Nationwide Childrens Hosp, 700 Childrens Dr, Columbus, OH 43205 USA. EM hayes.705@osu.edu RI Hoffman, Timothy/E-3253-2011; OI Hoffman, Timothy/0000-0001-7715-8197 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 1747-079X J9 CONGENIT HEART DIS JI Congenit. Heart Dis. PD MAY-JUN PY 2013 VL 8 IS 3 BP E88 EP E91 DI 10.1111/j.1747-0803.2012.00681.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 158ST UT WOS:000319993900007 PM 22676698 ER PT J AU Cyganek, K Hebda-Szydlo, A Skupien, J Janas, I Walczyk, J Lipowska, A Borys, S Malecki, MT AF Cyganek, Katarzyna Hebda-Szydlo, Alicja Skupien, Jan Janas, Izabela Walczyk, Joanna Lipowska, Anna Borys, Sebastian Malecki, Maciej T. TI Postpregnancy Glycemic Control and Weight Changes in Type 1 Diabetic Women SO DIABETES CARE LA English DT Article ID SUBCUTANEOUS INSULIN INFUSION; PREGNANCY OUTCOMES; IMPACT AB OBJECTIVE-Pregnancy in type 1 diabetes requires excellent glycemic control. Most pregnant type 1 diabetic women achieve normoglycemia; however, there is scarce data on their postdelivery characteristics. We aimed to examine postpregnancy glycemic control and weight changes in type 1 diabetes. RESEARCH DESIGN AND METHODS-We identified and followed (median 20 months) 254 women with singleton pregnancies receiving postdelivery medical care at a single institution. RESULTS-Study subjects were 28.3 +/- 4.7 years of age (mean +/- SD), with a diabetes duration of 12.0 +/- 7.7 years. Mean A1C before conception was 6.9 +/- 1.4%, and preconception weight and BMI were 64.4 +/- 10.0 kg and 23.9 +/- 3.3 kg/m(2), respectively. Mean A1C decreased during pregnancy, reaching 5.7 +/- 0.8% in the third trimester. We observed a mean weight gain of 14.4 +/- 6.5 kg during pregnancy. Within 6 months after delivery, A1C increased by 0.8% (P < 0.0001) compared with the last trimester, and body weight and BMI were 4.4 kg and 2.5 kg/m(2) higher (P < 0.0001) compared with the preconception baseline. A1C further deteriorated by 0.8% until the end of follow-up. For women in the "pregnancy planning" program (n = 117), A1C > 12 months after delivery was Worse compared with before conception (7.1 vs. 6.5%, P = 0.0018), whereas in women with unplanned pregnancies, it was similar to the pregestational levels (7.3 vs.7.4%, P = 0.59). Weight and BMI in the entire study group did not return to prepregnancy levels and were 2.5 kg (P = 0.0079) and 0.9 kg/m(2) higher (P = 0.0058). CONCLUSIONS-In this clinical observation, type 1 diabetic women showed postpregnancy deterioration in glycemic control and were unable to return to prepregnancy weight. Type 1 diabetic women seem to require special attention after delivery to meet therapeutic targets. C1 [Cyganek, Katarzyna; Hebda-Szydlo, Alicja; Janas, Izabela; Walczyk, Joanna; Borys, Sebastian; Malecki, Maciej T.] Univ Hosp, Krakow, Poland. [Skupien, Jan] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Lipowska, Anna] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Malecki, Maciej T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. RP Malecki, MT (reprint author), Univ Hosp, Krakow, Poland. EM malecki_malecki@yahoo.cm FU Polish Ministry of Science [N N407 414436]; Jagiellonian University Medical College FX This work was supported by the Polish Ministry of Science (Grant N N407 414436) and by the Jagiellonian University Medical College. NR 12 TC 5 Z9 5 U1 0 U2 2 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 MAY PY 2013 VL 36 IS 5 BP 1083 EP 1087 DI 10.2337/dc12-1340 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155WW UT WOS:000319782100004 PM 23250804 ER PT J AU Morrison, F Shubina, M Goldberg, SI Turchin, A AF Morrison, Fritha Shubina, Maria Goldberg, Saveli I. Turchin, Alexander TI Performance of Primary Care Physicians and Other Providers on Key Process Measures in the Treatment of Diabetes SO DIABETES CARE LA English DT Article ID BLOOD-PRESSURE; HEALTH-CARE; TREATMENT INTENSIFICATION; BONFERRONI PROCEDURE; ENCOUNTER FREQUENCY; COMORBIDITY INDEX; GLYCEMIC CONTROL; QUALITY-MEASURES; MULTIPLE TESTS; CONTINUITY AB OBJECTIVE-Studies have shown that patients without a consistent primary care provider have inferior outcomes. However, little is known about the mechanisms for these effects. This study aims to determine whether primary care physicians (PCPs) provide more frequent medication intensification, lifestyle counseling, and patient encounters than other providers in the primary care setting. RESEARCH DESIGN AND METHODS-This retrospective cohort study included 584,587 encounters for 27,225 patients with diabetes and elevated A1C, blood pressure, and/or LDL cholesterol monitored for at least 2 years. Encounters occurred at primary care practices affiliated with two teaching hospitals in eastern Massachusetts. RESULTS-Of the encounters documented, 83% were with PCPs, 13% were with covering physicians, and 5% were with midlevel providers. In multivariable analysis, the odds of medication intensification were 49% (P < 0.0001) and 26% (P < 0.0001) higher for PCPs than for covering physicians and midlevel providers, respectively, whereas the odds of lifestyle counseling were 91% (P < 0.0001) and 21% (P = 0.0015) higher. During visits with acute complaints, covering physicians were even less likely, by a further 52% (P < 0.0001), to intensify medications, and midlevel providers were even less likely, by a further 41% (P < 0.0001), to provide lifestyle counseling. Compared with PCPs, the hazard ratios for time to the next encounter after a visit without acute complaints were 1.11 for covering physicians and 1.19 for midlevel providers (P < 0.0001 for both). CONCLUSIONS-PCPs provide better care through higher rates of medication intensification and lifestyle counseling. Covering physicians and midlevel providers may enable more frequent encounters when PCP resources are constrained. C1 [Morrison, Fritha; Shubina, Maria; Turchin, Alexander] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Goldberg, Saveli I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Turchin, Alexander] Harvard Univ, Sch Med, Boston, MA USA. [Turchin, Alexander] Partners HealthCare Syst, Qual Performance Management, Boston, MA USA. RP Turchin, A (reprint author), Brigham & Womens Hosp, Div Endocrinol, 75 Francis St, Boston, MA 02115 USA. EM aturchin@partners.org FU Agency for Healthcare Research and Quality [5RI8HS017030]; National library of Medicine [5RCILM010460]; Diabetes Action Research and Education Foundation FX This study was supported in part by grants from the Agency for Healthcare Research and Quality (5RI8HS017030), the National library of Medicine (5RCILM010460), and the Diabetes Action Research and Education Foundation. The funding sources had no role in the design and conduct of the study, collection, management, analysis, or interpretation of the study or in the preparation, review, or approval of the manuscript. NR 48 TC 6 Z9 7 U1 2 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2013 VL 36 IS 5 BP 1147 EP 1152 DI 10.2337/dc12-1382 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155WW UT WOS:000319782100015 PM 23230095 ER PT J AU Jensen, MK Bartz, TM Mukamal, KJ Djousse, L Kizer, JR Tracy, RP Zieman, SJ Rimm, EB Sscovick, DS Shlipak, M Ix, JH AF Jensen, Majken K. Bartz, Traci M. Mukamal, Kenneth J. Djousse, Luc Kizer, Jorge R. Tracy, Russell P. Zieman, Susan J. Rimm, Eric B. Siscovick, David S. Shlipak, Michael Ix, Joachim H. TI Fetuin-A, Type 2 Diabetes, and Risk of Cardiovascular Disease in Older Adults The Cardiovascular Health Study SO DIABETES CARE LA English DT Article ID ALPHA(2)-HEREMANS-SCHMID GLYCOPROTEIN/FETUIN-A; RECEPTOR TYROSINE KINASE; INSULIN-RESISTANCE; ASSOCIATION; INHIBITOR; SERUM; CALCIFICATION; MORTALITY; DIALYSIS; MELLITUS AB OBJECTIVE-Fetuin-A, a hepatic secretory protein that simultaneously inhibits arterial calcification and insulin action, is associated with type 2 diabetes, but its association with cardiovascular disease (CVD) is uncertain. Preliminary studies suggest that the association of fetuin-A with CVD might differ among individuals with or without type 2 diabetes. RESEARCH DESIGN AND METHODS-This was a prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008. RESULTS-Mean age was 75 years, and 61% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95% Cl, 0.88-0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93 1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85-0.97) and 0.87 (0.79-0.95), respectively]. CONCLUSIONS-The association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes. C1 [Jensen, Majken K.; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Djousse, Luc] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA USA. [Djousse, Luc] Boston Vet Affairs Healthcare Syst, Boston, MA USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Populat Hlth, Bronx, NY 10467 USA. [Tracy, Russell P.] Univ Vermont, Colchester Res Facil, Dept Pathol, Colchester, VT USA. [Zieman, Susan J.] NIA, NIH, Bethesda, MD 20892 USA. [Rimm, Eric B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Shlipak, Michael] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Gen Internal Med, San Francisco, CA 94143 USA. [Shlipak, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Shlipak, Michael] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Ix, Joachim H.] Univ Calif San Diego, Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, San Diego, CA 92103 USA. RP Jensen, MK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM mkjensen@hsph.harvard.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute (NHLBI) [R01 HL094555]; NHLBI [N01 HC-85079, N01 HC-85080, N01 HC-85081, N01 HC-85082, N01 HC-85083, N01 HC-85084, N01 HC-85085, N01HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01 HC-75150, N01 HC-54133, N01-HC85239, U01 HL080295] FX The study was supported by a National Heart, Lung, and Blood Institute (NHLBI) grant (R01 HL094555). The CHS was supported by contract numbers N01 HC-85079 through N01HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01 HC-75150, N01 HC-54133, and N01-HC85239, and grant number U01 HL080295 from the NHLBI, with additional contributions from the National Institute of Neurologic Disorders and Stroke. This material is the result of work supported with resources of the VA San Diego Healthcare System. NR 31 TC 39 Z9 41 U1 1 U2 5 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 MAY PY 2013 VL 36 IS 5 BP 1222 EP 1228 DI 10.2337/dc12-1591 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155WW UT WOS:000319782100026 PM 23250801 ER PT J AU Hayashi, T Boyko, EJ Sato, KK McNeely, MJ Leonetti, DL Kahn, SE Fujimoto, WY AF Hayashi, Tomoshige Boyko, Edward J. Sato, Kyoko Kogawa McNeely, Marguerite J. Leonetti, Donna L. Kahn, Steven E. Fujimoto, Wilfred Y. TI Patterns of Insulin Concentration During the OGTT Predict the Risk of Type 2 Diabetes in Japanese Americans SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL DYSFUNCTION; FASTING GLUCOSE; RESISTANCE; SENSITIVITY; SECRETION; CLAMP; MODEL; MEN AB OBJECTIVE-To examine whether the patterns of insulin concentration during the oral glucose tolerance test (OGTT) predict type 2 diabetes. RESEARCH DESIGN AND METHODS-We followed 400 nondiabetic Japanese Americans for 10-11 years. Insulin concentrations at 30, 60, and 120 min during a 2-h 75-g OGTT at baseline were used to derive the following possible patterns of insulin: pattern 1 (30-min peak, higher insulin level at 60 than at 120 min), pattern 2 (30-min peak, lower or equal level at 60 vs. 120 min), pattern 3 (60-min peak); pattern 4 (120-mm peak, lower level at 30 than at 60 min), and pattern 5 (120-min peak, equal or higher level at 30 vs. 60 mm). Insulin sensitivity was estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Insulin secretion was estimated by the insulinogenic index (IGI) [Delta insulin/Delta glucose (30-0 min)] and disposition index (IGI/HOMA-IR). RESULTS-There were 86 incident cases of type 2 diabetes. The cumulative incidence was 3.2, 9.8, 15.4, 47.8, and 37.5% for patterns 1, 2, 3, 4, and 5, respectively. Compared with pattern 1, patterns 4 and 5, characterized by a lasting late insulin response, were associated with significantly less insulin sensitivity as measured by the Matsuda index and lower early insulin response by the disposition index. The multiple-adjusted odds ratios of type 2 diabetes were 12.55 (95% Cl 4.79-32.89) for pattern 4 and 8.34(2.38-29.27) for patterns compared with patterns 1 and 2. This association was independent of insulin secretion and sensitivity. CONCLUSIONS-The patterns of insulin concentration during an OGTT strongly predict the development of type 2 diabetes. C1 [Hayashi, Tomoshige; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Hayashi, Tomoshige; Sato, Kyoko Kogawa] Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Osaka 558, Japan. [Boyko, Edward J.; McNeely, Marguerite J.; Fujimoto, Wilfred Y.] Univ Washington, Dept Med, Seattle, WA USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. EM eboyko@u.washington.edu RI Hayashi, Tomoshige/N-8508-2015; OI Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health [DK-31170, HL-49293, DK-02654]; Japanese Ministry of Education, Science, Sports, and Culture [23390177]; King County Japanese-American community FX This work was supported by National Institutes of Health grants DK-31170, HL-49293, and DK-02654; facilities and services were provided by the Diabetes and Endocrinology Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. T.H. was supported in part by a research grant from the Japanese Ministry of Education, Science, Sports, and Culture (23390177). VA Puget Sound Health Care System provided support for the participation of E.J.B. and S.E.K.; The authors gratefully acknowledge the skilled assistance of staff members, especially Jane B. Shofer of the Center for Studies in Demography and Ecology, University of Washington. The authors are grateful to the King County Japanese-American community for their support and cooperation. NR 20 TC 10 Z9 10 U1 0 U2 6 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 MAY PY 2013 VL 36 IS 5 BP 1229 EP 1235 DI 10.2337/dc12-0246 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155WW UT WOS:000319782100027 PM 23275353 ER PT J AU Franks, PW Pearson, E Florez, JC AF Franks, Paul W. Pearson, Ewan Florez, Jose C. TI Gene-Environment and Gene-Treatment Interactions in Type 2 Diabetes SO DIABETES CARE LA English DT Review ID BODY-MASS INDEX; IMPAIRED GLUCOSE-TOLERANCE; GENOME-WIDE ASSOCIATION; LIFE-STYLE INTERVENTION; DIETARY-FAT INTAKE; PREVENTION PROGRAM; PHYSICAL-ACTIVITY; INSULIN-RESISTANCE; FASTING GLUCOSE; GLYCEMIC TRAITS C1 [Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Pearson, Ewan] Univ Dundee, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Dept Med, Boston, MA 02114 USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA. RP Franks, PW (reprint author), Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. EM paul.franks@med.lu.se FU Excellence in Diabetes Research in Sweden (EXODIAB); Lund University; Umea University; Region Skane Health Authority; Swedish Diabetes Association; Swedish Heart-Lung Foundation; Swedish Research Council; European Union; Novo Nordisk; National Institutes of Health (National Institute of Child Health and Human Development); National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK-072041, R01 DK-088214.A1] FX P.W.F. is funded by Excellence in Diabetes Research in Sweden (EXODIAB), Lund University, Umea University, Region Skane Health Authority, the Swedish Diabetes Association, the Swedish Heart-Lung Foundation, the Swedish Research Council, the European Union, Novo Nordisk, and the National Institutes of Health (National Institute of Child Health and Human Development). J.C.F. is supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01 DK-072041 and R01 DK-088214.A1. NR 68 TC 37 Z9 38 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2013 VL 36 IS 5 BP 1413 EP 1421 DI 10.2337/dc12-2211 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155WW UT WOS:000319782100053 PM 23613601 ER PT J AU Abramson, JS AF Abramson, Jeremy S. TI High-dose chemotherapy and autologous stem cell transplantation for secondary central nervous system lymphoma: many are called, but few are chosen SO HAEMATOLOGICA LA English DT Editorial Material ID NON-HODGKIN-LYMPHOMA; PRIMARY CNS LYMPHOMA; ELDERLY-PATIENTS; RECURRENT CNS; RISK-FACTORS; FOLLOW-UP; RITUXIMAB; TRIAL; RELAPSE; LENALIDOMIDE C1 [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. [Abramson, Jeremy S.] Harvard Univ, Sch Med, Boston, MA USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. EM jabramson@partners.org NR 21 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 2013 VL 98 IS 5 BP 662 EP 664 DI 10.3324/haematol.2013.084285 PG 3 WC Hematology SC Hematology GA 157LX UT WOS:000319898700007 PM 23633540 ER PT J AU Clapp, JD Grubaugh, AL Allen, JG Mahoney, J Oldham, JM Fowler, JC Ellis, T Elhai, JD Frueh, BC AF Clapp, Joshua D. Grubaugh, Anouk L. Allen, Jon G. Mahoney, Jane Oldham, John M. Fowler, J. Christopher Ellis, Tom Elhai, Jon D. Frueh, B. Christopher TI Modeling Trajectory of Depressive Symptoms Among Psychiatric Inpatients: A Latent Growth Curve Approach SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID LENGTH-OF-STAY; INVENTORY-II; DECREASING LENGTH; HOSPITAL STAY; UNITED-STATES; CARE; PSYCHOTHERAPY; OUTCOMES; ANTIDEPRESSANTS; DISORDERS AB Objective: Changes in the parameters of inpatient psychiatric care have inspired a sizable literature exploring correlates of prolonged intervention as well as symptom change over varying lengths of hospitalization. However, existing data offer limited insight regarding the nature of symptom change over time. Objectives of this longitudinal research were to (1) model the trajectory of depressive symptoms within an inpatient psychiatric sample, (2) identify characteristics associated with unique patterns of change, and (3) evaluate the magnitude of expected gains using objective clinical benchmarks. Method: Participants included 1,084 psychiatric inpatients treated between April 2008 and December 2010. Latent growth curve modeling was used to determine the trajectory of Beck Depression Inventory II depressive symptoms in response to treatment. Age, gender, trauma history, prior hospitalization, and DSM-IV diagnoses were examined as potential moderators of recovery. Results: Results indicate a nonlinear model of recovery, with symptom reductions greatest following admission and slowing gradually over time. Female gender, probable trauma exposure, prior psychiatric hospitalization, and primary depressive diagnosis were associated with more severe trajectories. Diagnosis of alcohol/substance use, by contrast, was associated with more moderate trajectories. Objective benchmarks occurred relatively consistently across patient groups, with clinically significant change occurring between 2-4 weeks after admission. Conclusions: The nonlinear trajectory of recovery observed in these data provides insight regarding the dynamics of inpatient recovery. Across all patient groups, symptom reduction was most dramatic in the initial week of hospitalization. However, notable improvement continued for several weeks after admission. Results suggest that timelines for adequate inpatient care are largely contingent on program-specific goals. C1 [Clapp, Joshua D.; Grubaugh, Anouk L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Grubaugh, Anouk L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Clapp, Joshua D.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Allen, Jon G.; Mahoney, Jane; Oldham, John M.; Fowler, J. Christopher; Ellis, Tom] Menninger Clin, Houston, TX USA. [Allen, Jon G.; Mahoney, Jane; Oldham, John M.; Fowler, J. Christopher; Ellis, Tom] Baylor Coll Med, Houston, TX 77030 USA. [Ellis, Tom] Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. [Ellis, Tom] Univ Toledo, Dept Psychiat, Toledo, OH 43606 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. RP Clapp, JD (reprint author), Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. EM jclapp@uwyo.edu OI Ellis, Thomas/0000-0002-4496-5280 FU Menninger Foundation; McNair Medical Institute; National Institute of Mental Health (NIMH); NIMH [T32 MH18869] FX This research was supported in part by funding from the Menninger Foundation, the McNair Medical Institute, and the National Institute of Mental Health (NIMH). Dr Frueh is a McNair Scholar. Dr Clapp was a NIMH-sponsored intern at the Medical University of South Carolina (T32 MH18869) during the development of this project. NR 55 TC 12 Z9 12 U1 1 U2 10 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2013 VL 74 IS 5 BP 492 EP 499 DI 10.4088/JCP.12m07842 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 157IW UT WOS:000319890800005 PM 23759452 ER PT J AU Bouchard, DR Porneala, B Janssen, I Langlois, MF Baillargeon, JP Fox, CS Meigs, JB D'Agostino, RB Pencina, M Hivert, MF AF Bouchard, Danielle R. Porneala, Bianca Janssen, Ian Langlois, Marie-France Baillargeon, Jean-Patrice Fox, Caroline S. Meigs, James B. D'Agostino, Ralph B., Sr. Pencina, Michael Hivert, Marie-France TI Risk of type 2 diabetes and cumulative excess weight exposure in the Framingham Offspring Study SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Adults; Aging; BMI; Diagnosis; Epidemiology ID OBESE WOMEN; PACK-YEAR; MELLITUS; DURATION; BMI; HYPERTENSION; ASSOCIATION; PREVENTION; PREVALENCE; PATTERNS AB Aim: Mid-life obesity is associated with T2D risk. However, less is known about the cumulative effect of obesity during adulthood. Methods: Framingham Offspring Study participants who had an examination at 35 +/- 2 years and were initially free of T2D were included in this study (N=1026). A cumulative excess weight (CEW) score (year*kg/m(2)) was calculated until T2D diagnostic or the end of follow-up. Results: Eighty-four individuals (8.2%) developed T2D over 20 +/- 6 years. Mean CEW scores were 118.+/- 114.6 year*kg/m(2) in individuals who developed T2D and 30.2 +/- 91.4 year*kg/m(2) in those who did not develop T2D (P<0.01). T2D risk was doubled for each standard deviation increase in the CEW score (OR=1.99 [1.64-2.40]; P<0.001). However, CEW score was only significantly associated with T2D incidence for participants with a baseline BMI<25 kg/m(2) (OR=2.13 [136-336]; P<0.001). Conclusions: Accumulating weight between the mid-thirties to the mid-fifties increases the risk of developing T2D. However, BMI in mid-thirties remains a stronger predictor of T2D risk. (C) 2013 Elsevier Inc. All rights reserved. C1 [Bouchard, Danielle R.] Univ Manitoba, Fac Kinesiol & Recreat Management, Winnipeg, MB, Canada. [Bouchard, Danielle R.] Hlth Leisure & Human Performance Res Inst, Winnipeg, MB, Canada. [Porneala, Bianca] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Janssen, Ian] Queens Univ, Dept Community Hlth Epidemiol, Kingston, ON, Canada. [Janssen, Ian] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON, Canada. [Langlois, Marie-France; Baillargeon, Jean-Patrice; Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [Langlois, Marie-France; Baillargeon, Jean-Patrice; Hivert, Marie-France] CHU Sherbrooke, Etienne LeBel Clin Res Ctr, Sherbrooke, PQ J1H 5N4, Canada. [Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Fox, Caroline S.] Brigham Womens Hosp, Dept Endocrinol, Boston, MA USA. [Meigs, James B.; Hivert, Marie-France] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Pencina, Michael] Boston Univ, Dept Biostat, Boston, MA 02215 USA. RP Hivert, MF (reprint author), Dept Med, Div Endocrinol, Sherbrooke, PQ J1H 5N4, Canada. EM Marie-France.Hivert@USherbrooke.ca RI Janssen, Ian/B-7700-2009 FU TheNational Heart, Lung, and Blood Institute (NHLBI); Fonds de Recherche du Quebec-Sante (FRQ-S); Canadian Diabetes Association (CDA); FRQ-S; NIDDK [K24 DK080140] FX TheNational Heart, Lung, and Blood Institute (NHLBI) supported the Framingham study. The NHLBI had no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation of the manuscript.; MFH is supported by a Scholar Award (junior 1 level) from the Fonds de Recherche du Quebec-Sante (FRQ-S) and was awarded a Canadian Diabetes Association (CDA) Clinician Scientist award. MFL is the recipient of an FRQ-S National Researcher Award. JPB is the recipient of an FRQ-S Senior Award. JBM is supported by NIDDK K24 DK080140. NR 32 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 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAY-JUN PY 2013 VL 27 IS 3 BP 214 EP 218 DI 10.1016/j.jdiacomp.2012.11.009 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 158YR UT WOS:000320011600004 PM 23312789 ER PT J AU Brown, RT Kiely, DK Bharel, M Mitchell, SL AF Brown, Rebecca T. Kiely, Dan K. Bharel, Monica Mitchell, Susan L. TI Factors Associated with Geriatric Syndromes in Older Homeless Adults SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Homeless people; aged; middle aged; geriatric syndromes ID MINI-MENTAL-STATE; TRAUMATIC BRAIN-INJURY; SERVICES TASK-FORCE; RISK-FACTORS; SAN-FRANCISCO; HEALTH-STATUS; PRIMARY-CARE; ALCOHOL-USE; POPULATION; FALLS AB Although older homeless adults have high rates of geriatric syndromes, risk factors for these syndromes are not known. We used multivariable regression models to estimate the association of subject characteristics with the total number of geriatric syndromes in 250 homeless adults aged 50 years and older. Geriatric syndromes included falls, cognitive impairment, frailty, major depression, sensory impairment, and urinary incontinence. A higher total number of geriatric syndromes was associated with having less than a high school education, medical comorbidities (diabetes and arthritis), alcohol and drug use problems, and difficulty performing one or more activities of daily living. Clinicians who care for older homeless patients with these characteristics should consider screening them for geriatric syndromes. Moreover, this study identifies potentially modifiable risk factors associated with the total number of geriatric syndromes in older homeless adults. This knowledge may provide targets for clinical interventions to improve the health of older homeless patients. C1 [Brown, Rebecca T.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Brown, Rebecca T.] San Francisco VA Med Ctr, San Francisco, CA 94122 USA. [Kiely, Dan K.; Mitchell, Susan L.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Bharel, Monica] Boston Healthcare Homeless Program, Boston, MA USA. [Bharel, Monica] Boston Med Ctr, Dept Med, Boston, MA USA. [Bharel, Monica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. RP Brown, RT (reprint author), San Francisco VA Med Ctr, 4150 Clement St,181G, San Francisco, CA 94122 USA. EM rebecca.brown@ucsf.edu FU NIA NIH HHS [T32 AG023480, K24 AG033640, T32 AG000212] NR 54 TC 6 Z9 6 U1 0 U2 8 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 MAY PY 2013 VL 24 IS 2 BP 456 EP 468 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 153VU UT WOS:000319631400005 PM 23728022 ER PT J AU Doran, KM Ragins, KT Gross, CP Zerger, S AF Doran, Kelly M. Ragins, Kyle T. Gross, Cary P. Zerger, Suzanne TI Medical Respite Programs for Homeless Patients: A Systematic Review SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Review DE Respite care; aftercare; subacute care; homeless people; hospitalization; patient discharge ID SHELTER-BASED CONVALESCENCE; CASE-MANAGEMENT PROGRAM; LENGTH-OF-STAY; ADULTS; CARE; INTERVENTIONS; QUALITY; COSTS AB Medical respite programs provide care to homeless patients who are too sick to be on the streets or in a traditional shelter, but not sick enough to warrant inpatient hospitalization. They are designed to improve the health of homeless patients while also decreasing costly hospital use. Although there is increasing interest in implementing respite programs, there has been no prior systematic review of their effectiveness. We conducted a comprehensive search for studies of medical respite program outcomes in multiple biomedical and sociological databases, and the grey literature. Thirteen articles met inclusion criteria. The articles were heterogeneous in methods, study quality, inclusion of a comparison group, and outcomes examined. Available evidence showed that medical respite programs reduced future hospital admissions, inpatient days, and hospital readmissions. They also resulted in improved housing outcomes. Results for emergency department use and costs were mixed but promising. Future research utilizing adequate comparison groups is needed. C1 [Doran, Kelly M.; Gross, Cary P.] Yale Univ, Sch Med YU SOM, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. [Doran, Kelly M.] US Dept Vet Affairs, New Haven, CT 06520 USA. [Zerger, Suzanne] Ctr Social Innovat, Needham, MA USA. RP Doran, KM (reprint author), Yale Univ, Sch Med YU SOM, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. EM kelly.doran@yale.edu NR 27 TC 11 Z9 11 U1 0 U2 10 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 MAY PY 2013 VL 24 IS 2 BP 499 EP 524 PG 26 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 153VU UT WOS:000319631400008 PM 23728025 ER PT J AU Renfrew, MR Taing, E Cohen, MJ Betancourt, JR Pasinski, R Green, AR AF Renfrew, Megan R. Taing, Elizabeth Cohen, Marya J. Betancourt, Joseph R. Pasinski, Roger Green, Alexander R. TI Barriers to Care for Cambodian Patients with Diabetes: Results from a Qualitative Study SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Health care disparities; diabetes mellitus; type 2/diagnosis; culture; cultural competence; health literacy; qualitative research; focus groups; Cambodia ethnology; United States ID SOUTHEAST-ASIAN REFUGEES; POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; ETHNIC DISPARITIES; UNITED-STATES; CLINICAL CARE; WEIGHT CHANGE; RISK-FACTOR; PREVALENCE; OUTCOMES AB Racial and ethnic disparities in diabetes care have been well documented. While root causes have been explored for some minority groups, less is known about smaller immigrant populations such as Cambodians. In this study, we sought to explore the potential barriers to care for Cambodian patients with diabetes. We conducted five focus groups with three study groups: health care providers, bilingual Khmer frontline staff, and Cambodian patients with diabetes. Focus groups findings revealed that certain cultural beliefs, low health literacy, and language barriers strongly affect Cambodian patients' understanding of diabetes and self-management, as well as clinicians' ability to care effectively for Cambodian patients with diabetes. Our study supports previous literature and also adds several new insights not previously described. We recommend education for health care providers on patient-centered, cross-cultural care with an emphasis on the needs of Cambodians as well as culturally appropriate diabetes education for patients. C1 [Renfrew, Megan R.; Taing, Elizabeth] Massachusetts Gen Hosp, Dispar Solut Ctr, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Cohen, Marya J.] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Cohen, Marya J.; Betancourt, Joseph R.; Pasinski, Roger; Green, Alexander R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Betancourt, Joseph R.; Green, Alexander R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Betancourt, Joseph R.; Green, Alexander R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Pasinski, Roger] Massachusetts Gen Hosp, Revere HealthCare Ctr, Boston, MA 02114 USA. EM mrrenfrew@partners.org NR 98 TC 2 Z9 2 U1 3 U2 16 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 MAY PY 2013 VL 24 IS 2 BP 633 EP 655 PG 23 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 153VU UT WOS:000319631400016 PM 23728033 ER PT J AU Taplin, ME AF Taplin, Mary-Ellen TI Secondary Hormone Therapy for Castration-Resistant Prostate Cancer SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID INCREASED SURVIVAL; ANDROGEN RECEPTOR; ABIRATERONE; CHEMOTHERAPY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Taplin, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2013 VL 27 IS 5 BP 371 EP + PG 3 WC Oncology SC Oncology GA 153RV UT WOS:000319621100003 PM 25184257 ER PT J AU Ott, PA Hodi, FS AF Ott, Patrick A. Hodi, F. Stephen TI Treatment for Advanced Melanoma: New Drugs, New Opportunities, New Challenges SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID METASTATIC MELANOMA; BRAF; VEMURAFENIB; INHIBITION; COMBINATION; IPILIMUMAB; ANTIBODY; CANCER; SAFETY C1 [Ott, Patrick A.; Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ott, Patrick A.; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. RP Ott, PA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2013 VL 27 IS 5 BP 381 EP + PG 3 WC Oncology SC Oncology GA 153RV UT WOS:000319621100005 PM 25184259 ER PT J AU Kaaya, S Eustache, E Lapidos-Salaiz, I Musisi, S Psaros, C Wissow, L AF Kaaya, Sylvia Eustache, Eddy Lapidos-Salaiz, Ilana Musisi, Seggane Psaros, Christina Wissow, Lawrence TI Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness SO PLOS MEDICINE LA English DT Editorial Material ID TO-CHILD TRANSMISSION; QUALITY-OF-LIFE; PRIMARY-CARE; ANTIRETROVIRAL TREATMENT; COLLABORATIVE CARE; INFECTED CHILDREN; ALCOHOL-USE; HEALTH; SERVICES; DISORDERS C1 [Kaaya, Sylvia] Muhimbili Univ Hlth & Allied Sci, Sch Med, Dar Es Salaam, Tanzania. [Eustache, Eddy] Zanmi Lasante Partners Hlth, Cent Plateau, Haiti. [Lapidos-Salaiz, Ilana] US Agcy Int Dev, Off HIV AIDS, Washington, DC 20523 USA. [Musisi, Seggane] Makerere Univ, Sch Med, Kampala, Uganda. [Psaros, Christina] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wissow, Lawrence] Johns Hopkins Univ, Ctr Mental Hlth Pediat Primary Care, Baltimore, MD USA. RP Kaaya, S (reprint author), Muhimbili Univ Hlth & Allied Sci, Sch Med, Dar Es Salaam, Tanzania. EM skaaya@gmail.com FU NIMH NIH HHS [K23 MH096651, P20 MH086048] NR 42 TC 26 Z9 26 U1 4 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAY PY 2013 VL 10 IS 5 AR e1001447 DI 10.1371/journal.pmed.1001447 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 154JK UT WOS:000319670900022 PM 23700389 ER PT J AU Tsai, AC AF Tsai, Alexander C. TI Intimate Partner Violence and Population Mental Health: Why Poverty and Gender Inequities Matter SO PLOS MEDICINE LA English DT Editorial Material ID RANDOMIZED-CONTROLLED-TRIAL; SUB-SAHARAN AFRICA; COMMUNITY-LEVEL; PREVENTION; WOMEN; INTERVENTION; METAANALYSIS; CARE; DEPRESSION; OUTCOMES C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIMH NIH HHS [K23 MH-096620, K23 MH096620] NR 45 TC 10 Z9 10 U1 3 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAY PY 2013 VL 10 IS 5 AR e1001440 DI 10.1371/journal.pmed.1001440 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 154JK UT WOS:000319670900015 PM 23667344 ER PT J AU Yeh, JM Hur, C Schrag, D Kuntz, KM Ezzati, M Stout, N Ward, Z Goldie, SJ AF Yeh, Jennifer M. Hur, Chin Schrag, Deb Kuntz, Karen M. Ezzati, Majid Stout, Natasha Ward, Zachary Goldie, Sue J. TI Contribution of H-pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model SO PLOS MEDICINE LA English DT Article ID LUNG-CANCER MORTALITY; UNITED-STATES; CIGARETTE-SMOKING; STOMACH-CANCER; RISK-FACTORS; PRIMARY PREVENTION; TOBACCO SMOKING; SECULAR TRENDS; EPIDEMIOLOGY; ADULTS AB Background: Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence. Methods and Findings: We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%-58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%-21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%-100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men. Conclusions: Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts. C1 [Yeh, Jennifer M.; Ward, Zachary; Goldie, Sue J.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Schrag, Deb] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Ezzati, Majid] Univ London Imperial Coll Sci Technol & Med, London, England. [Stout, Natasha] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Yeh, JM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM jyeh@hsph.harvard.edu OI Ward, Zachary/0000-0002-4007-2207; Hur, Chin/0000-0002-2819-7576 FU National Institutes of Health's National Cancer Institute [K07-CA143044] FX JMY was funded by the National Institutes of Health's National Cancer Institute (K07-CA143044). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 13 Z9 13 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAY PY 2013 VL 10 IS 5 AR e1001451 DI 10.1371/journal.pmed.1001451 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 154JK UT WOS:000319670900026 PM 23700390 ER PT J AU Stineman, MG Zhang, GY Kurichi, JE Zhang, Z Streim, JE Pan, Q Xie, DW AF Stineman, Margaret G. Zhang, Guangyu Kurichi, Jibby E. Zhang, Zi Streim, Joel E. Pan, Qiang Xie, Dawei TI Prognosis for Functional Deterioration and Functional Improvement in Late Life Among Community-Dwelling Persons SO PM&R LA English DT Article ID OLDER-PEOPLE; LIMITATION PATHWAYS; ELDERLY-PEOPLE; HEALTH; DISABILITY; REHABILITATION; INDEPENDENCE; TRANSITIONS; VALIDATION; MORTALITY AB Objective: To examine how health-related, socioeconomic, and environmental factors combine to influence the onset of activity of daily living (ADL) limitations or prognosis for death or further functional deterioration or improvement among elderly people. Design: A national representative sample with 2-year follow-up. Setting: Community-dwelling people. Participants: Included were 9447 persons (>= 70 years of age) in the United States from the Second Longitudinal Study of Aging who were interviewed in 1994, 1995, or 1996. Methods: Self- or proxy-reported health conditions, ADLs expressed as 5 stages describing severity and pattern of limitations, and other baseline characteristics were obtained. A multinomial logistic regression model was used to predict stage transitions. Because of incomplete follow-up (17.7% of baseline sample), primary analyses were determined by multiple imputation to address potential bias associated with loss to follow-up. Main Outcome Measurement: ADL stage transitions in 2 years (death, deteriorated, stable, and improved ADL function). Results: In the imputed-case analysis, the percentages for those who died, deteriorated, were stable, and improved were 12.6%, 32.7%, 48.4%, and 6.2%, respectively. Persons at a mild stage of ADL limitation were most likely to deteriorate further. Persons at advanced stages were most likely to die. Married people and high school graduates had a lower likelihood of deterioration. The risk of mortality and functional deterioration increased with age. Certain conditions, such as diabetes, were associated both with mortality and functional deterioration; other conditions, such as cancer, were associated with mortality only, and arthritis was associated only with functional deterioration. Conclusions: Although overlap occurs, different clinical traits are associated with mortality, functional deterioration, and functional improvement. ADL stages might aid physical medicine and rehabilitation clinicians and researchers in developing and monitoring disability management strategies targeted to maintaining and enhancing self-care among community-dwelling older people. C1 [Stineman, Margaret G.; Kurichi, Jibby E.; Zhang, Zi; Pan, Qiang; Xie, Dawei] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Stineman, Margaret G.] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Zhang, Guangyu] Univ Maryland, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. [Streim, Joel E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Streim, Joel E.] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network VISN 4, Philadelphia, PA USA. RP Stineman, MG (reprint author), 423 Guardian Dr,904 Blockley Hall, Philadelphia, PA 19104 USA. EM mstinema@exchange.upenn.edu FU nonprofit/government agencies, NIA [R01 AG032420-01A1] FX grant support for research from nonprofit/government agencies, NIA, grant (#R01 AG032420-01A1) NR 46 TC 11 Z9 11 U1 4 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAY PY 2013 VL 5 IS 5 BP 360 EP 371 DI 10.1016/j.pmrj.2013.02.008 PG 12 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 156SO UT WOS:000319844400002 PM 23454447 ER PT J AU Liang, CL Han, S AF Liang, Chiawen Lucy Han, Steve TI Neuromuscular Junction Disorders SO PM&R LA English DT Article ID EATON-MYASTHENIC-SYNDROME; REPETITIVE NERVE-STIMULATION; GRAVIS; ELECTROMYOGRAPHY; EPIDEMIOLOGY; DIAGNOSIS; MUSCLES AB Disorders of the neuromuscular junction, such as myasthenia gravis and Lambert-Eaton myasthenic syndrome, constitute an important and treatable class of diseases. Both disorders are typically caused by an immunologically mediated attack on discrete components of the neuromuscular junction, compromise the efficacy of neurotransmitter transmission, and produce clinically distinct syndromes of fatigable muscle weakness. Although the history, clinical examination, and routine antibody testing can be diagnostic in many cases, specialized neurophysiological tests, such as repetitive nerve stimulation and single-fiber electromyography, are essential tools in the diagnostic evaluation of patients with more complicated or atypical conditions. In this review, we introduce primary disorders of the neuromuscular junction, and discuss the salient clinical and laboratory workup appropriate for recognizing these disorders, and the typical findings seen on electrodiagnostic testing with repetitive nerve stimulation and single-fiber electromyography. C1 [Liang, Chiawen Lucy] CNS Multispecialty Clin, Wellesley, MA 02481 USA. [Han, Steve] Massachusetts Gen Hosp, Dept Neurol, Neuromuscular Div, Boston, MA 02114 USA. RP Liang, CL (reprint author), CNS Multispecialty Clin, 65 Walnut St,Suite 150, Wellesley, MA 02481 USA. EM lucypmr@gmail.com FU American Academy of Neurology/ALS Association Career Development Award; Harvard Catalyst KL2 MeRIT award FX Disclosures outside this publication: grants, American Academy of Neurology/ALS Association Career Development Award; Harvard Catalyst KL2 MeRIT award NR 29 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAY PY 2013 VL 5 IS 5 SU S BP S81 EP S88 DI 10.1016/j.pmrj.2013.03.016 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 156SQ UT WOS:000319844600012 PM 23524069 ER PT J AU Di Leone, BAL Vogt, D Gradus, JL Street, AE Giasson, HL Resick, PA AF Di Leone, Brooke A. L. Vogt, Dawne Gradus, Jaimie L. Street, Amy E. Giasson, Hannah L. Resick, Patricia A. TI Predictors of Mental Health Care Use Among Male and Female Veterans Deployed in Support of the Wars in Afghanistan and Iraq SO PSYCHOLOGICAL SERVICES LA English DT Article DE veteran; mental health; gender; military; service use ID POSTTRAUMATIC STRESS SYMPTOMATOLOGY; WOMEN VETERANS; ADMINISTRATION CARE; MILITARY SERVICE; SAMPLE; RISK; QUESTIONNAIRE; STRENGTHS; BARRIERS; SEEKING AB What factors predict whether Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans who need mental health care receive that care? The present research examined factors associated with a need for care, sociodemographic characteristics, deployment experiences, and perceptions of care as gender-specific predictors of overall mental health care use and Veterans Affairs (VA) mental health care use for male and female OEF/OIF veterans (N = 1,040). Only veterans with a probable need for mental health care, as determined by scores on self-report measures of mental health symptomatology, were included in the sample. Overall, predictors of service use were similar for women and men. A notable exception was the finding that lower income predicted use of both overall and VA mental health care for women, but not men. In addition, sexual harassment was a unique predictor of VA service use for women, whereas non-White race was predictive of VA service use for men only. Knowledge regarding the factors that are associated with use of mental health care (broadly and at VA) is critical to ensuring that veterans who need mental health care receive it. C1 [Di Leone, Brooke A. L.; Vogt, Dawne; Gradus, Jaimie L.; Street, Amy E.; Giasson, Hannah L.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Di Leone, Brooke A. L.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Vogt, Dawne; Gradus, Jaimie L.; Street, Amy E.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Di Leone, BAL (reprint author), VA Boston HCS, Ctr Org Leadership & Management Res 152M, 150 South Huntington Ave, Boston, MA 02130 USA. EM brooke.dileone@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 NR 35 TC 13 Z9 13 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2013 VL 10 IS 2 SI SI BP 145 EP 151 DI 10.1037/a0032088 PG 7 WC Psychology, Clinical SC Psychology GA 156DW UT WOS:000319802300002 PM 23730960 ER PT J AU Ben Barnes, J Nickerson, A Adler, AB Litz, BT AF Ben Barnes, J. Nickerson, Angela Adler, Amy B. Litz, Brett T. TI Perceived Military Organizational Support and Peacekeeper Distress: A Longitudinal Investigation SO PSYCHOLOGICAL SERVICES LA English DT Article DE stress; posttraumatic stress; perceived organizational support; peacekeeping; structural equation modeling ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; SOCIAL SUPPORT; DEPRESSION; SYMPTOMS; PTSD; IRAQ; SYMPTOMATOLOGY; RESILIENCE; TRAUMA AB Many professions vital to the safety of society require workers to face high magnitude and potentially traumatizing events. Because this routine exposure can cause high levels of stress in workers, it is important to investigate factors that contribute to both risk of posttraumatic stress disorder (PTSD), and healthy responses to stress. Although some research has found social support to mitigate the effects of posttraumatic stress symptoms, scant research has investigated organizational support. The aim of the present study is to investigate the temporal relationship between stress symptoms and perceived organizational support in a sample of 1,039 service members deployed to the peacekeeping mission to Kosovo. Participants completed self-report measures of stress symptoms and perceived organizational support at 4 study time points. Bivariate latent difference score structural equation modeling was utilized to examine the temporal relationship among stress and perceived organizational support. In general, across the 4 time points, latent PCL scores evidenced a salient and negative relationship to subsequent POS latent difference scores. However, no significant relationship was found between latent POS variables and subsequent PCL latent difference scores. Findings suggest that prior stress symptoms are influencing service member's perceptions of the supportiveness of their organization such that increased prior stress is associated with worsening perceptions of support. These results illustrate that targeting stress directly may potentiate the positive influence of organizational support and that institutional support programs should be adapted to better account for the negative biases increased distress may encourage. C1 [Ben Barnes, J.; Litz, Brett T.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Nickerson, Angela] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia. [Adler, Amy B.] Walter Reed Army Inst Res, US Army Med Res Unit Europe, Heidelberg, Germany. [Litz, Brett T.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. RP Litz, BT (reprint author), VA Boston Healthcare Syst, Vet Epidemiol Res & Informat Ctr, 150 South Huntington Ave 116-B4, Boston, MA 02130 USA. EM brett.litz@va.gov NR 50 TC 0 Z9 0 U1 2 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2013 VL 10 IS 2 SI SI BP 177 EP 185 DI 10.1037/a0032607 PG 9 WC Psychology, Clinical SC Psychology GA 156DW UT WOS:000319802300006 ER PT J AU Lehavot, K Der-Martirosian, C Simpson, TL Sadler, AG Washington, DL AF Lehavot, Keren Der-Martirosian, Claudia Simpson, Tracy L. Sadler, Anne G. Washington, Donna L. TI Barriers to Care for Women Veterans With Posttraumatic Stress Disorder and Depressive Symptoms SO PSYCHOLOGICAL SERVICES LA English DT Article DE women veterans; posttraumatic stress disorder; depression; barriers to care; health care ID HEALTH ADMINISTRATION PATIENTS; FEMALE VETERANS; RANDOMIZED-TRIAL; MEDICAL ILLNESS; SERVICE USE; VA; AFFAIRS; IRAQ; AFGHANISTAN; PTSD AB As the number of women veterans continues to rise, an issue of concern is whether those with mental health symptoms experience disproportionate barriers to care. The purpose of this study was to examine unmet medical needs and barriers to health care among women veterans who screened positive for lifetime posttraumatic stress disorder (PTSD), current depressive symptoms, both or neither. Using the National Survey of Women Veterans dataset (N = 3,593), we compared women veterans corresponding to these 4 groups on whether they had unmet medical needs in the past year, reasons for unmet needs, and barriers to using VA care for those not currently doing so. The majority of women veterans who screened positive for both PTSD and depressive symptoms had unmet medical care needs in the prior 12 months (59%), compared to 30% of women with PTSD symptoms only, 18% of those with depressive symptoms only, and 16% of women with neither set of symptoms. Among those reporting unmet medical needs (n = 840), those with both PTSD and depressive symptoms were more likely than the other groups to identify affordability as a reason for going without or delaying care. Among women veterans not using VA health care (n = 1,677), women with both PTSD and depressive symptoms were more likely to report not knowing if they were eligible for VA benefits and were less likely to have health insurance to cover care outside of the VA. These data highlight specific areas of vulnerability of women veterans with comorbid PTSD and depressive symptoms and identify areas of concern as VA and other health facilities work to ensure equitable access to care. C1 [Lehavot, Keren; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Der-Martirosian, Claudia; Washington, Donna L.] Ctr Excellence Study Healthcare Provider Behav, VA Greater Los Angeles Hlth Serv Res & Dev, Sepulveda, CA USA. [Simpson, Tracy L.] Univ Washington, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98195 USA. [Sadler, Anne G.] Univ Iowa, Carver Coll Med, Iowa City VA Med Ctr, Iowa City, IA 52242 USA. [Sadler, Anne G.] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. [Washington, Donna L.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Lehavot, K (reprint author), 1660 S Columbian Way S-116-POC, Seattle, WA 98108 USA. EM klehavot@uw.edu NR 46 TC 6 Z9 6 U1 2 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2013 VL 10 IS 2 SI SI BP 203 EP 212 DI 10.1037/a0031596 PG 10 WC Psychology, Clinical SC Psychology GA 156DW UT WOS:000319802300009 PM 23730964 ER PT J AU Simpson, TL Balsam, KF Cochran, BN Lehavot, K Gold, SD AF Simpson, Tracy L. Balsam, Kimberly F. Cochran, Bryan N. Lehavot, Keren Gold, Sari D. TI Veterans Administration Health Care Utilization Among Sexual Minority Veterans SO PSYCHOLOGICAL SERVICES LA English DT Article DE veterans; health care utilization; lesbian; gay; bisexual ID HATE-CRIME VICTIMIZATION; BEHAVIORAL-MODEL; BISEXUAL ADULTS; STRESS-DISORDER; PTSD CHECKLIST; SERVICES USE; ACCESS; GAY; WOMEN; PREVALENCE AB According to recent census reports, nearly a million veterans have a same-sex partner, yet little is known about them or their use of Veterans Health Care Administration (VHA) services. Gay, lesbian, and bisexual (GLB) veterans recruited from the community (N = 356) completed an on-line survey to assess their rates of VHA utilization and whether they experience specific barriers to accessing VHA services. Andersen's model of health care utilization was adapted to provide an analytic and conceptual framework. Overall, 45.5% reported lifetime VHA utilization and 28.7% reported past-year VHA utilization. Lifetime VHA health care utilization was predicted by positive service connection, positive screen for both posttraumatic stress disorder (PTSD) and depression, and history of at least one interpersonal trauma during military service related to respondent's GLB status. Past-year VHA health care utilization was predicted by female gender, positive service connection, positive screen for both PTSD and depression, lower physical functioning, a history of military interpersonal trauma related to GLB status, and no history of stressful experiences initiated by the military to investigate or punish GLB status. Rates of VHA utilization by GLB veterans in this sample are comparable to those reported by VHA Central Office for all veterans. Of those who utilized VHA services, 33% reported open communication about their sexual orientation with VHA providers. Twenty-five percent of all participants reported avoiding at least one VHA service because of concerns about stigma. Stigma and lack of communication between GLB veterans and their providers about sexual orientation are areas of concern for VHA. C1 [Simpson, Tracy L.; Lehavot, Keren; Gold, Sari D.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Simpson, Tracy L.; Lehavot, Keren; Gold, Sari D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Balsam, Kimberly F.] Univ Washington, Dept Social Work, Seattle, WA 98195 USA. [Cochran, Bryan N.] Univ Montana, Dept Psychol, Missoula, MT 59812 USA. RP Simpson, TL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM tracy.simpson@va.gov NR 45 TC 16 Z9 16 U1 3 U2 23 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2013 VL 10 IS 2 SI SI BP 223 EP 232 DI 10.1037/a0031281 PG 10 WC Psychology, Clinical SC Psychology GA 156DW UT WOS:000319802300011 PM 23730965 ER PT J AU Macdonald, A Greene, CJ Torres, JG Frueh, BC Morland, LA AF Macdonald, Alexandra Greene, Carolyn J. Torres, Jennifer G. Frueh, B. Christopher Morland, Leslie A. TI Concordance Between Clinician-Assessed and Self-Reported Symptoms of Posttraumatic Stress Disorder Across Three Ethnoracial Groups SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; diagnostic assessment; cultural; ethnic minorities ID ADMINISTERED PTSD SCALE; ASIAN-AMERICAN; MENTAL-HEALTH; ANXIETY DISORDERS; COLLEGE-STUDENTS; NONINFERIORITY; VETERANS AB Posttraumatic stress disorder (PTSD) is a significant health problem that affects people from all ethnoracial groups. In the United States, investigators have found that minority groups, particularly Asian Americans, are more likely to withdraw from treatment and to display poor health treatment outcomes compared with Caucasians. Despite the extant research regarding ethnicity and treatment, limited research exists focusing on the relationship between ethnicity and the assessment of mental health symptoms. Previous literature has found that Asian Americans may underreport mental health symptoms. Relatively less empirical work has been conducted with indigenous populations, especially those of the Pacific Islands, such as Native Hawaiians, Samoans, and Tahitians. Questions remain as to whether the method of assessment may influence symptom reporting. For example, researchers have not studied whether or not clinician-assessed ratings of mental health symptoms differ from self-report measures. The current study examined the concordance between clinician-assessed and self-reported ratings of PTSD severity in male veterans with PTSD who identified themselves as Asian American, Native Hawaiian/Pacific Islander, or Caucasian. Results suggest moderate concordance between clinician-administered and self-report PTSD assessments. Findings from this study can be used to develop more accurate methods of capturing PTSD symptoms among Asian Americans, Native Hawaiians/Pacific Islanders, and other minority groups. C1 [Macdonald, Alexandra] VA Boston Hlth Care Syst, Boston, MA USA. [Macdonald, Alexandra] Boston Univ, Sch Med, Boston, MA 02215 USA. [Greene, Carolyn J.] Dept Vet Affairs Palo Hlth Care Syst, Natl Ctr PTSD, Disseminat & Training Div, Palo Alto, CA USA. [Greene, Carolyn J.] Dept Vet Affairs Pacific Isl Hlth Care Syst, Natl Ctr PTSD, Pacific Isl Div, Honolulu, HI USA. [Torres, Jennifer G.] VA Boston Hlth Care Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Morland, Leslie A.] Dept Vet Affairs Pacific Isl Hlth Care Syst, Natl Ctr PTSD, Pacific Isl Div, Honolulu, HI USA. RP Macdonald, A (reprint author), VA Boston Hlth Care Syst, 150 South Huntington Ave, Jamaica Plain, MA 02130 USA. EM alexandra.macdonald@va.gov NR 42 TC 6 Z9 6 U1 2 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAY PY 2013 VL 5 IS 3 BP 201 EP 208 DI 10.1037/a0031879 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 149GU UT WOS:000319307800001 ER PT J AU Charney, ME Keane, TM AF Charney, Meredith E. Keane, Terence M. TI The Psychological, Psychosocial, and Physical Health Status of HIV-Positive Refugees: A Comparative Analysis SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE HIV; refugees; trauma ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOMETRIC PROPERTIES; ANTIRETROVIRAL MEDICATION; MENTAL-HEALTH; COMORBIDITY; PREDICTORS; CHECKLIST; ADHERENCE; EVENTS; PTSD AB Refugees living with HIV are a relatively new group being resettled in the United States. In an effort to more fully understand the current status of refugees living with HIV, 84 HIV-positive adults including 26 refugees, 25 Puerto Rican individuals, and 33 individuals born in the U.S. were interviewed. We assessed psychological, psychosocial, and physical health domains across these groups to collect comparative information on the status of HIV-positive refugees. Results revealed that HIV-positive refugee individuals experienced greater problems in functioning than the other groups with the most significant differences observed in psychosocial functioning. These results underscore the importance of approaching refugee mental health from a multidisciplinary framework and have implications for the development of interventions for resettled HIV-positive refugees. C1 [Charney, Meredith E.; Keane, Terence M.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Charney, Meredith E.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Charney, ME (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM mecharney@partners.org NR 33 TC 0 Z9 0 U1 0 U2 1 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAY PY 2013 VL 5 IS 3 BP 209 EP 216 DI 10.1037/a0027506 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 149GU UT WOS:000319307800003 ER PT J AU Khan, S Cohen, D AF Khan, Sheraz Cohen, David TI Note: Magnetic noise from the inner wall of a magnetically shielded room SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID MAGNETOENCEPHALOGRAPHY; BRAIN AB We measured the thermal magnetic noise generated by the inner high-permeability wall of a magnetically shielded room. This room houses a magnetoencephalogram (MEG), which contains 102 "small" identical magnetometers. For the measurement, we created two large magnetometers by summing the outputs of 46 magnetometers equally on the helmet's left and right side, to look at the summed noise of the right and left vertical walls. From these summed outputs, we calculated the rms noise amplitude due to all six walls at the MEG location to be similar to 0.5 f T/root Hz at 100 Hz, only slowly rising with lower frequency. This is well below the system noise of each small MEG magnetometer, hence is negligible for the MEG. (C) 2013 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License. C1 [Khan, Sheraz] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Khan, Sheraz; Cohen, David] Harvard Univ, MIT, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Cohen, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. [Cohen, David] MIT, Francis Bitter Magnet Lab, Cambridge, MA 02139 USA. RP Cohen, D (reprint author), Harvard Univ, MIT, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. EM davcohen@mit.edu OI Khan, Sheraz/0000-0002-6792-3577 NR 10 TC 2 Z9 2 U1 0 U2 7 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD MAY PY 2013 VL 84 IS 5 AR 056101 DI 10.1063/1.4802845 PG 3 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 158UO UT WOS:000319999300075 PM 23742599 ER PT J AU Lee, J Quintana, FA Muller, P Trippa, L AF Lee, Jaeyong Quintana, Fernando A. Mueller, Peter Trippa, Lorenzo TI Defining Predictive Probability Functions for Species Sampling Models SO STATISTICAL SCIENCE LA English DT Article DE Species sampling prior; exchangeable partition probability functions; prediction probability functions ID NORMALIZED RANDOM MEASURES; BAYESIAN DENSITY-ESTIMATION; PRIORS; MIXTURES; REPRESENTATION; DISTRIBUTIONS; CONSISTENCY; PARTITIONS AB We review the class of species sampling models (SSM). In particular, we investigate the relation between the exchangeable partition probability function (EPPF) and the predictive probability function (PPF). It is straightforward to define a PPF from an EPPF, but the converse is not necessarily true. In this paper we introduce the notion of putative PPFs and show novel conditions for a putative PPF to define an EPPF. We show that all possible PPFs in a certain class have to define (unnormalized) probabilities for cluster membership that are linear in cluster size. We give a new necessary and sufficient condition for arbitrary putative PPFs to define an EPPF. Finally, we show posterior inference for a large class of SSMs with a PPF that is not linear in cluster size and discuss a numerical method to derive its PPF. Key words and phrases: Species sampling prior, exchangeable partition C1 [Lee, Jaeyong] Seoul Natl Univ, Dept Stat, Seoul 151747, South Korea. [Quintana, Fernando A.] Pontificia Univ Catolica Chile, Dept Estadist, Santiago 22, Chile. [Mueller, Peter] Univ Texas Austin, Dept Math, Austin, TX 78712 USA. [Trippa, Lorenzo] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Trippa, Lorenzo] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Lee, J (reprint author), Seoul Natl Univ, Dept Stat, Seoul 151747, South Korea. EM leejyc@gmail.com; quintana@mat.puc.cl; pmueller@math.utexas.edu; ltrippa@jimmy.harvard.edu FU National Research Foundation of Korea (NRF); Korea government (MEST) [2011-0030811]; FONDECYT [1100010]; NIH/NCI [CA075981] FX Jaeyong Lee was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0030811). Fernando Quintana was supported by Grant FONDECYT 1100010. Peter Muller was partially funded by Grant NIH/NCI CA075981. NR 38 TC 6 Z9 6 U1 3 U2 8 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 2013 VL 28 IS 2 BP 209 EP 222 DI 10.1214/12-STS407 PG 14 WC Statistics & Probability SC Mathematics GA 157JL UT WOS:000319892300004 PM 24368874 ER PT J AU Puram, SV Hasserjian, RP Faquin, WC Lin, HW Rocco, JW AF Puram, Sidharth V. Hasserjian, Robert P. Faquin, William C. Lin, Harrison W. Rocco, James W. TI Castleman disease presenting in the neck: Report of a case and review of the literature SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Review ID LYMPH-NODE HYPERPLASIA; HIV-INFECTION AB Castleman disease is a rare lymphoproliferative disorder with two primary subtypes that vary in presentation and course. Unicentric Castleman disease (UCD) presents as a solitary mass, most commonly in the mediastinum, and rarely in the head and neck. In contrast to multicentric Castleman disease (MCD), which features peripheral lymphadenopathy and numerous systemic symptoms, UCD is not typically associated with generalized symptoms. Here, we present an unusual case of UCD presenting as a slowly expanding, isolated neck mass in a 29-year-old woman. This case demonstrates the distinguishing clinical, radiologic, and histologic findings unique to UCD, which is often misdiagnosed as lymphoma or other malignant process. These findings stand in contrast to those observed in MCD patients, and hence, offer insight into the practical aspects of diagnosis and management of Castleman disease in the head and neck. Published by Elsevier Inc. C1 [Puram, Sidharth V.; Faquin, William C.; Lin, Harrison W.; Rocco, James W.] Massachusetts Eye & Ear Infirm, Div Head & Neck Surg, Dept Otolaryngol, Boston, MA 02114 USA. [Hasserjian, Robert P.; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rocco, James W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rocco, James W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Puram, SV (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM spuram@partners.org NR 19 TC 5 Z9 5 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAY-JUN PY 2013 VL 34 IS 3 BP 239 EP 244 DI 10.1016/j.amjoto.2012.11.007 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 141TJ UT WOS:000318749100011 PM 23375540 ER PT J AU Wyatt, GE Gomez, CA Hamilton, AB Valencia-Garcia, D Gant, LM Graham, CE AF Wyatt, Gail E. Gomez, Cynthia A. Hamilton, Alison B. Valencia-Garcia, Dellanira Gant, Larry M. Graham, Charles E. TI The Intersection of Gender and Ethnicity in HIV Risk, Interventions, and Prevention New Frontiers for Psychology SO AMERICAN PSYCHOLOGIST LA English DT Article DE HIV; gender; ethnicity; sociocultural; intersectionality ID AFRICAN-AMERICANS; POSITIVE WOMEN; UNITED-STATES; PUBLIC-HEALTH; IMMUNODEFICIENCY SYNDROME; SAN-FRANCISCO; SEXUAL-ABUSE; SELF-ESTEEM; BLACK-MEN; AIDS AB This article articulates a contextualized understanding of gender and ethnicity as interacting social determinants of HIV risk and acquisition, with special focus on African Americans and Hispanics/Latinos-2 ethnic groups currently at most risk for HIV/AIDS acquisition in the United States. First, sex and gender are defined. Second, a conceptual model of gender, ethnicity, and HIV risk and resilience is presented. Third, a historical backdrop of gender and ethnic disparities is provided, with attention to key moments in history when notions of the intersections between gender, ethnicity, and HIV have taken important shifts. Finally, new frontiers in psychology are presented, with recommendations as to how psychology as a discipline can better incorporate considerations of gender and ethnicity as not only HIV risk factors but also as potential avenues of resilience in ethnic families and communities. Throughout the article, we promulgate the notion of a syndemic intersectional approach, which provides a critical framework for understanding and building the conditions that create and sustain overall community health by locating gendered lived experiences and expectations within the layered conceptual model ranging from the biological self to broader societal structures that define and constrain personal decisions, behaviors, actions, resources, and consequences. For ethnic individuals and populations, health disparities, stress and depression, substance abuse, and violence and trauma are of considerable concern, especially with regard to HIV risk, infection, and treatment. The conceptual model poses new frontiers for psychology in HIV policy, research, interventions, and training. C1 [Wyatt, Gail E.; Hamilton, Alison B.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Gomez, Cynthia A.; Valencia-Garcia, Dellanira] San Francisco State Univ, Hlth Equ Inst, San Francisco, CA USA. [Hamilton, Alison B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gant, Larry M.; Graham, Charles E.] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. RP Wyatt, GE (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,38-232 NPI,Box 175919, Los Angeles, CA 90024 USA. EM gwyatt@mednet.ucla.edu NR 108 TC 12 Z9 13 U1 7 U2 27 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD MAY-JUN PY 2013 VL 68 IS 4 SI SI BP 247 EP 260 DI 10.1037/a0032744 PG 14 WC Psychology, Multidisciplinary SC Psychology GA 146FS UT WOS:000319075900005 PM 23688092 ER PT J AU Willers, H Azzoli, CG Santivasi, WL Xia, F AF Willers, Henning Azzoli, Christopher G. Santivasi, Wil L. Xia, Fen TI Basic Mechanisms of Therapeutic Resistance to Radiation and Chemotherapy in Lung Cancer SO CANCER JOURNAL LA English DT Review DE Lung cancer; cytotoxic therapies; DNA repair pathways ID GROWTH-FACTOR RECEPTOR; HOMOLOGOUS RECOMBINATION REPAIR; CISPLATIN-BASED CHEMOTHERAPY; SQUAMOUS-CELL CARCINOMA; DNA-REPAIR; TUMOR VOLUME; PHASE-III; POLY(ADP-RIBOSE) POLYMERASE; ADJUVANT CHEMOTHERAPY; CONCURRENT CHEMORADIATION AB In recent years, there have been multiple breakthroughs in our understanding of lung cancer biology. Despite significant advances in molecular targeted therapies, DNA-damaging cytotoxic therapies will remain the mainstay of lung cancer management for the near future. Similar to the concept of personalized targeted therapies, there is mounting evidence that perturbations in DNA repair pathways are common in lung cancers, altering the resistance of the affected tumors to many chemotherapeutics as well as radiation. Defects in DNA repair may be due to a multitude of mechanisms including gene mutations, epigenetic events, and alterations in signal transduction pathways such as epidermal growth factor receptor and phosphoinositide 3-kinase/AKT. Functional biomarkers that assess the subcellular localization of central repair proteins in response to DNA damage may prove useful for individualization of cytotoxic therapies including poly(adenosine diphosphate-ribose) polymerase inhibitors. A better mechanistic understanding of cellular sensitivity and resistance to DNA damaging agents should facilitate the development of novel, individualized treatment approaches. Absolute resistance to radiation therapy, however, does not exist. To some extent, radiation therapy will always have to remain unselective and indiscriminant to eradicate persistent, drug-resistant tumor stem cell pools. C1 [Willers, Henning] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol,Med Sch, Boston, MA 02114 USA. [Azzoli, Christopher G.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol,Dept Med,Med Sch, Boston, MA 02114 USA. [Santivasi, Wil L.; Xia, Fen] Ohio State Univ, Coll Med, Dept Radiat Oncol, Columbus, OH 43210 USA. RP Xia, F (reprint author), Ohio State Univ, Coll Med, Dept Radiat Oncol, Columbus, OH 43210 USA. EM Fen.Xia@osumc.edu RI Xia, Fen/G-3708-2013; Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer [NCI P50 CA090578]; Proton Therapy Research and Treatment Center [C06 CA059267] FX H. W. is currently receiving partial support from the Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, NCI P50 CA090578, and the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. F. X. is currently receiving R01 NIH NCI CA163838. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 101 TC 26 Z9 29 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAY-JUN PY 2013 VL 19 IS 3 BP 200 EP 207 DI 10.1097/PPO.0b013e318292e4e3 PG 8 WC Oncology SC Oncology GA 152UV UT WOS:000319557700004 PM 23708066 ER PT J AU Cottini, F Lautenschlaeger, T AF Cottini, Francesca Lautenschlaeger, Tim TI Predictors of Biomarkers Guiding Targeted Therapeutic Strategies in Locally Advanced Lung Cancer SO CANCER JOURNAL LA English DT Review DE Biomarker; lung cancer; EGFR; KRAS; ALK; ERCC1; RPM1; review ID GROWTH-FACTOR-RECEPTOR; EML4-ALK FUSION GENE; PREVIOUSLY TREATED PATIENTS; VINORELBINE PLUS CISPLATIN; RANDOMIZED PHASE-II; ADJUVANT CHEMOTHERAPY; TYROSINE KINASE; DNA-REPAIR; PROGNOSTIC-SIGNIFICANCE; ACQUIRED-RESISTANCE AB Lung cancer accounts for the majority of cancer-related deaths worldwide. We sought out to summarize the current state of molecular predictors for response and toxicity in locally advanced lung cancer. Several changes have been introduced in recent years in the standard-of-care treatment of advanced non-small cell lung cancer based on the identification of specific molecular alterations that determine response probability to certain therapies. Eligibility for these treatments is assessed by a biomarker test, evaluating if the molecular alteration is present or not in a patient's tumor. In particular, tissue testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations is currently recommended for certain patients with advanced non-small cell lung cancer, whereas excision repair cross-complementation group 1 and ribonucleotide reductase 1 as markers for outcome after platinum and gemcitabine therapy are promising but are currently not recommended outside a clinical trial. However, their application to the therapy of locally advanced disease is still mostly investigational. Moreover, additional candidate markers for response and toxicity for locally advanced lung cancer are under further investigation. C1 [Cottini, Francesca] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lautenschlaeger, Tim] Ohio State Univ, Dept Radiat Oncol, Columbus, OH 43210 USA. RP Lautenschlaeger, T (reprint author), Ohio State Univ, Dept Radiat Oncol, 410 W 12th Ave, Columbus, OH 43210 USA. EM TL@osumc.edu NR 86 TC 1 Z9 1 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD MAY-JUN PY 2013 VL 19 IS 3 BP 263 EP 271 DI 10.1097/PPO.0b013e318297216a PG 9 WC Oncology SC Oncology GA 152UV UT WOS:000319557700011 PM 23708073 ER PT J AU Pretorius, E Lipinski, B AF Pretorius, Etheresia Lipinski, Boguslaw TI Thromboembolic ischemic stroke changes red blood cell morphology SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Red blood cells; Thromboembolic ischemic stroke AB Background or Introduction: Stroke is one of the most debilitating diseases causing morbidity and mortality worldwide. During ischemic stroke, erythrocytes undergo oxidative and proteolytic changes resulting not only in inflammation but also in changes in cellular rheology. During the event, fibrin fibers, which are typically a fine net, clot abnormally to form a clot of dense matted deposits (DMDs). This atypical coagulum causes blood cells to be trapped in the mesh. Methods: Here we study red blood cell (RBC) ultrastructure in thromboembolic ischemic stroke using high resolution scanning electron microscopy. Results: We show that RBCs in patients change shape, with membrane extensions that form close interactions with the DMDs. Conclusions: We suggest that the RBC membrane changes and resulting DMD interactions play a pivotal role in the persistent presence of thrombi. This ultrastructural observation might open a renewed debate regarding possible additional structural and biochemical roles of RBCs in the circulatory system. (C) 2013 Elsevier Inc. All rights reserved. C1 [Pretorius, Etheresia] Univ Pretoria, Fac Hlth Sci, Dept Physiol, ZA-0007 Arcadia, South Africa. [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Pretorius, E (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Physiol, Private Bag x323, ZA-0007 Arcadia, South Africa. EM resia.pretorius@up.ac.za OI Pretorius, Etheresia/0000-0002-9108-2384 FU Medical Research Council of South Africa FX The Medical Research Council of South Africa funded the research of E. Pretorius. NR 5 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD MAY-JUN PY 2013 VL 22 IS 3 BP 241 EP 242 DI 10.1016/j.carpath.2012.11.005 PG 2 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 153YV UT WOS:000319639600009 PM 23312065 ER PT J AU Ekundayo, OJ Saver, JL Fonarow, GC Schwamm, LH Xian, Y Zhao, X Hernandez, AF Peterson, ED Cheng, EM AF Ekundayo, Olaniyi James Saver, Jeffrey L. Fonarow, Gregg C. Schwamm, Lee H. Xian, Ying Zhao, Xin Hernandez, Adrian F. Peterson, Eric D. Cheng, Eric M. TI Patterns of Emergency Medical Services Use and Its Association With Timely Stroke Treatment Findings From Get With the Guidelines-Stroke SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE emergency medical services; Get With the Guidelines-Stroke; stroke ID TRANSIENT ISCHEMIC ATTACK; TISSUE-PLASMINOGEN ACTIVATOR; HEALTH-CARE DASH; NORTH-CAROLINA; POPULATION; KNOWLEDGE; DELAY; INTERVENTION; STATEMENT; COMMUNITY AB Background-Prior studies found that only about half of stroke patients arrived at hospitals via emergency medical services (EMSs), yet since then, there have been efforts to increase public awareness that time is brain. Using contemporary Get With the Guidelines-Stroke data, we assessed nationwide EMS use by stroke patients. Methods and Results-We analyzed data from 204 591 patients with ischemic and hemorrhagic stroke admitted to 1563 Get With the Guidelines-Stroke participating hospitals with data on National Institute of Health Stroke Score and insurance status. Hospital arrival by EMSs was observed in 63.7% of patients. Older patients, those with Medicaid and Medicare insurance, and those with severe stroke were more likely to activate EMSs. In contrast, minority race and ethnicity and living in rural communities were associated with decreased odds of EMS use. EMS transport was independently associated with earlier arrival (onset-to-door time, <= 3 hours; adjusted odds ratio, 2.00; 95% confidence interval, 1.93-2.08), prompter evaluation (more patients with door-to-imaging time, <= 25 minutes; odds ratio, 1.89; 95% confidence interval, 1.78-2.00), more rapid treatment (more patients with door-to-needle time, <= 60 minutes; odds ratio, 1.44; 95% confidence interval, 1.28-1.63), and more eligible patients to be treated with tissue-type plasminogen activator if onset is <= 2 hours (67% versus 44%; odds ratio, 1.47; 95% confidence interval, 1.33-1.64). Conclusions-Although EMS use is independently associated with more rapid evaluation and treatment of stroke, more than one third of stroke patients fail to use EMSs. Interventions aimed at increasing EMS activation should target populations at risk, particularly younger patients and those of minority race and ethnicity. C1 [Ekundayo, Olaniyi James] Meharry Med Coll, Dept Family & Community Med, Nashville, TN 37208 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, UCLA Stroke Ctr, Los Angeles, CA USA. [Ekundayo, Olaniyi James; Saver, Jeffrey L.; Cheng, Eric M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Ahmanson UCLA Cardiomyopathy Ctr, Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Xian, Ying; Zhao, Xin; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Ekundayo, OJ (reprint author), Meharry Med Coll, Dept Family & Community Med, 1005 Dr DB. Todd Jr Blvd,Old Hosp Bldg,Ste C216, Nashville, TN 37208 USA. EM jekundayo@mmc.edu RI Hernandez, Adrian F./A-7818-2016 OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association (AHA); National Institutes of Health/National Institute of Neurological Disorders and Stroke [K23NS058571]; National Institutes of Health; Agency for Healthcare Research and Quality; AHA [0675060N] FX Drs Ekundayo, Fonarow, Saver, Xian, Hernandez, Peterson, and Cheng are supported by an award from the American Heart Association (AHA) Pharmaceutical Roundtable and David and Stevie Spina. Dr Cheng is supported by a career development award from National Institutes of Health/National Institute of Neurological Disorders and Stroke (K23NS058571). Dr Fonarow serves as a member of the AHA GWTG Steering Committee; receives research support from the National Institutes of Health (significant) and Agency for Healthcare Research and Quality (significant); and serves as a consultant to Novartis (significant). Dr Saver serves as a member of the GWTG Science Subcommittee; serves as a scientific consultant regarding trial design and conduct to CoAxia, Concentric Medical, Talacris, Ferrer, Photothera, Brainsgate, Sygnis, and Ev3; received lecture honoraria from Ferrer; and is an employee of the University of California, which holds a patent on retriever devices for stroke. Drs Zhao and Hernandez are members of the Duke Clinical Research Institute, which serves as the AHA GWTG data coordinating center. Dr Hernandez is a recipient of an AHA Pharmaceutical Roundtable grant (0675060N); has received a research grant from Johnson & Johnson; and has received honorarium from AstraZeneca and Amgen. Dr Peterson has received research grants from Lilly, Johnson & Johnson, Bristol-Myers Squibb, Sanofi-Aventis, and Merck-Schering Plough partnership. Dr Peterson serves as principle investigator of the Data Analytic Center for AHA GWTG. Dr Schwamm serves as chair of the AHA GWTG Steering Committee; serves as a consultant to the Research Triangle Institute and the Massachusetts Department of Public Health; and serves on the Steering Committee for Lundbeck's Desmoteplase in Acute Ischemic Stroke (DIAS4) clinical trial. NR 34 TC 26 Z9 26 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2013 VL 6 IS 3 BP 262 EP 269 DI 10.1161/CIRCOUTCOMES.113.000089 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 150LS UT WOS:000319392600006 PM 23633218 ER PT J AU Qian, F Fonarow, GC Smith, EE Xian, Y Pan, WQ Hannan, EL Shaw, BA Glance, LG Peterson, ED Eapen, ZJ Hernandez, AF Schwamm, LH Bhatt, DL AF Qian, Feng Fonarow, Gregg C. Smith, Eric E. Xian, Ying Pan, Wenqin Hannan, Edward L. Shaw, Benjamin A. Glance, Laurent G. Peterson, Eric D. Eapen, Zubin J. Hernandez, Adrian F. Schwamm, Lee H. Bhatt, Deepak L. TI Racial and Ethnic Differences in Outcomes in Older Patients With Acute Ischemic Stroke SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE disparities; outcome; race and ethnicity; stroke ID AMERICAN-HEART-ASSOCIATION; NORTHERN MANHATTAN STROKE; QUALITY-OF-CARE; GUIDELINES-STROKE; HEALTH-CARE; PLASMINOGEN-ACTIVATOR; MORTALITY; DISPARITIES; POPULATION; BLACKS AB Background-Little is known as to whether long-term outcomes of acute ischemic stroke (AIS) vary by race/ethnicity. Using the American Heart Association Get With The Guidelines-Stroke registry linked with Medicare claims data set, we examined whether 30-day and 1-year outcomes differed by race/ethnicity among older patients with AIS. Methods and Results-We analyzed 200 900 patients with AIS >65 years of age (170 694 non-Hispanic whites, 85.0%; 20 514 non-Hispanic blacks, 10.2%; 6632 Hispanics, 3.3%; 3060 non-Hispanic Asian Americans, 1.5%) from 926 US centers participating in the Get With The Guidelines-Stroke program from April 2003 through December 2008. Compared with whites, other racial and ethnic groups were on average younger and had a higher median score on the National Institutes of Health Stroke Scale. Whites had higher 30-day unadjusted mortality than other groups (white versus black versus Hispanic versus Asian=15.0% versus 9.9% versus 11.9% versus 11.1%, respectively). Whites also had higher 1-year unadjusted mortality (31.7% versus 28.6% versus 28.1% versus 23.9%, respectively) but lower 1-year unadjusted all-cause rehospitalization (54.7% versus 62.5% versus 60.0% versus 48.6%, respectively). After risk adjustment, Asian American patients with AIS had lower 30-day and 1-year mortality than white, black, and Hispanic patients. Relative to whites, black and Hispanic patients had higher adjusted 1-year all-cause rehospitalization (black: adjusted odds ratio, 1.28 [95% confidence interval, 1.21-1.37]; Hispanic: adjusted odds ratio, 1.22 [95% confidence interval, 1.11-1.35]), whereas Asian patients had lower odds (adjusted odds ratio, 0.83 [95% confidence interval, 0.74-0.94]). Conclusions-Among older Medicare beneficiaries with AIS, there were significant differences in long-term outcomes by race/ethnicity, even after adjustment for stroke severity, other prognostic variables, and hospital characteristics. C1 [Qian, Feng; Hannan, Edward L.; Shaw, Benjamin A.] SUNY Albany, Rensselaer, NY 12144 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Xian, Ying; Pan, Wenqin; Peterson, Eric D.; Eapen, Zubin J.; Hernandez, Adrian F.] Duke Univ, Durham, NC USA. [Glance, Laurent G.] Univ Rochester, Rochester, NY USA. [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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. RP Qian, F (reprint author), SUNY Albany, Sch Publ Hlth, Dept Hlth Policy Management & Behav, GEC Room 169,1 Univ Pl, Rensselaer, NY 12144 USA. EM fqian@albany.edu RI Smith, Eric/C-5443-2012; Hernandez, Adrian F./A-7818-2016 OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 NR 46 TC 22 Z9 22 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2013 VL 6 IS 3 BP 284 EP 292 DI 10.1161/CIRCOUTCOMES.113.000211 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 150LS UT WOS:000319392600009 PM 23680966 ER PT J AU Ko, DT Wijeysundera, HC Jackevicius, CA Yousef, A Wang, J Tu, JV AF Ko, Dennis T. Wijeysundera, Harindra C. Jackevicius, Cynthia A. Yousef, Altayyeb Wang, Julie Tu, Jack V. TI Diabetes Mellitus and Cardiovascular Events in Older Patients With Myocardial Infarction Prescribed Intensive-Dose and Moderate-Dose Statins SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute coronary syndrome; intensive-dose statins; new-onset diabetes mellitus ID ACUTE CORONARY SYNDROMES; MORTALITY PREDICTION RULES; HEART-DISEASE MORTALITY; LIPID-LOWERING THERAPY; ELDERLY-PATIENTS; ADMINISTRATIVE DATA; METAANALYSIS; ONTARIO; RISK; ASSOCIATION AB Background-Practice guidelines recommend intensive-dose statins for patients with acute coronary syndrome, but recent data about the risk of new-onset diabetes mellitus have raised concerns about its use. Our main objective was to evaluate the association between intensive statin therapy and new-onset diabetes mellitus in patients with myocardial infarction and to evaluate the association of intensive statin therapy with long-term adverse clinical outcomes. Methods and Results-A propensity score-matched cohort was created consisting of 17 080 patients with myocardial infarction aged >65 years old, hospitalized in Ontario, Canada, from 2004 to 2010. Clinical outcomes were compared in patients prescribed intensive-dose versus moderate-dose statins at hospital discharge. At 5 years, 13.6% of patients receiving intensive-dose statins and 13.0% of patients receiving moderate-dose statins had new-onset diabetes, which was not significantly different (P=0.19). By contrast, the 5-year rate of death or acute coronary syndrome was significantly lower at 44.8% in the intensive-dose statin group compared with 46.5% in the moderate-dose group (P=0.044). The reduction in combined clinical outcome was driven mainly by a significantly lower rate of acute coronary syndrome (P=0.039) associated with intensive-dose statins. No significant difference in mortality rates (34.8% in both groups) was observed between the treatment groups during the study period (P=0.89). Conclusions-In older patients with myocardial infarction, we found intensive-dose statin therapy to be effective in reducing repeat hospitalization for acute coronary syndrome. The rate of new-onset diabetes mellitus at long term was not significantly different between intensive-dose and moderate-dose statins. C1 [Ko, Dennis T.; Wijeysundera, Harindra C.; Jackevicius, Cynthia A.; Yousef, Altayyeb; Wang, Julie; Tu, Jack V.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Ko, Dennis T.; Wijeysundera, Harindra C.; Tu, Jack V.] Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Toronto, ON M4N 3M5, Canada. [Ko, Dennis T.; Wijeysundera, Harindra C.; Jackevicius, Cynthia A.; Tu, Jack V.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Pomona, CA USA. [Jackevicius, Cynthia A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Ko, DT (reprint author), Inst Clin Evaluat Sci G1 06, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM dennis.ko@ices.on.ca OI Ko, Dennis/0000-0001-6840-8051 FU Institute for Clinical Evaluative Sciences; Ontario Ministry of Health and Long-Term Care; Canadian Institutes of Health Research [102487]; Canada Research Chair in Health Services Research; Heart and Stroke Foundation of Ontario FX This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. The opinions, results and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by the Institute for Clinical Evaluative Sciences or the Ontario Ministry of Health and Long-term Care is intended or should be inferred.; The analysis of this study was supported by a Canadian Institutes of Health Research operating grant MOP (102487). Dr Ko is supported by a Canadian Institutes of Health Research New Investigator Award. Dr Tu is supported by a Canada Research Chair in Health Services Research and a Career Investigator Award from the Heart and Stroke Foundation of Ontario. NR 32 TC 20 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2013 VL 6 IS 3 BP 315 EP 322 DI 10.1161/CIRCOUTCOMES.111.000015 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 150LS UT WOS:000319392600013 PM 23674307 ER PT J AU Sternfeld, B LaCroix, A Caan, BJ Dunn, AL Newton, KM Reed, SD Guthrie, KA Booth-LaForce, C Sherman, KJ Cohen, L Freeman, MP Carpenter, JS Hunt, JR Roberts, M Ensrud, KE AF Sternfeld, Barbara LaCroix, Andrea Caan, Bette J. Dunn, Andrea L. Newton, Katherine M. Reed, Susan D. Guthrie, Katherine A. Booth-LaForce, Cathryn Sherman, Karen J. Cohen, Lee Freeman, Marlene P. Carpenter, Janet S. Hunt, Julie R. Roberts, Melanie Ensrud, Kristine E. TI Design and methods of a multi-site, multi-behavioral treatment trial for menopausal symptoms: The MsFLASH experience SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Vasomotor symptoms; Randomized controlled trial; Yoga; Exercise; Omega-3 fatty acids; Factorial design ID RANDOMIZED CONTROLLED-TRIAL; HEART-RATE-VARIABILITY; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; UNITED-STATES; HOT FLUSHES; HEALTH; YOGA; OMEGA-3-FATTY-ACIDS; TRANSITION AB Background: Behavioral strategies are recommended for menopausal symptoms, but little evidence exists regarding efficacy. Purpose: Describe design and methodology of a randomized controlled 3 by 2 factorial trial of yoga, exercise and omega-3 fatty acids. Methods: Women from three geographic areas with a weekly average of >= 14 hot flashes/night sweats, who met exclusion/inclusion criteria, were randomized to 12 weeks of: 1) yoga classes and daily home practice; 2) supervised, facility-based aerobic exercise training; or 3) usual activity. Women in each arm were further randomized to either omega-3 supplement or placebo. Standardized training, on-going monitoring, and site visits were adopted to ensure consistency across sites and fidelity to the intervention. Participant adherence to the intervention protocol was monitored continuously, and retention was actively encouraged by staff. Information on adverse events was systematically collected. Results: Of 7377 women who responded to mass mailings, 355 (4.8%) were randomized; mean age was 54.7 (sd = 3.7), 26.2% were African American, 81.7% were post-menopausal, and mean baseline frequency of daily hot flashes/night sweats was 7.6 (sd = 3.8). Adherence of >= 80% was 59% for yoga, 77% for exercise training, and 80% for study pills. Final week 12 data were collected from 95.2% Conclusions: Conducting a multi-site, multi-behavioral randomized trial for menopausal symptoms is challenging but feasible. Benefits included cost-effective study design, centralized recruitment, and methodologic standardization. (C) 2013 Elsevier Inc. All rights reserved. C1 [Sternfeld, Barbara; Caan, Bette J.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [LaCroix, Andrea; Guthrie, Katherine A.; Hunt, Julie R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Dunn, Andrea L.] Klein Buendel Inc, Denver, CO USA. [Newton, Katherine M.; Sherman, Karen J.] Grp Hlth Res Inst, Seattle, WA USA. [Reed, Susan D.] Univ Washington, Sch Med, Seattle, WA USA. [Booth-LaForce, Cathryn] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Cohen, Lee; Freeman, Marlene P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Roberts, Melanie] Natl Inst Fitness & Sport, Indianapolis, IN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, VA Med Ctr, Dept Med & Epidemiol, Minneapolis, MN 55455 USA. RP Sternfeld, B (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Barbara.sternfeld@kp.org FU National Institute of Aging (NIA); Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Center for Complementary and Alternative Medicine (NCCAM); Office of Research and Women's Health (ORWH); NIA At the Indiana University site [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Indiana Clinical and Translational Sciences Institute; National Institutes of Health, National Center for Research Resources [UL1 RR025761]; Clinical and Translational Sciences Award FX This study was supported by a cooperative agreement issued by the National Institute of Aging (NIA), in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Research and Women's Health (ORWH), and grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700 from the NIA At the Indiana University site, the project was funded in part with support from the Indiana Clinical and Translational Sciences Institute, funded in part by grant UL1 RR025761 from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award. NR 31 TC 14 Z9 14 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAY PY 2013 VL 35 IS 1 BP 25 EP 34 DI 10.1016/j.cct.2013.02.009 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 153YD UT WOS:000319637800004 PM 23462342 ER PT J AU Berge, EM Bowles, DW Flaig, TW Lam, ET Jimeno, A AF Berge, E. M. Bowles, D. W. Flaig, T. W. Lam, E. T. Jimeno, A. TI TIVOZANIB: PRACTICAL IMPLICATIONS FOR RENAL CELL CARCINOMA AND OTHER SOLID TUMORS SO DRUGS OF TODAY LA English DT Article DE Tivozanib; VEGFR-1 (FLT-1) inhibitors; VEGFR-2 (FLK-1/KDR) inhibitors; VEGFR-3 (FLT-4) inhibitors; TIVO ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; PHASE-III TRIAL; ANTITUMOR-ACTIVITY; DOUBLE-BLIND; LUNG-CANCER; RETROSPECTIVE ANALYSIS; SELECTIVE INHIBITOR; AXITINIB AG-013736; 1ST-LINE TREATMENT AB Tivozanib is a recently developed, small-molecule tyrosine kinase inhibitor with specific affinity for the vascular endothelial growth factor receptor (VEGFR) family of kinases. Given known relevance of VHL (Von Hippel-Lindau disease tumor suppressor) deregulation in the clear cell variant of renal cell carcinoma, renal cell carcinoma remains an area of interest and subject of recent registration trials with this approach. TIVO-1, a phase III study evaluating tivozanib versus sorafenib in the first-line setting, met its primary endpoint of progression-free survival (11.9 months for tivozanib vs. 9.1 months for sorafenib), with a manageable toxicity profile, leading to formal consideration of regulatory approval in this setting. This review focuses on the preclinical development, pharmacokinetics and early clinical activity of tivozanib in renal cell carcinoma and other solid tumors. C1 [Berge, E. M.; Bowles, D. W.; Flaig, T. W.; Lam, E. T.; Jimeno, A.] Univ Colorado, Sch Med, Div Med Oncol, Denver, CO USA. [Bowles, D. W.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Jimeno, A (reprint author), Univ Colorado, Sch Med, Div Med Oncol, 12801 East 17th Ave,MS 8117, Aurora, CO 80045 USA. EM antonio.jimeno@ucdenver.edu FU Novartis; GlaxoSmithKline; Pfizer; Bayer/Onyx; Genentech; Bristol-Myers Squibb; Argos; Exelixis FX T. Flaig sits on the advisory board of GTx, and has acted as a consultant for sanofi-aventis. he has received clinical trial funding from Novartis, GlaxoSmithKline, Pfizer, Bayer/Onyx and Genentech. E. Lam has received research funding from Bristol-Myers Squibb, Argos, Genentech and Exelixis. The other authors state no conflicts of interest. NR 78 TC 5 Z9 5 U1 0 U2 4 PU PROUS SCIENCE, SAU-THOMSON REUTERS PI BARCELONA PA 398 PROVENCA, 08025 BARCELONA, SPAIN SN 1699-3993 EI 1699-4019 J9 DRUG TODAY JI Drugs Today PD MAY PY 2013 VL 49 IS 5 BP 303 EP 315 DI 10.1358/dot.2013.49.5.1960218 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 155PC UT WOS:000319759400002 PM 23724410 ER PT J AU Jennesson, M van Eeghen, AM Caruso, PA Paolini, JL Thiele, EA AF Jennesson, Melanie van Eeghen, Agnies M. Caruso, Paul A. Paolini, Jan L. Thiele, Elizabeth A. TI Clobazam therapy of refractory epilepsy in tuberous sclerosis complex SO EPILEPSY RESEARCH LA English DT Article DE Epilepsy; Drug therapy; Anticonvulsants; Clobazam ID ADD-ON THERAPY; CHILDREN; EFFICACY; LAMOTRIGINE; EXPERIENCE AB Clobazam (CLB) was recently approved by the FDA, but has not been evaluated in tuberous sclerosis complex (TSC). We retrospectively reviewed a cohort of patients with TSC and refractory epilepsy who started CLB over a 5-year period. Clinical characteristics and number of tubers on MRI were assessed. Duration of therapy, therapeutic response and adverse events were recorded. CLB was prescribed in 29 adults and children of whom 72% were cognitively impaired, with a median age at seizure onset of 5 months. Mean duration of CLB therapy was 17.3 months with a 12 and 24-month estimated retention rate of 82% and 68%, respectively. Twenty patients (69%) reported a good response (>50% seizure reduction) at the end of the titration, and six patients (21%) remained good responders after 12 months of CLB therapy. Adverse events occurred in 13 patients, predominantly somnolence and behavioral disorders. One quarter of the responders reported improvement in behavior. No predictive factor for a good response could be identified. CLB appears to be a well-tolerated and valuable option for treatment of refractory epilepsy in TSC. (C) 2012 Published by Elsevier B.V. C1 [Jennesson, Melanie; van Eeghen, Agnies M.; Paolini, Jan L.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA. [Caruso, Paul A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Carol and James Herscot Center for Tuberous Sclerosis Complex; "association des Amis de l'American Memorial Hospital de Reims" (France) FX This study was supported by the Carol and James Herscot Center for Tuberous Sclerosis Complex.; Dr. Jennesson receives financial assistance from the "association des Amis de l'American Memorial Hospital de Reims" (France). NR 28 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAY PY 2013 VL 104 IS 3 BP 269 EP 274 DI 10.1016/j.eplepsyres.2012.10.010 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 150DC UT WOS:000319369400011 PM 23219029 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Chronic heart failure: a look through the rear view mirror SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID NATRIURETIC PEPTIDE; MORTALITY; MORBIDITY; DEATH C1 Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc Med,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc Med,Brigham & Womens Hosp, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 7 TC 6 Z9 6 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 MAY PY 2013 VL 34 IS 19 BP 1391 EP 1392 DI 10.1093/eurheartj/ehs363 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 151MN UT WOS:000319464700005 PM 23103661 ER PT J AU Murphy, SA AF Murphy, Sabina A. TI When 'digoxin use' is not the same as 'digoxin use': lessons from the AFFIRM trial SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID PROPENSITY SCORE C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Murphy, SA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. EM smurphy15@partners.org NR 9 TC 10 Z9 10 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 MAY PY 2013 VL 34 IS 20 BP 1465 EP 1467 DI 10.1093/eurheartj/eht087 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 151MQ UT WOS:000319465000005 PM 23592709 ER PT J AU Rice, TR Sher, L AF Rice, T. R. Sher, L. TI Killing in combat and suicide risk SO EUROPEAN PSYCHIATRY LA English DT Letter DE Suicide; Epidemiology; Suicide risk assessment; Veterans; Military combat; Aggression ID MENTAL-HEALTH SYMPTOMS; WAR VETERANS; IMPACT C1 [Rice, T. R.; Sher, L.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Sher, L.] James P Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Rice, TR (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM Timothy.Rice@mssm.edu NR 9 TC 3 Z9 3 U1 0 U2 5 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 MAY PY 2013 VL 28 IS 4 BP 261 EP 261 DI 10.1016/j.eurpsy.2012.10.001 PG 1 WC Psychiatry SC Psychiatry GA 152RL UT WOS:000319548700010 PM 23182848 ER PT J AU Cano, T Morales-Quezada, JL Bikson, M Fregni, F AF Cano, Thais Morales-Quezada, Jorge Leon Bikson, Marom Fregni, Felipe TI Methods to focalize noninvasive electrical brain stimulation: principles and future clinical development for the treatment of pain SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Editorial Material DE brain mapping; clinical practice; electrical stimulation; electrical stimulation therapy; neuronal plasticity; pain; transcranial direct current stimulation; transcranial magnetic stimulation ID MOTOR CORTEX; HD-TDCS; ELECTROTHERAPY; MODULATION C1 [Cano, Thais; Morales-Quezada, Jorge Leon; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Lab Neuromodulat, Boston, MA 02115 USA. [Cano, Thais; Morales-Quezada, Jorge Leon; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bikson, Marom] CUNY City Coll, Dept Biomed Engn, New York, NY 10031 USA. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Lab Neuromodulat, Boston, MA 02115 USA. EM fregni.felipe@mgh.harvard.edu NR 23 TC 6 Z9 6 U1 1 U2 7 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD MAY PY 2013 VL 13 IS 5 BP 465 EP 467 DI 10.1586/ERN.13.41 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 150EK UT WOS:000319372800002 PM 23621302 ER PT J AU Manchikanti, L Boswell, MV Hirsch, JA AF Manchikanti, Laxmaiah Boswell, Mark V. Hirsch, Joshua A. TI Lessons learned in the abuse of pain-relief medication: a focus on healthcare costs SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE abuse; adverse consequences; chronic pain; diversion; healthcare costs; lessons learned; misuse; opioid use; opioids ID CHRONIC NONCANCER PAIN; LOW-BACK-PAIN; PRESCRIPTION OPIOID ABUSE; PHYSICIANS ASIPP GUIDELINES; MASS-SPECTROMETRY LC/MS/MS; CHRONIC NONMALIGNANT PAIN; ILLICIT DRUG-USE; UNITED-STATES; OVERDOSE DEATHS; PRESCRIBING PATTERNS AB The increasing prevalence of chronic pain with its major societal impact and the escalating use of opioids in managing it, along with their misuse, abuse, associated fatalities and costs, are epidemics in modern medicine. Over the past two decades, multiple lessons have been learned addressing various issues of abuse. Multiple measures have already been incorporated and more are expected to be incorporated in the future, which in turn may curtail the abuse of drugs and reduce healthcare costs, but these measures may also jeopardize access to appropriate pain treatment. This manuscript describes the lessons learned from the misuse, abuse and diversion of opioids, escalating healthcare costs and the means to control this epidemic. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah; Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40202 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 126 TC 18 Z9 18 U1 2 U2 17 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD MAY PY 2013 VL 13 IS 5 BP 527 EP 544 DI 10.1586/ERN.13.33 PG 18 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 150EK UT WOS:000319372800014 PM 23621310 ER PT J AU Bhatia, RS Milford, CE Picard, MH Weiner, RB AF Bhatia, R. Sacha Milford, Creagh E. Picard, Michael H. Weiner, Rory B. TI An Educational Intervention Reduces the Rate of Inappropriate Echocardiograms on an Inpatient Medical Service SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE appropriate use criteria; feedback; resident education; transthoracic echocardiography ID APPROPRIATE USE CRITERIA; CARDIOLOGY FOUNDATION/AMERICAN SOCIETY; TRANSTHORACIC ECHOCARDIOGRAPHY; REMINDER MESSAGES; RANDOMIZED-TRIAL; PRIMARY-CARE; IMPROVEMENT; REFERRALS; FEEDBACK; QUALITY AB OBJECTIVES This study sought to prospectively study the impact of an appropriate use criteria (AUC)-based educational intervention on transthoracic echocardiography (TIE) ordering among house staff on the inpatient general internal medicine service at an academic medical center. BACKGROUND AUC for TIE were developed in response to concerns about inappropriate use of TIE. To date, educational interventions based on the AUC to reduce inappropriate use of TIT have not been prospectively studied. METHODS A prospective, time series analysis of an educational intervention was conducted and then compared with TIE ordering on the same medical service during a control period. The intervention consisted of: 1) a lecture to house staff on the 2011 AUC for TIE; 2) a pocket card that applied the AUC to common clinical scenarios; and 3) biweekly e-mail feedback regarding ordering behavior. TIE ordering was tracked over the intervention period on a daily basis and feedback reports were e-mailed at 2-week intervals. The primary outcome was the proportion of inappropriate and appropriate TIE ordered during the intervention period. RESULTS Of all TTEs ordered in the control and study periods, 99% and 98%, respectively, were classifiable using the 2011 AUC. During the study period, there was a 26% reduction in the number of TTE ordered per day compared with the number ordered during the control period (2.9 vs. 3.9 TIE, p < 0.001). During the study period, the proportion of inappropriate TIE was significantly lower (5% vs. 13%, p < 0.001) and the proportion of appropriate TIE was significantly higher (93% vs. 84%, p < 0.001). CONCLUSIONS A simple educational intervention produced a significant reduction in the proportion of inappropriate TIE and increased the proportion of appropriate TIT ordered on an inpatient academic medical service. This study provides a practical approach for using the AUC to reduce the number of inappropriate TIE. Further study in other practice environments is warranted. (J Am Coll Cardiol Img 2013;6:545-55) (C) 2013 by the American College of Cardiology Foundation C1 [Bhatia, R. Sacha; Milford, Creagh E.; Picard, Michael H.; Weiner, Rory B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org OI Picard, Michael/0000-0002-9264-3243 FU Massachusetts General Physicians Organization Clinical Innovation Award FX This study was funded by the Massachusetts General Physicians Organization Clinical Innovation Award. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 25 TC 43 Z9 43 U1 0 U2 1 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 MAY PY 2013 VL 6 IS 5 BP 545 EP 555 DI 10.1016/j.jcmg.2013.01.010 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 154CH UT WOS:000319648600002 PM 23582360 ER PT J AU Taiwo, B Hunt, PW Gandhi, RT Ellingson, A McKenna, M Jacobson, JM Gripshover, B Bosch, RJ AF Taiwo, Babafemi Hunt, Peter W. Gandhi, Rajesh T. Ellingson, Andrew McKenna, Matthew Jacobson, Jeffrey M. Gripshover, Barbara Bosch, Ronald J. TI CD8+T-Cell Activation in HIV-1-Infected Patients Experiencing Transient Low-level Viremia During Antiretroviral Therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 19th Conference on Retroviruses and Opportunistic Infections (CROI) CY MAR 05-08, 2012 CL Seattle, WA DE low level; viremia; blip; immune; activation; CD8(+) ID HIV-INFECTED PATIENTS; INTERMITTENT VIREMIA; IMMUNE ACTIVATION; VIRAL SUPPRESSION; DRUG-RESISTANCE; BLIPS; RECONSTITUTION; INDIVIDUALS; REPLICATION; RESERVOIR AB Transient low-level viremia (TLLV) of 50-400 HIV RNA copies per milliliter is common during antiretroviral therapy, but its pathogenesis, consequences, and optimal management are unclear. Heightened immune activation is associated with detrimental outcomes, including impaired CD4(+) T-cell reconstitution. Using CD38/HLA-DR expression on CD8(+) T cells measured in 2 large studies, we determined associations between TLLV and immune activation levels before, during, and after TLLV. We found that TLLV does not significantly change CD8(+) T-cell activation and that higher CD8(+) T-cell activation during viral suppression <50 copies per milliliter is associated with a modest increase in the risk of a subsequent TLLV. C1 [Taiwo, Babafemi] Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA. [Hunt, Peter W.] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA. [Ellingson, Andrew; McKenna, Matthew; Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Jacobson, Jeffrey M.] Drexel Univ, Coll Med, Div Infect Dis & HIV MED, Philadelphia, PA 19104 USA. [Gripshover, Barbara] Case Western Reserve Univ, Div Infect Dis & HIV MED, Cleveland, OH USA. RP Taiwo, B (reprint author), Northwestern Univ, Div Infect Dis, 645 N Michigan Ave,Suite 900, Chicago, IL 60611 USA. EM b-taiwo@northwestern.edu FU NIAID NIH HHS [U01 AI068636, UM1 AI069496, U01AI068636, UM1 AI069471, U01 AI068634, UM1 AI069412, U01AI68634] NR 25 TC 13 Z9 13 U1 0 U2 4 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 MAY 1 PY 2013 VL 63 IS 1 BP 101 EP 104 DI 10.1097/QAI.0b013e3182895af4 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 146SW UT WOS:000319112200023 PM 23392463 ER PT J AU Schmults, CD Karia, PS Carter, JB Han, JL Qureshi, AA AF Schmults, Chrysalyne D. Karia, Pritesh S. Carter, Joi B. Han, Jiali Qureshi, Abrar A. TI Factors Predictive of Recurrence and Death From Cutaneous Squamous Cell Carcinoma A 10-Year, Single-Institution Cohort Study SO JAMA DERMATOLOGY LA English DT Article ID ADJUVANT RADIOTHERAPY; SPECIMENS FORMALIN; SKIN EXCISION; RISK; METASTASES; SHRINKAGE; SURGERY; CANCER; NECK; HEAD AB Importance: Although most cases of cutaneous squamous cell carcinoma (CSCC) are easily cured with surgery or ablation, a subset of these tumors recur, metastasize, and cause death. We conducted the largest study of CSCC outcomes since 1968. Objective: To identify risk factors independently associated with poor outcomes in primary CSCC. Design: A 10-year retrospective cohort study. Setting: An academic hospital in Boston. Participants: Nine hundred eighty-five patients with 1832 tumors. Main Outcomes and Measures: Subhazard ratios for local recurrence, nodal metastasis, disease-specific death, and all-cause death adjusted for presence of known prognostic risk factors. Results: The median follow-up was 50 (range, 2-142) months. Local recurrence occurred in 45 patients (4.6%) during the study period; 36 (3.7%) developed nodal metastases; and 21 (2.1%) died of CSCC. In multivariate competing risk analyses, independent predictors for nodal metastasis and disease-specific death were a tumor diameter of at least 2 cm (subhazard ratios, 7.0 [95% CI, 2.2-21.6] and 15.9 [4.8-52.3], respectively), poor differentiation (6.1 [2.5-14.9] and 6.7 [2.7-16.5], respectively), invasion beyond fat (9.3 [2.8-31.1] and 13.0 [4.3-40.0], respectively), and ear or temple location (3.8 [1.1-13.4] and 5.9 [1.3-26.7], respectively). Perineural invasion was also associated with disease-specific death (subhazard ratio, 3.6 [95% CI, 1.1-12.0]), as was anogenital location, but few cases were anogenital. Overall death was associated with poor differentiation (subhazard ratio, 1.3 [95% CI, 1.1-1.6]) and invasion beyond fat (1.7 [1.1-2.8]). Conclusions and Relevance: Cutaneous squamous cell carcinoma carries a low but significant risk of metastasis and death. In this study, patients with CSCC had a 3.7% risk of metastasis and 2.1% risk of diseasespecific death. Tumor diameter of at least 2 cm, invasion beyond fat, poor differentiation, perineural invasion, and ear, temple, or anogenital location were risk factors associated with poor outcomes. Accurate risk estimation of outcomes from population-based data and clinical trials proving the utility of disease-staging modalities and adjuvant therapy is needed. C1 [Schmults, Chrysalyne D.; Karia, Pritesh S.; Han, Jiali; Qureshi, Abrar A.] Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Sch Med, Boston, MA 02115 USA. [Carter, Joi B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Schmults, CD (reprint author), Brigham & Womens Hosp, Dept Dermatol, 1153 Ctr St,Ste 4349, Jamaica Plain, MA 02130 USA. EM cschmults@partners.org NR 26 TC 52 Z9 52 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD MAY PY 2013 VL 149 IS 5 BP 541 EP 547 PG 7 WC Dermatology SC Dermatology GA 154JV UT WOS:000319672100005 PM 23677079 ER PT J AU Hamilton, JR Parvataneni, R Stuart, SE Chren, MM AF Hamilton, Jeffrey R. Parvataneni, Rupa Stuart, Sarah E. Chren, Mary-Margaret TI Rerecurrence 5 Years After Treatment of Recurrent Cutaneous Basal Cell and Squamous Cell Carcinoma SO JAMA DERMATOLOGY LA English DT Letter ID MOHS MICROGRAPHIC SURGERY C1 [Hamilton, Jeffrey R.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Parvataneni, Rupa; Stuart, Sarah E.; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, San Francisco, CA USA. RP Chren, MM (reprint author), Univ Calif San Francisco, Dept Dermatol, Mt Zion Canc Res Bldg,2340 Sutter St,Room N412,Ma, San Francisco, CA 94143 USA. EM chrenm@derm.ucsf.edu FU NIAMS NIH HHS [K24 AR052667, R01 AR054983] NR 5 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD MAY PY 2013 VL 149 IS 5 BP 616 EP 618 PG 4 WC Dermatology SC Dermatology GA 154JV UT WOS:000319672100026 PM 23677098 ER PT J AU Shive, M Bhatt, M Cantino, A Kvedar, J Jethwani, K AF Shive, Melissa Bhatt, Mehul Cantino, Andrew Kvedar, Joseph Jethwani, Kamal TI Perspectives on Acne: What Twitter Can Teach Health Care Providers SO JAMA DERMATOLOGY LA English DT Letter C1 [Shive, Melissa] Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA 94143 USA. [Shive, Melissa] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Bhatt, Mehul] Harvard Univ, Sch Business, Boston, MA 02163 USA. [Cantino, Andrew] Iterat Labs LLC, San Francisco, CA USA. [Kvedar, Joseph; Jethwani, Kamal] Dept Dermatol, Boston, MA USA. [Bhatt, Mehul] Harvard Univ, Sch Med, Boston, MA USA. [Kvedar, Joseph; Jethwani, Kamal] Partners Healthcare, Ctr Connected Hlth, Boston, MA USA. [Kvedar, Joseph; Jethwani, Kamal] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Jethwani, K (reprint author), Ctr Connected Hlth, 25 New Chardon St, Boston, MA 02114 USA. EM kjethwani@partners.org NR 5 TC 9 Z9 10 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD MAY PY 2013 VL 149 IS 5 BP 621 EP 622 PG 2 WC Dermatology SC Dermatology GA 154JV UT WOS:000319672100028 PM 23677100 ER PT J AU Liou, AP AF Liou, A. P. TI DIGESTIVE PHYSIOLOGY OF THE PIG SYMPOSIUM: G protein-coupled receptors in nutrient chemosensation and gastrointestinal hormone secretion SO JOURNAL OF ANIMAL SCIENCE LA English DT Article; Proceedings Paper CT 12th International Symposium on Digestive Physiology of Pigs CY MAY 29-JUN 01, 2012 CL Keystone, CO DE carbohydrate sensing; enteroendocrine; intestinal chemosensation; lipid sensing; protein sensing; taste receptors ID CALCIUM-SENSING RECEPTOR; GLUCAGON-LIKE PEPTIDE-1; CHAIN FATTY-ACIDS; EXTRACELLULAR CA2+-SENSING RECEPTOR; ENTEROENDOCRINE STC-1 CELLS; RAT SMALL-INTESTINE; STIMULATE CHOLECYSTOKININ SECRETION; BITTER TASTE RECEPTORS; MOUSE SMALL-INTESTINE; SWEET TASTE AB The gastrointestinal tract is a highly effective and efficient organ system that digests and absorbs nutrients, contributes to the regulation of glucose homeostasis, and signals postprandial satiety. A network of enteroendocrine cells orchestrates these events through the release of neuropeptide hormones secreted in response to the specific nutrient components within the intraluminal milieu. Nutrient chemosensing by these cells is mediated by cell membrane proteins that have been localized to hormone-producing cells. However, functional studies of the nutrient detection abilities of the endocrine cell population have been limited due to its rare and singly distributed cell type. Recent technological advances have enabled investigations with primary endocrine cells that promise to enhance our current understanding of enteroendocrine cell biology. This review focuses on a particular subset of chemosensing receptors, the G protein-coupled receptors (GPCR), that have been identified as putative nutrient sensors of the major macronutrients, lipids, proteins, and carbohydrates by enteroendocrine cells. The contributions of these receptors in directly activating and stimulating hormone secretion in several subsets of enteroendocrine cells will be discussed, based on evidence gathered by functional studies in animal models, in vitro studies in endocrine cell lines, and newly described findings in primary endocrine cells. Key insights in chemosensory detection and hormone secretion from enteroendocrine cells may help further the studies in larger animal models and guide the formulation of feed or supplements to influence the gastrointestinal signals regulating optimal food intake, absorptive capacity, and growth. C1 [Liou, A. P.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Liou, A. P.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Liou, AP (reprint author), Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. EM aliou@partners.org FU Lucta S. A. (Barcelona, Spain); American Society of Animal Science; Journal of Animal Science FX Based on a presentation at the preconference symposium titled "Gut Chemosensing: Integrating nutrition, gut function and metabolism in pigs" preceding the 12th International Symposium on Digestive Physiology of Pigs in Keystone, Colorado, May 29 to June 1, 2012, with publication sponsored by Lucta S. A. (Barcelona, Spain), the American Society of Animal Science, and the Journal of Animal Science. NR 107 TC 9 Z9 10 U1 2 U2 25 PU AMER SOC ANIMAL SCIENCE PI CHAMPAIGN PA PO BOX 7410, CHAMPAIGN, IL 61826-7410 USA SN 0021-8812 EI 1525-3163 J9 J ANIM SCI JI J. Anim. Sci. PD MAY PY 2013 VL 91 IS 5 BP 1946 EP 1956 DI 10.2527/jas.2012-5910 PG 11 WC Agriculture, Dairy & Animal Science SC Agriculture GA 154TA UT WOS:000319697600003 PM 23230119 ER PT J AU Kaji, I Akiba, Y Kaunitz, JD AF Kaji, I. Akiba, Y. Kaunitz, J. D. TI DIGESTIVE PHYSIOLOGY OF THE PIG SYMPOSIUM: Involvement of gut chemosensing in the regulation of mucosal barrier function and defense mechanisms SO JOURNAL OF ANIMAL SCIENCE LA English DT Article; Proceedings Paper CT 12th International Symposium on Digestive Physiology of Pigs CY MAY 29-JUN 01, 2012 CL Keystone, CO DE anion secretion; bicarbonate; duodenum; enteroendocrine cells; glucagon-like peptides; serotonin ID DUODENAL ENTEROENDOCRINE CELLS; INTESTINAL EPITHELIUM; BICARBONATE SECRETION; ENDOCRINE-CELLS; RAT DUODENUM; PEPTIDASE-IV; BLOOD-FLOW; RECEPTOR; GUSTDUCIN; RELEASE AB Meal ingestion is followed by release of numerous hormones from enteroendocrine cells interspersed among the epithelial cells lining the intestine. Recently, the de-orphanization of G protein-coupled receptor (GPCR)-type nutrient receptors, expressed on the apical membranes of enteroendocrine cells, has suggested a plausible mechanism whereby luminal nutrients trigger the release of gut hormones. Activation of nutrient receptors triggers intracellular signaling mechanisms that promote exocytosis of hormone-containing granules into the submucosal space. Hormones released by foregut enteroendocrine cells include the glucagon-like peptides (GLP) affecting glycemic control (GLP-1) and releasing proproliferative, hypertrophy-inducing growth factors (GLP-2). The foregut mucosa, being exposed to pulses of concentrated HCl, is protected by a system of defense mechanisms, which includes epithelial bicarbonate and mucus secretion and augmentation of mucosal blood flow. We have reported that luminal co-perfusion of AA with nucleotides in anesthetized rats releases GLP-2 into the portal vein, associated with increased bicarbonate and mucus secretion and mucosal blood flow. The GLP-2 increases bicarbonate secretion via release of vasoactive intestinal peptide (VIP) from myenteric nerves. Luminal bile acids also release gut hormones due to activation of the bile-acid receptor known as G Protein-Coupled Receptor (GPR) 131, G Protein Bile Acid Receptor (GPBAR) 1, or Takeda G Protein-Coupled Receptor (TGR) 5, also expressed on enteroendocrine cells. The GLP are metabolized by dipeptidyl peptidase IV (DPPIV), an enzyme of particular interest to pharmaceutical, because its inhibition increases plasma concentrations of GLP-1 to treat diabetes. We have also reported that DPPIV inhibition enhances the secretory effects of nutrient-evoked GLP-2. Understanding the release mechanism and the metabolic pathways of gut hormones is of potential utility to the formulation of feedstuff additives that, by increasing nutrient absorption due to increased mucosal mass, can increase yields. C1 [Kaji, I.; Akiba, Y.; Kaunitz, J. D.] Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst, WLAVA Med Ctr, Los Angeles, CA 90095 USA. [Kaji, I.; Akiba, Y.; Kaunitz, J. D.] Univ Calif Los Angeles, David Geffen Sch Med, Brentwood Biomed Res, Los Angeles, CA 90095 USA. [Kaji, I.; Akiba, Y.; Kaunitz, J. D.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Kaji, I.; Akiba, Y.; Kaunitz, J. D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Kaji, I.] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan. RP Kaunitz, JD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst, WLAVA Med Ctr, Los Angeles, CA 90095 USA. EM jake@ucla.edu FU Lucta S.A. (Barcelona, Spain); American Society of Animal Science; Journal of Animal Science; Japan Society for the Promotion of Science; Ajinomoto, Japan; Department of Veterans Affairs; NIH-NIDDK [R01 DK54221] FX Based on a presentation at the preconference symposium titled "Gut Chemosensing: Integrating nutrition, gut function and metabolism in pigs" preceding the 12th International Symposium on Digestive Physiology of Pigs in Keystone, Colorado, May 29-June 1, 2012, with publication sponsored by Lucta S.A. (Barcelona, Spain), the American Society of Animal Science, and the Journal of Animal Science.; We thank Bea Palileo for her assistance with manuscript preparation. Supported by funding from a Grant-in-Aid for Japan Society for the Promotion of Science Fellow (I. Kaji), a research grant from Ajinomoto, Japan (Y. Akiba), Department of Veterans Affairs Merit Review Award (J.D. Kaunitz), and NIH-NIDDK R01 DK54221 (J.D. Kaunitz). NR 32 TC 5 Z9 6 U1 1 U2 18 PU AMER SOC ANIMAL SCIENCE PI CHAMPAIGN PA PO BOX 7410, CHAMPAIGN, IL 61826-7410 USA SN 0021-8812 EI 1525-3163 J9 J ANIM SCI JI J. Anim. Sci. PD MAY PY 2013 VL 91 IS 5 BP 1957 EP 1962 DI 10.2527/jas.2012-5941 PG 6 WC Agriculture, Dairy & Animal Science SC Agriculture GA 154TA UT WOS:000319697600004 PM 23345558 ER PT J AU Sharifi, M Marshall, G Marshall, R Bottino, C Goldman, R Sequist, T Taveras, EM AF Sharifi, Mona Marshall, Gareth Marshall, Richard Bottino, Clement Goldman, Roberta Sequist, Thomas Taveras, Elsie M. TI Accelerating Progress in Reducing Childhood Obesity Disparities: Exploring Best Practices of Positive Outliers SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Editorial Material DE Obesity; disparities; children; positive outliers ID WEIGHT-LOSS MAINTENANCE; HEART-DISEASE RISK; PEER-SUPPORT; RANDOMIZED-TRIAL; COST-EFFECTIVENESS; AFRICAN-AMERICANS; CONTROL REGISTRY; US CHILDREN; DEVIANCE; INTERVENTION AB Childhood obesity rates may have plateaued in some U.S. population subgroups, yet overall rates remain high and racial/ethnic and socioeconomic disparities appear to be widening. Successful strategies and best practices to inform obesity interventions and accelerate progress in reducing disparities in childhood obesity can be found among people who can be categorized as positive outliers, i.e., individuals who have succeeded, where many others have not, in changing their health behaviors, reducing their body mass index, and developing resilience in the context of adverse built and social environments. In this commentary, we discuss the central premise of a positive outlier approach and how successful strategies learned from positive outliers can be generalized and promoted to accelerate progress in childhood obesity. C1 [Sharifi, Mona; Marshall, Gareth] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA USA. [Sharifi, Mona; Marshall, Gareth] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Sharifi, Mona; Bottino, Clement] Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA USA. [Marshall, Richard; Sequist, Thomas] Harvard Vanguard Med Associates, Dept Pediat, Boston, MA USA. [Goldman, Roberta] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Sequist, Thomas] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Taveras, Elsie M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taveras, EM (reprint author), 100 Cambridge St, Boston, MA 02114 USA. EM etavaras@partners.org NR 40 TC 4 Z9 4 U1 0 U2 6 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 MAY PY 2013 VL 24 IS 2 SU S BP 193 EP 199 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 151VB UT WOS:000319487300018 PM 23727974 ER PT J AU Maciejewski, PK Prigerson, HG AF Maciejewski, Paul K. Prigerson, Holly G. TI Emotional Numbness Modifies the Effect of End-of-Life Discussions on End-of-Life Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Cancer; terminal illness; end-of-life care; communication; numbness; psychological reactions; grief; dissociation ID ILL PATIENTS; NEAR-DEATH; DISSOCIATION; COMMUNICATION; QUESTIONNAIRE; ASSOCIATIONS; PROGNOSIS; SYMPTOMS; DISTRESS; OUTCOMES AB Context. Overall, end-of-life (EOL) discussions are unrelated to psychological distress and associated with lower rates of aggressive care near death. Nevertheless, patients who report that they feel emotionally numb about their illness might encounter difficulties cognitively processing an EOL discussion. Objectives. We hypothesized that emotional numbness would modify the effect of EOL discussions on the receipt of less aggressive EOL care. Methods. Data were derived from structured interviews with 290 participants in the federally-funded Coping with Cancer Study, a multisite, prospective cohort study of patients with advanced cancer followed-up till their death. Patients' reports of EOL discussions with their physician and emotional numbness were assessed at a median of 4.6 months before their death. Information about aggressive EOL care (i.e., ventilation, resuscitation in the last week of life, death in the intensive care unit) was obtained from postmortem caregiver interviews and medical charts. Main and interactive effects of EOL discussions and emotional numbness on aggressive EOL care, adjusting for potential confounds, were evaluated using multiple logistic regression. Results. The likelihood of aggressive EOL care associated with having EOL discussions increased by a factor of nine (adjusted odds ratio = 9.02, 95% CI 1.37, 59.6, P = 0.022) for every unit increase in a patient's emotional numbness score. Conclusion. Emotional numbness diminishes a patient's capacity to benefit from EOL discussions. The EOL decision making may be more effective if clinical communications with emotionally numb patients are avoided. (C) 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Maciejewski, Paul K.; Prigerson, Holly G.] Harvard Univ, Brigham & Womens Hosp, Dept Psychiat, Sch Med, Boston, MA 02115 USA. [Maciejewski, Paul K.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA. [Maciejewski, Paul K.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 1134 Dana Bldg,450 Brookline Ave, Boston, MA 02115 USA. EM holly_prigerson@dfci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106370, CA 156732] FX This research was supported in part by the following grants to Dr. H. G. Prigerson: MH63892 from the National Institute of Mental Health, and CA 106370 and CA 156732 from the National Cancer Institute. Neither author has relationships with any entities having financial interest in this topic. NR 19 TC 10 Z9 10 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2013 VL 45 IS 5 BP 841 EP 847 DI 10.1016/j.jpainsymman.2012.04.003 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 145YU UT WOS:000319056800010 PM 22926093 ER PT J AU Johansen, KL AF Johansen, Kirsten L. TI Obesity and Body Composition for Transplant Wait-List Candidacy-Challenging or Maintaining the BMI Limits? SO JOURNAL OF RENAL NUTRITION LA English DT Article ID MASS INDEX; RENAL-TRANSPLANTATION; WEIGHT; ASSOCIATIONS; RECIPIENTS; MORTALITY; OUTCOMES; IMPACT; GRAFT AB Most kidney transplantation programs have a maximum body mass index (BMI) above which they will not place a patient on the active waiting list. However, obesity is common among patients with end-stage renal disease (ESRD), and weight loss is difficult, resulting in many patients being denied the opportunity to be considered for a transplant. BMI limits are in place because of data that outcomes are worse among obese transplant recipients than among those with lower BMI. However, the data to suggest that patient and graft survival are affected by obesity are not consistent, and obese patients with ESRD have better survival after kidney transplantation compared with remaining on dialysis. Therefore, it is important to carefully examine the question of BMI limits to ensure that we are achieving the right balance and making the best use of donated kidneys. (C) 2013 by the National Kidney Foundation, Inc. All rights reserved. C1 [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Johansen, KL (reprint author), Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU National Institutes of Health [N01-DK-7-0005] FX This work was supported in part by National Institutes of Health contract N01-DK-7-0005. The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the U.S. government. NR 14 TC 5 Z9 5 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 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD MAY PY 2013 VL 23 IS 3 BP 207 EP 209 DI 10.1053/j.jrn.2013.02.005 PG 3 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 147XF UT WOS:000319203500014 PM 23611548 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Point: The New England Journal of Medicine Article Suggesting Overdiagnosis From Mammography Screening Is Scientifically Incorrect and Should Be Withdrawn SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID BREAST-CANCER INCIDENCE; MORTALITY; AGE C1 Harvard Univ, Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Breast Imaging Div,Dept Radiol,Sch Med, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Breast Imaging Div,Dept Radiol,Sch Med, 15 Parkman St,ACC Suite 240, Boston, MA 02114 USA. EM dkopans@partners.org NR 10 TC 16 Z9 16 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2013 VL 10 IS 5 BP 317 EP 319 DI 10.1016/j.jacr.2013.01.024 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146NR UT WOS:000319098300007 PM 23542028 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Counterpoint: The New England Journal of Medicine Article Suggesting Overdiagnosis From Mammography Screening Is Scientifically Correct and Should Not Be Withdrawn Response SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID SUPPORT C1 Harvard Univ, Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Breast Imaging Div,Dept Radiol,Sch Med, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Breast Imaging Div,Dept Radiol,Sch Med, 15 Parkman St,ACC Suite 240, Boston, MA 02114 USA. EM dkopans@partners.org NR 4 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2013 VL 10 IS 5 BP 324 EP 324 DI 10.1016/j.jacr.2013.01.015 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146NR UT WOS:000319098300010 ER PT J AU Woodard, PK White, RD Abbara, S Araoz, PA Cury, RC Dorbala, S Earls, JP Hoffmann, U Hsu, JY Jacobs, JE Javidan-Nejad, C Krishnamurthy, R Mammen, L Martin, ET Ryan, T Shah, AB Steiner, RM Vogel-Claussen, J White, CS AF Woodard, Pamela K. White, Richard D. Abbara, Suhny Araoz, Philip A. Cury, Ricardo C. Dorbala, Sharmila Earls, James P. Hoffmann, Udo Hsu, Joe Y. Jacobs, Jill E. Javidan-Nejad, Cylen Krishnamurthy, Rajesh Mammen, Leena Martin, Edward T. Ryan, Thomas Shah, Amar B. Steiner, Robert M. Vogel-Claussen, Jens White, Charles S. TI ACR Appropriateness Criteria Chronic Chest Pain-Low to Intermediate Probability of Coronary Artery Disease SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; chronic chest pain; low probability of coronary artery disease; intermediate probability of coronary artery disease ID CHRONIC STABLE ANGINA; CARDIOVASCULAR MAGNETIC-RESONANCE; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ASSOCIATION TASK-FORCE; EMERGENCY-DEPARTMENT; AMERICAN-COLLEGE; PROGNOSTIC VALUE; CT ANGIOGRAPHY; PRACTICE GUIDELINES; SYNDROME-X AB Chronic chest pain can arise from a variety of etiologies. However, of those potential causes, the most life-threatening include cardiac disease. Chronic cardiac chest pain may be caused either by ischemia or atherosclerotic coronary artery disease or by other cardiac-related etiologies, such as pericardial disease. To consider in patients, especially those who are at low risk for coronary artery disease, are etiologies of chronic noncardiac chest pain. Noncardiac chest pain is most commonly related to gastroesophageal reflux disease or other esophageal diseases. Alternatively, it may be related to costochondritis, arthritic or degenerative diseases, old trauma, primary or metastatic tumors, or pleural disease. Rarely, noncardiac chest pain may be referred pain from organ systems below the diaphragm, such as the gallbladder. The ACR 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Woodard, Pamela K.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [White, Richard D.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Abbara, Suhny; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Araoz, Philip A.] Mayo Clin, Rochester, MN USA. [Cury, Ricardo C.] Baptist Hosp Miami, Kendall, FL USA. [Dorbala, Sharmila] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dorbala, Sharmila] Soc Nucl Med & Mol Imaging, Reston, VA USA. [Earls, James P.] Fairfax Radiol Consultants, Fairfax, VA USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Hsu, Joe Y.] Kaiser Permanente, Los Angeles, CA USA. [Jacobs, Jill E.] NYU Med Ctr, New York, NY 10016 USA. [Javidan-Nejad, Cylen] Washington Univ, Sch Med, St Louis, MO USA. [Krishnamurthy, Rajesh] Texas Childrens Hosp, Houston, TX 77030 USA. [Mammen, Leena] Adv Radiol Serv, Grand Rapids, MI USA. [Martin, Edward T.] Oklahoma Heart Inst, Tulsa, OK USA. [Martin, Edward T.; Ryan, Thomas] Amer Coll Cardiol, Washington, DC USA. [Ryan, Thomas] Ohio State Univ, Heart & Vasc Ctr, Columbus, OH 43210 USA. [Shah, Amar B.] Westchester Med Ctr, Valhalla, NY USA. [Steiner, Robert M.] Temple Univ Hlth Syst, Philadelphia, PA USA. [Vogel-Claussen, Jens] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [White, Charles S.] Univ Maryland Hosp, Baltimore, MD 21201 USA. RP Woodard, PK (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM woodardp@mir.wustl.edu OI White, Richard D./0000-0002-1133-7819 FU Astellas Pharma US Inc; GE Healthcare (Milwaukee, Wisconsin); National Institutes of Health (Bethesda, Maryland) FX Dr Araoz performs core laboratory analysis for Medtronic, Inc (Minneapolis, Minnesota). Dr Cury is a consultant for Astellas Pharma US Inc (Northbrook, Illinois) and has received research grants from Astellas Pharma US Inc and GE Healthcare (Milwaukee, Wisconsin). Dr Dorbala has received a research grant from Astellas Pharma US Inc and is funded by a K23 grant from the National Institutes of Health (Bethesda, Maryland). NR 38 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2013 VL 10 IS 5 BP 329 EP 334 DI 10.1016/j.jacr.2013.01.018 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146NR UT WOS:000319098300013 PM 23542027 ER PT J AU Gunn, AJ Sahani, DV Bennett, SE Choy, G AF Gunn, Andrew J. Sahani, Dushyant V. Bennett, Susan E. Choy, Garry TI Re: "Recent Measures to Improve Radiology Reporting: Perspectives From Primary Care Physicians" Response SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Letter C1 [Gunn, Andrew J.; Sahani, Dushyant V.; Bennett, Susan E.; Choy, Garry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gunn, Andrew J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Sahani, Dushyant V.; Bennett, Susan E.; Choy, Garry] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gunn, AJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,FND 216, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2013 VL 10 IS 5 BP 387 EP 388 DI 10.1016/j.jacr.2013.03.008 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146NR UT WOS:000319098300029 PM 23642883 ER PT J AU Segata, N Boernigen, D Tickle, TL Morgan, XC Garrett, WS Huttenhower, C AF Segata, Nicola Boernigen, Daniela Tickle, Timothy L. Morgan, Xochitl C. Garrett, Wendy S. Huttenhower, Curtis TI Computational meta'omics for microbial community studies SO MOLECULAR SYSTEMS BIOLOGY LA English DT Review DE meta'omics; microbial communities; microbiome computational models ID RIBOSOMAL-RNA GENE; COMPARATIVE-ANALYSIS SYSTEM; DISTAL GUT MICROBIOTA; DE-NOVO ASSEMBLER; SINGLE-CELL; METAGENOMIC SEQUENCES; UNCULTURED MICROORGANISMS; TAXONOMIC CLASSIFICATION; METABOLIC PATHWAYS; GENOMIC FRAGMENTS AB Complex microbial communities are an integral part of the Earth's ecosystem and of our bodies in health and disease. In the last two decades, culture-independent approaches have provided new insights into their structure and function, with the exponentially decreasing cost of high-throughput sequencing resulting in broadly available tools for microbial surveys. However, the field remains far from reaching a technological plateau, as both computational techniques and nucleotide sequencing platforms for microbial genomic and transcriptional content continue to improve. Current microbiome analyses are thus starting to adopt multiple and complementary meta'omic approaches, leading to unprecedented opportunities to comprehensively and accurately characterize microbial communities and their interactions with their environments and hosts. This diversity of available assays, analysis methods, and public data is in turn beginning to enable microbiome-based predictive and modeling tools. We thus review here the technological and computational meta'omics approaches that are already available, those that are under active development, their success in biological discovery, and several outstanding challenges. C1 [Segata, Nicola; Boernigen, Daniela; Tickle, Timothy L.; Morgan, Xochitl C.; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Boernigen, Daniela; Tickle, Timothy L.; Morgan, Xochitl C.; Garrett, Wendy S.; Huttenhower, Curtis] Broad Inst MIT & Harvard, Cambridge, MA USA. [Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM chuttenh@hsph.harvard.edu OI Morgan, Xochitl/0000-0002-6264-6961; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794 FU NIH [1R01CA154426, 1R01HG005969]; Danone Research [PLF-5972-GD]; Juvenile Diabetes Research Foundation [17-2011-529]; NSF [DBI-1053486]; ARO [W911NF-11-1-0473] FX We thank Felix Jouwai Wong for assistance with figures, the members of the Huttenhower and Garrett labs for their input and thoughtful discussions, and Mihai Pop for his in-depth investigation of metagenome assembly in the human microbiome. This work was supported by NIH 1R01CA154426 and Danone Research PLF-5972-GD to WSG, the Juvenile Diabetes Research Foundation 17-2011-529 (Ramnik Xavier), NIH 1R01HG005969, NSF CAREER DBI-1053486, and ARO W911NF-11-1-0473 to CH. NR 175 TC 90 Z9 93 U1 8 U2 179 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD MAY PY 2013 VL 9 AR 666 DI 10.1038/msb.2013.22 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156QE UT WOS:000319836700003 PM 23670539 ER PT J AU Wolk, DA Mancuso, L Kliot, D Arnold, SE Dickerson, BC AF Wolk, David A. Mancuso, Lauren Kliot, Daria Arnold, Steven E. Dickerson, Bradford C. TI Familiarity-based memory as an early cognitive marker of preclinical and prodromal AD SO NEUROPSYCHOLOGIA LA English DT Article DE Memory; Recollection; Familiarity; Alzheimer's disease; Medial temporal lobe; Preclinical Alzheimer's disease; Mild cognitive impairment ID MEDIAL TEMPORAL-LOBE; ALZHEIMERS ASSOCIATION WORKGROUPS; POSITRON-EMISSION-TOMOGRAPHY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; RECOGNITION MEMORY; NEUROFIBRILLARY TANGLES; CORTICAL SURFACE; AMYLOID BURDEN; OLDER-ADULTS AB There is great interest in the development of cognitive markers that differentiate "normal" age-associated cognitive change from that of Alzheimer's disease (AD) in its prodromal (i.e., mild cognitive impairment; MCI) or even preclinical stages. Dual process models posit that recognition memory is supported by the dissociable processes of recollection and familiarity. Familiarity-based memory has generally been considered to be spared during normal aging, but it remains controversial whether this type of memory is impaired in early AD. Here, we describe findings of estimates of recollection and familiarity in young adults (YA), cognitively normal older adults (CN), and patients with amnestic-MCI (a-MCI). These measures in the CN and a-MCI patients were then related to a structural imaging biomarker of AD that has previously been demonstrated to be sensitive to preclinical and prodromal AD, the Cortical Signature of AD (ADsig). Consistent with much work in the literature, recollection, but not familiarity, was impaired in CN versus YA. Replicating our prior findings, a-MCI patients displayed impairment in both familiarity and recollection. Finally, the familiarity measure was correlated with the ADsig biomarker across the CN and a-MCI group, as well as within the CN adults alone. No other standard psychometric measure was as highly associated with the ADsig, suggesting that familiarity may be a sensitive biomarker of AD-specific brain changes in preclinical and prodromal AD and that it may offer a qualitatively distinct measure of early AD memory impairment relative to normal age-associated change. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Wolk, David A.; Mancuso, Lauren; Kliot, Daria; Arnold, Steven E.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wolk, David A.; Mancuso, Lauren; Kliot, Daria; Arnold, Steven E.] Univ Penn, Penn Memory Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Arnold, Steven E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. RP Wolk, DA (reprint author), Penn Memory Ctr, 3615 Chestnut St,212, Philadelphia, PA USA. EM david.wolk@uphs.upenn.edu FU NIH [K23-AG028018, P30AG010124, R01AG29411, R21AG29840, P50-AG005134]; Alzheimer's Association [NIRG-12-242765] FX This work was supported by grants from NIH, including K23-AG028018, P30AG010124, R01AG29411, R21AG29840, P50-AG005134, and the Alzheimer's Association (NIRG-12-242765). NR 83 TC 19 Z9 21 U1 0 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAY PY 2013 VL 51 IS 6 BP 1094 EP 1102 DI 10.1016/j.neuropsychologia.2013.02.014 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 152MK UT WOS:000319535600008 PM 23474075 ER PT J AU Vuoksimaa, E Panizzon, MS Chen, CH Eyler, LT Fennema-Notestine, C Fiecas, MJA Fischl, B Franz, CE Grant, MD Jak, AJ Lyons, MJ Neale, MC Thompson, WK Tsuang, MT Xian, H Dale, AM Kremen, WS AF Vuoksimaa, Eero Panizzon, Matthew S. Chen, Chi-Hua Eyler, Lisa T. Fennema-Notestine, Christine Fiecas, Mark Joseph A. Fischl, Bruce Franz, Carol E. Grant, Michael D. Jak, Amy J. Lyons, Michael J. Neale, Michael C. Thompson, Wesley K. Tsuang, Ming T. Xian, Hong Dale, Anders M. Kremen, William S. TI Cognitive reserve moderates the association between hippocampal volume and episodic memory in middle age SO NEUROPSYCHOLOGIA LA English DT Article DE Cognitive reserve; General cognitive ability; Episodic memory; Hippocampus; Verbal learning ID ALZHEIMERS-DISEASE; EDUCATION; PERFORMANCE; IMPAIRMENT; BRAIN; DECLINE; AD; ENVIRONMENT; HYPOTHESIS; PATHOLOGY AB Cognitive reserve is hypothesized to help people withstand greater brain pathology without manifesting clinical symptoms, and may be regarded as a preventive factor of dementia. It is unclear whether the effect of cognitive reserve is evident only among the older adults or after conversion to dementia, or if it can also be seen earlier in life before the prominent effects of cognitive aging become apparent. While finding a main effect of cognitive reserve on cognitive outcome may be consistent with the reserve hypothesis, in our view, it is unnecessary to invoke the idea of reserve if only a main effect is present. Rather, it is the interaction between a measure of reserve and a brain measure on cognitive outcome that is key for confirming that the effects of brain pathology affect people differently according to their cognitive reserve. We studied whether general cognitive ability at an average age of 20 years, as a direct measure of cognitive reserve, moderates the association between hippocampal volume and episodic memory performance in 494 middle-aged men ages 51 to 60. Whereas there was no statistically significant direct relationship between hippocampal volume and episodic memory performance in middle age, we found a statistically significant interaction such that there was a positive association between hippocampal volume and episodic memory only among people with lower general cognitive ability at age 20, i.e., lower levels of cognitive reserve. Our results provide support for the hypothesis that cognitive reserve moderates the relationship between brain structure and cognition in middle age, well before the onset of dementia. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Vuoksimaa, Eero; Panizzon, Matthew S.; Chen, Chi-Hua; Eyler, Lisa T.; Fennema-Notestine, Christine; Fiecas, Mark Joseph A.; Franz, Carol E.; Jak, Amy J.; Thompson, Wesley K.; Tsuang, Ming T.; Dale, Anders M.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Vuoksimaa, Eero; Panizzon, Matthew S.; Chen, Chi-Hua; Fiecas, Mark Joseph A.; Franz, Carol E.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, Twin Res Lab, La Jolla, CA 92093 USA. [Vuoksimaa, Eero] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Chen, Chi-Hua; Fiecas, Mark Joseph A.; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Eyler, Lisa T.] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, San Diego, CA USA. [Fennema-Notestine, Christine] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Boston, MA USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Grant, Michael D.; Lyons, Michael J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Neale, Michael C.] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Tsuang, Ming T.] Sch Publ Hlth, Boston, MA USA. [Xian, Hong] St Louis Vet Affairs Med Ctr, Res Serv, St Louis, MO USA. [Xian, Hong] St Louis Univ, Sch Publ Hlth, Dept Biostat, St Louis, MO 63103 USA. [Jak, Amy J.; Kremen, William S.] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, La Jolla, CA USA. RP Vuoksimaa, E (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr MC0738, La Jolla, CA 92093 USA. EM eero.vuoksimaa@helsinki.fi OI Fennema-Notestine, Christine/0000-0002-6527-6361; Lyons, Michael/0000-0001-6516-9219 FU National Institute on Aging [R01 AG022982, R01 AG018386, R01 AG022381, R01 AG018384]; National Institute of Drug Abuse [DA029475]; National Institute of Neurological Disorders and Stroke [NS056883]; National Center for Research Resources [P41-RR14075, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [EB006758]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [NS052585-01, 1R21NS072652-01, 1R01NS070963]; Ellison Medical Foundation; Academy of Finland; Sigrid Juselius Foundation FX This work was supported by grants from the National Institute on Aging [R01 AG022982, R01 AG018386, and R01 AG022381, R01 AG018384]; National Institute of Drug Abuse [DA029475]; National Institute of Neurological Disorders and Stroke [NS056883], National Center for Research Resources [P41-RR14075, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [EB006758]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [NS052585-01, 1R21NS072652-01, 1R01NS070963]; the Ellison Medical Foundation; Academy of Finland; and a Sigrid Juselius Foundation Fellowship (E.V.). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIA or the NIH. NR 46 TC 5 Z9 5 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAY PY 2013 VL 51 IS 6 BP 1124 EP 1131 DI 10.1016/j.neuropsychologia.2013.02.022 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 152MK UT WOS:000319535600012 PM 23499725 ER PT J AU Knaul, FM Chabner, BA AF Knaul, Felicia M. Chabner, Bruce A. TI Announcing a New Section: Global Health and Cancer SO ONCOLOGIST LA English DT Editorial Material C1 [Knaul, Felicia M.] Harvard Global Equ Initiat, Boston, MA 02115 USA. [Chabner, Bruce A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Knaul, Felicia M.] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. [Chabner, Bruce A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Knaul, FM (reprint author), Harvard Global Equ Initiat, 651 Huntington Ave,FXB Bldg, Boston, MA 02115 USA. EM felicia_knaul@harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2013 VL 18 IS 5 BP 485 EP 486 DI 10.1634/theoncologist.2013-0158 PG 2 WC Oncology SC Oncology GA 152UA UT WOS:000319555600001 ER PT J AU Yao, JC Lagunes, DR Kulke, MH AF Yao, James C. Lagunes, Diane Reidy Kulke, Matthew H. TI Targeted Therapies in Neuroendocrine Tumors (NET): Clinical Trial Challenges and Lessons Learned SO ONCOLOGIST LA English DT Article DE Everolimus; Neuroendocrine tumors; Octreotide; Sunitinib; Trial design ID PHASE-II TRIALS; PROGRESSION-FREE SURVIVAL; MALIGNANT CARCINOID-SYNDROME; ENETS CONSENSUS GUIDELINES; PROGNOSTIC-FACTORS; ANTICANCER AGENTS; DRUG-DEVELOPMENT; CHROMOGRANIN-A; SOLID TUMORS; MANAGEMENT AB In the past 3 years, we have witnessed the completion of four randomized phase Ill studies in neuroendocrine tumors and the approval of two new drugs, everolimus and sunitinib, for the treatment of patients with well-differentiated pancreatic neuroendocrine tumors. These studies demonstrate a shift from case series and single-arm studies toward prospective, randomized controlled clinical trials and evidence-based therapy in the neuroendocrine tumor field. However, the clinical development of these agents also highlights the potential challenges awaiting other new drugs in this area. Herein, we discuss the strengths and weaknesses of the most recent phase II and phase III neuroendocrine tumor studies and discuss how limitations inherent in current trial design can lead to potential pitfalls. We also discuss how trial design can be improved, with the hope of increasing the number of drugs successfully developed to treat patients with neuroendocrine tumors. C1 [Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lagunes, Diane Reidy] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yao, JC (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jyao@mdanderson.org FU Novartis Pharmaceuticals Corporation FX The everolimus phase II and III studies discussed in this review were funded by Novartis Pharmaceuticals Corporation. The studies were designed by the academic investigators and representatives of the sponsor. Data were collected with the use of the sponsor's data management systems and were analyzed by the sponsor's statistical team. All authors contributed to the interpretation of data and to subsequent writing, reviewing, and amending of the manuscript. All authors vouch for the accuracy and completeness of the reported data. NR 60 TC 17 Z9 17 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2013 VL 18 IS 5 BP 525 EP 532 DI 10.1634/theoncologist.2012-0434 PG 8 WC Oncology SC Oncology GA 152UA UT WOS:000319555600008 PM 23615698 ER PT J AU Faris, JE Blaszkowsky, LS McDermott, S Guimaraes, AR Szymonifka, J Huynh, MA Ferrone, CR Wargo, JA Allen, JN Dias, LE Kwak, EL Lillemoe, KD Thayer, SP Murphy, JE Zhu, AX Sahani, DV Wo, JY Clark, JW Fernandez-del Castillo, C Ryan, DP Hong, TS AF Faris, Jason E. Blaszkowsky, Lawrence S. McDermott, Shaunagh Guimaraes, Alexander R. Szymonifka, Jackie Huynh, Mai Anh Ferrone, Cristina R. Wargo, Jennifer A. Allen, Jill N. Dias, Lauren E. Kwak, Eunice L. Lillemoe, Keith D. Thayer, Sarah P. Murphy, Janet E. Zhu, Andrew X. Sahani, Dushyant V. Wo, Jennifer Y. Clark, Jeffrey W. Fernandez-del Castillo, Carlos Ryan, David P. Hong, Theodore S. TI FOLFIRINOX in Locally Advanced Pancreatic Cancer: The Massachusetts General Hospital Cancer Center Experience SO ONCOLOGIST LA English DT Article DE FOLFIRINOX; Locally advanced pancreatic cancer; Neoadjuvant; RO resection; Chemoradiation ID PHASE-III; CHEMORADIATION; GEMCITABINE; CHEMORADIOTHERAPY; CHEMOTHERAPY; ADENOCARCINOMA; CARCINOMA; TRIAL AB The objective of our retrospective institutional experience is to report the overall response rate, R0 resection rate, progression-free survival, and safety/toxicity of neoadjuvant FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Patients with LAPC treated with FOLFIRINOX were identified via the Massachusetts General Hospital Cancer Center pharmacy data base. Demographic information, clinical characteristics, and safety/tolerability data were compiled. Formal radiographic review was performed to determine overall response rates (ORRs). Twenty-two patients with LAPC began treatment with FOLFIRINOX between July 2010 and February 2012. The ORR was 27.3%, and the median progression-free survival was 11.7 months. Five of 22 patients were able to undergo SO resections following neoadjuvant FOLFIRINOX and chemoradiation. Three of the five patients have experienced distant recurrence within 5 months. Thirty-two percent of patients required at least one emergency department visit or hospitalization while being treated with FOLFIRINOX. FOLFIRINOX possesses substantial activity in patients with LAPC. The use of FOLFIRINOX was associated with conversion to resectability in >20% of patients. However, the recurrences following SO resection in three of five patients and the toxicities observed with the use of this regimen raise important questions about how to best treat patients with LAPC.. C1 [Faris, Jason E.; Blaszkowsky, Lawrence S.; Allen, Jill N.; Kwak, Eunice L.; Murphy, Janet E.; Zhu, Andrew X.; Clark, Jeffrey W.; Ryan, David P.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Huynh, Mai Anh; Wo, Jennifer Y.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [McDermott, Shaunagh; Guimaraes, Alexander R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Szymonifka, Jackie; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Ferrone, Cristina R.; Lillemoe, Keith D.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Gen & Gastrointestinal Surg, Boston, MA 02114 USA. [Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. [Dias, Lauren E.] North Shore Canc Ctr, Dept Hematol Oncol, Danvers, MA USA. RP Faris, JE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7E,55 Fruit St, Boston, MA 02114 USA. EM jfaris@partners.org FU NCI NIH HHS [P01 CA117969, P50 CA127003]; NIBIB NIH HHS [K08 EB012859] NR 17 TC 69 Z9 69 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2013 VL 18 IS 5 BP 543 EP 548 DI 10.1634/theoncologist.2012-0435 PG 6 WC Oncology SC Oncology GA 152UA UT WOS:000319555600010 PM 23657686 ER PT J AU Misiukiewicz, KJ Camille, N Tishler, R Haddad, R Limaye, S Posner, M AF Misiukiewicz, Krzysztof J. Camille, Nadia Tishler, Roy Haddad, Robert Limaye, Sewanti Posner, Marshall TI Organ Preservation for Adenoid Cystic Carcinoma of the Larynx SO ONCOLOGIST LA English DT Article DE Adenoid cystic carcinoma; Cancer; Case series; Chemoradiotherapy; Larynx; Organ-sparing; Organ preservation; Local regional control ID LOCALLY ADVANCED HEAD; NECK-CANCER; RADIOTHERAPY; CHEMORADIOTHERAPY; CHEMOTHERAPY; PACLITAXEL; EXPERIENCE; RADIATION; CARBOPLATIN; SURGERY AB Objectives. Two cases of adenoid cystic carcinoma (ACC) of the larynx were treated with chemoradiotherapy (CRT) for organ preservation. We reviewed case series and current literature to contrast the potential role of primary CRT as an organ-sparing modality with standard laryngectomy and radiotherapy in patients with laryngeal ACC. Methods. Two treatment-naive patients with laryngeal ACC treated at Dana-Farber Cancer Institute between 2002 and 2007 were identified. Both patients were offered standard laryngectomy followed by adjuvant radiotherapy or organ-sparing treatment modality. Results. Both patients were males, aged 57 and 73. The patients completed a course of combined chemoradiotherapy with weekly carboplatin and paclitaxel and 7-8 weeks of radiotherapy to a total dose of 6,600 and 7,000 cGy over 50 and 57 days, respectively. There were no treatment breaks or delays because of toxicity. The major toxicities reported by both patients, as anticipated, were Grade 3 mucositis, desquamative dermatitis, and severe dysphagia, all of which resolved. Both patients are alive with local regional control and functional larynx; one at 112+ months with pulmonary metastases at 54 months, and the other disease free at 60+ months. Conclusions. Definitive chemoradiation with weekly carboplatin and paclitaxel may be a potential alternative to the current standard of surgery and radiation for patients with locally advanced laryngeal ACC who request an organ-sparing approach. In this group of patients, salvage laryngectomy may be reserved for those who are locally recurrent or chemoradiotherapy resistant. Although CRT provided long-term local regional control in our two patients, there are evident limitations in obtaining evidence for a determination of treatment of rare diseases. This report provides support for following an organ preservation plan in selected patients. C1 [Misiukiewicz, Krzysztof J.; Camille, Nadia; Posner, Marshall] Mt Sinai Sch Med, Dept Med Hematol & Med Oncol, New York, NY 10029 USA. [Tishler, Roy; Limaye, Sewanti] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Haddad, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Misiukiewicz, KJ (reprint author), Mt Sinai Sch Med, Dept Med Hematol & Med Oncol, 19E 98th St, New York, NY 10029 USA. EM Krzysztof.Misiukiewicz@mssm.edu NR 28 TC 5 Z9 6 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2013 VL 18 IS 5 BP 579 EP 583 DI 10.1634/theoncologist.2012-0349 PG 5 WC Oncology SC Oncology GA 152UA UT WOS:000319555600014 PM 23615699 ER PT J AU Bhasin, MK Dusek, JA Chang, BH Joseph, MG Denninger, JW Fricchione, GL Benson, H Libermann, TA AF Bhasin, Manoj K. Dusek, Jeffery A. Chang, Bei-Hung Joseph, Marie G. Denninger, John W. Fricchione, Gregory L. Benson, Herbert Libermann, Towia A. TI Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways SO PLOS ONE LA English DT Article ID PROTEIN REFERENCE DATABASE; SET ENRICHMENT ANALYSIS; NF-KAPPA-B; NITRIC-OXIDE; OXIDATIVE-STRESS; PSYCHOLOGICAL STRESS; RISK-FACTORS; GENOME-WIDE; EXPRESSION; MEDITATION AB The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-kappa B pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-kappa B-associated upstream and downstream targets that mitigates stress. C1 [Bhasin, Manoj K.; Denninger, John W.; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Denninger, John W.; Fricchione, Gregory L.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Benson, Herbert] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Bhasin, Manoj K.; Libermann, Towia A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. [Bhasin, Manoj K.; Joseph, Marie G.; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, BIDMC Genom & Prote Ctr, Boston, MA 02215 USA. [Dusek, Jeffery A.] Abbott NW Hosp, Inst Hlth & Healing, Minneapolis, MN 55407 USA. [Chang, Bei-Hung] VA Boston Healthcare Syst, Boston, MA USA. [Chang, Bei-Hung] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA USA. RP Libermann, TA (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. EM tliberma@bidmc.harvard.edu OI Libermann, Towia/0000-0002-4006-8179; Dusek, Jeffery/0000-0001-9581-0564 FU Centers for Disease Control and Prevention (CDC) [H75/CCH123424, R01 DP000339]; National Center for Complementary and Alternative Medicine (NCCAM) [RO1 AT006464-01]; NCRR, National Institutes of Health (The Harvard-Thorndike GCRC) [M01 RR01032] FX The study was funded by grants H75/CCH123424 and R01 DP000339 from the Centers for Disease Control and Prevention (CDC) (HB), RO1 AT006464-01 from the National Center for Complementary and Alternative Medicine (NCCAM) (HB) and grant M01 RR01032 from the NCRR, National Institutes of Health (The Harvard-Thorndike GCRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 49 Z9 49 U1 4 U2 46 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 MAY 1 PY 2013 VL 8 IS 5 AR e62817 DI 10.1371/journal.pone.0062817 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 147KY UT WOS:000319167000076 PM 23650531 ER PT J AU Shah, M Lee, G Lefebvre, DR Kronberg, B Loomis, S Brauner, SC Turalba, A Rhee, DJ Freitag, SK Pasquale, LR AF Shah, Mamta Lee, Grace Lefebvre, Daniel R. Kronberg, Benjamin Loomis, Stephanie Brauner, Stacey C. Turalba, Angela Rhee, Douglas J. Freitag, Suzanne K. Pasquale, Louis R. TI A Cross-Sectional Survey of the Association between Bilateral Topical Prostaglandin Analogue Use and Ocular Adnexal Features SO PLOS ONE LA English DT Article ID SMOOTH-MUSCLE-CELLS; ORBITAL FAT; MATRIX METALLOPROTEINASES; BIMATOPROST THERAPY; LID SULCUS; LATANOPROST; INVOLVEMENT; TRAVOPROST AB We studied the relation between prostaglandin analogue use and ocular adnexal features. We used a prospective, cross-sectional study involving 157 current, 15 past, and 171 never users of prostaglandin analogues. Patients 50 years of age or older and without conditions affecting ocular adnexal anatomy underwent glaucoma medication use history, external digital photography and systematic external adnexal exam. Two masked readers assessed the digital photos for upper lid dermatochalasis and lower lid steatoblepharon using a validated grading scheme. Another masked clinical examiner also assessed upper lid ptosis, levator muscle function, and inferior scleral show. We performed ordinal logistic regression analysis accounting for multiple covariates to assess the relation between prostaglandin analogue use and adnexal features. Multivariable analyses indicated there was a 230-fold increased risk of incremental involution of dermatochalasis (odds ratio (OR) = 2.30; 95% confidence interval (CI) 1.43-3.69; p = 5.44E-04) and a 249-fold increased risk of incremental loss of lower lid steatoblepharon (OR = 2.49; 95% CI, 1.54-4.03; p = 1.98E-04) associated with current prostaglandin analogue use (bimatoprost 0.03%, travoprost 0.005%, or latanoprost 0.004%) versus prostaglandin analogue never or past users. Upper lid ptosis (OR = 4.04; 95% CI, 2.43-6.72; p = 7.37E-08), levator dysfunction (OR = 7.51; 95% CI, 3.39-16.65; p = 6.74E-07) and lower lid retraction (OR = 2.60; 95% CI, 1.58-4.28; p = 1.72E-04) were highly associated with current prostaglandin analogue use versus prostaglandin analogue never or past users. The associations between prostaglandin analogue use and deepening of the upper lid sulci and between prostaglandin analogue use and loss of inferior periorbital fat are confirmed in this multivariable analysis. The associations between prostaglandin analogue use and levator muscle dysfunction and between prostaglandin analogue use and upper lid ptosis represent significant side effects that could impact visual function in glaucoma patients. C1 [Shah, Mamta] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Lee, Grace; Lefebvre, Daniel R.; Kronberg, Benjamin; Loomis, Stephanie; Brauner, Stacey C.; Turalba, Angela; Rhee, Douglas J.; Freitag, Suzanne K.; Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Shah, M (reprint author), Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. EM mshah@bu.edu FU Research to Prevent Blindness (RPB) Medical Student Fellowship; Harvard Glaucoma Center of Excellence and a Distinguished Ophthalmology Scholar award FX The study is supported by the Research to Prevent Blindness (RPB) Medical Student Fellowship 2011-2012. The Harvard Glaucoma Center of Excellence and a Distinguished Ophthalmology Scholar award support Dr. LRP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 14 Z9 15 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2013 VL 8 IS 5 AR e61638 DI 10.1371/journal.pone.0061638 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 147KY UT WOS:000319167000019 PM 23650502 ER PT J AU Huang, LL Wan, JB Wang, B He, CW Ma, H Li, TW Kang, JX AF Huang, Li-Li Wan, Jian-Bo Wang, Bin He, Cheng-Wei Ma, Huan Li, Tian-Wang Kang, Jing X. TI Suppression of acute ethanol-induced hepatic steatosis by docosahexaenoic acid is associated with downregulation of stearoyl-CoA desaturase 1 and inflammatory cytokines SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Alcoholic liver disease; Hepatic steatosis; Docosahexaenoic acid; Stearoyl-CoA desaturase 1; Inflammatory cytokines ID ALCOHOLIC-LIVER-DISEASE; POLYUNSATURATED FATTY-ACIDS; ELEMENT-BINDING PROTEIN-1; FISH-OIL; OXIDATIVE-STRESS; GENE-EXPRESSION; MICE; INJURY; RATS; DEFICIENCY AB Excessive alcohol consumption can lead to hepatic steatosis. Omega-3 (n-3) polyunsaturated fatty acids (PUFA) have been shown to be effective in reducing hepatic accumulation of triglycerides (TG) by downregulation of TG biosynthesis in the liver. The aim of this study was to examine whether supplementation with the n-3 PUFA, docosahexaenoic acid (DHA), can effectively reduce acute alcohol-induced hepatic steatosis. Acute alcohol-induced hepatic steatosis was generated in 9-week-old male mice (C57BL/6J) by oral gavage of ethanol (4.7 g/kg BW) diluted in water (60%, v/v), with or without DHA (250 mg/kg BW), every 12 h for 3 administrations. Compared to the control (ethanol-alone) group, animals supplemented with DHA were protected against ethanol-induced TG accumulation in the liver. Accordingly, hepatic stearoyl-CoA desaturase-1 (SCD-1) expression, serum alanine aminotransferase (ALT) activity, and the levels of inflammatory cytokines (such as IL-6 and TNF-alpha) in the liver were significantly reduced, whereas the expression of heme oxygenase-1 (HO-1), an enzyme that can improve cell survival in liver tissue, was markedly increased in DHA-supplemented mice compared to the control animals. There were no differences in serum TG level and hepatic production of reactive oxygen species (ROS) between the two groups. Our findings demonstrate that DHA supplementation protects against acute ethanol-induced hepatic steatosis, which may be associated with reduced expression of SCD-1 and inflammatory cytokines. (c) 2013 Elsevier Ltd. All rights reserved. C1 [Huang, Li-Li; Wan, Jian-Bo; Wang, Bin; He, Cheng-Wei; Ma, Huan; Li, Tian-Wang; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Huang, Li-Li; Wan, Jian-Bo; Wang, Bin; He, Cheng-Wei; Ma, Huan; Li, Tian-Wang; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Huang, Li-Li] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Obstet & Gynecol, Guangzhou 510275, Guangdong, Peoples R China. [Wan, Jian-Bo; He, Cheng-Wei] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Peoples R China. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Room 4001,149 13th St, Charlestown, MA 02129 USA. EM jxkang@partners.org RI Wan, Jian-Bo/D-8368-2014 OI Wan, Jian-Bo/0000-0002-6750-2617 FU E-fund Education Foundation, Guangzhou, China FX This study is partially supported by the E-fund Education Foundation, Guangzhou, China. NR 44 TC 21 Z9 22 U1 1 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY PY 2013 VL 88 IS 5 BP 347 EP 353 DI 10.1016/j.plefa.2013.02.002 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 152RU UT WOS:000319549600003 PM 23474173 ER PT J AU Zhang, JJ Zhang, LJ Ye, XX Chen, LY Zhang, LT Gao, YH Kang, JX Cai, C AF Zhang, Junjie Zhang, Lijian Ye, Xiaoxia Chen, Liyu Zhang, Liangtao Gao, Yihua Kang, Jing X. Cai, Chun TI Characteristics of fatty acid distribution is associated with colorectal cancer prognosis SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Fatty acid; Colorectal cancer; Gas chromatography; Mass spectrometry ID ALPHA-LINOLENIC ACID; BREAST-CANCER; PROSTATE-CANCER; PLASMA PHOSPHOLIPIDS; ADIPOSE-TISSUE; CELL-GROWTH; OLEIC-ACID; RISK; ERYTHROCYTE; PROLIFERATION AB To investigate tissue fatty acid distribution in relation to the incidence of colorectal cancer prognosis, adjacent normal tissue and cancerous tissue from 35 samples of clinically incident colorectal cancer were obtained. Fatty acids were measured in the colorectal mucosa phospholipid fraction by gas chromatography mass spectrometry. Palmitoleic acid and oleic acid were significantly lower in colorectal cancerous tissue, ranging from 20% to 50% less than the adjacent normal tissue. The omega-6 (n-6) fatty acid family members (20:2, 20:3, 20:4 and 22:4) were higher by 1-3 fold in cancerous colorectal tissue. Contrary with the high level of n-6 fatty acids, about a 37% to 87% reduction in EPA and DHA was observed in colorectal cancerous tissue. A higher level of linoleic acid and arachidonic acid was detected in the C cancer stage than in the B cancer stage (p < 0.05), but a lower level of oleic acid and docosahexenoic acid was detected in the C cancer stage (p < 0.05). The fatty acid distribution of colorectal tissue is strongly linked to the incidence of colorectal cancer. This study also provides scientific basis for identifying novel biomarkers for the diagnosis and treatment of cancer. (c) 2013 Elsevier Ltd. All rights reserved. C1 [Zhang, Junjie; Zhang, Lijian; Ye, Xiaoxia; Chen, Liyu; Zhang, Liangtao; Gao, Yihua; Cai, Chun] Guangdong Med Coll, Zhanjiang 524023, Guangdong, Peoples R China. [Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Zhang, LJ (reprint author), Guangdong Med Coll, 2 Eastern Wenming Rd, Zhanjiang 524023, Guangdong, Peoples R China. EM gdmczlj@sina.com FU National Natural Science Foundation of China FX This work was supported by a grant from The National Natural Science Foundation of China. NR 45 TC 9 Z9 9 U1 1 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY PY 2013 VL 88 IS 5 BP 355 EP 360 DI 10.1016/j.plefa.2013.02.005 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 152RU UT WOS:000319549600004 PM 23465412 ER PT J AU Yuppa, DP Nichols, S AF Yuppa, David Peter Nichols, Scott TI Amiodarone-Induced Delirium in Advanced Cancer: A Case Report SO PSYCHOSOMATICS LA English DT Article C1 [Yuppa, David Peter; Nichols, Scott] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. RP Yuppa, DP (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,SW411, Boston, MA 02215 USA. EM davidyuppa@gmail.com NR 9 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2013 VL 54 IS 3 BP 294 EP 296 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 151WQ UT WOS:000319491500014 PM 23218061 ER PT J AU Van Tyne, D Martin, MJ Gilmore, MS AF Van Tyne, Daria Martin, Melissa J. Gilmore, Michael S. TI Structure, Function, and Biology of the Enterococcus faecalis Cytolysin SO TOXINS LA English DT Review DE cytolysin; lantibiotic; bacteriocin ID HOST BACILLUS-SUBTILIS; STREPTOCOCCUS-FAECALIS; LIPID-II; HEMOLYSIN BACTERIOCIN; ANTIMICROBIAL RESISTANCE; PATHOGENICITY ISLAND; LANTIBIOTIC NISIN; PROKARYOTIC CELLS; VIRULENCE FACTORS; IN-VITRO AB Enterococcus faecalis is a Gram-positive commensal member of the gut microbiota of a wide range of organisms. With the advent of antibiotic therapy, it has emerged as a multidrug resistant, hospital-acquired pathogen. Highly virulent strains of E. faecalis express a pore-forming exotoxin, called cytolysin, which lyses both bacterial and eukaryotic cells in response to quorum signals. Originally described in the 1930s, the cytolysin is a member of a large class of lanthionine-containing bacteriocins produced by Gram-positive bacteria. While the cytolysin shares some core features with other lantibiotics, it possesses unique characteristics as well. The current understanding of cytolysin biosynthesis, structure/function relationships, and contribution to the biology of E. faecalis are reviewed, and opportunities for using emerging technologies to advance this understanding are discussed. C1 [Gilmore, Michael S.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Microbiol & Immunobiol, Boston, MA 02114 USA. RP Gilmore, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM michael_gilmore@meei.harvard.edu FU NIH/NIAID [AI083214]; NIH [AI072360, EY08289] FX Portions of this work were supported by the NIH/NIAID supported Harvard-wide Program on Antibiotic Resistance (AI083214), and by NIH research grants to examine different aspects of the pathogenesis of enterococci (AI072360, EY08289). The authors also thank current and former members of the Gilmore Laboratory for input and feedback during the preparation of this manuscript. NR 99 TC 25 Z9 25 U1 0 U2 36 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD MAY PY 2013 VL 5 IS 5 BP 895 EP 911 DI 10.3390/toxins5050895 PG 17 WC Toxicology SC Toxicology GA 151CO UT WOS:000319438400003 PM 23628786 ER PT J AU Bovenberg, MSS Degeling, MH Tannous, BA AF Bovenberg, M. Sarah S. Degeling, M. Hannah Tannous, Bakhos A. TI Advances in stem cell therapy against gliomas SO TRENDS IN MOLECULAR MEDICINE LA English DT Review DE neural stem cells; mesenchymal stem cells; hematopoietic stem cells; cell therapy; glioma; clinical trials; gene therapy; prodrug; oncolytic virus ID MESENCHYMAL STROMAL CELLS; HEMATOPOIETIC PROGENITOR CELLS; HUMAN BRAIN-TUMORS; GENE-THERAPY; BONE-MARROW; MALIGNANT GLIOMA; BREAST-CANCER; GLIOBLASTOMA-MULTIFORME; ONCOLYTIC ADENOVIRUS; NEURAL PRECURSORS AB Malignant gliomas are one of the most lethal cancers, and despite extensive research very little progress has been made in improving prognosis. Multimodality treatment combining surgery, radiation, and chemotherapy is the current gold standard, but effective treatment remains difficult due to the invasive nature and high recurrence of gliomas. Stem cell-based therapy using neural, mesenchymal, or hematopoietic stem cells may be an alternative approach because it is tumor selective and allows targeted therapy that spares healthy brain tissue. Stem cells can be used to establish a long-term antitumor response by stimulating the immune system and delivering prodrug, metabolizing genes, or oncolytic viruses. In this review, we discuss current trends and the latest developments in stem cell therapy against malignant gliomas from both the experimental laboratory and the clinic. C1 [Bovenberg, M. Sarah S.; Degeling, M. Hannah; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Neurosci Ctr, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Bovenberg, M. Sarah S.; Degeling, M. Hannah; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Bovenberg, M. Sarah S.; Degeling, M. Hannah] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurosci Ctr, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. EM btannous@hms.harvard.edu FU National Institutes of Health; National Institute of Neurological Disorders and Stroke [1R01NS064983]; National Cancer Institute [1R01CA166077]; Fulbright scholarship; Saal van Zwanenberg Foundation; VSB fonds; Dr Hendrik Muller Vaderlandschfonds; Dutch Cancer Foundation (KWF Kankerbestrijding); Hersenstichting brain fund; Jo Keur (Leiden hospital) FX B.A.T. is supported by grants from the National Institutes of Health, the National Institute of Neurological Disorders and Stroke (1R01NS064983) and the National Cancer Institute (1R01CA166077). M.H.D. is supported by a Fulbright scholarship, the Saal van Zwanenberg Foundation, VSB fonds, Dr Hendrik Muller Vaderlandschfonds, the Dutch Cancer Foundation (KWF Kankerbestrijding), the Hersenstichting brain fund, as well as the Jo Keur (Leiden hospital). M.S.B. is supported by a Fulbright scholarship, the Huygens Scholarship Program, VSB fonds and the Saal van Zwanenberg Foundation. The authors would like to thank Mr Romain Amante for assistance in drawing Figure 2. NR 91 TC 12 Z9 14 U1 3 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 EI 1471-499X J9 TRENDS MOL MED JI Trends Mol. Med PD MAY PY 2013 VL 19 IS 5 BP 281 EP 291 DI 10.1016/j.molmed.2013.03.001 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 155AH UT WOS:000319717300003 PM 23537753 ER PT J AU Mattsson, N Andreasson, U Persson, S Carrillo, MC Collins, S Chalbot, S Cutler, N Dufour-Rainfray, D Fagan, AM Heegaard, NHH Hsiung, GYR Hyman, B Iqbal, K Lachno, DR Lleo, A Lewczuk, P Molinuevo, JL Parchi, P Regeniter, A Rissman, R Rosenmann, H Sancesario, G Schroder, J Shaw, LM Teunissen, CE Trojanowski, JQ Vanderstichele, H Vandijck, M Verbeek, MM Zetterberg, H Blennow, K Kaser, SA AF Mattsson, Niklas Andreasson, Ulf Persson, Staffan Carrillo, Maria C. Collins, Steven Chalbot, Sonia Cutler, Neal Dufour-Rainfray, Diane Fagan, Anne M. Heegaard, Niels H. H. Hsiung, Ging-Yuek Robin Hyman, Bradley Iqbal, Khalid Lachno, D. Richard Lleo, Alberto Lewczuk, Piotr Molinuevo, Jose L. Parchi, Piero Regeniter, Axel Rissman, Robert Rosenmann, Hanna Sancesario, Giuseppe Schroeder, Johannes Shaw, Leslie M. Teunissen, Charlotte E. Trojanowski, John Q. Vanderstichele, Hugo Vandijck, Manu Verbeek, Marcel M. Zetterberg, Henrik Blennow, Kaj Kaeser, Stephan A. CA Alzheimers Assoc QC Program TI CSF biomarker variability in the Alzheimer's Association quality control program SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Cerebrospinal fluid; Biomarkers; External assurance; Quality control; Proficiency testing ID CEREBROSPINAL-FLUID BIOMARKERS; NEUROCHEMICAL DEMENTIA DIAGNOSTICS; MILD COGNITIVE IMPAIRMENT; NATIONAL INSTITUTE; DISEASE; TAU; RECOMMENDATIONS; WORKGROUPS; GUIDELINES AB Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods: Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Molndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. Results: A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). Conclusions: The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan; Zetterberg, Henrik; Blennow, Kaj] Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad,Inst Neurosci & Physiol, Clin Neurochem Lab,Dept Psychiat & Neurochem, Molndal, Sweden. [Mattsson, Niklas] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA. [Carrillo, Maria C.] Alzheinzers Assoc, Chicago, IL USA. [Collins, Steven] Univ Melbourne, Dept Pathol, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia. [Chalbot, Sonia; Iqbal, Khalid] New York State Inst Basic Res, Staten Isl, NY USA. [Cutler, Neal] Worldwide Clin Trials, Beverly Hills, CA USA. [Dufour-Rainfray, Diane] CHRU Tours, Nucl Med Lab, Tours, France. [Dufour-Rainfray, Diane] Univ Tours, Val Loire Univ, PRES Ctr, Tours, France. [Dufour-Rainfray, Diane] Univ Tours, Val Loire Univ, PRES Ctr, UMR INSERM Imagerie & Cerveau U930, Tours, France. [Fagan, Anne M.] Washington Univ, St Louis, MO USA. [Heegaard, Niels H. H.] Statens Serum Inst, Dept Clin Biochem Immunol & Genet, DK-2300 Copenhagen, Denmark. [Hsiung, Ging-Yuek Robin] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Hyman, Bradley] MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Lachno, D. Richard] Eli Lilly & Co, Windlesham, Surrey, England. [Lleo, Alberto] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Lewczuk, Piotr] Univ Klinikum Erlangen, Erlangen, Germany. [Molinuevo, Jose L.] ICN Hosp Clin & Univ, Neurol Serv, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain. [Molinuevo, Jose L.] Pasqual Maragall Fdn, Barcelona, Spain. [Parchi, Piero] Univ Bologna, Inst Neurol Sci, Bologna, Italy. [Parchi, Piero] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy. [Regeniter, Axel] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Rissman, Robert] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Rosenmann, Hanna] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Sancesario, Giuseppe] Univ Roma Tor Vergata, Gen Hosp, Rome, Italy. [Schroeder, Johannes] Univ Klinikum Heidelberg, Sekt Gerontopsychiat, Heidelberg, Germany. [Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Philadelphia, PA 19104 USA. [Teunissen, Charlotte E.] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Amsterdam, Netherlands. [Vanderstichele, Hugo] ADx NeuroSci, Ghent, Belgium. [Vandijck, Manu] Innogenet Nv, Ghent, Belgium. [Verbeek, Marcel M.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain, Dept Neurol, NL-6525 ED Nijmegen, Netherlands. [Verbeek, Marcel M.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain, Dept Lab Med, NL-6525 ED Nijmegen, Netherlands. [Zetterberg, Henrik] UCL, Inst Neurol, London, England. [Kaeser, Stephan A.] Univ Tubingen, Tubingen, Germany. RP Mattsson, N (reprint author), Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad,Inst Neurosci & Physiol, Clin Neurochem Lab,Dept Psychiat & Neurochem, Molndal, Sweden. EM niklas.mattsson@neuro.gu.se RI Otto, Markus/F-4304-2015; Verbeek, Marcel/D-1971-2010; Vecsei, Laszlo/B-2066-2010; Parchi, Piero/L-9833-2015; Chiasserini, Davide/K-7074-2016; OI Otto, Markus/0000-0003-4273-4267; Molinuevo, Jose Luis/0000-0003-0485-6001; Kummer, Markus/0000-0002-0993-2918; Vecsei, Laszlo/0000-0001-8037-3672; Parchi, Piero/0000-0002-9444-9524; Chiasserini, Davide/0000-0002-1169-3258; Collins, Steven/0000-0002-5245-6611 FU NIA NIH HHS [P01 AG026276, P50 AG005131, P50 AG005134, P50 AG005681] NR 28 TC 116 Z9 118 U1 4 U2 40 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2013 VL 9 IS 3 BP 251 EP 261 DI 10.1016/j.jalz.2013.01.010 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 147QZ UT WOS:000319183400001 PM 23622690 ER PT J AU Royall, DR Palmer, RF AF Royall, Donald R. Palmer, Raymond F. TI Alzheimer's disease pathology does not mediate the association between depressive symptoms and subsequent cognitive decline SO ALZHEIMERS & DEMENTIA LA English DT Article DE Aging; Alzheimer's disease; Depression; Longitudinal; Neuropathology ID OLDER PERSONS; MISSING DATA; RISK-FACTOR; DEMENTIA; IMPAIRMENT; CRITERIA; PLAQUES; TANGLES; WORK; AD AB Background: Depressive symptoms in nondemented individuals appear to hasten the progression from mild cognitive impairment to clinical Alzheimer's disease (AD) and double the risk of incident AD. However, the mechanism(s) by which depression might affect this risk has not been well established. The purpose of this analysis was to test the hypothesis that AD pathology mediates depression's apparent effect on the risk of dementia conversion using longitudinally collected psychometric testing and autopsy data from the Honolulu-Asia Aging Study. Methods: Latent factor variables representing AD, cortical Lewy body (CLB), and ischemic neuropathology were tested as potential mediators of the association between the Center for Epidemiological Studies depression scale (CES-D) score and the 10-year prospective rate of cognitive decline, adjusted for baseline cognition, age, education, total number of medications, and brain weight at autopsy. Results: CES-D scores, neurofibrillary tangle counts, CLB counts, and ischemic lesions each made significant independent contributions to cognitive decline. However, CES-D scores were not significantly associated with any pathological variable; thus the pathological variables were not mediators of the effect of CES-D scores on cognitive decline. Conclusions: Subsyndromal depressive symptoms are significantly associated with subsequent cognitive decline. Although the effect is relatively modest, it is stronger than that of amyloid-related neuropathologies and independent of that of neurofibrillary tangles, cortical Lewy bodies, and ischemic lesions. Our results argue against the role of AD-related neuropathology as a mediator of depression's effect on cognitive decline, but cannot rule out a significant mediation effect in a subset of cases, perhaps with more severe baseline depressive symptoms. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Royall, Donald R.; Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Royall, Donald R.] Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, South Texas Vet Hlth Syst, San Antonio, TX 78284 USA. RP Royall, DR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. EM royall@uthscsa.edu FU National Institute of Neurological Disorders and Stroke (National Institutes of Health, USA) [NSO48123-01]; Julia and Van Buren Parr professorship in Aging and Geriatric Psychiatry; NINDS [NS048123-01, N01-AG-4-2149]; National Institute on Aging [U01 AG0 19349] FX HAAS data were provided by Lon R. White, the HAAS Principal Investigator, but the HAAS staff were not further involved in the analysis or interpretation of the data. This work was funded by National Institute of Neurological Disorders and Stroke (National Institutes of Health, USA), grant number NSO48123-01. HAAS neuropathological data were entirely generated by a team of 4 expert neuropathologists under the leadership of Dr. William Markesbery (deceased), with the oversight of Lon R. White, the HAAS Principal Investigator. Other members of the team were Dr. John Hardman (deceased), Dr. James Nelson (retired), and Dr. Daron Davis (who left the study for a clinical practice in 2001). D.R.R. and R.F.P. were funded by the Julia and Van Buren Parr professorship in Aging and Geriatric Psychiatry. The authors accept full responsibility for all analyses, results, and interpretations.; This work has been supported by NINDS R21 Grant NS048123-01, contract N01-AG-4-2149, and grant U01 AG0 19349 from the National Institute on Aging. NR 33 TC 15 Z9 15 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2013 VL 9 IS 3 BP 318 EP 325 DI 10.1016/j.jalz.2011.11.009 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 147QZ UT WOS:000319183400009 PM 23154050 ER PT J AU Rountree, SD Atri, A Lopez, OL Doody, RS AF Rountree, Susan D. Atri, Alireza Lopez, Oscar L. Doody, Rachelle S. TI Effectiveness of antidementia drugs in delaying Alzheimer's disease progression SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Clinical trials; Therapeutics ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; MEMANTINE TREATMENT; OPEN-LABEL; CHOLINESTERASE INHIBITION; GLOBAL FUNCTION; DONEPEZIL; MODERATE; EFFICACY AB Background: Randomized controlled trials (RCTs) provide safety and efficacy data for regulatory approval of antidementia drugs, but offer limited data regarding real-world effectiveness. Long-term observational controlled studies (LTOCs) extend our understanding by providing longitudinal data across multiple stages of Alzheimer's disease (AD). Methods: Comparisons of strengths, limitations, evidence level, and results for monotherapy (cholinesterase inhibitors) and combination therapy (cholinesterase inhibitors + memantine) in RCTs versus LTOCs were made. Results: Similar to RCTs, LTOCs have shown that both monotherapy and combination therapy are associated with slower cognitive and functional decline. Combination therapy is associated with better cognitive outcomes and greater delays in time to nursing home admission versus monotherapy or no treatment. Persistent antidementia drug treatment is associated with slower decline in cognition, daily function, and global severity, even in patients with advanced disease. Conclusions: LTOCs provide complementary evidence regarding effectiveness of antidementia therapy over many years, a time course relevant to AD management. These findings also provide compelling arguments in favor of using LTOCs to estimate effectiveness, risk benefit, and costs of AD treatments. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Rountree, Susan D.; Doody, Rachelle S.] Baylor Coll Med, Dept Neurol, Alzheimers Dis & Memory Disorders Ctr, Houston, TX 77030 USA. [Atri, Alireza] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Atri, Alireza] Neurol Memory Disorders Unit, Boston, MA USA. [Atri, Alireza] ENRM VA Med Ctr, GRECC, Bedford, MA USA. [Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Rountree, SD (reprint author), Baylor Coll Med, Dept Neurol, Alzheimers Dis & Memory Disorders Ctr, Houston, TX 77030 USA. EM rountree@bcm.edu OI Atri, Alireza/0000-0003-4405-6973 FU Forest Laboratories, Inc. (PL); Forest Research Institute; National Institute on Aging FX This article summarizes a roundtable discussion, funded by Forest Laboratories, Inc. (PL), that was held in conjunction with the International Conference on Alzheimer's Disease on July 12, 2010. Prescott Medical Communications Group (Chicago, IL) provided the authors with assistance in preparing slides for the roundtable event and manuscript timelines and formatting; however, neither FLI nor Prescott Medical Communications Group provided input into the manuscript content. The authors were compensated by FLI for participation in the roundtable discussion, but no compensation was provided in conjunction with this manuscript.; Conflicts of interest pertaining to Forest Laboratories, Inc., the sponsor of the roundtable held in conjunction with the International Conference on Alzheimer's Disease, 2010. S.D.R., Investigator-Initiated Grant Funding: Forest Research Institute; Honorarium: Forest Research Institute, for attending this roundtable. A.A., Continuing Medical Education (CME), Education Media and Lecture Honoraria: Forest, Prescott Medical Communications, Harvard Medical School CME, Massachusetts General Hospital Academy of Medical Educators and Reed Medical Education, Merz, Lundbeck, Turner White Communications; Consultant: Forest Research Institute; Investigator-Initiated Grant Funding: Forest Research Institute, National Institute on Aging. O.L.L., Consultant: Lundbeck, Pfizer. R.S.D. Honorarium: Forest Research Institute, for attending this roundtable. NR 54 TC 23 Z9 23 U1 1 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2013 VL 9 IS 3 BP 338 EP 345 DI 10.1016/j.jalz.2012.01.002 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 147QZ UT WOS:000319183400012 PM 23102979 ER PT J AU Grill, JD Karlawish, J Elashoff, D Vickrey, BG AF Grill, Joshua D. Karlawish, Jason Elashoff, David Vickrey, Barbara G. TI Risk disclosure and preclinical Alzheimer's disease clinical trial enrollment SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Preclinical; Prevention; Predementia; Recruitment; Risk; Clinical trial ID GENETIC RISK; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RECOMMENDATIONS; CHALLENGES AB To identify the facilitators and barriers to preclinical Alzheimer's disease (AD) clinical trial recruitment, 50 cognitively normal participants were interviewed after being randomized to one of two hypothetical AD risk scenarios: (1) the general age-related risk for AD, or (2) being at 50% increased risk for AD. Participants provided uncued barriers and facilitators to the hypothetical decision of whether they would enroll. Thirteen themes of facilitators and five themes of barriers were identified. The most common barrier was fear related to taking study drug. Those randomized to being at increased risk for AD more frequently cited lowering personal risk as a facilitator (P = .01) and less frequently cited time as a barrier to enrollment (P = .02). These results suggest potential challenges to preclinical AD clinical trial recruitment and that disclosing risk information may enhance enrollment. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Grill, Joshua D.; Elashoff, David] Univ Calif Los Angeles, Mary Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA. [Grill, Joshua D.; Vickrey, Barbara G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Karlawish, Jason] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Dept Med Eth, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Penn Memory Ctr, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Penn Ctr Bioeth, Philadelphia, PA 19104 USA. [Elashoff, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Vickrey, Barbara G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Grill, JD (reprint author), Univ Calif Los Angeles, Mary Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA. EM jgrill@mednet.ucla.edu FU NIA [AG016570]; Sidell Kagan Foundation; Marian S. Ware Alzheimer Program FX This work was supported by NIA AG016570 and the Sidell Kagan Foundation. Dr. J.K. is supported by the Marian S. Ware Alzheimer Program. The authors are grateful to the volunteer participants who made this work possible and to Dr. Po H. Lu who participated in the cutting-and-sorting analyses. NR 14 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2013 VL 9 IS 3 BP 356 EP 359 DI 10.1016/j.jalz.2012.03.001 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 147QZ UT WOS:000319183400014 PM 23141383 ER PT J AU Sherman, AV Gubitz, AK Al-Chalabi, A Bedlack, R Berry, J Conwit, R Harris, BT Horton, DK Kaufmann, P Leitner, ML Miller, R Shefner, J Vonsattel, JP Mitsumoto, H AF Sherman, Alexander V. Gubitz, Amelie K. Al-Chalabi, Ammar Bedlack, Richard Berry, James Conwit, Robin Harris, Brent T. Horton, D. Kevin Kaufmann, Petra Leitner, Melanie L. Miller, Robert Shefner, Jeremy Vonsattel, Jean Paul Mitsumoto, Hiroshi TI Infrastructure resources for clinical research in amyotrophic lateral sclerosis SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE Amyotrophic lateral sclerosis (ALS); motor neuron disease (MND); clinical research infrastructure; North America; Europe ID NEURON DISEASE; STEM-CELLS; ALS; EPIDEMIOLOGY AB Clinical trial networks, shared clinical databases, and human biospecimen repositories are examples of infrastructure resources aimed at enhancing and expediting clinical and/or patient oriented research to uncover the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disease that leads to the paralysis of voluntary muscles. The current status of such infrastructure resources, as well as opportunities and impediments, were discussed at the second Tarrytown ALS meeting held in September 2011. The discussion focused on resources developed and maintained by ALS clinics and centers in North America and Europe, various clinical trial networks, U. S. government federal agencies including the National Institutes of Health (NIH), the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC), and several voluntary disease organizations that support ALS research activities. Key recommendations included 1) the establishment of shared databases among individual ALS clinics to enhance the coordination of resources and data analyses; 2) the expansion of quality-controlled human biospecimen banks; and 3) the adoption of uniform data standards, such as the recently developed Common Data Elements (CDEs) for ALS clinical research. The value of clinical trial networks such as the Northeast ALS (NEALS) Consortium and the Western ALS (WALS) Consortium was recognized, and strategies to further enhance and complement these networks and their research resources were discussed. C1 [Sherman, Alexander V.] Massachusetts Gen Hosp, NCRI, Boston, MA 02114 USA. [Gubitz, Amelie K.; Conwit, Robin; Kaufmann, Petra] NINDS, NIH, Bethesda, MD 20892 USA. [Al-Chalabi, Ammar] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London WC2R 2LS, England. [Bedlack, Richard] Duke Inst Brain Sci, Sch Med, Div Neurol, Durham, NC USA. [Berry, James] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Harris, Brent T.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [Horton, D. Kevin] Agcy Tox Subst & Dis Registry, Div Toxicol & Human Hlth Sci, Atlanta, GA USA. [Leitner, Melanie L.] Prize4Life, Cambridge, MA USA. [Miller, Robert] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA USA. [Shefner, Jeremy] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Vonsattel, Jean Paul] Columbia Univ, New York Presbyterian Hosp, Med Ctr, Dept Pathol & Cell Biol, New York, NY USA. [Mitsumoto, Hiroshi] Columbia Univ, Dept Neurol, Med Ctr, Eleanor & Lou Gehrig MDA ALS Res Ctr, New York, NY USA. RP Sherman, AV (reprint author), Massachusetts Gen Hosp, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM avsherman@partners.org RI Al-Chalabi, Ammar/E-5361-2010 OI Al-Chalabi, Ammar/0000-0002-4924-7712 NR 22 TC 7 Z9 7 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD MAY PY 2013 VL 14 SU 1 BP 53 EP 61 DI 10.3109/21678421.2013.779058 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 145KH UT WOS:000319014100006 PM 23678880 ER PT J AU Chad, DA Bidichandani, S Bruijn, L Capra, JD Dickie, B Ferguson, J Figlewicz, D Forsythe, M Kaufmann, P Kirshner, A Monti, W AF Chad, David A. Bidichandani, Sanjay Bruijn, Lucie Capra, J. Donald Dickie, Brian Ferguson, John Figlewicz, Denise Forsythe, Melissa Kaufmann, Petra Kirshner, Annette Monti, William TI Funding agencies and disease organizations: Resources and recommendations to facilitate ALS clinical research SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE ALS; funding agencies; patient voluntary organizations AB Ten groups presented their perspectives on facilitating clinical research in ALS including four federal agencies, four disease organizations, one foundation and one advocacy group. The federal agencies (National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, Office of Rare Diseases Research, Department of Defense) encourage fostering a team approach between pre-clinical and clinical research investigators, coordinating with patient groups in the early phases of clinical studies, enhancing private and public partnerships, and investigating the interplay between genetic susceptibility and environmental exposure. The disease organizations (Muscular Dystrophy Association, ALS Association, ALS Society of Canada, and the Motor Neurone Disease Association UK) support fellowship training programs to develop ALS clinician scientists, and encourage work on the epidemiology of ALS, on genetic and epigenetic mechanisms that are relevant to ALS pathogenesis, on developing ALS registries and biobanks, and building bridges of collaboration among study groups. The Foundation supports innovative projects, including stem-cell research, and Patient Advocacy is committed to supporting excellence in ALS research and patient care, and believes strongly in enhancing communication between patients and members of the research community. C1 [Chad, David A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickie, Brian] Motor Neuron Dis Assoc, Northampton, England. [Ferguson, John] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [Figlewicz, Denise] ALS Soc Canada, Bethesda, MD USA. [Forsythe, Melissa] USA, Med Res & Mat Command, Congressionally Directed Med Res Programs Off, Bethesda, MD USA. [Kaufmann, Petra] NINDS, NIH, Bethesda, MD 20892 USA. [Kirshner, Annette] NIEHS, NIH, Bethesda, MD USA. [Monti, William] ALS Advocacy, New York, NY USA. RP Chad, DA (reprint author), Neuromuscular Diagnost Ctr, 165 Cambridge St,Suite 820,CPZ 8, Boston, MA 02114 USA. EM dchad@partners.org NR 0 TC 1 Z9 1 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD MAY PY 2013 VL 14 SU 1 BP 62 EP 66 DI 10.3109/21678421.2013.778588 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 145KH UT WOS:000319014100007 PM 23678881 ER PT J AU Chad, DA Rowland, LP Armon, C Bedlack, R Durham, H Factor-Litvak, P Heiman-Patterson, T Heitzman, D Lacomis, D Ludolph, A Maragakis, N Miller, R Pattee, G Shoesmith, C Sorenson, E Turner, MR AF Chad, David A. Rowland, Lewis P. Armon, Carmel Bedlack, Richard Durham, Heather Factor-Litvak, Pam Heiman-Patterson, Terry Heitzman, Daragh Lacomis, David Ludolph, Albert Maragakis, Nicholas Miller, Robert Pattee, Gary Shoesmith, Christen Sorenson, Eric Turner, Martin R. TI Peer recommendations on how to improve clinical research, and Conference wrap-up SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE ALS; clinical research; peer recommendations ID HEXANUCLEOTIDE REPEAT; ALS; C9ORF72; FTD AB To promote clinical and patient oriented research, as part of the Second International ALS Conference in Tarrytown, NY, USA, seven pairs of clinicians and scientists were asked to lead discussions with meeting attendees on six major topics (one of which was discussed by two groups); each one the focus of a 90-min Breakout Session. Approximately 25 meeting attendees participated in each session. The Breakout Sessions considered six major themes: 1) Approaches to encourage clinicians to engage in more clinical research to discover the pathogenesis and cause of ALS; 2) Exploring avenues to build more effective partnerships between basic scientists and ALS physicians; 3) Increasing patient interest and commitment to participating in non-trial clinical research; 4) Brainstorming about factors that are most critical to the discovery of the pathogenesis and cause of ALS; 5) Finding ways to incorporate clinical research projects into clinical trials; and 6) Developing state-of-the-art epidemiological studies to solve the mystery of ALS. In this paper, we present the reports from each of the Breakout Sessions; and we provide a wrap-up of the entire conference. C1 [Chad, David A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rowland, Lewis P.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Armon, Carmel] Baystate Med Ctr, Div Neurol, Springfield, MA USA. [Bedlack, Richard] Duke Univ, Med Ctr, Duke ALS Clin, Durham, NC USA. [Durham, Heather] McGill Univ, Dept Neurol, Montreal, PQ H3A 2T5, Canada. [Factor-Litvak, Pam] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Heiman-Patterson, Terry] Drexel Univ, Dept Neurol, Coll Med, Philadelphia, PA 19104 USA. [Heitzman, Daragh] Texas Neurol, Dallas, TX USA. [Lacomis, David] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Ludolph, Albert] Univ Ulm, Dept Neurol, D-89069 Ulm, Germany. [Maragakis, Nicholas] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Miller, Robert] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA USA. [Pattee, Gary] Univ Nebraska Med Ctr, Dept Neurol, Omaha, NE USA. [Shoesmith, Christen] London Hlth Sci Ctr, Dept Neurol, London, ON, Canada. [Sorenson, Eric] Mayo Clin, Dept Neurol, Rochester, MN USA. [Turner, Martin R.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England. RP Chad, DA (reprint author), Neuromuscular Diagnost Ctr, 165 Cambridge St,Suite 820,CPZ 8, Boston, MA 02114 USA. EM dchad@partners.org OI Turner, Martin/0000-0003-0267-3180 FU Medical Research Council [G0701923]; NIEHS NIH HHS [R01 ES016348] NR 7 TC 1 Z9 1 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD MAY PY 2013 VL 14 SU 1 BP 67 EP 73 DI 10.3109/21678421.2013.778605 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 145KH UT WOS:000319014100008 PM 23678882 ER PT J AU Vincenzi, B Borba, CPC Gray, DA Copeland, PM Wang, XY Fan, XD Aragam, GG Henderson, DC AF Vincenzi, Brenda Borba, Christina P. C. Gray, Deborah A. Copeland, Paul M. Wang, Xingyue Fan, Xiaoduo Aragam, Gowri G. Henderson, David C. TI An exploratory study examining lipid-lowering medications in reducing fasting serum lipids in schizophrenia patients treated with atypical antipsychotics SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE schizophrenia; fibrate treatment; statin treatment; metabolic disorders; atypical antipsychotics ID CORONARY-HEART-DISEASE; LIPOPROTEIN SUBPARTICLE PROFILES; SIMVASTATIN PLUS FENOFIBRATE; MIXED DYSLIPIDEMIA; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; HDL CHOLESTEROL; WEIGHT-GAIN; METABOLIC SYNDROME; RISK-FACTOR AB BACKGROUND: We present a retrospective study examining response to treatment with fibrates or statins in schizophrenia patients. METHODS: We identified the patient population using the Research Patient Data Registry. Demographic data, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL cholesterol (non-HDL-C) levels were obtained before initiation of treatment with lipid-lowering medication (LLM) and after LLM treatment was initiated (N = 183). RESULTS: Treatment with LLMs resulted in a statistically significant decrease in total cholesterol, triglycerides, LDL-C, and non-HDL-C. An independent-samples t test comparing the statin treatment-alone group with the fibrate treatment-alone group showed a significant reduction in triglyceride levels from baseline to 1-year follow-up in the fibrate treatment-alone group. CONCLUSIONS: The results of this study indicate that schizophrenia patients respond to LLMs in a manner consistent with the general population. Future studies would benefit from a larger sample, as well as comparisons between more specific treatment groups, such as those defined by type of statin or fibrate, to observe differential effects on specific markers of dyslipidemia in this population. C1 [Vincenzi, Brenda; Gray, Deborah A.; Wang, Xingyue; Aragam, Gowri G.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Borba, Christina P. C.; Fan, Xiaoduo; Henderson, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schizophrenia Program, Boston, MA USA. [Copeland, Paul M.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Vincenzi, B (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM bvincenzi@partners.org FU Novartis; Otsuka FX Dr. Vincenzi, Dr. Borba, Ms. Gray, Ms. Wang, and Ms. Aragam report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Copeland is a consultant to sanofi-aventis. Dr. Fan is a consultant to Eli Lilly and Company. Dr. Henderson receives grant or research support from Novartis and Otsuka and is a consultant to Alkermes. NR 54 TC 7 Z9 7 U1 2 U2 4 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 EI 1547-3325 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD MAY PY 2013 VL 25 IS 2 BP 141 EP 148 PG 8 WC Psychiatry SC Psychiatry GA 149HL UT WOS:000319309500009 PM 23638445 ER PT J AU Vielma, SA Klein, RL Levingston, CA Young, MRI AF Vielma, Silvana A. Klein, Richard L. Levingston, Corinne A. Young, M. Rita I. TI Premalignant Lesions Skew Spleen Cell Responses to Immune Modulation by Adipocytes SO ANTICANCER RESEARCH LA English DT Article DE Adipocytes; cytokines; immune regulation; inflammation; premalignant lesion cells ID REGULATORY T-CELLS; CANCER-RISK; INSULIN-RESISTANCE; BREAST-CANCER; OBESITY; CYTOKINES; LEPTIN; INFLAMMATION; ADIPOKINES; DIFFERENTIATION AB Obesity can promote a chronic inflammatory state and is associated with an increased risk for cancer. Since adipocytes can produce mediators that can regulate conventional immune cells, this study sought to determine if the presence of premalignant oral lesions would skew how immune cells respond to adipocyte-derived mediators to create an environment that may be more favorable for their progression toward cancer. While media conditioned by adipocytes stimulated normal spleen cell production of the T helper (Th) type-1 cytokines interleukin (IL)-2, interferon-gamma (IFN-gamma), IL-12 and granulocyte-monocyte colony-stimulating factor (GM CSF), media from premalignant lesion cells either blocked or had no added affect on the adipocyte-stimulated Th1 cytokine production. In contrast, media conditioned by premalignant lesion cells exacerbated adipocyte-stimulated spleen cell production of the Th2 cytokines IL-10 and IL-13, although it did not further enhance the adipocyte-stimulated spleen cell production of IL-4 and TGF-beta. The premalignant lesion environment also heightened the adipocyte-stimulated spleen cell production of the inflammatory mediators IL 1 alpha, IL-1 beta, IL-6 and IL-9, although it did not further increase the adipocyte-stimulated production of tumor necrosis factor-alpha (TNF-alpha). IL 17 production was unaffected by the adipocyte-derived mediators, but was synergistically triggered by adding media from premalignant lesion cells. These stimulatory effects on spleen cell production of Th2 and inflammatory mediators were not induced in the absence of media conditioned by adipocytes. In contrast, media conditioned by adipocytes did not stimulate production of predominantly monocyte-derived chemokine C-X-C motif ligand (CXCL)9, chemokine C-C motif ligand (CCL)3 or CCL4, although it stimulated production of CCL2 and the predominantly T cell-derived chemokine CCL5, which was the only chemokine whose production was further increased by media from premalignant lesions. These results suggest that the responsiveness of spleen cells to adipocyte-derived mediators is influenced by mediators from premalignant lesion cells to favor conventional immune cell production of a Th2 and inflammatory cytokines. C1 [Vielma, Silvana A.; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. [Klein, Richard L.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Dept Hematol Oncol, Charleston, SC 29425 USA. [Vielma, Silvana A.] Univ Los Andes, Dept Clin Microbiol & Parasitol, Merida, Venezuela. [Klein, Richard L.; Levingston, Corinne A.; Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM Rita.Young@va.gov FU Biomedical Laboratory of the Department of Veterans Affairs; Department of Veterans Affairs; National Institute of Health [I01-CX000100, R01 CA128837, R01 DE018268] FX This work was supported by the Biomedical Laboratory and Clinical Sciences Programs of the Department of Veterans Affairs. and by grants from the National Institute of Health awarded to M. Rita I. Young (I01-CX000100, R01 CA128837 and R01 DE018268). NR 45 TC 2 Z9 2 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY PY 2013 VL 33 IS 5 BP 1809 EP 1818 PG 10 WC Oncology SC Oncology GA 148GR UT WOS:000319233100004 PM 23645725 ER PT J AU Martinez-Pastor, B Cosentino, C Mostoslavsky, R AF Martinez-Pastor, Barbara Cosentino, Claudia Mostoslavsky, Raul TI A Tale of Metabolites: The Cross-Talk between Chromatin and Energy Metabolism SO CANCER DISCOVERY LA English DT Editorial Material ID HISTONE ACETYLATION AB Mitochondrial metabolism influences histone and DNA modifications by retrograde signaling and activation of transcriptional programs. Considering the high number of putative sites for acetylation and methylation in chromatin, we propose in this perspective article that epigenetic modifications might impinge on cellular metabolism by affecting the pool of acetyl-CoA and S-adenosylmethionine. Cancer Discov; 3(5); 497-501. (C) 2013 AACR. C1 [Martinez-Pastor, Barbara; Cosentino, Claudia; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Mostoslavsky, R (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Simches Bldg CPZN 4208, Boston, MA 02114 USA. EM rmostoslavsky@mgh.harvard.edu FU NCI NIH HHS [R01 CA175727]; NIDDK NIH HHS [DK088190-01A1, R01 DK088190]; NIGMS NIH HHS [GM093072-01, R01 GM093072] NR 15 TC 22 Z9 22 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2013 VL 3 IS 5 BP 497 EP 501 DI 10.1158/2159-8290.CD-13-0059 PG 5 WC Oncology SC Oncology GA 147ZI UT WOS:000319210600021 PM 23658298 ER PT J AU Sanda, T Tyner, JW Gutierrez, A Ngo, VN Glover, J Chang, BH Yost, A Ma, WX Fleischman, AG Zhou, WJ Yang, YD Kleppe, M Ahn, Y Tatarek, J Kelliher, MA Neuberg, DS Levine, RL Moriggl, R Muller, M Gray, NS Jamieson, CHM Weng, AP Staudt, LM Druker, BJ Look, AT AF Sanda, Takaomi Tyner, Jeffrey W. Gutierrez, Alejandro Ngo, Vu N. Glover, Jason Chang, Bill H. Yost, Arla Ma, Wenxue Fleischman, Angela G. Zhou, Wenjun Yang, Yandan Kleppe, Maria Ahn, Yebin Tatarek, Jessica Kelliher, Michelle A. Neuberg, Donna S. Levine, Ross L. Moriggl, Richard Mueller, Mathias Gray, Nathanael S. Jamieson, Catriona H. M. Weng, Andrew P. Staudt, Louis M. Druker, Brian J. Look, A. Thomas TI TYK2-STAT1-BCL2 Pathway Dependence in T-cell Acute Lymphoblastic Leukemia SO CANCER DISCOVERY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACTIVATING MUTATIONS; KINASE INHIBITOR; LUNG-CANCER; INTERLEUKIN-10; BCL-2; RECEPTOR; LYMPHOMA; TARGETS; JAK1 AB Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effector STAT1, in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently showed TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK activity induced T-ALL cell death. Activation of this TYK2-STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of interleukin (IL)-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the antiapoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2-STAT1-BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway. SIGNIFICANCE: In recent years, "pathway dependence" has been revealed in specific types of human cancer, which can be important because they pinpoint proteins that are particularly vulnerable to antitumor-targeted inhibition (so-called Achilles' heel proteins). Here, we use RNAi technology to identify a novel oncogenic pathway that involves aberrant activation of the TYK2 tyrosine kinase and its downstream substrate, STAT1, which ultimately promotes T-ALL cell survival through the upregulation of BCL2 expression. Cancer Discov; 3(5); 564-77. (C) 2013 AACR. C1 [Sanda, Takaomi; Gutierrez, Alejandro; Ahn, Yebin; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Zhou, Wenjun; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Gutierrez, Alejandro; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Tatarek, Jessica; Kelliher, Michelle A.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA. [Tyner, Jeffrey W.; Fleischman, Angela G.; Druker, Brian J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Glover, Jason; Chang, Bill H.] Oregon Hlth & Sci Univ, Dept Pediat, Div Pediat Hematol & Oncol, Portland, OR 97239 USA. [Druker, Brian J.] Howard Hughes Med Inst, Portland, OR USA. [Ngo, Vu N.] City Hope Natl Med Ctr, Beckman Res Inst, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA. [Ma, Wenxue] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Ma, Wenxue; Jamieson, Catriona H. M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Yost, Arla; Weng, Andrew P.] BC Canc Agcy, Terry Fox Lab, Dept Pathol, Vancouver, BC, Canada. [Yang, Yandan; Staudt, Louis M.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Kleppe, Maria; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Moriggl, Richard] Univ Vet Med Vienna, Ludwig Boltzmann Inst Canc Res, Vienna, Austria. [Mueller, Mathias] Univ Vet Med Vienna, Inst Anim Breeding & Genet, Vienna, Austria. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer Bldg,Rm 630,450 Brookline Ave, Boston, MA 02215 USA. EM drukerb@ohsu.edu; thomas_look@dfci.harvard.edu RI Kleppe, Maria/C-6341-2014; Weng, Andrew/I-5015-2014; OI Fleischman, Angela/0000-0002-3701-6079; Chang, Bill/0000-0003-3783-1820; Moriggl, Richard/0000-0003-0918-9463; Kleppe, Maria/0000-0002-4372-6704; Gutierrez, Alejandro/0000-0002-0249-9007; Tyner, Jeffrey/0000-0002-2133-0960 FU William Lawrence and Blanche Hughes Fund; Leukemia & Lymphoma Society; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute [4R00CA151457-03]; Oregon Clinical and Translational Research Institute (OCTRI) from the National Center for Research Resources (NRCC), a component of the NIH [UL1 RR024140]; NIH Roadmap for Medical Research; NIH [NCI 1K99CA157951, NCI 1K08CA133103]; Children's Leukemia Research Association; Japan Society for the Promotion of Science; Oregon Child Health Research Center; Austrian Science Fund FWF [SFB F28]; NCI [5P01CA109901, NCI 5P01CA68484]; Alex's Lemonade Stand Foundation Bridge grant; European Molecular Biology Organization (EMBO) long-term fellowship; CIHR/Terry Fox Foundation; California Institute for Regenerative Medicine (CIRM) [TR21789, RN2-00910-1, DR1-01430]; Leichtag Family Foundation; Ratner Family Foundation; [5P30CA069533] FX This work was supported in part by the William Lawrence and Blanche Hughes Fund, the Leukemia & Lymphoma Society, and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. J.W. Tyner is supported by grants from the National Cancer Institute (4R00CA151457-03) and the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NRCC), a component of the NIH, and the NIH Roadmap for Medical Research. T. Sanda is supported by NIH grant NCI 1K99CA157951, Children's Leukemia Research Association, and the Japan Society for the Promotion of Science. A. Gutierrez is supported by NIH grant NCI 1K08CA133103 and is a scholar of the American Society of Hematology-Amos Medical Faculty Development Program. B.H. Chang is supported by the Oregon Child Health Research Center and is a St. Baldrick's Scholar. R. Moriggl and M. Muller are supported by grant SFB F28 of the Austrian Science Fund FWF. A.T. Look and D.S. Neuberg are supported by NCI grants 5P01CA109901 and NCI 5P01CA68484, and A.T. Look is supported by an Alex's Lemonade Stand Foundation Bridge grant. B.J. Druker is an investigator of the Howard Hughes Medical Institute and principal investigator of the OHSU cancer center support grant 5P30CA069533. M. Kleppe is supported by the European Molecular Biology Organization (EMBO) long-term fellowship. R.L. Levine is a Scholar of the Leukemia and Lymphoma Society. A. Yost and A.P. Weng are supported by a CIHR/Terry Fox Foundation program project grant. W. Ma and C.H.M. Jamieson are supported by the California Institute for Regenerative Medicine (CIRM) grants (TR21789; RN2-00910-1; DR1-01430) as well as the Leichtag Family Foundation and the Ratner Family Foundation. NR 47 TC 42 Z9 42 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2013 VL 3 IS 5 BP 564 EP 577 DI 10.1158/2159-8290.CD-12-0504 PG 14 WC Oncology SC Oncology GA 147ZI UT WOS:000319210600027 PM 23471820 ER PT J AU Maki, T Hayakawa, K Pham, LDD Xing, CH Lo, EH Arai, K AF Maki, Takakuni Hayakawa, Kazuhide Pham, Loc-Duyen D. Xing, Changhong Lo, Eng H. Arai, Ken TI Biphasic Mechanisms of Neurovascular Unit Injury and Protection in CNS Diseases SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Neurovascular unit; stroke; central nervous system injury; neuroprotection; remodeling; astrocyte; cerebral endothelial cell; microglia ID BLOOD-BRAIN-BARRIER; AMYOTROPHIC-LATERAL-SCLEROSIS; ENDOTHELIAL GROWTH-FACTOR; OLIGODENDROCYTE PRECURSOR CELLS; AMYLOID-BETA CLEARANCE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; IN-VIVO; MATRIX METALLOPROTEINASES AB In the past decade, evidence has emerged that there is a variety of bidirectional cell-cell and/or cell-extracellular matrix interactions within the neurovascular unit (NVU), which is composed of neuronal, glial, and vascular cells along with extracellular matrix. Many central nervous system diseases, which lead to NVU dysfunction, have common features such as glial activation/transformation and vascular/blood-brain-barrier alteration. These phenomena show dual opposite roles, harmful at acute phase and beneficial at chronic phase. This diverse heterogeneity may induce biphasic clinical courses, i.e. degenerative and regenerative processes in the context of dynamically coordinated cell-cell/cell-matrix interactions in the NVU. A deeper understanding of the seemingly contradictory actions in cellular levels is essential for NVU protection or regeneration to suppress the deleterious inflammatory reactions and promote adaptive remodeling after central nervous system injury. This mini-review will present an overview of recent progress in the biphasic roles of the NVU and discuss the clinical relevance of NVU responses associated with central nervous system diseases, such as stroke and other chronic neurodegenerative diseases. C1 Massachusetts Gen Hosp, Dept Radiol & Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Arai, K (reprint author), Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU Research Abroad from the Japan Society for the Promotion of Science; Deane Foundation; American Heart Association; National Institutes of Health FX This work was supported in part by Research Abroad from the Japan Society for the Promotion of Science (T.M.), the Deane Foundation (E.H.L and K.A.), American Heart Association (E.H.L and K.A.), and National Institutes of Health (E.H.L and K.A.). The authors thank Drs. Ji Hae Seo and Nobukazu Miyamoto for many helpful discussions. NR 175 TC 28 Z9 29 U1 1 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD MAY PY 2013 VL 12 IS 3 BP 302 EP 315 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 145CE UT WOS:000318990800004 PM 23469847 ER PT J AU Leak, RK Zhang, LL Stetler, RA Weng, ZF Li, PY Atkins, GB Gao, YQ Chen, J AF Leak, Rehana K. Zhang, Lili Stetler, R. Anne Weng, Zhongfang Li, Peiying Atkins, G. Brandon Gao, Yanqin Chen, Jun TI HSP27 Protects the Blood-Brain Barrier Against Ischemia-Induced Loss of Integrity SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Endothelial cell; heat shock protein; HSP25; HSPB1; microvessel; stroke; tight junction; vascular ID HEAT-SHOCK-PROTEIN; FOCAL CEREBRAL-ISCHEMIA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTRACEREBRAL HEMORRHAGE; CYTOCHROME-C; CELL-DEATH; ISCHEMIA/REPERFUSION INJURY; MOLECULAR CHAPERONES; NEURONAL INJURY; PRECURSOR CELLS AB Loss of integrity of the blood-brain barrier (BBB) in stroke victims initiates a devastating cascade of events including extravasation of blood-borne molecules, water, and inflammatory cells deep into brain parenchyma. Thus, it is important to identify mechanisms by which BBB integrity can be maintained in the face of ischemic injury in experimental stroke. We previously demonstrated that the phylogenetically conserved small heat shock protein 27 (HSP27) protects against transient middle cerebral artery occlusion (tMCAO). Here we show that HSP27 transgenic overexpression also maintains the integrity of the BBB in mice subjected to tMCAO. Extravasation of endogenous IgG antibodies and exogenous FITC-albumin into the brain following tMCAO was reduced in transgenic mice, as was total brain water content. HSP27 overexpression abolished the appearance of TUNEL-positive profiles in microvessel walls. Transgenics also exhibited less loss of microvessel proteins following tMCAO. Notably, primary endothelial cell cultures were rescued from oxygen-glucose deprivation (OGD) by lentiviral HSP27 overexpression according to four viability assays, supporting a direct effect on this cell type. Finally, HSP27 overexpression reduced the appearance of neutrophils in the brain and inhibited the secretion of five cytokines. These findings reveal a novel role for HSP27 in attenuating ischemia/reperfusion injury - the maintenance of BBB integrity. Endogenous upregulation of HSP27 after ischemia in wild-type animals may exert similar protective functions and warrants further investigation. Exogenous enhancement of HSP27 by rational drug design may lead to future therapies against a host of injuries, including but not limited to a harmful breach in brain vasculature. C1 [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Zhang, Lili; Stetler, R. Anne; Weng, Zhongfang; Li, Peiying; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Zhang, Lili; Stetler, R. Anne; Weng, Zhongfang; Li, Peiying; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Zhang, Lili; Stetler, R. Anne; Weng, Zhongfang; Li, Peiying; Chen, Jun] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Sch Med, Pittsburgh, PA 15213 USA. [Atkins, G. Brandon] Case Western Reserve Univ, Case Cardiovasc Res Inst, Dept Med, Sch Med, Cleveland, OH 44106 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, Dept Neurol, S507 Biomed Sci Tower, 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 Mylan School of Pharmacy at Duquesne University; VA Merit Review grant; National Institutes of Neurological Disorders and Stroke [NS043802, NS045048, NS036736, NS056118]; Chinese Natural Science Foundation [30670642, 30870794, 81020108021]; VA Research Career Scientist Award; RK Mellon Endowed Chair from UPMC FX RKL and LZ contributed equally to this work. RKL, LZ, RAS, ZW, and PL performed the experiments and analyzed the data. RKL wrote the manuscript. JC and YG designed the experiments, analyzed the data, and helped write the manuscript. GBA contributed new research reagents. The authors acknowledge the administrative assistance of Pat Strickler, Deb Wilson, Mary Caruso, and Jackie Farrer. RKL was supported by a startup from the Mylan School of Pharmacy at Duquesne University. JC was supported by VA Merit Review grant and National Institutes of Neurological Disorders and Stroke grants NS043802, NS045048, NS036736, and NS056118. YG was supported by Chinese Natural Science Foundation grants 30670642, 30870794, and 81020108021. JC is a recipient of the VA Research Career Scientist Award and the RK Mellon Endowed Chair from UPMC. NR 61 TC 6 Z9 7 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD MAY PY 2013 VL 12 IS 3 BP 325 EP 337 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 145CE UT WOS:000318990800006 PM 23469858 ER PT J AU Richards, D Larkin, M Milaszewski, K Javier, E Casey, T Grey, M AF Richards, Denise Larkin, Mary Milaszewski, Kerry Javier, Elaine Casey, Terri Grey, Margaret TI Learning Needs of Youth With Type 2 Diabetes SO DIABETES EDUCATOR LA English DT Article ID SELF-MANAGEMENT EDUCATION; CHILDREN AB Purpose The purpose of this study was to examine reports of diabetes learning needs by youth with type 2 diabetes and their family support person (FSP) and to examine correlations of these perceptions with demographic variables. Methods Data were analyzed from the Participant Needs Assessment (PNA), a routinely self-administered questionnaire designed to assess learning needs, in 191 youth (mean age = 14.0 +/- 1.9 years, duration 8.78 +/- 6.30 months; 36% black, non-Hispanic; 40% Hispanic; 20% white) enrolled in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Youth and their FSPs completed the PNA at scheduled study visits, rating their learning needs on a 5-point scale, with higher scores indicating higher needs. Paired t tests and ANOVA were used. Results There were no differences in reported learning needs by gender, although scores on the Teen Issues scale approached significance, with girls reporting higher needs than boys. Youth and FSPs were similar on their reports of needs on 3 scales (Ordinary Day, Nutrition, and Living With Diabetes), but youth reported higher needs than FSPs on Focus and Teen Issues. Controlling for duration of diabetes, these differences between youth and FSPs persisted. In general, learning needs for both youth and FSPs decreased over time. Conclusions Youth with type 2 diabetes and their FSPs have high levels of ongoing learning needs despite completion of a standard diabetes education program. Continued assessment of learning needs, follow-up education, and behavioral approaches are warranted for these high-risk youth. C1 [Richards, Denise; Larkin, Mary; Javier, Elaine] Mass Gen Hosp, Boston, MA 02114 USA. [Milaszewski, Kerry] Joslin Diabet Ctr, Boston, MA 02215 USA. [Casey, Terri] Univ Case Med Ctr, Cleveland, OH USA. [Grey, Margaret] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. RP Richards, D (reprint author), Mass Gen Hosp, 50 Staniford St,Suite 340, Boston, MA 02114 USA. EM drichards1@partners.org NR 10 TC 0 Z9 0 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2013 VL 39 IS 3 BP 314 EP 319 DI 10.1177/0145721713485305 PG 6 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 148DR UT WOS:000319223600003 PM 23589327 ER PT J AU Brown-Guion, SY Youngerman, SM Hernandez-Tejada, MA Dismuke, CE Egede, LE AF Brown-Guion, Stephanie Y. Youngerman, Stephanie M. Hernandez-Tejada, Melba A. Dismuke, Clara E. Egede, Leonard E. TI Racial/Ethnic, Regional, and Rural/Urban Differences in Receipt of Diabetes Education SO DIABETES EDUCATOR LA English DT Article ID CARE; INTERVENTION; METAANALYSIS; PERCEPTIONS; ADULTS AB Purpose The objective of this study is to examine the differences in receipt of diabetes education according to risk factors that are associated with the disease, including race/ethnicity, region, and rural/urban location. Methods National data from the 2007 Medical Expenditure Panel Survey (MEPS) were analyzed to examine likelihood of receipt of diabetes education in terms of race, urban/rural location, and region. Results Of 1747 adults with type 2 diabetes, 65.6% were white, 15% black, and 19.4% other. In addition, 49.3% were male, 50.6% female; 46.9% were under age 64; 39.8% had more than high school; 34.1% were from low-income households, 35.1% middle income, and 30.8% high income; 39.5% lived in the South while other regions were equally represented; 80.6% lived in rural areas; 63.7% did not receive any type 2 diabetes education. Patients in the South were least likely to receive education (67.5% did not). Logistic regression demonstrated that being black (odds ratio [OR] = 1.38, 95% confidence interval [CI], 1.03-1.84) and living in an urban area (OR = 1.40, 95% CI, 1.00-1.97) were associated with a higher likelihood of receiving diabetes education. By contrast, being 65 or older was associated with lower probability of receiving education (OR = 0.59, 95% CI, 0.40-0.87), as was lack of insurance (OR = 0.54, 95% CI, 0.33-0.88) Conclusions Being black independently increased likelihood of receiving diabetes education, but living in rural areas, being uninsured, and living in the South reduced chances one would receive this helpful information. Therefore, further research should examine benefits of leveraging technology such as telemedicine to improve delivery of diabetes education to those living in rural areas. C1 [Brown-Guion, Stephanie Y.; Hernandez-Tejada, Melba A.; Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Youngerman, Stephanie M.; Dismuke, Clara E.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu NR 27 TC 3 Z9 3 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2013 VL 39 IS 3 BP 327 EP 334 DI 10.1177/0145721713480002 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 148DR UT WOS:000319223600005 PM 23482514 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI How to Catch a Suspicious Bleeding Site in Flagrante SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Gastrointestinal bleeding; Gastrointestinal endoscopy; Geometric probability; Medical decision analysis; Outcome research; Probability theory AB In search for a source of gastrointestinal bleeding, endoscopy frequently reveals mucosal lesions of questionable dignity. To investigate the probability of ascertaining conclusive evidence for gastrointestinal bleeding from a suspicious mucosal lesion through a single or multiple consecutive endoscopies. A mathematical model is developed to estimate the probability of successful diagnosis of a bleeding gastrointestinal lesion associated with single or multiple endoscopies. The probability of a successful confirmation through endoscopy depends on the length of time that signs of recent bleed persist at the site of the mucosal lesion and on the number of repeat endoscopies that one is willing to invest in confirmation. Assuming persistence of endoscopic evidence for 6-12 hours after the initial bleeding, a single endoscopy is associated with a 22 %-38 % chance of observing a suspicious site with clear evidence of bleeding. Using potentially up to 2 additional repeat endoscopies can raise such chances to 52 %-76 %. The rates of success may provide useful guidance in scheduling endoscopies for the work-up of gastrointestinal bleeding and decision making about the utility of repeat endoscopy in instances of suspicious but inconclusive mucosal lesions. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol Hepatol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2013 VL 58 IS 5 BP 1194 EP 1197 DI 10.1007/s10620-012-2488-6 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 149VU UT WOS:000319350300009 PM 23179160 ER PT J AU Surti, B Spiegel, B Ippoliti, A Vasiliauskas, EA Simpson, P Shih, DQ Targan, SR McGovern, DPB Melmed, GY AF Surti, Bijal Spiegel, Brennan Ippoliti, Andrew Vasiliauskas, Eric A. Simpson, Peter Shih, David Q. Targan, Stephan R. McGovern, Dermot P. B. Melmed, Gil Y. TI Assessing Health Status in Inflammatory Bowel Disease Using a Novel Single-Item Numeric Rating Scale SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Crohn's disease; Ulcerative colitis; Inflammatory bowel disease; Health related quality of life; Patient reported outcome ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; CROHNS-DISEASE; RHEUMATOID-ARTHRITIS; CLINICAL-TRIALS; PHYSICIANS PERSPECTIVES; ULCERATIVE-COLITIS; ACTIVITY INDEX; PATIENT; PERCEPTIONS AB Current instruments used to measure disease activity and health-related quality of life in patients with Crohn's disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome that can capture the patient's overall perception of health. The aim of this study was to assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC. We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn's disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC. The patient-reported NRS showed excellent correlation with CDAI (R (2) = 0.59, p < 0.0001), IBDQ (R (2) = 0.66, p < 0.0001), and HBI (R (2) = 0.32, p < 0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R (2) = 0.25, p < 0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change. The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC. C1 [Surti, Bijal; Ippoliti, Andrew; Vasiliauskas, Eric A.; Simpson, Peter; Shih, David Q.; Targan, Stephan R.; McGovern, Dermot P. B.; Melmed, Gil Y.] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 USA. [Surti, Bijal; Spiegel, Brennan] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Spiegel, Brennan] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Outcomes Res, Digest Dis Res Ctr, Los Angeles, CA USA. RP Melmed, GY (reprint author), Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, 8635 W 3rd St 960 Wv, Los Angeles, CA 90048 USA. EM Gil.Melmed@cshs.org FU Centocor, Inc.; USPHS [PO1DK046763, DK062413]; Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute; Helmsley Foundation; European Union; Crohn's and Colitis Foundation of America; Feintech Family Chair in IBD; Joshua L. and Lisa Z. Greer Chair in IBD Genetics FX This study was funded in part by an unrestricted Investigator-Initiated grant from Centocor, Inc. The authors gratefully acknowledge Dr Fasiha Kanwal and Dr Ron Hays (UCLA) for methodologic input and Dr Patricio Ibanez (Cedars-Sinai) for assistance with patient recruitment. IBD Research at Cedars-Sinai that contributed to this study is supported by USPHS grant PO1DK046763, DK062413 and the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute Research Funds. Project investigators are support by The Helmsley Foundation, The European Union and the Crohn's and Colitis Foundation of America (D.P.B.M.), The Feintech Family Chair in IBD (S.R.T.), The Joshua L. and Lisa Z. Greer Chair in IBD Genetics (D.P.B.M.). NR 51 TC 5 Z9 5 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2013 VL 58 IS 5 BP 1313 EP 1321 DI 10.1007/s10620-012-2500-1 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 149VU UT WOS:000319350300025 PM 23250673 ER PT J AU Hochedlinger, K AF Hochedlinger, Konrad TI Understanding cellular reprogramming and pluripotency SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Conference of the British-Society-for-Gene-and-Cell-Therapy (BSGCT) CY APR 17-19, 2013 CL Univ London, Royal Holloway, Egham, ENGLAND SP British Soc Gene & Cell Therapy (BSGCT) HO Univ London, Royal Holloway C1 [Hochedlinger, Konrad] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2013 VL 24 IS 5 BP A9 EP A9 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 146TN UT WOS:000319114700025 ER PT J AU Ahn, KY Hur, H Kim, DH Min, J Jeong, DH Chu, SH Lee, JW Ligibel, JA Meyerhardt, JA Jones, LW Jeon, JY Kim, NK AF Ahn, Ki-Yong Hur, Hyuk Kim, Dong-Hyun Min, Jihee Jeong, Duck Hyoun Chu, Sang Hui Lee, Ji Won Ligibel, Jennifer A. Meyerhardt, Jeffrey A. Jones, Lee W. Jeon, Justin Y. Kim, Nam Kyu TI The effects of inpatient exercise therapy on the length of hospital stay in stages I-III colon cancer patients: randomized controlled trial SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Article DE Exercise; Paralytic ileus; Colectomy; Recovery ID CLINICAL-TRIAL; MULTIMODAL OPTIMIZATION; ENHANCED RECOVERY; SURGICAL CARE; SURGERY; MANAGEMENT; RESECTION; REHABILITATION; METAANALYSIS; PROTOCOL AB This study aimed to examine the effects of a postsurgical, inpatient exercise program on postoperative recovery in operable colon cancer patients We conducted the randomized controlled trial with two arms: postoperative exercise vs. usual care. Patients with stages I-III colon cancer who underwent colectomy between January and December 2011 from the Colorectal Cancer Clinic, were recruited for the study. Subjects in the intervention group participated in the postoperative inpatient exercise program consisted of twice daily exercise, including stretching, core, balance, and low-intensity resistance exercises. The usual care group was not prescribed a structured exercise program. The primary endpoint was the length of hospital stay. Secondary endpoints were time to flatus, time to first liquid diet, anthropometric measurements, and physical function measurements. A total of 31 (86.1 %) patients completed the trial, with adherence to exercise interventions at 84.5 %. The mean length of hospital stay was 7.82 +/- 1.07 days in the exercise group compared with 9.86 +/- 2.66 days in usual care (mean difference, 2.03 days; 95 % confidence interval (CI), -3.47 to -0.60 days; p = 0.005) in per-protocol analysis. The mean time to flatus was 52.18 +/- 21.55 h in the exercise group compared with 71.86 +/- 29.2 h in the usual care group (mean difference, 19.69 h; 95 % CI, -38.33 to -1.04 h; p = 0.036). Low-to-moderate-intensity postsurgical exercise reduces length of hospital stay and improves bowel motility after colectomy procedure in patients with stages I-III colon cancer. C1 [Ahn, Ki-Yong; Kim, Dong-Hyun; Min, Jihee; Jeon, Justin Y.] Yonsei Univ, Dept Sport & Leisure Studies, Seoul 120749, South Korea. [Hur, Hyuk; Kim, Dong-Hyun; Kim, Nam Kyu] Yonsei Univ, Coll Med, Dept Surg, Seoul 120752, South Korea. [Chu, Sang Hui] Yonsei Univ, Coll Nursing, Nursing policy Res Inst, Dept Clin Nursing Sci,Biobehav Res Ctr, Seoul 120749, South Korea. [Lee, Ji Won] Yonsei Univ, Coll Med, Dept Family Med, Seoul, South Korea. [Ligibel, Jennifer A.; Meyerhardt, Jeffrey A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jones, Lee W.] Duke Canc Inst, Durham, NC USA. RP Jeon, JY (reprint author), Yonsei Univ, Dept Sport & Leisure Studies, 134 Seodaemun Gu, Seoul 120749, South Korea. EM jjeon@yonsei.ac.kr; namkyuk@yuhs.ac OI Kim, Nam-Kyu/0000-0003-0639-5632 FU national research foundation of Korea (NRF), Ministry of Education [2011-0004892] FX The current study was supported by the national research foundation of Korea (NRF), Ministry of Education (No. 2011-0004892). NR 15 TC 4 Z9 4 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-1958 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD MAY PY 2013 VL 28 IS 5 BP 643 EP 651 DI 10.1007/s00384-013-1665-1 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 142HY UT WOS:000318789200006 PM 23417645 ER PT J AU Solin, LJ Gray, R Baehner, FL Butler, SM Hughes, LL Yoshizawa, C Cherbavaz, DB Shak, S Page, DL Sledge, GW Davidson, NE Ingle, JN Perez, EA Wood, WC Sparano, JA Badve, S AF Solin, Lawrence J. Gray, Robert Baehner, Frederick L. Butler, Steven M. Hughes, Lorie L. Yoshizawa, Carl Cherbavaz, Diana B. Shak, Steven Page, David L. Sledge, George W., Jr. Davidson, Nancy E. Ingle, James N. Perez, Edith A. Wood, William C. Sparano, Joseph A. Badve, Sunil TI A Multigene Expression Assay to Predict Local Recurrence Risk for Ductal Carcinoma In Situ of the Breast SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURGICAL ADJUVANT BREAST; GENE-EXPRESSION; EUROPEAN ORGANIZATION; CONSERVING THERAPY; CANCER; TAMOXIFEN; PROJECT; RADIOTHERAPY; RADIATION; PROTOCOL AB Background For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics. Methods The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. All statistical tests were two-sided. Results There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6%, 26.7%, and 25.9%, respectively, and for an invasive IBE, 3.7%, 12.3%, and 19.2%, respectively (both log rank P = .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P = .02). Conclusions The DCIS Score quantifies IBE risk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria. C1 [Solin, Lawrence J.] Albert Einstein Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19141 USA. [Gray, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gray, Robert] Eastern Cooperat Oncol Grp Coordinating Ctr, Boston, MA USA. [Baehner, Frederick L.; Butler, Steven M.; Yoshizawa, Carl; Cherbavaz, Diana B.; Shak, Steven] Genom Hlth Inc, Redwood City, CA USA. [Baehner, Frederick L.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Hughes, Lorie L.] City Hope Natl Med Ctr, Cartersville, GA USA. [Page, David L.] Vanderbilt Univ, Dept Pathol, Nashville, TN USA. [Sledge, George W., Jr.] Indiana Univ, Dept Med Oncol, Indianapolis, IN 46204 USA. [Badve, Sunil] Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA. [Davidson, Nancy E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Wood, William C.] Emory Univ, Dept Surg, Atlanta, GA 30322 USA. [Sparano, Joseph A.] Albert Einstein Coll Med, Dept Med Oncol, Montefiore Med Ctr, New York, NY USA. RP Solin, LJ (reprint author), Albert Einstein Med Ctr, Dept Radiat Oncol, 5501 Old York Rd, Philadelphia, PA 19141 USA. EM solin@einstein.edu FU Public Health Service Grants [CA23318, CA66636, CA21115, CA13650, CA49883, CA49957, CA39229, CA25224, CA14958]; National Cancer Institute; National Institutes of Health; Department of Health and Human Services; Genomic Health, Inc.; Breast Cancer Research Foundation FX This work was supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA13650, CA49883, CA49957, CA39229, CA25224, and CA14958, and by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. Other supporting grants include Genomic Health, Inc. and The Breast Cancer Research Foundation. NR 44 TC 149 Z9 151 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD MAY PY 2013 VL 105 IS 10 BP 701 EP 710 DI 10.1093/jnci/djt067 PG 10 WC Oncology SC Oncology GA 149JS UT WOS:000319315700009 PM 23641039 ER PT J AU Hoffman, RM Koyama, T Fan, KH Albertsen, PC Barry, MJ Goodman, M Hamilton, AS Potosky, AL Stanford, JL Stroup, AM Penson, DF AF Hoffman, Richard M. Koyama, Tatsuki Fan, Kang-Hsien Albertsen, Peter C. Barry, Michael J. Goodman, Michael Hamilton, Ann S. Potosky, Arnold L. Stanford, Janet L. Stroup, Antoinette M. Penson, David F. TI Mortality After Radical Prostatectomy or External Beam Radiotherapy for Localized Prostate Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ANDROGEN SUPPRESSION; RADIATION-THERAPY; SURVIVAL; MEN; OUTCOMES; TERM AB Background No randomized trials have compared survival outcomes for men with localized prostate cancer (PC) being treated with radical prostatectomy (RP) or external beam radiotherapy (EBRT). The goal of the study, therefore, was to estimate the association of RP (compared with EBRT) with overall and PC mortality. Methods We analyzed an observational cohort from the population-based Prostate Cancer Outcomes Study, which included men aged 55 to 74 years diagnosed with localized PC between October 1994 and October 1995 who underwent either RP (n = 1164) or EBRT (n = 491) within 1 year of diagnosis. Patients were followed until death or study end (December 31, 2010). Overall and disease-specific mortality were assessed with multivariable survival analysis, with propensity scores to adjust for potential treatment selection confounders (demographics, comorbidities, and tumor characteristics). All statistical tests were two-sided. Results After 15 years of follow-up, there were 568 deaths, including 104 from PC. RP was associated with statistically significant advantages for overall (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.53 to 0.70, P < .0001.) and disease-specific mortality (HR = 0.35, 95% CI = 0.26 to 0.49, P < .0001.). Mortality benefits for RP were also observed within treatment propensity quintiles, when subjects were pair-matched on propensity scores, and in subgroup analyses based on age, tumor characteristics, and comorbidity. Conclusions Population-based observational data on men diagnosed with localized PC in the mid-1990s suggest a mortality benefit associated with RP vs EBRT. Possible explanations include residual selection bias or a true survival advantage. Results might be less applicable for men facing treatment decisions today. C1 [Hoffman, Richard M.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Hoffman, Richard M.] New Mexico VA Healthcare Syst, Med Serv, Albuquerque, NM USA. [Albertsen, Peter C.] Univ Connecticut, Sch Med, Dept Surg, Div Urol, Farmington, CT USA. [Barry, Michael J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Goodman, Michael] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Potosky, Arnold L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Stroup, Antoinette M.] Univ Utah, Salt Lake City, UT USA. [Koyama, Tatsuki; Fan, Kang-Hsien] Vanderbilt Univ, Dept Biostat, Nashville, TN 37203 USA. [Koyama, Tatsuki; Fan, Kang-Hsien] Vanderbilt Univ, Ctr Quantitat Sci, Nashville, TN 37203 USA. [Penson, David F.] Vanderbilt Univ, Dept Urol Surg, Nashville, TN 37203 USA. [Penson, David F.] Vanderbilt Univ, Ctr Surg Qual & Outcomes Res, Nashville, TN 37203 USA. [Penson, David F.] VA Tennessee Valley Geriatr Res Educ & Clin Ctr, Nashville, TN USA. RP Penson, DF (reprint author), Vanderbilt Univ, Med Ctr, 2525W End Ave,Ste 600, Nashville, TN 37203 USA. EM david.penson@vanderbilt.edu FU National Cancer Institute, National Institutes of Health, Bethesda, MD [R01-CA114524]; [N01-PC-67007]; [N01-PC-67009]; [N01-PC-67010]; [N01-PC-67006]; [N01-PC-67005]; [N01-PC-67000] FX This study was supported by the National Cancer Institute, National Institutes of Health, Bethesda, MD, through grant R01-CA114524 and the following contracts from the each of the participating institutions: N01-PC-67007, N01-PC-67009, N01-PC-67010, N01-PC-67006, N01-PC-67005, and N01-PC-67000. NR 33 TC 32 Z9 33 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD MAY PY 2013 VL 105 IS 10 BP 711 EP 718 DI 10.1093/jnci/djt059 PG 8 WC Oncology SC Oncology GA 149JS UT WOS:000319315700010 PM 23615689 ER PT J AU Joh, HK Giovannucci, EL Bertrand, KA Lim, S Cho, E AF Joh, Hee-Kyung Giovannucci, Edward L. Bertrand, Kimberly A. Lim, Soo Cho, Eunyoung TI Predicted Plasma 25-Hydroxyvitamin D and Risk of Renal Cell Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID VITAMIN-D-RECEPTOR; TOTAL-ENERGY-INTAKE; PROSPECTIVE COHORT; ULTRAVIOLET-B; UNITED-STATES; CARCINOMA; MORTALITY; EPIDEMIOLOGY; METAANALYSIS; EXPRESSION AB Background Although the kidney is a primary organ for vitamin D metabolism, the association between vitamin D and renal cell cancer (RCC) remains unclear. Methods We prospectively evaluated the association between predicted plasma 25-hydroxyvitamin D [25(OH)D] and RCC risk among 72 051 women and 46 380 men in the period from 1986 to 2008. Predicted plasma 25(OH)D scores were computed using validated regression models that included major determinants of vitamin D status (race, ultraviolet B flux, physical activity, body mass index, estimated vitamin D intake, alcohol consumption, and postmenopausal hormone use in women). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. All statistical tests were two-sided. Results During 22 years of follow-up, we documented 201 cases of incident RCC in women and 207 cases in men. The multivariable hazard ratios between extreme quintiles of predicted 25(OH)D score were 0.50 (95% CI = 0.32 to 0.80) in women, 0.59 (95% CI = 0.37 to 0.94) in men, and 0.54 (95% CI = 0.39 to 0.75; P-trend < .001) in the pooled cohorts. An increment of 10 ng/mL in predicted 25(OH)D score was associated with a 44% lower incidence of RCC (pooled HR = 0.56, 95% CI = 0.42 to 0.74). We found no statistically significant association between vitamin D intake estimated from food-frequency questionnaires and RCC incidence. Conclusion Higher predicted plasma 25(OH)D levels were associated with a statistically significantly lower risk of RCC in men and women. Our findings need to be confirmed by other prospective studies using valid markers of long-term vitamin D status. C1 [Joh, Hee-Kyung] Seoul Natl Univ, Coll Med, Dept Med, Seoul, South Korea. [Joh, Hee-Kyung] Seoul Natl Univ, Dept Family Med, Hlth Serv Ctr, Seoul, South Korea. [Giovannucci, Edward L.; Bertrand, Kimberly A.; Cho, Eunyoung] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Giovannucci, Edward L.; Bertrand, Kimberly A.; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Bertrand, Kimberly A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lim, Soo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Lim, Soo] Seoul Natl Univ, Coll Med, Songnam, South Korea. [Lim, Soo] Seoul Natl Univ, Bundang Hosp, Songnam, South Korea. RP Cho, E (reprint author), Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu FU National Institutes of Health [CA87969, CA55075]; Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Programs of Research Excellence (SPORE) [NIH P50CA101942]; Nutritional Epidemiology of Cancer Training Grant [R25 CA098566] FX This study was supported by research grant CA87969 and CA55075 from the National Institutes of Health, and Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Programs of Research Excellence (SPORE; NIH P50CA101942). KAB was supported by the Nutritional Epidemiology of Cancer Training Grant (R25 CA098566). NR 40 TC 15 Z9 15 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD MAY PY 2013 VL 105 IS 10 BP 726 EP 732 DI 10.1093/jnci/djt082 PG 7 WC Oncology SC Oncology GA 149JS UT WOS:000319315700012 PM 23568327 ER PT J AU Thompson, BR Douglass, JA Ellis, MJ Kelly, VJ O'Hehir, RE King, GG Verbanck, S AF Thompson, Bruce R. Douglass, Jo A. Ellis, Matthew J. Kelly, Vanessa J. O'Hehir, Robyn E. King, Gregory G. Verbanck, Sylvia TI Peripheral lung function in patients with stable and unstable asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Severe asthma; acinar airways; peripheral gas mixing ID INERT-GAS WASHOUT; VENTILATION HETEROGENEITY; COMPUTED-TOMOGRAPHY; RESPIRATORY SOCIETY; AIRWAY INVOLVEMENT; NITROGEN WASHOUT; FUNCTION-TESTS; DISTAL LUNG; INFLAMMATION; ADULTS AB Background: Exacerbations of asthma are thought to be caused by airflow obstruction resulting from airway inflammation, bronchospasm, and mucus plugging. Histologic evidence suggests the small airways, including acinar air spaces, are involved; however, this has not been corroborated in vivo by measurements of peripheral small-airway function. Objective: We sought to determine whether asthma severity is linked to small-airway function, particularly in patients with acute severe asthma. Methods: Eighteen subjects admitted for an asthma exacerbation underwent lung function testing, including measures of acinar ventilation heterogeneity (S-acin) and conductive ventilation heterogeneity (S-cond) using the multiple-breath nitrogen washout. Treatment requirement was defined according to Global Initiative for Asthma scores. Data were compared with those obtained in 19 patients with stable asthma. Results: For the asthma exacerbation group, the median FEV1 was 59% of predicted value (95% CI, 45% to 75% of predicted value), the median S-cond value was 185% of predicted value (95% CI, 119% to 245% of predicted value), and the median S-acin value was 225% of predicted value (95% CI, 143% to 392% of predicted value). FEV1 (percent predicted) was correlated with S-acin (percent predicted) values (Spearman rho = -0.67, P =.006) but not with S-cond (percent predicted) values (P >.1). The Global Initiative for Asthma score was significantly related to S-acin (percent predicted) (Spearman rho = 0.59, P = .016) but not to S-cond (percent predicted) values (P >.1). The unstable group was characterized by considerably lower forced vital capacity (P <. 001) and higher S-cond (P =.001) values than the unstable group. In a subgroup of 11 unstable patients who could be reviewed after 4 weeks, FEV1, forced vital capacity, S-acin, and S-cond values showed marked improvements. Conclusion: Our findings suggest that unstable asthma is characterized by a combined abnormality in the acinar and conductive lung zones, both of which are partly reversible. Functional abnormality in the acinar lung zone in particular showed a direct correlation with airflow obstruction and treatment requirement in patients with acute severe asthma. C1 [Thompson, Bruce R.; Ellis, Matthew J.; O'Hehir, Robyn E.] Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic 3004, Australia. [Thompson, Bruce R.; Ellis, Matthew J.; O'Hehir, Robyn E.] Monash Univ, Melbourne, Vic 3004, Australia. [Thompson, Bruce R.; Ellis, Matthew J.; O'Hehir, Robyn E.; King, Gregory G.] Cooperat Res Ctr Asthma & Airways, Sydney, NSW, Australia. [Douglass, Jo A.] Royal Melbourne Hosp, Dept Clin Immunol & Allergy, Parkville, Vic 3050, Australia. [Douglass, Jo A.] Univ Melbourne, Parkville, Vic 3052, Australia. [Kelly, Vanessa J.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Kelly, Vanessa J.] Harvard Univ, Sch Med, Boston, MA USA. [King, Gregory G.] Woolcock Inst Med Res, Sydney, NSW, Australia. [Verbanck, Sylvia] Vrije Univ Brussel, Acad Hosp, Div Resp, Brussels, Belgium. RP Thompson, BR (reprint author), Alfred Hosp, Dept Allergy Immunol & Resp Med, Lung Funct Lab, Commercial Rd, Melbourne, Vic 3004, Australia. EM b.thompson@alfred.org.au RI O'Hehir, Robyn/H-3627-2011; OI O'Hehir, Robyn/0000-0002-3489-7595; Thompson, Bruce/0000-0002-5885-0652 FU Cooperative Research Centre for Asthma and Airways; National Health and Medical Research Council, Australia; National Health and Medical Research Council; AstraZeneca; GlaxoSmithKline,; Novartis; Pharmaxis; Pharmaxis, and the Asthma Foundation FX Support for this study was provided by the Cooperative Research Centre for Asthma and Airways and the National Health and Medical Research Council, Australia.; Disclosure of potential conflict of interest: B. R. Thompson, M. J. Ellis, V. J. Kelly, R. E. O'Hchir, and S. Verbanck have received grants from the National Health and Medical Research Council and the Cooperative Research Centre for Asthma and Airways. J. A. Douglass has received grants from the National Health and Medical Research Council and the Cooperative Research Centre for Asthma and Airways; is on an advisory board for Novartis; has received payment for lectures from AstraZeneca, GlaxoSmithKline, and Novartis; and has received royalties from Health Press Limited. G. G. King has received grants from the National Health and Medical Research Council, GlaxoSmithKline, Boehringer Ingelheim, Pharmaxis, and the Asthma Foundation; has received travel support from GlaxoSmithKline, Novartis, AstraZeneca, Boehringer Ingelheim, and Pfizer; has received subject payments for clinical trials from Pharmaxis; and is part of a consultancy agreement between GlaxoSmithKline, Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer, and the Woolcock Institute of Medical Research, and his research group receives an unrestricted allocation as part of the monies received from the consultancy agreements. NR 37 TC 30 Z9 30 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2013 VL 131 IS 5 BP 1322 EP 1328 DI 10.1016/j.jaci.2013.01.054 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 144AU UT WOS:000318912200007 PM 23561802 ER PT J AU Mehling, M Brinkmann, V Burgener, AV Gubser, P Luster, AD Kappos, L Hess, C AF Mehling, Matthias Brinkmann, Volker Burgener, Anne-Valerie Gubser, Patrick Luster, Andrew D. Kappos, Ludwig Hess, Christoph TI Homing frequency of human T cells inferred from peripheral blood depletion kinetics after sphingosine-1-phosphate receptor blockade SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID MULTIPLE-SCLEROSIS; LYMPH-NODES; SUBSETS; LYMPHOCYTES; FTY720; MEMORY C1 [Mehling, Matthias; Burgener, Anne-Valerie; Gubser, Patrick; Hess, Christoph] Univ Basel Hosp, Dept Biomed, Immunobiol Lab, CH-4031 Basel, Switzerland. [Mehling, Matthias; Burgener, Anne-Valerie; Gubser, Patrick; Hess, Christoph] Univ Basel Hosp, Med Outpatient Dept, CH-4031 Basel, Switzerland. [Mehling, Matthias; Kappos, Ludwig] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland. [Mehling, Matthias; Kappos, Ludwig] Univ Basel Hosp, Dept Biomed, Clin Neuroimmunol Lab, CH-4031 Basel, Switzerland. [Brinkmann, Volker] Novartis Inst BioMed Res, Dept Autoimmun Transplantat & Inflammat, Basel, Switzerland. [Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. RP Mehling, M (reprint author), Univ Basel Hosp, Dept Biomed, Immunobiol Lab, CH-4031 Basel, Switzerland. EM chess@uhbs.ch NR 12 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2013 VL 131 IS 5 BP 1440 EP + DI 10.1016/j.jaci.2012.12.1520 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 144AU UT WOS:000318912200031 PM 23434284 ER PT J AU Vaduganathan, M Gheorghiade, M AF Vaduganathan, Muthiah Gheorghiade, Mihai TI Return of Digoxin and Recovery of Renal Function SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID DECOMPENSATED HEART-FAILURE; EVEREST TRIAL; DYSFUNCTION; OUTCOMES C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 North Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu NR 18 TC 3 Z9 3 U1 0 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 MAY PY 2013 VL 19 IS 5 BP 303 EP 305 DI 10.1016/j.cardfail.2013.03.006 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 148LQ UT WOS:000319246500002 PM 23663811 ER PT J AU Milfred-Laforest, SK Chow, SL Didomenico, RJ Dracup, K Ensor, CR Gattis-Stough, W Heywood, JT Lindenfeld, J Page, RL Patterson, JH Vardeny, O Massie, BM AF Milfred-Laforest, Sherry K. Chow, Sheryl L. Didomenico, Robert J. Dracup, Kathleen Ensor, Christopher R. Gattis-Stough, Wendy Heywood, J. Thomas Lindenfeld, Joann Page, Robert L. Patterson, J. Herbert Vardeny, Orly Massie, Barry M. TI Clinical Pharmacy Services in Heart Failure: An Opinion Paper From the Heart Failure Society of America and American College of Clinical Pharmacy Cardiology Practice and Research Network SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; clinical pharmacist; multidisciplinary team; heart transplant ID UNITED-STATES HOSPITALS; ADVERSE DRUG-REACTIONS; INPATIENT MEDICATION RECONCILIATION; VENTRICULAR ASSIST DEVICE; PRESCRIBER ORDER ENTRY; INTENSIVE-CARE-UNIT; PHARMACEUTICAL CARE; CARDIOVASCULAR-DISEASE; TRANSPLANT RECIPIENT; MANAGEMENT PROGRAM AB Background: Heart failure (BF) care takes place in multiple settings, with a variety of providers, and generally involves patients who have multiple comorbidities. This situation is a "perfect storm" of factors that predispose patients to medication errors. Methods and Results: The goals of this paper are to outline potential roles for clinical pharmacists in a multidisciplinary BF team, to document outcomes associated with interventions by clinical pharmacists, to recommend minimum training for clinical pharmacists engaged in HF care, and to suggest financial strategies to support clinical pharmacy services within a multidisciplinary team. As patients transition from inpatient to outpatient settings and between multiple caregivers, pharmacists can positively affect medication reconciliation and education, assure consistency in management that results in improvements in patient satisfaction and medication adherence, and reduce medication errors. For mechanical circulatory support and heart transplant teams, the Centers for Medicare and Medicaid Services considers the participation of a transplant pharmacology expert (e.g., clinical pharmacist) to be a requirement for accreditation, given the highly specialized and complex drug regimens used. Although reports of outcomes from pharmacist interventions have been mixed owing to differences in study design, benefits such as increased use of evidence-based therapies, decreases in HF hospitalizations and emergency department visits, and decreases in all-cause readmissions have been demonstrated. Clinical pharmacists participating in HF or heart transplant teams should have completed specialized postdoctoral training in the form of residencies and/or fellowships in cardiovascular and/or transplant pharmacotherapy, and board certification is recommended. Financial mechanisms to support pharmacist participation in the HF teams are variable. Conclusions: Positive outcomes associated with clinical pharmacist activities support the value of making this resource available to HF teams. C1 [Milfred-Laforest, Sherry K.] Louis Stokes Cleveland VA Med Ctr, Dept Pharm, Cleveland, OH USA. [Chow, Sheryl L.] Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA. [Didomenico, Robert J.] Univ Illinois, Coll Pharm, Chicago, IL USA. [Dracup, Kathleen] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Ensor, Christopher R.] Univ Pittsburgh, Coll Pharm, Pittsburgh, PA USA. [Gattis-Stough, Wendy] Campbell Univ, Coll Pharm & Hlth Sci, Dept Clin Res, Buies Creek, NC 27506 USA. [Heywood, J. Thomas] Scripps Clin, Dept Med, La Jolla, CA 92037 USA. [Lindenfeld, Joann] Univ Colorado Denver, Dept Med, Div Cardiol, Heart Transplantat Program, Aurora, CO USA. [Page, Robert L.] Univ Colorado Denver, Sch Pharm, Aurora, CO USA. [Page, Robert L.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Patterson, J. Herbert] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA. [Vardeny, Orly] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. [Vardeny, Orly] Univ Wisconsin, Sch Med, Madison, WI USA. [Massie, Barry M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Chow, SL (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E 2nd St, Pomona, CA 91766 USA. EM schow@westernu.edu; barry.massie@va.gov RI Stough, Wendy/R-4287-2016; OI Stough, Wendy/0000-0001-8290-1205; DiDomenico, Robert/0000-0002-9374-8012 FU Medtronic; Gambro; St. Jude; Zensun; Otsuka; Novartis; Amgen FX J. Thomas Heywood has received speaking honoraria from Actelion, Medtronic, St Jude, and Thoratec; is a consultant for Actelion, Medtronic, and Thoratec; and has received research grants from Medtronic and Gambro and fellowship support from St. Jude. JoAnn Lindenfeld is a consultant for St Jude, Boston Scientific, and Abbott and has received a research grant from Zensun. J. Herbert Patterson has received speaking honoraria from Otsuka, is a consultant for Otsuka and Novartis, and has received research grants from Otsuka, Novartis, and Amgen. All of the other authors report no potential conflict of interest. NR 136 TC 8 Z9 9 U1 2 U2 15 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 MAY PY 2013 VL 19 IS 5 BP 354 EP 369 DI 10.1016/j.cardfail.2013.02.002 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 148LQ UT WOS:000319246500009 PM 23663818 ER PT J AU Bahraini, N Brenner, LA AF Bahraini, Nazanin Brenner, Lisa A. TI Screening for TBI and Persistent Symptoms Provides Opportunities for Prevention and Intervention SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Editorial Material ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MALE VIETNAM VETERANS; WAR-ZONE STRESSORS; FEMALE; SOLDIERS C1 [Bahraini, Nazanin; Brenner, Lisa A.] VA VISN Mental Illness Res Educ & Clin Ctr MIRECC, Denver, CO USA. [Bahraini, Nazanin; Brenner, Lisa A.] Univ Colorado, Denver Sch Med, Dept Psychiat, Aurora, CO USA. [Bahraini, Nazanin] Univ Colorado, Denver Sch Med, Dept Neurol, Aurora, CO USA. [Brenner, Lisa A.] Univ Colorado, Denver Sch Med, Dept Phys Med & Rehabil, Aurora, CO USA. RP Brenner, LA (reprint author), Denver VA Med Ctr, VISN MIRECC 19, 1055 Clermont St, Denver, CO 80220 USA. EM lisa.brenner@va.gov NR 22 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD MAY-JUN PY 2013 VL 28 IS 3 BP 223 EP 226 DI 10.1097/HTR.0b013e318291dab7 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 149PS UT WOS:000319334000010 PM 23661075 ER PT J AU Collier, TL Liang, SH Vasdev, N AF Collier, Thomas Lee Liang, Steven H. Vasdev, Neil TI Interfacing of a NanoTek microfluidic system with an H-Cube continuous-flow hydrogenation reactor and a GE FXN synthesizer SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Collier, Thomas Lee] Advion Inc, Ithaca, NY USA. [Collier, Thomas Lee; Liang, Steven H.; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Collier, Thomas Lee; Liang, Steven H.; Vasdev, Neil] Harvard Univ, Sch Med, Boston, MA 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 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAY PY 2013 VL 56 SU 1 MA P386 BP S473 EP S473 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 140ZD UT WOS:000318694100474 ER PT J AU Liang, SH Collier, TL Rotstein, B Lewis, R Steck, M Vasdev, N AF Liang, Steven H. Collier, T. Lee Rotstein, Benjamin Lewis, Rebecca Steck, Mia Vasdev, Neil TI Deprotection and reduction of F-18-labeled compounds by rapid flow hydrogenation SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Liang, Steven H.; Collier, T. Lee; Rotstein, Benjamin; Lewis, Rebecca; Steck, Mia; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. [Liang, Steven H.; Collier, T. Lee; Rotstein, Benjamin; Lewis, Rebecca; Steck, Mia; Vasdev, Neil] Harvard Univ, Sch Med, Boston, MA USA. [Collier, T. Lee] Advion Inc, Ithaca, NY USA. [Lewis, Rebecca] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAY PY 2013 VL 56 SU 1 MA P084 BP S171 EP S171 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 140ZD UT WOS:000318694100172 ER PT J AU Reiner, T Keliher, EJ Emmetiere, F Lewis, JS Weissleder, R AF Reiner, Thomas Keliher, Edmund J. Emmetiere, Fabien Lewis, Jason S. Weissleder, Ralph TI Tetrazines/trans-cyclooctenes and their application as chemically orthogonal reaction partners in radiochemical synthesis SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Reiner, Thomas; Emmetiere, Fabien; Lewis, Jason S.; Weissleder, Ralph] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Keliher, Edmund J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAY PY 2013 VL 56 SU 1 MA O-047 BP S47 EP S47 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 140ZD UT WOS:000318694100048 ER PT J AU Otis, JD Sanderson, K Hardway, C Pincus, M Tun, C Soumekh, S AF Otis, John D. Sanderson, Kristen Hardway, Christina Pincus, Michael Tun, Carlos Soumekh, Sharona TI A Randomized Controlled Pilot Study of a Cognitive-Behavioral Therapy Approach for Painful Diabetic Peripheral Neuropathy SO JOURNAL OF PAIN LA English DT Article DE Cognitive-behavioral therapy; neuropathic pain; chronic pain; diabetes; treatment ID LOW-BACK-PAIN; QUALITY-OF-LIFE; UPDATED GUIDELINES; CONTROLLED-TRIAL; METAANALYSIS; DEPRESSION; IMPACT; INVENTORY; HEADACHE; MODELS AB The purpose of the present pilot study was to assess the efficacy of cognitive-behavioral therapy (CBT) for painful diabetic peripheral neuropathy. This was a randomized, treatment as usual (TAU), controlled, nonblinded intervention pilot study with a 4-month follow-up conducted in a VA medical center. It was hypothesized that participants who received CBT, as compared to those who received TAU, would report significant decreases on self-report measures of pain severity, interference, and depressive symptoms from pretreatment to 4-month follow-up. Participants meeting inclusion criteria were randomly assigned to 1 of the study conditions. Of the 20 eligible participants, 12 were randomized to CBT and 8 were randomized to TAU. Participants randomized to CBT showed significant decreases on measures of pain severity (B = -.54) and pain interference (B = -.77) from pretreatment to 4-month follow-up. There were no significant changes in the TAU participants' scores on measures of pain severity (B = .00) or pain interference (B = -.09). Neither CBT nor TAU participants showed significant changes in their levels of depressive symptoms from pretreatment to 4-month follow-up. CBT may be an effective treatment approach for reducing pain severity and interference associated with painful diabetic peripheral neuropathy. Perspective: The results of this study suggest that engaging patients in CBT for painful diabetic peripheral neuropathy may provide them the skills to become more active and experience less pain. Published by Elsevier Inc. on behalf of the American Pain Society C1 [Otis, John D.; Tun, Carlos; Soumekh, Sharona] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Otis, John D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sanderson, Kristen] Univ Florida, Gainesville, FL USA. [Hardway, Christina] Merrimack Coll, N Andover, MA 01845 USA. [Pincus, Michael] UMass Mem Med Ctr, Worcester, MA USA. [Soumekh, Sharona] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otis, JD (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM johnotis@bu.edu OI Otis, John/0000-0002-5441-7421 FU Veterans of Foreign Wars (VFW) FX This work was supported by a grant from the Veterans of Foreign Wars (VFW) to the diabetes research program at VA Boston Healthcare System, Boston, MA. NR 31 TC 8 Z9 8 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD MAY PY 2013 VL 14 IS 5 BP 475 EP 482 DI 10.1016/j.jpain.2012.12.013 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 145QT UT WOS:000319032600006 PM 23452825 ER PT J AU Agar, M Ko, DN Sheehan, C Chapman, M Currow, DC AF Agar, Meera Ko, Danielle N. Sheehan, Caitlin Chapman, Michael Currow, David C. TI Informed Consent in Palliative Care Clinical Trials: Challenging but Possible SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PULMONARY-ARTERY CATHETERS; END-OF-LIFE; PROXY CONSENT; EMERGENCY RESEARCH; CAPACITY; VALIDITY; PHASE AB Obtaining informed consent is a key protection that should be afforded universally to people using health services and the basis around which any participation in clinical trials is built. Randomized controlled effectiveness studies are necessary to answer key questions in hospice and palliative care, in order to help systematically improve the quality of care. In order to be properly generalizable, such trials need to have broad inclusion criteria to reflect the population most likely to be affected by the condition. The inclusion of patients who are seriously ill, and therefore potentially vulnerable, requires careful exploration of ethical and legal principles that underpin informed consent. Specific challenges in obtaining informed consent for randomised clinical trials (RCTs) in clinically unstable populations such as hospice and palliative care include higher rates of people with impaired cognitive capacity as well as interventional studies in clinical situations which may present as a sudden change in condition. None of these challenges is unique to hospice and palliative care research, but the combination and frequency with which they are encountered require systematic and considered solutions. This article outlines five different ethically valid consent approaches and discusses their applicability to hospice and palliative care research trials. These include: consent by the patient (at the time of enrolment, in advance of the study, or delayed until after the study has commenced); a proxy (or legally authorised representative); or a consent waiver. Increased use of the less traditional modes of informed consent may lead to greater participation rates in hospice and palliative care trials, thereby improving the evidence base more rapidly in part by better reflecting the population served and hence improving generalizability. C1 [Agar, Meera; Sheehan, Caitlin; Currow, David C.] Flinders Univ S Australia, Discipline Palliat & Support Serv, Bedford Pk, SA 5042, Australia. [Agar, Meera] Braeside Hosp, Dept Palliat Care, Hammond Care, Prairiewood, NSW, Australia. [Agar, Meera] Univ New S Wales, South West Sydney Clin Sch, Liverpool, NSW, Australia. [Ko, Danielle N.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Sheehan, Caitlin] Cunningham Ctr Palliat Care, Darlinghurst, NSW, Australia. [Sheehan, Caitlin] Sacred Heart Ctr, Darlinghurst, NSW, Australia. [Chapman, Michael] Sunshine Hosp, Western Hlth, Dept Geriatr Med, St Albans, Vic, Australia. RP Currow, DC (reprint author), Flinders Univ S Australia, Discipline Palliat & Support Serv, Daws Rd, Daw Pk, SA 5041, Australia. EM david.currow@flinders.edu.au OI Currow, David/0000-0003-1988-1250 NR 47 TC 7 Z9 7 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY PY 2013 VL 16 IS 5 BP 485 EP 491 DI 10.1089/jpm.2012.0422 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 145GV UT WOS:000319004100007 PM 23631612 ER PT J AU Martinez-Gamboa, L Lesemann, K Kuckelkorn, U Scheffler, S Ghannam, K Hahne, M Gaber-Elsner, T Egerer, K Naumann, L Buttgereit, F Dorner, T Kloetzel, PM Burniester, GR Faustman, DL Feist, E AF Martinez-Gamboa, Lorena Lesemann, Karsten Kuckelkorn, Ulrike Scheffler, Sonja Ghannam, Khetam Hahne, Martin Gaber-Elsner, Timo Egerer, Karl Naumann, Lydia Buttgereit, Frank Doerner, Thomas Kloetzel, Peter M. Burniester, Gerd R. Faustman, Denise L. Feist, Eugen TI Gene Expression of Catalytic Proteasome Subunits and Resistance Toward Proteasome Inhibition of B Lymphocytes from Patients with Primary Sjogren Syndrome SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE PROTEASOME SYSTEM; PROTEASOME INHIBITION; SJOGREN SYNDROME; B LYMPHOCYTES ID NF-KAPPA-B; MULTIPLE-MYELOMA CELLS; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; 20S PROTEASOME; SALIVARY-GLANDS; T-CELLS; PROINFLAMMATORY CYTOKINES; DEFECTIVE APOPTOSIS; AUTOIMMUNE-DISEASES AB Objective. Dysregulation of proteasome subunit beta 1i expression has been shown in total blood mononuclear cells (PBMC) from patients with primary Sjogren syndrome (pSS), a B cell-driven systemic autoimmune disorder. Methods. Proteasome activation was investigated in sorted blood cells from patients with pSS and controls by measuring transcript levels of constitutive (beta 1/beta 2/beta 5) and corresponding immunoproteasome catalytic subunits (beta 1i/beta 2i/beta 5i) using real-time PCR. At protein level, beta 1i protein expression was analyzed by immunoblotting. Functional effects of proteasome inhibition on proteolytic activity and induction of apoptosis were also evaluated in cellular subsets. Results. The proteasome was found to be activated in pSS, with upregulation of gene expression of catalytic proteasome subunits. Western blot analysis revealed decreased beta 1i protein expression in pSS B lymphocytes, with decreased protein despite increased messenger RNA (mRNA) levels. After proteasome inhibition in vitro, proteolytic activity was less reduced and resistance to apoptosis was increased in B lymphocytes compared to other cells. Conclusion. In pSS, catalytic subunits of the proteasome are upregulated at the mRNA level, while dysregulation of subunit beta 1i is attributed to B lymphocytes. B cell resistance after proteasome inhibition differs from the classical concept of increased susceptibility toward inhibition in activated cells, supporting the novel notion that susceptibility depends on cellular intrinsic factors and on proteasome activation. C1 [Martinez-Gamboa, Lorena; Lesemann, Karsten; Scheffler, Sonja; Ghannam, Khetam; Hahne, Martin; Gaber-Elsner, Timo] Charite, Dept Rheumatol & Clin Immunol, Rheumatol Res Lab, D-13353 Berlin, Germany. [Kuckelkorn, Ulrike; Kloetzel, Peter M.] Charite, Dept Biochem, D-13353 Berlin, Germany. German Rheumatol Res Ctr DRFZ, Berlin, Germany. Berlin Brandenburg Ctr Regenerat Therapies BCRT, Berlin, Germany. Dept Rheurnatol & Clin Immunol, Berlin, Germany. [Faustman, Denise L.; Feist, Eugen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA USA. RP Martinez-Gamboa, L (reprint author), Charite Forschungslab Rheumatol, AG Feist, Campus Mitte,Virchowweg 10,Nordflugel,5 Stock,Cha, D-10117 Berlin, Germany. EM lorena.martinez_g@charite.de FU German Ministry for Economy and Technology (BMWi) [ZIM KF2088101MD8]; DFG [FE470/3-1]; SFB650 (TP17 Targeting of memory plasma cells secreting pathogenic antibodies); Sjogren's Syndrome Foundation FX Supported by the German Ministry for Economy and Technology (BMWi, ZIM KF2088101MD8), the DFG (FE470/3-1), the SFB650 (TP17 Targeting of memory plasma cells secreting pathogenic antibodies), and the Sjogren's Syndrome Foundation. NR 69 TC 5 Z9 5 U1 2 U2 5 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2013 VL 40 IS 5 BP 663 EP 673 DI 10.3899/jrheum.120680 PG 11 WC Rheumatology SC Rheumatology GA 147MO UT WOS:000319171900020 PM 23504381 ER PT J AU Dello Russo, N AF Dello Russo, Nicholas TI COST OF EDUCATION SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID ORAL-HEALTH; MIDLEVEL PROVIDERS C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Dent, Boston, MA 02114 USA. RP Dello Russo, N (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Dent, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2013 VL 144 IS 5 BP 464 EP + PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 147RM UT WOS:000319184700004 PM 23633689 ER PT J AU Seldin, EB AF Seldin, Edward B. TI MIDLEVEL PROVIDERS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Seldin, EB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2013 VL 144 IS 5 BP 464 EP 464 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 147RM UT WOS:000319184700003 PM 23633688 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI CBCT FINDINGS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID INCIDENTAL FINDINGS; PREDICT; RISK C1 [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. [Friedlander, Arthur H.] VA Greater Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA USA. RP Friedlander, AH (reprint author), Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2013 VL 144 IS 5 BP 466 EP + PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 147RM UT WOS:000319184700005 PM 23633690 ER PT J AU De Freitas, J Falls, BA Haque, OS Bursztajn, HJ AF De Freitas, Julian Falls, Brian A. Haque, Omar S. Bursztajn, Harold J. TI Vulnerabilities to misinformation in online pharmaceutical marketing SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Review ID HEALTH INFORMATION; CONSUMERS SEARCH; FOCUS GROUPS; INTERNET; SEEKING AB Given the large percentage of Internet users who search for health information online, pharmaceutical companies have invested significantly in online marketing of their products. Although online pharmaceutical marketing can potentially benefit both physicians and patients, it can also harm these groups by misleading them. Indeed, some pharmaceutical companies have been guilty of undue influence, which has threatened public health and trust. We conducted a review of the available literature on online pharmaceutical marketing, undue influence and the psychology of decision-making, in order to identify factors that contribute to Internet users' vulnerability to online pharmaceutical misinformation. We find five converging factors: Internet dependence, excessive trust in the veracity of online information, unawareness of pharmaceutical company influence, social isolation and detail fixation. As the Internet continues to change, it is important that regulators keep in mind not only misinformation that surrounds new web technologies and their contents, but also the factors that make Internet users vulnerable to misinformation in the first place. Psychological components are a critical, although often neglected, risk factor for Internet users becoming misinformed upon exposure to online pharmaceutical marketing. Awareness of these psychological factors may help Internet users attentively and safely navigate an evolving web terrain. C1 [De Freitas, Julian] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Falls, Brian A.] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02169 USA. [Haque, Omar S.] Harvard Univ, Sch Med, Program Psychiat & Law, Boston, MA 02138 USA. [Bursztajn, Harold J.] Harvard Univ, Sch Med, Dept Psychiat, Program Psychiat & Law,BIDMC Psychiat, Cambridge, MA 02138 USA. RP Bursztajn, HJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Program Psychiat & Law,BIDMC Psychiat, Cambridge, MA 02138 USA. EM harold_bursztajn@hms.harvard.edu NR 30 TC 6 Z9 6 U1 1 U2 13 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD MAY PY 2013 VL 106 IS 5 BP 184 EP 189 DI 10.1177/0141076813476679 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 148JA UT WOS:000319239400012 PM 23761527 ER PT J AU Kasotakis, G Sideris, A Yang, YC de Moya, M Alam, H King, DR Tompkins, R Velmahos, G AF Kasotakis, George Sideris, Antonis Yang, Yuchiao de Moya, Marc Alam, Hasan King, David R. Tompkins, Ronald Velmahos, George CA Inflammation Host Response Injury TI Aggressive early crystalloid resuscitation adversely affects outcomes in adult blunt trauma patients: An analysis of the Glue Grant database SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Crystalloid; resuscitation; outcomes; blunt trauma; Glue Grant ID MULTIPLE ORGAN FAILURE; RESPIRATORY-DISTRESS-SYNDROME; LACTATED RINGERS SOLUTION; FRESH-FROZEN PLASMA; MAJOR ABDOMINAL-SURGERY; TISSUE OXYGEN-TENSION; FLUID RESUSCITATION; HEMORRHAGIC-SHOCK; MASSIVE TRANSFUSION; BLOOD-TRANSFUSION AB BACKGROUND: Evidence suggests that aggressive crystalloid resuscitation is associated with significant morbidity in various clinical settings. We wanted to assess whether aggressive early crystalloid resuscitation adversely affects outcomes in adult blunt trauma patients. METHODS: Datawere derived from the Glue Grant database. Our primary outcome measurewas all-cause in-hospital mortality. Secondary outcomes included days on mechanical ventilation; intensive care unit (ICU) and hospital length of stay (LOS); inflammatory (acute lung injury and adult respiratory distress syndrome, or multiple-organ failure) and resuscitation-related morbidity (abdominal and extremity compartment syndromes or acute renal failure) and nosocomial infections (ventilator-associated pneumonia, bloodstream, urinary tract, and surgical site infections). RESULTS: In our sample of 1,754 patients, in-hospital mortality was not affected, but ventilator days (p < 0.001) as well as ICU (p = 0.009) and hospital (p = 0.002) LOS correlated strongly with the amount of crystalloids infused in the first 24 hours after injury. Amount of crystalloid resuscitation was also associated with the development of adult respiratory distress syndrome (p < 0.001), multiple-organ failure (p < 0.001), bloodstream (p = 0.001) and surgical site infections (p < 0.001), as well as abdominal (p < 0.001) and extremity compartment syndromes (p = 0.028) in a dose-dependent fashion, when age, Glasgow Coma Scale (GCS), severity of injury and acute physiologic derangement, comorbidities, as well as colloid and blood product transfusions were controlled for. CONCLUSION: Crystalloid resuscitation is associated with a substantial increase in morbidity, as well as ICU and hospital LOS in adult blunt trauma patients. (Copyright (c) 2013 by Lippincott Williams Wilkins) C1 [Kasotakis, George; Sideris, Antonis; Yang, Yuchiao; de Moya, Marc; Alam, Hasan; King, David R.; Tompkins, Ronald; Velmahos, George; Inflammation Host Response Injury] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Crit Care, Boston, MA 02114 USA. RP Kasotakis, G (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gkasotakis@mail.harvard.edu FU NIGMS NIH HHS [R24 GM102656, U54 GM062119] NR 48 TC 37 Z9 38 U1 0 U2 7 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 MAY PY 2013 VL 74 IS 5 BP 1215 EP 1221 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 149JZ UT WOS:000319316600007 PM 23609270 ER PT J AU Sillesen, M Johansson, PI Rasmussen, LS Jin, G Jepsen, CH Imam, AM Hwabejire, J Lu, J Duggan, M Velmahos, G deMoya, M Alam, HB AF Sillesen, Martin Johansson, Par I. Rasmussen, Lars S. Jin, Guang Jepsen, Cecilie H. Imam, Ayehsa M. Hwabejire, John Lu, Jennifer Duggan, Michael Velmahos, George deMoya, Marc Alam, Hasan B. TI Platelet activation and dysfunction in a large-animal model of traumatic brain injury and hemorrhage SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Platelets; hemorrhage; traumatic brain injury; inflammation; swine ID INTRACRANIAL HEMORRHAGE; COAGULOPATHY; TISSUE; CD40; PROGRESSION; SHOCK AB BACKGROUND: Traumatic brain injury (TBI) and hemorrhage are the leading causes of trauma-related mortality. Both TBI and hemorrhage are associated with coagulation disturbances, including platelet dysfunction. We hypothesized that platelet dysfunction could be detected early after injury, and that this dysfunction would be associated with early activation, as measured by circulating levels of platelet activation markers. METHODS: A total of 33 swine were allocated to TBI and hypotension (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation only). Animals in the TBI/Hemorrhage group were left hypotensive, defined as mean arterial pressure of 35 mm Hg, for 2 hours. Blood samples were drawn at baseline and 3 minutes and 15 minutes following injury as well as following 2 hours of shock. Samples were analyzed for platelet aggregation using impedance aggregometry with agonists collagen, arachidonic acid, and adenosine diphosphate (ADP) and thromboelastography (TEG) and circulating levels of platelet activation markers transforming growth factor-A (TGF-A), CD40 ligand, and sP-selectin. RESULTS: Platelet ADP aggregation was significantly lower in the TBI/Hemorrhage group when compared with the control group 15 minutes following injury (62.4 vs. 80.4 U, p = 0.03) as well as following 2 hours of hypotension (59.9 vs. 73.5 U, p < 0.01). The latter was associated with lower TEG measured clot strength (TEG-MA, 74.1 vs. 79.4 mm, p = 0.05). No difference in collagen or arachidonic acid aggregation was observed. TGF-A levels were significantly higher in the TBI/Hemorrhage group following 2 hours of hypotension (1,764 vs. 1,252 pg/mL, p = 0.01). No differences in CD40 ligand or sP-selectin levels were observed. CONCLUSION: In this combined model of TBI and hemorrhage, a significantly lower ADP-induced platelet aggregation was detected 15 minutes following injury that was further aggravated during the 2-hour shock period. This dysfunction was associated with an increase in platelet activation marker TGF-A. (C) 2013 by Lippincott Williams & Wilkins C1 [Sillesen, Martin; Rasmussen, Lars S.] Copenhagen Univ Hosp, Rigshosp, Dept Anesthesia, Ctr Head & Orthoped, Copenhagen, Denmark. [Johansson, Par I.; Jepsen, Cecilie H.] Copenhagen Univ Hosp, Rigshosp, Capital Reg Blood Bank, Copenhagen, Denmark. [Sillesen, Martin; Jepsen, Cecilie H.; Imam, Ayehsa M.; Hwabejire, John; Lu, Jennifer; Duggan, Michael; Velmahos, George; deMoya, Marc; Alam, Hasan B.] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Johansson, Par I.] Univ Texas Med Sch Houston, Dept Surg, Houston, TX USA. [Jin, Guang; Alam, Hasan B.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu RI Johansson, Par/P-9283-2015; OI Johansson, Par/0000-0001-9778-5964; Rasmussen, Lars/0000-0002-7480-3004 FU US Army Medical Research and Materiel Command [GRANTT00521959]; Copenhagen University Hospital, Rigshospitalet (Denmark); Laerdal Foundation (Norway); Aase and Ejnar Danielsen Foundation (Denmark); Olof Norlander Foundation (Sweden); Maersk Foundation (Denmark); Tryg Foundation (Denmark); Lundbeck Foundation (Denmark) FX The study was funded by a grant from the US Army Medical Research and Materiel Command (GRANTT00521959) to H.B.A., grants from Copenhagen University Hospital, Rigshospitalet (Denmark), The Laerdal Foundation (Norway), The Aase and Ejnar Danielsen Foundation (Denmark), The Olof Norlander Foundation (Sweden), and The Maersk Foundation (Denmark) to M.S. L.S.R. has received funding from the Tryg Foundation (Denmark). P.I.J. received funding from the Lundbeck Foundation (Denmark). The Multiplate machine was on unconditional loan from US Distributor Diapharma Group Inc. (West Chester, OH) for the duration of the study, while the TEG-5000 machine was on unconditional loan from Haemonetics Corp. (Braintree, MA). These companies did not participate in study planning, execution, data analysis, or manuscript preparation. NR 23 TC 23 Z9 23 U1 1 U2 14 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 MAY PY 2013 VL 74 IS 5 BP 1252 EP 1259 DI 10.1097/TA.0b013e31828c7a6b PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 149JZ UT WOS:000319316600017 PM 23609275 ER PT J AU Ursiny, M Eisner, BH AF Ursiny, Michal Eisner, Brian H. TI Cost-Effectiveness of Anti-Retropulsion Devices for Ureteroscopic Lithotripsy SO JOURNAL OF UROLOGY LA English DT Article DE ureter; ureteral calculi; ureteroscopy; lithotripsy; disposable equipment ID PROXIMAL URETERAL STONES; HOLMIUM-YAG LASER; IN-VITRO; PNEUMATIC LITHOTRIPSY; CLINICAL-TRIAL; PREVENTION; MIGRATION; CONE; FRAGMENTATION; GENERATION AB Purpose: We evaluated the cost-effectiveness of anti-retropulsion devices used during ureteroscopic lithotripsy. Materials and Methods: A decision analysis model was constructed to compare the cost-effectiveness of ureteroscopic lithotripsy with vs without an anti-retropulsion device. The risk of stone retropulsion was determined from published data in the English language literature. Expected value calculations were used to determine whether the additional cost of a device would be cost-effective to prevent secondary procedures used to treat retropulsed stones. Device cost was determined using the average cost of all commercially available devices. Results: It became cost-effective to use an anti-retropulsion device at or above a 6.3% retropulsion rate. The weighted probability of retropulsion with vs without an anti-retropulsion device was 98.1% vs 83.7%. The estimated costs of secondary procedures needed to treat retropulsed stones were $5,290 for shock wave lithotripsy and $6,390 for ureteroscopy. Average device cost was $278. Thus, the average additional cost of ureteroscopic lithotripsy with vs without an anti-migration device would be $384 vs $952. Conclusions: It is cost-effective to use an anti-retropulsion device at a retropulsion rate of greater than 6.3%. C1 [Ursiny, Michal; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Kidney Stone Ctr, Boston, MA USA. RP Eisner, BH (reprint author), Massachusetts Gen Hosp, Dept Neurol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org FU Endourological Society FX Supported by an Endourological Society grant (MU). NR 19 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2013 VL 189 IS 5 BP 1762 EP 1766 DI 10.1016/j.juro.2012.11.085 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 148QZ UT WOS:000319262900045 PM 23159589 ER PT J AU Lech, M Gunthner, R Lorenz, G Ryu, M Grobmayr, R Susanti, H Kobayashi, KS Flavell, RA Anders, HJ AF Lech, Maciej Guenthner, Roman Lorenz, Georg Ryu, Mi Groebmayr, Regina Susanti, Heni Kobayashi, Koichi S. Flavell, Richard A. Anders, Hans-Joachim TI IRAK-M IN RENAL FIBROSIS UPON UNILATERAL URETERAL OBSTRUCTION SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 50th European-Renal-Association - European-Dialysis-and-Transplant-Association Congress CY MAY 18-21, 2013 CL Istanbul, TURKEY SP European Renal Assoc (ERA), European Dialysis & Transplant Assoc (EDTA) C1 [Lech, Maciej; Guenthner, Roman; Lorenz, Georg; Ryu, Mi; Groebmayr, Regina; Susanti, Heni; Anders, Hans-Joachim] Klinikum Univ Munchen, Nephrol Zentrum, Med Klin & Poliklin 4, Munich, Germany. [Kobayashi, Koichi S.; Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, Sect Immunobiol, New Haven, CT 06510 USA. [Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 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 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 2013 VL 28 SU 1 BP 190 EP 190 PG 1 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 151ZF UT WOS:000319498201078 ER PT J AU de Borst, MH Hajhosseiny, R Tamez, H Wenger, J Thadhani, R Goldsmith, DJ AF de Borst, Martin H. Hajhosseiny, Reza Tamez, Hector Wenger, Julia Thadhani, Ravi Goldsmith, David J. TI META-ANALYSIS OF THE IMPACT OF VITAMIN D RECEPTOR ACTIVATORS FOR REDUCTION OF PROTEINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 50th European-Renal-Association - European-Dialysis-and-Transplant-Association Congress CY MAY 18-21, 2013 CL Istanbul, TURKEY SP European Renal Assoc (ERA), European Dialysis & Transplant Assoc (EDTA) C1 [de Borst, Martin H.] Univ Med Ctr Groningen, Dept Med, Div Nephrol, NL-9713 AV Groningen, Netherlands. [de Borst, Martin H.] Univ Groningen, Groningen, Netherlands. [Tamez, Hector; Wenger, Julia; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Hajhosseiny, Reza; Goldsmith, David J.] Guys Campus Kings Hlth Partners AHSC, London, England. 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 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 2013 VL 28 SU 1 BP 366 EP 366 PG 1 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 151ZF UT WOS:000319498202114 ER PT J AU Manchikanti, L Falco, FJE Benyamin, R Helm, S Singh, V Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Benyamin, Ramsin Helm, Standiford, II Singh, Vijay Hirsch, Joshua A. TI Value-Based Interventional Pain Management: A Review of Medicare National and Local Coverage Determination Policies SO PAIN PHYSICIAN LA English DT Review DE Interventional pain management; interventional techniques; national coverage determinations (NCDs); local coverage determinations (LCDs); contractor medical director (CMD); Centers for Medicare and Medicaid Services (CMS); Department of Health and Human Services (HHS); guidelines; evidence-based medicine; evidence development with coverage ID LOW-BACK-PAIN; SPINAL-CORD STIMULATION; INTERLAMINAR EPIDURAL INJECTIONS; EVIDENCE-BASED MEDICINE; MEDIAL BRANCH BLOCKS; PERIPHERAL-NERVE STIMULATION; ACTIVE-CONTROL TRIAL; 2-YEAR FOLLOW-UP; CLINICAL-PRACTICE GUIDELINES; LUMBAR SURGERY SYNDROME AB Major policies, regulations, and practice patterns related to interventional pain management are dependent on Medicare policies which include national coverage policies - national coverage determinations (NCDs), and local coverage policies -local coverage determinations (LCDs). The NCDs are Medicare coverage policies issued by the Centers for Medicare and Medicaid Services (CMS). The process used by the CMS in deciding what is and what is not medically necessary is lengthy, involving a review of evidence-based literature on the subject, expert opinion, and public comments. In contrast, LCDs are rules and Medicare coverage that are issued by regional contractors and fiscal intermediaries when an NCD has not addressed the policy at issue. The evidence utilized in preparing LCDs includes the highest level of evidence which is based on published authoritative evidence derived from definitive randomized clinical trials or other definitive studies, and general acceptance by the medical community (standard of practice), as supported by sound medical evidence. In addition, the intervention must be safe and effective and appropriate including duration and frequency that is considered appropriate for the item or service in terms of whether it is furnished in accordance with accepted standards of medical practice for the diagnosis or treatment of the patient's condition or to improve the function. In addition, the safe and effective provision includes that service must be furnished in a setting appropriate to the patient's medical needs and condition, ordered and furnished by qualified personnel, the service must meet, but does not exceed, the patient's medical need, and be at least as beneficial as an existing and available medically appropriate alternative. The LCDs are prepared with literature review, state medical societies, and carrier advisory committees (CACs) of which interventional pain management is a member. The LCDs may be appealed by beneficiaries. The NCDs are prepared by the CMS following a request for a national coverage decision after an appropriate national coverage request along with a draft decision memorandum, and public comments. After the request, the staff review, external technology assessment, Medicare Evidence Development and Coverage Advisory Committee (MedCAC) assessment, public comments, a draft decision memorandum may be posted which will be followed by a final decision and implementation instructions. This decision may be appealed to the department appeals board, but may be difficult to reverse. This manuscript describes NCDs and LCDs and the process of development, their development, issues related to the development, and finally their relation to interventional pain management. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Pain Med Fellowship Program, Philadelphia, PA 19140 USA. [Benyamin, Ramsin] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin] Univ Illinois, Coll Med, Urbana, IL USA. [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Hills, CA USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Endovasc Neurosurg & Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Cephalon/Teva; AstraZeneca; Purdue Pharma, LP FX Dr. Helm is a clinical investigator with Epimed and receives research support from Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP. He has attended an advisory group meeting for Activas. NR 273 TC 22 Z9 22 U1 2 U2 7 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2013 VL 16 IS 3 BP E145 EP E180 PG 36 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 149SN UT WOS:000319341600003 PM 23703416 ER PT J AU Manchikanti, L Falco, FJE Pampati, V Cash, KA Benyamin, RM Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Pampati, Vidyasagar Cash, Kimberly A. Benyamin, Ramsin M. Hirsch, Joshua A. TI Cost Utility Analysis of Caudal Epidural Injections in the Treatment of Lumbar Disc Herniation, Axial or Discogenic Low Back Pain, Central Spinal Stenosis, and Post Lumbar Surgery Syndrome SO PAIN PHYSICIAN LA English DT Review DE Caudal epidural injections; chronic low back pain; lumbar disc herniation; lumbar discogenic pain; lumbar spinal stenosis; lumbar post surgery syndrome; cost utility analysis; cost effectiveness analysis; quality-adjusted life years ID RANDOMIZED CONTROLLED-TRIAL; ACTIVE-CONTROL TRIAL; 2-YEAR FOLLOW-UP; FACET JOINT INTERVENTIONS; DOUBLE-BLIND TRIAL; PHYSICIANS ASIPP GUIDELINES; MANAGING CHRONIC PAIN; AFFORDABLE CARE ACT; NONOPERATIVE TREATMENT; SYSTEMATIC EVALUATION AB Background: In this era of escalating health care costs and the questionable effectiveness of multiple interventions, cost effectiveness or cost utility analysis has become the cornerstone of evidence-based medicine, and has an influence coverage decisions. Even though multiple cost effectiveness analysis studies have been performed over the years, extensive literature is lacking for interventional techniques. Cost utility analysis studies of epidural injections for managing chronic low back pain demonstrated highly variable results including a lack of cost utility in randomized trials and contrasting results in observational studies. There has not been any cost utility analysis studies of epidural injections in large randomized trials performed in interventional pain management settings. Objectives: To assess the cost utility of caudal epidural injections in managing chronic low back pain secondary to lumbar disc herniation, axial or discogenic low back pain, lumbar central spinal stenosis, and lumbar post surgery syndrome. Study Design: This analysis is based on 4 previously published randomized trials. Setting: A private, specialty referral interventional pain management center in the United States. Methods: Four randomized trials were conducted assessing the clinical effectiveness of caudal epidural injections with or without steroids for lumbar disc herniation, lumbar discogenic or axial low back pain, lumbar central spinal stenosis, and post surgery syndrome. A cost utility analysis was performed with direct payment data for a total of 480 patients over a period of 2 years from these 4 trials. Outcome included various measures with significant improvement defined as at least a 50% improvement in pain reduction and disability status. Results: The results of 4 randomized controlled trials of low back pain with 480 patients with a 2 year follow-up with the actual reimbursement data showed cost utility for one year of quality-adjusted life year (QALY) of $2,206 for disc herniation, $2,136 for axial or discogenic pain without disc herniation, $2,155 for central spinal stenosis, and $2,191 for post surgery syndrome. All patients showed significant improvement clinically and showed positive results in the cost utility analysis with an average cost per one year QALY of $2,172.50 for all patients and $1,966.03 for patients judged to be successful. The results of this assessment show a better cost utility or lower cost of managing chronic, intractable low back pain with caudal epidural injections at a QALY that is similar or lower in price than medical therapy only, physical therapy, manipulation, and surgery in most cases. Limitations: The limitations of this cost utility analysis include that it is a single center evaluation, even though 480 patients were included in the analysis. Further, only the costs of interventional procedures and physician visits were included. The benefits of returning to work were not assessed. Conclusion: This cost utility analysis of caudal epidural injections in the treatment of disc herniation, axial or discogenic low back pain, central spinal stenosis, and post surgery syndrome in the lumbar spine shows the clinical effectiveness and cost utility of these injections at less than $2,200 per one year of QALY. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar; Cash, Kimberly A.] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Pain Med Fellowship Program, Philadelphia, PA 19140 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Urbana, IL USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Endovasc Neurosurg & Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 103 TC 41 Z9 42 U1 7 U2 18 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2013 VL 16 IS 3 BP E129 EP E143 PG 15 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 149SN UT WOS:000319341600002 PM 23703415 ER PT J AU Avery, LL Scheinfeld, MH AF Avery, Laura L. Scheinfeld, Meir H. TI Imaging of Penile and Scrotal Emergencies SO RADIOGRAPHICS LA English DT Article ID SEGMENTAL TESTICULAR INFARCTION; RADIOLOGIC-PATHOLOGICAL CORRELATION; COLOR DOPPLER ULTRASOUND; BELL-CLAPPER DEFORMITY; HIGH-FLOW PRIAPISM; FOURNIERS GANGRENE; DIAGNOSIS; TRAUMA; MANAGEMENT; TORSION AB Penile and scrotal emergencies are uncommon, but when they do occur, urgent or emergent diagnosis and treatment are necessary. Emergent conditions of the male genitalia are primarily infectious, traumatic, or vascular. Infectious conditions, such as epididymitis and epididymo-orchitis, are well evaluated at ultrasonography (US), and their key findings include heterogeneity and hyperemia. Pyocele and abscess may also be seen at US. Fournier gangrene is best evaluated at computed tomography, which depicts subcutaneous gas. Vascular conditions, such as testicular torsion, infarction, penile Mondor disease, and priapism, are well evaluated at duplex Doppler US. The key imaging finding of testicular torsion and infarction is a lack of blood flow in the testicle or a portion of the testicle. Penile Mondor disease is characterized by a lack of flow to and noncompressibility of the superficial dorsal vein of the penis. Clinical examination and history are usually adequate for diagnosis of priapism, but Doppler US may help confirm the diagnosis. Traumatic injuries of the penis and scrotum are initially imaged with US, which depicts whether the penile corpora and testicular seminiferous tubules are contained by the tunicae albuginea; herniation of contents and discontinuity of the tunica albuginea indicate rupture. In some cases, magnetic resonance imaging may be performed because of its ability to directly depict discontinuity of the tunica albuginea. Radiologists must closely collaborate with emergency physicians, surgeons, and urologists to quickly and efficiently diagnose or rule out emergent conditions of the male genitalia to facilitate prompt and appropriate treatment. C1 [Avery, Laura L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Emergency Radiol, Boston, MA 02114 USA. [Scheinfeld, Meir H.] Albert Einstein Coll Med, Montefiore Med Ctr, Div Emergency Radiol, Bronx, NY 10467 USA. RP Avery, LL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Emergency Radiol, 55 Fruit St, Boston, MA 02114 USA. EM Lavery@partners.org OI Scheinfeld, Meir H/0000-0001-8880-4318 NR 85 TC 13 Z9 15 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2013 VL 33 IS 3 BP 721 EP 740 DI 10.1148/rg.333125158 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146SR UT WOS:000319111700011 PM 23674771 ER PT J AU Cai, W Kim, SH Lee, JG Yoshida, H AF Cai, Wenli Kim, Se Hyung Lee, June-Goo Yoshida, Hiroyuki TI Informatics in Radiology Dual-Energy Electronic Cleansing for Fecal-Tagging CT Colonography(1) SO RADIOGRAPHICS LA English DT Article ID VIRTUAL COLONOSCOPY; COMPUTED-TOMOGRAPHY; CATHARTIC PREPARATION; RECONSTRUCTION; SEGMENTATION; FEASIBILITY; EXPERIENCE; FILTRATION; NEOPLASIA; ACCURACY AB Electronic cleansing (EC) is an emerging technique for the removal of tagged fecal materials at fecal-tagging computed tomographic (CT) colonography. However, existing EC methods may generate various types of artifacts that severely impair the quality of the cleansed CT colonographic images. Dual-energy fecal-tagging CT colonography is regarded as a nextgeneration imaging modality. EC that makes use of dual-energy fecal-tagging CT colonographic images promises to be effective in reducing cleansing artifacts by means of applying the material decomposition capability of dual-energy CT. The dual-energy index (DEI), which is calculated from the relative change in the attenuation values of a material at two different photon energies, is a reliable and effective indicator for differentiating tagged fecal materials from various types of tissues on fecal-tagging CT colonographic images. A DEI-based dual-energy EC scheme uses the DEI to help differentiate the colonic lumen-including the luminal air, tagged fecal materials, and air-tagging mixture-from the colonic soft-tissue structures, and then segments the entire colonic lumen for cleansing of the tagged fecal materials. As a result, dual-energy EC can help identify partialvolume effects in the air-tagging mixture and inhomogeneous tagging in residual fecal materials, the major causes of EC artifacts. This technique has the potential to significantly improve the quality of EC and promises to provide images of a cleansed colon that are free of the artifacts commonly observed with conventional single-energy EC methods. C1 [Cai, Wenli; Lee, June-Goo; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli; Lee, June-Goo; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Se Hyung] Seoul Natl Univ Hosp, Dept Radiol, Coll Med, Seoul 110744, South Korea. RP Cai, W (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,400C, Boston, MA 02114 USA. EM Cai.Wenli@mgh.harvard.edu FU NIH/NCI; National Cancer Institute [R01CA131718, R01CA095279]; American Cancer Society FX H.Y.: Related financial activities: grants from NIH/NCI. Other financial activities: royalties from the University of Chicago, patent holder with Hologic and MEDIAN Technologies. W.C.: Related financial activities: grant from the American Cancer Society. Other financial activities: none.; The work was supported by the National Cancer Institute [grant numbers R01CA131718, R01CA095279]. NR 54 TC 9 Z9 9 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2013 VL 33 IS 3 BP 891 EP 912 DI 10.1148/rg.333125039 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146SR UT WOS:000319111700021 PM 23479680 ER PT J AU Ullrich, PM Lincoln, RK Tackett, MJ Miskevics, S Smith, BM Weaver, FM AF Ullrich, Philip M. Lincoln, Randi K. Tackett, M. Jan Miskevics, Scott Smith, Bridget M. Weaver, Frances M. TI Pain, Depression, and Health Care Utilization Over Time After Spinal Cord Injury SO REHABILITATION PSYCHOLOGY LA English DT Article DE spinal cord injury; pain; depression; health care ID PHYSICAL-DISABILITIES; COGNITIVE DISTORTION; VETERANS; ANXIETY; PEOPLE; MANAGEMENT; SYMPTOMS; RISK; BIAS; USA AB Objective: The aim of this research was to examine comorbid pain and depression after spinal cord injury (SCI) in terms of: frequency, longitudinal course, and associations with medical conditions and use of SCI specialty care. Method: Three consecutive standardized annual psychological evaluations were reviewed for 286 persons with SCI receiving care at an SCI specialty care center. Chart abstraction included medical and demographic information, a depression scale, and a pain scale. Administrative databases were used to collect SCI specialty care utilization data. Participants were categorized as having elevated pain, elevated depression, both elevated pain and depression, or neither elevated, using cut-off scores on the pain and depression scales. ANOVA and repeated measures ANOVA were used to compare study groups. Results: Approximately 20% of the sample showed both elevated pain and depression at Year 1. Persons with elevated pain and depression showed higher scores on those measures than did persons with either pain or depression alone. Pain scores tended to be stable over time. Depression scores tended to improve over 3 years, but persons with elevated pain and depression showed less improvement on depression scores than did persons with depression alone. Persons with pain and depression tended to utilize more SCI specialty care. Conclusions: Pain and depression are often comorbid after SCI. This comorbidity is associated with higher pain and depression severity, more persistent pain and depression over time, and more use of SCI specialty care. Comorbid pain and depression should be anticipated among persons with SCI and addressed in care plans. C1 [Ullrich, Philip M.; Lincoln, Randi K.; Tackett, M. Jan] VA Puget Sound Healthcare Syst, Spinal Cord Injury & Disorders Serv, Dept Vet Affairs, Seattle, WA USA. [Ullrich, Philip M.; Lincoln, Randi K.; Tackett, M. Jan] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Miskevics, Scott] Spinal Cord Injury Qual Enhancement Res Initiat, Dept Vet Affairs, Hines, IL USA. [Miskevics, Scott] Edward Hines Jr Dept Vet Affairs Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Smith, Bridget M.; Weaver, Frances M.] Loyola Univ, Dept Vet Affairs, Chicago, IL 60611 USA. [Smith, Bridget M.; Weaver, Frances M.] Loyola Univ, Spinal Cord Injury Qual Enhancement Res Initiat, Chicago, IL 60611 USA. [Smith, Bridget M.; Weaver, Frances M.] Loyola Univ, Ctr Management Complex Chron Care, Edward Hines Jr Dept Vet Affairs Hosp, Chicago, IL 60611 USA. [Smith, Bridget M.; Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Program Hlth Serv Res, Chicago, IL 60611 USA. RP Ullrich, PM (reprint author), 128 NAT,1660 S Columbian Way, Seattle, WA 98108 USA. EM philip.ullrich@va.gov NR 55 TC 9 Z9 9 U1 1 U2 15 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD MAY PY 2013 VL 58 IS 2 BP 158 EP 165 DI 10.1037/a0032047 PG 8 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 150DH UT WOS:000319369900005 PM 23713727 ER PT J AU Weisbord, SD AF Weisbord, Steven D. TI Sexual Dysfunction and Quality of Life in Patients on Maintenance Dialysis SO SEMINARS IN DIALYSIS LA English DT Article ID MALE HEMODIALYSIS-PATIENTS; ERECTILE DYSFUNCTION; SILDENAFIL TREATMENT; DEPRESSION; WOMEN; ASSOCIATION; VARDENAFIL; MANAGEMENT; PAIN C1 [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu NR 18 TC 4 Z9 4 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2013 VL 26 IS 3 BP 278 EP 280 DI 10.1111/sdi.12068 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 146DL UT WOS:000319069300009 PM 23458106 ER PT J AU Fung, CH Martin, JL Igodan, U Jouldjian, S Alessi, C AF Fung, Constance H. Martin, Jennifer L. Igodan, Uyi Jouldjian, Stella Alessi, Cathy TI The association between difficulty using positive airway pressure equipment and adherence to therapy: a pilot study SO SLEEP AND BREATHING LA English DT Article DE Sleep-disordered breathing; Therapy; Patient compliance; Patient outcome assessment ID OBSTRUCTIVE SLEEP-APNEA; PRIMARY-CARE PATIENTS; CPAP ADHERENCE; HEALTH; OUTCOMES; ADULTS AB Little is known about the ease of use of positive airway pressure (PAP) equipment and whether PAP equipment usability is associated with adherence. This pilot project aims to determine whether perceived difficulty with the mechanics of using PAP equipment is associated with nonadherence. Within a larger study of insomnia treatments, we screened (via telephone interview) 148 adults for sleep apnea/prior PAP use and asked them to describe the degree of difficulty putting on their PAP mask, adjusting their mask straps, turning dials/pushing PAP machine buttons, disconnecting tubing, and removing the machine's water chamber (five items; five-point Likert-like scale) and to report their PAP use (0 versus a parts per thousand yen1 days in the past week). Mean age of participants was 66.7 years (SD 7.0). Thirty respondents (20.3 %) reported at least "some difficulty" with at least one aspect of PAP equipment usability, and 15 respondents (10.1 %) reported at least "quite a lot of difficulty" with one or more aspects of PAP equipment usability. Of the participants, 43.9 % reported not using PAP equipment at all during the past week. Participants (73.3 %) with substantial PAP equipment difficulty (at least quite a lot of difficulty) versus 40.6 % without substantial difficulty reported zero nights of PAP use in the past week (chi-square 5.86, p = .015). Difficulty using PAP equipment is associated with PAP nonadherence. Studies are needed to confirm these findings and to identify determinants of poor usability. If findings are confirmed, strategies could be developed to improve PAP usability, which may improve adherence. C1 [Fung, Constance H.; Martin, Jennifer L.; Igodan, Uyi; Jouldjian, Stella; Alessi, Cathy] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC 11E, North Hills, CA 91343 USA. [Fung, Constance H.; Martin, Jennifer L.; Alessi, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Fung, CH (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM constance.h.fung@gmail.com FU Department of Veterans Affairs Advanced Geriatrics Fellowship Program, Veterans Administration Health Services Research and Development [Alessi IIR 08-295]; American Federation for Aging Research; John A. Hartford Foundation; Centers of Excellence National Program; Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center FX This study was supported by the Department of Veterans Affairs Advanced Geriatrics Fellowship Program, Veterans Administration Health Services Research and Development (Alessi IIR 08-295); American Federation for Aging Research, The John A. Hartford Foundation, the Centers of Excellence National Program; and Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center. The authors thank our project manager, Karen Josephson, the study coordinators, Terry Vandenberg and Sergio Martinez, and our research staff who assisted with the telephone interviews, Ana Grigorian, Jessica Bautista, and Rebecca Saia. All work was completed at VA Greater Los Angeles Healthcare System. NR 32 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1520-9512 J9 SLEEP BREATH JI Sleep Breath. PD MAY PY 2013 VL 17 IS 2 BP 853 EP 859 DI 10.1007/s11325-012-0779-y PG 7 WC Clinical Neurology; Respiratory System SC Neurosciences & Neurology; Respiratory System GA 146FR UT WOS:000319075800062 PM 23149875 ER PT J AU Shimatsu, Y Yamada, K Horii, W Hirakata, A Sakamoto, Y Waki, S Sano, J Saitoh, T Sahara, H Shimizu, A Yazawa, H Sachs, DH Nunoya, T AF Shimatsu, Yoshiki Yamada, Kazuhiko Horii, Wataru Hirakata, Atsushi Sakamoto, Yuji Waki, Shiori Sano, Junichi Saitoh, Toshiki Sahara, Hisashi Shimizu, Akira Yazawa, Hajime Sachs, David H. Nunoya, Tetsuo TI Production of cloned NIBS (Nippon Institute for Biological Science) and alpha-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates SO XENOTRANSPLANTATION LA English DT Article DE -1; 3-galactosyltransferase knockout; embryo transfer; GalT-KO MGH miniature; miniature pigs; Nippon Institute for Biological Science miniature pigs; somatic cell nuclear transfer ID ALPHA-1,3-GALACTOSYLTRANSFERASE GENE; EMBRYOS; CLONING; ADULT; DONORS; CALVES; XENOTRANSPLANTATION; REJECTION; SWINE AB Background Nuclear transfer (NT) technologies offer a means for producing the genetically modified pigs necessary to develop swine models for mechanistic studies of disease processes as well as to serve as organ donors for xenotransplantation. Most previous studies have used commercial pigs as surrogates. Method and Results In this study, we established a cloning technique for miniature pigs by somatic cell nuclear transfer (SCNT) using Nippon Institute for Biological Science (NIBS) miniature pigs as surrogates. Moreover, utilizing this technique, we have successfully produced an -1, 3-galactosyltransferase knockout (GalT-KO) miniature swine. Fibroblasts procured from a NIBS miniature pig fetus were injected into 1312 enucleated oocytes. The cloned embryos were transferred to 11 surrogates of which five successfully delivered 13 cloned offspring; the production efficiency was 1.0% (13/1312). In a second experiment, lung fibroblasts obtained from neonatal GalT-KO MGH miniature swine were used as donor cells and 1953 cloned embryos were transferred to 12 surrogates. Six cloned offspring were born from five surrogates, a production efficiency of 0.3% (6/1953). Conclusions These results demonstrate successful establishment of a miniature pig cloning technique by SCNT using NIBS miniature pigs as surrogates. To our knowledge, this is the first demonstration of successful production of GalT-KO miniature swine using miniature swine surrogates. This technique could help to ensure a stable supply of the cloned pigs through the use of miniature pig surrogates and could expand production in countries with limited space or in facilities with special regulations such as specific pathogen-free or good laboratory practice. C1 [Shimatsu, Yoshiki; Horii, Wataru; Sakamoto, Yuji; Sano, Junichi; Saitoh, Toshiki] Nippon Inst Biol Sci, Dept Res & Dev, Hokuto, Yamanashi 4080041, Japan. [Yamada, Kazuhiko; Hirakata, Atsushi; Waki, Shiori; Sahara, Hisashi] Kagoshima Univ, Ctr Adv Biomed Sci & Swine Res, Div Organ Replacement & Xenotransplantat Surg, Kagoshima 8908520, Japan. [Yamada, Kazuhiko; Shimizu, Akira; Sachs, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Yazawa, Hajime; Nunoya, Tetsuo] Nippon Inst Biol Sci, Tokyo, Japan. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Organ Transplantat Tolerance & Xenotransplantat L, Sch Med,MGH East,Transplantat Biol Res Ctr, Bldg 149-9014,13th St, Boston, MA 02129 USA. EM shimatsu@nibs.or.jp; kaz.yamada@tbrc.mgh.harvard.edu FU Ministry of Education, Science, Sports, Culture and Technology of Japan; NIH/NIAID FX We thank Dr. Byeong-Chun Lee (College of Veterinary Medicine, Seoul National University) for technical advice and Mr. Scott Arn for breeding and maintenance of the MGH GalT-KO miniature swine heard. We also thank Dr. Robert Hawley, Dr. Isabel Hanekamp and Dr. Masayuki Tasaki for their critical review of this manuscript. This work was supported by Grant-in-Aid for Scientific Research (A) from the Ministry of Education, Science, Sports, Culture and Technology of Japan (KY) and 2P01AI45897-11A1 from NIH/NIAID (DHS and KY). NR 40 TC 8 Z9 11 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY-JUN PY 2013 VL 20 IS 3 BP 157 EP 164 DI 10.1111/xen.12031 PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 150QO UT WOS:000319406100004 PM 23581451 ER PT J AU Waldo, SW Armstrong, EJ Kulkarni, A Hoffmayer, K Kinlay, S Hsue, P Ganz, P McCabe, JM AF Waldo, Stephen W. Armstrong, Ehrin J. Kulkarni, Ameya Hoffmayer, Kurt Kinlay, Scott Hsue, Priscilla Ganz, Peter McCabe, James M. TI Comparison of Clinical Characteristics and Outcomes of Cardiac Arrest Survivors Having Versus Not Having Coronary Angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; LONG-TERM PROGNOSIS; TO-BALLOON TIME; INTERVENTION; RESUSCITATION; ANGIOPLASTY; ASSOCIATION; MORTALITY; REGISTRY; IMPACT AB Prompt percutaneous coronary intervention is associated with improved survival in patients presenting with cardiac arrest. Few studies; however, have focused on patients with cardiac arrest not selected for coronary angiography. The aim of the present study was to evaluate the clinical characteristics and outcomes of patients with cardiac arrest denied emergent angiography. Patients with cardiac arrest were identified within a registry that included all catheterization laboratory activations from 2008 to 2012. Logistic regression and proportional-hazards models were created to assess the clinical characteristics and mortality associated with denying emergent angiography. Among 664 patients referred for catheterization, 110 (17%) had cardiac arrest, and 26 of these patients did not undergo emergent angiography. Most subjects (69%) were turned down for angiography for clinical reasons and a minority for perceived futility (27%). After multivariate adjustment, pulseless electrical activity as the initial arrest rhythm (adjusted odds ratio [AOR] 13.27, 95% confidence interval [CI] 1.76 to 100.12), <1.0 mm of ST-segment elevation (AOR 10.26,95% CI 1.68 to 62.73), female gender (AOR 4.45, 95% CI 1.04 to 19.08), and advancing age (AOR 1.10 per year, 95% CI 1.04 to 1.16) were associated with increased odds of with-holding angiography. The mortality rate was markedly higher for patients who were denied emergent angiography (hazard ratio 3.64, 95% CI 2.05 to 6.49), even after adjustment for medical acuity (hazard ratio 2.29, 95% CI 1.19 to 4.41). In conclusion, Older subjects, women, and patients without ST-segment elevation were more commonly denied emergent angiography after cardiac arrest. Patients denied emergent angiography had increased mortality that persisted after adjustment for illness severity. (C) 2013 Elsevier Inc. All rights reserved. C1 [Waldo, Stephen W.; Hoffmayer, Kurt; Hsue, Priscilla; Ganz, Peter] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. [Armstrong, Ehrin J.] Univ Calif Davis, Dept Med, Div Cardiovasc Med, Davis, CA 95616 USA. [Kulkarni, Ameya] Massachusetts Gen Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02114 USA. [Kinlay, Scott; McCabe, James M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Waldo, SW (reprint author), Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. EM stephen.waldo@ucsf.edu NR 26 TC 14 Z9 14 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2013 VL 111 IS 9 BP 1253 EP 1258 DI 10.1016/j.amjcard.2013.01.267 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142WI UT WOS:000318827900003 PM 23391104 ER PT J AU Ziogas, DC Gras-Miralles, B Mustafa, S Geiger, BM Najarian, RM Nagel, JM Flier, SN Popov, Y Tseng, YH Kokkotou, E AF Ziogas, Dimitrios C. Gras-Miralles, Beatriz Mustafa, Sarah Geiger, Brenda M. Najarian, Robert M. Nagel, Jutta M. Flier, Sarah N. Popov, Yury Tseng, Yu-Hua Kokkotou, Efi TI Anti-melanin-concentrating hormone treatment attenuates chronic experimental colitis and fibrosis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE melanin-concentrating hormone; inflammatory bowel disease; Crohn's disease; ulcerative colitis; experimental colitis; chronic dextran sodium sulfate colitis; intestinal fibrosis; myofibroblasts ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; INTESTINAL INFLAMMATION; GROWTH-FACTORS; IGF-I; EXPRESSION; CELLS; MYOFIBROBLASTS; MICE; PROLIFERATION AB Fibrosis represents a major complication of several chronic diseases, including inflammatory bowel disease (IBD). Treatment of IBD remains a clinical challenge despite several recent therapeutic advances. Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide shown to regulate appetite and energy balance. However, accumulating evidence suggests that MCH has additional biological effects, including modulation of inflammation. In the present study, we examined the efficacy of an MCH-blocking antibody in treating established, dextran sodium sulfate-induced experimental colitis. Histological and molecular analysis of mouse tissues revealed that mice receiving anti-MCH had accelerated mucosal restitution and lower colonic expression of several proinflammatory cytokines, as well as fibrogenic genes, including COL1A1. In parallel, they spared collagen deposits seen in the untreated mice, suggesting attenuated fibrosis. These findings raised the possibility of perhaps direct effects of MCH on myofibroblasts. Indeed, in biopsies from patients with IBD, we demonstrate expression of the MCH receptor MCHR1 in alpha-smooth muscle actin(+) subepithelial cells. CCD-18Co cells, a primary human colonic myofibroblast cell line, were also positive for MCHR1. In these cells, MCH acted as a profibrotic modulator by potentiating the effects of IGF-1 and TGF-beta on proliferation and collagen production. Thus, by virtue of combined anti-inflammatory and anti-fibrotic effects, blocking MCH might represent a compelling approach for treating IBD. C1 [Ziogas, Dimitrios C.; Gras-Miralles, Beatriz; Mustafa, Sarah; Geiger, Brenda M.; Najarian, Robert M.; Nagel, Jutta M.; Flier, Sarah N.; Popov, Yury; Kokkotou, Efi] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Kokkotou, E (reprint author), Beth Israel Deaconess Med Ctr, Dana 501,330 Brookline Ave, Boston, MA 02215 USA. EM ekokkoto@bidmc.harvard.edu OI Gras-Miralles, Beatriz/0000-0002-5943-7755; Popov, Yury V./0000-0001-7973-942X FU National Institutes of Health [R01-DK080058]; Broad Medical Research Program of The Broad Foundation [IBD-0165]; Harvard Clinical Nutrition Research Center [P30-DK040561]; American Gastroenterological Association Foundation FX This work was supported by research grant R01-DK080058 from the National Institutes of Health, IBD-0165 from the Broad Medical Research Program of The Broad Foundation, P30-DK040561 from the Harvard Clinical Nutrition Research Center, and an American Gastroenterological Association Foundation Grant to E. Kokkotou. NR 49 TC 3 Z9 3 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2013 VL 304 IS 10 BP G876 EP G884 DI 10.1152/ajpgi.00305.2012 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 144VD UT WOS:000318968100004 PM 23538494 ER PT J AU Kim, JI Kim, J Jang, HS Noh, MR Lipschutz, JH Park, KM AF Kim, Jee In Kim, Jinu Jang, Hee-Seong Noh, Mi Ra Lipschutz, Joshua H. Park, Kwon Moo TI Reduction of oxidative stress during recovery accelerates normalization of primary cilia length that is altered after ischemic injury in murine kidneys SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE primary cilia; reactive oxygen species; ERK; ischemia; ROS ID INDUCED FUNCTIONAL INJURY; MAPK KINASE ACTIVATION; RENAL CILIA; URETERAL OBSTRUCTION; MOUSE; MICE; REPERFUSION; PROGRESSION; PREVENTION; FLAGELLA AB The primary cilium is a microtubule-based nonmotile organelle that extends from the surface of cells, including renal tubular cells. Here, we investigated the alteration of primary cilium length during epithelial cell injury and repair, following ischemia/reperfusion (I/R) insult, and the role of reactive oxygen species in this alteration. Thirty minutes of bilateral renal ischemia induced severe renal tubular cell damage and an increase of plasma creatinine (PCr) concentration. Between 8 and 16 days following the ischemia, the increased PCr returned to normal range, although without complete histological restoration. Compared with the primary cilium length in normal kidney tubule cells, the length was shortened 4 h and 1 day following ischemia, increased over normal 8 days after ischemia, and then returned to near normal 16 days following ischemia. In the urine of I/R-subjected mice, acetylated tubulin was detected. The cilium length of proliferating cells was shorter than that in nonproliferating cells. Mature cells had shorter cilia than differentiating cells. Treatment with Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, during the recovery of damaged kidneys accelerated normalization of cilia length concomitant with a decrease of oxidative stress and morphological recovery in the kidney. In the Madin-Darby canine kidney (MDCK) cells, H2O2 treatment caused released ciliary fragment into medium, and MnTMPyP inhibited the deciliation. The ERK inhibitor U0126 inhibited elongation of cilia in normal and MDCK cells recovering from H2O2 stress. Taken together, our results suggest that primary cilia length reflects cell proliferation and the length of primary cilium is regulated, at least, in part, by reactive oxygen species through ERK. C1 [Kim, Jee In; Kim, Jinu; Jang, Hee-Seong; Noh, Mi Ra; Park, Kwon Moo] Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu, South Korea. [Kim, Jee In; Jang, Hee-Seong; Park, Kwon Moo] Kyungpook Natl Univ, Sch Med, Cardiovasc Res Inst, Taegu, South Korea. [Lipschutz, Joshua H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Lipschutz, Joshua H.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Park, KM (reprint author), Kyungpook Natl Univ, Sch Med, Dept Anat, 101 Dongindong 2Ga, Junggu 700422, Daegu, South Korea. EM kmpark@knu.ac.kr OI Jang, Hee-Seong/0000-0002-9620-351X FU Kyungpook National University Research Fund; National Research Foundation; Korean Government [NRF-2011-220-E00001]; Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A111366] FX This research was supported by the Kyungpook National University Research Fund 2012, a National Research Foundation Grant funded by the Korean Government (NRF-2011-220-E00001 to K. M. Park), and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111366 to K. M. Park). NR 35 TC 6 Z9 6 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2013 VL 304 IS 10 BP F1283 EP F1294 DI 10.1152/ajprenal.00427.2012 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 144UM UT WOS:000318966100007 PM 23515720 ER PT J AU Tapias, LF Muniappan, A Wright, CD Gaissert, HA Wain, JC Morse, CR Donahue, DM Mathisen, DJ Lanuti, M AF Tapias, Luis F. Muniappan, Ashok Wright, Cameron D. Gaissert, Henning A. Wain, John C. Morse, Christopher R. Donahue, Dean M. Mathisen, Douglas J. Lanuti, Michael TI Short and Long-Term Outcomes After Esophagectomy for Cancer in Elderly Patients 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 AGE; ESOPHAGUS; CARCINOMA; SURGERY; OCTOGENARIANS; MORTALITY; CARDIA AB Background. As worldwide life expectancy rises, the number of candidates for surgical treatment of esophageal cancer over 70 years will increase. This study aims to examine outcomes after esophagectomy in elderly patients. Methods. This study is a retrospective review of 474 patients undergoing esophagectomy for cancer during 2002 to 2011. A total of 334 (70.5%) patients were less than 70 years old (group A), 124 (26.2%) 70 to 79 years (group B), and 16 (3.4%) 80 years or greater (group C). We analyzed the effect of age on outcome variables including overall and disease specific survival. Results. Major morbidity was observed to occur in 115 (35.6%) patients of group A, 58 (47.9%) of group B, and 10 (62.5%) of group C (p = 0.010). Mortality, both 30-day and 90-day was observed in 2 (0.6%) and 7 (2.2%) of group A, 4 (3.2%) and 7 (6.1%) of group B, and 1 (6.3%) and 2 (14.3%) of group C, respectively (p = 0.032 and p = 0.013). Anastomotic leak was observed in 16 (4.8%) patients of group A, 6 (4.8%) of group B, and 0 (0%) of group C (p = 0.685). Anastomotic stricture (defined by the need for 2 dilations) was observed in 76 (22.8%) of groupA, 13 (10.5%) of group B, and 1 (6.3%) of group C (p = 0.005). Five-year overall and disease specific survival was 64.8% and 72.4% for group A, 41.7% and 53.4% for group B, 49.2% and 49.2% for group C patients (p = 0.0006), respectively. Conclusions. Esophagectomy should be carefully considered in patients 70 to 79 years old and can be justified with low mortality. Outcomes in octogenarians are worse suggesting esophagectomy be considered on a case by case basis. Stricture rate is inversely associated to age. (C) 2013 by The Society of Thoracic Surgeons C1 [Tapias, Luis F.; Muniappan, Ashok; Wright, Cameron D.; Gaissert, Henning A.; Wain, John C.; Morse, Christopher R.; Donahue, Dean M.; Mathisen, Douglas J.; Lanuti, Michael] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Lanuti, M (reprint author), 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@partners.org FU NCATS NIH HHS [UL1 TR000170, 8UL1TR000170 05,] NR 18 TC 17 Z9 20 U1 0 U2 2 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 MAY PY 2013 VL 95 IS 5 BP 1741 EP 1748 DI 10.1016/j.athoracsur.2013.01.084 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 144VO UT WOS:000318969500058 PM 23500043 ER PT J AU Manoach, DS Wamsley, EJ Shinn, AK Tucker, MA Ono, KE McKinley, SK Ely, AV Goff, DC Stickgold, R AF Manoach, Dara S. Wamsley, Erin J. Shinn, Ann K. Tucker, Matthew A. Ono, Kim E. McKinley, Sophia K. Ely, Alice V. Goff, Donald C. Stickgold, Robert TI Can we Improve Cognitive Function in Schizophrenia by Treating Abnormal Sleep? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE sleep spindles; schizophrenia; memory; eszopiclone; cognition C1 [Manoach, Dara S.; Ono, Kim E.; Goff, Donald C.] Massachusetts Gen Hosp, Charlestown, MA USA. [Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wamsley, Erin J.; Tucker, Matthew A.; McKinley, Sophia K.; Ely, Alice V.; Stickgold, Robert] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Shinn, Ann K.] McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 66 BP 21S EP 22S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800067 ER PT J AU Spencer, K AF Spencer, Kevin TI When Gamma Goes Up: Increased Gamma and Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE schizophrenia; gamma oscillation; NMDA receptor hypofunction C1 [Spencer, Kevin] Harvard Univ, Sch Med, VA Boston Healthcare Syst, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 91 BP 29S EP 30S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800092 ER PT J AU Rabinak, CA Angstadt, M Sripada, CS Milad, MR Liberzon, I Phan, KL AF Rabinak, Christine A. Angstadt, Mike Sripada, Chandra S. Milad, Mohammed R. Liberzon, Israel Phan, K. Luan TI Cannabinoid Facilitation of Extinction Recall via Increased Recruitment of Prefrontal-Hippocampal Circuitry in Healthy Humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE cannabinoid; fear extinction; cognitive enhancer; prefrontal cortex; fMRI C1 [Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; Liberzon, Israel; Phan, K. Luan] Univ Michigan, Ann Arbor, MI 48109 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Boston, MA USA. [Phan, K. Luan] Univ Illinois, Chicago, IL 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 105 BP 34S EP 34S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800106 ER PT J AU Fanous, A Ripke, S Amdur, R Bigdeli, T Holmans, P Corvin, A Corvin, A Kendler, K AF Fanous, Ayman Ripke, Stephan Amdur, Richard Bigdeli, Tim Holmans, Peter Corvin, Aiden Corvin, Aiden Kendler, Kenneth CA Schizophrenia Psychiat Genomics Co TI Genome-wide Association Study of Symptomatic Dimensions of Schizophrenia in the Psychiatric Genomics Consortium SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE schizophrenia; psychosis; symptom; genetic; gwas C1 [Fanous, Ayman; Amdur, Richard] Georgetown Univ, Washington, DC USA. [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Bigdeli, Tim; Kendler, Kenneth] Virginia Commonwealth Univ, Richmond, VA USA. [Holmans, Peter] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Corvin, Aiden; Corvin, Aiden] Trinity Coll Dublin, Dublin, Ireland. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 114 BP 37S EP 37S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800115 ER PT J AU Coombs, G Loggia, ML Buckner, RL Greve, DN Holt, DJ AF Coombs, Garth Loggia, Marco L. Buckner, Randy L. Greve, Douglas N. Holt, Daphne J. TI Amygdala Perfusion is Predicted by its Functional Connectivity with the Ventromedial Prefrontal Cortex and Negative Affect SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Amygdala; Functional connectivity; Arterial spin labeling; Negative affect; Resting state C1 [Coombs, Garth; Loggia, Marco L.; Buckner, Randy L.; Greve, Douglas N.; Holt, Daphne J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Coombs, Garth; Loggia, Marco L.; Buckner, Randy L.; Greve, Douglas N.; Holt, Daphne J.] Harvard Univ, Sch Med, Boston, MA USA. [Coombs, Garth; Buckner, Randy L.] Harvard Univ, Cambridge, MA 02138 USA. [Coombs, Garth; Loggia, Marco L.; Buckner, Randy L.; Greve, Douglas N.; Holt, Daphne J.] MGH HST MIT Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 154 BP 50S EP 50S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800155 ER PT J AU Hayes, JP Miller, D Lafleche, G Salat, D Verfaellie, M AF Hayes, Jasmeet P. Miller, Danielle Lafleche, Ginette Salat, David Verfaellie, Mieke TI Shared and Distinct White Matter Signatures Associated with PTSD and Mild TBI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE PTSD; TBI; diffusion tensor imaging; white matter; blast induced neurotrauma C1 [Hayes, Jasmeet P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Hayes, Jasmeet P.; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA. [Miller, Danielle; Lafleche, Ginette] Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02118 USA. [Salat, David] VA Boston Healthcare Syst, Neuroimaging Res Ctr Vet, Boston, MA USA. [Salat, David] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 163 BP 53S EP 53S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800164 ER PT J AU Lasko, NB Elman, I Gurvits, TV Tschibelu, E Spring, JD Pitman, RK AF Lasko, Natasha B. Elman, Igor Gurvits, Tamara V. Tschibelu, Evelyne Spring, Justin D. Pitman, Roger K. TI Neurological Soft Signs in Individuals with Pathological Gambling SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Pathological Gambling; Neurological Soft Signs; Copy Figure Test; constructional apraxia; visual agnosia C1 [Lasko, Natasha B.] Massachisetts Gen Hosp, Charlestown, MA USA. [Elman, Igor] Providence VA Med Ctr, Providence, RI USA. [Elman, Igor; Tschibelu, Evelyne] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Somerville, MA USA. [Gurvits, Tamara V.; Spring, Justin D.; Pitman, Roger K.] Massachisetts Gen Hospita, Charlestown, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 178 BP 58S EP 58S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800179 ER PT J AU Pitman, RK Marin, MF Vitek, ME Orr, SP Goldberg, J AF Pitman, Roger K. Marin, Marie-France Vitek, Mary Ellen Orr, Scott P. Goldberg, Jack TI Post-Traumatic Stress Disorder Symptoms and Their Relationship to Trauma Exposure SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Post-Traumatic Stress Disorder; Nightmares; Twin Study; Symptom Specificity; Mississippi Scale for Combat-Related PTSD C1 [Pitman, Roger K.; Marin, Marie-France; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Vitek, Mary Ellen; Goldberg, Jack] Seattle Epidemiol Res & Informat Ctr, Vietnam Era Twin Registry, Dept Vet Affairs, Dept Epidemiol, Seattle, WA USA. [Vitek, Mary Ellen; Goldberg, Jack] Univ Washington, Seattle, WA 98195 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 192 BP 62S EP 62S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800193 ER PT J AU Rosenbaum, BL Bui, E Holt, DJ Orr, SP Pitman, RK Milad, MR AF Rosenbaum, Blake L. Bui, Eric Holt, Daphne J. Orr, Scott P. Pitman, Roger K. Milad, Mohammed R. TI Do Sociodemographic Factors Really Predict Variance in Conditioned Fear? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Fear conditioning; Fear Extinction; Sociodemographic Factors; Skin Conductance C1 [Rosenbaum, Blake L.; Bui, Eric; Holt, Daphne J.; Orr, Scott P.; Pitman, Roger K.; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rosenbaum, Blake L.; Bui, Eric; Holt, Daphne J.; Orr, Scott P.; Pitman, Roger K.; Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 193 BP 62S EP 63S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800194 ER PT J AU Jensen, KP Kranzler, HR Stein, MB Gelernter, J AF Jensen, Kevin P. Kranzler, Henry R. Stein, Murray B. Gelernter, Joel TI The Effects of a Predicted MAP2K5 Microrna Target Site SNP on Risk for Anxiety and Depressive Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE anxiety; depression; genetics; microRNA; GWAS C1 [Jensen, Kevin P.; Gelernter, Joel] Yale Univ Sch Med, Dept Psychiat, West Haven, CT USA. [Jensen, Kevin P.; Gelernter, Joel] VA CT Hlth Care Ctr, West Haven, CT USA. [Kranzler, Henry R.] Univ Penn Perelman Sch Med, Dept Psychiat, Philadelphia, PA USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, MIRECC VISN4, Philadelphia, PA USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Gelernter, Joel] Yale Univ Sch Med, Dept Genet, West Haven, CT USA. [Gelernter, Joel] Yale Univ Sch Med, Dept Neurobiol, West Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 208 BP 67S EP 67S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800209 ER PT J AU Evans, KC McLaren, DG Song, TY Patel, A Dougherty, DD AF Evans, Karleyton C. McLaren, Donald G. Song, Tian-Yue Patel, Achint Dougherty, Darin D. TI Hypercapnia Evokes Exaggerated Amygdalar Cerebral Blood Flow in Panic Disorder: An Arterial Spin Labeled FMRI Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Panic; fMRI; amygdala; CBF; ASL C1 [Evans, Karleyton C.; McLaren, Donald G.; Song, Tian-Yue; Patel, Achint; Dougherty, Darin D.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 224 BP 73S EP 73S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800224 ER PT J AU Marin, MF Staples, LK VanElzakker, MB Pace-Schott, EF Lasko, NB Pitman, RK Shin, LM Milad, MR AF Marin, Marie-France Staples, Lindsay K. VanElzakker, Michael B. Pace-Schott, Edward F. Lasko, Natasha B. Pitman, Roger K. Shin, Lisa M. Milad, Mohammed R. TI Medial Prefrontal Cortex Resting Glucose Metabolism Predicts Fear Learning and Extinction in Post-Traumatic Stress Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE post-traumatic stress disorder; fear extinction; dorsal anterior cingulate cortex; ventromedial prefrontal cortex; skin conductance C1 [Marin, Marie-France; Staples, Lindsay K.; VanElzakker, Michael B.; Pace-Schott, Edward F.; Lasko, Natasha B.; Pitman, Roger K.; Shin, Lisa M.; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Staples, Lindsay K.; VanElzakker, Michael B.; Shin, Lisa M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Pace-Schott, Edward F.; Lasko, Natasha B.; Pitman, Roger K.; Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 225 BP 73S EP 73S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800225 ER PT J AU Mueller-Pfeiffer, C Zeffiro, T O'Gorman, R Michels, L Baumann, P Spring, JD Wood, NE Rufer, M Pitman, RK Orr, SP AF Mueller-Pfeiffer, Christoph Zeffiro, Thomas O'Gorman, Ruth Michels, Lars Baumann, Peter Spring, Justin D. Wood, Nellie E. Rufer, Michael Pitman, Roger K. Orr, Scott P. TI Cortical Modulation of Autonomic Responses to Salient Auditory Stimuli SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Functional magnetic resonance imaging; Unconditioned response; Autonomic nervous system; Saliency C1 [Mueller-Pfeiffer, Christoph; Spring, Justin D.; Wood, Nellie E.; Pitman, Roger K.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph; Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA. [Mueller-Pfeiffer, Christoph; Baumann, Peter; Rufer, Michael] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph] Ctr Educ & Res COEUR, Psychiat Serv Cty St Gallen North, Wil, Switzerland. [Zeffiro, Thomas] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. [O'Gorman, Ruth; Michels, Lars] Univ Childrens Hosp Zurich, Ctr MR Res, Zurich, Switzerland. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 226 BP 73S EP 73S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800226 ER PT J AU Rosso, IM Britton, JC Stewart, SE Papamiditriou, G Killgore, WDS Makris, N Wilhelm, S Jenike, MA Rauch, SL AF Rosso, Isabelle M. Britton, Jennifer C. Stewart, S. Evelyn Papamiditriou, George Killgore, William D. S. Makris, Nikos Wilhelm, Sabine Jenike, Michael A. Rauch, Scott L. TI Brain White Matter Integrity and Association with Age at Onset in Pediatric Obsessive-Compulsive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE obsessive-compulsive disorder; childhood; diffusion tensor imaging; corpus callosum; thalamus C1 [Rosso, Isabelle M.; Killgore, William D. S.; Jenike, Michael A.; Rauch, Scott L.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA USA. [Britton, Jennifer C.] Univ Miami, Miami, FL USA. [Stewart, S. Evelyn] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Papamiditriou, George; Makris, Nikos; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Britton, Jennifer/J-4501-2013; Stewart, Evelyn/K-6961-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 232 BP 75S EP 75S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800232 ER PT J AU Webb, CA Killgore, WDS Britton, JC Schwab, ZJ Price, LM Weiner, MR Gold, AL Rosso, IM Simon, NM Pollack, MH Rauch, SL AF Webb, Christian A. Killgore, William D. S. Britton, Jennifer C. Schwab, Zachary J. Price, Lauren M. Weiner, Melissa R. Gold, Andrea L. Rosso, Isabelle M. Simon, Naomi M. Pollack, Mark H. Rauch, Scott L. TI Comparing Categorical versus Dimensional Predictors of Functional Response Across Three Anxiety Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Amygdala; Insula; PTSD; Social anxiety; Specific phobia C1 [Webb, Christian A.; Killgore, William D. S.; Schwab, Zachary J.; Rosso, Isabelle M.; Rauch, Scott L.] McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA 02178 USA. [Britton, Jennifer C.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Price, Lauren M.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Weiner, Melissa R.; Gold, Andrea L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, Boston, MA 02114 USA. [Pollack, Mark H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RI Britton, Jennifer/J-4501-2013 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 230 BP 75S EP 75S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800230 ER PT J AU Weber, M Killgore, WDS Rosso, IM Britton, JC Simon, NM Pollack, MH Rauch, SL AF Weber, Mareen Killgore, William D. S. Rosso, Isabelle M. Britton, Jennifer C. Simon, Naomi M. Pollack, Mark H. Rauch, Scott L. TI Gray Matter Correlates of Posttraumatic Stress Disorder - A Voxel-Based Morphometry Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE PTSD; Amygdala; Hippocampus; Morphometry C1 [Weber, Mareen; Killgore, William D. S.; Rosso, Isabelle M.; Rauch, Scott L.] McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA 02178 USA. [Britton, Jennifer C.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, Boston, MA 02114 USA. [Pollack, Mark H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RI Britton, Jennifer/J-4501-2013 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 231 BP 75S EP 75S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800231 ER PT J AU Spring, JD Wood, NE Marin, MF Lasko, NB Mueller-Pfeiffer, C Pitman, RK Orr, SP AF Spring, Justin D. Wood, Nellie E. Marin, Marie-France Lasko, Natasha B. Mueller-Pfeiffer, Christoph Pitman, Roger K. Orr, Scott P. TI Pre-Reactivation Propranolol Fails to Reduce Skin Conductance Reactivity to Fear-Conditioned Stimuli SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE post-traumatic stress disorder; memory reconsolidation; fear conditioning; anxiety; propranolol C1 [Spring, Justin D.; Wood, Nellie E.; Marin, Marie-France; Lasko, Natasha B.; Mueller-Pfeiffer, Christoph; Pitman, Roger K.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lasko, Natasha B.; Mueller-Pfeiffer, Christoph; Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Mueller-Pfeiffer, Christoph] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph] Ctr Educ & Res COEUR, Psychiat Serv Cty St Gallen North, Wil, Switzerland. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 308 BP 99S EP 100S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800307 ER PT J AU Wood, NE Spring, JD Marin, MF Lasko, NB Orr, SP Pitman, RK AF Wood, Nellie E. Spring, Justin D. Marin, Marie-France Lasko, Natasha B. Orr, Scott P. Pitman, Roger K. TI Effect of Pre-Reactivation Mifepristone and D-Cycloserine on Subsequent Physiological Responding During Traumatic Imagery in PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE post-traumatic stress disorder; memory reconsolidation; mifepristone; d-cycloserine; psychophysiology C1 [Wood, Nellie E.; Spring, Justin D.; Marin, Marie-France; Lasko, Natasha B.; Orr, Scott P.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lasko, Natasha B.; Orr, Scott P.; Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 320 BP 103S EP 103S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800319 ER PT J AU Shvil, E Sullivan, GM Schafer, S Campeas, M Joyner, E Wager, T Markowitz, J Milad, MR Neria, Y AF Shvil, Erel Sullivan, Gregory M. Schafer, Scott Campeas, Miriam Joyner, Emily Wager, Tor Markowitz, John Milad, Mohammed R. Neria, Yuval TI Sex Differences in Fear Perception and Processing in PTSD - An FMRI Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE fMRI; Skin conductance response; Posttraumatic stress disorder; Fear processing; Gender C1 [Shvil, Erel; Sullivan, Gregory M.; Markowitz, John; Neria, Yuval] Columbia Univ, New York, NY USA. [Shvil, Erel; Sullivan, Gregory M.; Campeas, Miriam; Joyner, Emily; Markowitz, John; Neria, Yuval] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Schafer, Scott; Wager, Tor] Univ Colorado, Boulder, CO 80309 USA. [Milad, Mohammed R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 336 BP 108S EP 108S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800335 ER PT J AU Spencer, KM AF Spencer, Kevin M. TI Electrophysiological Measures of Stimulus-Specific Plasticity in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE schizophrenia; plasticity; event-related potentials; gamma oscillations C1 [Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 365 BP 118S EP 118S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800361 ER PT J AU Woodward, SH Kuo, JR Kaloupek, DG AF Woodward, Steven H. Kuo, Janice R. Kaloupek, Danny G. TI Amygdala Volume in Combat-Exposed Veterans with and without PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE PTSD; amygdala C1 [Woodward, Steven H.] Palo Alto VA Healthcare Syst, Palo Alto, CA USA. [Kuo, Janice R.] Ryerson Univ, Toronto, ON, Canada. [Kaloupek, Danny G.] VA New England Hlth Care Syst, Natl Ctr PTSD, Boston, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 389 BP 125S EP 125S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800385 ER PT J AU Aranovich, G McClure, SM Shanbhag, H Roach, BJ Mathalon, DH AF Aranovich, Gabriel McClure, Samuel M. Shanbhag, Harshad Roach, Brian J. Mathalon, Daniel H. TI Neural Correlates of Delay Discounting for Monetary Rewards in Chronic Cigarette Smokers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Discounting; Medial Prefrontal Cortex; DLPFC; Ventral Striatum; Addiction C1 [Aranovich, Gabriel; Shanbhag, Harshad; Roach, Brian J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Aranovich, Gabriel; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McClure, Samuel M.] Stanford Univ, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 404 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800400 ER PT J AU Lee, PH AF Lee, Phil H. TI Genome-Wide Analyses of Brain-Imaging Phenotypes Reveal Enriched Association of Neuronal and Psychiatric Genes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE imaging genetics; functional connectiviity; genome wide association study; pathway analysis; network analysis C1 [Lee, Phil H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 439 BP 141S EP 141S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800435 ER PT J AU Roffman, JL Silverstein, NJ Holmes, AJ Lee, PH Hollinshead, MO Smoller, JW Buckner, RL AF Roffman, Joshua L. Silverstein, Noah J. Holmes, Avram J. Lee, Phil H. Hollinshead, Marisa O. Smoller, Jordan W. Buckner, Randy L. TI Genetic Variation Across the Folate Metabolic Pathway Influences Cortical Thickness in Healthy Individuals SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Cortical thickness; Folate; Schizophrenia; Neurodevelopment C1 [Roffman, Joshua L.; Silverstein, Noah J.; Holmes, Avram J.; Lee, Phil H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Hollinshead, Marisa O.; Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Charlestown, MA USA. [Smoller, Jordan W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 440 BP 141S EP 142S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800436 ER PT J AU Chou, TN Deckersbach, T Coombs, G Corse, AK Arulpragasam, A Marioutina, M Dougherty, DD AF Chou, Tina Deckersbach, Thilo Coombs, Garth Corse, Andrew K. Arulpragasam, Amanda Marioutina, Mariya Dougherty, Darin D. TI The Neural Effective Connectivity of the Aftereffects of Emotion SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE fMRI; PPI; emotion; corticolimbic network; default network C1 [Chou, Tina; Coombs, Garth] Harvard Univ, Cambridge, MA 02138 USA. [Chou, Tina; Deckersbach, Thilo; Coombs, Garth; Corse, Andrew K.; Arulpragasam, Amanda; Marioutina, Mariya; Dougherty, Darin D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 509 BP 161S EP 162S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800497 ER PT J AU Hazlett, EA Fernandez, N Sasso, S Mascitelli, KA New, AS Goodman, M AF Hazlett, Erin A. Fernandez, Nicolas Sasso, Scott Mascitelli, Kathryn A. New, Antonia S. Goodman, Marianne TI Larger Startle-Eyeblink Amplitude During Unpleasant Pictures = Greater Severity of Suicidal Behavior: A Promising Endophenotype For RDOC SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE affective startle eyeblink; suicide; emotion regulation; psychophysiology; suicidal behavior C1 [Hazlett, Erin A.; New, Antonia S.; Goodman, Marianne] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Hazlett, Erin A.; Fernandez, Nicolas; Sasso, Scott; Mascitelli, Kathryn A.; New, Antonia S.; Goodman, Marianne] James J Peters VAMC, Mental Illness Res Educ & Clin Ctr, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 512 BP 162S EP 162S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800500 ER PT J AU Ramanathan, D Mathalon, DH Ford, J Brown, GG Stern, H Mueller, B Greve, DN McCarthy, G Voyvodic, J Berger, A Glover, G Diaz, M Yetter, E Ozyurt, B Jorgensen, KW Wible, CG Van Erp, TGM Turner, J Thompson, WK Shanbhag, H Potkin, SG AF Ramanathan, Dhakshin Mathalon, Daniel H. Ford, Judith Brown, Gregory G. Stern, Hal Mueller, Bryon Greve, Douglas N. McCarthy, Gregory Voyvodic, James Berger, Aysenil Glover, Gary Diaz, Michele Yetter, Elizabeth Ozyurt, Burak Jorgensen, Kasper W. Wible, Cynthia G. Van Erp, Theo G. M. Turner, Jessica Thompson, Wesley K. Shanbhag, Harshad Potkin, Steven G. TI Role of Ventral Prefrontal Cortex in Reorientation to Vs. Regulation of Emotional Distractors During Concurrent Cognitive Task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE emotion; regulation; distraction; prefrontal; VLPFC C1 [Ramanathan, Dhakshin; Mathalon, Daniel H.; Ford, Judith; Jorgensen, Kasper W.; Shanbhag, Harshad] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Ramanathan, Dhakshin; Mathalon, Daniel H.; Ford, Judith; Jorgensen, Kasper W.; Shanbhag, Harshad] San Francisco VA Med Ctr, San Francisco, CA USA. [Brown, Gregory G.; Yetter, Elizabeth] VA San Diego Healthcare Syst, Dept Psychiat, San Diego, CA USA. [Brown, Gregory G.; Yetter, Elizabeth] Univ Calif San Diego, San Diego, CA 92103 USA. [Stern, Hal] Univ Calif Irvine, Dept Stat, Irvine, CA USA. [Mueller, Bryon] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [McCarthy, Gregory] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Voyvodic, James; Diaz, Michele; Potkin, Steven G.] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC USA. [Berger, Aysenil] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Glover, Gary] Stanford Univ, Stanford, CA 94305 USA. [Ozyurt, Burak; Thompson, Wesley K.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Wible, Cynthia G.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02401 USA. [Wible, Cynthia G.] Brockton VAMC, Brockton, MA USA. [Van Erp, Theo G. M.] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. [Turner, Jessica] Mind Res Network, Albuquerque, NM USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 521 BP 165S EP 165S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800509 ER PT J AU Dunn, EC AF Dunn, Erin C. TI Genetic Variants Modify the Association Between Developmental Timing of Child Maltreatment and Symptoms of Depression In Young Adulthood: Results from the National Longitudinal Study on Adolescent Health SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE depression; gene-environment interaction; timing of child maltreatment; sensitive period C1 [Dunn, Erin C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 544 BP 173S EP 173S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800532 ER PT J AU Camprodon, JA Dougherty, D Duffy, AM Peters, AT Peckham, AD Rodman, AM Rauch, S Deckersbach, T AF Camprodon, Joan A. Dougherty, D. Duffy, A. M. Peters, A. T. Peckham, A. D. Rodman, A. M. Rauch, S. Deckersbach, T. TI Neural Correlates of Executive Dysfunction in Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE bipolar disorder; cognition; frontol lobe function; neuroimaging; fMRI C1 [Camprodon, Joan A.; Dougherty, D.; Duffy, A. M.; Peters, A. T.; Peckham, A. D.; Rodman, A. M.; Rauch, S.; Deckersbach, T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Camprodon, Joan A.; Dougherty, D.; Rauch, S.; Deckersbach, T.] Harvard Univ, Sch Med, Boston, MA USA. [Rauch, S.] McLean Hosp, Belmont, MA 02178 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 619 BP 196S EP 197S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800607 ER PT J AU Perez-Rodriguez, MM New, AS Yuan, QP Zhou, ZF Hodgkinson, C Goodman, M Koenigsberg, HW Goldstein, KE Goldman, D Siever, LJ Hazlett, EA AF Perez-Rodriguez, M. Mercedes New, Antonia S. Yuan, Qiaoping Zhou, Zhifeng Hodgkinson, Colin Goodman, Manrianne Koenigsberg, Harold W. Goldstein, Kim E. Goldman, David Siever, Larry J. Hazlett, Erin A. TI Impaired Extinction of Amygdala Response to Unpleasant Pictures in Borderline Personality Disorder Associated with BDNF genotype SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE BDNF; habituation; emotional processing; amygdala; borderline personality disorder C1 [Perez-Rodriguez, M. Mercedes; New, Antonia S.; Goodman, Manrianne; Koenigsberg, Harold W.; Goldstein, Kim E.; Siever, Larry J.; Hazlett, Erin A.] Mt Sinai Sch Med, New York, NY USA. [Perez-Rodriguez, M. Mercedes; New, Antonia S.; Goodman, Manrianne; Siever, Larry J.; Hazlett, Erin A.] James J Peters VAMC, Mirecc, Bronx, NY USA. [Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David] NIAAA, Rockville, MD 20852 USA. [Koenigsberg, Harold W.] James J Peters VAMC, Mhcc, Bronx, NY USA. RI Perez Rodriguez, Maria/B-9410-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 629 BP 200S EP 200S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800617 ER PT J AU Greenberg, MS Wood, NE Spring, JD Nagurney, JT Zafonte, RD Gurvits, TV Pitman, RK AF Greenberg, Mark S. Wood, Nellie E. Spring, Justin D. Nagurney, John T. Zafonte, Ross D. Gurvits, Tamara V. Pitman, Roger K. TI Neurological Soft Signs in Mild Traumatic Brain Injury (MTBI) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE mild traumatic brain injury; concussion; recovery of function; post-concussive syndrome C1 [Greenberg, Mark S.; Gurvits, Tamara V.; Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Greenberg, Mark S.; Wood, Nellie E.; Spring, Justin D.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greenberg, Mark S.; Zafonte, Ross D.] Spaulding Rehabil Hosp, Boston, MA USA. [Nagurney, John T.] Massachusetts Gen Hosp, Emergency Serv, Boston, MA 02114 USA. [Nagurney, John T.; Zafonte, Ross D.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 653 BP 208S EP 208S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800641 ER PT J AU Marder, SR AF Marder, Stephen R. TI Glutamate-Related Treatment Strategies in Schizophrenia Patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Glutamate; Neurocognition; Negative Symptoms C1 [Marder, Stephen R.] Univ Calif Los Angeles, VA Greater LA Hlth Care Syst, Los Angeles, CA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 706 BP 225S EP 226S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801016 ER PT J AU Orr, SP AF Orr, Scott P. TI Psychophysiological Markers for PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE PTSD; Psychophysiology; Diagnosis C1 [Orr, Scott P.] Massachusetts Gen Hosp, Charlestown, MA USA. [Orr, Scott P.] Harvard Univ, Sch Med, Charlestown, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 731 BP 234S EP 234S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801041 ER PT J AU Rasmusson, AM AF Rasmusson, Ann M. TI Integration of Neuroendocrinological Markers for PTSD with Relevance to PTSD Risk, Recovery, and Treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE PTSD; Neuroendocrinology; Neuroactive Steroids; Biomarkers; Fear Conditioning C1 [Rasmusson, Ann M.] VA Boston Healthcare Syst, Boston, MA USA. [Rasmusson, Ann M.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 733 BP 234S EP 234S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801043 ER PT J AU Deckersbach, T Corse, AK Chou, T Arulpragasam, A Kaur, N Rauch, SL Nierenberg, AA Dougherty, DD AF Deckersbach, Thilo Corse, Andrew K. Chou, Tina Arulpragasam, Amanda Kaur, Navneet Rauch, Scott L. Nierenberg, Andrew A. Dougherty, Darin D. TI Attention and Positive Affect in Bipolar Disorder: An FMRI Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE attention; positive affect; cognition; bipolar disorder; emotion regulation C1 [Deckersbach, Thilo; Corse, Andrew K.; Chou, Tina; Arulpragasam, Amanda; Kaur, Navneet; Rauch, Scott L.; Nierenberg, Andrew A.; Dougherty, Darin D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chou, Tina] Harvard Univ, Cambridge, MA 02138 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 838 BP 268S EP 268S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801148 ER PT J AU Lau, E Weber, K Delaney-Busch, N Ustine, C Fanucci, K Hamalainen, M Kuperberg, GR AF Lau, Ellen Weber, Kirsten Delaney-Busch, Nate Ustine, Candida Fanucci, Kristina Hamalainen, Matti Kuperberg, Gina R. TI Spatiotemporal Imaging of Language Reveals Dissociations Between Prediction Generation and Belief Updating in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE schizophrenia; language; prediction error; fMRI; MEG/ERP C1 [Lau, Ellen; Weber, Kirsten; Delaney-Busch, Nate; Ustine, Candida; Fanucci, Kristina; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Boston, MA 02111 USA. [Lau, Ellen; Weber, Kirsten; Delaney-Busch, Nate; Ustine, Candida; Fanucci, Kristina; Hamalainen, Matti; Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lau, Ellen; Weber, Kirsten; Delaney-Busch, Nate; Ustine, Candida; Fanucci, Kristina; Hamalainen, Matti; Kuperberg, Gina R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Lau, Ellen; Kuperberg, Gina R.] Univ Maryland, Dept Linguist, College Pk, MD 20742 USA. RI Hamalainen, Matti/C-8507-2013 NR 0 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 843 BP 269S EP 270S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801153 ER PT J AU Hall, MH Levy, DL Salisbury, DF Cohen, BM Lohan, M Ongur, D Smoller, JW AF Hall, Mei-Hua Levy, Deborah L. Salisbury, Dean F. Cohen, Bruce M. Lohan, Mary Oenguer, Dost Smoller, Jordan W. TI Comparing Auditory Event Related Potential Deficits in Schizophrenia and Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE schizophrenia; bipolar disorder; event related potentials; cognitive dysfunction C1 [Hall, Mei-Hua; Lohan, Mary; Oenguer, Dost] Harvard Univ, McLean Hosp, Sch Med, Psychot Disorders Div, Belmont, MA USA. [Levy, Deborah L.] Harvard Univ, McLean Hosp, Sch Med, Psychol Res Lab, Belmont, MA USA. [Salisbury, Dean F.] Univ Pittsburgh, Sch Med, Clin Neurophysiol Res Lab, Pittsburgh, PA USA. [Cohen, Bruce M.] Harvard Univ, McLean Hosp, Sch Med, Shervert Frazier Res Inst, Belmont, MA USA. [Smoller, Jordan W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 844 BP 270S EP 270S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801154 ER PT J AU Hay, RA Roach, BJ Attygalle, SS Cadenhead, K Carrion, R Bachman, P Johannesen, J Duncan, E Belger, A Niznikiewicz, M McCarley, RW Light, G Pillay, N Addington, J Cannon, T Cornblatt, B McGlashan, T Perkins, D Seidman, L Tsuang, M Walker, E Woods, S Donkers, F Mathalon, DH AF Hay, Rachel A. Roach, Brian J. Attygalle, Suneth S. Cadenhead, Kristin Carrion, Ricardo Bachman, Peter Johannesen, Jason Duncan, Erica Belger, Aysenil Niznikiewicz, Margaret McCarley, Robert W. Light, Gregory Pillay, Neelan Addington, Jean Cannon, Tyrone Cornblatt, Barbara McGlashan, Thomas Perkins, Diana Seidman, Larry Tsuang, Ming Walker, Elaine Woods, Scott Donkers, Franc Mathalon, Daniel H. CA NAPLS Consortium TI Mismatch Negativity Abnormalities Are Associated with Poorer Functioning in Youth at Clinical High Risk for Psychosis: Evidence from the NAPLS Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Mismatch negativity; Schizophrenia; Social Function; Prodrome; High Risk C1 [Hay, Rachel A.; Roach, Brian J.; Attygalle, Suneth S.; Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hay, Rachel A.; Roach, Brian J.; Attygalle, Suneth S.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cadenhead, Kristin; Light, Gregory; Tsuang, Ming] Univ Calif San Diego, San Diego, CA 92103 USA. [Carrion, Ricardo; Cornblatt, Barbara] Zucker Hillside Hosp, New York, NY USA. [Bachman, Peter] Univ Calif Los Angeles, Los Angeles, CA USA. [Johannesen, Jason; Cannon, Tyrone; McGlashan, Thomas; Woods, Scott] Yale Univ, New Haven, CT USA. [Duncan, Erica; Walker, Elaine] Emory Univ, Atlanta, GA 30322 USA. [Duncan, Erica] Atlanta VAMC, Atlanta, GA USA. [Belger, Aysenil; Perkins, Diana; Donkers, Franc] Univ N Carolina, Chapel Hill, NC USA. [Niznikiewicz, Margaret; McCarley, Robert W.; Seidman, Larry] Harvard Univ, Boston, MA 02115 USA. [Pillay, Neelan; Addington, Jean] Univ Calgary, Calgary, AB, Canada. RI Donkers, Franc/H-2391-2013 OI Donkers, Franc/0000-0002-8252-0426 NR 0 TC 1 Z9 1 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 850 BP 272S EP 272S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801160 ER PT J AU Brandel, M Ford, JM Turner, JA Van Erp, TG Voyvodic, J Preda, A Belger, A Bustillo, J O'Leary, D Mueller, B Lim, KO McEwen, SC Calhoun, VD Diaz, M Glover, G Greve, D Wible, C Vaidya, J Potkin, SG Mathalon, DH AF Brandel, Michael Ford, Judith M. Turner, Jessica A. Van Erp, Theodorus G. Voyvodic, James Preda, Adrian Belger, Aysenil Bustillo, Juan O'Leary, Daniel Mueller, Bryon Lim, Kelvin O. McEwen, Sarah C. Calhoun, Vince D. Diaz, Michelle Glover, Gary Greve, Douglas Wible, Cindy Vaidya, Jatin Potkin, Steven G. Mathalon, Daniel H. CA FBIRN TI Reduced Amplitude of Low Frequency Bold Fluctuations in Resting State FMRI is AssociatedwWith Attention Deficits in Schizophrenia: Evidence from the FBIRN Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Resting State fMRI; Schizophrenia; Attention; Amplitude of Low Frequency Fluctuations; Default Mode C1 [Brandel, Michael; Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brandel, Michael; Ford, Judith M.; Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA USA. [Turner, Jessica A.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Van Erp, Theodorus G.; Preda, Adrian; Potkin, Steven G.] Univ Calif Irvine, Irvine, CA USA. [Voyvodic, James; Diaz, Michelle] Duke Univ, Raleigh, NC USA. [Belger, Aysenil] Univ N Carolina, Chapel Hill, NC USA. [Bustillo, Juan; Calhoun, Vince D.] Univ New Mexico, Albuquerque, NM 87131 USA. [O'Leary, Daniel; Vaidya, Jatin] Univ Iowa, Iowa City, IA USA. [Mueller, Bryon; Lim, Kelvin O.] Univ Minnesota, Minneapolis, MN USA. [McEwen, Sarah C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Glover, Gary] Stanford Univ, Stanford, CA 94305 USA. [Greve, Douglas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wible, Cindy] Harvard Univ, Boston, MI 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 856 BP 274S EP 274S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801166 ER PT J AU Vinogradov, S AF Vinogradov, Sophia TI Heterogeneity in Cognitive Improvement After Intensive Cognitive Training in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE schizophrenia; cognition; cortical plasticity; cognitive training C1 [Vinogradov, Sophia] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 857 BP 274S EP 274S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801167 ER PT J AU del Re, EC Niznikiewicz, M Hosokawa, T McCarley, RW Spencer, KM AF del Re, Elisabetta C. Niznikiewicz, Margaret Hosokawa, Taiga McCarley, Robert W. Spencer, Kevin M. TI Habituation of Novelty and Target Stimulus-Evoked ERPS in First Episode Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat C1 [del Re, Elisabetta C.] VA Boston Healthcare Syst, Psychiat, Brookline, MA USA. [del Re, Elisabetta C.; Niznikiewicz, Margaret; Hosokawa, Taiga; McCarley, Robert W.; Spencer, Kevin M.] Harvard Univ, Boston, MA 02115 USA. [Niznikiewicz, Margaret; Hosokawa, Taiga; McCarley, Robert W.; Spencer, Kevin M.] VA Boston Healthcare Syst, Psychiat, Brockton, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 864 BP 276S EP 276S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801174 ER PT J AU Perez-Rodriguez, MM Shen, PH Bevilacqua, L Yuang, QP Zhou, ZF Hodgkinson, C Ripoll, L Goodman, M Koenigsberg, H Goldman, D Siever, LJ New, AS AF Perez-Rodriguez, M. Mercedes Shen, Pei-Hong Bevilacqua, Laura Yuang, Qiaoping Zhou, Zhifeng Hodgkinson, Colin Ripoll, Luis Goodman, Marianne Koenigsberg, Harold Goldman, David Siever, Larry J. New, Antonia S. TI Oxytocin Gene Variants Modulate Core Dimensions of Borderline Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Oxytocin; Single Nucleotide Polymorphism; Empathy; Impulsivity; Aggression C1 [Perez-Rodriguez, M. Mercedes; Ripoll, Luis; Goodman, Marianne; Koenigsberg, Harold; Siever, Larry J.; New, Antonia S.] James J Peters VAMC, Mt Sinai Sch Med, New York, NY USA. [Perez-Rodriguez, M. Mercedes; Ripoll, Luis; Goodman, Marianne; Koenigsberg, Harold; Siever, Larry J.; New, Antonia S.] James J Peters VAMC, MIRECC, New York, NY USA. [Shen, Pei-Hong; Bevilacqua, Laura; Yuang, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David] NIAAA, Lab Neurogenet, NIH, Rockville, MD 20852 USA. RI Perez Rodriguez, Maria/B-9410-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993 NR 0 TC 0 Z9 0 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 891 BP 285S EP 285S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801201 ER PT J AU Yao, JK Dougherty, GG Reddy, RD Montrose, DM Matson, WR Kaddurah-Daouk, R Keshavan, M AF Yao, Jeffrey K. Dougherty, George G. Reddy, Ravinder D. Montrose, Debra M. Matson, Wayne R. Kaddurah-Daouk, Rima Keshavan, Matcheri TI Interactions between Purine Metabolites and Monoamine Neurotransmitters in First-Episode Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Schizophrenia; First-episode psychosis; Purine catabolism; Monoamine neurotransmitters C1 [Yao, Jeffrey K.; Dougherty, George G.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.; Dougherty, George G.; Reddy, Ravinder D.; Montrose, Debra M.; Keshavan, Matcheri] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Matson, Wayne R.] Bedford VA Med Ctr, Med Res Serv, Bedford, MA USA. [Kaddurah-Daouk, Rima] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Keshavan, Matcheri] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Keshavan, Matcheri] Harvard Univ, Boston, MA 02115 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 913 BP 291S EP 291S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801221 ER PT J AU Palzes, V AF Palzes, Vanessa TI Predictions Break Down Between Motor Plans and Their Consequences in Schizophrneia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Schizophrenia; ERP; Corollary discharge; Prediction error C1 [Palzes, Vanessa] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 931 BP 297S EP 297S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801239 ER PT J AU Forsyth, JK McEwen, S Gee, DG Addington, J Bearden, CE Cadenhead, KS Cornblatt, BA Mathalon, DH McGlashan, TH Perkins, DO Seidman, LJ Tsuang, MT Walker, EF Woods, SW Cannon, TD AF Forsyth, Jennifer K. McEwen, Sarah Gee, Dylan G. Addington, Jean Bearden, Carrie E. Cadenhead, Kristin S. Cornblatt, Barbara A. Mathalon, Daniel H. McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Cannon, Tyrone D. TI Abnormalities of Neural Activation During Working Memory Predict Conversion to Psychosis in Clinical High-Risk Youth: A Preliminary Analysis from the North American Prodrome Longitudinal Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE schizophrenia; fMRI; prodromal; working memory; clinical high-risk C1 [Forsyth, Jennifer K.; McEwen, Sarah; Gee, Dylan G.; Bearden, Carrie E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Addington, Jean] Univ Calgary, Calgary, AB, Canada. [Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, San Diego, CA 92103 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Long Isl City, NY USA. [Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McGlashan, Thomas H.; Woods, Scott W.; Cannon, Tyrone D.] Yale Univ, New Haven, CT USA. [Perkins, Diana O.] Univ N Carolina, Chapel Hill, NC USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Elaine F.] Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 938 BP 300S EP 300S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801246 ER EF