FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kuiatse, I Thomas, SK Weber, DM Stein, AM Wang, M Shah, JJ Treon, SP Ansell, SM Orlowski, RZ AF Kuiatse, Isere Thomas, Sheeba K. Weber, Donna M. Stein, Adam M. Wang, Michael Shah, Jatin J. Treon, Steven P. Ansell, Stephen M. Orlowski, Robert Z. TI Inhibition of Spleen Tyrosine Kinase with Fostamatinib Shows Pre-Clinical Activity Against Models of Waldenstrom Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kuiatse, Isere; Thomas, Sheeba K.; Weber, Donna M.; Stein, Adam M.; Shah, Jatin J.; Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ansell, Stephen M.] Mayo Clin, Div Hematol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 3723 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601343 ER PT J AU Kumar, SK Berdeja, JG Niesvizky, R Lonial, S Hamadani, M Stewart, AK Roy, V Hari, P Vescio, R Berg, D Lin, JC Di Bacco, A Gupta, N Hui, AM Richardson, PG AF Kumar, Shaji K. Berdeja, Jesus G. Niesvizky, Ruben Lonial, Sagar Hamadani, Mehdi Stewart, A. Keith Roy, Vivek Hari, Parameswaran Vescio, Robert Berg, Deborah Lin, Jianchang Di Bacco, Alessandra Gupta, Neeraj Hui, Ai-Min Richardson, Paul G. TI A Phase 1/2 Study of Weekly MLN9708, an Investigational Oral Proteasome Inhibitor, in Combination with Lenalidomide and Dexamethasone in Patients with Previously Untreated Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kumar, Shaji K.] Mayo Clin, Div Hematol, Rochester, MN USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Niesvizky, Ruben] Cornell Univ, Ctr Excellence Lymphoma & Myeloma, Weill Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Hamadani, Mehdi] W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. [Stewart, A. Keith] Mayo Clin, Coll Med, Scottsdale, AZ USA. [Roy, Vivek] Mayo Clin, Jacksonville, FL 32224 USA. [Hari, Parameswaran] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Vescio, Robert] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Berg, Deborah; Lin, Jianchang; Di Bacco, Alessandra; Gupta, Neeraj; Hui, Ai-Min] Millennium Pharmaceut Inc, Cambridge, MA USA. [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 7 Z9 7 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 332 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902128 ER PT J AU Kumar, SK Berdeja, JG Niesvizky, R Lonial, S Hamadani, M Stewart, AK Roy, V Hari, P Vescio, R Berg, D Lin, JC Di Bacco, A Gupta, N Hui, AM Richardson, PG AF Kumar, Shaji K. Berdeja, Jesus G. Niesvizky, Ruben Lonial, Sagar Hamadani, Mehdi Stewart, A. Keith Roy, Vivek Hari, Parameswaran Vescio, Robert Berg, Deborah Lin, Jianchang Di Bacco, Alessandra Gupta, Neeraj Hui, Ai-Min Richardson, Paul G. TI A Phase 1/2 Study of Weekly MLN9708, an Investigational Oral Proteasome Inhibitor, in Combination with Lenalidomide and Dexamethasone in Patients with Previously Untreated Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kumar, Shaji K.] Mayo Clin, Div Hematol, Rochester, MN USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Niesvizky, Ruben] Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Ctr Excellence Lymphoma & Myeloma, New York, NY 10021 USA. [Lonial, Sagar] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. [Hamadani, Mehdi] W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. [Stewart, A. Keith] Mayo Clin, Coll Med, Scottsdale, AZ USA. [Roy, Vivek] Mayo Clin, Jacksonville, FL 32224 USA. [Hari, Parameswaran] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Vescio, Robert] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Berg, Deborah; Lin, Jianchang; Di Bacco, Alessandra; Gupta, Neeraj; Hui, Ai-Min] Millennium Pharmaceut Inc, Cambridge, MA USA. [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 332 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901304 ER PT J AU Landau, DA Carter, S Stojanov, P Stevenson, KE Mckenna, A Lawrence, M Sougnez, C Sivachenko, A Wang, LL Mang, WD Sachet, S Vartanov, AR Fernandes, SM Cibulskis, K Tesar, B Gabriel, S Meyerson, M Lander, ES Neuberg, DS Brown, JR Getz, G Wu, CJ AF Landau, Dan-Avi Carter, Scott Stojanov, Petar Stevenson, Kristen E. Mckenna, Aaron Lawrence, Michael Sougnez, Carrie Sivachenko, Andrey Wang, Lili Mang, Wandi Sachet, Shukla Vartanov, Alexander R. Fernandes, Stacey M. Cibulskis, Kristian Tesar, Bethany Gabriel, Stacey Meyerson, Matthew Lander, Eric S. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. TI The Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Landau, Dan-Avi; Wang, Lili; Mang, Wandi; Sachet, Shukla; Vartanov, Alexander R.; Fernandes, Stacey M.; Tesar, Bethany; Meyerson, Matthew; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Carter, Scott; Stojanov, Petar; Mckenna, Aaron; Lawrence, Michael; Sougnez, Carrie; Sivachenko, Andrey; Cibulskis, Kristian; Gabriel, Stacey; Lander, Eric S.; Getz, Gad] Broad Inst, Cambridge, MA USA. [Stevenson, Kristen E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 5 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900026 ER PT J AU Lane, AA van Bodegom, D Chapuy, B Alexe, G Sullivan, TJ Tivey, T Day, T Crispino, J Fox, E Stegmaier, K Weinstock, D AF Lane, Andrew A. van Bodegom, Diederik Chapuy, Bjoern Alexe, Gabriela Sullivan, Timothy J. Tivey, Trevor Day, Tovah Crispino, John Fox, Edward Stegmaier, Kimberly Weinstock, David TI Trisomy of the Down Syndrome Critical Region Suppresses Precursor B-Cell Differentiation and Promotes B-Cell Transformation Associated with Altered Expression of Polycomb Repressor Complex 2 Targets SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lane, Andrew A.; van Bodegom, Diederik; Chapuy, Bjoern; Alexe, Gabriela; Sullivan, Timothy J.; Tivey, Trevor; Day, Tovah; Fox, Edward; Stegmaier, Kimberly; Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Crispino, John] Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 115 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900344 ER PT J AU Leen, AM Bollard, CM Mendizabal, AM Shpall, EJ Szabolcs, P Antin, JH Kapoor, N Pai, SY Rowley, SD Kebriaei, P Grilley, BJ Gee, AP Brenner, MK Rooney, CM Heslop, HE AF Leen, Ann M. Bollard, Catherine M. Mendizabal, Adam M. Shpall, Elizabeth J. Szabolcs, Paul Antin, Joseph H. Kapoor, Neena Pai, Sung-Yun Rowley, Scott D. Kebriaei, Partow Grilley, Bambi J. Gee, Adrian P. Brenner, Malcolm K. Rooney, Cliona M. Heslop, Helen E. TI Multicenter Study of "off-the-Shelf" Third Party Virus-Specific T Cells (VSTs) to Treat Adenovirus (Adv), Cytomegalovirus (CMV) or Epstein Barr Virus (EBV) Infection After Hemopoietic Stem Cell Transplantation (HSCT) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Leen, Ann M.; Bollard, Catherine M.; Grilley, Bambi J.; Heslop, Helen E.] Methodist Hosp, Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Mendizabal, Adam M.] EMMES Corp, Rockville, MD USA. [Shpall, Elizabeth J.; Kebriaei, Partow] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Szabolcs, Paul] Duke Univ, Med Ctr, Dept Pediat, Div Blood & Marrow Transplantat, Durham, NC 27706 USA. [Szabolcs, Paul] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27706 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Kapoor, Neena] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Pai, Sung-Yun] Boston Childrens Hosp, Boston, MA USA. [Rowley, Scott D.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 457 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902203 ER PT J AU Leen, AM Bollard, CM Mendizabal, AM Shpall, EJ Szabolcs, P Antin, JH Kapoor, N Pai, SY Rowley, SD Kebriaei, P Grilley, BJ Gee, AP Brenner, MK Rooney, CM Heslop, HE AF Leen, Ann M. Bollard, Catherine M. Mendizabal, Adam M. Shpall, Elizabeth J. Szabolcs, Paul Antin, Joseph H. Kapoor, Neena Pai, Sung-Yun Rowley, Scott D. Kebriaei, Partow Grilley, Bambi J. Gee, Adrian P. Brenner, Malcolm K. Rooney, Cliona M. Heslop, Helen E. TI Multicenter Study of "off-the-Shelf" Third Party Virus-Specific T Cells (VSTs) to Treat Adenovirus (Adv), Cytomegalovirus (CMV) or Epstein Barr Virus (EBV) Infection After Hemopoietic Stem Cell Transplantation (HSCT) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Leen, Ann M.; Bollard, Catherine M.; Grilley, Bambi J.; Heslop, Helen E.] Baylor Coll Med, Methodist Hosp, Texas Childrens Hosp, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Mendizabal, Adam M.] EMMES Corp, Rockville, MD USA. [Shpall, Elizabeth J.; Kebriaei, Partow] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Szabolcs, Paul] Duke Univ, Med Ctr, Div Blood & Marrow Transplantat, Dept Pediat, Durham, NC 27706 USA. [Szabolcs, Paul] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27706 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Kapoor, Neena] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Pai, Sung-Yun] Boston Childrens Hosp, Boston, MA USA. [Rowley, Scott D.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 457 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902003 ER PT J AU Leleu, X Hebraud, B Fouquet, G Roussel, M Caillot, D Chretien, ML Arnulf, B Szalat, R Garderet, L Benajiba, L Pegourie, B Regny, C Royer, B Caulier, A Stoppa, AM Garciaz, S Touzeau, C Fermand, JP Facon, T Attal, M Moreau, P AF Leleu, Xavier Hebraud, Benjamin Fouquet, Guillemette Roussel, Murielle Caillot, Denis Chretien, Marie-Lorraine Arnulf, Bertrand Szalat, Raphael Garderet, Laurent Benajiba, Lina Pegourie, Brigitte Regny, Caroline Royer, Bruno Caulier, Alexis Stoppa, Anne-Marie Garciaz, Sylvain Touzeau, Cyrille Fermand, Jean-Paul Facon, Thierry Attal, Michel Moreau, Philippe TI Consolidation with Vtd Significantly Improves the Complete Remission (CR) Rate Following Vtd Induction and Single Autologous Stem Cell Transplantation (auto) in Multiple Myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Leleu, Xavier; Facon, Thierry] CHRU, Hop Claude Huriez, Serv Malad Sang, Lille, France. [Hebraud, Benjamin; Roussel, Murielle; Attal, Michel] Hop Purpan, Hematol Clin, Toulouse, France. [Fouquet, Guillemette] Hop Claude Huriez, Lille, France. [Caillot, Denis] Univ Hosp, Dijon, France. [Chretien, Marie-Lorraine] CHU, Hematol Clin, Dijon, France. [Arnulf, Bertrand] Hop St Louis, APHP, Paris, France. [Szalat, Raphael] Hop St Louis, Dept Hematol & Immunol, Paris, France. [Benajiba, Lina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pegourie, Brigitte; Regny, Caroline] CHU Grenoble, Hop A Michallon, F-38043 Grenoble, France. [Royer, Bruno; Caulier, Alexis] CHU, Hop Sud, Amiens, France. [Stoppa, Anne-Marie] Inst J Paoli I Calmettes, Hematol Clin, F-13009 Marseille, France. [Touzeau, Cyrille; Moreau, Philippe] CHU Nantes, F-44035 Nantes 01, France. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 3096 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601167 ER PT J AU Li, LQ Nellore, A McDonough, S Politikos, I Kim, H Nikiforow, S Antin, JH Ballen, KK Cutler, C Ritz, J Boussiotis, VA AF Li, Lequn Nellore, Anoma McDonough, Sean Politikos, Ioannis Kim, Haesook Nikiforow, Sarah Antin, Joseph H. Ballen, Karen K. Cutler, Corey Ritz, Jerome Boussiotis, Vassiliki A. TI Prostaglandin E-2 (PGE(2)) Alters the Molecular and Functional Properties of Umbilical Cord Blood T Cells Via Modulating Wnt/beta-Catenin Signaling SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Li, Lequn; Nellore, Anoma; Politikos, Ioannis; Boussiotis, Vassiliki A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [McDonough, Sean; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Kim, Haesook] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 226 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901090 ER PT J AU Liao, W Jordaan, G Sharma, S AF Liao, Wei Jordaan, Gwen Sharma, Sanjai TI Rasgrf1 Overexpression Amplifies B Cell Receptor Signaling in Chronic Lymphocytic Leukemia Specimens SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Liao, Wei; Jordaan, Gwen] UCLA W Los Angeles VA, Hematol Oncol, Northridge, CA USA. [Sharma, Sanjai] Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 926 PG 1 WC Hematology SC Hematology GA 074UG UT WOS:000313838902035 ER PT J AU Lin, HYF AF Lin, Herbert Yih-Fuu TI The Liver as a Conductor of Systemic Iron Regulation: the Central Role of Hepcidin and BMP Signaling SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lin, Herbert Yih-Fuu] Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 22 PG 1 WC Hematology SC Hematology GA 074UG UT WOS:000313838900006 ER PT J AU Liu, SH Walker, S Nelson, E Cirulli, R Xiang, M Qi, J Bradner, JE Frank, D AF Liu, Suhu Walker, Sarah Nelson, Erik Cirulli, Robert Xiang, Michael Qi, Jun Bradner, James E. Frank, David TI Targeting STAT5 in Leukemia Through Inhibition of Bromodomain Proteins SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Liu, Suhu; Walker, Sarah; Nelson, Erik; Cirulli, Robert; Xiang, Michael; Qi, Jun; Bradner, James E.; Frank, David] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 399 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902061 ER PT J AU Liu, SH Walker, S Nelson, E Cirulli, R Xiang, M Qi, J Bradner, JE Frank, D AF Liu, Suhu Walker, Sarah Nelson, Erik Cirulli, Robert Xiang, Michael Qi, Jun Bradner, James E. Frank, David TI Targeting STAT5 in Leukemia Through Inhibition of Bromodomain Proteins SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Liu, Suhu; Walker, Sarah; Nelson, Erik; Cirulli, Robert; Xiang, Michael; Qi, Jun; Bradner, James E.; Frank, David] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 399 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901237 ER PT J AU Locke, FL Pidala, J Storer, B Martin, PJ Pulsipher, MA Chauncey, T Jacobsen, N Kroeger, N Walker, I Territo, MC Light, S Laport, GG Nademanee, A Powles, R Keating, A Socie, G Anasetti, C AF Locke, Frederick L. Pidala, Joseph Storer, Barry Martin, Paul J. Pulsipher, Michael A. Chauncey, Thomas Jacobsen, Niels Kroeger, Nikolaus Walker, Irwin Territo, Mary C. Light, Susan Laport, Ginna G. Nademanee, Auayporn Powles, Raymond Keating, Armand Socie, Gerard Anasetti, Claudio TI The Anti-CD25 Antibody Daclizumab Delays Treg Reconstitution, Promotes CD4 Memory, and Does Not Prevent Acute or Chronic Gvhd After Allogeneic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Locke, Frederick L.; Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Storer, Barry; Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Martin, Paul J.] Univ Washington, Seattle, WA 98195 USA. [Pulsipher, Michael A.] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Chauncey, Thomas] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Jacobsen, Niels] Rigshosp, Copenhagen Univ Hosp, Copenhagen, Denmark. [Kroeger, Nikolaus] Univ Med Ctr Hamburg Eppendorf, Ctr Oncol, Bone Marrow Transplantat Unit, Hamburg, Germany. [Walker, Irwin] McMaster Univ, Hamilton, ON, Canada. [Territo, Mary C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Light, Susan] Bristol Myers Squibb Co, New York, NY 10154 USA. [Laport, Ginna G.] Stanford Univ, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Nademanee, Auayporn] City Hope Natl Med Ctr, Hematol & Stem Cell Transplantat, Duarte, CA USA. [Powles, Raymond] Parkside Oncol Clin, Wimbledon, England. [Keating, Armand] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Socie, Gerard] Hosp St Louis, Paris, France. [Anasetti, Claudio] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL 33612 USA. [Anasetti, Claudio] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 4195 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604134 ER PT J AU Long, M Neufeld, EJ Elisofon, S Kim, HB Blume, E Rodig, N Boyer, D Grace, RF AF Long, Michelle Neufeld, Ellis J. Elisofon, Scott Kim, Heung B. Blume, Elizabeth Rodig, Nancy Boyer, Debra Grace, Rachael F. TI Treatments and Outcomes of Immune Cytopenias Following Pediatric Solid Organ Transplant SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Neufeld, Ellis J.; Grace, Rachael F.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 5154 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605434 ER PT J AU Lonial, S Baz, R Bahlis, NJ Chen, CI Anderson, KC Chen, M Zaki, M Richardson, PG AF Lonial, Sagar Baz, Rachid Bahlis, Nizar J. Chen, Christine I. Anderson, Kenneth C. Chen, Min Zaki, Mohamed Richardson, Paul G. TI Improvement in Clinical Benefit Parameters with Pomalidomide (POM) in Combination with Low-Dose Dexamethasone (LoDEX) in Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Results From a Phase 2 Study SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lonial, Sagar] Emory Univ, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA. [Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Bahlis, Nizar J.] Univ Calgary, Div Hematol, So Alberta Canc Res Inst, Calgary, AB, Canada. [Chen, Christine I.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Anderson, Kenneth C.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Chen, Min; Zaki, Mohamed] Celgene Corp, Summit, NJ USA. [Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4052 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603048 ER PT J AU Lucena-Araujo, AR Jacomo, RH Kim, HT Melo, RA Bittencourt, R Pasquini, R Pagnano, KB Fagundes, E Chauffaille, MDLF Chiattone, CS Kwaan, HC Gallagher, RE Niemeyer, CM Schrier, SL Tallman, MS Grimwade, D Ganser, A Berliner, N Ribeiro, R Falcao, RP Lo-Coco, F Lowenberg, B Sanz, MA Rego, EM AF Lucena-Araujo, Antonio R. Jacomo, Rafael Henriques Kim, Haesook T. Melo, Raul A. Bittencourt, Rosane Pasquini, Ricardo Pagnano, Katia B. Fagundes, Evandro Chauffaille, Maria de Lourdes L. F. Chiattone, Carlos S. Kwaan, Hau C. Gallagher, Robert E. Niemeyer, Charlotte M. Schrier, Stanley L. Tallman, Martin S. Grimwade, David Ganser, Arnold Berliner, Nancy Ribeiro, Raul Falcao, Roberto P. Lo-Coco, Francesco Lowenberg, Bob Angel Sanz, Miguel Rego, Eduardo M. TI Aberrant Expression of the MLL5, BAALC, ID1, and WT1 Genes Is Associated with Higher Induction Mortality and Poorer Overall Survival in Acute Promyelocytic Leukemia Patients Treated with ATRA and Anthracycline-Based Chemotherapy: An International Consortium On Acute Promyelocytic Leukemia Study SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lucena-Araujo, Antonio R.; Jacomo, Rafael Henriques; Falcao, Roberto P.] Univ Sao Paulo, Ctr Cell Based Therapy, BR-14049 Ribeirao Preto, Brazil. [Kim, Haesook T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Melo, Raul A.] HEMOPE, Recife, PE, Brazil. [Bittencourt, Rosane] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. [Pasquini, Ricardo] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. [Pagnano, Katia B.] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Natl Inst Sci & Technol Blood, Campinas, SP, Brazil. [Fagundes, Evandro] Univ Fed Minas Gerais, Clin Hosp, Belo Horizonte, MG, Brazil. [Chauffaille, Maria de Lourdes L. F.] UNIFESP EPM, Sect Hematol & Blood Transfus, Dept Clin & Expt Oncol, Sao Paulo, Brazil. [Chiattone, Carlos S.] Santa Casa Med Sch, Sao Paulo, Brazil. [Kwaan, Hau C.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gallagher, Robert E.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Niemeyer, Charlotte M.] Univ Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, D-79106 Freiburg, Germany. [Schrier, Stanley L.] Stanford Univ, Dept Med Hematol, Sch Med, Stanford, CA 94305 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Grimwade, David] Kings Coll London, Dept Med & Mol Genet, Sch Med, London WC2R 2LS, England. [Ganser, Arnold] Hannover Med Sch, Hannover, Germany. [Berliner, Nancy] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ribeiro, Raul] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Lo-Coco, Francesco] Univ Roma Tor Vergata, Rome, Italy. [Lowenberg, Bob] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Angel Sanz, Miguel] Hosp Univ La Fe, Dept Clin Hematol, Valencia, Spain. [Rego, Eduardo M.] Med Sch Ribeirao Preto, Ribeirao Preto, Brazil. RI Rego, Eduardo/A-1058-2012 OI Rego, Eduardo/0000-0003-1567-4086 NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 1407 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838905226 ER PT J AU Lugt, MTV Braun, TM Hanash, S Ferrara, JLM Ritz, J Ho, VT Antin, JH Zhang, Q Chin, A Gomez, A Harris, AC Levine, JE Choi, SW Couriel, D Reddy, P Paczesny, S AF Lugt, Mark T. Vander Braun, Thomas M. Hanash, Samir Ferrara, James L. M. Ritz, Jerome Ho, Vincent T. Antin, Joseph H. Zhang, Qing Chin, Alice Gomez, Aurelie Harris, Andrew C. Levine, John E. Choi, Sung W. Couriel, Daniel Reddy, Pavan Paczesny, Sophie TI Plasma ST2 Concentrations Predict Development of Acute Gvhd and Non-Relapse Mortality SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Hanash, Samir; Zhang, Qing; Chin, Alice] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Levine, John E.] Univ Michigan, Pediat Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 466 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901370 ER PT J AU Ma, DD Ramachandran, A Chang, YL Lin, JH Zhang, WH Tai, YT Munshi, NC Handin, RI AF Ma, Dongdong Ramachandran, Aravind Chang, Yali Lin, Jianhong Zhang, Weihong Tai, Yu-Tzu Munshi, Nikhil C. Handin, Robert I. TI Differences in the Angiogenic Response and Subsequent Growth of Plasma Cells From Myeloma and MGUS Patients Xenografted Into Zebrafish Embryos SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ma, Dongdong] Harvard Univ, Sch Med, Boston, MA USA. [Tai, Yu-Tzu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 2912 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905327 ER PT J AU Macalalad, AR Chen, L Guerin, A Luo, JY Wu, EQ Griffin, JD AF Macalalad, Alexander R. Chen, Lei Guerin, Annie Luo, Jiayuan Wu, Eric Qiong Griffin, James D. TI Comparison of Treatment Changes for Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched From Imatinib to Nilotinib or Dasatinib As Second-Line Therapy SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Macalalad, Alexander R.; Guerin, Annie; Luo, Jiayuan; Wu, Eric Qiong] Anal Grp Inc, Consulting, Boston, MA USA. [Chen, Lei] Novartis Pharmaceut, E Hanover, NJ USA. [Griffin, James D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4443 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605362 ER PT J AU Macalalad, AR Chen, L Guerin, A Luo, JY Wu, EQ Griffin, JD AF Macalalad, Alexander R. Chen, Lei Guerin, Annie Luo, Jiayuan Wu, Eric Qiong Griffin, James D. TI Characteristics of Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched to Nilotinib or Dasatinib As Second-Line Therapy SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Macalalad, Alexander R.; Guerin, Annie; Luo, Jiayuan; Wu, Eric Qiong] Anal Grp Inc, Consulting, Boston, MA USA. [Griffin, James D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4447 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605358 ER PT J AU Mahindra, A Saad, AA Zhang, MJ Zhong, XB Dispenzieri, A Krishnan, A Lonial, S Pasquini, MC Hari, P AF Mahindra, Anuj Saad, Ayman A. Zhang, Mei-Jie Zhong, Xiaobo Dispenzieri, Angela Krishnan, Amrita Lonial, Sagar Pasquini, Marcelo C. Hari, Parameswaran TI Hematopoietic Cell Transplant Co-Morbidity Index (HCTCI) and Multiple Myeloma (MM) Survival After Autologous Hematopoietic Cell Transplantation (AHCT) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mahindra, Anuj] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Saad, Ayman A.] Univ Alabama Birmingham, Birmingham, AL USA. [Zhong, Xiaobo; Pasquini, Marcelo C.; Hari, Parameswaran] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. [Dispenzieri, Angela] Mayo Clin, Transplant Ctr, Dept Med, Rochester, MN USA. [Krishnan, Amrita] City Hope Natl Med Ctr, Dept Med, Duarte, CA 91010 USA. [Lonial, Sagar] Emory Univ, Div BMT, Winship Canc Inst Hematol & Med Oncol, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 4217 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906216 ER PT J AU Mansour, MR Sanda, T Lawton, LN Li, XY Kreslavsky, T Novina, C von Boehmer, H Young, R Look, AT AF Mansour, Marc R. Sanda, Takaomi Lawton, Lee N. Li, Xiaoyu Kreslavsky, Taras Novina, Carl von Boehmer, Harald Young, Richard Look, A. Thomas TI The TAL1 Complex Represses the FBXW7 Tumor Suppressor Through Mir-223 in Human T-Cell Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mansour, Marc R.] Dana Farber Canc Inst, Boston, MA USA. [Lawton, Lee N.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Li, Xiaoyu; Kreslavsky, Taras; Novina, Carl; von Boehmer, Harald] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Young, Richard] Whitehead Insititute, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 1296 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902270 ER PT J AU Marcucci, G Maharry, K Metzeler, KH Volinia, S Wu, YZ Mrozek, K Nicolet, D Kohlschimdt, J Whitman, S Mendler, JH Schwind, S Becker, H Eisfeld, AK Carroll, AJ Powell, BL Kolitz, JE Garzon, R Caligiuri, MA Stone, RM Bloomfield, CD AF Marcucci, Guido Maharry, Kati Metzeler, Klaus H. Volinia, Stefano Wu, Yue-Zhong Mrozek, Krzysztof Nicolet, Deedra Kohlschimdt, Jessica Whitman, Susan Mendler, Jason H. Schwind, Sebastian Becker, Heiko Eisfeld, Ann-Kathrin Carroll, Andrew J. Powell, Bayard L. Kolitz, Jonathan E. Garzon, Ramiro Caligiuri, Michael A. Stone, Richard M. Bloomfield, Clara D. TI The Clinical Role of Micrornas (miRs) in Cytogenetically Normal (CN) Acute Myeloid Leukemia (AML): miR-155 Upregulation Independently Identifies High-Risk Patients (Pts) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Marcucci, Guido; Maharry, Kati; Metzeler, Klaus H.; Volinia, Stefano; Wu, Yue-Zhong; Mrozek, Krzysztof; Nicolet, Deedra; Kohlschimdt, Jessica; Whitman, Susan; Mendler, Jason H.; Schwind, Sebastian; Becker, Heiko; Eisfeld, Ann-Kathrin; Garzon, Ramiro; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Kolitz, Jonathan E.] Hofstra N Shore LIJ Sch Med, Dept Med, Hempstead, NY USA. [Caligiuri, Michael A.] Ohio State Univ, Med Scientist Training Program, Columbus, OH 43210 USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stone, Richard M.] HMS, Boston, MA USA. RI Volinia, Stefano/A-3029-2010; Garzon, Ramiro/E-3104-2011 OI Volinia, Stefano/0000-0003-0910-3893; NR 0 TC 0 Z9 0 U1 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 1387 PG 3 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603105 ER PT J AU Mauro, MJ Cortes, JE Kim, DW Pinilla-Ibarz, J le Coutre, P Paquette, R Chuah, C Nicolini, FE Apperley, J Khoury, HJ Talpaz, M DiPersio, JF DeAngelo, DJ Abruzzese, E Rea, D Baccarani, M Muller, MC Gambacorti-Passerini, C Wong, S Dorer, DJ Knickerbocker, RK Rivera, VM Clackson, T Turner, CD Haluska, FG Guilhot, F Deininger, MW Hochhaus, A Hughes, T Goldman, JM Shah, N Kantarjian, HM AF Mauro, Michael J. Cortes, Jorge E. Kim, Dong-Wook Pinilla-Ibarz, Javier le Coutre, Philipp Paquette, Ronald Chuah, Charles Nicolini, Franck E. Apperley, Jane Khoury, H. Jean Talpaz, Moshe DiPersio, John F. DeAngelo, Daniel J. Abruzzese, Elisabetta Rea, Delphine Baccarani, Michele Muller, Martin C. Gambacorti-Passerini, Carlo Wong, Stephane Dorer, David J. Knickerbocker, Ronald Keith Rivera, Victor M. Clackson, Tim Turner, Christopher D. Haluska, Frank G. Guilhot, Francois Deininger, Michael W. Hochhaus, Andreas Hughes, Timothy Goldman, John M. Shah, Neil Kantarjian, Hagop M. CA PACE Study Grp TI Multivariate Analyses of the Clinical and Molecular Parameters Associated with Efficacy and Safety in Patients with Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph plus ALL) Treated with Ponatinib in the PACE Trial SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mauro, Michael J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Cortes, Jorge E.; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Kim, Dong-Wook] Catholic Univ Korea, Coll Med, Seoul St Marys Hosp, Div Hematol, Seoul, South Korea. [Pinilla-Ibarz, Javier] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [le Coutre, Philipp] Charite, D-13353 Berlin, Germany. [Paquette, Ronald] Univ Calif Los Angeles, Div Hematol Oncol, Los Angeles, CA USA. [Chuah, Charles] Singapore Gen Hosp, Dept Hematol, Canc & Stem Cell Biol Program, Duke NUS Grad Med Sch, Singapore, Singapore. [Nicolini, Franck E.] Ctr Hosp Lyon Sud, F-69310 Pierre Benite, France. [Apperley, Jane] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, Hammersmith Hosp, London, England. [Khoury, H. Jean] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Talpaz, Moshe] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [DiPersio, John F.] Washington Univ, St Louis, MO USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abruzzese, Elisabetta] Univ Roma Tor Vergata, Osped S Eugenio, Rome, Italy. [Rea, Delphine] Hop St Louis, Serv Malad Sang, Paris, France. [Rea, Delphine] Hop St Louis, EA3518, Paris, France. [Baccarani, Michele] Univ Bologna, Bologna, Italy. [Muller, Martin C.] Univ Med Mannheim, Med Klin 3, Mannheim, Germany. [Gambacorti-Passerini, Carlo] Univ Milano Bicocca, Azienda Osped San Gerardo, Unita Ric Clin Ematol, Monza, Italy. [Wong, Stephane] MolecularMD Corp, Portland, OR USA. [Dorer, David J.; Knickerbocker, Ronald Keith; Rivera, Victor M.; Clackson, Tim; Turner, Christopher D.; Haluska, Frank G.; PACE Study Grp] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. [Guilhot, Francois] CHU Poitiers, Poitiers, France. [Deininger, Michael W.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Hochhaus, Andreas] Univ Klinikum Jena, Dept Hematol & Oncol, Jena, Germany. [Hughes, Timothy] SA Pathol, RAH Site Div Haematol, Adelaide, SA, Australia. [Goldman, John M.] Univ London Imperial Coll Sci Technol & Med, Dept Hematol, London, England. [Shah, Neil] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. NR 0 TC 4 Z9 4 U1 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 3747 PG 3 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601318 ER PT J AU Mayeur, C Leyton, PA Kolodziej, SA Bloch, KD AF Mayeur, Claire Leyton, Patricio A. Kolodziej, Starsha A. Bloch, Kenneth D. TI TGF beta Signaling Regulates Hepcidin Gene Expression SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mayeur, Claire; Leyton, Patricio A.; Kolodziej, Starsha A.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 992 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600313 ER PT J AU Mehra, M Cossrow, N Stellhorn, RA Vermeulen, J Desai, A Munshi, NC AF Mehra, Maneesha Cossrow, Nicole Stellhorn, Robert A. Vermeulen, Jessica Desai, Avinash Munshi, Nikhil C. TI Use of a Claims Database to Characterize and Estimate the Incidence of Castleman's Disease SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mehra, Maneesha; Stellhorn, Robert A.] Janssen Global Serv LLC, Global Market Access, Raritan, NJ USA. [Cossrow, Nicole] Janssen Global Serv, Global Market Access, Horsham, PA USA. [Vermeulen, Jessica] Janssen Biol Europe, Oncol, NL-2333 CD Leiden, Netherlands. [Desai, Avinash] Janssen Global Serv LLC, Global Med Affairs, Raritan, NJ USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 4253 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906180 ER PT J AU Mimura, N Ohguchi, H Cirstea, D Cottini, F Gorgun, GT Minami, J Suzuki, R Shimomura, T Utsugi, T Hideshima, T Anderson, KC AF Mimura, Naoya Ohguchi, Hiroto Cirstea, Diana Cottini, Francesca Gorgun, Gullu Topal Minami, Jiro Suzuki, Rikio Shimomura, Toshiyasu Utsugi, Teruhiro Hideshima, Teru Anderson, Kenneth C. TI TAS-117, a Novel Selective Akt Inhibitor Demonstrates Significant Growth Inhibition in Multiple Myeloma Cells in Vitro and in Vivo SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mimura, Naoya; Ohguchi, Hiroto; Cottini, Francesca; Gorgun, Gullu Topal; Minami, Jiro; Suzuki, Rikio; Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Cirstea, Diana] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Shimomura, Toshiyasu; Utsugi, Teruhiro] TAIHO PHARMACEUT CO LTD, Tsukuba Res Ctr, Tsukuba, Ibaraki, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 942 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902019 ER PT J AU Mimura, N Ohguchi, H Cirstea, D Cottini, F Gorgun, GT Minami, J Suzuki, R Shimomura, T Utsugi, T Hideshima, T Anderson, KC AF Mimura, Naoya Ohguchi, Hiroto Cirstea, Diana Cottini, Francesca Gorgun, Gullu Topal Minami, Jiro Suzuki, Rikio Shimomura, Toshiyasu Utsugi, Teruhiro Hideshima, Teru Anderson, Kenneth C. TI TAS-117, a Novel Selective Akt Inhibitor Demonstrates Significant Growth Inhibition in Multiple Myeloma Cells in Vitro and in Vivo SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mimura, Naoya; Ohguchi, Hiroto; Cottini, Francesca; Gorgun, Gullu Topal; Minami, Jiro; Suzuki, Rikio; Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Cirstea, Diana] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Shimomura, Toshiyasu; Utsugi, Teruhiro] Taiho Pharmaceut Co Ltd, Tsukuba Res Ctr, Tsukuba, Ibaraki, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 942 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901195 ER PT J AU Morris, CR Kim, HY Wood, JC Trachtenberg, F Klings, ES Porter, JB Sweeters, N Olivieri, NF Kwiatkowski, JL Singer, ST Taher, AT Neufeld, EJ Thompson, AA Sachdev, V Larkin, SK Suh, JH Kuypers, FA Vichinsky, E AF Morris, Claudia R. Kim, Hae-Young Wood, John C. Trachtenberg, Felicia Klings, Elizabeth S. Porter, John B. Sweeters, Nancy Olivieri, Nancy F. Kwiatkowski, Janet L. Singer, Sylvia Titi Taher, Ali T. Neufeld, Ellis J. Thompson, Alexis A. Sachdev, Vandana Larkin, Sandra K. Suh, Jung H. Kuypers, Frans A. Vichinsky, Elliott TI Sildenafil Therapy in Patients with Thalassemia and an Elevated Tricuspid Regurgitant Jet Velocity (TRV) On Doppler Echocardiography At Risk for Pulmonary Hypertension: Report From the Thalassemia Clinical Research Network SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Morris, Claudia R.] Emory Univ, Sch Med, Atlanta, GA USA. [Kim, Hae-Young; Trachtenberg, Felicia] New England Res Inst, Watertown, MA 02172 USA. [Wood, John C.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Klings, Elizabeth S.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Porter, John B.] UCL, London, England. [Sweeters, Nancy; Singer, Sylvia Titi; Vichinsky, Elliott] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. [Olivieri, Nancy F.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Kwiatkowski, Janet L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Taher, Ali T.] Amer Univ Beirut, Beirut, Lebanon. [Neufeld, Ellis J.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Thompson, Alexis A.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Sachdev, Vandana] NHLBI, Cardiovasc & Pulm Med Branch, NIH, Bethesda, MD 20892 USA. [Suh, Jung H.] Childrens Hosp Oakland, Res Inst, Nutr & Metab Ctr, Oakland, CA 94609 USA. NR 0 TC 2 Z9 2 U1 1 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 1023 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602048 ER PT J AU Morrison, JF Grace, RF Saxena, K Neufeld, EJ AF Morrison, Jacqueline F. Grace, Rachael F. Saxena, Kapil Neufeld, Ellis J. TI High Diagnostic Utility of Second-Day Factor VIII Levels to Assess Pediatric Hemophilia A Pharmacokinetics SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Morrison, Jacqueline F.; Grace, Rachael F.; Saxena, Kapil; Neufeld, Ellis J.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 3368 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602316 ER PT J AU Motyckova, G Fega, KR Sherman, AE DeAngelo, DJ Abel, GA Steensma, D Wadleigh, M Stone, RM Driver, JA AF Motyckova, Gabriela Fega, K. Rebecca Sherman, Alexander E. DeAngelo, Daniel J. Abel, Gregory A. Steensma, David Wadleigh, Martha Stone, Richard M. Driver, Jane A. TI Geriatric Assessment Variables Add Prognostic Value to the International Prognostic Scoring System SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Motyckova, Gabriela; DeAngelo, Daniel J.; Abel, Gregory A.; Steensma, David; Wadleigh, Martha; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fega, K. Rebecca] Univ Arizona, Coll Med Phoenix, Phoenix, AZ USA. [Sherman, Alexander E.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Driver, Jane A.] VA Boston Med Ctr, Geriatr Res Educ & Clin Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4933 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605070 ER PT J AU Motyckova, G Sherman, AE Fega, KR DeAngelo, DJ Abel, GA Steensma, D Wadleigh, M Stone, RM Driver, JA AF Motyckova, Gabriela Sherman, Alexander E. Fega, K. Rebecca DeAngelo, Daniel J. Abel, Gregory A. Steensma, David Wadleigh, Martha Stone, Richard M. Driver, Jane A. TI Prospective Cohort Study of Geriatric Assessment in Older Patients with Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Motyckova, Gabriela; DeAngelo, Daniel J.; Steensma, David; Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sherman, Alexander E.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Fega, K. Rebecca] Univ Arizona, Coll Med Phoenix, Phoenix, AZ USA. [Abel, Gregory A.; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Driver, Jane A.] VA Boston Med Ctr, Ctr Geriatr Res Educ & Clin, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4285 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906148 ER PT J AU Mullins, ES Shaw, MA McElhinney, KE Kombrinck, KW Flick, MJ Brill, A Wagner, DD Degen, JL AF Mullins, Eric S. Shaw, Maureen A. McElhinney, Kathryn E. Kombrinck, Keith W. Flick, Matthew J. Brill, Alexander Wagner, Denisa D. Degen, Jay L. TI Mice with Genetic Modifications in Prothrombin Limiting Activation Cleavage Events to Meizothrombin Survive to Adulthood, but Exhibit Alterations in Hemostasis and Thrombus Formation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mullins, Eric S.; Shaw, Maureen A.; Kombrinck, Keith W.; Degen, Jay L.] Cincinnati Childrens Res Fdn, Canc & Blood Dis Inst, Cincinnati, OH USA. [McElhinney, Kathryn E.; Flick, Matthew J.] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH USA. [Brill, Alexander; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Program Cellular & Mol Med,Boston Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 496 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902164 ER PT J AU Mullins, ES Shaw, MA McElhinney, KE Kombrinck, KW Flick, MJ Brill, A Wagner, DD Degen, JL AF Mullins, Eric S. Shaw, Maureen A. McElhinney, Kathryn E. Kombrinck, Keith W. Flick, Matthew J. Brill, Alexander Wagner, Denisa D. Degen, Jay L. TI Mice with Genetic Modifications in Prothrombin Limiting Activation Cleavage Events to Meizothrombin Survive to Adulthood, but Exhibit Alterations in Hemostasis and Thrombus Formation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mullins, Eric S.; Shaw, Maureen A.; Kombrinck, Keith W.; Degen, Jay L.] Cincinnati Childrens Res Fdn, Canc & Blood Dis Inst, Cincinnati, OH USA. [McElhinney, Kathryn E.; Flick, Matthew J.] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH USA. [Brill, Alexander; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Program Cellular & Mol Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 496 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901340 ER PT J AU Munshi, NC Abonour, R Beck, JT Bensinger, W Facon, T Stockerl-Goldstein, K Baz, R Siegel, DS Neben, K Lonial, S Suvannasankha, A Bilic, S Chica, S Mukhopadhyay, S Isaacs, R Jagannath, S AF Munshi, Nikhil C. Abonour, Rafat Beck, Joseph T. Bensinger, William Facon, Thierry Stockerl-Goldstein, Keith Baz, Rachid Siegel, David S. Neben, Kai Lonial, Sagar Suvannasankha, Attaya Bilic, Sanela Chica, Sandra Mukhopadhyay, Subhendu Isaacs, Randi Jagannath, Sundar TI Early Evidence of Anabolic Bone Activity of BHQ880, a Fully Human Anti-DKK1 Neutralizing Antibody: Results of a Phase 2 Study in Previously Untreated Patients with Smoldering Multiple Myeloma At Risk for Progression SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Abonour, Rafat] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Beck, Joseph T.] Highlands Oncol Grp, Fayetteville, AR USA. [Bensinger, William] Univ Washington, Seattle, WA 98195 USA. [Facon, Thierry] Hop Claude Huriez, Serv Malad Sang, Lille, France. [Stockerl-Goldstein, Keith] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Neben, Kai] Univ Klinikum Heidelberg, Med Klin 5, Heidelberg, Germany. [Lonial, Sagar] Emory Univ, Div BMT, Winship Canc Inst Hematol & Med Oncol, Atlanta, GA 30322 USA. [Suvannasankha, Attaya] Indiana Univ Sch Med, Indianapolis, IN USA. [Suvannasankha, Attaya] Richard L RoudeBush VA Med Ctr, Indianapolis, IN USA. [Bilic, Sanela; Chica, Sandra; Mukhopadhyay, Subhendu; Isaacs, Randi] Novartis Pharmaceut, E Hanover, NJ USA. [Jagannath, Sundar] Mt Sinai Sch Med, Multiple Myeloma Program, New York, NY USA. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 7 Z9 7 U1 1 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 331 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902129 ER PT J AU Munshi, NC Abonour, R Beck, JT Bensinger, W Facon, T Stockerl-Goldstein, K Baz, R Siegel, DS Neben, K Lonial, S Suvannasankha, A Bilic, S Chica, S Mukhopadhyay, S Isaacs, R Jagannath, S AF Munshi, Nikhil C. Abonour, Rafat Beck, Joseph T. Bensinger, William Facon, Thierry Stockerl-Goldstein, Keith Baz, Rachid Siegel, David S. Neben, Kai Lonial, Sagar Suvannasankha, Attaya Bilic, Sanela Chica, Sandra Mukhopadhyay, Subhendu Isaacs, Randi Jagannath, Sundar TI Early Evidence of Anabolic Bone Activity of BHQ880, a Fully Human Anti-DKK1 Neutralizing Antibody: Results of a Phase 2 Study in Previously Untreated Patients with Smoldering Multiple Myeloma At Risk for Progression SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Abonour, Rafat] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Beck, Joseph T.] Highlands Oncol Grp, Fayetteville, AR USA. [Bensinger, William] Univ Washington, Seattle, WA 98195 USA. [Facon, Thierry] Hop Claude Huriez, Serv Malad Sang, Lille, France. [Stockerl-Goldstein, Keith] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Neben, Kai] Univ Klinikum Heidelberg, Med Klin 5, Heidelberg, Germany. [Lonial, Sagar] Emory Univ, Div BMT, Winship Canc Inst Hematol & Med Oncol, Atlanta, GA 30322 USA. [Suvannasankha, Attaya] Indiana Univ Sch Med, Indianapolis, IN USA. [Suvannasankha, Attaya] Richard L RoudeBush VA Med Ctr, Indianapolis, IN USA. [Bilic, Sanela; Chica, Sandra; Mukhopadhyay, Subhendu; Isaacs, Randi] Novartis Pharmaceut, E Hanover, NJ USA. [Jagannath, Sundar] Mt Sinai Sch Med, Multiple Myeloma Program, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 331 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901305 ER PT J AU Murase, K Kawano, Y Ryan, J Matsuoka, KI Bascug, G McDonough, S Smith, RW Lazo-Kallanian, S Daley, J Koreth, J Soiffer, RJ Letai, AG Ritz, J AF Murase, Kazuyuki Kawano, Yutaka Ryan, Jeremy Matsuoka, Ken-ichi Bascug, Gregory McDonough, Sean Smith, Robert W. Lazo-Kallanian, Suzan Daley, John Koreth, John Soiffer, Robert J. Letai, Anthony G. Ritz, Jerome TI Apoptotic Pathways of Human Regulatory T Cells in Chronic Graft Versus Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 225 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901089 ER PT J AU Nikiforow, S Kim, HT Bindra, B McDonough, S Glotzbecker, B Armand, P Koreth, J Ho, VT Alyea, EP Ritz, J Soiffer, RJ Antin, JH Cutler, C AF Nikiforow, Sarah Kim, Haesook T. Bindra, Bhavjot McDonough, Sean Glotzbecker, Brett Armand, Philippe Koreth, John Ho, Vincent T. Alyea, Edwin P., III Ritz, Jerome Soiffer, Robert J. Antin, Joseph H. Cutler, Corey TI A Phase I Study of Alemtuzumab Dosing for Steroid-Refractory Chronic Graft-Versus-Host Disease SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Bindra, Bhavjot; McDonough, Sean; Glotzbecker, Brett; Armand, Philippe; Koreth, John; Ho, Vincent T.; Alyea, Edwin P., III; Ritz, Jerome; Soiffer, Robert J.; Antin, Joseph H.; Cutler, Corey] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 744 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900215 ER PT J AU Nonami, A Sattler, M Weisberg, EL Liu, QS Zhang, JM Adelmant, G Marto, JA Kohl, N Kung, AL Sim, T Gray, NS Griffin, JD AF Nonami, Atsushi Sattler, Martin Weisberg, Ellen L. Liu Qingsong Zhang, Jianming Adelmant, Guillaume Marto, Jarrod A. Kohl, Nancy Kung, Andrew L. Sim, Taebo Gray, Nathanael S. Griffin, James D. TI Deciphering the Critical Pathways of Mutant N-RAS in AML Using Small Molecule Inhibitors SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Nonami, Atsushi; Sattler, Martin; Weisberg, Ellen L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kohl, Nancy; Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA USA. [Sim, Taebo] Korea Inst Sci & Technol, Taejon, South Korea. NR 0 TC 0 Z9 0 U1 1 U2 5 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 NOV 16 PY 2012 VL 120 IS 21 MA 2455 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602226 ER PT J AU Novakovic, VA Lu, JH Gilbert, GE AF Novakovic, Valerie A. Lu, Junhong Gilbert, Gary E. TI Antibody ESH4, Against the Factor VIII C2 Domain, Causes a Remote Change near the Factor IXa Active Site and Inhibition That Is Related to Membrane Composition SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Novakovic, Valerie A.] VA Boston Healthcare Syst, Res, Boston, MA USA. [Lu, Junhong] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res, W Roxbury, MA USA. [Gilbert, Gary E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Med Dept,VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 3355 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602329 ER PT J AU O'Neill, DW Jiang, YJ Leary, E Yavanian, G Eminli, S Marasco, WA AF O'Neill, David W. Jiang, Yajuan Leary, Elizabeth Yavanian, Gregory Eminli, Sarah Marasco, Wayne A. TI A Lin-CD45-CD34+Population of Extracellular Vesicles in Human Blood That Mimics Very Small Embryonic-Like Stem Cells (VSELs) by Flow Cytometry SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [O'Neill, David W.; Jiang, Yajuan; Leary, Elizabeth; Yavanian, Gregory; Eminli, Sarah] NeoStem Inc, Cambridge, MA USA. [Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 4750 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604230 ER PT J AU Obholz, KL DeAngelo, DJ Mauro, MJ Shah, N Smith, BD Bowser, A Peterson, ED Radich, JP AF Obholz, Kevin L. DeAngelo, Daniel J. Mauro, Michael J. Shah, Neil Smith, B. Douglas Bowser, Andrew Peterson, Eric D. Radich, Jerald P. TI Clinical Impact of an Internet-Based Tool to Help Guide Therapeutic Changes While Monitoring Patients with Chronic Myeloid Leukemia Receiving First-Line Tyrosine Kinase Inhibitor Therapy SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Obholz, Kevin L.; Bowser, Andrew] Clin Care Opt LLC, Reston, VA USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mauro, Michael J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Shah, Neil] Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA 94143 USA. [Smith, B. Douglas] Sidney Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, Baltimore, MD USA. [Peterson, Eric D.] Annenberg Ctr Hlth Sci Eisenhower, Rancho Mirage, CA USA. [Radich, Jerald P.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4279 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906154 ER PT J AU Odejide, OO DeAngelo, DJ Cronin, AM Bernazzoli, ZA Jacobson, JO Rodig, SJ Mazeika, TJ Earles, KD Abel, GA AF Odejide, Oreofe O. DeAngelo, Daniel J. Cronin, Angel M. Bernazzoli, Zachary A. Jacobson, Joseph O. Rodig, Scott J. Mazeika, Teresa J. Earles, Kristofer D. Abel, Gregory A. TI Impact of Operator Techniques On Quality of Bone Marrow Assessment SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Odejide, Oreofe O.; DeAngelo, Daniel J.; Cronin, Angel M.; Bernazzoli, Zachary A.; Jacobson, Joseph O.; Mazeika, Teresa J.; Earles, Kristofer D.; Abel, Gregory A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 2055 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603240 ER PT J AU Omer, AK Ziakas, PD Anagnostou, T Kourkoumpetis, T McAfee, SL Dey, BR Attar, EC Chen, YBA Spitzer, TR Mylonakis, EE Ballen, KK AF Omer, Aazim Kamal Ziakas, Panayiotis D. Anagnostou, Theodora Kourkoumpetis, Themistoklis McAfee, Steven L. Dey, Bimalangshu R. Attar, Eyal C. Chen, Yi-Bin A. Spitzer, Thomas R. Mylonakis, Eleftherios E. Ballen, Karen K. TI Higher Infused Cell Dose Is Associated with a Decreased Risk of Invasive Fungal Infections After Allogeneic Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Omer, Aazim Kamal] N Shore Med Ctr, Salem, MA USA. [Ziakas, Panayiotis D.] Univ Athens, Sch Med, Dept Pathophysiol, GR-11527 Athens, Greece. [Anagnostou, Theodora] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Infect Dis Div, Boston, MA USA. [Kourkoumpetis, Themistoklis] Boston Univ, Sch Med, Med Ctr, Boston, MA 02215 USA. [McAfee, Steven L.; Attar, Eyal C.; Chen, Yi-Bin A.; Spitzer, Thomas R.; Ballen, Karen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Leukemia & Bone Marrow Transplant, Boston, MA USA. [Dey, Bimalangshu R.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Mylonakis, Eleftherios E.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4134 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604194 ER PT J AU Org, T Duan, D Montel-Hagen, A Ferrari, R Van Handel, B Sasidharan, R Orkin, SH Kurdistani, S Mikkola, H AF Org, Tonis Duan, Dan Montel-Hagen, Amelie Ferrari, Roberto Van Handel, Ben Sasidharan, Rajkumar Orkin, Stuart H. Kurdistani, Siavash Mikkola, Hanna TI Scl/Tal1 Directly Activates Hematopoiesis and Represses Cardiogenesis During Mesodermal Diversification SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Van Handel, Ben] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst,Howard H, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 3446 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604081 ER PT J AU Ouyang, D Plutschow, A Pogge, E Ponader, S Rabincoich, G Neuberg, DS Engert, A Shipp, MA AF Ouyang, Ding Pluetschow, Annette Pogge, Elke Ponader, Sabine Rabincoich, Gabriel Neuberg, Donna S. Engert, Andreas Shipp, Margaret A. TI Galectin-1 Serum Levels Reflect Tumor Burden and Adverse Clinical Features in Hodgkin Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ouyang, Ding; Neuberg, Donna S.; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pluetschow, Annette; Pogge, Elke; Ponader, Sabine; Engert, Andreas] Univ Hosp Cologne, German Hodgkin Study Grp, Cologne, Germany. [Rabincoich, Gabriel] Inst Biol & Med Expt, Lab Immunopatol, RA-1428 Buenos Aires, DF, Argentina. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 51 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900113 ER PT J AU Pal, J Lu, RQ Nanjappa, P Vahia, AV Shammas, MA Munshi, NC AF Pal, Jagannath Lu, Renquan Nanjappa, Puru Vahia, Ankit V. Shammas, Masood A. Munshi, Nikhil C. TI Direct Evidence and Functional Significance of DNA Repair by Telomerase in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Nanjappa, Puru; Vahia, Ankit V.; Shammas, Masood A.] VA Hlth Care Syst, Boston, MA USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4416 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605107 ER PT J AU Pardanani, A Gotlib, J Gupta, V Roberts, AW Wadleigh, M Sirhan, S Bavisotto, LM Kawashima, J Kowalski, M Tefferi, A AF Pardanani, Animesh Gotlib, Jason Gupta, Vikas Roberts, Andrew W. Wadleigh, Martha Sirhan, Shireen Bavisotto, Linda M. Kawashima, Jun Kowalski, Mark Tefferi, Ayalew TI Phase I/II Study of CYT387, a JAK1/JAK2 Inhibitor for the Treatment of Myelofibrosis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pardanani, Animesh; Tefferi, Ayalew] Mayo Clin, Dept Internal Med, Div Hematol, Rochester, MN USA. [Gotlib, Jason] Stanford Canc Inst, Stanford, CA USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Roberts, Andrew W.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Wadleigh, Martha] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sirhan, Shireen] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Bavisotto, Linda M.] Porta Clin, Seattle, WA USA. [Kawashima, Jun; Kowalski, Mark] YMBioSciences Inc, Mississauga, ON, Canada. NR 0 TC 3 Z9 3 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 178 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900279 ER PT J AU Parkin, B Ouillette, P Li, YF Li, C Shedden, K Malek, S AF Parkin, Brian Ouillette, Peter Li, Yifeng Li, Cheng Shedden, Kerby Malek, Sami TI Clonal Evolution and Devolution Following Chemotherapy in Adult Acute Myelogenous Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Parkin, Brian; Ouillette, Peter; Li, Yifeng; Malek, Sami] Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Li, Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 2487 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602194 ER PT J AU Pasquini, MC Logan, BR Ho, VT McCarthy, PL Cooke, KR Rizzo, JD Zhu, XC Sorror, ML AF Pasquini, Marcelo C. Logan, Brent R. Ho, Vincent T. McCarthy, Philip L., Jr. Cooke, Kenneth R. Rizzo, J. Douglas Zhu, Xiaochun Sorror, Mohamed L. TI Comorbidity Index (CI) in Autologous Hematopoietic Cell Transplantation (HCT) for Malignant Diseases: Validation of the HCT-CI SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pasquini, Marcelo C.; Zhu, Xiaochun] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McCarthy, Philip L., Jr.] Roswell Pk Canc Inst, BMT Program, Buffalo, NY 14263 USA. [Cooke, Kenneth R.] Case Western Reserve Univ, Sch Med Pediat, Cleveland, OH 44106 USA. [Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 814 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901050 ER PT J AU Pidala, J Chai, XY Kurland, B Arora, M Cutler, C Flowers, MED Inamoto, Y Jagasia, M Khera, N Palmer, J Vogelsang, G Lee, SJ AF Pidala, Joseph Chai, Xiaoyu Kurland, Brenda Arora, Mukta Cutler, Corey Flowers, Mary E. D. Inamoto, Yoshi Jagasia, Madan Khera, Nandita Palmer, Jeanne Vogelsang, Georgia Lee, Stephanie J. TI Gastrointestinal and Hepatic Involvement in Chronic Gvhd: An Analysis From the Chronic Gvhd Consortium SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Flowers, Mary E. D.; Inamoto, Yoshi] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Khera, Nandita] Mayo Clin Arizona, Phoenix, AZ USA. [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Vogelsang, Georgia] Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 1940 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903051 ER PT J AU Plesner, T Lokhorst, H Gimsing, P Nahi, H Lisby, S Richardson, PG AF Plesner, Torben Lokhorst, Henk Gimsing, Peter Nahi, Hareth Lisby, Steen Richardson, Paul G. TI Daratumumab, a CD38 Monoclonal Antibody in Patients with Multiple Myeloma - Data From a Dose-Escalation Phase I/II Study SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Plesner, Torben] Vejle Hosp, Dept Hematol, Vejle, Denmark. [Lokhorst, Henk] Univ Med Ctr Utrecht, Dept Hematol, Utrecht, Netherlands. [Gimsing, Peter] Univ Copenhagen, Copenhagen, Denmark. [Nahi, Hareth] Karolinska Inst, Stockholm, Sweden. [Lisby, Steen] Genmab AS, Copenhagen, Denmark. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 16 Z9 16 U1 1 U2 7 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 NOV 16 PY 2012 VL 120 IS 21 MA 73 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900092 ER PT J AU Politikos, I Kim, H Brown, J McDonough, S Li, LQ Cutler, C Antin, JH Ballen, KK Ritz, J Boussiotis, VA AF Politikos, Ioannis Kim, Haesook Brown, Julia McDonough, Sean Li, Lequn Cutler, Corey Antin, Joseph H. Ballen, Karen K. Ritz, Jerome Boussiotis, Vassiliki A. TI Recovery of Thymic Epithelial Cells and T Cell Immune Reconstitution After Cord Blood Transplantation in Adults Depends On Angiogenesis and Neovascularization SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Politikos, Ioannis; Brown, Julia; Li, Lequn; Boussiotis, Vassiliki A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Kim, Haesook] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [McDonough, Sean; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 4175 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604154 ER PT J AU Rajasagi, M Keskin, D Kim, J Zhang, WD Shukla, S De Luca, D Sidney, J Brusic, V Neuberg, DS Getz, G Lander, ES Hacohen, N Wu, CJ AF Rajasagi, Mohini Keskin, Derin Kim, Jintaek Zhang, Wandi Shukla, Sachet De Luca, David Sidney, John Brusic, Vladimir Neuberg, Donna S. Getz, Gad Lander, Eric S. Hacohen, Nir Wu, Catherine J. TI Systematic Identification of Personal Mutated Tumor-Specific Neoantigens in CLL SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Rajasagi, Mohini; Keskin, Derin; Kim, Jintaek; Zhang, Wandi; Brusic, Vladimir; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Shukla, Sachet; De Luca, David; Getz, Gad; Lander, Eric S.; Hacohen, Nir] Broad Inst, Cambridge, MA USA. [Sidney, John] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 954 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901183 ER PT J AU Raje, N Hari, PN Vogl, DT Jagannath, S Orlowski, RZ Supko, JG Stephenson, P Jones, SS Wheeler, C Lonial, S AF Raje, Noopur Hari, Parameswaran N. Vogl, Dan T. Jagannath, Sundar Orlowski, Robert Z. Supko, Jeffrey G. Stephenson, Patricia Jones, Simon S. Wheeler, Catherine Lonial, Sagar TI Rocilinostat (ACY-1215), a Selective HDAC6 Inhibitor, Alone and in Combination with Bortezomib in Multiple Myeloma: Preliminary Results From the First-in-Humans Phase I/II Study SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hari, Parameswaran N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Vogl, Dan T.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Jagannath, Sundar] Mt Sinai Sch Med, Multiple Myeloma Program, New York, NY USA. [Orlowski, Robert Z.] UT MD Anderson Canc Ctr, Houston, TX USA. [Supko, Jeffrey G.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Stephenson, Patricia] Rho Inc, Chapel Hill, NC USA. [Jones, Simon S.; Wheeler, Catherine] Acetylon Pharmaceut, Boston, MA USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 4061 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603039 ER PT J AU Raje, N Vescio, R Montgomery, CW Hadala, JT Warsi, G Ericson, SG Anderson, KC AF Raje, Noopur Vescio, Robert Montgomery, Charles W. Hadala, Joseph T. Warsi, Ghulam Ericson, Solveig G. Anderson, Kenneth C. TI Bone Marker-Directed Dosing of Zoledronic Acid for the Prevention of Skeletal Complications in Patients with Multiple Myeloma: Final Results of the Z-MARK Study SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Vescio, Robert] Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Montgomery, Charles W.] Hematol & Oncol Associates, Bridgepoint, MS USA. [Hadala, Joseph T.; Warsi, Ghulam; Ericson, Solveig G.] Novartis Pharmaceut, E Hanover, NJ USA. [Anderson, Kenneth C.] Dana Farber Partners Canc Care Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 4077 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603023 ER PT J AU Raje, N Faber, EA Richardson, PG Schiller, GJ Hohl, RJ Cohen, AD Forero, A Carpenter, SP Cronier, D Kaiser, C Wooldridge, JE Anderson, KC AF Raje, Noopur Faber, Edward Anthony, Jr. Richardson, Paul G. Schiller, Gary J. Hohl, Raymond J. Cohen, Adam D. Forero, Andres Carpenter, Susan P. Cronier, Damien Kaiser, Christopher Wooldridge, James E. Anderson, Kenneth C. TI Phase 1 Study of Tabalumab, a Human Anti-BAFF Antibody and Bortezomib in Patients with Previously-Treated Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Faber, Edward Anthony, Jr.] Univ Nebraska Med Ctr, Div Oncol Hematol, Omaha, NE USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Schiller, Gary J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hohl, Raymond J.] Univ Iowa, Coll Med, Iowa City, IA USA. [Cohen, Adam D.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Forero, Andres] Univ Alabama Birmingham, Birmingham, AL USA. [Carpenter, Susan P.] Eli Lilly & Co, Lilly Biotechnol Ctr, San Diego, CA USA. [Kaiser, Christopher] Eli Lilly & Co, Stat Oncol, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 447 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902213 ER PT J AU Raje, N Faber, EA Richardson, PG Schiller, GJ Hohl, RJ Cohen, AD Forero, A Carpenter, SP Cronier, D Kaiser, C Wooldridge, JE Anderson, KC AF Raje, Noopur Faber, Edward Anthony, Jr. Richardson, Paul G. Schiller, Gary J. Hohl, Raymond J. Cohen, Adam D. Forero, Andres Carpenter, Susan P. Cronier, Damien Kaiser, Christopher Wooldridge, James E. Anderson, Kenneth C. TI Phase 1 Study of Tabalumab, a Human Anti-BAFF Antibody and Bortezomib in Patients with Previously-Treated Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Faber, Edward Anthony, Jr.] Univ Nebraska Med Ctr, Div Hematol Oncol, Omaha, NE USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Schiller, Gary J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hohl, Raymond J.] Univ Iowa, Coll Med, Iowa City, IA USA. [Cohen, Adam D.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Forero, Andres] Univ Alabama Birmingham, Birmingham, AL USA. [Carpenter, Susan P.] Eli Lilly, Lilly Biotechnol Ctr, San Diego, CA USA. [Kaiser, Christopher] Eli Lilly & Co, Stat Oncol, Indianapolis, IN 46285 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 447 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902013 ER PT J AU Reddy, MM Deshpande, A Nonami, A Weisberg, EL Chowdary, TK Griffin, JD Sattler, M AF Reddy, Mamatha M. Deshpande, Anagha Nonami, Atsushi Weisberg, Ellen L. Chowdary, Tirumala K. Griffin, James D. Sattler, Martin TI BCR-ABL Transformation Requires Glycogen Synthase 1 (GYS1) Expression for Cell Growth and Increased Glycogen Production SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Reddy, Mamatha M.; Deshpande, Anagha; Nonami, Atsushi; Weisberg, Ellen L.; Sattler, Martin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chowdary, Tirumala K.] Natl Inst Sci Educ & Res, Sch Biol Sci, Bhubaneswar, Orissa, India. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 1673 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600366 ER PT J AU Richardson, PG Jakubowiak, A Bahlis, NJ Siegel, DS Chen, CI Chen, M Zaki, M Larkins, G Anderson, KC AF Richardson, Paul G. Jakubowiak, Andrzej Bahlis, Nizar J. Siegel, David S. Chen, Christine I. Chen, Min Zaki, Mohamed Larkins, Gail Anderson, Kenneth C. TI Treatment Outcomes with Pomalidomide (POM) in Combination with Low-Dose Dexamethasone (LoDex) in Patients with Relapsed and Refractory Multiple Myeloma (RRMM) and Del(17p13) and/or t(4;14)(p16;q32) Cytogenetic Abnormalities Who Have Received Prior Therapy with Lenalidomide (LEN) and Bortezomib (BORT) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jakubowiak, Andrzej] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Bahlis, Nizar J.] Univ Calgary, Div Hematol, So Alberta Canc Res Inst, Calgary, AB, Canada. [Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Chen, Christine I.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Chen, Min; Zaki, Mohamed; Larkins, Gail] Celgene Corp, Summit, NJ USA. [Anderson, Kenneth C.] Emory Univ, Sch Med, Atlanta, GA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4053 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603047 ER PT J AU Richardson, PG Triplett, BM Kernan, NA Grupp, SA Arai, S Haut, PR Gillio, AP Tudone, E Sardella, M Bandiera, V Heringa, C Lehmann, LE Soiffer, RJ Niederwieser, D AF Richardson, Paul G. Triplett, Brandon M. Kernan, Nancy A. Grupp, Stephan A. Arai, Sally Haut, Paul R. Gillio, Alfred P., III Tudone, Elena Sardella, Marco Bandiera, Valeria Heringa, Carin Lehmann, Leslie E. Soiffer, Robert J. Niederwieser, Dietger CA Defibrotide Study Grp TI Evaluation of Defibrotide (DF) in the Treatment of Hepatic Veno-Occlusive Disease (VOD) in Non-Stem Cell Transplant (non-SCT) Chemotherapy Patients (pts): Results From the Treatment IND (T-IND) Expanded Access Protocol and the Compassionate Use Program (CUP) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Triplett, Brandon M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, Pediat BMT Serv, New York, NY 10021 USA. [Grupp, Stephan A.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Arai, Sally] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Haut, Paul R.] Indiana Univ, Dept Pediat, Div Hematol Oncol, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Gillio, Alfred P., III] Hackensack Univ, Med Ctr, Tomorrows Childrens Inst, Hackensack, NJ USA. [Tudone, Elena; Sardella, Marco; Bandiera, Valeria; Heringa, Carin; Defibrotide Study Grp] Gentium SpA, Dept Sci, Villa Guardia, Italy. [Soiffer, Robert J.] Dana Farber Canc Inst, Div Hematol Malignancies, Dept Med Oncol, Boston, MA 02115 USA. [Niederwieser, Dietger] Univ Leipzig, Dept Hematol Oncol, D-04109 Leipzig, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 3041 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601222 ER PT J AU Richardson, PG Jagannath, S Moreau, P Jakubowiak, A Raab, MS Facon, T Vij, R White, DJ Reece, D Benboubker, L Zonder, JA Deng, W Kroog, G Singhal, AK Lonial, S AF Richardson, Paul G. Jagannath, Sundar Moreau, Philippe Jakubowiak, Andrzej Raab, Marc S. Facon, Thierry Vij, Ravi White, Darrell J. Reece, Donna Benboubker, Lotfi Zonder, Jeffrey A. Deng, Wei Kroog, Glenn Singhal, Anil K. Lonial, Sagar TI A Phase 2 Study of Elotuzumab (Elo) in Combination with Lenalidomide and Low-Dose Dexamethasone (Ld) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (R/R MM): Updated Results SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Moreau, Philippe] Univ Hosp Hotel Dieu, Dept Hematol, Nantes, France. [Jakubowiak, Andrzej] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Raab, Marc S.] Heidelberg Univ, Med Ctr, Heidelberg, Germany. [Raab, Marc S.] German Canc Res Ctr, Heidelberg, Germany. [Facon, Thierry] Hop Claude Huriez, Serv Malad Sang, Lille, France. [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [White, Darrell J.] Queen Elizabeth 2 Hlth Sci Ctr, Div Hematol, Halifax, NS, Canada. [Reece, Donna] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Benboubker, Lotfi] Hop Bretonneau, Ctr Reg Cancerol Henry Kaplan CHRU Tours, Serv Hematol & Therapies Cellulaires, Tours, France. [Zonder, Jeffrey A.] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Deng, Wei; Singhal, Anil K.] Abbott Biotherapeut Corp, Redwood City, CA USA. [Kroog, Glenn] Bristol Myers Squibb Co, Princeton, NJ USA. [Lonial, Sagar] Emory Univ, Div BMT, Winship Canc Inst Hematol & Med Oncol, Atlanta, GA 30322 USA. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 6 Z9 6 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 202 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901066 ER PT J AU Richardson, PG Hofmeister, CC Siegel, D Lonial, S Zaki, M Hua, Y Shah, S Wang, JM Anderson, KC AF Richardson, Paul G. Hofmeister, Craig C. Siegel, David Lonial, Sagar Zaki, Mohamad Hua, Ye Shah, Sheetal Wang, Jianming Anderson, Kenneth C. TI MM-005: A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib, and Low-Dose Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Hofmeister, Craig C.] Ohio State Univ, Div Hematol, Dept Internal Med, Columbus, OH 43210 USA. [Siegel, David] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Lonial, Sagar] Emory Univ, Div BMT, Winship Canc Inst Hematol & Med Oncol, Atlanta, GA 30322 USA. [Zaki, Mohamad; Hua, Ye; Shah, Sheetal; Wang, Jianming] Celgene Corp, Summit, NJ USA. [Anderson, Kenneth C.] Emory Univ, Sch Med, Atlanta, GA USA. RI Hofmeister, Craig/E-3256-2011 OI Hofmeister, Craig/0000-0003-4816-1607 NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 727 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900232 ER PT J AU Richardson, PG Smith, A Kernan, NA Grupp, SA Arai, S Triplett, BM Haut, PR Chan, K Symons, HJ Horn, BN Gillio, AP Boyer, M Krishnan, A Lehmann, LE Martin, PL Mineishi, S Shore, TB Simms-Waldrip, T Antin, JH Hannah, AL Hume, R Tudone, E Heringa, C Soiffer, RJ AF Richardson, Paul G. Smith, Angela Kernan, Nancy A. Grupp, Stephan A. Arai, Sally Triplett, Brandon M. Haut, Paul R. Chan, Kawah Symons, Heather J. Horn, Biljana N. Gillio, Alfred P., III Boyer, Michael Krishnan, Antrita Lehmann, Leslie E. Martin, Paul L. Mineishi, Shin Shore, Tsiporah B. Simms-Waldrip, Tiffany Antin, Joseph H. Hannah, Alison L. Hume, Robin Tudone, Elena Heringa, Carin Soiffer, Robert J. CA Defibrotide Study Grp TI Results of a Large Prospective Study On the Use of Defibrotide (DF) in the Treatment of Hepatic Veno-Occlusive Disease (VOD) in Hematopoietic Stem Cell Transplant (HSCT). Early Intervention Improves Outcome - Updated Results of a Treatment IND (T-IND) Expanded Access Protocol SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Smith, Angela] Univ Minnesota, Div Pediat Hematol Oncol Bone & Marrow Transplant, Minneapolis, MN USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Grupp, Stephan A.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Arai, Sally] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Triplett, Brandon M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Haut, Paul R.] Indiana Univ, Dept Pediat, Div Hematol Oncol, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Chan, Kawah] Methodist Childrens Hosp, Texas Transplant Inst, San Antonio, TX USA. [Symons, Heather J.] Johns Hopkins Univ, Baltimore, MD USA. [Horn, Biljana N.] UCSF Benioff Childrens Hosp, Blood & Marrow Transplant Program, San Francisco, CA USA. [Gillio, Alfred P., III] Hackensack Univ, Tomorrows Childrens Inst, Med Ctr, Hackensack, NJ USA. [Boyer, Michael] Primary Clildrens Med Ctr, Salt Lake City, UT USA. [Krishnan, Antrita] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA. [Antin, Joseph H.; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [Martin, Paul L.] Duke Univ, Durham, NC USA. [Mineishi, Shin] Univ Alabama Birmingham, BMT Cell Therapy Program, Birmingham, AL USA. [Shore, Tsiporah B.] New York Presbyterian Hosp, Weill Cornell Med Coll, Div Hematol Oncol, New York, NY USA. [Simms-Waldrip, Tiffany] UT SW Med Ctr, Dallas, TX USA. [Hannah, Alison L.; Hume, Robin; Tudone, Elena; Heringa, Carin; Defibrotide Study Grp] Gentium SpA, Dept Sci, Villa Guardia, Italy. NR 0 TC 1 Z9 1 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 738 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900221 ER PT J AU Roccaro, AM Sacco, A Ungari, M Maiso, P Manier, S Quang, P Aljaway, Y Zboralski, D Kruschinski, A Facchetti, F Rossi, G Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Ungari, Marco Maiso, Patricia Manier, Salomon Phong Quang Aljaway, Yosra Zboralski, Dirk Kruschinski, Anna Facchetti, Fabio Rossi, Giuseppe Ghobrial, Irene M. TI In Vivo Targeting of Stromal-Derived Factor-1 As a Strategy to Prevent Myeloma Cell Dissemination to Distant Bone Marrow Niches SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ungari, Marco] Univ Brescia, Dept Pathol, Brescia, Italy. [Zboralski, Dirk; Kruschinski, Anna] NOXXON Pharma AG, Berlin, Germany. [Facchetti, Fabio] Spedali Civil Brescia, Div Pathol, I-25125 Brescia, Italy. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 440 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902220 ER PT J AU Rorije, NMG Shea, MM Satyanarayana, G Hammond, SP Ho, VT Baden, LR Antin, JH Soiffer, RJ Marty, FM AF Rorije, Nienke M. G. Shea, Margaret M. Satyanarayana, Gowri Hammond, Sarah P. Ho, Vincent T. Baden, Lindsey R. Antin, Joseph H. Soiffer, Robert J. Marty, Francisco M. TI BK Virus Disease Following Allogeneic Stem Cell Transplantation: A Cohort Analysis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Rorije, Nienke M. G.; Shea, Margaret M.; Satyanarayana, Gowri; Hammond, Sarah P.; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Ho, Vincent T.; Antin, Joseph H.; Soiffer, Robert J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 1927 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903064 ER PT J AU Saber, W Cutler, C Nakamura, R Zhang, MJ Atallah, E Rizzo, JD Maziarz, RT Cortes, JE Kalaycio, M Horowitz, MM AF Saber, Wael Cutler, Corey Nakamura, Ryotaro Zhang, Mei-Jie Atallah, Ehab Rizzo, J. Douglas Maziarz, Richard T. Cortes, Jorge E. Kalaycio, Matt Horowitz, Mary M. TI Comparison of Outcomes After Related and Unrelated Hematopoietic Cell Transplantation in Adults with Myelodysplastic Syndromes: A Report From the Center for International Blood and Marrow Transplant Research (CIBMTR) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Cutler, Corey; Rizzo, J. Douglas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Cortes, Jorge E.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Kalaycio, Matt] Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 355 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838902105 ER PT J AU Saber, W Cutler, C Nakamura, R Zhang, MJ Atallah, E Rizzo, JD Maziarz, RT Cortes, JE Kalaycio, M Horowitz, MM AF Saber, Wael Cutler, Corey Nakamura, Ryotaro Zhang, Mei-Jie Atallah, Ehab Rizzo, J. Douglas Maziarz, Richard T. Cortes, Jorge E. Kalaycio, Matt Horowitz, Mary M. TI Comparison of Outcomes After Related and Unrelated Hematopoietic Cell Transplantation in Adults with Myelodysplastic Syndromes: A Report From the Center for International Blood and Marrow Transplant Research (CIBMTR) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Saber, Wael; Rizzo, J. Douglas; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Milwaukee, WI USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Cortes, Jorge E.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Kalaycio, Matt] Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 355 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838901281 ER PT J AU Sadrzadeh, H Deysher, N Jamali, L Brunner, AM Drapkin, BJ Ballen, KK Attar, EC Amrein, PC McAfee, SL Fathi, AT AF Sadrzadeh, Hossein Deysher, Nathan Jamali, Layli Brunner, Andrew M. Drapkin, Benjamin J. Ballen, Karen K. Attar, Eyal C. Amrein, Philip C. McAfee, Steven L. Fathi, Amir T. TI Granulocytic Sarcoma, A Single-Institution Survey of Clinical Presentation and Trajectory SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Sadrzadeh, Hossein; Brunner, Andrew M.; Drapkin, Benjamin J.; Ballen, Karen K.; Attar, Eyal C.; Amrein, Philip C.; McAfee, Steven L.; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 1041 PG 3 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602032 ER PT J AU Sanda, T Tyner, JW Gutierrez, A Ngo, VN Glover, JM Chang, BH Yost, AJ Weng, AP Ma, WX Tatarek, J Fleischman, AG Ahn, Y Yang, YD Zhou, WJ Neuberg, DS Moriggl, R Muller, M Kelliher, M Jamieson, C Gray, NS Staudt, LM Druker, BJ Look, T AF Sanda, Takaomi Tyner, Jeffrey W. Gutierrez, Alejandro Ngo, Vu N. Glover, Jason M. Chang, Bill H. Yost, Arla J. Weng, Andrew P. Ma, Wenxue Tatarek, Jessica Fleischman, Angela G. Ahn, Yebin Yang, Yandan Zhou, Wenjun Neuberg, Donna S. Moriggl, Richard Mueller, Mathias Kelliher, Michelle Jamieson, Catriona Gray, Nathanael S. Staudt, Louis M. Druker, Brian J. Look, Thomas TI TYK2-STAT1 Pathway Positively Regulates BCL2 Gene Expression in T-Cell Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Tyner, Jeffrey W.; Glover, Jason M.; Chang, Bill H.; Fleischman, Angela G.; Druker, Brian J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Ngo, Vu N.] City Hope Natl Med Ctr, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA USA. [Yost, Arla J.] BC Canc Agcy, Terry Fox Lab, Vancouver, BC, Canada. [Weng, Andrew P.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Ma, Wenxue] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Tatarek, Jessica] UMass Med Sch, Worcester, MA USA. [Zhou, Wenjun] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Moriggl, Richard] Ludwig Boltzmann Inst Canc Res, Vienna, Austria. [Mueller, Mathias] Univ Vet Med Vienna, Dept Biomed Sci, Vienna, Austria. [Kelliher, Michelle] Univ Massachusetts, Sch Med, Worcester, MA USA. [Staudt, Louis M.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RI Weng, Andrew/I-5015-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 1470 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905163 ER PT J AU Santo, L Cirstea, D Wang, B Yao, TP Wu, JY Waterman, P Jeon, D Bouxsein, M Louis, L Lotinun, S Baron, R Eda, H Nemani, N Mahindra, A Yee, AJ Hideshima, T Anderson, KC Jones, SS Raje, N AF Santo, Loredana Cirstea, Diana Wang, Bin Yao, Tso-Pang Wu, Joy Y. Waterman, Peter Jeon, Derrick Bouxsein, Mary Louis, Leeann Lotinun, Sutada Baron, Roland Eda, Homare Nemani, Neeharika Mahindra, Anuj Yee, Andrew J. Hideshima, Teru Anderson, Kenneth C. Jones, Simon S. Raje, Noopur TI Role of Selective HDAC6 Inhibition On Multiple Myeloma Bone Disease SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Santo, Loredana; Cirstea, Diana; Eda, Homare; Nemani, Neeharika; Mahindra, Anuj; Yee, Andrew J.; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Wang, Bin; Yao, Tso-Pang] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC USA. [Wu, Joy Y.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Waterman, Peter; Jeon, Derrick] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Bouxsein, Mary; Louis, Leeann] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA 02215 USA. [Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Jones, Simon S.] Acetylon Pharmaceut Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 328 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902132 ER PT J AU Santo, L Cirstea, D Wang, B Yao, TP Wu, JY Waterman, P Jeon, D Bouxsein, M Louis, L Lotinun, S Baron, R Eda, H Nemani, N Mahindra, A Yee, AJ Hideshima, T Anderson, KC Jones, SS Raje, N AF Santo, Loredana Cirstea, Diana Wang, Bin Yao, Tso-Pang Wu, Joy Y. Waterman, Peter Jeon, Derrick Bouxsein, Mary Louis, Leeann Lotinun, Sutada Baron, Roland Eda, Homare Nemani, Neeharika Mahindra, Anuj Yee, Andrew J. Hideshima, Teru Anderson, Kenneth C. Jones, Simon S. Raje, Noopur TI Role of Selective HDAC6 Inhibition On Multiple Myeloma Bone Disease SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Santo, Loredana; Cirstea, Diana; Eda, Homare; Nemani, Neeharika; Mahindra, Anuj; Yee, Andrew J.; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Wang, Bin; Yao, Tso-Pang] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC USA. [Wu, Joy Y.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Waterman, Peter; Jeon, Derrick] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Bouxsein, Mary; Louis, Leeann] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA 02215 USA. [Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Jones, Simon S.] Acetylon Pharmaceut Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 328 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901308 ER PT J AU Satyanarayana, G Hammond, S Kim, HT McDonough, S Brown, J Politikos, I Li, LQ Viscidi, R Broge, T Koralnik, I Cutler, C Ballen, KK Antin, JH Marty, FM Ritz, J Tan, CS Boussiotis, VA AF Satyanarayana, Gowri Hammond, Sarah Kim, Haesook T. McDonough, Sean Brown, Julia Politikos, Ioannis Li, Lequn Viscidi, Raphael Broge, Thomas Koralnik, Igor Cutler, Corey Ballen, Karen K. Antin, Joseph H. Marty, Francisco M. Ritz, Jerome Tan, C. Sabrina Boussiotis, Vassiliki A. TI BK Virus Reactivation After Double Umbilical Cord Blood Transplantation in Adults Correlates with Tregs and Delayed Reconstitution of CD4(+) and CD8(+) T Effector Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Hammond, Sarah; Marty, Francisco M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [McDonough, Sean; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Viscidi, Raphael] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Broge, Thomas; Koralnik, Igor] Harvard Univ, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Sch Med, Boston, MA 02215 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4174 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604155 ER PT J AU Scheuplein, F Macdonald, S Zeigler, B Lebel, E Thariath, A Truneh, A Mashal, R Nathan, DG Schaub, R AF Scheuplein, Felix Macdonald, Susan Zeigler, Brandon LeBel, Elen Thariath, Abraham Truneh, Alem Mashal, Robert Nathan, David G. Schaub, Robert TI Cynomolgus Monkey Invariant NKT (iNKT) Cells Recover Following Depletion by Treatment with the Anti-Invariant T Cell Receptor Antibody NKTT120 SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Scheuplein, Felix; Macdonald, Susan; Thariath, Abraham; Truneh, Alem; Mashal, Robert; Schaub, Robert] NKT Therapeut, Waltham, MA USA. [Zeigler, Brandon; LeBel, Elen] MPI Res, Mattawan, MI USA. [Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 4836 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604405 ER PT J AU Schroyens, WA O'Connell, CL Lacy, MQ Attar, EC Raje, N Somer, BG Rosado, FG Hoyer, J Feinstein, DI Sykes, DB AF Schroyens, Wilfried A. O'Connell, Casey L. Lacy, Martha Q. Attar, Eyal C. Raje, Noopur Somer, Bradley G. Rosado, Flavia G. Hoyer, James Feinstein, Donald I. Sykes, David B. TI TEMPI: A Reversible Syndrome Following Treatment with Bortezomib SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Schroyens, Wilfried A.] Univ Antwerp Hosp, Edegem, Belgium. [O'Connell, Casey L.; Feinstein, Donald I.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Lacy, Martha Q.] Mayo Clin, Div Hematol, Rochester, MN USA. [Attar, Eyal C.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Hoyer, James] Mayo Clin, Lab Med & Pathol, Rochester, MN USA. [Sykes, David B.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 NOV 16 PY 2012 VL 120 IS 21 MA 986 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600319 ER PT J AU Shi, JL Gilbert, GE AF Shi, Jialan Gilbert, Gary E. TI Putative Phospholipid "scramblase" of Scott Syndrome, TMEM16F/Ano6, Mediates Phosphatidylserine Exposure On Filopodia and Cell Margins of Viable Endothelial Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Shi, Jialan; Gilbert, Gary E.] Harvard Univ, Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst,Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 2180 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905256 ER PT J AU Siegel, DS Richardson, PG Baz, R Chen, M Zaki, M Anderson, KC AF Siegel, David S. Richardson, Paul G. Baz, Rachid Chen, Min Zaki, Mohamed Anderson, Kenneth C. TI Pomalidomide (POM) with Low-Dose Dexamethasone (LoDEX) in Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Impact of Renal Function on Patient Outcomes SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Chen, Min; Zaki, Mohamed] Celgene Corp, Summit, NJ USA. NR 0 TC 6 Z9 6 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4072 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603028 ER PT J AU Singh, P Hoggatt, J Hu, PR Pelus, LM AF Singh, Pratibha Hoggatt, Jonathan Hu, Peirong Pelus, Louis M. TI Sinusoidal Endothelial CD26 Cleavage of Neuropeptide Y Regulates Transendothelial Migration and Mobilization of Hematopoietic Stem and Progenitor Cells in Response to G-CSF SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Singh, Pratibha; Hu, Peirong; Pelus, Louis M.] Indiana Univ Sch Med, Indianapolis, IN USA. [Hoggatt, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Stem Cell Inst, Boston, MA USA. OI Singh, Preet Paul/0000-0001-8936-8191 NR 0 TC 1 Z9 1 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 2347 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601113 ER PT J AU Slayton, WB Schultz, KR Jones, T Raetz, E Devidas, M Pulsipher, MA Loh, M Chang, BH Carroll, WL Borowitz, MJ Silverman, LB Brown, VI Winick, N Carroll, AJ Heerema, NA Gastier-Foster, JM Wood, BL Mizrahy, SL Merchant, TE Hunger, SP AF Slayton, William B. Schultz, Kirk R. Jones, Tamekia Raetz, Elizabeth Devidas, Meenakshi Pulsipher, Michael A. Loh, Mignon Chang, Bill H. Carroll, William L. Borowitz, Michael J. Silverman, Lewis B. Brown, Valerie I. Winick, Naomi Carroll, Andrew J. Heerema, Nyla A. Gastier-Foster, Julie M. Wood, Brent L. Mizrahy, Sherri L. Merchant, Thomas E. Hunger, Stephen P. TI Continuous Dose Dasatinib Is Safe and Feasible in Combination with Intensive Chemotherapy in Pediatric Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL): Children's Oncology Group (COG) Trial AALL0622 SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Slayton, William B.] Univ Florida, Coll Med, Dept Pediat Hem Onc, Gainesville, FL USA. [Schultz, Kirk R.] British Columbia Childrens Hosp, Div Pediat Hem Onc BMT, Vancouver, BC V6H 3V4, Canada. [Jones, Tamekia] Univ Florida, Sch Med, Gainesville, FL USA. [Raetz, Elizabeth] NYU, Langone Med Ctr, New York, NY USA. [Devidas, Meenakshi] Univ Florida, Dept Epidemiol & Hlth Policy Res Med, Gainesville, FL USA. [Pulsipher, Michael A.] Univ Utah, Salt Lake City, UT USA. [Loh, Mignon] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chang, Bill H.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. [Borowitz, Michael J.] Johns Hopkins Univ, Baltimore, MD USA. [Silverman, Lewis B.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Brown, Valerie I.] Vanderbilt Univ, Nashville, TN 37212 USA. [Winick, Naomi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Heerema, Nyla A.] Ohio State Univ, Columbus, OH 43210 USA. [Gastier-Foster, Julie M.] Ohio State Univ Lab Med Pathol, Nationwide Clildrens Hosp, Columbus, OH USA. [Wood, Brent L.] Seattle Canc Care Alliance, Seattle, WA USA. [Merchant, Thomas E.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Hunger, Stephen P.] Univ Colorado, Pediat Hematol Oncol BMT, Coll Med, Aurora, CO USA. NR 0 TC 1 Z9 1 U1 1 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 137 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900322 ER PT J AU Sonis, ST Antin, JH Alterovitz, G AF Sonis, Stephen T. Antin, Joseph H. Alterovitz, Gil TI SNP-Based Bayesian Networks Define Oral Mucositis Risk in Patients Receiving Stomatotoxic Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Sonis, Stephen T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [Alterovitz, Gil] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 735 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900224 ER PT J AU Sorror, ML Logan, BR Zhu, XC Rizzo, JD Cooke, KR McCarthy, PL Ho, VT Storer, B Pasquini, MC AF Sorror, Mohamed L. Logan, Brent R. Zhu, Xiaochun Rizzo, J. Douglas Cooke, Kenneth R. McCarthy, Philip L., Jr. Ho, Vincent T. Storer, Barry Pasquini, Marcelo C. TI Prospective Validation of the Predictive Power of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) for HCT Outcomes At US Transplant Centers: A Center for International Blood and Marrow Transplant Research (CIBMTR) Study SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Sorror, Mohamed L.; Storer, Barry] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sorror, Mohamed L.; Storer, Barry] Univ Washington, Seattle, WA 98195 USA. [Logan, Brent R.; Zhu, Xiaochun; Rizzo, J. Douglas; Pasquini, Marcelo C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Cooke, Kenneth R.] Case Western Reserve Univ, Sch Med Pediat, Cleveland, OH 44106 USA. [McCarthy, Philip L., Jr.] Roswell Pk Canc Inst, BMT Program, Buffalo, NY 14263 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 733 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838900226 ER PT J AU Springer, TA Kim, J AF Springer, Timothy A. Kim, Jongseong TI Activation of A1 Domain Adhesiveness in von Willebrand Factor by Elongational Force SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Springer, Timothy A.; Kim, Jongseong] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 16 PG 1 WC Hematology SC Hematology GA 074UG UT WOS:000313838900015 ER PT J AU Stadtmauer, EA Ratanatharathorn, V Yeh, RF Freytes, CO Toro, JJ Akpek, G Sahovic, EA Tricot, GJ Shaughnessy, PJ White, DJ Rodriguez, TE Solomon, SR Yu, LH Patil, S Sun, YP Armstrong, E Smith, A Elekes, A Kato, K Reece, D AF Stadtmauer, Edward A. Ratanatharathorn, Voravit Yeh, Rosa F. Freytes, Cesar O. Toro, Juan J. Akpek, Gorgun Sahovic, Entezam A. Tricot, Guido J. Shaughnessy, Paul J. White, Darrell J. Rodriguez, Tulio E. Solomon, Scott R. Yu, Louie H. Patil, Shiva Sun, Yiping Armstrong, Elizabeth Smith, Angela Elekes, Agnes Kato, Kazunobu Reece, Donna TI Final Report of Safety and Efficacy From a Novel Conditioning Regimen, Individualized Once-Daily Intravenous Busulfan with Bortezomib, in Relapsed Multiple Myeloma Patients Undergoing a Second Autologous Hematopoietic Stem Cell Transplantation. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Ratanatharathorn, Voravit] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Yeh, Rosa F.; Yu, Louie H.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98104 USA. [Freytes, Cesar O.] S Vet Hlth Care Syst, BMT, San Antonio, TX USA. [Toro, Juan J.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Akpek, Gorgun] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Sahovic, Entezam A.] Western Penn Canc Inst, Cell Transplantat Program, Pittsburgh, PA USA. [Tricot, Guido J.] Univ Utah, Sch Med, Div Hematol, BMT & Myeloma Program, Salt Lake City, UT USA. [Shaughnessy, Paul J.] Texas Transplant Inst, San Antonio, TX USA. [White, Darrell J.] Queen Elizabeth 2 Hlth Sci Ctr, Div Hematol, Halifax, NS, Canada. [Rodriguez, Tulio E.] Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. [Solomon, Scott R.] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Patil, Shiva; Sun, Yiping; Armstrong, Elizabeth; Smith, Angela; Elekes, Agnes; Kato, Kazunobu] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Reece, Donna] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 3080 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601183 ER PT J AU Steensma, DP Komrokji, RS Stone, RM List, AF Garcia-Manero, G Huber, J Dennison, B Sekeres, MA AF Steensma, David P. Komrokji, Rami S. Stone, Richard M. List, Alan F. Garcia-Manero, Guillermo Huber, John Dennison, Betsy Sekeres, Mikkael A. TI Disparity in Perceptions of Disease, Treatment Effectiveness and Treatment Adherence Between Physicians and Patients with Myelodysplastic Syndromes (MDS) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Steensma, David P.; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Komrokji, Rami S.; List, Alan F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Huber, John] Aplast Anemia & MDS Int Fdn, Rockville, MD USA. [Dennison, Betsy] Clar Commun, Pompton Lakes, NJ USA. [Sekeres, Mikkael A.] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 4949 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605085 ER PT J AU Stone, RM Driscoll, C Galinsky, I Wadleigh, M Steensma, DP Avigan, D Amrein, PC Liu, SY Griffin, JD McAfee, SL Attar, EC Ballen, KK Fox, E DeAngelo, DJ AF Stone, Richard M. Driscoll, Caitlin Galinsky, Ilene Wadleigh, Martha Steensma, David P. Avigan, David Amrein, Philip C. Liu, Suiyang Griffin, James D. McAfee, Steven L. Attar, Eyal C. Ballen, Karen K. Fox, Edward DeAngelo, Daniel J. TI A Phase I Trial of Escalating Dose of the Rapamycin Analog Everolimus in Combination with the Kinase Inhibitor Midostaurin in Patients (pts) with Relapsed, Refractory or Poor Prognosis Acute Myeloid Leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Stone, Richard M.; Driscoll, Caitlin; Galinsky, Ilene; Wadleigh, Martha; Steensma, David P.; Liu, Suiyang; Griffin, James D.; Fox, Edward; DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Amrein, Philip C.; McAfee, Steven L.; Attar, Eyal C.; Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 3627 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600271 ER PT J AU Stroopinsky, D Rosenblatt, J Mills, H Nardella, C Ito, K Yin, L Rajabi, H Vasir, B Kufe, T Luptakova, K Arnason, JE Levine, JD Joyce, R Tzachanis, D Boussiotis, VA Galinsky, I Stone, RM Reiter, Y Pandolfi, PP Kufe, D Avigan, D AF Stroopinsky, Dina Rosenblatt, Jacalyn Mills, Heidi Nardella, Caterina Ito, Keisuke Yin, Li Rajabi, Hasan Vasir, Baldev Kufe, Turner Luptakova, Katarina Arnason, Jon E. Levine, James D. Joyce, Robin Tzachanis, Dimitrios Boussiotis, Vassiliki A. Galinsky, Ilene Stone, Richard M. Reiter, Yoram Pandolfi, Pier Paolo Kufe, Donald Avigan, David TI Targeting Leukemia Initiating Cells by MUC1-C Subunit Inhibition SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Stroopinsky, Dina; Rosenblatt, Jacalyn; Mills, Heidi; Nardella, Caterina; Ito, Keisuke; Kufe, Turner; Luptakova, Katarina; Arnason, Jon E.; Levine, James D.; Joyce, Robin; Tzachanis, Dimitrios; Boussiotis, Vassiliki A.; Pandolfi, Pier Paolo; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Yin, Li; Rajabi, Hasan; Vasir, Baldev; Galinsky, Ilene; Stone, Richard M.; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reiter, Yoram] Technion Israel Inst Technol, Haifa, Israel. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 3583 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906074 ER PT J AU Sundaravel, S Bhagat, TD Schinke, C Ebenezer, D Liu, H Yu, YT Pellagatti, A Boultwood, J Yajnik, V Artz, A Verma, A Wickrema, A AF Sundaravel, Sriram Bhagat, Tushar D. Schinke, Carolina Ebenezer, David Liu, Hui Yu, Yiting Pellagatti, Andrea Boultwood, Jacqueline Yajnik, Vijay Artz, Andrew Verma, Amit Wickrema, Amittha TI Aberrant Expression of DOCK4 Leads to Disruption of the F-Actin Skeleton and Altered Membrane Stability in MDS Erythroblasts and Mature Erythrocytes SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Sundaravel, Sriram; Verma, Amit; Wickrema, Amittha] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Bhagat, Tushar D.; Schinke, Carolina; Yu, Yiting; Verma, Amit] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Liu, Hui] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Pellagatti, Andrea] John Radcliffe Hosp, Oxford OX3 9DU, England. [Boultwood, Jacqueline] Univ Oxford, Radcliffe Dept Med, Oxford, England. [Yajnik, Vijay] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 924 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902037 ER PT J AU Sundaravel, S Bhagat, TD Schinke, C Ebenezer, D Liu, H Yu, YT Pellagatti, A Boultwood, J Yajnik, V Artz, A Verma, A Wickrema, A AF Sundaravel, Sriram Bhagat, Tushar D. Schinke, Carolina Ebenezer, David Liu, Hui Yu, Yiting Pellagatti, Andrea Boultwood, Jacqueline Yajnik, Vijay Artz, Andrew Verma, Amit Wickrema, Amittha TI Aberrant Expression of DOCK4 Leads to Disruption of the F-Actin Skeleton and Altered Membrane Stability in MDS Erythroblasts and Mature Erythrocytes SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Sundaravel, Sriram; Artz, Andrew; Wickrema, Amittha] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Bhagat, Tushar D.; Schinke, Carolina; Yu, Yiting; Verma, Amit] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Liu, Hui] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Pellagatti, Andrea] John Radcliffe Hosp, Oxford OX3 9DU, England. [Boultwood, Jacqueline] Univ Oxford, Radcliffe Dept Med, Oxford, England. [Yajnik, Vijay] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 924 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901213 ER PT J AU Sykes, DB Haynes, MK Tolliday, N Waller, A Cobert, JM Szekely, BA Hasaka, TP Sklar, L Zon, LI Scadden, DT AF Sykes, David B. Haynes, Mark K. Tolliday, Nicola Waller, Anna Cobert, Julien M. Szekely, Brian A. Hasaka, Tom P. Sklar, Larry Zon, Leonard I. Scadden, David T. TI Identifying Small Molecules That Overcome HoxA9-Mediated Differentiation Arrest in Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Sykes, David B.; Cobert, Julien M.; Szekely, Brian A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Haynes, Mark K.; Waller, Anna; Sklar, Larry] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tolliday, Nicola; Hasaka, Tom P.] Broad Inst, Cambridge, MA USA. [Cobert, Julien M.] Harvard Stem Cell Inst, Boston, MA USA. [Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 3513 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604014 ER PT J AU Tai, YT Landesman, Y Acharya, C Zhong, MY Calle, Y Cea, M Hu, YG Cagnetta, A Tannenbaum, D Chen, M Munshi, A Senapedis, W Saint-Martin, JR Kashyap, T Ying, HQ McCauley, D Shacham, S Kauffman, M Gu, YM Wu, LZ Schey, S Kung, AL Munshi, NC Richardson, PG Anderson, KC AF Tai, Yu-Tzu Landesman, Yosef Acharya, Chirag Zhong, Mike Y. Calle, Yolanda Cea, Michele Hu, Yiguo Cagnetta, Antonia Tannenbaum, Daniel Chen, Michelle Munshi, Aditya Senapedis, William Saint-Martin, Jean-Richard Kashyap, Trinayan Ying, Haoqiang McCauley, Dilara Shacham, Sharon Kauffman, Michael Gu, Yumei Wu, Lizi Schey, Stephen Kung, Andrew L. Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. TI CRM1 Blockade by Novel Inhibitors of Nuclear Export (SINEs) Inhibits Multiple Myeloma Cell Growth, Osteoclastogenesis, and Myeloma-Induced Osteolysis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Tai, Yu-Tzu; Acharya, Chirag; Cea, Michele; Cagnetta, Antonia; Munshi, Aditya] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Tai, Yu-Tzu; Acharya, Chirag; Cea, Michele; Cagnetta, Antonia; Munshi, Aditya] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Landesman, Yosef] Karyopharm Therapeut Inc, Natick, MA USA. [Calle, Yolanda] Kings Coll London, Dept Haematol Med, London WC2R 2LS, England. [Hu, Yiguo; Munshi, Nikhil C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Saint-Martin, Jean-Richard; Kashyap, Trinayan; Ying, Haoqiang; Shacham, Sharon; Kauffman, Michael] Karyopharm Therapeut Inc, Natick, MA USA. [Gu, Yumei; Wu, Lizi] Univ Florida, Shands Canc Ctr, Gainesville, FL 32611 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 326 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902134 ER PT J AU Tai, YT Landesman, Y Acharya, C Zhong, MY Calle, Y Cea, M Hu, YG Cagnetta, A Tannenbaum, D Chen, M Munshi, A Senapedis, W Saint-Martin, JR Kashyap, T Ying, HQ McCauley, D Shacham, S Kauffman, M Gu, YM Wu, LZ Schey, S Kung, AL Munshi, NC Richardson, PG Anderson, KC AF Tai, Yu-Tzu Landesman, Yosef Acharya, Chirag Zhong, Mike Y. Calle, Yolanda Cea, Michele Hu, Yiguo Cagnetta, Antonia Tannenbaum, Daniel Chen, Michelle Munshi, Aditya Senapedis, William Saint-Martin, Jean-Richard Kashyap, Trinayan Ying, Haoqiang McCauley, Dilara Shacham, Sharon Kauffman, Michael Gu, Yumei Wu, Lizi Schey, Stephen Kung, Andrew L. Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. TI CRM1 Blockade by Novel Inhibitors of Nuclear Export (SINEs) Inhibits Multiple Myeloma Cell Growth, Osteoclastogenesis, and Myeloma-Induced Osteolysis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Tai, Yu-Tzu; Acharya, Chirag; Cea, Michele; Cagnetta, Antonia; Munshi, Aditya] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Tai, Yu-Tzu; Acharya, Chirag; Cea, Michele; Cagnetta, Antonia; Munshi, Aditya] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Landesman, Yosef; Ying, Haoqiang; Shacham, Sharon; Kauffman, Michael] Karyopharm Therapeut Inc, Natick, MA USA. [Calle, Yolanda] Kings Coll London, Dept Haematol Med, London WC2R 2LS, England. [Hu, Yiguo; Munshi, Nikhil C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [McCauley, Dilara] Karyopharm Therapeut, Boston, MA USA. [Gu, Yumei; Wu, Lizi] Univ Florida, Shands Canc Ctr, Gainesville, FL USA. [Schey, Stephen] Kings Coll Hosp, London, England. [Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 326 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901310 ER PT J AU Terriou, L Gasmi, H Manier, S Plantier, I Wetterwald, M Lionne-Huyghe, P Robu, D Tricot, S Yakoub-Agha, I Simon, N Odou, P Morschhauser, F AF Terriou, Louis Gasmi, Hanane Manier, Salomon Plantier, Isabelle Wetterwald, Marc Lionne-Huyghe, Pauline Robu, Daniela Tricot, Sabine Yakoub-Agha, Ibrahim Simon, Nicolas Odou, Pascal Morschhauser, Franck TI 90-Yttrium Ibritumomab Tiuxetan (Zevalin) and BEAM Chemotherapy (Z-BEAM) Vs BEAM for Autologous Stem Cell Transplantation in Lymphoma: Toxicity and Long Term Outcome From a Retrospective Multicentric Study of 123 Patients SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Manier, Salomon] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Plantier, Isabelle] Hop Roubaix, Roubaix, France. [Wetterwald, Marc] CHD Dunkerque, Dunkerque, France. [Robu, Daniela] CH Lens, Lens, France. [Tricot, Sabine] Hop Valenciennes, Dept Hematol, Valenciennes, France. [Yakoub-Agha, Ibrahim] UAM Allogreffes CSH, Lille, France. [Gasmi, Hanane; Simon, Nicolas; Odou, Pascal] CHRU LILLE, Fac Pharmaceut & Biol Sci, Lab Biopharm, EA4481, Lille, France. [Morschhauser, Franck] CHU Lille, Dept Hematol, F-59037 Lille, France. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 2726 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603371 ER PT J AU Tesar, B Werner, L Hanna, M Improgo, MR Pochet, N Fernandes, SM Macconaill, L Regev, A Freedman, AS Neuberg, DS Freedman, ML Brown, JR AF Tesar, Bethany Werner, Lillian Hanna, Megan Improgo, Ma Reina Pochet, Nathalie Fernandes, Stacey M. Macconaill, Laura Regev, Aviv Freedman, Arnold S. Neuberg, Donna S. Freedman, Matthew L. Brown, Jennifer R. TI Risk Alleles Identified in Genome-Wide Association Studies Are Associated with Expression Quantitative Trait Loci in Chronic Lymphocytic Leukemia. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Tesar, Bethany; Improgo, Ma Reina] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Werner, Lillian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hanna, Megan] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Pochet, Nathalie; Regev, Aviv] Broad Inst, Cambridge, MA USA. [Fernandes, Stacey M.; Macconaill, Laura; Freedman, Arnold S.; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freedman, Matthew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Broad Inst Harvard & MIT, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 2875 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905364 ER PT J AU Thakar, MS Logan, BR Pasquini, MC McCarthy, PL Ho, VT Cooke, KR Zhu, XC Rizzo, JD Sorror, ML AF Thakar, Monica S. Logan, Brent R. Pasquini, Marcelo C. McCarthy, Philip L., Jr. Ho, Vincent T. Cooke, Kenneth R. Zhu, Xiaochun Rizzo, J. Douglas Sorror, Mohamed L. TI The Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) Can Prospectively Discriminate Risks Affecting Overall Survival in Pediatric and Adult Patients with Non-Malignant Diseases SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pasquini, Marcelo C.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [McCarthy, Philip L., Jr.] Roswell Pk Canc Inst, BMT Program, Buffalo, NY 14263 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cooke, Kenneth R.] Case Western Reserve Univ, Sch Med Pediat, Cleveland, OH 44106 USA. [Zhu, Xiaochun] Med Coll Wisconsin CIBMTR, Milwaukee, WI USA. [Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 737 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900222 ER PT J AU Thanarajasingam, G Kim, HT Cutler, C Ho, VT Koreth, J Alyea, EP Antin, JH Soiffer, RJ Armand, P AF Thanarajasingam, Gita Kim, Haesook T. Cutler, Corey Ho, Vincent T. Koreth, John Alyea, Edwin P., III Antin, Joseph H. Soiffer, Robert J. Armand, Philippe TI Outcome and Prognostic Factors for Patients Who Relapse After Allogeneic Stem Cell Transplantation. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Thanarajasingam, Gita] Mayo Clin, Rochester, MN USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Koreth, John; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 3069 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601194 ER PT J AU Tomasetti, C Kantarjian, HM Ramchandani, R Jabbour, E Quintas-Cardama, A Parmigiani, G Cortes, JE AF Tomasetti, Cristian Kantarjian, Hagop M. Ramchandani, Ritesh Jabbour, Elias Quintas-Cardama, Alfonso Parmigiani, Giovanni Cortes, Jorge E. TI The Average Baseline BCR-ABL Levels Are Significantly Higher in Patients with Resistance to Dasatinib As First-Line Treatment for Early Chronic Phase Chronic Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Tomasetti, Cristian; Ramchandani, Ritesh] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kantarjian, Hagop M.; Jabbour, Elias; Quintas-Cardama, Alfonso; Cortes, Jorge E.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4436 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605369 ER PT J AU Toretta, CL Niemierko, A Coughlin, E McAfee, SL Dey, BR Ballen, KK Attar, EC Chen, YBA Spitzer, TR Winkfield, KM AF Toretta, Cara L. Niemierko, Andrzej Coughlin, Erin McAfee, Steven L. Dey, Bimalangshu R. Ballen, Karen K. Attar, Eyal C. Chen, Yi-Bin A. Spitzer, Thomas R. Winkfield, Karen M. TI Long-Term Outcomes of Myeloablative Hematopoietic Cell Transplantation Using Total Body Irradiation Prior to Systemic Therapy SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [McAfee, Steven L.; Dey, Bimalangshu R.; Ballen, Karen K.; Attar, Eyal C.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Chen, Yi-Bin A.; Spitzer, Thomas R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Leukemia & Bone Marrow Transplant, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4552 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605501 ER PT J AU Trowbridge, JJ Li, MJ Roberts, CWM Orkin, SH AF Trowbridge, Jennifer J. Li, Mingjie Roberts, Charles W. M. Orkin, Stuart H. TI Genetic or Pharmacological Reductions in DNA Methylation Selectively Inhibit Peripheral T-Cell Lymphomagenesis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Trowbridge, Jennifer J.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Harvard Stem Cell Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pediat Oncol,Dana Farber Canc Inst,Harvard S, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 2760 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603337 ER PT J AU Vaja, V Sun, CC Cappellini, MD Lin, HYF Babitt, JL AF Vaja, Valentina Sun, Chia Chi Cappellini, Maria D. Lin, Herbert Yih-Fuu Babitt, Jodie L. TI A Hepcidin Inhibitor Mobilizes Iron for Incorporation Into Red Blood Cells in an Adenine-Induced Chronic Kidney Disease Model in Rats SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Vaja, Valentina; Cappellini, Maria D.] Univ Milan, Dept Internal Med, Fdn Ist Ricovero & Cura Carattere Sci Ca Granda, Milan, Italy. [Sun, Chia Chi; Lin, Herbert Yih-Fuu; Babitt, Jodie L.] Massachusetts Gen Hosp, Program Membrane Biol, Div Nephrol, Ctr Syst Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 2082 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603213 ER PT J AU Vander Lugt, MT Braun, TM Hanash, S Ferrara, JLM Ritz, J Ho, VT Antin, JH Zhang, Q Chin, A Gomez, A Harris, AC Levine, JE Choi, SW Couriel, D Reddy, P Paczesny, S AF Vander Lugt, Mark T. Braun, Thomas M. Hanash, Samir Ferrara, James L. M. Ritz, Jerome Ho, Vincent T. Antin, Joseph H. Zhang, Qing Chin, Alice Gomez, Aurelie Harris, Andrew C. Levine, John E. Choi, Sung W. Couriel, Daniel Reddy, Pavan Paczesny, Sophie TI Plasma ST2 Concentrations Predict Development of Acute Gvhd and Non-Relapse Mortality SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Hanash, Samir; Zhang, Qing; Chin, Alice] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Levine, John E.] Univ Michigan, Pediat Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 466 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902194 ER PT J AU Vij, R Chang, BY Berdeja, JG Huff, CA Lendvai, N Tai, YT Chang, S Moussa, D Buggy, JJ Elias, L Richardson, PG AF Vij, Ravi Chang, Betty Y. Berdeja, Jesus G. Huff, Carol Ann Lendvai, Nikoletta Tai, Yu-Tzu Chang, Stella Moussa, Davina Buggy, Joseph J. Elias, Laurence Richardson, Paul G. TI Early Changes in Cytokines, Chemokines and Indices of Bone Metabolism in a Phase 2 Study of the Bruton Tyrosine Kinase (Btk) Inhibitor, Ibrutinib (PCI-32765) in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Vij, Ravi] Washington Univ Sch Med, Div Oncol, Dept Med, St Louis, MO USA. [Chang, Betty Y.; Chang, Stella; Elias, Laurence] Pharmacyclics, Res, Sunnyvale, CA USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Huff, Carol Ann] Johns Hopkins Univ, Baltimore, MD USA. [Lendvai, Nikoletta] Mem Sloan Kettering Canc Ctr, Myeloma Lymphoma Serv, New York, NY 10021 USA. [Moussa, Davina; Buggy, Joseph J.] Pharmacyclics Inc, Sunnyvale, CA USA. [Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 1 U1 1 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 4039 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603061 ER PT J AU Vij, R Hofmeister, CC Richardson, PG Jagannath, S Siegel, DS Baz, R Chen, M Zaki, M Larkins, G Anderson, KC AF Vij, Ravi Hofmeister, Craig C. Richardson, Paul G. Jagannath, Sundar Siegel, David S. Baz, Rachid Chen, Min Zaki, Mohamed Larkins, Gail Anderson, Kenneth C. TI Pomalidomide (POM) with Low-Dose Dexamethasone (LoDEX) in Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Outcomes Based on Prior Treatment Exposure SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [Hofmeister, Craig C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Chen, Min; Zaki, Mohamed; Larkins, Gail] Celgene Corp, Summit, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 4070 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603030 ER PT J AU Vrooman, LM Stevenson, KE Harris, M Neuberg, DS Sallan, SE Silverman, LB AF Vrooman, Lynda M. Stevenson, Kristen E. Harris, Marian Neuberg, Donna S. Sallan, Stephen E. Silverman, Lewis B. TI Intensified Chemotherapy Regimen for Very High Risk Childhood B-Precursor Acute Lymphoblastic Leukemia (B-ALL): Results From Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05-01 SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Vrooman, Lynda M.; Neuberg, Donna S.; Sallan, Stephen E.; Silverman, Lewis B.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Stevenson, Kristen E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 3563 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906094 ER PT J AU Wagner, LI Zhao, FM Williams, ME Gascoyne, RD Krauss, JC Cella, D Horning, SJ Kahl, BS AF Wagner, Lynne I. Zhao, Fengmin Williams, Michael E. Gascoyne, Randy D. Krauss, John C. Cella, David Horning, Sandra J. Kahl, Brad S. TI Quality of Life Results From Eastern Cooperative Oncology Group Protocol E4402 (RESORT): A Randomized Phase III Study Comparing Two Different Rituximab Dosing Strategies for Indolent Non-Hodgkin's Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wagner, Lynne I.; Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Boston, MA USA. [Williams, Michael E.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Gascoyne, Randy D.] BC Canc Agcy, Ctr Lymphoid Canc, Dept Pathol, Vancouver, BC, Canada. [Krauss, John C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Horning, Sandra J.] Genentech Inc, Clin Dev Hem Onc, San Francisco, CA 94080 USA. [Kahl, Brad S.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 235 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901099 ER PT J AU Wang, HF Zang, CZ Taing, L Wong, HF Yashiro-Ohtani, Y Blacklow, S Pear, WS Liu, XS Aster, JC AF Wang, Hongfang Zang, Chongzhi Taing, Len Wong, Hoifung Yashiro-Ohtani, Yumi Blacklow, Stephen Pear, Warren S. Liu, X. Shirley Aster, Jon C. TI Genome-Wide Analysis of NOTCH1, ETS Family Factors, and RUNX1 Binding in Human T Lymphoblastic Leukemia Cells Reveals Distinct Regulatory Elements SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wang, Hongfang; Wong, Hoifung; Aster, Jon C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zang, Chongzhi; Taing, Len; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zang, Chongzhi; Taing, Len; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Yashiro-Ohtani, Yumi; Pear, Warren S.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Blacklow, Stephen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. RI Zang, Chongzhi/D-1445-2011 NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 1277 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902289 ER PT J AU Wang, LD Ficarro, SB Sullivan, J Marto, JA Wagers, AJ AF Wang, Leo D. Ficarro, Scott B. Sullivan, Jessica Marto, Jarrod A. Wagers, Amy J. TI Novel Nano-Scale Phosphoproteomic Identification of Pathways Responsible for Hematopoietic Stem and Progenitor Cell Mobilization and Malignant Transformation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wang, Leo D.] Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 4085 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603015 ER PT J AU Watts, JM Zickl, L Litzow, MR Luger, SM Lazarus, HM Cassileth, PA Fernandez, HF Douer, D Paietta, E Rowe, JM Tallman, MS AF Watts, Justin M. Zickl, Lynette Litzow, Mark R. Luger, Selina M. Lazarus, Hillard M. Cassileth, Peter A. Fernandez, Hugo F. Douer, Dan Paietta, Elisabeth Rowe, Jacob M. Tallman, Martin S. TI Practically All Patients with Acute Myeloid Leukemia (AML) in Continuous Complete Remission for 3 Years or More Are Cured of Their Disease: The ECOG Experience SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Watts, Justin M.; Douer, Dan; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Zickl, Lynette] Dana Farber Canc Inst, Boston, MA 02115 USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Luger, Selina M.] Univ Penn, Philadelphia, PA 19104 USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Cassileth, Peter A.] Univ Miami, Miami, FL USA. [Fernandez, Hugo F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Paietta, Elisabeth] Montefiore Med Ctr, Bronx, NY 10467 USA. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 132 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838900327 ER PT J AU Wei, Y Chen, R Dimicoli, S Bueso-Ramos, CE Neuberg, DS Pierce, SA Yang, H Jia, Y Zheng, H Fang, ZH Nguyen, M Fernandez, M Wang, SA Kantarjian, HM Garcia-Manero, G AF Wei, Yue Chen, Rui Dimicoli, Sophie Bueso-Ramos, Carlos E. Neuberg, Donna S. Pierce, Sherry A. Yang, Hui Jia, Yu Zheng, Hong Fang, Zhihong Nguyen, Martin Fernandez, Michael Wang, Sa A. Kantarjian, Hagop M. Garcia-Manero, Guillermo TI Deregulation of TLR2-JMJD3 Innate Immunity Signaling, Including a Rare TLR2 SNP As a Potential Somatic Mutation, in Myelodysplastic Syndromes (MDS) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wei, Yue; Dimicoli, Sophie; Pierce, Sherry A.; Yang, Hui; Jia, Yu; Zheng, Hong; Fang, Zhihong; Kantarjian, Hagop M.; Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Chen, Rui] Baylor Coll Med, Houston, TX 77030 USA. [Bueso-Ramos, Carlos E.; Nguyen, Martin; Fernandez, Michael; Wang, Sa A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 1700 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600339 ER PT J AU Weigert, O van Bodegom, D Bird, L Saur, A Tivey, T Kopp, N Kung, AL Weinstock, D AF Weigert, Oliver van Bodegom, Diederik Bird, Liat Saur, Amy Tivey, Trevor Kopp, Nadja Kung, Andrew L. Weinstock, David TI Newer-Generation HSP90 Inhibitors Have Potent Activity Against Human Mantle Cell Lymphoma in Vitro and in Vivo SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 1651 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601006 ER PT J AU Weigert, O Kopp, N Bolla, S Odejide, O Toscano, D Lunning, MA Teruya-Feldstein, J Louissaint, A Rodig, SJ Horwitz, SM Weinstock, D AF Weigert, Oliver Kopp, Nadja Bolla, Sudha Odejide, Oreofe Toscano, Dan Lunning, Matthew A. Teruya-Feldstein, Julie Louissaint, Abner Rodig, Scott J. Horwitz, Steven M. Weinstock, David TI A Targeted Mutational Landscape of Angioimmunoblastic T-Cell Lymphoma: Association Between Advanced Age and Mutations in TET2 and DNMT3A SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Weigert, Oliver; Kopp, Nadja; Bolla, Sudha; Odejide, Oreofe; Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Toscano, Dan; Lunning, Matthew A.; Teruya-Feldstein, Julie; Horwitz, Steven M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Louissaint, Abner] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 299 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901163 ER PT J AU Weinacht, KG Felgentreff, K Devine, A Schambach, A Al-herz, W Notarangelo, LD AF Weinacht, Katja G. Felgentreff, Kerstin Devine, Alex Schambach, Axel Al-herz, Waleed Notarangelo, Luigi Daniele TI Induced Pluripotent Stem Cells From a Patient with Reticular Dysgenesis Recapitulate Defective Myelopoiesis in-Vitro: A Disease Model to Enhance Our Understanding of a Rare Disease. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Weinacht, Katja G.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Schambach, Axel] Hannover Med Sch, Dept Expt Hematol, Hannover, Germany. [Al-herz, Waleed] Kuwait Univ, Dept Pediat Immunol, Safat 13060, Kuwait. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 2142 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905294 ER PT J AU Welch, S Armand, P Kim, HT LaCasce, AS Jacobsen, E Davids, MS Jacobson, CA Fisher, DC Brown, JR Freedman, AS Coughlin, E Chen, YBA AF Welch, Sarah Armand, Philippe Kim, Haesook T. LaCasce, Ann S. Jacobsen, Eric Davids, Matthew S. Jacobson, Caron A. Fisher, David C. Brown, Jennifer R. Freedman, Arnold S. Coughlin, Erin Chen, Yi-Bin A. TI Prognostic Factors for Patients with Diffuse Large B Cell Lymphoma and Transformed Indolent Lymphoma Undergoing Autologous Stem Cell Transplantation in the PET Era SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Welch, Sarah] Boston Univ, Sch Med, Div Grad Med Sci, Boston, MA 02118 USA. [Davids, Matthew S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Coughlin, Erin; Chen, Yi-Bin A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 1980 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903011 ER PT J AU Whitman, S Kohlschmidt, J Maharry, K Nicolet, D Schwind, S Becker, H Metzeler, KH Mrozek, K Mendler, JH Eisfeld, AK Volinia, S Powell, BL Carter, TH Kolitz, JE Stone, RM Park, IK Caligiuri, MA Marcucci, G Bloomfield, CD AF Whitman, Susan Kohlschmidt, Jessica Maharry, Kati Nicolet, Deedra Schwind, Sebastian Becker, Heiko Metzeler, Klaus H. Mrozek, Krzysztof Mendler, Jason H. Eisfeld, Ann-Kathrin Volinia, Stefano Powell, Bayard L. Carter, Thomas H. Kolitz, Jonathan E. Stone, Richard M. Park, Il-Kyoo Caligiuri, Michael A. Marcucci, Guido Bloomfield, Clara D. TI Adverse Prognostic Impact of GAS6 Expression in De Novo Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) (CALGB 8461, 9665, 20202; Alliance) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Whitman, Susan; Kohlschmidt, Jessica; Maharry, Kati; Nicolet, Deedra; Schwind, Sebastian; Becker, Heiko; Metzeler, Klaus H.; Mrozek, Krzysztof; Mendler, Jason H.; Eisfeld, Ann-Kathrin; Volinia, Stefano; Park, Il-Kyoo; Marcucci, Guido; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Carter, Thomas H.] Univ Iowa, Iowa City, IA USA. [Kolitz, Jonathan E.] N Shore Univ Hosp, Dept Med, Lake Success, NY USA. [Kolitz, Jonathan E.] Long Isl Jewish Med Ctr, Lake Success, NY USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stone, Richard M.] HMS, Boston, MA USA. [Caligiuri, Michael A.] Ohio State Univ, Integrated Biomed Sci Grad Program, Columbus, OH 43210 USA. [Bloomfield, Clara D.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. RI Volinia, Stefano/A-3029-2010; Mrozek, Krzysztof/A-3142-2008 OI Volinia, Stefano/0000-0003-0910-3893; NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 1293 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838902273 ER PT J AU Witzig, TE Hong, FX Micallef, IN Gascoyne, RD Dogan, A Wagner, H Advani, RH Kahl, BS Horning, SJ AF Witzig, Thomas E. Hong, Fangxin Micallef, Ivana N. Gascoyne, Randy D. Dogan, Ahmet Wagner, Henry, Jr. Advani, Ranjana H. Kahl, Brad S. Horning, Sandra J. TI A Phase II Trial of R-CHOP Followed by Zevalin Radioimmunotherapy for Patients with Previously Untreated Stages I and II CD20+Diffuse Large Cell Non-Hodgkin's Lymphoma: an Eastern Cooperative Oncology Group Study (E3402). SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Witzig, Thomas E.; Micallef, Ivana N.] Mayo Clin, Div Hematol, Rochester, MN USA. [Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gascoyne, Randy D.] BC Canc Agcy, Dept Pathol, Ctr Lymphoid Canc, Vancouver, BC, Canada. [Dogan, Ahmet] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Wagner, Henry, Jr.] Penn State Hershey Canc Inst, Div Radiat Oncol, Hershey, PA USA. [Advani, Ranjana H.] Stanford Univ, Sch Med, Div Oncol, Stanford, CA 94305 USA. [Kahl, Brad S.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 2687 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903106 ER PT J AU Woo, AJ Huang, H Piers, T Cantor, AB AF Woo, Andrew J. Huang, Hui Piers, Taylor Cantor, Alan B. TI Essential Role of the Transcription Factor ZBP-89 in Lymphopoiesis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 Boston Childrens Hosp, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 277 PG 1 WC Hematology SC Hematology GA 074UG UT WOS:000313838901141 ER PT J AU Wu, CJ AF Wu, Catherine J. TI Understanding the Role of Mutations in SF3B1 and Splicing in Chronic Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 15 PG 1 WC Hematology SC Hematology GA 074UG UT WOS:000313838900016 ER PT J AU Xu, J Shao, Z Glass, K Bauer, DE Pinello, L Van Handel, B Hou, S Stamatoyannopoulos, JA Mikkola, HKA Yuan, GC Orkin, SH AF Xu, Jian Shao, Zhen Glass, Kimberly Bauer, Daniel E. Pinello, Luca Van Handel, Ben Hou, Serena Stamatoyannopoulos, John A. Mikkola, Hanna K. A. Yuan, Guo-Cheng Orkin, Stuart H. TI Genomic Determinants of Human Fetal and Adult Erythroid Gene Expression SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Glass, Kimberly; Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Bauer, Daniel E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. [Van Handel, Ben; Mikkola, Hanna K. A.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. [Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Orkin, Stuart H.] Childrens Hosp, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 1227 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902339 ER PT J AU Yang, G Zhou, YS Liu, X Xu, L Cao, Y Patterson, CJ Tai, YT Anderson, KC Hunter, Z Treon, SP AF Yang, Guang Zhou, Yangsheng Liu, Xia Xu, Lian Cao, Yang Patterson, Christopher J. Tai, Yu-Tzu Anderson, Kenneth C. Hunter, Zachary Treon, Steven P. TI MYD88 L265P Promotes Survival of Waldenstrom's Macroglobulinemia Cells by Activation of Bruton's Tyrosine Kinase SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Yang, Guang; Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhou, Yangsheng; Liu, Xia; Xu, Lian; Cao, Yang] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Patterson, Christopher J.] Dana Farber Canc Inst, Waldenstroms Macroglubulinemia Ctr, Boston, MA 02115 USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 897 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900362 ER PT J AU Yen, K Wang, F Schalm, S Hansen, E Straley, K Kernytsky, A Choe, S Liu, W Popovici-Muller, J Travins, J Yang, H Silverman, L Aurore, JL Kaelin, WG Gross, S Dang, L Salituro, F Saunders, J Dorsch, M Agresta, S Schenkein, DP Su, M Biller, S AF Yen, Katharine Wang, Fang Schalm, Stefanie Hansen, Erica Straley, Kimberly Kernytsky, Andrew Choe, Sung Liu, Wei Popovici-Muller, Janeta Travins, Jeremy Yang, Hua Silverman, Lee Aurore, Julie Losman Kaelin, William G., Jr. Gross, Stefan Dang, Lenny Salituro, Frank Saunders, Jeffrey Dorsch, Marion Agresta, Samuel Schenkein, David P. Su, Michael Biller, Scott TI Mutation Selective IDH Inhibitors Mediate Histone and DNA Methylation Changes SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Yen, Katharine; Wang, Fang; Schalm, Stefanie; Hansen, Erica; Straley, Kimberly; Kernytsky, Andrew; Choe, Sung; Liu, Wei; Popovici-Muller, Janeta; Travins, Jeremy; Yang, Hua; Silverman, Lee; Gross, Stefan; Dang, Lenny; Dorsch, Marion; Agresta, Samuel; Schenkein, David P.; Su, Michael; Biller, Scott] Agios Pharmaceut, Cambridge, MA USA. [Aurore, Julie Losman] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. [Salituro, Frank] Sage Therapeut, Cambridge, MA USA. [Saunders, Jeffrey] Ember Therapeut, Boston, MA USA. NR 0 TC 0 Z9 0 U1 3 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 NOV 16 PY 2012 VL 120 IS 21 MA 3509 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604018 ER PT J AU Yoo, E Vasuthasawat, A Tran, D Lichtenstein, A Morrison, S AF Yoo, Esther Vasuthasawat, Alex Danh Tran Lichtenstein, Alan Morrison, Sherie TI Anti-CD138-IFN alpha Fusion Proteins Are Effective in Treating Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lichtenstein, Alan] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Morrison, Sherie] Univ Calif Los Angeles, MIMG, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 939 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902022 ER PT J AU Yoo, E Vasuthasawat, A Tran, D Lichtenstein, A Morrison, S AF Yoo, Esther Vasuthasawat, Alex Danh Tran Lichtenstein, Alan Morrison, Sherie TI Anti-CD138-IFN alpha Fusion Proteins Are Effective in Treating Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lichtenstein, Alan] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Morrison, Sherie] Univ Calif Los Angeles, MIMG, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2012 VL 120 IS 21 MA 939 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901198 ER PT J AU Yusuf, RZ Acharya, SS Yu, VWC Saez, B Cobert, JM Doench, J Bullinger, L S'aulis, D Lee, D Palchaudhuri, R Uzosike, AC Duvet, M Logan, DJ Das, S Cook, CM Churchill, M Scadden, E Warraich, G Liu, H Chattopadhyay, S Brown, A Sykes, SM Sykes, DB Mercier, F Carpenter, AE Armstrong, SA Vander Heiden, M Ebert, BL Kung, AL Rizzo, WB Mukherjee, S Scadden, DT AF Yusuf, Rushdia Z. Acharya, Sanket S. Yu, Vionnie W. C. Saez, Borja Cobert, Julien M. Doench, John Bullinger, Lars S'aulis, Dana Lee, Dongjun Palchaudhuri, Rahul Uzosike, Akachimere C. Duvet, Mildred Logan, David J. Das, Sudeshna Cook, Colleen M. Churchill, Michael Scadden, Elizabeth Warraich, Gohar Liu, Hao Chattopadhyay, Shrikanta Brown, Adam Sykes, Stephen M. Sykes, David B. Mercier, Francois Carpenter, Anne E. Armstrong, Scott A. Vander Heiden, Matthew Ebert, Benjamin L. Kung, Andrew L. Rizzo, William B. Mukherjee, Siddhartha Scadden, David T. TI Aldehyde Dehydrogenase 3a2 (Aldh3a2) Represents a Distinct Metabolic Vulnerability in MLL-AF9 AML Leukemia Initiating Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Yusuf, Rushdia Z.; Acharya, Sanket S.; Saez, Borja; Palchaudhuri, Rahul; Cook, Colleen M.; Sykes, Stephen M.; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol,Ctr Regenerat Med, Boston, MA 02115 USA. [Acharya, Sanket S.] Harvard Univ, Grad Program Immunol, Boston, MA 02115 USA. [Doench, John; Duvet, Mildred; Logan, David J.; Chattopadhyay, Shrikanta; Brown, Adam; Carpenter, Anne E.] Broad Inst MIT & Harvard, Boston, MA USA. [Bullinger, Lars] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany. [S'aulis, Dana; Rizzo, William B.] Univ Nebraska Med Ctr, Omaha, NE USA. [Churchill, Michael; Mukherjee, Siddhartha] Columbia Univ, Sch Med, Dept Med, New York, NY 10027 USA. [Churchill, Michael; Mukherjee, Siddhartha] Columbia Univ, Sch Med, Irving Canc Res Ctr, New York, NY 10027 USA. [Sykes, David B.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Armstrong, Scott A.] Childrens Hosp, Boston, MA 02115 USA. [Vander Heiden, Matthew] MIT, Koch Inst Canc Res, Cambridge, MA 02139 USA. [Ebert, Benjamin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. [Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Ctr Canc, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 208 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901072 ER PT J AU Zhang, WH Lin, JH Ma, DD Kwart, AH Ramachandran, A He, S Swagata, S Tai, YT Anderson, KC Handin, RI Munshi, NC AF Zhang, Weihong Lin, Jianhong Ma, Dongdong Kwart, Ariel H. Ramachandran, Aravind He, Shirley Swagata, Sharma Tai, Yu-Tzu Anderson, Kenneth C. Handin, Robert I. Munshi, Nikhil C. TI A Clinically Relevant Zebrafish in Vivo Model of Human Multiple Myeloma (MM) to Study Disease Biology and Preclinical Therapeutic Efficacy SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ma, Dongdong] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Handin, Robert I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 4078 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603022 ER PT J AU Zhao, XH Lwin, T Zhang, XW Huang, A Wang, J Marquez, VE Chen-Kiang, S Bradner, JE Dalton, WS Sotomayor, EM Tao, JG AF Zhao, Xiaohong Lwin, Tint Zhang, Xinwei Huang, Andy Wang, Jian Marquez, Victor E. Chen-Kiang, Selina Bradner, James E. Dalton, William S. Sotomayor, Eduardo M. Tao, Jianguo TI Silencing c-Myc Using Myc Inhibitor JQ1 and EZH2 Inhibitor DZNep Blocks Converging Survival Signals in Aggressive B-Cell Lymphomas SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Zhao, Xiaohong] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Tao, Jianguo] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Pathol, Tampa, FL 33612 USA. [Zhang, Xinwei] Tianjin Med Univ, Canc Inst & Hosp, Dept Biotherapy, Tianjin, Peoples R China. [Huang, Andy; Wang, Jian] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Marquez, Victor E.] NCI, Frederick, MD 21701 USA. [Chen-Kiang, Selina] Weill Cornell Med Coll, New York, NY USA. [Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dalton, William S.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL USA. [Dalton, William S.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Expt Therapeut Program, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 16 PY 2012 VL 120 IS 21 MA 4618 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049606049 ER PT J AU Zhou, Z Rademaker, AW Gordon, LI LaCasce, AS Vanderplas, A Crosby-Thompson, A Zelenetz, AD Abel, GA Rodriguez, MA Nademanee, A Kaminski, MS Czuczman, MS Millenson, M Niland, J Friedberg, JW Winter, JN AF Zhou, Zheng Rademaker, Alfred W. Gordon, Leo I. LaCasce, Ann S. Vanderplas, Ann Crosby-Thompson, Allison Zelenetz, Andrew D. Abel, Gregory A. Rodriguez, Maria A. Nademanee, Auayporn Kaminski, Mark S. Czuczman, Myron S. Millenson, Michael Niland, Joyce Friedberg, Jonathan W. Winter, Jane N. TI An Enhanced International Prognostic Index (IPI) for Patients with Diffuse Large B-Cell Lymphoma (DLBCL) in the Rituximab Era Using the National Comprehensive Cancer Network (NCCN) Database. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Zhou, Zheng] Northwestern Univ, Dept Med, Feinberg Sch Med, NW Mem Hosp,Div Hematol Oncol, Chicago, IL 60611 USA. [Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [LaCasce, Ann S.; Crosby-Thompson, Allison; Abel, Gregory A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vanderplas, Ann] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Rodriguez, Maria A.] UT MD Anderson Canc Ctr, Houston, TX USA. [Nademanee, Auayporn] City Hope Natl Med Ctr, Hematol & Stem Cell Transplantat, Duarte, CA USA. [Kaminski, Mark S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. [Millenson, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Niland, Joyce] City Hope Natl Med Ctr, Data Coordinating Ctr, Duarte, CA 91010 USA. [Friedberg, Jonathan W.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Winter, Jane N.] Northwestern Univ, Dept Med, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2012 VL 120 IS 21 MA 2656 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838903137 ER PT J AU Pham, MHT Bonello, GB Castiblanco, J Le, T Sigala, J He, WJ Mummidi, S AF Pham, Minh-Hieu T. Bonello, Gregory B. Castiblanco, John Le, Tuan Sigala, Jose He, Weijing Mummidi, Srinivas TI The rs1024611 Regulatory Region Polymorphism Is Associated with CCL2 Allelic Expression Imbalance SO PLOS ONE LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTIMA-MEDIA THICKNESS; SINGLE-NUCLEOTIDE POLYMORPHISMS; MCP-1 GENE POLYMORPHISM; FUNCTIONAL PROMOTER POLYMORPHISM; TYPE-2 DIABETES-MELLITUS; CORONARY-ARTERY-DISEASE; PULMONARY TUBERCULOSIS; CAROTID ATHEROSCLEROSIS AB CC chemokine ligand 2 (CCL2) is the most potent monocyte chemoattractant and inter-individual differences in its expression level have been associated with genetic variants mapping to the cis-regulatory regions of the gene. An A to G polymorphism in the CCL2 enhancer region at position -2578 (rs1024611; A>G), was found in most studies to be associated with higher serum CCL2 levels and increased susceptibility to a variety of diseases such as HIV-1 associated neurological disorders, tuberculosis, and atherosclerosis. However, the precise mechanism by which rs1024611influences CCL2 expression is not known. To address this knowledge gap, we tested the hypothesis that rs1024611G polymorphism is associated with allelic expression imbalance (AEI) of CCL2. We used haplotype analysis and identified a transcribed SNP in the 3'UTR (rs13900; C>T) can serve as a proxy for the rs1024611 and demonstrated that the rs1024611G allele displayed a perfect linkage disequilibrium with rs13900T allele. Allele-specific transcript quantification in lipopolysaccharide treated PBMCs obtained from heterozygous donors showed that rs13900T allele were expressed at higher levels when compared to rs13900C allele in all the donors examined suggesting that CCL2 is subjected to AEI and that that the allele containing rs1024611G is preferentially transcribed. We also found that AEI of CCL2 is a stable trait and could be detected in newly synthesized RNA. In contrast to these in vivo findings, in vitro assays with haplotype-specific reporter constructs indicated that the haplotype bearing rs1024611G had a lower or similar transcriptional activity when compared to the haplotype containing rs1024611A. This discordance between the in vivo and in vitro expression studies suggests that the CCL2 regulatory region polymorphisms may be functioning in a complex and context-dependent manner. In summary, our studies provide strong functional evidence and a rational explanation for the phenotypic effects of the CCL2 rs1024611G allele. C1 [Pham, Minh-Hieu T.; Bonello, Gregory B.; Castiblanco, John; Le, Tuan; Sigala, Jose; He, Weijing; Mummidi, Srinivas] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX 78229 USA. [Pham, Minh-Hieu T.; Bonello, Gregory B.; Castiblanco, John; Le, Tuan; Sigala, Jose; He, Weijing; Mummidi, Srinivas] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Mummidi, S (reprint author), S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX 78229 USA. EM mummidi@uthscsa.edu RI CASTIBLANCO, JOHN/B-6599-2009; Mummidi, Srinivas/C-1004-2008; OI CASTIBLANCO, JOHN/0000-0002-7965-9822; Mummidi, Srinivas/0000-0002-4068-6380; CASTIBLANCO, JOHN/0000-0003-2556-3697 FU Veterans Affairs Office of Research and Development-Biomedical Laboratory Research and Development Service Award [I01BX000975]; Department of Veterans Affairs Career Development Award-2 [1IK2BX001276-01A1]; National Institutes of Health (NIMH and NINDS) FX This work is supported by the Veterans Affairs Office of Research and Development-Biomedical Laboratory Research and Development Service Award (I01BX000975) to SM. TL is supported by a Department of Veterans Affairs Career Development Award-2 (1IK2BX001276-01A1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The brain samples for examining the CCL2 AEI were obtained from National Neurological AIDS bank (5U01MH083500, NS38841), The Manhattan HIV Brain Bank (U01MH083501, R24MH59724), and the Texas Repository for AIDS Neuropathogenesis Research (U01MH083507, R24 NS 38841) that are part of the National NeuroAIDS Tissue Consortium that is funded by the National Institutes of Health (NIMH and NINDS). NR 96 TC 9 Z9 9 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 NOV 16 PY 2012 VL 7 IS 11 AR e49498 DI 10.1371/journal.pone.0049498 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048BN UT WOS:000311885300048 PM 23166687 ER PT J AU Kreslavsky, T Gleimer, M Miyazaki, M Choi, Y Gagnon, E Murre, C Sicinski, P von Boehmer, H AF Kreslavsky, Taras Gleimer, Michael Miyazaki, Masaki Choi, Yoon Gagnon, Etienne Murre, Cornelis Sicinski, Piotr von Boehmer, Harald TI beta-Selection-Induced Proliferation Is Required for alpha beta T Cell Differentiation SO IMMUNITY LA English DT Article ID PRE-TCR; LYMPHOCYTE DEVELOPMENT; THYMOCYTE DEVELOPMENT; IN-VIVO; C-MYC; NOTCH; PROMOTES; KINASE; GAMMA; SURVIVAL AB Proliferation and differentiation are tightly coordinated to produce an appropriate number of differentiated cells and often exhibit an antagonistic relationship. Developing T cells, which arise in the thymus from a minute number of bone-marrow-derived progenitors, undergo a major expansion upon pre-T cell receptor (TCR) expression. The burst of proliferation coincides with differentiation toward the alpha beta T cell lineage-but the two processes were previously thought to be independent from one another, although both were driven by signaling from pre-TCR and Notch receptors. Here we report that proliferation at this step was not only absolutely required for differentiation but also that its ectopic activation was sufficient to substantially rescue differentiation in the absence of Notch signaling. Consistently, pharmacological inhibition of the cell cycle machinery also blocked differentiation in vivo. Thus the proliferation step is strictly required prior to differentiation of immature thymocytes. C1 [Kreslavsky, Taras; Gleimer, Michael; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Choi, Yoon; Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Miyazaki, Masaki; Murre, Cornelis] Univ Calif San Diego, Dept Mol Biol, La Jolla, CA 92093 USA. [Gagnon, Etienne] Univ Montreal, Dept Microbiol & Immunol, Inst Rech Immunol & Cancerol, Montreal, PQ H3T1J4, Canada. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu FU National Institutes of Health [R01 A145846, R01 A151378] FX We would like to thank J.C. Zuniga-Pflucker J.M. Adams, M. Dose, F. Gounari, H. Cantor, and A. Capobianco for providing reagents and mice and G. Turchinovich, D. Gray, M. Herold, H.-J. Kim, C. Daniel, and S. Schlenner for helpful discussions. The authors are grateful to V. Schmidt and G. Singh for technical assistance. These studies were supported by National Institutes of Health Grants R01 A145846 and R01 A151378. NR 34 TC 25 Z9 25 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 16 PY 2012 VL 37 IS 5 BP 840 EP 853 DI 10.1016/j.immuni.2012.08.020 PG 14 WC Immunology SC Immunology GA 042GP UT WOS:000311460000011 PM 23159226 ER PT J AU Desmond, CR Atwal, RS Xia, JR Truant, R AF Desmond, Carly R. Atwal, Randy Singh Xia, Jianrun Truant, Ray TI Identification of a Karyopherin beta 1/beta 2 Proline-Tyrosine Nuclear Localization Signal in Huntingtin Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GREEN FLUORESCENT PROTEIN; MESSENGER-RNA EXPORT; IMPORTIN-ALPHA; DISEASE; TRANSPORT; FRAGMENTS; PROTEOLYSIS; TOXICITY; MULTIPLE; BRAINS AB Among the known pathways of protein nuclear import, the karyopherin beta 2/transportin pathway is only the second to have a defined nuclear localization signal (NLS) consensus. Huntingtin, a 350-kDa protein, has defined roles in the nucleus, as well as a CRM1/exportin-dependent nuclear export signal; however, the NLS and exact pathway of import have remained elusive. Here, using a live cell assay and affinity chromatography, we show that huntingtin has a karyopherin beta 2-dependent prolinetyrosine (PY)-NLS in the amino terminus of the protein. This NLS comprises three consensus components: a basic charged sequence, a downstream conserved arginine, and a PY sequence. Unlike the classic PY-NLS, which has an unstructured intervening sequence between the consensus components, we show that a beta sheet structured region separating the consensus elements is critical for huntingtin NLS function. The huntingtin PY-NLS is also capable of import through the importin/karyopherin beta 1 pathway but was not functional in all cell types tested. We propose that this huntingtin PY-NLS may comprise a new class of multiple import factor-dependent NLSs with an internal structural component that may regulate NLS activity. C1 [Desmond, Carly R.; Xia, Jianrun; Truant, Ray] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada. [Atwal, Randy Singh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Truant, R (reprint author), HSC 4N54,1200 Main St W, Hamilton, ON L8N 3Z5, Canada. EM truantr@mcmaster.ca FU Huntington Society of Canada; CHDI Inc.; Krembil Foundation; Canadian Institutes of Health Research Operating Grant [MOP-119391] FX This work was supported by the Huntington Society of Canada, CHDI Inc., the Krembil Foundation, and the Canadian Institutes of Health Research Operating Grant MOP-119391 (to R.T.). NR 35 TC 12 Z9 12 U1 0 U2 3 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 NOV 16 PY 2012 VL 287 IS 47 DI 10.1074/jbc.M112.412379 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039GY UT WOS:000311233800032 PM 23012356 ER PT J AU Lee, KH Biswas, A Liu, YJ Kobayashi, KS AF Lee, Kyoung-Hee Biswas, Amlan Liu, Yuen-Joyce Kobayashi, Koichi S. TI Proteasomal Degradation of Nod2 Protein Mediates Tolerance to Bacterial Cell Wall Components SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMPAIRED ANTIGEN PRESENTATION; INNATE IMMUNE-RESPONSES; MONOPHOSPHORYL-LIPID-A; NF-KAPPA-B; ENDOTOXIN TOLERANCE; HUMAN MONOCYTES; MURAMYL-DIPEPTIDE; BLAU-SYNDROME; SEPTIC SHOCK; MOLECULAR-MECHANISMS AB The innate immune system serves as the first line of defense by detecting microbes and initiating inflammatory responses. Although both Toll-like receptor (TLR) and nucleotide binding domain and leucine-rich repeat (NLR) proteins are important for this process, their excessive activation is hazardous to hosts; thus, tight regulation is required. Endotoxin tolerance is refractory to repeated lipopolysaccharide (LPS) stimulation and serves as a host defense mechanism against septic shock caused by an excessive TLR4 response during Gram-negative bacterial infection. Gram-positive bacteria as well as their cell wall components also induce shock. However, the mechanism underlying tolerance is not understood. Here, we show that activation of Nod2 by its ligand, muramyl dipeptide (MDP) in the bacterial cell wall, induces rapid degradation of Nod2, which confers MDP tolerance in vitro and in vivo. Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation. Upon MDP stimulation, Hsp90 rapidly dissociates from Nod2, which subsequently undergoes ubiquitination and proteasomal degradation. The SOCS-3 protein induced by Nod2 activation further facilitates this degradation process. Therefore, Nod2 protein stability is a key factor in determining responsiveness to MDP stimulation. This indicates that TLRs and NLRs induce a tolerant state through distinct molecular mechanisms that protect the host from septic shock. C1 [Kobayashi, Koichi S.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Microbial & Mol Pathogenesis, College Stn, TX 77843 USA. [Lee, Kyoung-Hee; Biswas, Amlan; Liu, Yuen-Joyce; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Lee, Kyoung-Hee; Biswas, Amlan; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. RP Kobayashi, KS (reprint author), Texas A&M Hlth Sci Ctr, Coll Med, Dept Microbial & Mol Pathogenesis, 415A Reynolds Med Bldg, College Stn, TX 77843 USA. EM kobayashi@medicine.tamhsc.edu FU National Institutes of Health [R01DK074738]; Crohn's and Colitis Foundation of America FX This work was supported, in whole or in part, by National Institutes of Health Grant R01DK074738 (to K. S. K.). This work was also supported by a grant from the Crohn's and Colitis Foundation of America (to K. S. K.).; Recipient of Crohn's and Colits Foundation of America research fellowship. NR 68 TC 26 Z9 27 U1 0 U2 12 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 NOV 16 PY 2012 VL 287 IS 47 DI 10.1074/jbc.M112.410027 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039GY UT WOS:000311233800048 PM 23019338 ER PT J AU Shi, XZ Wallis, AM Gerard, RD Voelker, KA Grange, RW DePinho, RA Garry, MG Garry, DJ AF Shi, Xiaozhong Wallis, Alicia M. Gerard, Robert D. Voelker, Kevin A. Grange, Robert W. DePinho, Ronald A. Garry, Mary G. Garry, Daniel J. TI Foxk1 promotes cell proliferation and represses myogenic differentiation by regulating Foxo4 and Mef2 SO JOURNAL OF CELL SCIENCE LA English DT Article DE Foxk1; Foxo4; Mef2; Cell proliferation; Cell differentiation ID SKELETAL-MUSCLE; DNA-BINDING; TRANSCRIPTION FACTORS; SIGNALING PATHWAYS; CRYSTAL-STRUCTURE; PROGENITOR CELLS; GENE-EXPRESSION; SATELLITE CELL; STEM-CELLS; MICE AB In response to severe injury, adult skeletal muscle exhibits a remarkable regenerative capacity due to a resident muscle stem/progenitor cell population. While a number of factors are expressed in the muscle progenitor cell (MPC) population, the molecular networks that govern this cell population remain an area of active investigation. In this study, utilizing knockdown techniques and overexpression of Foxk1 in the myogenic lineage, we observed dysregulation of Foxo and Mef2 downstream targets. Utilizing an array of technologies, we establish that Foxk1 represses the transcriptional activity of Foxo4 and Mef2 and physically interacts with Foxo4 and Mef2, thus promoting MPC proliferation and antagonizing the myogenic lineage differentiation program, respectively. Correspondingly, knockdown of Foxk1 in C2C12 myoblasts results in cell cycle arrest, and Foxk1 overexpression in C2C12CAR myoblasts retards muscle differentiation. Collectively, we have established that Foxk1 promotes MPC proliferation by repressing Foxo4 transcriptional activity and inhibits myogenic differentiation by repressing Mef2 activity. These studies enhance our understanding of the transcriptional networks that regulate the MPC population and muscle regeneration. C1 [Shi, Xiaozhong; Wallis, Alicia M.; Garry, Mary G.; Garry, Daniel J.] Univ Minnesota Twin Cities, Lillehei Heart Inst, Minneapolis, MN 55455 USA. [Gerard, Robert D.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Voelker, Kevin A.; Grange, Robert W.] USA Polytech Inst & State Univ, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst,Dept Genet, Boston, MA 02115 USA. RP Garry, DJ (reprint author), Univ Minnesota Twin Cities, Lillehei Heart Inst, Minneapolis, MN 55455 USA. EM garry@umn.edu FU National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin) [5R01AR047850, 5R01AR055906]; Robert A. and Renee E. Belfer Institute for Applied Cancer Science FX Funding support was obtained from the National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin) [grant numbers 5R01AR047850 and 5R01AR055906 to D.J.G.]. R.A.D. is supported by the Robert A. and Renee E. Belfer Institute for Applied Cancer Science. Deposited in PMC for release after 12 months. NR 59 TC 12 Z9 12 U1 1 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 15 PY 2012 VL 125 IS 22 BP 5329 EP 5337 DI 10.1242/jcs.105239 PG 9 WC Cell Biology SC Cell Biology GA 084BU UT WOS:000314511900009 PM 22956541 ER PT J AU Bair, AM Turman, MV Vaine, CA Panettieri, RA Soberman, RJ AF Bair, Angela M. Turman, Melissa V. Vaine, Christine A. Panettieri, Reynold A., Jr. Soberman, Roy J. TI The nuclear membrane leukotriene synthetic complex is a signal integrator and transducer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID COLONY-STIMULATING FACTOR; CYTOSOLIC PHOSPHOLIPASE A(2); ARACHIDONIC-ACID RELEASE; HUMAN-NEUTROPHILS; 5-LIPOXYGENASE-ACTIVATING PROTEIN; HUMAN-LEUKOCYTES; POLYMORPHONUCLEAR LEUKOCYTES; TRANSLOCATION; DOMAIN; CELLS AB Leukotrienes (LTs) are lipid-signaling molecules derived from arachidonic acid (AA) that initiate and amplify inflammation. To initiate LT formation, the 5-lipoxygenase (5-LO) enzyme translocates to nuclear membranes, where it associates with its scaffold protein, 5-lipoxygenase-activating protein (FLAP), to form the core of the multiprotein LT synthetic complex. FLAP is considered to function by binding free AA and facilitating its use as a substrate by 5-LO to form the initial LT, LTA(4). We used a combination of fluorescence lifetime imaging microscopy, cell biology, and biochemistry to identify discrete AA-dependent and AA-independent steps that occur on nuclear membranes to control the assembly of the LT synthetic complex in polymorphonuclear leukocytes. The association of AA with FLAP changes the configuration of the scaffold protein, enhances recruitment of membrane-associated 5-LO to form complexes with FLAP, and controls the closeness of this association. Granulocyte monocyte colony-stimulating factor provides a second AA-independent signal that controls the closeness of 5-LO and FLAP within complexes but not the number of complexes that are assembled. Our results demonstrate that the LT synthetic complex is a signal integrator that transduces extracellular signals to modulate the interaction of 5-LO and FLAP. C1 [Bair, Angela M.; Turman, Melissa V.; Vaine, Christine A.; Soberman, Roy J.] Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA 02129 USA. [Panettieri, Reynold A., Jr.] Univ Penn, Airways Biol Initiat, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. RP Soberman, RJ (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA 02129 USA. EM Soberman@helix.mgh.harvard.edu OI Vaught, Melissa/0000-0001-7627-8330 FU National Institutes of Health [R01 AI068871, K01 DK089145-01A1, AI068871-04S1, 1S10RR027931, 1R01HL097796, T32 DK007540-22] FX We thank Kristin White of Massachusetts General Hospital for her assistance in confocal microscopy. This work was supported by National Institutes of Health Grants R01 AI068871 (R.J.S. and A. M. B.), K01 DK089145-01A1 (A. M. B.), R01 ARRA supplement AI068871-04S1 (M. V. T., C. A. V., R.J.S.), 1S10RR027931 (R.J.S.), 1R01HL097796 (R.J.S., A. M. B., R. A. P.), and T32 DK007540-22 (A. M. B. and M.V.T.). NR 43 TC 12 Z9 13 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV 15 PY 2012 VL 23 IS 22 BP 4456 EP 4464 DI 10.1091/mbc.E12-06-0489 PG 9 WC Cell Biology SC Cell Biology GA 082PP UT WOS:000314404700011 PM 23015755 ER PT J AU Saoiabi, S El Asri, S Laghzizil, A Saoiabi, A Ackerman, JL Coradin, T AF Saoiabi, S. El Asri, S. Laghzizil, A. Saoiabi, A. Ackerman, J. L. Coradin, T. TI Lead and zinc removal from aqueous solutions by aminotriphosphonate-modified converted natural phosphates SO CHEMICAL ENGINEERING JOURNAL LA English DT Article DE Natural phosphate; Apatite; Porous material; Surface functionalization; Heavy metals ID HEAVY-METALS REMOVAL; ACTIVATED CARBON; WASTE-WATER; HYDROXYAPATITE; ADSORPTION; EQUILIBRIUM; APATITE; MECHANISMS; SORPTION; MODELS AB Apatite particles prepared from natural phosphate rock and grafted with nitrilotris(methylene)triphosphonate (NTP) were evaluated for Pb2+ and Zn2+ sorption from aqueous solutions. Sorption capacities as high as 640 mg g(-1) and 300 mg g(-1) could be obtained for the highest organic content (10 wt.%). Analysis of the sorption isotherms using Langmuir, Freundlich and Dubinin-Kaganer-Radushkevich models revealed that Pb2+ ions have a larger affinity for apatite (sorption energy approximate to 8 kJ mol(-1)) than for NTP so that organo-modified surfaces led to a heterogenous adsorption process. In contrast, Zn2+ interacts weakly (sorption energy approximate to 1 kJ mol(-1)) and similarly with the mineral surface and the organic moieties following a homogenous sorption process. Such an association of organic metal ligands with reactive apatite surfaces within porous materials appears as a promising strategy to obtain efficient adsorbents at low cost and limited environmental impact. (C) 2012 Elsevier B.V. All rights reserved. C1 [Saoiabi, S.; El Asri, S.; Laghzizil, A.; Saoiabi, A.] Univ Mohamed V Agdal, Fac Sci, Lab Chim Phys Gen, Rabat, Morocco. [Ackerman, J. L.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Biomat Lab, Charlestown, MA 02129 USA. [Ackerman, J. L.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Coradin, T.] Univ Paris 06, CNRS, Coll France, F-75005 Paris, France. RP Laghzizil, A (reprint author), Univ Mohamed V Agdal, Fac Sci, Lab Chim Phys Gen, BP 1014, Rabat, Morocco. EM thibaud.coradin@upmc.fr RI Coradin, Thibaud/L-8932-2013; Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 NR 42 TC 9 Z9 9 U1 5 U2 41 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1385-8947 J9 CHEM ENG J JI Chem. Eng. J. PD NOV 15 PY 2012 VL 211 BP 233 EP 239 DI 10.1016/j.cej.2012.09.017 PG 7 WC Engineering, Environmental; Engineering, Chemical SC Engineering GA 073SE UT WOS:000313762000029 ER PT J AU Hacking, SA Boyraz, P Powers, BM Sen-Gupta, E Kucharski, W Brown, CA Cook, EP AF Hacking, S. A. Boyraz, P. Powers, B. M. Sen-Gupta, E. Kucharski, W. Brown, C. A. Cook, E. P. TI Surface roughness enhances the osseointegration of titanium headposts in non-human primates SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Non-human primate; Skull anchored headpost; Titanium implant; Surface texture; Osseointegration ID RABBIT INTRAMEDULLARY MODEL; TOTAL HIP-ARTHROPLASTY; BEHAVING MONKEYS; IMPLANT FIXATION; DENTAL IMPLANTS; BONE INGROWTH; TOPOGRAPHY; DEFECTS; ALLOY; ACID AB It is well recognized that micrometer and nanometer sized surface features enhance the skeletal attachment of implants within bone. However, little is known regarding the integration of implants placed outside the bone but in contact with the surface. Loosening of chronic skull anchored headposts in non-human primate based experiments can be a factor. The purpose of this study was to evaluate the effect of a simple and easily applied surface texture on bone apposition to titanium implants fixed to the periosteal surface of the skull. Implants possessed either a polished surface or a textured surface created by grit-basting followed by acid etching. The percent of bone in contact with the implant surface (bone apposition) to three polished and three textured implants was evaluated in one adult female monkey after 14 weeks. Upon harvest, implants were processed for undecalcified histology and regions of bone apposition were quantified using backscatter electron microscopy and digital image analysis. The bone apposition to textured implants was 62 +/- 20% and to polished implants was 42 +/- 21%. The application of a peak-and-pit like texture to the surface of titanium implants significantly increased bone apposition to titanium implants placed on the periosteal surface of the skull. This study demonstrates that titanium headposts can easily be modified to improve osseointegration using equipment and supplies available to most neurophysiological laboratories. In addition, implant texturing may have utility in areas including skeletal trauma and reconstruction where devices are placed in contact with the bone surface. (C) 2012 Elsevier B.V. All rights reserved. C1 [Boyraz, P.; Sen-Gupta, E.; Kucharski, W.; Cook, E. P.] McGill Univ, Dept Physiol, McIntyre Med Sci, Montreal, PQ H3G 1Y6, Canada. [Hacking, S. A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hacking, S. A.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. [Powers, B. M.; Brown, C. A.] Worcester Polytech Inst, WPI Surface Metrol Lab, Worcester, MA 01609 USA. RP Cook, EP (reprint author), McGill Univ, Dept Physiol, McIntyre Med Sci, Room 1225,3655 Sir William Osler, Montreal, PQ H3G 1Y6, Canada. EM Erik.cook@mcgill.ca FU CIHR; NSERC FX We would like to thank Stephen G. Nuara for anesthesia and technical assistance during surgeries. Dr. J Aizenberg for SEM use and Dr. J. Barralet for use of his sectioning saw. This work was supported by operating funds from CIHR and NSERC (EPC). We are grateful to Olympus for the use of the LEXT4000 scanning laser confocal microscope that was used to measure the surface topographies and to Digital Surf for Mountains Map which was used to analyze the measured topographies. NR 40 TC 11 Z9 11 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV 15 PY 2012 VL 211 IS 2 BP 237 EP 244 DI 10.1016/j.jneumeth.2012.09.002 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 060CG UT WOS:000312753500008 PM 22975472 ER PT J AU Cajigas, I Malik, WQ Brown, EN AF Cajigas, I. Malik, W. Q. Brown, E. N. TI nSTAT: Open-source neural spike train analysis toolbox for Matlab SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Open-source; Point process; Generalized linear models; Neuroscience; Statistics; Data analysis; Signal processing; Spike trains ID FREELY-MOVING RAT; POINT PROCESS FRAMEWORK; TIME-RESCALING THEOREM; HEART-RATE-VARIABILITY; MAXIMUM-LIKELIHOOD; STATISTICAL-MODELS; FIRING SYNCHRONY; PLACE UNITS; HIPPOCAMPAL; RECONSTRUCTION AB Over the last decade there has been a tremendous advance in the analytical tools available to neuro-scientists to understand and model neural function. In particular, the point process - generalized linear model (PP-GLM) framework has been applied successfully to problems ranging from neuro-endocrine physiology to neural decoding. However, the lack of freely distributed software implementations of published PP-GLM algorithms together with problem-specific modifications required for their use, limit wide application of these techniques. In an effort to make existing PP-GLM methods more accessible to the neuroscience community, we have developed nSTAT - an open source neural spike train analysis toolbox for Matlabe (R). By adopting an object-oriented programming (OOP) approach, nSTAT allows users to easily manipulate data by performing operations on objects that have an intuitive connection to the experiment (spike trains, covariates, etc.), rather than by dealing with data in vector/matrix form. The algorithms implemented within nSTAT address a number of common problems including computation of pen-stimulus time histograms, quantification of the temporal response properties of neurons, and characterization of neural plasticity within and across trials. nSTAT provides a starting point for exploratory data analysis, allows for simple and systematic building and testing of point process models, and for decoding of stimulus variables based on point process models of neural function. By providing an open-source toolbox, we hope to establish a platform that can be easily used, modified, and extended by the scientific community to address limitations of current techniques and to extend available techniques to more complex problems. (C) 2012 Elsevier B.V. All rights reserved. C1 [Cajigas, I.; Malik, W. Q.; Brown, E. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Cajigas, I.; Brown, E. N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Cajigas, I.; Malik, W. Q.; Brown, E. N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Cajigas, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM iahn@mit.edu FU NIH [F31NS058275] FX This work was supported by NIH F31NS058275 - "Automated and Adaptive Lower Extremity Neuro-Rehabilitation for Stroke" to Iahn Cajigas. The authors are indebted to Riccardo Barbieri and Simona Temereanca (Harvard Medical School), Marnie Phillips, Laura Lewis, and Demba Ba (MIT), and Gordon Pipa (Max Planck Institute for Brain Research) for providing the data used to make the examples. The authors would like to thank the reviewers for their constructive comments and suggestions for improving the manuscript, and the members of the MIT Neuroscience Statistics Research Lab for their collegial support. NR 74 TC 9 Z9 9 U1 1 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV 15 PY 2012 VL 211 IS 2 BP 245 EP 264 DI 10.1016/j.jneumeth.2012.08.009 PG 20 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 060CG UT WOS:000312753500009 PM 22981419 ER PT J AU Greenwald, JL McDermott, S Dighe, AS AF Greenwald, Jeffrey L. McDermott, Shaunagh Dighe, Anand S. TI Case 35-2012: A 69-Year-Old Chronically Ill Man with Weakness, Anorexia, and Diffuse Pain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RENAL-TRANSPLANTATION; ADRENAL INSUFFICIENCY; DISEASE C1 [Greenwald, Jeffrey L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [McDermott, Shaunagh] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Greenwald, Jeffrey L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dighe, Anand S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [McDermott, Shaunagh] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Greenwald, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU Society of Hospital Medicine FX Dr. Greenwald reports receiving grant support to his institution from the Society of Hospital Medicine. No other potential conflict of interest relevant to this article was reported. NR 10 TC 0 Z9 0 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 NOV 15 PY 2012 VL 367 IS 20 BP 1940 EP 1948 DI 10.1056/NEJMcpc1209437 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 036MB UT WOS:000311029300012 PM 23150962 ER PT J AU Don, C Gupta, PP Witzke, C Kesarwani, M Cubeddu, RJ Inglessis, I Palacios, IF AF Don, Creighton Gupta, Pritha P. Witzke, Christian Kesarwani, Manoj Cubeddu, Roberto J. Inglessis, Ignacio Palacios, Igor F. TI Patients With Small Left Ventricular Size Undergoing Balloon Aortic Valvuloplasty Have Worse Intraprocedural Outcomes SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE aortic valve stenosis; left ventricular hypertrophy; hypertrophic obstructive cardiomyopathy; subaortic stenosis ID ASYMMETRIC SEPTAL HYPERTROPHY; LONG-TERM SURVIVAL; HIGH-RISK PATIENTS; VALVE-REPLACEMENT; ELDERLY-PATIENTS; WALL THICKNESS; STENOSIS; CARDIOMYOPATHY; MORTALITY; DISEASE AB Objectives: To evaluate the impact of left ventricular (LV) chamber size on procedural and hospital outcomes of patients undergoing aortic valvuloplasty. Background: Balloon aortic valvuloplasty (BAV) is used as an integral step during transcatheter aortic valve implantation. Patients with small, thickened ventricles are thought to have more complications during and following BAV. Methods: Retrospective study of consecutive patients with severe, symptomatic calcific aortic stenosis who underwent retrograde BAV at Massachusetts General Hospital. We compared patients with left ventricular end-diastolic diameters (LVEDD) <4.0 cm (n = 31) to those with LVEDD >= 4.0 cm (n = 78). Baseline and procedural characteristics as well as clinical outcomes were compared. Multivariate logistic regression was used for the adjusted analysis. Results: Patients with smaller LV chamber size were mostly women (80.7% vs. 19.4%, P < 0.01) and had a smaller body surface area (BSA), (1.61 +/- 0.20 m(2) vs. 1.79 +/- 0.25 m(2), P < 0.01). Patients with smaller LV chamber size had higher ejection fractions and thicker ventricles. Otherwise, baseline characteristics were similar. The intraprocedural composite of death, cardiopulmonary arrest, intubation, hemodynamic collapse, and tamponade was higher for patients with LVEDD <4.0 cm (32.3% v. 11.5%, P = 0.01). Adjusting for age, gender, BSA, LV pressure, and New York Heart Association class, LVEDD <4.0 cm remained an independent predictor of procedural (OR 5.1, 95% CI 1.4-18.2) and in-hospital complications (OR 3.8, 95% CI 1.2-11.6). Conclusions: Compared to patients undergoing BAV with LVEDD >= 4.0 cm, those with smaller LV chambers had worse procedural and in-hospital outcomes. (C) 2012 Wiley Periodicals, Inc. C1 [Don, Creighton] Univ Washington, Dept Gen Med, Div Cardiol, Med Ctr, Seattle, WA 98195 USA. [Don, Creighton; Witzke, Christian; Cubeddu, Roberto J.; Inglessis, Ignacio; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cubeddu, Roberto J.] Aventura Hosp & Med Ctr, Div Cardiol, Miami, FL USA. RP Don, C (reprint author), Univ Washington, Dept Gen Med, Div Cardiol, Med Ctr, 1959 NE Pacific St,Box 356422, Seattle, WA 98195 USA. EM cwdon@u.washington.edu FU National Center for Research Resources (NCRR) [KL2 RR025015] FX Grant sponsor: National Center for Research Resources (NCRR); grant number: KL2 RR025015 NR 37 TC 4 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 15 PY 2012 VL 80 IS 6 BP 946 EP 954 DI 10.1002/ccd.24287 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 051RL UT WOS:000312144600013 PM 22926957 ER PT J AU Rocha-Singh, KJ Jaff, M Joye, J Laird, J Ansel, G Schneider, P AF Rocha-Singh, Krishna J. Jaff, Michael Joye, James Laird, John Ansel, Gary Schneider, Peter CA VIVA Phys TI Major Adverse Limb Events and Wound Healing Following Infrapopliteal Artery Stent Implantation in Patients with Critical Limb Ischemia: The XCELL Trial SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral vascular disease; critical limb ischemia; infrapopliteal; stents ID CRITICAL LEG ISCHEMIA; INFRAINGUINAL BYPASS; TISSUE LESIONS; ANGIOPLASTY; DISEASE; METAANALYSIS; EXPERIENCE; MANAGEMENT; CALL AB Background: Percutaneous transluminal angioplasty (PTA) with stent deployment of infrapopliteal arteries is an accepted but unproven therapy for patients with critical limb ischemia (CLI). We evaluated the safety and effectiveness of the Xpert (TM) self-expanding nitinol stent (Abbott Vascular, Redwood City, CA) in Rutherford Class 4-6 subjects with infrapopliteal lesions of 4-15 cm in length. Methods and Results: 120 patients (140 limbs, 212 implanted devices) underwent primary infrapopliteal nitinol stent deployment as part of this multicenter registry. The primary endpoint was 12-month amputation-free survival (AFS); secondary endpoints included limb salvage, target lesion revascularization (TLR), 6-month angiographic patency, and 6- and 12-month outcomes of wound healing and pain relief. Despite a 6-month binary stent restenosis rate of 68.5%, the 12-month AFS rate was 78.3%. Stratified according to baseline Rutherford classes 4, 5 and 6, the 12-month AFS rates were 100%, 77.3%, and 55.2%, respectively, and freedom from major amputation rates were 100%, 90.9%, and 70.1%, respectively. The 12-month freedom from major amputation rate and clinically driven TLR were 89.6% and 70.1%, respectively. The 6-and 12-month complete wound-healing rates were 49.0% and 54.4%, respectively. Rutherford class 4 patients had significant pain relief through 12-months (P<0.05). Conclusions: Primary infrapopliteal nitinol stenting to treat CLI is safe and effective in improving 6-and 12-month clinical outcomes. (C) 2012 Wiley Periodicals, Inc. C1 [Rocha-Singh, Krishna J.] St Johns Hosp, Springfield, IL USA. [Jaff, Michael] Massachusetts Gen Hosp, Dept Vasc Med, Boston, MA 02114 USA. [Joye, James] El Camino Hosp, Dept Cardiol, Mountain View, CA USA. [Laird, John] Univ Calif Davis, Dept Cardiololgy, Sacramento, CA 95817 USA. [Ansel, Gary] Riverside Methodist Hosp, Dept Cardiol, Columbus, OH 43214 USA. [Schneider, Peter] Kaiser Permanente Hosp, Dept Vasc Surg, Honolulu, HI USA. RP Rocha-Singh, KJ (reprint author), 317 N 7th St, Springfield, IL 62701 USA. EM ksingh@prairieheart.com FU Abbott Vascular FX Krishna Rocha-Singh: Member, Board of Directors, VIVA Physicians, a 501 (c) 3 not-for-profit physician education and research organization. Michael Jaff: Abbott Vascular: Non-compensated advisor; Member, Board of Directors, VIVA Physicians. James Joye: Abbott Vascular: Consultant, Educational and Research Grant Support; Board of Directors, VIVA Physicians. Gary Ansel: Abbott Vascular Advisory Board; Board of Directors, VIVA Physicians Peter Schneider: Abbott Vascular Advisory Board; Board of Directors, VIVA Physicians John Laird: Abbott Vascular: Consultant; Member, Board of Directors, VIVA Physicians. NR 28 TC 28 Z9 29 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 15 PY 2012 VL 80 IS 6 BP 1042 EP 1051 DI 10.1002/ccd.24485 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 051RL UT WOS:000312144600032 PM 22605682 ER PT J AU Choi, BD Fecci, PE Sampson, JH AF Choi, Bryan D. Fecci, Peter E. Sampson, John H. TI Regulatory T Cells Move in When Gliomas Say "I DO" SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID BRAIN-TUMORS; CTLA-4 BLOCKADE; COMPARTMENT; SURVIVAL; IMMUNITY AB Indoleamine 2,3-dioxygenase (IDO) is an enzyme with known immunosuppressive and tolerogenic effects in cancer. Mounting evidence has associated IDO expression with the induction of regulatory T cells (Treg) and malignant progression. IDO inhibition may therefore provide a promising therapeutic approach for glioblastoma, where the need for novel treatment is great. Clin Cancer Res; 18(22); 6086-8. (C)2012 AACR. C1 [Choi, Bryan D.; Sampson, John H.] Duke Univ, Preston Robert Tisch Brain Tumor Ctr, Duke Brain Tumor Immunotherapy Program, Div Neurosurg,Dept Surg,Med Ctr, Durham, NC 27710 USA. [Fecci, Peter E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Sampson, JH (reprint author), Duke Univ, Preston Robert Tisch Brain Tumor Ctr, Duke Brain Tumor Immunotherapy Program, Div Neurosurg,Dept Surg,Med Ctr, Box 3050, Durham, NC 27710 USA. EM john.sampson@duke.edu FU NIH [5R01-CA135272-04, 5P50-NS020023-29, 3R25-NS065731-03S1]; Pediatric Brain Tumor Foundation; Ben and Catherine Ivy Foundation; Cancer Research Institute FX This work was supported in part by the NIH 5R01-CA135272-04 (to J.H. Sampson), 5P50-NS020023-29 (to D. D. Bigner and J.H. Sampson), 3R25-NS065731-03S1 (to J.H. Sampson), as well as grants from the Pediatric Brain Tumor Foundation (to D. D. Bigner and J.H. Sampson), Ben and Catherine Ivy Foundation (to J.H. Sampson), and Cancer Research Institute (to B. D. Choi). NR 12 TC 8 Z9 8 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2012 VL 18 IS 22 BP 6086 EP 6088 DI 10.1158/1078-0432.CCR-12-2801 PG 3 WC Oncology SC Oncology GA 050AC UT WOS:000312023800002 PM 23052252 ER PT J AU Bogusz, AM Baxter, RHG Currie, T Sinha, P Sohani, AR Kutok, JL Rodig, SJ AF Bogusz, Agata M. Baxter, Richard H. G. Currie, Treeve Sinha, Papiya Sohani, Aliyah R. Kutok, Jeffery L. Rodig, Scott J. TI Quantitative Immunofluorescence Reveals the Signature of Active B-cell Receptor Signaling in Diffuse Large B-cell Lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PROTEIN-TYROSINE KINASES; ANTIGEN-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; FORKHEAD TRANSCRIPTION; BREAST-CANCER; SYK; SURVIVAL; AKT; ACTIVATION AB Purpose: B-cell receptor (BCR)-mediated signaling is important in the pathogenesis of a subset of diffuse large B-cell lymphomas (DLBCL) and the BCR-associated kinases SYK and BTK have recently emerged as potential therapeutic targets. We sought to identify a signature of activated BCR signaling in DLBCL to aid the identification of tumors that may be most likely to respond to BCR-pathway inhibition. Experimental Design: We applied quantitative immunofluorescence (qIF) using antibodies to phosphorylated forms of proximal BCR signaling kinases LYN, SYK, and BTK and antibody to BCR-associated transcription factor FOXO1 on BCR-cross-linked formalin-fixed paraffin-embedded (FFPE) DLBCL cell lines as a model system and on two clinical cohorts of FFPE DLBCL specimens (n = 154). Results: A robust signature of active BCR signaling was identified and validated in BCR-cross-linked DLBCL cell lines and in 71/154 (46%) of the primary DLBCL patient specimens. Further analysis of the primary biopsy samples revealed increased nuclear exclusion of FOXO1 among DLBCL with qIF evidence of active BCR signaling compared with those without (P = 0.004). Nuclear exclusion of FOXO1 was also detected in a subset of DLBCL without evidence of proximal BCR signaling suggesting that alternative mechanisms for PI3K/AKT activation may mediate FOXO1 subcellular localization in these cases. Conclusion: This study establishes the feasibility of detecting BCR activation in primary FFPE biopsy specimens of DLBCL. It lays a foundation for future dissection of signal transduction networks in DLBCL and provides a potential platform for evaluating individual tumors in patients receiving novel therapies targeting the BCR pathway. Clin Cancer Res; 18(22); 6122-35. (C)2012 AACR. C1 [Bogusz, Agata M.; Currie, Treeve; Sinha, Papiya; Kutok, Jeffery L.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Baxter, Richard H. G.] Yale Univ, Dept Chem, New Haven, CT USA. RP Rodig, SJ (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jeff.kutok@infi.com; srodig@partners.org RI Baxter, Richard/F-3027-2013; OI Baxter, Richard/0000-0001-5140-1726 FU NIH under Ruth L. Kirschstein National Research Service Award from the National Heart, Lung and Blood Institute [T32HL007627] FX This research was supported by the NIH under Ruth L. Kirschstein National Research Service Award T32HL007627 from the National Heart, Lung and Blood Institute. NR 55 TC 18 Z9 20 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2012 VL 18 IS 22 BP 6122 EP 6135 DI 10.1158/1078-0432.CCR-12-0397 PG 14 WC Oncology SC Oncology GA 050AC UT WOS:000312023800007 PM 22966017 ER PT J AU Waldron, L Ogino, S Hoshida, Y Shima, K Reed, AEM Simpson, PT Baba, Y Nosho, K Segata, N Vargas, AC Cummings, MC Lakhani, SR Kirkner, GJ Giovannucci, E Quackenbush, J Golub, TR Fuchs, CS Parmigiani, G Huttenhower, C AF Waldron, Levi Ogino, Shuji Hoshida, Yujin Shima, Kaori Reed, Amy E. McCart Simpson, Peter T. Baba, Yoshifumi Nosho, Katsuhiko Segata, Nicola Vargas, Ana Cristina Cummings, Margaret C. Lakhani, Sunil R. Kirkner, Gregory J. Giovannucci, Edward Quackenbush, John Golub, Todd R. Fuchs, Charles S. Parmigiani, Giovanni Huttenhower, Curtis TI Expression Profiling of Archival Tumors for Long-term Health Studies SO CLINICAL CANCER RESEARCH LA English DT Article ID PARAFFIN-EMBEDDED TISSUE; GENE-EXPRESSION; COLORECTAL-CANCER; NURSES HEALTH; COLON-CANCER; MICROARRAYS; SAMPLES; SIGNATURES; FOLATE; WOMEN AB Purpose: More than 20 million archival tissue samples are stored annually in the United States as formalin-fixed, paraffin-embedded (FFPE) blocks, but RNA degradation during fixation and storage has prevented their use for transcriptional profiling. New and highly sensitive assays for whole-transcriptome microarray analysis of FFPE tissues are now available, but resulting data include noise and variability for which previous expression array methods are inadequate. Experimental Design: We present the two largest whole-genome expression studies from FFPE tissues to date, comprising 1,003 colorectal cancer (CRC) and 168 breast cancer samples, combined with a meta-analysis of 14 new and published FFPE microarray datasets. We develop and validate quality control (QC) methods through technical replication, independent samples, comparison to results from fresh-frozen tissue, and recovery of expected associations between gene expression and protein abundance. Results: Archival tissues from large, multicenter studies showed a much wider range of transcriptional data quality relative to smaller or frozen tissue studies and required stringent QC for subsequent analysis. We developed novel methods for such QC of archival tissue expression profiles based on sample dynamic range and per-study median profile. This enabled validated identification of gene signatures of microsatellite instability and additional features of CRC, and improved recovery of associations between gene expression and protein abundance of MLH1, FASN, CDX2, MGMT, and SIRT1 in CRC tumors. Conclusions: These methods for large-scale QC of FFPE expression profiles enable study of the cancer transcriptome in relation to extensive clinicopathological information, tumor molecular biomarkers, and long-term lifestyle and outcome data. Clin Cancer Res; 18(22); 6136-46. (C)2012 AACR. C1 [Waldron, Levi; Segata, Nicola; Parmigiani, Giovanni; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Waldron, Levi; Quackenbush, John; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Ogino, Shuji; Shima, Kaori; Baba, Yoshifumi; Nosho, Katsuhiko; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kirkner, Gregory J.; Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Golub, Todd R.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Hoshida, Yujin] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, Tisch Canc Inst, Div Liver Dis,Dept Med, New York, NY USA. [Reed, Amy E. McCart; Simpson, Peter T.; Vargas, Ana Cristina; Cummings, Margaret C.; Lakhani, Sunil R.] Univ Queensland, UQ Ctr Clin Res, Herston, Qld, Australia. [Lakhani, Sunil R.] Univ Queensland, Sch Med, Herston, Qld, Australia. [Cummings, Margaret C.; Lakhani, Sunil R.] Pathol Queensland Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM chuttenh@hsph.harvard.edu RI cummings, margaret/B-5747-2011; Simpson, Peter/F-1225-2010; OI Simpson, Peter/0000-0002-4816-8289; Waldron, Levi/0000-0003-2725-0694; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794 FU U.S. National Institute of Health (NIH) [P01 CA087969, P01 CA55075, P50 CA127003, R01 CA151993]; National Science Foundation [NSF DBI-1053486]; DFCI Friends; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Wesley Research Institute, Australia; National Breast Cancer Foundation, Australia; Ludwiq Institute of Cancer Research FX This work was supported by U.S. National Institute of Health (NIH) grants P01 CA087969 (to S. E. Hankinson), P01 CA55075 (to W. C. Willett), P50 CA127003 (to C. S. Fuchs), and R01 CA151993 (to S. Ogino), by the National Science Foundation grant NSF DBI-1053486 (to C. Huttenhower), and by grants from DFCI Friends, the Bennett Family Fund, the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance, and the Wesley Research Institute, Australia. P. T. Simpson and A. C. Vargas are recipients of fellowships from the National Breast Cancer Foundation, Australia and the Ludwiq Institute of Cancer Research, respectively. The content is solely the responsibility of the authors and does not represent the official views of any funders. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 11 Z9 11 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2012 VL 18 IS 22 BP 6136 EP 6146 DI 10.1158/1078-0432.CCR-12-1915 PG 11 WC Oncology SC Oncology GA 050AC UT WOS:000312023800008 PM 23136189 ER PT J AU Di Martino, MT Leone, E Amodio, N Foresta, U Lionetti, M Pitari, MR Cantafio, MEG Gulla, A Conforti, F Morelli, E Tomaino, V Rossi, M Negrini, M Ferrarini, M Caraglia, M Shammas, MA Munshi, NC Anderson, KC Neri, A Tagliaferri, P Tassone, P AF Di Martino, Maria T. Leone, Emanuela Amodio, Nicola Foresta, Umberto Lionetti, Marta Pitari, Maria R. Cantafio, Maria E. Gallo Gulla, Annamaria Conforti, Francesco Morelli, Eugenio Tomaino, Vera Rossi, Marco Negrini, Massimo Ferrarini, Manlio Caraglia, Michele Shammas, Masood A. Munshi, Nikhil C. Anderson, Kenneth C. Neri, Antonino Tagliaferri, Pierosandro Tassone, Pierfrancesco TI Synthetic miR-34a Mimics as a Novel Therapeutic Agent for Multiple Myeloma: In Vitro and In Vivo Evidence SO CLINICAL CANCER RESEARCH LA English DT Article ID PLASMA-CELL LEUKEMIA; TUMOR-SUPPRESSOR; GENE-EXPRESSION; MICRORNAS; CANCER; APOPTOSIS; P53; ACTIVATION; TARGETS; MODEL AB Purpose: Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. Experimental Design: Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. Results: Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. Conclusions: Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a-based treatment strategies in MM patients. Clin Cancer Res; 18(22); 6260-70. (C)2012 AACR. C1 [Di Martino, Maria T.; Leone, Emanuela; Amodio, Nicola; Foresta, Umberto; Pitari, Maria R.; Cantafio, Maria E. Gallo; Gulla, Annamaria; Morelli, Eugenio; Tomaino, Vera; Rossi, Marco; Tagliaferri, Pierosandro; Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. [Conforti, Francesco] Magna Graecia Univ Catanzaro, Pathol Unit, I-88100 Catanzaro, Italy. [Lionetti, Marta; Neri, Antonino] Univ Milan, Dept Med Sci, IRCCS Policlin Fdn, Milan, Italy. [Negrini, Massimo] Univ Ferrara, Dept Expt & Diagnost Med, Interdept Ctr Canc Res, I-44100 Ferrara, Italy. [Ferrarini, Manlio] Univ Genoa, Div Med Oncol C, Ist Nazl Ric Canc, Genoa, Italy. [Ferrarini, Manlio] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Caraglia, Michele] Univ Naples 2, Dept Biochem & Biophys, Naples, Italy. [Shammas, Masood A.; Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Shammas, Masood A.; Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, Boston, MA USA. [Tassone, Pierfrancesco] Temple Univ, Coll Sci & Technol, Philadelphia, PA 19122 USA. RP Tassone, P (reprint author), Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Viale Europa, I-88100 Catanzaro, Italy. EM tassone@unicz.it RI Negrini, Massimo/J-2377-2016; Caraglia, Michele/N-5670-2015; Amodio, Nicola/K-7335-2016; OI Negrini, Massimo/0000-0002-0007-1920; Caraglia, Michele/0000-0003-2408-6091; Amodio, Nicola/0000-0002-1345-4410; neri, antonino/0000-0001-9047-5912; Ferrarini, Manlio/0000-0002-6154-2570; ROSSI, Marco/0000-0002-7258-475X FU Italian Association for Cancer Research (AIRC) [9980] FX This work has been supported by funds of Italian Association for Cancer Research (AIRC), PI: PT. "Special Program Molecular Clinical Oncology-5 per mille" n. 9980, 2010/15. NR 52 TC 82 Z9 82 U1 3 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2012 VL 18 IS 22 BP 6260 EP 6270 DI 10.1158/1078-0432.CCR-12-1708 PG 11 WC Oncology SC Oncology GA 050AC UT WOS:000312023800020 PM 23035210 ER PT J AU Baselga, J Mita, AC Schoffski, P Dumez, H Rojo, F Tabernero, J DiLea, C Mietlowski, W Low, C Huang, J Dugan, M Parker, K Walk, E van Oosterom, A Martinelli, E Takimoto, CH AF Baselga, Jose Mita, Alain C. Schoffski, Patrick Dumez, Herlinde Rojo, Frederico Tabernero, Josep DiLea, Clifford Mietlowski, William Low, Christie Huang, Jerry Dugan, Margaret Parker, Kathryn Walk, Eric van Oosterom, Allan Martinelli, Erika Takimoto, Chris H. TI Using Pharmacokinetic and Pharmacodynamic Data in Early Decision Making Regarding Drug Development: A Phase I Clinical Trial Evaluating Tyrosine Kinase Inhibitor, AEE788 SO CLINICAL CANCER RESEARCH LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; ADVANCED SOLID TUMORS; FACTOR RECEPTOR; MONOCLONAL-ANTIBODY; CANCER; ANGIOGENESIS; ANTAGONISTS; BIOMARKERS; CARCINOMA; ONCOLOGY AB Purpose: In this first-in-human study of AEE788, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), HER-2, and VEGFR-2, a comprehensive pharmacodynamic program was implemented in addition to the evaluation of safety, pharmacokinetics, and preliminary efficacy of AEE788 in cancer patients. Experimental design: Patients with advanced, solid tumors received escalating doses of oral AEE788 once daily. Primary endpoints were to determine dose-limiting toxicities (DLTs) and maximum-tolerated dose (MTD). A nonlinear model (Emax model) was used to describe the relationship between AEE788 exposure and target-pathway modulation in skin and tumor tissues. Results: Overall, 111 patients were treated (25 to 550 mg/day). DLTs included rash and diarrhea; MTD was 450 mg/day. Effects on biomarkers correlated to serum AEE788 concentrations. The concentration at 50% inhibition (IC50) for EGFR in skin (0.033 mmol/L) and tumor (0.0125 mmol/L) were similar to IC50 in vitro suggesting skin may be surrogate tissue for estimating tumor EGFR inhibition. No inhibition of p-MAPK and Ki67 was observed in skin vessels at <= MTD. Hence, AEE788 inhibited EGFR, but not VEGFR, at doses <= MTD. A total of 16 of 96 evaluable patients showed a >10% shrinkage of tumor size; one partial response was observed. Conclusion: Our pharmacodynamic-based study showed effective inhibition of EGFR, but not of VEGFR at tolerable AEE788 doses. Emax modeling integrated with biomarker data effectively guided real-time decision making in the early development of AEE788. Despite clinical activity, target inhibition of only EGFR led to discontinuation of further AEE788 development. Clin Cancer Res; 18(22); 6364-72. (C) 2012 AACR. C1 [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Mita, Alain C.; Takimoto, Chris H.] Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA. [Schoffski, Patrick; Dumez, Herlinde; van Oosterom, Allan] Catholic Univ Louvain, Leuven Canc Inst, Univ Hosp Leuven, B-3000 Louvain, Belgium. [Rojo, Frederico; Tabernero, Josep] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, E-08193 Barcelona, Spain. [DiLea, Clifford; Mietlowski, William; Low, Christie; Huang, Jerry; Dugan, Margaret; Parker, Kathryn] Novartis Pharmaceut, E Hanover, NJ USA. [Walk, Eric] Ventana Med Syst Inc, Tucson, AZ USA. [Martinelli, Erika] Univ Naples 2, Naples, Italy. RP Baselga, J (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM baselgaj@mskcc.org RI Rojo, Federico/S-6551-2016; OI Erika, Martinelli/0000-0002-0291-475X FU Novartis Pharmaceuticals Corporation FX J. Baselga and P. Schoffski are consultants/members of an advisory board for Novartis Pharmaceuticals Corporation; P. Schoffski and C. H. Takimoto received research grants/support from Novartis Pharmaceuticals Corporation; P. Schoffski received honoraria for speakers bureau from Novartis Pharmaceuticals Corporation; W. Mietlowski, M. Dugan, and J. Huang have ownership interest in and are employees of Novartis Pharmaceuticals Corporation; C. Low and K. Parker are employees of Novartis Pharmaceuticals Corporation; H. Dumez, E. Martinelli, A. C. Mita, J. Tabernero, A. van Oosterom, and E. Walk have nothing to disclose. NR 23 TC 9 Z9 10 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2012 VL 18 IS 22 BP 6364 EP 6372 DI 10.1158/1078-0432.CCR-12-1499 PG 9 WC Oncology SC Oncology GA 050AC UT WOS:000312023800030 PM 23014528 ER PT J AU Bates, DO Catalano, PJ Symonds, KE Varey, AHR Ramani, P O'Dwyer, PJ Giantonio, BJ Meropol, NJ Benson, AB Harper, SJ AF Bates, David O. Catalano, Paul J. Symonds, Kirsty E. Varey, Alex H. R. Ramani, Pramila O'Dwyer, Peter J. Giantonio, Bruce J. Meropol, Neal J. Benson, Al Bowen Harper, Steven J. TI Association between VEGF Splice Isoforms and Progression-Free Survival in Metastatic Colorectal Cancer Patients Treated with Bevacizumab SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER; VEGF(165)B; EXPRESSION; BIOMARKERS; THERAPY; VARIANT; MICE; NEOVASCULARIZATION; FLUOROURACIL AB Purpose: Bevacizumab improves survival for patients with metastatic colorectal cancer with chemotherapy, but no proven predictive markers exist. The VEGF-A splice form, VEGF(165)b, anti-angiogenic in animal models, binds bevacizumab. We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF(165b) levels treated with bevacizumab. Experimental Design: Blinded tumor samples from the phase III trial of FOLFOX4 +/- bevacizumab were assessed for VEGF(165)b and VEGF(total) by immunohistochemistry and scored relative to normal tissue. A predictive index (PI) was derived from the ratio of VEGF(165b):VEGF(total) for 44 samples from patients treated with FOLFOX + bevacizumab (arm A) and 53 samples from patients treated with FOLFOX4 (arm B), and PFS, and overall survival (OS) analyzed on the basis of PI relative to median ratio. Results: Unadjusted analysis of PFS showed significantly better outcome for individuals with VEGF(165b):VEGFtotal ratio scores below median treated with FOLFOX4 + bevacizumab compared with FOLFOX4 alone (median, 8.0 vs. 5.2 months; P < 0.02), but no effect of bevacizumab on PFS in patients with VEGF(165b): VEGF(total) ratio >median (5.9 vs. 6.3 months). These findings held after adjustment for other clinical and demographic features. OS was increased in arm A (median, 13.6 months) compared with arm B (10.6 months) in the low VEGF(165b) group, but this did not reach statistical significance. There was no difference in the high VEGF(165b): VEGF(total) group between FOLFOX + bevacizumab (10.8 months) and FOLFOX alone (11.3months). Conclusion: Low VEGF(165b): VEGF(total) ratio may be a predictive marker for bevacizumab in metastatic colorectal cancer, and individuals with high relative levels may not benefit. Clin Cancer Res; 18(22); 6384-91. (C) 2012 AACR. C1 [Bates, David O.] Univ Bristol, Microvasc Res Labs, Bristol Heart Inst, Dept Physiol & Pharmacol,Sch Vet Sci, Bristol BS2 8EJ, Avon, England. [Ramani, Pramila] Bristol Royal Infirm & Gen Hosp, Dept Pathol, Bristol, Avon, England. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Dwyer, Peter J.; Giantonio, Bruce J.] Univ Penn, Philadelphia, PA 19104 USA. [Meropol, Neal J.] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Benson, Al Bowen] Northwestern Univ, Chicago, IL 60611 USA. RP Bates, DO (reprint author), Univ Bristol, Microvasc Res Labs, Bristol Heart Inst, Dept Physiol & Pharmacol,Sch Vet Sci, Southwell St, Bristol BS2 8EJ, Avon, England. EM Dave.Bates@bristol.ac.uk RI Varey, Alex/A-8349-2013; OI Varey, Alex/0000-0001-8705-3321; Bates, David/0000-0003-4850-2360 FU Genentech; Precision Therapeutics; Cancer Research UK [CF11392/A8451]; Association for International Cancer Research [07-0605]; Public Health Service [CA23318, CA66636, CA21115, CA15488, CA27525, CA17145 CA139003-01]; National Cancer Institute, NIH; Department of Health and Human Services; Richard Bright VEGF Research Trust; North Bristol Cancer Research Fund FX This work is original and has not previously been published. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. B.J. Giantonio has received honoraria from Roche and Genentech, ABB research funding and consultancy from Genentech. P.J. O'Dwyer has received research support from Genentech. N.J. Meropol received consulting fees from Precision Therapeutics. D.O. Bates and S.J. Harper are inventors on the patent describing VEGF165b and use of antibodies, including as biomarkers. No potential conflicts of interest were disclosed by the other authors.; This study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D.) and supported in part by Cancer Research UK CF11392/A8451, Association for International Cancer Research (07-0605), Public Health Service grants CA23318, CA66636, CA21115, CA15488, CA27525, CA17145 CA139003-01, and from the National Cancer Institute, NIH, and the Department of Health and Human Services, and Richard Bright VEGF Research Trust and North Bristol Cancer Research Fund. NR 24 TC 30 Z9 31 U1 0 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2012 VL 18 IS 22 BP 6384 EP 6391 DI 10.1158/1078-0432.CCR-12-2223 PG 8 WC Oncology SC Oncology GA 050AC UT WOS:000312023800032 PM 23104894 ER PT J AU Sharma, S Dubinett, S Salgia, R AF Sharma, Sherven Dubinett, Steven Salgia, Ravi TI CD14(+)S100A9(+) Myeloid-derived Suppressor Cells Portend Decreased Survival in Patients with Advanced Lung Cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 [Sharma, Sherven; Dubinett, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Los Angeles, CA 90095 USA. [Sharma, Sherven; Dubinett, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Med Lab, Los Angeles, CA USA. [Sharma, Sherven; Dubinett, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Salgia, Ravi] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Los Angeles, CA 90095 USA. FU NCATS NIH HHS [UL1 TR000124] NR 5 TC 2 Z9 3 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2012 VL 186 IS 10 BP 940 EP 941 DI 10.1164/rccm.201209-1597ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 046LI UT WOS:000311766100005 PM 23155211 ER PT J AU Seddon, JA Furin, JJ Gale, M Barrientos, HD Hurtado, RM Amanullah, F Ford, N Starke, JR Schaaf, HS AF Seddon, James A. Furin, Jennifer J. Gale, Marianne Del Castillo Barrientos, Hernan Hurtado, Rocio M. Amanullah, Farhana Ford, Nathan Starke, Jeffrey R. Schaaf, H. Simon CA Sentinel Project Pediat Drug-Resis TI Caring for Children with Drug-Resistant Tuberculosis Practice-based Recommendations SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE pediatrics; child; drug resistance ID HUMAN-IMMUNODEFICIENCY-VIRUS; 2ND-LINE ANTITUBERCULOSIS DRUGS; WESTERN CAPE PROVINCE; HIV-INFECTED CHILDREN; RURAL SOUTH-AFRICA; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; ISONIAZID-RESISTANT; CHILDHOOD TUBERCULOSIS; CLINICAL-FEATURES AB The management of children with drug-resistant tuberculosis (DR-TB) is challenging, and it is likely that in many places, the roll-out of molecular diagnostic testing will lead to more children being diagnosed. There is a limited evidence base to guide optimal treatment and follow-up in the pediatric population; in existing DR-TB guidelines, the care of children is often relegated to small "special populations" sections. This article seeks to address this gap by providing clinicians with practical advice and guidance. This is achieved through review of the available literature on pediatric DR-TB, including research studies and international guidelines, combined with consensus opinion from a team of experts who have extensive experience in the care of children with DR-TB in a wide variety of contexts and with varying resources. The review covers treatment initiation, regimen design and treatment duration, management of comorbid conditions, treatment monitoring, adverse events, adherence promotion, and infection control, all within a multidisciplinary environment. C1 [Seddon, James A.] Univ London London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Clin Res, London WC1E 7HT, England. [Furin, Jennifer J.] Case Western Reserve Univ, Sch Med, Div Infect Dis, TB Res Unit, Cleveland, OH 44106 USA. [Gale, Marianne] Med Sans Frontieres, Sydney, NSW, Australia. [Del Castillo Barrientos, Hernan] Inst Nacl Salud Nino, Serv Neumol, Lima, Peru. [Del Castillo Barrientos, Hernan] Union Nacl TB, Lima, Peru. [Hurtado, Rocio M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hurtado, Rocio M.] Global Hlth Comm, Boston, MA USA. [Hurtado, Rocio M.] Harvard Univ, Sch Med, Boston, MA USA. [Amanullah, Farhana] Indus Hosp, Karachi, Pakistan. [Ford, Nathan] Med Sans Frontieres, Geneva, Switzerland. [Starke, Jeffrey R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Schaaf, H. Simon] Tygerberg Childrens Hosp, Cape Town, South Africa. [Seddon, James A.; Schaaf, H. Simon] Univ Stellenbosch, Fac Med & Hlth Sci, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Cape Town, South Africa. RP Seddon, JA (reprint author), Univ Stellenbosch, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Fac Med & Hlth Sci, Clin Bldg,Room 0085,POB 19063, ZA-7505 Tygerberg, South Africa. EM jseddon@sun.ac.za OI Seddon, James/0000-0002-2296-2302 FU TREAT TB, USAID [GHN-A-00-08-00004-00]; Sir Halley Steward Trust; South African Medical Research Council; National Research Foundation of South Africa FX This work was supported by grant GHN-A-00-08-00004-00 from TREAT TB, USAID (J.A.S. and H.S.S.), the Sir Halley Steward Trust (J.A.S.), the South African Medical Research Council (H.S.S.), and the National Research Foundation of South Africa (H.S.S.). NR 121 TC 33 Z9 33 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2012 VL 186 IS 10 BP 953 EP 964 DI 10.1164/rccm.201206-1001CI PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 046LI UT WOS:000311766100010 PM 22983960 ER PT J AU Wu, CJ AF Wu, Catherine J. TI CLL clonal heterogeneity: an ecology of competing subpopulations SO BLOOD LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; EVOLUTION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2012 VL 120 IS 20 BP 4117 EP 4118 DI 10.1182/blood-2012-09-452805 PG 2 WC Hematology SC Hematology GA 044QN UT WOS:000311637400001 PM 23160186 ER PT J AU Bacher, U Klyuchnikov, E Le-Rademacher, J Carreras, J Armand, P Bishop, MR Bredeson, CN Cairo, MS Fenske, TS Freytes, CO Gale, RP Gibson, J Isola, LM Inwards, DJ Laport, GG Lazarus, HM Maziarz, RT Wiernik, PH Schouten, HC Slavin, S Smith, SM Vose, JM Waller, EK Hari, PN AF Bacher, Ulrike Klyuchnikov, Evgeny Le-Rademacher, Jennifer Carreras, Jeanette Armand, Philippe Bishop, Michael R. Bredeson, Christopher N. Cairo, Mitchell S. Fenske, Timothy S. Freytes, Cesar O. Gale, Robert Peter Gibson, John Isola, Luis M. Inwards, David J. Laport, Ginna G. Lazarus, Hillard M. Maziarz, Richard T. Wiernik, Peter H. Schouten, Harry C. Slavin, Shimon Smith, Sonali M. Vose, Julie M. Waller, Edmund K. Hari, Parameswaran N. CA CIBMTR Lymphoma Working Comm TI Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity? SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; BONE-MARROW-TRANSPLANTATION; ALLOGENEIC TRANSPLANTATION; MALIGNANT-LYMPHOMA; AGGRESSIVE LYMPHOMA; HOST-DISEASE; CHEMOTHERAPY; RITUXIMAB; GRAFT; SURVIVAL AB The best conditioning regimen before allogeneic transplantation for high-risk diffuse large B-cell lymphoma (DLBCL) remains to be clarified. We analyzed data from 396 recipients of allotransplants for DLBCL receiving myeloablative (MAC; n = 165), reduced intensity (RIC; n = 143), or nonmyeloablative conditioning (NMAC; n = 88) regimens. Acute and chronic GVHD rates were similar across the groups. Five-year nonrelapse mortality (NRM) was higher in MAC than RIC and NMAC (56% vs 47% vs 36%; P = .007). Five-year relapse/progression was lower in MAC than in RIC/NMAC (26% vs 38% vs 40%; P = .031). Five-year progression-free survival (15%-25%) and overall survival (18%-26%) did not differ significantly between the cohorts. In multivariate analysis, NMAC and more recent transplant year were associated with lower NRM, whereas a lower Karnofsky performance score (< 90), prior relapse resistant to therapy, and use of unrelated donors were associated with higher NRM. NMAC transplants, no prior use of rituximab, and prior relapse resistant to therapy were associated with a greater risk of relapse/progression. In conclusion, allotransplantation with RIC or NMAC induces long-term progressionfree survival in selected DLBCL patients with a lower risk of NRM but with higher risk of lymphoma progression or relapse. (Blood. 2012; 120(20): 4256-4262) C1 [Bacher, Ulrike; Klyuchnikov, Evgeny] Univ Hamburg, Dept Stem Cell Transplantat, D-20246 Hamburg, Germany. [Bacher, Ulrike] MLL Munich Leukemia Lab, Munich, Germany. [Le-Rademacher, Jennifer; Carreras, Jeanette; Hari, Parameswaran N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bredeson, Christopher N.] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada. [Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [Fenske, Timothy S.] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USA. [Freytes, Cesar O.] S Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, London, England. [Gibson, John] Royal Prince Alfred Hosp, Inst Haematol, Camperdown, NSW 2050, Australia. [Isola, Luis M.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Inwards, David J.] Mayo Clin, Rochester, MN USA. [Laport, Ginna G.] Stanford Hosp & Clin, Stanford, CA USA. [Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wiernik, Peter H.] New York Med Coll, Bronx, NY USA. [Schouten, Harry C.] Acad Ziekenhuis, Maastricht, Netherlands. [Slavin, Shimon] Int Ctr Cell Therapy & Canc Immunotherapy, Tel Aviv, Israel. [Smith, Sonali M.] Univ Chicago Hosp, Chicago, IL 60637 USA. [Vose, Julie M.] Nebraska Med Ctr, Omaha, NE USA. [Waller, Edmund K.] Emory Univ Hosp, Atlanta, GA 30322 USA. RP Bacher, U (reprint author), Univ Hamburg, Dept Stem Cell Transplantat, Martinistr 52, D-20246 Hamburg, Germany. EM u.bacher@uke.de OI Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute [5U01HL069294]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases [U24-CA76518]; NHLBI; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos Inc; Amgen Inc; Angioblast FX The CIBMTR is supported by the National Cancer Institute, the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (Public Health Service Grant/Cooperative Agreement U24-CA76518); NHLBI and National Cancer Institute (Grant/Cooperative Agreement 5U01HL069294); Health Resources and Services Administration (contract HHSH234200637015C); the Office of Naval Research (grants N00014-06-1-0704 and N00014-08-1-0058); and the following: Allos Inc; Amgen Inc; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America Inc; Gamida Cell Teva Joint Venture Ltd; Genentech Inc; Genzyme Corporation; GlaxoSmithKline; HistoGenetics Inc; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Merck & Co Inc; Millennium: Takeda Oncology Co; Milliman USA Inc; Miltenyi Biotec Inc; National Marrow Donor Program; Optum Healthcare Solutions Inc; Osiris Therapeutics Inc; Otsuka America Pharmaceutical Inc; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix Inc; StemCyte, A Global Cord Blood Therapeutics Co; Stemsoft Software Inc; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience Inc; THERAKOS Inc; and Wellpoint Inc. NR 27 TC 38 Z9 41 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2012 VL 120 IS 20 BP 4256 EP 4262 DI 10.1182/blood-2012-06-436725 PG 7 WC Hematology SC Hematology GA 044QN UT WOS:000311637400022 PM 23007405 ER PT J AU Kumar, ATN AF Kumar, Anand T. N. TI Direct Monte Carlo computation of time-resolved fluorescence in heterogeneous turbid media SO OPTICS LETTERS LA English DT Article ID PHOTON MIGRATION; TISSUES; TOMOGRAPHY; SIMULATION AB We show that a multiexponential model for time-resolved fluorescence allows the use of an absorption-perturbation Monte Carlo (MC) approach based on stored photon path histories. This enables the rapid fitting of fluorescence yield, lifetimes, and background tissue absorptions in complex heterogeneous media within a few seconds, without the need for temporal convolutions or MC recalculation of photon path lengths. We validate this method using simulations with both a slab and a heterogeneous model of the mouse head. (C) 2012 Optical Society of America C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu FU National Institutes of Health [R01 EB015325] FX This work was supported by the National Institutes of Health grant R01 EB015325. NR 12 TC 6 Z9 6 U1 1 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD NOV 15 PY 2012 VL 37 IS 22 BP 4783 EP 4785 PG 3 WC Optics SC Optics GA 038JA UT WOS:000311169800073 PM 23164912 ER PT J AU Woodard, LE Li, XH Malani, N Kaja, A Hice, RH Atkinson, PW Bushman, FD Craig, NL Wilson, MH AF Woodard, Lauren E. Li, Xianghong Malani, Nirav Kaja, Aparna Hice, Robert H. Atkinson, Peter W. Bushman, Frederic D. Craig, Nancy L. Wilson, Matthew H. TI Comparative Analysis of the Recently Discovered hAT Transposon TcBuster in Human Cells SO PLOS ONE LA English DT Article ID INTEGRATION SITE SELECTION; CANCER GENE DISCOVERY; SLEEPING-BEAUTY; IN-VIVO; ELEMENT; GENOME; DNA; MUTAGENESIS; DROSOPHILA; THERAPY AB Background: Transposons are useful tools for creating transgenic organisms, insertional mutagenesis, and genome engineering. TcBuster, a novel hAT-family transposon system derived from the red flour beetle Tribolium castaneum, was shown to be highly active in previous studies in insect embryoes. Methodology/Principal Findings: We tested TcBuster for its activity in human embryonic kidney 293 (HEK-293) cells. Excision footprints obtained from HEK-293 cells contained small insertions and deletions consistent with a hAT-type repair mechanism of hairpin formation and non-homologous end-joining. Genome-wide analysis of 23,417 piggyBac, 30,303 Sleeping Beauty, and 27,985 TcBuster integrations in HEK-293 cells revealed a uniquely different integration pattern when compared to other transposon systems with regards to genomic elements. TcBuster experimental conditions were optimized to assay TcBuster activity in HEK-293 cells by colony assay selection for a neomycin-containing transposon. Increasing transposon plasmid increased the number of colonies, whereas gene transfer activity dependent on codon-optimized transposase plasmid peaked at 100 ng with decreased colonies at the highest doses of transposase DNA. Expression of the related human proteins Buster1, Buster3, and SCAND3 in HEK-293 cells did not result in genomic integration of the TcBuster transposon. TcBuster, Tol2, and piggyBac were compared directly at different ratios of transposon to transposase and found to be approximately comparable while having their own ratio preferences. Conclusions/Significance: TcBuster was found to be highly active in mammalian HEK-293 cells and represents a promising tool for mammalian genome engineering. C1 [Woodard, Lauren E.; Kaja, Aparna; Wilson, Matthew H.] Baylor Coll Med, Dept Med, Div Nephrol, Houston, TX 77030 USA. [Hice, Robert H.; Atkinson, Peter W.] Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA. [Hice, Robert H.; Atkinson, Peter W.] Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA. [Li, Xianghong; Craig, Nancy L.] Johns Hopkins Sch Med, Dept Mol Biol & Genet, Howard Hughes Med Inst, Baltimore, MD USA. [Malani, Nirav; Bushman, Frederic D.] Univ Penn, Dept Microbiol, Perlman Sch Med, Philadelphia, PA 19104 USA. [Wilson, Matthew H.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. RP Wilson, MH (reprint author), Baylor Coll Med, Dept Med, Div Nephrol, Houston, TX 77030 USA. EM mhwilson@bcm.edu RI Wilson, Matthew/K-3193-2013; OI Bushman, Frederic/0000-0003-4740-4056 FU Department of Veteran's Affairs; National Institutes of Health [AI45741, GM76425, AI52845, 5T32DK062706, R01 DK093660] FX This work was supported by a grant from the Department of Veteran's Affairs [MHW] and by grants from the National Institutes of Health [AI45741 to PWA and NLC, GM76425 to NLC, AI52845 to FDB, and 5T32DK062706 to LEW]. NLC is an Investigator of the Howard Hughes Medical Institute. This work was supported in part by National Institutes of Health R01 DK093660 to MHW and the generous support of Dr. and Mrs. Harold M. Selzman. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 13 Z9 14 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 NOV 15 PY 2012 VL 7 IS 11 AR e42666 DI 10.1371/journal.pone.0042666 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 039UP UT WOS:000311272300001 PM 23166581 ER PT J AU Price, RL Bingmer, K Harkins, L Iwenofu, OH Kwon, CH Cook, C Pelloski, C Chiocca, EA AF Price, Richard L. Bingmer, Katherine Harkins, Lualhati Iwenofu, O. Hans Kwon, Chang-Hyuk Cook, Charles Pelloski, Christopher Chiocca, E. Antonio TI Cytomegalovirus Infection Leads to Pleomorphic Rhabdomyosarcomas in Trp53(+/-) Mice SO CANCER RESEARCH LA English DT Article ID SOFT-TISSUE SARCOMA; CELLS; GENE AB Cytomegalovirus (CMV) has been detected in several human cancers, but it has not proven to be oncogenic. However, recent studies have suggested mechanisms through which cytomegalovirus may modulate the tumor environment, encouraging its study as a positive modifier of tumorigenesis. In this study, we investigated the effects of cytomegalovirus infection in Trp53 heterozygous mice. Animals were infected with murine cytomegalovirus (MCMV) after birth at 2 days (P2) or 4 weeks of age and then monitored for tumor formation. Mice injected at 2 days of age developed tumors at a high frequency (43%) by 9 months of age. In contrast, only 3% of mock-infected or mice infected at 4 weeks developed tumors. The majority of tumors from P2 MCMV-infected mice were pleomorphic rhabdomyosarcomas (RMS) harboring MCMV DNA, RNA, and protein. An examination of clinical cases revealed that human RMS (embryonal, alveolar, and pleomorphic) harbored human cytomegalovirus IE1 and pp65 protein as well as viral RNA. Taken together, our findings offer support for the hypothesis that cytomegalovirus contributes to the development of pleomorphic RMS in the context of Trp53 mutation, a situation that occurs with high frequency in human RMS. Cancer Res; 72(22); 5669-74. (C) 2012 AACR. C1 [Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurol Surg, Boston, MA 02116 USA. [Chiocca, E. Antonio] Dana Farber Canc Inst, Boston, MA 02116 USA. [Price, Richard L.; Bingmer, Katherine; Kwon, Chang-Hyuk; Chiocca, E. Antonio] Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Neurooncol Ctr, Columbus, OH 43210 USA. [Kwon, Chang-Hyuk] Ohio State Univ, Med Ctr, James Comprehens Canc Ctr, Solid Tumor Program, Columbus, OH 43210 USA. [Iwenofu, O. Hans] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Cook, Charles] Ohio State Univ, Med Ctr, Dept Surg, Columbus, OH 43210 USA. [Pelloski, Christopher] Ohio State Univ, Med Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA. [Harkins, Lualhati] Univ Alabama Birmingham, Dept Med Hematol Oncol, Birmingham, AL USA. RP Chiocca, EA (reprint author), Brigham & Womens Hosp, Dept Neurol Surg, Boston, MA 02116 USA. EM EAChiocca@Partners.org RI Iwenofu, Obiajulu/E-3293-2011; Cook, Charles/D-5574-2009; Kwon, Chang-hyuk/E-3450-2011 OI Cook, Charles/0000-0003-4446-3616; FU American Medical Association Foundation; Viral Oncology Program Grant; Dardinger Neuro-oncology Fund; Jeffrey Thomas Hayden Foundation; OSU MBCG Program grant; OSU CCC Start-up Fund FX R.L. Price was funded by a seed grant from the American Medical Association Foundation. This study was funded by a Viral Oncology Program Grant, the Dardinger Neuro-oncology Fund, the Jeffrey Thomas Hayden Foundation (E.A. Chiocca), OSU MBCG Program grant (E.A. Chiocca and C.-H. Kwon), and OSU CCC Start-up Fund (C.-H. Kwon). NR 18 TC 13 Z9 13 U1 0 U2 2 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 NOV 15 PY 2012 VL 72 IS 22 BP 5669 EP 5674 DI 10.1158/0008-5472.CAN-12-2425 PG 6 WC Oncology SC Oncology GA 037YB UT WOS:000311141300004 PM 23002204 ER PT J AU Goldberg, I Auriel, E Russell, D Korczyn, AD AF Goldberg, I. Auriel, E. Russell, D. Korczyn, A. D. TI Microembolism, silent brain infarcts and dementia SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Dementia; Cardiovascular risk factors; Silent cerebral infarction; Cerebral microemboli; Atrial fibrillation; Leukoaraiosis; Doppler ultrasound ID WHITE-MATTER LESIONS; ATRIAL-FIBRILLATION; CEREBRAL MICROEMBOLI; HIPPOCAMPAL ATROPHY; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; EMBOLIC SIGNALS; DOPPLER; RISK; IMPAIRMENT AB Cognitive decline becomes more prevalent than ever in parallel with the increasing life expectancy of the population. Alzheimer' disease (AD) and cerebral vascular lesions are common in the elderly and represent, with increased age, the most frequent contributors to cognitive decline. It is now believed that these pathologies frequently coexist in the same brain. The border discriminating vascular dementia from AD is blurred and challenges our understanding of these clinical entities. Further research, at both basic and clinical levels, is mandatory in order to better understand the interactions of vascular ischemic injury and primary degenerative physiopathologies of the brain, in order to prevent and better manage patients with cognitive decline. We review recent published clinical evidence of silent brain ischemia as a contributor to cognitive decline and dementia. Microemboli, from both cardiac and vascular origins, have been shown to be associated with structural changes in the brain. The role of transcranial Doppler as an objective tool for detecting and quantifying microemboli is discussed in light of recent clinical evidence. (C) 2012 Elsevier B.V. All rights reserved. C1 [Goldberg, I.] Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Med Neurobiol, Dept Neurol, IL-91905 Jerusalem, Israel. [Goldberg, I.] Hebrew Univ Jerusalem, Fac Med, IL-91905 Jerusalem, Israel. [Auriel, E.] Harvard Univ, Sch Med, Boston, MA USA. [Auriel, E.] Massachusetts Gen Hosp, Dept Neurol, Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Russell, D.] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Neurol, N-0316 Oslo, Norway. [Korczyn, A. D.] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel. RP Goldberg, I (reprint author), Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Med Neurobiol, Dept Neurol, IL-91905 Jerusalem, Israel. EM ilan.goldberg@gmail.com RI Korczyn, Amos/C-3461-2017 OI Korczyn, Amos/0000-0003-0125-2579 NR 26 TC 15 Z9 15 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2012 VL 322 IS 1-2 SI SI BP 250 EP 253 DI 10.1016/j.jns.2012.02.021 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 033RV UT WOS:000310819500051 PM 22429666 ER PT J AU McEllistrem, MC Nahm, MH AF McEllistrem, M. Catherine Nahm, Moon H. TI Novel Pneumococcal Serotypes 6C and 6D: Anomaly or Harbinger SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID STREPTOCOCCUS-PNEUMONIAE SEROTYPE; CONJUGATE VACCINE; UNITED-STATES; NASOPHARYNGEAL CARRIAGE; INVASIVE DISEASE; SEROLOGICAL CHARACTERIZATION; MOLECULAR EPIDEMIOLOGY; QUELLUNG REACTION; SOUTH-KOREA; 1ST REPORT AB Clinical use of the 7-valent pneumococcal protein conjugate (PCV7) vaccine, which includes serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, dramatically reduced invasive pneumococcal disease (IPD); however, the effectiveness was diminished due to serotype shift. Although shift due to known serotypes was anticipated, shift by misidentified serotypes was unexpected. We describe the experience with newly recognized serotypes 6C and 6D, which were mistyped as serotypes 6A and 6B, respectively. Although serotype 6D caused only occasional infections, IPD due to serotype 6C disease expanded in the PCV7 era. Subsequent studies showed that PCV7 provided cross-protection against serotype 6A but not serotype 6C. The 13-valent pneumococcal protein conjugate (PCV13) vaccine, which includes PCV7 serotypes plus serotypes 1, 3, 5, 6A, 7F, 19A, may provide protection against IPD due to serotypes 6C and 6D. Regardless, this narrative illustrates the potential impact of unrecognized serotypes on the efficacy of a serotype-specific vaccine. C1 [McEllistrem, M. Catherine] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Nahm, Moon H.] Univ Alabama Birmingham, Birmingham, AL USA. RP McEllistrem, MC (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Univ Dr C,MS 130-U, Pittsburgh, PA 15240 USA. EM mary.mcellistrem@va.gov OI Nahm, Moon/0000-0002-6922-1042 FU NIH [AI-31473] FX This work was supported by an NIH grant AI-31473. NR 60 TC 14 Z9 14 U1 0 U2 2 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 NOV 15 PY 2012 VL 55 IS 10 BP 1379 EP 1386 DI 10.1093/cid/cis691 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 027SV UT WOS:000310374600020 PM 22903767 ER PT J AU Darouiche, RO Hull, RA AF Darouiche, Rabih O. Hull, Richard A. TI Bacterial Interference for Prevention of Urinary Tract Infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ESCHERICHIA-COLI 83972; LACTOBACILLUS VAGINAL SUPPOSITORIES; ASYMPTOMATIC BACTERIURIA; MICROBIAL COMMUNITIES; CATHETER ADHERENCE; PILOT TRIAL; PROBIOTICS; COLONIZATION; FIMBRIAE; BLADDER C1 [Darouiche, Rabih O.] Baylor Coll Med, Infect Dis Sect, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Darouiche, Rabih O.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Darouiche, Rabih O.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Darouiche, Rabih O.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Hull, Richard A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Infect Dis Sect, Michael E DeBakey Vet Affairs Med Ctr, 1333 Moursund Ave,Ste A221, Houston, TX 77030 USA. EM rdarouiche@aol.com FU ConjuGon FX Both authors are associated with Baylor College of Medicine, which has received grants from ConjuGon. R. O. D. is associated with the Multidisciplinary Alliance Against Device-Related Infections, which has also received grants from ConjuGon. NR 45 TC 16 Z9 16 U1 2 U2 25 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 NOV 15 PY 2012 VL 55 IS 10 BP 1400 EP 1407 DI 10.1093/cid/cis639 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 027SV UT WOS:000310374600024 PM 22828592 ER PT J AU Sperduto, PW Sneed, PK Roberge, D Shanley, R Luo, XH Luo, XH Weil, RJ Suh, J Bhatt, A Jensen, AW Brown, PD Shih, HA Kirkpatrick, J Gaspar, LE Fiveash, JB Knisely, JPS Lin, N Mehta, M AF Sperduto, Paul W. Sneed, Penny K. Roberge, David Shanley, Ryan Luo, Xianghua Luo, Xianghua Weil, Robert J. Suh, John Bhatt, Amit Jensen, Ashley W. Brown, Paul D. Shih, Helen A. Kirkpatrick, John Gaspar, Laurie E. Fiveash, John B. Knisely, Jonathan P. S. Lin, Nancy Mehta, Minesh TI Self-Referral in Radiation Oncology: Has Caveat Emptor Replaced Primum Non Nocere? Reply SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter ID GRADED PROGNOSTIC ASSESSMENT; BRAIN METASTASES; SURVIVAL C1 [Sperduto, Paul W.] Univ Minnesota Gamma Knife, Minneapolis Radiat Oncol, Minneapolis, MN USA. [Sneed, Penny K.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Roberge, David] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Shanley, Ryan; Luo, Xianghua] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Luo, Xianghua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Weil, Robert J.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [Suh, John] Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Bhatt, Amit] Univ Wisconsin, Dept Human Oncol, Madison, WI USA. [Jensen, Ashley W.; Brown, Paul D.] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Shih, Helen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kirkpatrick, John] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Gaspar, Laurie E.] Univ Colorado, Dept Radiat Oncol, Sch Med, Aurora, CO USA. [Fiveash, John B.] Univ Alabama Birmingham, Med Ctr Birmingham, Birmingham, AL USA. [Knisely, Jonathan P. S.] Hofstra Univ, Sch Med, Dept Radiat Med, Manhasset, NY USA. [Knisely, Jonathan P. S.] N Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. [Lin, Nancy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mehta, Minesh] Northwestern Univ, Dept Radiat Oncol, Chicago, IL 60611 USA. RP Sperduto, PW (reprint author), Univ Minnesota Gamma Knife, Minneapolis Radiat Oncol, Minneapolis, MN USA. NR 4 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2012 VL 84 IS 4 BP 875 EP 876 DI 10.1016/j.ijrobp.2012.03.050 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030IV UT WOS:000310565300018 PM 23078894 ER PT J AU Jung, DJ An, JH Kurokawa, K Jung, YC Kim, MJ Aoyagi, Y Matsushita, M Takahashi, S Lee, HS Takahashi, K Lee, BL AF Jung, Dong-Jun An, Jang-Hyun Kurokawa, Kenji Jung, Yoon-Chuel Kim, Min-Jung Aoyagi, Youko Matsushita, Misao Takahashi, Shinji Lee, Hee-Seung Takahashi, Kazue Lee, Bok Luel TI Specific Serum Ig Recognizing Staphylococcal Wall Teichoic Acid Induces Complement-Mediated Opsonophagocytosis against Staphylococcus aureus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MANNOSE-BINDING LECTIN; GRAM-POSITIVE BACTERIA; LIPOTEICHOIC ACID; HUMAN POLYMORPHONUCLEAR; SERINE-PROTEASE; 2 PARTS; ACTIVATION; OPSONIZATION; INFECTIONS; ANTIBODIES AB Wall teichoic acid (WTA) of Staphylococcus aureus is a major cell envelope-associated glycopolymer that is a key molecule in promoting colonization during S. aureus infection. The complement system plays a key role in the opsonization and clearance of pathogens. We recently reported that S. aureus WTA functions as a ligand of human serum mannose-binding lectin (MBL), a recognition molecule of the lectin complement pathway. Intriguingly, serum MBL in adults does not bind to WTA because of an inhibitory effect of serum anti-WTA-IgG. In this study, serum anti-WTA-IgG was purified to homogeneity using a purified S. aureus WTA-coupled affinity column to examine the biological function of human anti-WTA-IgG. The purified anti-WTA-IgG contained the IgG2 subclass as a major component and specifically induced C4 and C3 deposition on the S. aureus surface in the anti-WTA-IgG-depleted serum, but not in C1q-deficient serum. Furthermore, the anti-WTA-IgG-dependent C3 deposition induced phagocytosis of S. aureus cells by human polymorphonuclear leukocytes. These results demonstrate that serum anti-WTA-IgG is a real trigger for the induction of classical complement-dependent opsonophagocytosis against S. aureus. Our results also support the fact that a lack of the lectin complement pathway in MBL-deficient adults is compensated by Ag-specific, Ab-mediated adaptive immunity. The Journal of Immunology, 2012, 189: 4951-4959. C1 [Jung, Dong-Jun; An, Jang-Hyun; Kurokawa, Kenji; Kim, Min-Jung; Lee, Bok Luel] Pusan Natl Univ, Global Res Lab Insect Symbiosis, Coll Pharm, Pusan 609735, South Korea. [Jung, Yoon-Chuel; Lee, Hee-Seung] Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea. [Aoyagi, Youko; Takahashi, Shinji] Joshi Eiyoh Univ, Div Microbiol, Tokyo 1708481, Japan. [Matsushita, Misao] Tokai Univ, Dept Appl Biochem, Kanagawa 2591292, Japan. [Takahashi, Kazue] Harvard Univ, Dept Pediat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Lee, BL (reprint author), Pusan Natl Univ, Global Res Lab Insect Symbiosis, Coll Pharm, Pusan 609735, South Korea. EM brlee@pusan.ac.kr RI Lee, Hee-Seung/C-1627-2011 FU National Research Foundation, Korea [2012-0000110, 2011-002-7773, BK21] FX This work was supported by Programs 2012-0000110, 2011-002-7773, and BK21 of the National Research Foundation, Korea. NR 47 TC 16 Z9 18 U1 2 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2012 VL 189 IS 10 BP 4951 EP 4959 DI 10.4049/jimmunol.1201294 PG 9 WC Immunology SC Immunology GA 032IU UT WOS:000310710600029 PM 23071283 ER PT J AU Tamang, DL Pirzai, W Priebe, GP Traficante, DC Pier, GB Falck, JR Morisseau, C Hammock, BD McCormick, BA Gronert, K Hurley, BP AF Tamang, David L. Pirzai, Waheed Priebe, Gregory P. Traficante, David C. Pier, Gerald B. Falck, John R. Morisseau, Christophe Hammock, Bruce D. McCormick, Beth A. Gronert, Karsten Hurley, Bryan P. TI Hepoxilin A(3) Facilitates Neutrophilic Breach of Lipoxygenase-Expressing Airway Epithelial Barriers SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELOID DIFFERENTIATION FACTOR-88; PSEUDOMONAS-AERUGINOSA PNEUMONIA; FREE ARACHIDONIC-ACID; KAPPA-B PATHWAY; CYSTIC-FIBROSIS; LUNG INFECTION; PHOSPHOLIPASE A(2); HOST-DEFENSE; TRANSEPITHELIAL MIGRATION; STAPHYLOCOCCUS-AUREUS AB A feature shared by many inflammatory lung diseases is excessive neutrophilic infiltration. Neutrophil homing to airspaces involve multiple factors produced by several distinct cell types. Hepoxilin A(3) is a neutrophil chemoattractant produced by pathogen-infected epithelial cells that is hypothesized to facilitate neutrophil breach of mucosal barriers. Using a Transwell model of lung epithelial barriers infected with Pseudomonas aeruginosa, we explored the role of hepoxilin A(3) in neutrophil transepithelial migration. Pharmacological inhibitors of the enzymatic pathways necessary to generate hepoxilin A(3), including phospholipase A(2) and 12-lipoxygenase, potently interfere with P. aeruginosa-induced neutrophil transepithelial migration. Both transformed and primary human lung epithelial cells infected with P. aeruginosa generate hepoxilin A(3) precursor arachidonic acid. All four known lipoxygenase enzymes capable of synthesizing hepoxilin A(3) are expressed in lung epithelial cell lines, primary small airway epithelial cells, and human bronchial epithelial cells. Lung epithelial cells produce increased hepoxilin A(3) and lipid-derived neutrophil chemotactic activity in response to P. aeruginosa infection. Lipid-derived chemotactic activity is soluble epoxide hydrolase sensitive, consistent with hepoxilin A(3) serving a chemotactic role. Stable inhibitory structural analogs of hepoxilin A(3) are capable of impeding P. aeruginosa-induced neutrophil transepithelial migration. Finally, intranasal infection of mice with P. aeruginosa promotes enhanced cellular infiltrate into the airspace, as well as increased concentration of the 12-lipoxygenase metabolites hepoxilin A(3) and 12-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid. Data generated from multiple models in this study provide further evidence that hepoxilin A(3) is produced in response to lung pathogenic bacteria and functions to drive neutrophils across epithelial barriers. The Journal of Immunology, 2012, 189: 4960-4969. C1 [Tamang, David L.; Pirzai, Waheed; Hurley, Bryan P.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Tamang, David L.; Hurley, Bryan P.] Harvard Univ, Dept Pediat, Sch Med, Boston, MA 02115 USA. [Priebe, Gregory P.; Traficante, David C.; Pier, Gerald B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Morisseau, Christophe; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Morisseau, Christophe; Hammock, Bruce D.] Univ Calif Davis, Ctr Comprehens Canc, Davis, CA 95616 USA. [McCormick, Beth A.] Univ Massachusetts, Dept Microbiol & Physiol Syst, Sch Med, Worcester, MA 01655 USA. [Gronert, Karsten] Univ Calif Berkeley, Vis Sci Program, Sch Optometry, Berkeley, CA 94720 USA. RP Hurley, BP (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM bphurley@partners.org OI Pier, Gerald/0000-0002-9112-2331; Falck, John/0000-0002-9219-7845 FU National Institutes of Health [1 R01 AI095338-01A1, 5K22AI065425-02, EY016136, R01 GM31278, DK 56754, DK 33506]; Cystic Fibrosis Foundation [HURLEY08G0]; National Institute on Environmental Health Sciences [R01 ES002710]; National Institute of Allergy and Infectious Diseases [R01 AI091699]; Robert A. Welch Foundation [GL625910] FX This work was supported by National Institutes of Health Grants 1 R01 AI095338-01A1 and 5K22AI065425-02 and by Cystic Fibrosis Foundation Grant HURLEY08G0. K.G. was supported by National Institutes of Health Grant EY016136. C.M. and B.D.H. were supported by National Institute on Environmental Health Sciences Grant R01 ES002710 and National Institute of Allergy and Infectious Diseases Grant R01 AI091699. B.D.H. is a George and Judy Marcus Senior Fellow of the American Asthma Foundation. J.R.F. received financial support from National Institutes of Health Grant R01 GM31278 and the Robert A. Welch Foundation (GL625910). B.A.M. is supported by National Institutes of Health Grants DK 56754 and DK 33506. NR 67 TC 9 Z9 9 U1 2 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 NOV 15 PY 2012 VL 189 IS 10 BP 4960 EP 4969 DI 10.4049/jimmunol.1201922 PG 10 WC Immunology SC Immunology GA 032IU UT WOS:000310710600030 PM 23045615 ER PT J AU Steere, AC AF Steere, Allen C. TI Reinfection versus Relapse in Lyme Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID THERAPY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Steere, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 11 TC 3 Z9 3 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 NOV 15 PY 2012 VL 367 IS 20 BP 1950 EP 1951 DI 10.1056/NEJMe1211361 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 036MB UT WOS:000311029300013 PM 23150963 ER PT J AU Tomasiewicz, HC Jacobs, MM Wilkinson, MB Wilson, SP Nestler, EJ Hurd, YL AF Tomasiewicz, Hilarie C. Jacobs, Michelle M. Wilkinson, Matthew B. Wilson, Steven P. Nestler, Eric J. Hurd, Yasmin L. TI Proenkephalin Mediates the Enduring Effects of Adolescent Cannabis Exposure Associated with Adult Opiate Vulnerability SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Drug addiction; epigenetics; marijuana; nucleus accumbens; rat; striatopallidal ID HISTONE LYSINE METHYLATION; COCAINE-INDUCED PLASTICITY; CHROMATIN REGULATION; MAMMALIAN CHROMATIN; NUCLEUS-ACCUMBENS; X-CHROMOSOME; DRUG; HETEROCHROMATIN; TRANSCRIPTION; LOCALIZATION AB Background: Marijuana use by teenagers often predates the use of harder drugs, but the neurobiological underpinnings of such vulnerability are unknown. Animal studies suggest enhanced heroin self-administration (SA) and dysregulation of the endogenous opioid system in the nucleus accumbens shell (NAcsh) of adults following adolescent Delta(9)-tetrahydrocannabinol (THC) exposure. However, a causal link between proenkephalin (Penk) expression and vulnerability to heroin has yet to be established. Methods: To investigate the functional significance of NAcsh Penk tone, selective viral-mediated knockdown and overexpression of Penk was performed, followed by analysis of subsequent heroin SA behavior. To determine whether adolescent THC exposure was associated with chromatin alteration, we analyzed levels of histone H3 methylation in the NAcsh via chromatin immunoprecipitation at five sites flanking the Penk gene transcription start site. Results: Here we show that regulation of the Penk opioid neuropeptide gene in NAcsh directly regulates heroin SA behavior. Selective viral-mediated knockdown of Penk in striatopallidal neurons attenuates heroin SA in adolescent THC-exposed rats, whereas Penk overexpression potentiates heroin SA in THC-naive rats. Furthermore, we report that adolescent THC exposure mediates Penk upregulation through reduction of histone H3 lysine 9 (H3K9) methylation in the NAcsh, thereby disrupting the normal developmental pattern of H3K9 methylation. Conclusions: These data establish a direct association between THC-induced NAcsh Penk upregulation and heroin SA and indicate that epigenetic dysregulation of Penk underlies the long-term effects of THC. C1 [Tomasiewicz, Hilarie C.; Jacobs, Michelle M.; Nestler, Eric J.; Hurd, Yasmin L.] James J Peters VA Med Ctr, Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Tomasiewicz, Hilarie C.; Wilkinson, Matthew B.; Nestler, Eric J.; Hurd, Yasmin L.] James J Peters VA Med Ctr, Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Jacobs, Michelle M.; Nestler, Eric J.; Hurd, Yasmin L.] James J Peters VA Med Ctr, Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA. [Tomasiewicz, Hilarie C.; Jacobs, Michelle M.; Wilkinson, Matthew B.; Nestler, Eric J.; Hurd, Yasmin L.] James J Peters VA Med Ctr, Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. [Wilson, Steven P.] Univ S Carolina, Sch Med, Dept Pharmacol Physiol & Neurosci, Columbia, SC 29208 USA. RP Hurd, YL (reprint author), James J Peters VA Med Ctr, Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. EM Yasmin.hurd@mssm.edu FU National Institute on Drug Abuse [DA024929, T32 DA007135, DA08227, DA030359, DA19350] FX This work was funded by the National Institute on Drug Abuse, Grant Nos. DA024929 (HCT), T32 DA007135 (MMJ), DA08227 (EJN), DA030359 (YLH), and DA19350 (YLH). NR 34 TC 35 Z9 36 U1 1 U2 17 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 NOV 15 PY 2012 VL 72 IS 10 BP 803 EP 810 DI 10.1016/j.biopsych.2012.04.026 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 027KT UT WOS:000310351800007 PM 22683090 ER PT J AU Lin, NU Vanderplas, A Hughes, ME Theriault, RL Edge, SB Wong, YN Blayney, DW Niland, JC Winer, EP Weeks, JC AF Lin, Nancy U. Vanderplas, Ann Hughes, Melissa E. Theriault, Richard L. Edge, Stephen B. Wong, Yu-Ning Blayney, Douglas W. Niland, Joyce C. Winer, Eric P. Weeks, Jane C. TI Clinicopathologic Features, Patterns of Recurrence, and Survival Among Women With Triple-Negative Breast Cancer in the National Comprehensive Cancer Network SO CANCER LA English DT Article DE triple-negative; basal-like; breast cancer; outcomes; brain metastases; obesity; race ID GROWTH-FACTOR-I; BRAIN METASTASES; POSTMENOPAUSAL WOMEN; MOLECULAR SUBTYPES; RISK-FACTORS; BASAL; EPIDEMIOLOGY; POPULATION; PHENOTYPE; OUTCOMES AB BACKGROUND: The objective of this study was to describe clinicopathologic features, patterns of recurrence, and survival according to breast cancer subtype with a focus on triple-negative tumors. METHODS: In total, 15,204 women were evaluated who presented to National Comprehensive Cancer Network centers with stage I through III breast cancer between January 2000 and December 2006. Tumors were classified as positive for estrogen receptor (ER) and/or progesterone receptor (PR) (hormone receptor [HR]-positive) and negative for human epidermal growth factor receptor 2 (HER2); positive for HER2 and any ER or PR status (HER2-positive); or negative for ER, PR, and HER2 (triple-negative). RESULTS: Subtype distribution was triple-negative in 17% of women (n = 2569), HER2-positive in 17% of women (n = 2602), and HR-positive/HER2-negative in 66% of women (n = 10,033). The triple-negative subtype was more frequent in African Americans compared with Caucasians (adjusted odds ratio, 1.98; P < .0001). Premenopausal women, but not postmenopausal women, with high body mass index had an increased likelihood of having the triple-negative subtype (P = .02). Women with triple-negative cancers were less likely to present on the basis of an abnormal screening mammogram (29% vs 48%; P < .0001) and were more likely to present with higher tumor classification, but they were less likely to have lymph node involvement. Relative to HR-positive/HER2-negative tumors, triple-negative tumors were associated with a greater risk of brain or lung metastases; and women with triple-negative tumors had worse breast cancer-specific and overall survival, even after adjusting for age, disease stage, race, tumor grade, and receipt of adjuvant chemotherapy (overall survival: adjusted hazard ratio, 2.72; 95% confidence interval, 2.39-3.10; P < .0001). The difference in the risk of death by subtype was most dramatic within the first 2 years after diagnosis (overall survival for 0-2 years: OR, 6.10; 95% confidence interval, 4.81-7.74). CONCLUSIONS: Triple-negative tumors were associated with unique risk factors and worse outcomes compared with HR-positive/HER2-negative tumors. Cancer 2012. (C) 2012 American Cancer Society. C1 [Lin, Nancy U.; Winer, Eric P.; Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Vanderplas, Ann; Niland, Joyce C.] City Hope Comprehens Canc Ctr, Div Informat Sci, Duarte, CA USA. [Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Dept Populat Sci, Boston, MA 02215 USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Dept Breast & Soft Tissue Surg, Buffalo, NY 14263 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Blayney, Douglas W.] Univ Michigan, Dept Med Oncol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Blayney, Douglas W.] Stanford Univ, Ctr Canc, Dept Med Oncol, Palo Alto, CA 94304 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM nlin@partners.org FU National Cancer Institute Specialized Program of Research Excellence in Breast Cancer [NIH P50 CA089393]; National Comprehensive Cancer Network; Breast Cancer Research Foundation; American Society of Clinical Oncology Cancer Foundation; Berry Junior Faculty Award; Karen Webster and David Evans Research Fund; American Society of Clinical Oncology FX This study was supported by the National Cancer Institute Specialized Program of Research Excellence in Breast Cancer (NIH P50 CA089393), the National Comprehensive Cancer Network, the Breast Cancer Research Foundation, the American Society of Clinical Oncology Cancer Foundation, a Berry Junior Faculty Award, and the Karen Webster and David Evans Research Fund. Dr. Blayney has received salary support from the American Society of Clinical Oncology (as president). NR 39 TC 84 Z9 91 U1 1 U2 11 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 NOV 15 PY 2012 VL 118 IS 22 BP 5463 EP 5472 DI 10.1002/cncr.27581 PG 10 WC Oncology SC Oncology GA 029GW UT WOS:000310483800002 PM 22544643 ER PT J AU Nabors, LB Mikkelsen, T Hegi, ME Ye, XB Batchelor, T Lesser, G Peereboom, D Rosenfeld, MR Olsen, J Brem, S Fisher, JD Grossman, SA AF Nabors, L. Burt Mikkelsen, Thomas Hegi, Monika E. Ye, Xiaubu Batchelor, Tracy Lesser, Glenn Peereboom, David Rosenfeld, Myrna R. Olsen, Jeff Brem, Steve Fisher, Joy D. Grossman, Stuart A. CA New Approaches Brain Tumor Therapy TI A Safety Run-In and Randomized Phase 2 Study of Cilengitide Combined With Chemoradiation for Newly Diagnosed Glioblastoma (NABTT 0306) SO CANCER LA English DT Article DE glioblastoma; integrin; cilengitide; clinical trial; angiogenesis ID MALIGNANT GLIOMA; TEMOZOLOMIDE; MULTIFORME; THERAPY AB BACKGROUND: Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose for comparative clinical testing. METHODS: In total, 112 patients were accrued. Eighteen patients received standard radiation and temozolomide with cilengitide in a safety run-in phase followed by a randomized phase 2 trial with 94 patients assigned to either a 500 mg dose group or 2000 mg dose group. The trial was designed to estimate overall survival benefit compared with a New Approaches to Brain Tumor Therapy (NABTT) Consortium internal historic control and data from the published European Organization for Research and Treatment of Cancer (EORTC) trial EORTC 26981. RESULTS: Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for the patients in the 500 mg dose group, 20.8 months for patients in the 2000 mg dose group, 30 months for patients who had methylated O6-methylguanine-DNA methyltransferase (MGMT) status, and 17.4 months for patients who had unmethylated MGMT status. For patients aged =70 years, the median survival and survival at 24 months was superior to what was observed in the EORTC trial (20.7 months vs 14.6 months and 41% vs 27%, respectively; P = .008). CONCLUSIONS: Cilengitide was well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with glioblastoma multiforme regardless of MGMT methylation status. The authors concluded that, from an efficacy and safety standpoint, future trials of this agent in this population should use the 2000 mg dose. Cancer 2012. (c) 2012 American Cancer Society. C1 [Nabors, L. Burt] Univ Alabama Birmingham, Brain Tumor Treatment & Res Program, Birmingham, AL USA. [Mikkelsen, Thomas] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. [Hegi, Monika E.] Univ Lausanne Hosp, Dept Neurosurg, Lausanne, Switzerland. [Hegi, Monika E.] Univ Lausanne, Lausanne, Switzerland. [Ye, Xiaubu] Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [Batchelor, Tracy] Massachusetts Gen Hosp, Dept Neurooncol, Cambridge, MA USA. [Lesser, Glenn] Wake Forest Med Ctr, Dept Hematol Oncol, Wake Forest, NC USA. [Peereboom, David] Cleveland Clin, Brain Tumor Neurooncol Ctr, Cleveland, OH 44106 USA. [Rosenfeld, Myrna R.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Olsen, Jeff] Emory Univ, Dept Neurosurg, Atlanta, GA 30322 USA. [Brem, Steve] Hosp Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Fisher, Joy D.] New Approaches Brain Tumor Therapy Consortium, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Fisher, Joy D.] Univ Alabama Birmingham, Dept Neurosurg, Birmingham, AL USA. [Grossman, Stuart A.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Fisher, JD (reprint author), NABTT CNS Consortium, Canc Res Bldg 2,1550 Orleans St,Room 1M-16, Baltimore, MD 21231 USA. EM jfisher@jhmi.edu RI Hegi, Monika/O-4796-2015; OI Hegi, Monika/0000-0003-0855-6495; Rosenfeld, Myrna/0000-0001-5095-2534 FU National Institutes of Health [CA-62475]; Merck KGaA FX This work was supported by a grant from the National Institutes of Health (CA-62475).; T. Mikkelsen received research funding support from Merck KGaA, and T. Batchelor has acted as a consultant to EMD-Serono (the biopharmaceutical division of Merck KGaA). NR 15 TC 53 Z9 54 U1 0 U2 9 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 NOV 15 PY 2012 VL 118 IS 22 BP 5601 EP 5607 DI 10.1002/cncr.27585 PG 7 WC Oncology SC Oncology GA 029GW UT WOS:000310483800018 PM 22517399 ER PT J AU Feuer, EJ Lee, M Mariotto, AB Cronin, KA Scoppa, S Penson, DF Hachey, M Cynkin, L Carter, GA Campbell, D Percy-Laurry, A Zou, ZH Schrag, D Hankey, BF AF Feuer, Eric J. Lee, Minjung Mariotto, Angela B. Cronin, Kathy A. Scoppa, Steve Penson, David F. Hachey, Mark Cynkin, Laurie Carter, Ginger A. Campbell, David Percy-Laurry, Antoinette Zou, Zhaohui Schrag, Deborah Hankey, Benjamin F. TI The Cancer Survival Query System: Making Survival Estimates From the Surveillance, Epidemiology, and End Results Program More Timely and Relevant for Recently Diagnosed Patients SO CANCER LA English DT Article DE competing risk analysis; survival analysis; proportional hazards; prostate cancer; nomograms; prognosis; shared decision-making ID BREAST AB BACKGROUND: Population-based cancer registries that include patient follow-up generally provide information regarding net survival (ie, survival associated with the risk of dying of cancer in the absence of competing risks). However, registry data also can be used to calculate survival from cancer in the presence of competing risks, which is more clinically relevant. METHODS: Statistical methods were developed to predict the risk of death from cancer and other causes, as well as natural life expectancy if the patient did not have cancer based on a profile of prognostic factors including characteristics of the cancer, demographic factors, and comorbid conditions. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to calculate the risk of dying of cancer. Because the risks of dying of cancer versus other causes are assumed to be independent conditional on the prognostic factors, a wide variety of independent data sources can be used to calculate the risk of death from other causes. Herein, the risk of death from other causes was estimated using SEER and Medicare claims data, and was matched to the closest fitting portion of the US life table to obtain a health status-adjusted age. RESULTS: A nomogram was developed for prostate cancer as part of a Web-based Cancer Survival Query System that is targeted for use by physicians and patients to obtain information on a patient's prognosis. More nomograms currently are being developed. CONCLUSIONS: Nomograms of this type can be used as one tool to assist cancer physicians and their patients to better understand their prognosis and to weigh alternative treatment and palliative strategies. Cancer 2012. (c) 2012 American Cancer Society. C1 [Hankey, Benjamin F.] CANSTAT, Plano, TX 75024 USA. [Feuer, Eric J.; Lee, Minjung; Mariotto, Angela B.; Cronin, Kathy A.; Cynkin, Laurie; Percy-Laurry, Antoinette] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Scoppa, Steve; Hachey, Mark; Carter, Ginger A.; Campbell, David; Zou, Zhaohui] Informat Management Serv Inc, Silver Spring, MD USA. [Penson, David F.] Vanderbilt Univ, Med Ctr, Ctr Surg Qual & Outcomes Res, Nashville, TN USA. [Penson, David F.] Tennessee Valley Geriatr Res Educ & Clin Ctr GREC, Vet Adm, Nashville, TN USA. [Schrag, Deborah] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Hankey, BF (reprint author), CANSTAT, 6805 Colonnade Dr, Plano, TX 75024 USA. EM bhankey0411@aol.com FU National Cancer Institute FX Supported by the National Cancer Institute. NR 24 TC 11 Z9 14 U1 0 U2 3 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 NOV 15 PY 2012 VL 118 IS 22 BP 5652 EP 5662 DI 10.1002/cncr.27615 PG 11 WC Oncology SC Oncology GA 029GW UT WOS:000310483800025 PM 22569947 ER PT J AU Muriel, AC Moore, CW Baer, L Park, ER Kornblith, AB Pirl, W Prigerson, H Ing, J Rauch, PK AF Muriel, Anna C. Moore, Cynthia W. Baer, Lee Park, Elyse R. Kornblith, Alice B. Pirl, William Prigerson, Holly Ing, Jennifer Rauch, Paula K. TI Measuring Psychosocial Distress and Parenting Concerns Among Adults With Cancer The Parenting Concerns Questionnaire SO CANCER LA English DT Article DE psychosocial aspects; quality of life; psychometrics; parenting ID EARLY BREAST-CANCER; ADJUVANT CHEMOTHERAPY; FUNCTIONAL ASSESSMENT; PSYCHOLOGIC DISTRESS; PATIENTS PREFERENCES; DEPENDENT CHILDREN; TERMINAL CANCER; MOTHERS; FAMILY; POPULATION AB BACKGROUND: A 2-phase, mixed methods study was conducted to develop a Parenting Concerns Questionnaire (PCQ) for adults with cancer. Limited information about this area of psychosocial distress highlights the need for a measurement tool that can identify adult oncology patients with heightened parenting concerns who could benefit from additional intervention. METHODS: Telephone focus groups were conducted with 16 oncology patients who had children 18 years old and younger. Group interview transcripts were analyzed to generate qualitative themes and candidate items for the PCQ. A 38-item version of the questionnaire was completed by 173 oncology outpatients who had children 18 years old and under. Participants also completed the Distress Thermometer, HADS (Hospital Anxiety and Depression Scale), and FACT-G (Functional Assessment of Cancer TherapyGeneral). Exploratory factor analyses revealed the emergence of 3 subscales of 5 items each, yielding a 15-item questionnaire. Associations between total PCQ scores, standardized measures of distress, depression, anxiety, quality of life, and demographic and illness characteristics were examined. RESULTS: The 15-item PCQ demonstrates good internal consistency (Cronbach's alpha = .83). PCQ scores were significantly associated (P < .01) with standardized measures of psychosocial distress (Distress Thermometer, HADS, and FACT-G) in the expected directions. Higher PCQ scores were associated with female sex, single parenthood, metastatic or recurrent cancer, subjective understanding of incurable disease, comorbid chronic health condition, and current mental health treatment. CONCLUSIONS: The PCQ proved a reliable and valid measure of parenting distress among cancer patients, and thus merits further study. Cancer 2012;118:5671-8 (C) 2012 American Cancer Society. C1 [Muriel, Anna C.; Kornblith, Alice B.; Prigerson, Holly; Ing, Jennifer] Dana Farber Canc Inst, Boston, MA 02215 USA. [Moore, Cynthia W.; Baer, Lee; Park, Elyse R.; Pirl, William; Rauch, Paula K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Muriel, AC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 312, Boston, MA 02215 USA. EM amuriel@partners.org FU National Institutes of Health [R03 CA126394-01] FX Research supported by National Institutes of Health grant R03 CA126394-01. NR 33 TC 10 Z9 10 U1 2 U2 10 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 NOV 15 PY 2012 VL 118 IS 22 BP 5671 EP 5678 DI 10.1002/cncr.27572 PG 8 WC Oncology SC Oncology GA 029GW UT WOS:000310483800027 PM 22517236 ER PT J AU Vafai, SB Mootha, VK AF Vafai, Scott B. Mootha, Vamsi K. TI Mitochondrial disorders as windows into an ancient organelle SO NATURE LA English DT Review ID SKELETAL-MUSCLE MITOCHONDRIA; HEREDITARY OPTIC NEUROPATHY; BOVINE HEART-MITOCHONDRIA; RESPIRATORY-CHAIN; OXIDATIVE-PHOSPHORYLATION; COMPLEX-I; STEADY-STATE; CELL-PROLIFERATION; CALCIUM UNIPORTER; MEMBRANE-PROTEIN AB Much of our current knowledge about mitochondria has come from studying patients who have respiratory chain disorders. These disorders comprise a large collection of individually rare syndromes, each presenting in a unique and often devastating way. In recent years, there has been great progress in defining their genetic basis, but we still know little about the cascade of events that gives rise to such diverse pathology. Here, we review these disorders and explore them in the context of a contemporary understanding of mitochondrial evolution, biochemistry and genetics. Fully deciphering their pathogenesis is a challenging next step that will inspire the development of drug treatments for rare and common diseases. C1 [Vafai, Scott B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. [Vafai, Scott B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Vafai, Scott B.; Mootha, Vamsi K.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu FU National Institutes of Health FX We apologize to the many authors whose work we were unable to cite because of space limitations. We offer special thanks to D. Thorburn for careful review of the manuscript and his help with compiling an updated list of disease genes. We are grateful to S. Calvo, M. Jain, E. Rosen, V. Siegel and M. Gray for thoughtful feedback on the manuscript; J-.P. Mazat for providing a figure; M. Fleming, A. Sadun, M. Seidman, R. Mitchell, R. Saneto, D. McGuone and L. Rodriguez for providing clinical images; and G. Perkins and M. Ellisman for providing electron micrographs. We thank the National Institutes of Health for ongoing grant support. NR 98 TC 175 Z9 178 U1 9 U2 72 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 15 PY 2012 VL 491 IS 7424 BP 374 EP 383 DI 10.1038/nature11707 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 036MY UT WOS:000311031600034 PM 23151580 ER PT J AU Mitra, D Luo, X Morgan, A Wang, J Hoang, MP Lo, J Guerrero, CR Lennerz, JK Mihm, MC Wargo, JA Robinson, KC Devi, SP Vanover, JC D'Orazio, JA McMahon, M Bosenberg, MW Haigis, KM Haber, DA Wang, YS Fisher, DE AF Mitra, Devarati Luo, Xi Morgan, Ann Wang, Jin Hoang, Mai P. Lo, Jennifer Guerrero, Candace R. Lennerz, Jochen K. Mihm, Martin C. Wargo, Jennifer A. Robinson, Kathleen C. Devi, Suprabha P. Vanover, Jillian C. D'Orazio, John A. McMahon, Martin Bosenberg, Marcus W. Haigis, Kevin M. Haber, Daniel A. Wang, Yinsheng Fisher, David E. TI An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background SO NATURE LA English DT Article ID STEM-CELL FACTOR; DNA LESIONS; MELANOCYTES; MICE; MUTATIONS; RISK; PIGMENTATION; SENESCENCE; EXPRESSION; DAMAGE AB People with pale skin, red hair, freckles and an inability to tan-the 'red hair/fair skin' phenotype-are at highest risk of developing melanoma, compared to all other pigmentation types(1). Genetically, this phenotype is frequently the product of inactivating polymorphisms in the melanocortin 1 receptor (MC1R) gene. MC1R encodes a cyclic AMP-stimulating G-protein-coupled receptor that controls pigment production. Minimal receptor activity, as in red hair/fair skin polymorphisms, produces the red/yellow pheomelanin pigment, whereas increasing MC1R activity stimulates the production of black/brown eumelanin(2). Pheomelanin has weak shielding capacity against ultraviolet radiation relative to eumelanin, and has been shown to amplify ultraviolet-A-induced reactive oxygen species(3-5). Several observations, however, complicate the assumption that melanoma risk is completely ultraviolet-radiation-dependent. For example, unlike non-melanoma skin cancers, melanoma is not restricted to sun-exposed skin and ultraviolet radiation signature mutations are infrequently oncogenic drivers(6). Although linkage of melanoma risk to ultraviolet radiation exposure is beyond doubt, ultraviolet-radiation-independent events are likely to have a significant role(1,7). Here we introduce a conditional, melanocyte-targeted allele of the most common melanoma oncoprotein, BRAF(V600E), into mice carrying an inactivating mutation in the Mc1r gene (these mice have a phenotype analogous to red hair/fair skin humans). We observed a high incidence of invasive melanomas without providing additional gene aberrations or ultraviolet radiation exposure. To investigate the mechanism of ultraviolet-radiation-independent carcinogenesis, we introduced an albino allele, which ablates all pigment production on the Mc1r(e/e) background. Selective absence of pheomelanin synthesis was protective against melanoma development. In addition, normal Mc1r(e/e) mouse skin was found to have significantly greater oxidative DNA and lipid damage than albino Mc1r(e/e) mouse skin. These data suggest that the pheomelanin pigment pathway produces ultraviolet-radiation-independent carcinogenic contributions to melanomagenesis by a mechanism of oxidative damage. Although protection from ultraviolet radiation remains important, additional strategies may be required for optimal melanoma prevention. C1 [Mitra, Devarati; Morgan, Ann; Lo, Jennifer; Robinson, Kathleen C.; Devi, Suprabha P.; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Luo, Xi; Haigis, Kevin M.; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Wang, Jin; Guerrero, Candace R.; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Hoang, Mai P.; Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lennerz, Jochen K.] Univ Ulm, Inst Pathol, D-89070 Ulm, Germany. [Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Vanover, Jillian C.; D'Orazio, John A.] Univ Kentucky, Sch Med, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA. [McMahon, Martin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Bosenberg, Marcus W.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM dfisher3@partners.org OI , /0000-0002-9520-6874 FU National Institutes of Health [5R01 AR043369-16, R01-CA101864, F30 ES020663-01]; Dr Miriam and Sheldon G. Adelson Medical Research Foundation; US-Israel Binational Science Foundation; Melanoma Research Alliance FX We thank T. Kunisada for generously sharing K14-SCF mice and C. L. Evans for help with mouse skin irradiation. We also thank A. P. Codgill for help with primary tumour cell culture and A. Piris for pathology consultation as well as M. Haigis and Z. Abdel-Malik for discussions. This work was supported by the following grants from the National Institutes of Health 5R01 AR043369-16 (D.E.F.), R01-CA101864 (Y.W.) and F30 ES020663-01 (D.M.), as well as support from the Dr Miriam and Sheldon G. Adelson Medical Research Foundation, the US-Israel Binational Science Foundation, and the Melanoma Research Alliance (D.E.F.). NR 30 TC 140 Z9 142 U1 6 U2 92 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 15 PY 2012 VL 491 IS 7424 BP 449 EP + DI 10.1038/nature11624 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 036MY UT WOS:000311031600047 PM 23123854 ER PT J AU Pienaar, R Paldino, MJ Madan, N Krishnamoorthy, KS Alsop, DC Dehaes, M Grant, PE AF Pienaar, Rudolph Paldino, Michael J. Madan, Neel Krishnamoorthy, Kalpathy S. Alsop, David C. Dehaes, Mathieu Grant, P. Ellen TI A quantitative method for correlating observations of decreased apparent diffusion coefficient with elevated cerebral blood perfusion in newborns presenting cerebral ischemic insults SO NEUROIMAGE LA English DT Article DE Magnetic resonance imaging; Arterial spin labeling; Diffusion weighted imaging; Cerebral blood perfusion; Apparent diffusion coefficient; Ischemia ID NEONATAL BRAIN-INJURY; FLOW; ENCEPHALOPATHY; EVOLUTION; STROKE; SYSTEM; MRI AB In patients presenting with cerebral ischemic injury, the outcome of injured brain tissue quantified as decreased apparent diffusion coefficient (ADC) may depend on associated alterations in cerebral blood perfusion (CBP). This study proposes a non-biased method to quantify associations between ADC and CBP in newborns with global or focal cerebral ischemia. The study population consisted of nine neonates (age: 0 to 3 days) presenting with clinical and imaging evidence of ischemia (seven with global hypoxic ischemia, and two with focal arterial ischemic stroke) with decreased ADC. Six newborns without diffusion abnormalities on magnetic resonance (MR) imaging served as a comparative cohort (age: 0 days to 4 weeks). All patients underwent MR imaging including diffusion weighted imaging (DWI) to determine ADC and axial arterial spin labeling (ASL) to determine CBP. An algorithm was developed that uses the B0 volume from the DWI raw data as a reference, co-registers the ADC and ASL-CBP data to the B0, generates mask filters, and finally performs a statistical analysis to automatically select regions of interest (ROIs) with ADC or ASL-CBP values that deviate significantly from the rest of the brain. If ROIs are identified in this analysis, the algorithm then evaluates correlation based on ROI location and volume. A significant correlation was found between decreased ADC and elevated ASL-CBP with regions of elevated ASL-CBP typically larger than the corresponding ADC abnormality. The association between decreased diffusivity and increased ASL-CBP suggests that, for this cohort, cerebral ischemia is associated with hyperperfusion. (C) 2012 Elsevier Inc. All rights reserved. C1 [Pienaar, Rudolph; Dehaes, Mathieu; Grant, P. Ellen] Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA. [Pienaar, Rudolph; Paldino, Michael J.; Krishnamoorthy, Kalpathy S.; Alsop, David C.; Dehaes, Mathieu; Grant, P. Ellen] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Pienaar, Rudolph; Paldino, Michael J.; Grant, P. Ellen] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Dehaes, Mathieu; Grant, P. Ellen] Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. [Krishnamoorthy, Kalpathy S.] Massachusetts Gen Hosp, Pediat Neurol Unit, Boston, MA 02114 USA. [Alsop, David C.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Madan, Neel] Tufts Med Ctr, Dept Radiol, Boston, MA 02111 USA. RP Pienaar, R (reprint author), Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM rudolph.pienaar@childrens.harvard.edu RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 NR 33 TC 14 Z9 15 U1 2 U2 6 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 NOV 15 PY 2012 VL 63 IS 3 BP 1510 EP 1518 DI 10.1016/j.neuroimage.2012.07.062 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 027UK UT WOS:000310379100052 PM 22892333 ER PT J AU Nasr, S Tootell, RBH AF Nasr, Shahin Tootell, Roger B. H. TI Role of fusiform and anterior temporal cortical areas in facial recognition SO NEUROIMAGE LA English DT Article DE fMRI; Face recognition; Face inversion; Contrast reversal; FFA; Anterior temporal face patch ID SURFACE-BASED ANALYSIS; FACE RECOGNITION; CONGENITAL PROSOPAGNOSIA; OBJECT RECOGNITION; CEREBRAL-CORTEX; OCCIPITAL FACE; NEURAL BASIS; PERCEPTION; FMRI; INVERSION AB Recent fMRI studies suggest that cortical face processing extends well beyond the fusiform face area (FFA), including unspecified portions of the anterior temporal lobe. However, the exact location of such anterior temporal region(s), and their role during active face recognition, remain unclear. Here we demonstrate that (in addition to FFA) a small bilateral site in the anterior tip of the collateral sulcus ('AT: the anterior temporal face patch) is selectively activated during recognition of faces but not houses (a non-face object). In contrast to the psychophysical prediction that inverted and contrast reversed faces are processed like other non-face objects, both FFA and AT (but not other visual areas) were also activated during recognition of inverted and contrast reversed faces. However, response accuracy was better correlated to recognition-driven activity in AT, compared to FFA. These data support a segregated, hierarchical model of face recognition processing, extending to the anterior temporal cortex. (C) 2012 Elsevier Inc. All rights reserved. C1 [Nasr, Shahin; Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinioula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tootell, Roger B. H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Tootell, Roger B. H.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Tootell, Roger B. H.] MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Nasr, S (reprint author), Massachusetts Gen Hosp, Athinioula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM shahin@nmr.mgh.harvard.edu FU National Institutes of Health (NIH) [R01 MH67529, R01 EY017081]; Martinos Center for Biomedical Imaging; NCRR; MIND Institute FX We thank Xiaomin Yue, Garth Coombs and Ellen Lau for help with data collection, and Jon Polimini for help with imaging protocols. We thank Daphne Holt for review and suggestions on the manuscript. This study was supported by the National Institutes of Health (NIH grants R01 MH67529 and R01 EY017081 to RBHT), the Martinos Center for Biomedical Imaging, the NCRR, the MIND Institute. NR 64 TC 42 Z9 42 U1 1 U2 27 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 NOV 15 PY 2012 VL 63 IS 3 BP 1743 EP 1753 DI 10.1016/j.neuroimage.2012.08.031 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 027UK UT WOS:000310379100072 PM 23034518 ER PT J AU Rowson, M Willott, C Hughes, R Maini, A Martin, S Miranda, JJ Pollit, V Smith, A Wake, R Yudkin, JS AF Rowson, Mike Willott, Chris Hughes, Rob Maini, Arti Martin, Sophie Jaime Miranda, J. Pollit, Vicki Smith, Abi Wake, Rae Yudkin, John S. TI Conceptualising global health: theoretical issues and their relevance for teaching SO GLOBALIZATION AND HEALTH LA English DT Article DE Global health; Medical education; Undergraduate; Curriculum; Globalization; Equity ID COMPETENCES; EDUCATION AB Background: There has long been debate around the definition of the field of education, research and practice known as global health. In this article we step back from attempts at definition and instead ask what current definitions tell us about the evolution of the field, identifying gaps and points of debate and using these to inform discussions of how global health might be taught. Discussion: What we now know as global health has its roots in the late 19th century, in the largely colonial, biomedical pursuit of 'international health'. The twentieth century saw a change in emphasis of the field towards a much broader conceptualisation of global health, encompassing broader social determinants of health and a truly global focus. The disciplinary focus has broadened greatly to include economics, anthropology and political science, among others. There have been a number of attempts to define the new field of global health. We suggest there are three central areas of contention: what the object of knowledge of global health is, the types of knowledge to be used and around the purpose of knowledge in the field of global health. We draw a number of conclusions from this discussion. First, that definitions should pay attention to differences as well as commonalities in different parts of the world, and that the definitions of global health themselves depend to some extent on the position of the definer. Second, global health's core strength lies in its interdisciplinary character, in particular the incorporation of approaches from outside biomedicine. This approach recognises that political, social and economic factors are central causes of ill health. Last, we argue that definition should avoid inclusion of values. In particular we argue that equity, a key element of many definitions of global health, is a value-laden concept and carries with it significant ideological baggage. As such, its widespread inclusion in the definitions of global health is inappropriate as it suggests that only people sharing these values may be seen as 'doing' global health. Nevertheless, discussion of values should be a key part of global health education. Summary: Our discussions lead us to emphasise the importance of an approach to teaching global health that is flexible, interdisciplinary and acknowledges the different interpretations and values of those practising and teaching the field. C1 [Rowson, Mike; Willott, Chris] UCL Inst Global Hlth, London WC1N 1EH, England. [Hughes, Rob] UK Dept Int Dev, London SW1E 5HE, England. [Maini, Arti] NHS Ealing, London, England. [Jaime Miranda, J.] Univ Peruana Cayetano Heredia, CRONICAS Ctr Excelencia Enfermedades Cron, Sch Med, Lima, Peru. [Jaime Miranda, J.] Univ Peruana Cayetano Heredia, Dept Med, Sch Med, Lima, Peru. [Pollit, Vicki] Royal Coll Physicians, Natl Clin Guideline Ctr, London NW1 4LE, England. [Smith, Abi] Southmead Hosp, Bristol BS10 5NB, Avon, England. [Wake, Rae] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Wake, Rae] Juba Teaching Hosp, Juba, Sudan. [Yudkin, John S.] UCL, London, England. RP Rowson, M (reprint author), UCL Inst Global Hlth, 30 Guilford St, London WC1N 1EH, England. EM m.rowson@ucl.ac.uk RI yan, liu/A-1822-2015; OI yan, liu/0000-0001-8517-1084; Miranda, J. Jaime/0000-0002-4738-5468 NR 36 TC 15 Z9 17 U1 2 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8603 J9 GLOBALIZATION HEALTH JI Global. Health PD NOV 14 PY 2012 VL 8 AR 36 DI 10.1186/1744-8603-8-36 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 090OD UT WOS:000314987700001 PM 23148788 ER PT J AU Holman, AG Gabuzda, D AF Holman, Alexander G. Gabuzda, Dana TI A Machine Learning Approach for Identifying Amino Acid Signatures in the HIV Env Gene Predictive of Dementia SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ENHANCES MACROPHAGE TROPISM; CENTRAL-NERVOUS-SYSTEM; TYPE-1 R5 ENVELOPES; V3 LOOP; NEUROCOGNITIVE DISORDERS; CEREBROSPINAL-FLUID; AIDS PATIENTS; CHEMOKINE RECEPTORS AB The identification of nucleotide sequence variations in viral pathogens linked to disease and clinical outcomes is important for developing vaccines and therapies. However, identifying these genetic variations in rapidly evolving pathogens adapting to selection pressures unique to each host presents several challenges. Machine learning tools provide new opportunities to address these challenges. In HIV infection, virus replicating within the brain causes HIV-associated dementia (HAD) and milder forms of neurocognitive impairment in 20-30% of patients with unsuppressed viremia. HIV neurotropism is primarily determined by the viral envelope (env) gene. To identify amino acid signatures in the HIV env gene predictive of HAD, we developed a machine learning pipeline using the PART rule-learning algorithm and C4.5 decision tree inducer to train a classifier on a meta-dataset (n = 860 env sequences from 78 patients: 40 HAD, 38 non-HAD). To increase the flexibility and biological relevance of our analysis, we included 4 numeric factors describing amino acid hydrophobicity, polarity, bulkiness, and charge, in addition to amino acid identities. The classifier had 75% predictive accuracy in leave-one-out cross-validation, and identified 5 signatures associated with HAD diagnosis (p<0.05, Fisher's exact test). These HAD signatures were found in the majority of brain sequences from 8 of 10 HAD patients from an independent cohort. Additionally, 2 HAD signatures were validated against env sequences from CSF of a second independent cohort. This analysis provides insight into viral genetic determinants associated with HAD, and develops novel methods for applying machine learning tools to analyze the genetics of rapidly evolving pathogens. C1 [Holman, Alexander G.; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Holman, AG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Dana_Gabuzda@dfci.harvard.edu FU NCI NIH HHS [P30 CA006516, P30 CA06516]; NIAID NIH HHS [P30 AI060354]; NIDA NIH HHS [DP1 DA028994, DA28994]; NIMH NIH HHS [MH83588, R01 MH083588] NR 104 TC 5 Z9 5 U1 4 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 NOV 14 PY 2012 VL 7 IS 11 AR e49538 DI 10.1371/journal.pone.0049538 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038CD UT WOS:000311151900159 PM 23166702 ER PT J AU Quayle, SN Lee, JY Cheung, LWT Ding, L Wiedemeyer, R Dewan, RW Huang-Hobbs, E Zhuang, L Wilson, RK Ligon, KL Mills, GB Cantley, LC Chin, L AF Quayle, Steven N. Lee, Jennifer Y. Cheung, Lydia W. T. Ding, Li Wiedemeyer, Ruprecht Dewan, Robert W. Huang-Hobbs, Emmet Zhuang, Li Wilson, Richard K. Ligon, Keith L. Mills, Gordon B. Cantley, Lewis C. Chin, Lynda TI Somatic Mutations of PIK3R1 Promote Gliomagenesis SO PLOS ONE LA English DT Article ID HIGH-FREQUENCY; GLIOBLASTOMA-MULTIFORME; ANAPLASTIC ASTROCYTOMA; ENDOMETRIAL CANCER; PTEN; AKT; ACTIVATION; P85-ALPHA; GLIOMA; GENE AB The phosphoinositide 3-kinase (PI3K) pathway is targeted for frequent alteration in glioblastoma (GBM) and is one of the core GBM pathways defined by The Cancer Genome Atlas. Somatic mutations of PIK3R1 are observed in multiple tumor types, but the tumorigenic activity of these mutations has not been demonstrated in GBM. We show here that somatic mutations in the iSH2 domain of PIK3R1 act as oncogenic driver events. Specifically, introduction of a subset of the mutations identified in human GBM, in the nSH2 and iSH2 domains, increases signaling through the PI3K pathway and promotes tumorigenesis of primary normal human astrocytes in an orthotopic xenograft model. Furthermore, we show that cells that are dependent on mutant P85 alpha-mediated PI3K signaling exhibit increased sensitivity to a small molecule inhibitor of AKT. Together, these results suggest that GBM patients whose tumors carry mutant PIK3R1 alleles may benefit from treatment with inhibitors of AKT. C1 [Quayle, Steven N.; Wiedemeyer, Ruprecht; Dewan, Robert W.; Huang-Hobbs, Emmet; Zhuang, Li; Ligon, Keith L.; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Quayle, SN (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM lchin@mdanderson.org RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU Canadian Institutes of Health Research; NCI NIH HHS [P01CA095616, P30 CA016672, P50 CA098258, RC2CA148268, U01CA141508, U01CA168394, U24 CA143845, U24CA143845]; NIGMS NIH HHS [R01 GM041890] NR 22 TC 15 Z9 15 U1 1 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 NOV 14 PY 2012 VL 7 IS 11 AR e49466 DI 10.1371/journal.pone.0049466 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038CD UT WOS:000311151900147 PM 23166678 ER PT J AU Agasti, SS Liong, M Peterson, VM Lee, H Weissleder, R AF Agasti, Sarit S. Liong, Monty Peterson, Vanessa M. Lee, Hakho Weissleder, Ralph TI Photocleavable DNA Barcode-Antibody Conjugates Allow Sensitive and Multiplexed Protein Analysis in Single Cells SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TUMOR-CELLS; IMMUNO-PCR; STEM-CELLS; SENSORS AB DNA barcoding is an attractive technology, as it allows sensitive and multiplexed target analysis. However, DNA barcoding of cellular proteins remains challenging, primarily because barcode amplification and readout techniques are often incompatible with the cellular microenvironment. Here we describe the development and validation of a photocleavable DNA barcode-antibody conjugate method for rapid, quantitative, and multiplexed detection of proteins in single live cells. Following target binding, this method allows DNA barcodes to be photoreleased in solution, enabling easy isolation, amplification, and readout As a proof of principle, wedemonstrate sensitive and multiplexed detection of protein biomarkers in a variety of cancer cells. C1 [Agasti, Sarit S.; Liong, Monty; Peterson, Vanessa M.; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institutes of Health [2P50CA086355-12, R01EB010011, HHSN268201000044C] FX We thank H. J. Chung, K. S. Yang, K. Tran, and J. A. Hendricks for helpful discussions and Y. Fisher-Jeffes for reviewing the manuscript. This work was supported in part by the National Institutes of Health (Grants 2P50CA086355-12 and R01EB010011 and TPEN Contract HHSN268201000044C). NR 25 TC 20 Z9 20 U1 6 U2 71 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 NOV 14 PY 2012 VL 134 IS 45 BP 18499 EP 18502 DI 10.1021/ja307689w PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 038RP UT WOS:000311192100006 PM 23092113 ER PT J AU Hedden, T Mormino, EC Amariglio, RE Younger, AP Schultz, AP Becker, JA Buckner, RL Johnson, KA Sperling, RA Rentz, DM AF Hedden, Trey Mormino, Elizabeth C. Amariglio, Rebecca E. Younger, Alayna P. Schultz, Aaron P. Becker, J. Alex Buckner, Randy L. Johnson, Keith A. Sperling, Reisa A. Rentz, Dorene M. TI Cognitive Profile of Amyloid Burden and White Matter Hyperintensities in Cognitively Normal Older Adults SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PITTSBURGH COMPOUND-B; LATENT-VARIABLE ANALYSIS; ALZHEIMERS-DISEASE; IN-VIVO; FRONTAL-LOBE; EXECUTIVE FUNCTIONS; EPISODIC MEMORY; DEMENTIA; AGE; DEPOSITION AB Amyloid burden and white matter hyperintensities (WMH) are two common markers of neurodegeneration present in advanced aging. Each represents a potential early indicator of an age-related neurological disorder that impacts cognition. The presence of amyloid is observed in a substantial subset of cognitively normal older adults, but the literature remains equivocal regarding whether amyloid in nondemented populations is deleterious to cognition. Similarly, WMH are detected in many nondemented older adults and there is a body of evidence indicating that WMH are associated with decreased executive function and other cognitive domains. The current study investigated amyloid burden and WMH in clinically normal older adult humans aged 65-86 (N = 168) and examined each biomarker's relation with cognitive domains of episodic memory, executive function, and speed of processing. Factors for each domain were derived from a neuropsychological battery on a theoretical basis without reference to the relation between cognition and the biomarkers. Amyloid burden and WMH were not correlated with one another. Age was associated with lower performance in all cognitive domains, while higher estimated verbal intelligence was associated with higher performance in all domains. Hypothesis-driven tests revealed that amyloid burden and WMH had distinct cognitive profiles, with amyloid burden having a specific influence on episodic memory and WMH primarily associated with executive function but having broad (but lesser) effects on the other domains. These findings suggest that even before clinical impairment, amyloid burden and WMH likely represent neuropathological cascades with distinct etiologies and dissociable influences on cognition. C1 [Hedden, Trey; Younger, Alayna P.; Schultz, Aaron P.; Buckner, Randy L.; Sperling, Reisa A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Mormino, Elizabeth C.; Amariglio, Rebecca E.; Schultz, Aaron P.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Younger, Alayna P.; Schultz, Aaron P.; Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Becker, J. Alex; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Hedden, Trey; Buckner, Randy L.; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Amariglio, Rebecca E.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02115 USA. RP Hedden, T (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM hedden@nmr.mgh.harvard.edu FU National Center for Research Resources (NCRR)-National Institutes of Health; NCRR [1S10RR023401, 1S10RR019307, 1S10RR023043]; National Institute on Aging [P01 AG036694, P50 AG0513421, R01 AG034556, R01 AG027435, P41 RR14075, K01 AG040197]; Alzheimer's Association [IIRG-08-90934]; Howard Hughes Medical Institute FX This research was performed in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR)-National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant numbers 1S10RR023401, 1S10RR019307, and 1S10RR023043. Funding was provided by National Institute on Aging Grants P01 AG036694, P50 AG0513421, R01 AG034556, R01 AG027435, P41 RR14075, and K01 AG040197; The Alzheimer's Association Grant IIRG-08-90934; and by the Howard Hughes Medical Institute. We thank Lauren Wadsworth, Natacha Lorius, and Emily Shire for assistance during subject recruitment and data collection. The Massachusetts Alzheimer's Disease Research Center, Gad Marshall, Brendon Boot, and Mykol Larvie provided assistance with clinical and neuropsychological characterization of participants. The Massachusetts General Hospital Molecular Imaging PET Core provided assistance with amyloid imaging. Christopher Gidicsin, Jacqueline Maye, Bill Klunk, and Chet Mathis provided assistance with PiB imaging. Minjie Wu provided software for labeling WMH and Koene Van Dijk advised on the adaptation of this software. Donald McLaren provided valuable discussion. Dr. Herman Buschke and the Albert Einstein College of Medicine of Yeshiva University provided the Memory Capacity Test. NR 75 TC 65 Z9 65 U1 1 U2 13 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 NOV 14 PY 2012 VL 32 IS 46 BP 16233 EP 16242 DI 10.1523/JNEUROSCI.2462-12.2012 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 037GU UT WOS:000311091000017 PM 23152607 ER PT J AU Liu, YY Csoka, E Zhou, HJ Posfai, M AF Liu, Yang-Yu Csoka, Endre Zhou, Haijun Posfai, Marton TI Core Percolation on Complex Networks SO PHYSICAL REVIEW LETTERS LA English DT Article ID VERTEX-COVER PROBLEM; SCALE-FREE NETWORKS; RANDOM GRAPHS; EXPLOSIVE PERCOLATION; STATISTICAL-MECHANICS; DYNAMICS; MODEL AB We analytically solve the core percolation problem for complex networks with arbitrary degree distributions. We find that purely scale-free networks have no core for any degree exponents. We show that for undirected networks if core percolation occurs then it is continuous while for directed networks it is discontinuous (and hybrid) if the in- and out-degree distributions differ. We also find that core percolations on undirected and directed networks have completely different critical exponents associated with their critical singularities. C1 [Liu, Yang-Yu; Posfai, Marton] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Liu, Yang-Yu; Posfai, Marton] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Liu, Yang-Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Posfai, Marton] Eotvos Lorand Univ, Dept Phys Complex Syst, H-1053 Budapest, Hungary. [Zhou, Haijun] Chinese Acad Sci, Inst Theoret Phys, State Key Lab Theoret Phys, Beijing 100190, Peoples R China. [Posfai, Marton] Budapest Univ Technol & Econ, Dept Theoret Phys, H-1521 Budapest, Hungary. RP Liu, YY (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM ya.liu@neu.edu RI Zhou, Hai-Jun/A-9804-2009; OI Zhou, Hai-Jun/0000-0003-4228-4438; Liu, Yang-Yu/0000-0003-2728-4907 FU NS-CTA; US Army Research Laboratory [W911NF-09-2-0053]; DARPA [11645021]; DTRA [BRBAA07-J-2-0035]; ERC [227701]; KTIA-OTKA [77780]; NSFC [11121403] FX We thank B. A. W. Brinkman, N. Azimi, C. Song, G. Tsekenis, and Y. Li for discussions. This work was supported by NS-CTA sponsored by US Army Research Laboratory under Agreement No. W911NF-09-2-0053; DARPA under Agreement No. 11645021; DTRA award WMD BRBAA07-J-2-0035; the generous support of Lockheed Martin; MTA Renyi "Lendulet'' Groups and Graphs Research Group; ERC Advanced Research Grant No. 227701 and KTIA-OTKA Grant No. 77780; and NSFC Grant No. 11121403. All authors have contributed equally to this work. NR 37 TC 19 Z9 20 U1 4 U2 45 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 EI 1079-7114 J9 PHYS REV LETT JI Phys. Rev. Lett. PD NOV 14 PY 2012 VL 109 IS 20 AR 205703 DI 10.1103/PhysRevLett.109.205703 PG 5 WC Physics, Multidisciplinary SC Physics GA 037WL UT WOS:000311137100012 PM 23215509 ER PT J AU Koerte, IK Ertl-Wagner, B Reiser, M Zafonte, R Shenton, ME AF Koerte, Inga K. Ertl-Wagner, Birgit Reiser, Maximilian Zafonte, Ross Shenton, Martha E. TI White Matter Integrity in the Brains of Professional Soccer Players Without a Symptomatic Concussion SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Koerte, Inga K.] Harvard Univ, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Zafonte, Ross] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Ertl-Wagner, Birgit; Reiser, Maximilian] Univ Munich, Inst Clin Radiol, Munich, Germany. [Shenton, Martha E.] VA Boston Healthcare Syst, Boston, MA USA. RP Koerte, IK (reprint author), Harvard Univ, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. EM ikoerte@bwh.harvard.edu FU NINDS NIH HHS [R01 NS078337] NR 5 TC 64 Z9 64 U1 1 U2 12 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 NOV 14 PY 2012 VL 308 IS 18 BP 1859 EP 1861 DI 10.1001/jama.2012.13735 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 035NA UT WOS:000310952700016 PM 23150002 ER PT J AU Gaziano, JM Sesso, HD Christen, WG Bubes, V Smith, JP MacFadyen, J Schvartz, M Manson, JE Glynn, RJ Buring, JE AF Gaziano, J. Michael Sesso, Howard D. Christen, William G. Bubes, Vadim Smith, Joanne P. MacFadyen, Jean Schvartz, Miriam Manson, JoAnn E. Glynn, Robert J. Buring, Julie E. TI Multivitamins in the Prevention of Cancer in Men The Physicians' Health Study II Randomized Controlled Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LONG-TERM SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; BETA-CAROTENE; VITAMIN-E; PROSTATE-CANCER; BREAST-CANCER; COLON-CANCER; GENERAL-POPULATION; VEGETABLE INTAKE AB Context Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality. Objective To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men. Design, Setting, and Participants A large-scale, randomized, double-blind, placebo-controlled trial (Physicians' Health Study II) of 14 641 male US physicians initially aged 50 years or older (mean [SD] age, 64.3 [9.2] years), including 1312 men with a history of cancer at randomization, enrolled in a common multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011. Intervention Daily multivitamin or placebo. Main Outcome Measures Total cancer (excluding nonmelanoma skin cancer), with prostate, colorectal, and other site-specific cancers among the secondary end points. Results During a median (interquartile range) follow-up of 11.2 (10.7-13.3) years, there were 2669 men with confirmed cancer, including 1373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (multivitamin and placebo groups, 17.0 and 18.3 events, respectively, per 1000 person-years; hazard ratio [HR], 0.92; 95% CI, 0.86-0.998; P = .04). There was no significant effect of a daily multivitamin on prostate cancer (multivitamin and placebo groups, 9.1 and 9.2 events, respectively, per 1000 person-years; HR, 0.98; 95% CI, 0.88-1.09; P = .76), colorectal cancer (multivitamin and placebo groups, 1.2 and 1.4 events, respectively, per 1000 person-years; HR, 0.89; 95% CI, 0.68-1.17; P = .39), or other site-specific cancers. There was no significant difference in the risk of cancer mortality (multivitamin and placebo groups, 4.9 and 5.6 events, respectively, per 1000 person-years; HR, 0.88; 95% CI, 0.77-1.01; P = .07). Daily multivitamin use was associated with a reduction in total cancer among 1312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56-0.96; P = .02), but this did not differ significantly from that among 13 329 men initially without cancer (HR, 0.94; 95% CI, 0.87-1.02; P = .15; P for interaction = .07). Conclusion In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer. C1 [Gaziano, J. Michael; Sesso, Howard D.; Christen, William G.; Bubes, Vadim; Smith, Joanne P.; MacFadyen, Jean; Schvartz, Miriam; Manson, JoAnn E.; Glynn, Robert J.; Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02120 USA. [Gaziano, J. Michael; Sesso, Howard D.; Christen, William G.; Bubes, Vadim; Smith, Joanne P.; MacFadyen, Jean; Schvartz, Miriam; Manson, JoAnn E.; Glynn, Robert J.; Buring, Julie E.] Harvard Univ, Sch Med, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Sesso, Howard D.; Manson, JoAnn E.; Buring, Julie E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Glynn, Robert J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jmgaziano@partners.org FU National Institutes of Health (NIH) [CA 097193, CA 34944, CA 40360, HL 26490, HL 34595]; Veterans Administration; BASF Corporation; Tomato Products Wellness Council; Cambridge Theranostics Ltd.; Harvard University (Clinical Nutrition Research Center); DSM Nutritional Products Inc; Aurora Foundation; Bristol-Meyers Squibb; AstraZeneca; Novartis FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Gaziano reported receiving investigator-initiated research funding from the National Institutes of Health (NIH), the Veterans Administration, and the BASF Corporation; assistance with study agents and packaging from BASF Corporation and Pfizer (formerly Wyeth, American Home Products, and Lederle); and assistance with study packaging provided by DSM Nutritional Products Inc (formerly Roche Vitamins). Dr Sesso reported receiving investigator-initiated research funding from the NIH, the Tomato Products Wellness Council, and Cambridge Theranostics Ltd. Dr Christen reported receiving research funding support from the NIH, Harvard University (Clinical Nutrition Research Center), and DSM Nutritional Products Inc (formerly Roche Vitamins). Dr Manson reported receiving investigator-initiated research funding from the NIH, and assistance with study pills and packaging from BASF and Cognis Corporations for the Women's Antioxidant and Folic Acid Cardiovascular Study and from Pronova Bio-Pharma and Pharmavite for the VITamin D and OmegA-3 TriaL, and funding from the nonprofit Aurora Foundation. Dr Glynn reported receiving investigator-initiated research funding from the NIH, Bristol-Meyers Squibb, AstraZeneca, and Novartis; and signed a consulting agreement with Merck to give an invited talk. Dr Buring reported receiving investigator-initiated research funding from the NIH, and assistance with study pills and packaging from Natural Source Vitamin E Association and Bayer Healthcare for the Women's Health Study. No other authors reported any financial disclosures.; This work was supported by grants CA 097193, CA 34944, CA 40360, HL 26490, and HL 34595 from the NIH and an investigator-initiated grant from BASF Corporation. Study agents and packaging were provided by BASF Corporation and Pfizer (formerly Wyeth, American Home Products, and Lederle) and study packaging was provided by DSM Nutritional Products Inc (formerly Roche Vitamins). NR 47 TC 77 Z9 78 U1 0 U2 56 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 14 PY 2012 VL 308 IS 18 BP 1871 EP 1880 DI 10.1001/jama.2012.14641 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 035NA UT WOS:000310952700023 PM 23162860 ER PT J AU Levin, GP Robinson-Cohen, C de Boer, IH Houston, DK Lohman, K Liu, YM Kritchevsky, SB Cauley, JA Tanaka, T Ferrucci, L Bandinelli, S Patel, KV Hagstrom, E Michaelsson, K Melhus, H Wang, T Wolf, M Psaty, BM Siscovick, D Kestenbaum, B AF Levin, Gregory P. Robinson-Cohen, Cassianne de Boer, Ian H. Houston, Denise K. Lohman, Kurt Liu, Yongmei Kritchevsky, Stephen B. Cauley, Jane A. Tanaka, Toshiko Ferrucci, Luigi Bandinelli, Stefania Patel, Kushang V. Hagstrom, Emil Michaelsson, Karl Melhus, Hakan Wang, Thomas Wolf, Myles Psaty, Bruce M. Siscovick, David Kestenbaum, Bryan TI Genetic Variants and Associations of 25-Hydroxyvitamin D Concentrations With Major Clinical Outcomes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID D-RECEPTOR GENE; FALSE DISCOVERY RATE; VITAMIN-D DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D; OLDER-ADULTS; CANCER-RISK; 1,25-DIHYDROXYVITAMIN D-3; CARDIOVASCULAR-DISEASE; SEASONAL-VARIATION; FRACTURE RISK AB Context Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. Objective To investigate whether common variation within genes encoding the vitamin D-binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes. Design, Setting, and Participants Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n=922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n=835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n=970; follow-up: 1991-1995 through 2008) cohort studies. Main Outcome Measure Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up. Results Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism. Conclusion Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor. JAMA. 2012;308(18):1898-1905 www.jama.com C1 [Levin, Gregory P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Robinson-Cohen, Cassianne; de Boer, Ian H.; Psaty, Bruce M.; Siscovick, David; Kestenbaum, Bryan] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [de Boer, Ian H.; Psaty, Bruce M.; Siscovick, David; Kestenbaum, Bryan] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Patel, Kushang V.] Univ Washington, Dept Anasthesiol & Pain Med, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Patel, Kushang V.] Univ Washington, Ctr Pain Res Impact Measurement & Effectiveness, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Grp Hlth Res Inst & Cooperat, Seattle, WA 98195 USA. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Univ, Dept Internal Med, Winston Salem, NC 27109 USA. [Lohman, Kurt] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Lohman, Kurt; Liu, Yongmei] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Houston, Denise K.; Lohman, Kurt; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Hagstrom, Emil; Melhus, Hakan] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Michaelsson, Karl] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. [Wang, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Wolf, Myles] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Levin, GP (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM glevin11@uw.edu OI Kritchevsky, Stephen/0000-0003-3336-6781; Robinson-Cohen, Cassianne/0000-0003-4783-7046; Cauley, Jane A/0000-0003-0752-4408 FU Abbott Laboratories; National Institute on Aging, National Institutes of Health; American Society for Nutrition; Department of Veteran Affairs; Abbott Nutrition Health Institute; National Institutes of Health; Shire; Amgen; Abbott; Genzyme; Medtronic FX The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr de Boer reported receiving research grant funding from Abbott Laboratories. Dr Houston reported pending institutional grant support from the National Institute on Aging, National Institutes of Health; and receiving payment for lectures from the American Society for Nutrition, the Department of Veteran Affairs, and Abbott Nutrition Health Institute. Dr Wang reported serving as a consultant to Diasorin; receiving an investigatorinitiated grant from Diasorin; and receiving payment for lectures from Diasorin. Dr Wolf reported serving as a consultant to Abbott, Genzyme, Luitpold, Mitsubishi, Cytochroma, Astellas, and Kai; receiving institutional grants from the National Institutes of Health, Shire, and Amgen; receiving payment for lectures from Abbott, Genzyme, and Shire; and having a pending patent. Dr Psaty reported serving on a data and safety monitoring board for a clinical trial of a device funded by Zoll ZifeCor; and serving on a steering committee for the Yale Open Data Access Project funded by Medtronic. Dr Kestenbaum reported receiving institutional grant support from Amgen. No other authors reported disclosures. NR 46 TC 79 Z9 83 U1 0 U2 19 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 NOV 14 PY 2012 VL 308 IS 18 BP 1898 EP 1905 DI 10.1001/jama.2012.17304 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 035NA UT WOS:000310952700026 PM 23150009 ER PT J AU Rowson, M Smith, A Hughes, R Johnson, O Maini, A Martin, S Martineau, F Miranda, JJ Pollit, V Wake, R Willott, C Yudkin, JS AF Rowson, Mike Smith, Abi Hughes, Rob Johnson, Oliver Maini, Arti Martin, Sophie Martineau, Fred Miranda, J. Jaime Pollit, Vicki Wake, Rae Willott, Chris Yudkin, John S. TI The evolution of global health teaching in undergraduate medical curricula SO GLOBALIZATION AND HEALTH LA English DT Article DE Global health; International health; Medical education; Undergraduate; Curriculum ID INTERNATIONAL HEALTH; EDUCATION; STUDENTS; GLOBALIZATION; OPPORTUNITIES; COUNTRIES; SCHOOLS; ISSUES AB Background: Since the early 1990s there has been a burgeoning interest in global health teaching in undergraduate medical curricula. In this article we trace the evolution of this teaching and present recommendations for how the discipline might develop in future years. Discussion: Undergraduate global health teaching has seen a marked growth over the past ten years, partly as a response to student demand and partly due to increasing globalization, cross-border movement of pathogens and international migration of health care workers. This teaching has many different strands and types in terms of topic focus, disciplinary background, the point in medical studies in which it is taught and whether it is compulsory or optional. We carried out a survey of medical schools across the world in an effort to analyse their teaching of global health. Results indicate that this teaching is rising in prominence, particularly through global health elective/exchange programmes and increasing teaching of subjects such as globalization and health and international comparison of health systems. Our findings indicate that global health teaching is moving away from its previous focus on tropical medicine towards issues of more global relevance. We suggest that there are three types of doctor who may wish to work in global health - the 'globalised doctor', 'humanitarian doctor' and 'policy doctor' - and that each of these three types will require different teaching in order to meet the required competencies. This teaching needs to be inserted into medical curricula in different ways, notably into core curricula, a special overseas doctor track, optional student selected components, elective programmes, optional intercalated degrees and postgraduate study. Summary: We argue that teaching of global health in undergraduate medical curricula must respond to changing understandings of the term global health. In particular it must be taught from the perspective of more disciplines than just biomedicine, in order to reflect the social, political and economic causes of ill health. In this way global health can provide valuable training for all doctors, whether they choose to remain in their countries of origin or work abroad. C1 [Rowson, Mike; Willott, Chris] UCL Inst Global Hlth, London, England. [Smith, Abi] Southmead Hosptial, Womens Hlth, Bristol BS10 5NB, Avon, England. [Hughes, Rob] UK Dept Int Dev, London, England. [Johnson, Oliver] Kings Coll London, Kings Ctr Global Hlth, London WC2R 2LS, England. [Maini, Arti] NHS Ealing, London, England. [Martineau, Fred] London Sch Hyg & Trop Med, London WC1, England. [Miranda, J. Jaime] Univ Peruana Cayetano Heredia, CRON Ctr Excelencia Enfermedades Cron, Lima, Peru. [Miranda, J. Jaime] Univ Peruana Cayetano Heredia, Sch Med, Dept Med, Lima, Peru. [Pollit, Vicki] Royal Coll Physicians, Natl Clin Guideline Ctr, London NW1 4LE, England. [Wake, Rae] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Wake, Rae] Juba Teaching Hosp, Juba, South Sudan, Sudan. [Yudkin, John S.] UCL, London WC1E 6BT, England. RP Rowson, M (reprint author), UCL Inst Global Hlth, 30 Guilford St, London, England. EM m.rowson@ucl.ac.uk RI yan, liu/A-1822-2015; OI yan, liu/0000-0001-8517-1084; Martineau, Fred/0000-0001-7137-8252; Miranda, J. Jaime/0000-0002-4738-5468; Johnson, Oliver/0000-0001-8698-0553 NR 32 TC 14 Z9 15 U1 2 U2 30 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8603 J9 GLOBALIZATION HEALTH JI Global. Health PD NOV 13 PY 2012 VL 8 AR 35 DI 10.1186/1744-8603-8-35 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 066YB UT WOS:000313257200001 PM 23148763 ER PT J AU Kocarnik, BM Liu, CF Wong, ES Perkins, M Maciejewski, ML Yano, EM Au, DH Piette, JD Bryson, CL AF Kocarnik, Beverly Mielke Liu, Chuan-Fen Wong, Edwin S. Perkins, Mark Maciejewski, Matthew L. Yano, Elizabeth M. Au, David H. Piette, John D. Bryson, Chris L. TI Does the presence of a pharmacist in primary care clinics improve diabetes medication adherence? SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Pharmacist; Medication adherence; Diabetes mellitus; Oral hypoglycemic agent; Patient-centered medical home ID REFILL COMPLIANCE; GLYCEMIC CONTROL; VETERANS; MANAGEMENT; MELLITUS; HOME; TRANSFORMATION; PROGRAM; SYSTEM; TEAM AB Background: Although oral hypoglycemic agents (OHAs) are an essential element of therapy for the management of type 2 diabetes, OHA adherence is often suboptimal. Pharmacists are increasingly being integrated into primary care as part of the move towards a patient-centered medical home and may have a positive influence on medication use. We examined whether the presence of pharmacists in primary care clinics was associated with higher OHA adherence. Methods: This retrospective cohort study analyzed 280,603 diabetes patients in 196 primary care clinics within the Veterans Affairs healthcare system. Pharmacists presence, number of pharmacist full-time equivalents (FTEs), and the degree to which pharmacy services are perceived as a bottleneck in each clinic were obtained from the 2007 VA Clinical Practice Organizational Survey-Primary Care Director Module. Patient-level adherence to OHAs using medication possession ratios (MPRs) were constructed using refill data from administrative pharmacy databases after adjusting for patient characteristics. Clinic-level OHA adherence was measured as the proportion of patients with MPR >=80%. We analyzed associations between pharmacy measures and clinic-level adherence using linear regression. Results: We found no significant association between pharmacist presence and clinic-level OHA adherence. However, adherence was lower in clinics where pharmacy services were perceived as a bottleneck. Conclusions: Pharmacist presence, regardless of the amount of FTE, was not associated with OHA medication adherence in primary care clinics. The exact role of pharmacists in clinics needs closer examination in order to determine how to most effectively use these resources to improve patient-centered outcomes including medication adherence. C1 [Liu, Chuan-Fen; Wong, Edwin S.; Perkins, Mark; Au, David H.; Bryson, Chris L.] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA. [Liu, Chuan-Fen; Wong, Edwin S.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Kocarnik, Beverly Mielke; Bryson, Chris L.] Univ Washington, Div Gen Internal Med, Seattle, WA 98104 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Yano, Elizabeth M.] Los Angeles VA, Ctr Study Healthcare Provider Behav, Los Angeles, CA 91343 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Au, David H.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Piette, John D.] VA Ann Arbor Healthcare Syst, VA Ctr Clin Management Res, Ann Arbor, MI 48105 USA. [Piette, John D.] Univ Michigan, Dept Internal Med, Sch Med, Ann Arbor, MI 48109 USA. RP Wong, ES (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM edwin.wong@va.gov FU Gilead Sciences; Department of Veterans Affairs, Health Services Research and Development [IIR 07-068-2]; VA Health Services Research and Development Postdoctoral Fellowship [TPP 61-024]; VA Career Development Award [03-177] FX DHA reports serving as a consultant for Bosch Inc. and receiving grants from Gilead Sciences. All other authors declare that they have no competing interests.; This research was supported by an Investigator Initiated Research Award (IIR 07-068-2) from the Department of Veterans Affairs, Health Services Research and Development. Dr. Wong is supported by VA Health Services Research and Development Postdoctoral Fellowship TPP 61-024. Dr. Piette is a VA Senior Research Career Scientist; Dr. Maciejewski and Dr. Yano are VA Research Career Scientists. Dr. Bryson was supported by VA Career Development Award 03-177. NR 38 TC 4 Z9 4 U1 2 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD NOV 13 PY 2012 VL 12 AR 391 DI 10.1186/1472-6963-12-391 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 063WZ UT WOS:000313034000001 PM 23148570 ER PT J AU Hazan, R Que, YA Maura, D Rahme, LG AF Hazan, Ronen Que, Yok-Ai Maura, Damien Rahme, Laurence G. TI A method for high throughput determination of viable bacteria cell counts in 96-well plates SO BMC MICROBIOLOGY LA English DT Article DE Bacterial-count; CFU; Persisters; High-Throughput; Screen ID PERSISTER CELLS; QUANTIFICATION; GENES; PCR AB Background: There are several methods for quantitating bacterial cells, each with advantages and disadvantages. The most common method is bacterial plating, which has the advantage of allowing live cell assessment through colony forming unit (CFU) counts but is not well suited for high throughput screening (HTS). On the other hand, spectrophotometry is adaptable to HTS applications but does not differentiate between dead and living bacteria and has low sensitivity. Results: Here, we report a bacterial cell counting method termed Start Growth Time (SGT) that allows rapid and serial quantification of the absolute or relative number of live cells in a bacterial culture in a high throughput manner. We combined the methodology of quantitative polymerase chain reaction (qPCR) calculations with a previously described qualitative method of bacterial growth determination to develop an improved quantitative method. We show that SGT detects only live bacteria and is sensitive enough to differentiate between 40 and 400 cells/mL. SGT is based on the re-growth time required by a growing cell culture to reach a threshold, and the notion that this time is proportional to the number of cells in the initial inoculum. We show several applications of SGT, including assessment of antibiotic effects on cell viability and determination of an antibiotic tolerant subpopulation fraction within a cell population. SGT results do not differ significantly from results obtained by CFU counts. Conclusion: SGT is a relatively quick, highly sensitive, reproducible and non-laborious method that can be used in HTS settings to longitudinally assess live cells in bacterial cell cultures. C1 [Hazan, Ronen; Que, Yok-Ai; Maura, Damien; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. [Hazan, Ronen; Que, Yok-Ai; Maura, Damien; Rahme, Laurence G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hazan, Ronen; Que, Yok-Ai; Maura, Damien; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA. [Hazan, Ronen; Que, Yok-Ai; Maura, Damien; Rahme, Laurence G.] Shriners Hosp Children Boston, Boston, MA 02114 USA. [Hazan, Ronen] Israeli Inst Adv Res, IYAR, Rehovot, Israel. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu FU Shriners' research grant [8770]; National Institute of Health [AI063433]; Swiss National Science Foundation/Swiss Medical Association (FMH) [PASMP3-123226]; SICPA Foundation; Shriners' Hospitals Research Fellowship [8494] FX We thank Michal Levitzky-Shpinner for assisting with SGT data analysis. This work was supported by Shriners' research grant #8770 (LGR) and in part by the National Institute of Health grant AI063433. YAQ was supported by a Swiss National Science Foundation/Swiss Medical Association (FMH) grant #PASMP3-123226 and a grant from the SICPA Foundation. RH was supported by Shriners' Hospitals Research Fellowship #8494. NR 16 TC 10 Z9 10 U1 6 U2 30 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD NOV 13 PY 2012 VL 12 AR 259 DI 10.1186/1471-2180-12-259 PG 7 WC Microbiology SC Microbiology GA 064FE UT WOS:000313056800001 PM 23148795 ER PT J AU Brown, S Xia, GQ Luhachack, LG Campbell, J Meredith, TC Chen, C Winstel, V Gekeler, C Irazoqui, JE Peschel, A Walker, S AF Brown, Stephanie Xia, Guoqing Luhachack, Lyly G. Campbell, Jennifer Meredith, Timothy C. Chen, Calvin Winstel, Volker Gekeler, Cordula Irazoqui, Javier E. Peschel, Andreas Walker, Suzanne TI Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PBP2A; antibiotic resistance; beta lactam potentiation; murein; WTA glycosylation ID N-ACETYLGLUCOSAMINYLRIBITOL LINKAGES; BETA-LACTAM ANTIBIOTICS; BACILLUS-SUBTILIS; CELL-WALL; D-ALANINE; ENZYMATIC-SYNTHESIS; LIPOTEICHOIC ACID; PEPTIDOGLYCAN; BIOSYNTHESIS; GENE AB Staphylococcus aureus peptidoglycan (PG) is densely functionalized with anionic polymers called wall teichoic acids (WTAs). These polymers contain three tailoring modifications: D-alanylation, alpha-O-GlcNAcylation, and beta-O-GlcNAcylation. Here we describe the discovery and biochemical characterization of a unique glycosyltransferase, TarS, that attaches beta-O-GlcNAc (beta-O-N-acetyl-D-glucosamine) residues to S. aureus WTAs. We report that methicillin resistant S. aureus (MRSA) is sensitized to beta-lactams upon tarS deletion. Unlike strains completely lacking WTAs, which are also sensitive to beta-lactams, Delta tarS strains have no growth or cell division defects. Because neither alpha-O-GlcNAc nor beta-O-Glucose modifications can confer resistance, the resistance phenotype requires a highly specific chemical modification of the WTA backbone, beta-O-GlcNAc residues. These data suggest beta-O-GlcNAcylated WTAs scaffold factors required for MRSA resistance. The beta-O-GlcNAc transferase identified here, TarS, is a unique target for antimicrobials that sensitize MRSA to beta-lactams. C1 [Xia, Guoqing; Winstel, Volker; Gekeler, Cordula; Peschel, Andreas] Univ Tubingen, Cellular & Mol Microbiol Sect, Interfac Inst Microbiol & Infect Med, D-72076 Tubingen, Germany. [Brown, Stephanie; Campbell, Jennifer; Meredith, Timothy C.; Chen, Calvin; Walker, Suzanne] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Luhachack, Lyly G.; Irazoqui, Javier E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Dev Immunol,Dept Pediat, Boston, MA 02115 USA. RP Xia, GQ (reprint author), Univ Tubingen, Cellular & Mol Microbiol Sect, Interfac Inst Microbiol & Infect Med, Elfriede Aulhorn Str 6, D-72076 Tubingen, Germany. EM guoqing.xia@med.uni-tuebingen.de; suzanne_walker@hms.harvard.edu RI Irazoqui, Javier/A-8028-2013; Xia, Guoqing/C-2365-2015; OI Xia, Guoqing/0000-0003-4492-9156; Irazoqui, Javier/0000-0001-6553-1329 FU National Institutes of Health [1R01AI099144, P01AI083214, T32AI007061]; German Research Council [TRR34, SFB766] FX We thank Charles Sheahan, Patricia Sanchez-Carballo, and Otto Holst for NMR assistance and Christiane Goerke and Petra Kuhner for RT-PCR support. This work was supported by National Institutes of Health Grants 1R01AI099144 and P01AI083214 (to S.W.) and T32AI007061 (to S.B. and T.C.M.), as well as by German Research Council Grants TRR34 (to A.P.) and SFB766 (to G.X.). NR 42 TC 62 Z9 62 U1 2 U2 32 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 NOV 13 PY 2012 VL 109 IS 46 BP 18909 EP 18914 DI 10.1073/pnas.1209126109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043UY UT WOS:000311576300060 PM 23027967 ER PT J AU Moldt, B Rakasz, EG Schultz, N Chan-Hui, PY Swiderek, K Weisgrau, KL Piaskowski, SM Bergman, Z Watkins, DI Poignard, P Burton, DR AF Moldt, Brian Rakasz, Eva G. Schultz, Niccole Chan-Hui, Po-Ying Swiderek, Kristine Weisgrau, Kimberly L. Piaskowski, Shari M. Bergman, Zachary Watkins, David I. Poignard, Pascal Burton, Dennis R. TI Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE passive transfer; animal model; antibody prophylaxis ID SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS; MONOCLONAL-ANTIBODY; VAGINAL TRANSMISSION; PASSIVE TRANSFER; CHIMERIC VIRUS; MACAQUES; VACCINE; BROAD; AIDS; SIV AB Most animal studies using passive administration of HIV broadly neutralizing monoclonal antibodies (bnMAbs) have associated protection against high-dose mucosal viral challenge with relatively high serum concentrations of antibody. We recently identified several bnMAbs remarkable for their in vitro potency against HIV. Of these bnMAbs, PGT121 is one of the most broad and potent antibodies isolated to date and shows 10- to 100-fold higher neutralizing activity than previously characterized bnMAbs. To evaluate the protective potency of PGT121 in vivo, we performed a protection study in rhesus macaques. Animals were i. v. administered 5 mg/kg, 1 mg/kg, or 0.2 mg/kg PGT121 24 h before being vaginally challenged with a single high dose of chimeric simian-human immunodeficiency virus (SHIV)(SF162P3). Sterilizing immunity was achieved in all animals administered 5 mg/kg and 1 mg/kg and three of five animals administered 0.2 mg/kg PGT121, with corresponding average antibody serum concentrations of 95 mu g/mL, 15 mu g/mL, and 1.8 mu g/mL, respectively. The results suggest that a protective serum concentration for PGT121 is in the single-digit mu g/mL for SHIVSF162P3, showing that PGT121 can mediate sterilizing immunity at serum concentrations that are significantly lower than those observed in previous studies and that may be achievable through vaccination with the development of a suitable immunogen. C1 [Moldt, Brian; Schultz, Niccole; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Moldt, Brian; Schultz, Niccole; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Rakasz, Eva G.; Weisgrau, Kimberly L.; Piaskowski, Shari M.; Bergman, Zachary] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53711 USA. [Chan-Hui, Po-Ying; Swiderek, Kristine] Theraclone Sci Inc, Seattle, WA 98104 USA. [Watkins, David I.] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA. [Poignard, Pascal] Int AIDS Vaccine Initiat, New York, NY 10038 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02129 USA. RP Poignard, P (reprint author), Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM poignard@scripps.edu; burton@scripps.edu RI poignard, pascal/N-6678-2013 FU International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium; National Institutes of Allergy and Infectious Diseases [R01 AI33292, U19AI090970]; Center for HIV/AIDS Vaccine Immunology and Immunogen [UM1AI100663]; Ragon Institute of MGH, MIT, and Harvard; Alfred Benzon Fellowship FX We are grateful for the assistance provided by the Virology group, Wisconsin National Primate Research Center. The following reagents were obtained through the AIDS Research and Reference Reagent Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health: Original stock of SHIVSF162P3 from Drs. Janet Harouse, Cecilia Cheng-Mayer, Ranajit Pal; and the Division of AIDS, NIAID, and human rIL-2 from Dr. Maurice Gately, Hoffmann-La Roche Inc. This work was supported by the International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium (D.R.B. and P.P.); National Institutes of Allergy and Infectious Diseases Grants R01 AI33292 (to D.R.B.) and U19AI090970 (to P.P.), Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1AI100663 (to D.R.B.); The Ragon Institute of MGH, MIT, and Harvard (D.R.B.); and an Alfred Benzon Fellowship (to B.M.). NR 37 TC 171 Z9 172 U1 2 U2 10 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 NOV 13 PY 2012 VL 109 IS 46 BP 18921 EP 18925 DI 10.1073/pnas.1214785109 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043UY UT WOS:000311576300062 PM 23100539 ER PT J AU Sadik, CD Kim, ND Iwakura, Y Luster, AD AF Sadik, Christian D. Kim, Nancy D. Iwakura, Yoichiro Luster, Andrew D. TI Neutrophils orchestrate their own recruitment in murine arthritis through C5aR and Fc gamma R signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AUTOANTIBODY-MEDIATED ARTHRITIS; BONE-MARROW-TRANSPLANTATION; RHEUMATOID SYNOVIAL-FLUIDS; IMMUNE-COMPLEX ARTHRITIS; INFL AMMATORY ARTHRITIS; SERUM-INDUCED ARTHRITIS; MAST-CELLS; INFLAMMATORY ARTHRITIS; STERILE INFLAMMATION; GENE-EXPRESSION AB Neutrophil recruitment into the joint is a hallmark of inflammatory arthritides, including rheumatoid arthritis (RA). In a mouse model of autoantibody-induced inflammatory arthritis, neutrophils infiltrate the joint via multiple chemoattractant receptors, including the leukotriene B-4 (LTB4) receptor BLT1 and the chemokine receptors CCR1 and CXCR2. Once in the joint, neutrophils perpetuate their own recruitment by releasing LTB4 and IL-1 beta, presumably after activation by immune complexes deposited on joint structures. Two pathways by which immune complexes may activate neutrophils include complement fixation, resulting in the generation of C5a, and direct engagement of Fc gamma receptors (Fc gamma Rs). Previous investigations showed that this model of autoantibody-induced arthritis requires the C5a receptor C5aR and Fc gamma Rs, but the simultaneous necessity for both pathways was not understood. Here we show that C5aR and Fc gamma Rs work in sequence to initiate and sustain neutrophil recruitment in vivo. Specifically, C5aR activation of neutrophils is required for LTB4 release and early neutrophil recruitment into the joint, whereas Fc gamma R engagement upon neutrophils induces IL-1 beta release and subsequent neutrophil-active chemokine production, ensuring continued inflammation. These findings support the concept that immune complex-mediated leukocyte activation is not composed of overlapping and redundant pathways, but that each element serves a distinct and critical function in vivo, culminating in tissue inflammation. C1 [Sadik, Christian D.; Kim, Nancy D.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Sch Med, Boston, MA 02114 USA. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Sch Med, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu RI Sadik, Christian/E-8404-2012; Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 FU German Research Foundation (Deutsche Forschungsgemeinschaft) [Sa1960/1-1]; Arthritis Foundation; National Institutes of Health [R01AI050892, K08 AR054094] FX This study was supported by German Research Foundation (Deutsche Forschungsgemeinschaft) Grant Sa1960/1-1 (to C.D.S.), the Arthritis Foundation (C.D.S.), and National Institutes of Health Grants R01AI050892 (to A.D.L.) and K08 AR054094 (to N.D.K.). NR 64 TC 48 Z9 48 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 13 PY 2012 VL 109 IS 46 BP E3177 EP E3185 DI 10.1073/pnas.1213797109 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043UY UT WOS:000311576300008 PM 23112187 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Obstruction in Hypertrophic Cardiomyopathy How Often Does It Occur? Should It be Treated? If So, How? SO CIRCULATION LA English DT Editorial Material ID LEFT-VENTRICULAR OUTFLOW; SUBAORTIC STENOSIS; TRACT OBSTRUCTION; ALCOHOL ABLATION; AORTIC STENOSIS; GUIDELINES; REDUCTION; MYECTOMY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med,TIMI Study Grp, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med,TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 20 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 13 PY 2012 VL 126 IS 20 BP 2369 EP 2370 DI 10.1161/CIRCULATIONAHA.112.144667 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 036RW UT WOS:000311048800007 PM 23076969 ER PT J AU Truesdell, SS Mortensen, RD Seo, M Schroeder, JC Lee, JH LeTonqueze, O Vasudevan, S AF Truesdell, S. S. Mortensen, R. D. Seo, M. Schroeder, J. C. Lee, J. H. LeTonqueze, O. Vasudevan, S. TI MicroRNA-mediated mRNA Translation Activation in Quiescent Cells and Oocytes Involves Recruitment of a Nuclear microRNP SO SCIENTIFIC REPORTS LA English DT Article ID C VIRUS-RNA; XENOPUS-OOCYTES; IN-VIVO; PROTEIN; ARGONAUTE; REPRESSION; CYCLE; GW182; LOCALIZATION; BIOGENESIS AB MicroRNAs can promote translation of specific mRNAs in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes. We report that microRNA-mediated upregulation of target mRNAs in oocytes is dependent on nuclear entry of the microRNA; cytoplasmically-injected microRNA repress target mRNAs. Components of the activation microRNP, AGO, FXR1 (FXR1-iso-a) and miR16 are present in the nucleus and cytoplasm. Importantly, microRNA target mRNAs for upregulation, Myt1, TNF alpha and a reporter bearing the TNF alpha AU-rich, microRNA target sequence, are associated with AGO in immature oocyte nuclei and AGO2 in G0 human nuclei, respectively. mRNAs that are repressed or lack target sites are not associated with nuclear AGO. Crosslinking-coupled immunopurification revealed greater association of AGO2 with FXR1 in the nucleus compared to cytoplasm. Consistently, overexpression of FXR1-iso-a rescues activation of cytoplasmically-injected RNAs and in low density, proliferating cells. These data indicate the importance of a compartmentalized AGO2-FXR1-iso-a complex for selective recruitment for microRNA-mediated upregulation. C1 [Truesdell, S. S.; Mortensen, R. D.; Seo, M.; Schroeder, J. C.; Lee, J. H.; LeTonqueze, O.; Vasudevan, S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Vasudevan, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. EM vasudevan.shobha@mgh.harvard.edu FU Leukemia and Lymphoma Society Special Fellowship [3300-09]; Cancer Research Institute Investigator; D. and M-E Ryder, Smith Family Foundation FX This work was supported by a Leukemia and Lymphoma Society Special Fellowship 3300-09, a Cancer Research Institute Investigator, the D. and M-E Ryder, Smith Family Foundation Awards and MGH start-up funds to SV. We thank J.A. Steitz, C.J. Wilusz, S. Lee and S.I. Bukhari for critical reading and advice, M. Fritzler, D. Bloch and Z. Mourelatos for reagents. NR 60 TC 29 Z9 30 U1 0 U2 13 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 NOV 13 PY 2012 VL 2 AR 842 DI 10.1038/srep00842 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 037JJ UT WOS:000311099600002 PM 23150790 ER PT J AU O'Hagan, JJ Hernan, MA Walensky, RP Lipsitch, M AF O'Hagan, Justin J. Hernan, Miguel A. Walensky, Rochelle P. Lipsitch, Marc TI Reply to 'Declining adherence as a more likely explanation than frailty of the apparent decline in efficacy in the CAPRISA 004 trial' SO AIDS LA English DT Letter C1 [O'Hagan, Justin J.; Hernan, Miguel A.; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [O'Hagan, Justin J.; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. [Hernan, Miguel A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol, Boston, MA 02115 USA. RP O'Hagan, JJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM johagan@hsph.harvard.edu OI Walensky, Rochelle P./0000-0002-8795-379X NR 7 TC 0 Z9 0 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 NOV 13 PY 2012 VL 26 IS 17 BP 2262 EP 2263 DI 10.1097/QAD.0b013e328355cf0f PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 032WQ UT WOS:000310750800019 ER PT J AU Kathiresan, S AF Kathiresan, Sekar TI Will Cholesteryl Ester Transfer Protein Inhibition Succeed Primarily by Lowering Low-Density Lipoprotein Cholesterol? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE cardiovascular diseases; genetics; lipids; lipoproteins ID CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; CETP MASS; HIGH-RISK; PCSK9; SAFETY; GENE; HDL; HYPERCHOLESTEROLEMIA; POLYMORPHISM C1 [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kathiresan, Sekar] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan@partners.org NR 25 TC 14 Z9 14 U1 0 U2 6 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 NOV 13 PY 2012 VL 60 IS 20 BP 2049 EP 2052 DI 10.1016/j.jacc.2012.08.967 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 033GW UT WOS:000310783200007 PM 23083775 ER PT J AU Aragon, K Covinsky, K Miao, YH Boscardin, WJ Flint, L Smith, AK AF Aragon, Katherine Covinsky, Kenneth Miao, Yinghui Boscardin, W. John Flint, Lynn Smith, Alexander K. TI Use of the Medicare Posthospitalization Skilled Nursing Benefit in the Last 6 Months of Life SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HOME RESIDENTS; PALLIATIVE CARE; HOSPICE; END; HOSPITALIZATION; PAYMENT; DEATH AB Background: In the last 6 months of life, many older adults will experience a hospitalization, followed by a transfer to a skilled nursing facility (SNF) for additional care. We sought to examine patterns of Medicare post-hospitalization SNF use in the last 6 months of life. Methods: We used data from the Health and Retirement Study, a longitudinal survey of older adults, linked to Medicare claims (January 1994 through December 2007). We determined the number of individuals 65 years or older at death who had used the SNF benefit in the last 6 months of life. We report demographic, social, and clinical correlates of SNF use. We examined the relationship between place of death and hospice use for those residing in nursing homes and the community before the last 6 months of life. Results: The mean age at death among 5163 individuals was 82.8 years; 54.5% of the cohort were female, and 23.2% had resided in a nursing home. In total, 30.5% had used the SNF benefit in the last 6 months of life, and 9.2% had died while enrolled in the SNF benefit. The use of the SNF benefit was greater among patients who were 85 years or older, had at least a high school education, did not have cancer, resided in a nursing home, used home health services, and were expected to die soon (P < .01 for all). Of community dwellers who had used the SNF benefit, 42.5% died in a nursing home, 10.7% died at home, 38.8% died in the hospital, and 8.0% died elsewhere. In contrast, of community dwellers who did not use the SNF benefit, 5.3% died in a nursing home, 40.6% died at home, 44.3% died in the hospital, and 9.8% died elsewhere. Conclusions: Almost one-third of older adults receive care in a SNF in the last 6 months of life under the Medicare posthospitalization benefit, and 1 in 11 elders will die while enrolled in the SNF benefit. Palliative care services should be incorporated into SNF-level care. C1 [Covinsky, Kenneth; Boscardin, W. John; Flint, Lynn; Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94121 USA. [Aragon, Katherine] Univ Calif San Francisco, Dept Med, Div Palliat Care, San Francisco, CA 94121 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Biostat, San Francisco, CA 94121 USA. [Covinsky, Kenneth; Miao, Yinghui; Boscardin, W. John; Flint, Lynn; Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, 4150 Clement St,181G, San Francisco, CA 94121 USA. EM aksmith@ucsf.edu FU National Institute on Aging [K24AG029812]; National Center for Research Resources University of California, San Francisco-Clinical and Translational Science Institute [UL1 RR024131] FX This study was supported in part by grants K24AG029812 from the National Institute on Aging (Dr Covinsky) and UL1 RR024131 from the National Center for Research Resources University of California, San Francisco-Clinical and Translational Science Institute (Dr Smith). NR 24 TC 13 Z9 13 U1 5 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 12 PY 2012 VL 172 IS 20 BP 1573 EP 1579 DI 10.1001/archinternmed.2012.4451 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 035XR UT WOS:000310987300008 PM 23026981 ER PT J AU Gellad, W Mor, M Zhao, XH Donohue, J Good, C AF Gellad, Walid Mor, Maria Zhao, Xinhua Donohue, Julie Good, Chester TI Variation in Use of High-Cost Diabetes Mellitus Medications in the VA Healthcare System SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID MEDICARE C1 [Gellad, Walid; Mor, Maria; Zhao, Xinhua; Good, Chester] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Gellad, Walid; Good, Chester] Univ Pittsburgh, Dept Med, Div Gen Med, Pittsburgh, PA USA. [Mor, Maria] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Donohue, Julie] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Gellad, Walid] RAND Corp, Pittsburgh, PA USA. [Good, Chester] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. RP Gellad, W (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM walid.gellad@va.gov OI Donohue, Julie/0000-0003-2418-6017 NR 9 TC 10 Z9 10 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 12 PY 2012 VL 172 IS 20 BP 1608 EP 1609 DI 10.1001/archinternmed.2012.4482 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 035XR UT WOS:000310987300018 PM 23044980 ER PT J AU Haak, CS Bhayana, B Farinelli, WA Anderson, RR Haedersdal, M AF Haak, Christina S. Bhayana, Brijesh Farinelli, William A. Anderson, R. Rox Haedersdal, Merete TI The impact of treatment density and molecular weight for fractional laser-assisted drug delivery SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Laser-assisted drug delivery; Fractional CO2 laser; Transdermal drug delivery; Intradermal drug delivery; Topical treatment ID TRANSDERMAL DELIVERY; PHOTODYNAMIC THERAPY; PHOTOTHERMOLYSIS; MICROPORATION; LIDOCAINE; ABLATION; SKIN AB Ablative fractional lasers (AFXL) facilitate uptake of topically applied drugs by creating narrow open micro-channels into the skin, but there is limited information on optimal laser settings for delivery of specific molecules. The objective of this study was to investigate the impact of laser treatment density (% of skin occupied by channels) and molecular weight (MW) for fractional CO2 laser-assisted drug delivery. AFXL substantially increased intra-and transcutaneous delivery of polyethylene glycols (PEGs) in a MW range from 240 to 4300 Da (Nuclear Magnetic Resonance, p<0.01). Increasing laser density from 1 to 20% resulted in augmented intra-and transdermal delivery (p<0.01), but densities higher than 1% resulted in reduced delivery per channel. Mass spectrometry indicated that larger molecules have greater intracutaneous retention than transcutaneous penetration. At 5% density, median delivery of PEGs with mean MW of 400, 1000, 2050 and 3350 Da were respectively 0.87, 0.31, 0.23 and 0.15 mg intracutaneously and 0.72, 0.20. 0.08 and 0.03 mg transcutaneously, giving a 5.8- and 24.0-fold higher intra-and transcutaneous delivery of PEG400 than PEG3350 (p<0.01). This study substantiates that fractional CO2 laser treatment allows uptake of small and large molecules into and through human skin, and that laser density can be varied to optimize intracutaneous or transcutaneous delivery. (C) 2012 Elsevier B.V. All rights reserved. C1 [Haak, Christina S.; Haedersdal, Merete] Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, DK-2400 Copenhagen NV, Denmark. [Haak, Christina S.; Bhayana, Brijesh; Farinelli, William A.; Anderson, R. Rox; Haedersdal, Merete] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Haak, CS (reprint author), Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol D 92, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. EM christinahaak@dadlnet.dk NR 25 TC 18 Z9 19 U1 0 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD NOV 10 PY 2012 VL 163 IS 3 BP 335 EP 341 DI 10.1016/j.jconrel.2012.09.008 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 053JC UT WOS:000312266500008 PM 23000695 ER PT J AU Neuberg, DS AF Neuberg, Donna S. TI Reprise: Gemtuzumab Ozogamicin for Older Patients With Acute Myeloid Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Neuberg, DS (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2012 VL 30 IS 32 BP 3905 EP 3906 DI 10.1200/JCO.2012.43.6592 PG 2 WC Oncology SC Oncology GA 035AU UT WOS:000310914800009 PM 22987082 ER PT J AU Bellon, JR Wong, JS Burstein, HJ AF Bellon, Jennifer R. Wong, Julia S. Burstein, Harold J. TI Should Response to Preoperative Chemotherapy Affect Radiotherapy Recommendations After Mastectomy for Stage II Breast Cancer? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMASTECTOMY RADIATION IMPROVES; NEOADJUVANT CHEMOTHERAPY; LOCOREGIONAL RECURRENCE; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; CONSERVING THERAPY; NODE STATUS; RISK; IRRADIATION; SURVIVAL AB A healthy 38-year-old woman presents with a palpable mass at the two o'clock position of the left breast. Mammography discloses a 3.2-cm spiculated lesion corresponding with the palpable abnormality, and ultrasonography confirms a solid mass in the breast and an enlarged, 2.1-cm lymph node with a thickened cortex in the ipsilateral axilla. Ultrasound-guided core needle biopsy of the breast mass diagnoses an invasive ductal carcinoma, poorly differentiated (grade 3), with lymphovascular invasion. Lymph node fine-needle aspiration is positive for malignant cells. Immunohistochemical studies on the breast specimen indicate that the tumor is triple negative, lacking estrogen and progesterone receptors and human epidermal growth factor 2 expression. The patient receives preoperative chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel. She has a dramatic clinical response; the breast and axillary masses shrink rapidly with chemotherapy. At the time of mastectomy, she is found to have several foci of residual invasive cancer in the breast (largest focus, 0.3 cm), located in a 3-cm tumor bed showing treatment effect (Figs 1A to 1C). The margins are negative, as are all 11 axillary lymph nodes. Her pathologic response to neoadjuvant treatment is judged Miller-Payne grade 4. She is referred for consideration of postmastectomy irradiation. C1 [Bellon, Jennifer R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bellon, JR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 25 TC 4 Z9 5 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2012 VL 30 IS 32 BP 3916 EP 3920 DI 10.1200/JCO.2012.44.3358 PG 5 WC Oncology SC Oncology GA 035AU UT WOS:000310914800013 PM 23032626 ER PT J AU Mamounas, EP Anderson, SJ Dignam, JJ Bear, HD Julian, TB Geyer, CE Taghian, A Wickerham, DL Wolmark, N AF Mamounas, Eleftherios P. Anderson, Stewart J. Dignam, James J. Bear, Harry D. Julian, Thomas B. Geyer, Charles E., Jr. Taghian, Alphonse Wickerham, D. Lawrence Wolmark, Norman TI Predictors of Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From Combined Analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PREOPERATIVE CHEMOTHERAPY; COMPETING RISKS; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; CANCER PATIENTS; PROTOCOL B-27; MASTECTOMY; DOXORUBICIN; TAMOXIFEN; FAILURE AB Purpose The limited information on predictors of locoregional recurrence (LRR) after neoadjuvant chemotherapy (NC) has resulted in controversy about the optimal use of adjuvant radiotherapy and the timing of sentinel lymph node biopsy. Patients and Methods We examined patterns and predictors of LRR as first event in combined analysis of two National Surgical Adjuvant Breast and Bowel Project (NSABP) neoadjuvant trials. NC was either doxorubicin/cyclophosphamide (AC) alone or AC followed by neoadjuvant/adjuvant docetaxel. Lumpectomy patients received breast radiotherapy alone; mastectomy patients received no radiotherapy. Pathologic complete response was defined as the absence of invasive tumor in the breast. Multivariate analyses were used to identify independent predictors of LRR. The primary end point was time to LRR as first event. Results In 3,088 patients, 335 LRR events had occurred after 10 years of follow-up. The 10-year cumulative incidence of LRR was 12.3% for mastectomy patients (8.9% local; 3.4% regional) and 10.3% for lumpectomy plus breast radiotherapy patients (8.1% local; 2.2% regional). Independent predictors of LRR in lumpectomy patients were age, clinical nodal status (before NC), and pathologic nodal status/breast tumor response; in mastectomy patients, they were clinical tumor size (before NC), clinical nodal status (before NC), and pathologic nodal status/breast tumor response. By using these independent predictors, groups at low, intermediate, and high risk of LRR could be identified. Nomograms that incorporate these independent predictors were created. Conclusion In patients treated with NC, age, clinical tumor characteristics before NC, and pathologic nodal status/breast tumor response after NC can be used to predict risk for LRR and to optimize the use of adjuvant radiotherapy. J Clin Oncol 30:3960-3966. (C) 2012 by American Society of Clinical Oncology C1 [Mamounas, Eleftherios P.] Aultman Hlth Fdn, Canton, OH 44710 USA. [Mamounas, Eleftherios P.; Anderson, Stewart J.; Dignam, James J.; Bear, Harry D.; Julian, Thomas B.; Geyer, Charles E., Jr.; Taghian, Alphonse; Wickerham, D. Lawrence; Wolmark, Norman] Natl Surg Adjuvant Breast & Bowel Project Operat, Pittsburgh, PA USA. [Anderson, Stewart J.] Univ Pittsburgh, Pittsburgh, PA USA. [Julian, Thomas B.; Wickerham, D. Lawrence; Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. [Dignam, James J.] Univ Chicago, Chicago, IL 60637 USA. [Bear, Harry D.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Bear, Harry D.] Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. [Geyer, Charles E., Jr.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Taghian, Alphonse] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mamounas, EP (reprint author), Aultman Hlth Fdn, 2600 6th St SW, Canton, OH 44710 USA. EM tmamounas@aultman.com OI Anderson, Stewart/0000-0001-8948-0650 FU Public Health Service from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services [U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651] FX Supported in part by Public Health Service Grants No. U10CA-12027, U10CA-69974, U10CA-37377, and U10CA-69651 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 24 TC 114 Z9 126 U1 0 U2 9 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 NOV 10 PY 2012 VL 30 IS 32 BP 3960 EP 3966 DI 10.1200/JCO.2011.40.8369 PG 7 WC Oncology SC Oncology GA 035AU UT WOS:000310914800020 PM 23032615 ER PT J AU Ewertz, M Gray, KP Regan, MM Ejlertsen, B Price, KN Thurlimann, B Bonnefoi, H Forbes, JF Paridaens, RJ Rabaglio, M Gelber, RD Colleoni, M Lang, I Smith, IE Coates, AS Goldhirsch, A Mouridsen, HT AF Ewertz, Marianne Gray, Kathryn P. Regan, Meredith M. Ejlertsen, Bent Price, Karen N. Thuerlimann, Beat Bonnefoi, Herve Forbes, John F. Paridaens, Robert J. Rabaglio, Manuela Gelber, Richard D. Colleoni, Marco Lang, Istvan Smith, Ian E. Coates, Alan S. Goldhirsch, Aron Mouridsen, Henning T. TI Obesity and Risk of Recurrence or Death After Adjuvant Endocrine Therapy With Letrozole or Tamoxifen in the Breast International Group 1-98 Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BODY-MASS INDEX; POSTMENOPAUSAL WOMEN; METABOLIC SYNDROME; CANCER; CHEMOTHERAPY; ANASTROZOLE; EXPRESSION; ADIPOSITY; SEQUENCE; ESTRONE AB Purpose To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up. Patients and Methods This report analyzes 4,760 patients with breast cancer randomly assigned to 5 years of monotherapy with letrozole or tamoxifen in the BIG 1-98 trial with available information on BMI at randomization. Multivariable Cox modeling assessed the association of BMI with disease-free survival, overall survival (OS), breast cancer-free interval, and distant recurrence-free interval and tested for treatment-by-BMI interaction. Median follow-up was 8.7 years. Results Seventeen percent of patients have died. Obese patients (BMI >= 30 kg/m(2)) had slightly poorer OS (hazard ratio [HR] = 1.19; 95% CI, 0.99 to 1.44) than patients with normal BMI (< 25 kg/m(2)), whereas no trend in OS was observed in overweight (BMI 25 to < 30 kg/m(2)) versus normal-weight patients (HR = 1.02; 95% CI, 0.86 to 1.20). Treatment-by-BMI interactions were not statistically significant. The HRs for OS comparing obese versus normal BMI were HR = 1.22 (95% CI, 0.93 to 1.60) and HR = 1.18 (95% CI, 0.91 to 1.52) in the letrozole and tamoxifen groups, respectively. Conclusion There was no evidence that the benefit of letrozole over tamoxifen differed according to patients' BMI. J Clin Oncol 30:3967-3975. (C) 2012 by American Society of Clinical Oncology C1 [Ewertz, Marianne] Univ So Denmark, Odense Univ Hosp, Inst Clin Res, Odense, Denmark. [Ejlertsen, Bent] Univ Copenhagen Hosp, Danish Breast Canc Cooperat Grp Stat Ctr, DK-2100 Copenhagen, Denmark. [Ejlertsen, Bent] Univ Copenhagen Hosp, Rigshosp, DK-2100 Copenhagen, Denmark. [Mouridsen, Henning T.] Rigshosp, Danish Breast Canc Cooperat Grp, Copenhagen, Denmark. [Gray, Kathryn P.; Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA USA. [Gray, Kathryn P.; Regan, Meredith M.; Price, Karen N.; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res, Bern, Switzerland. [Rabaglio, Manuela] IBCSG Coordinating Ctr, Bern, Switzerland. [Rabaglio, Manuela] Univ Bern, Inselspital, CH-3010 Bern, Switzerland. [Goldhirsch, Aron] St Anna Clin, Swiss Ctr Breast Hlth, Lugano Sorengo, Switzerland. [Bonnefoi, Herve] Univ Bordeaux, FNCLCC Unicanc, Inst Bergonie, Bordeaux, France. [Forbes, John F.] Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2300, Australia. [Coates, Alan S.] Int Breast Canc Study Grp, Sydney, NSW, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Paridaens, Robert J.] Catholic Univ Louvain, Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Colleoni, Marco; Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Smith, Ian E.] Royal Marsden Hosp, London SW3 6JJ, England. RP Ewertz, M (reprint author), Univ So Denmark, Odense Univ Hosp, Dept Oncol ME, Inst Clin Res, Odense, Denmark. EM mew@dadlnet.dk FU Novartis; Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research; National Cancer Institute [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland FX The Breast International Group 1-98 trial was sponsored by Novartis and coordinated by International Breast Cancer Study Group (IBCSG). IBCSG is supported by Swedish Cancer Society, the Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, National Cancer Institute Grant No. CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland. NR 33 TC 41 Z9 41 U1 4 U2 11 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 NOV 10 PY 2012 VL 30 IS 32 BP 3967 EP 3975 DI 10.1200/JCO.2011.40.8666 PG 9 WC Oncology SC Oncology GA 035AU UT WOS:000310914800021 PM 23045588 ER PT J AU Fisch, MJ Lee, JW Cleeland, CS AF Fisch, Michael J. Lee, Ju-Whei Cleeland, Charles S. TI Clinically Based Palliative Care Training Is Needed Urgently for All Oncologists Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID SIMULATION; CANCER C1 [Fisch, Michael J.; Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fisch, MJ (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 7 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 NOV 10 PY 2012 VL 30 IS 32 BP 4043 EP 4043 DI 10.1200/JCO.2012.45.5691 PG 1 WC Oncology SC Oncology GA 035AU UT WOS:000310914800036 ER PT J AU Shah, SM Drage, MG Lichtman, AH Haddad, RI AF Shah, Sonali M. Drage, Michael G. Lichtman, Andrew H. Haddad, Robert I. TI Metastatic Human Papillomavirus-Positive Nasopharyngeal Carcinoma With an Unusual Pattern of Aggressive Hematogenous Spread SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CANCER C1 [Shah, Sonali M.; Haddad, Robert I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haddad, Robert I.] Harvard Univ, Sch Med, Boston, MA USA. [Drage, Michael G.; Lichtman, Andrew H.; Haddad, Robert I.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shah, SM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 7 TC 2 Z9 2 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 NOV 10 PY 2012 VL 30 IS 32 BP E321 EP E323 DI 10.1200/JCO.2012.42.3566 PG 3 WC Oncology SC Oncology GA 035AU UT WOS:000310914800001 PM 23008310 ER PT J AU Kunz, LM Yeh, RW Normand, SLT AF Kunz, Lauren M. Yeh, Robert W. Normand, Sharon-Lise T. TI Comparative effectiveness research: does one size fit all? SO STATISTICS IN MEDICINE LA English DT Article ID CAROTID-ARTERY STENOSIS; CLINICAL-TRIALS; ENDARTERECTOMY; ANGIOPLASTY; OUTCOMES AB In this commentary, we argue that although randomization has many benefits, not all questions we seek to answer fit into a randomized setting. Our argument utilizes the clinical setting of carotid atherosclerosis management where specific clinical questions are answered by using a variety of comparative effectiveness designs. Observational studies should not be ruled out when designing studies to address questions of comparative effectiveness. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Kunz, Lauren M.; Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yeh, Robert W.] Harvard Clin Res Inst, Boston, MA USA. RP Normand, SLT (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM sharon@hcp.med.harvard.edu FU Research Participation Program, Center for Devices and Radiological Health; Harvard Clinical Research Institute, Boston; FDA [1074629] FX Ms. Kunz was funded by the Research Participation Program, Center for Devices and Radiological Health, administered by the Oak Ridge Institute for Science and Education through an inter-agency agreement between the US Department of Energy and the US Food and Drug Administration (FDA). Dr. Yeh's effort was supported by the Harvard Clinical Research Institute, Boston. Dr. Normand was supported, in part, by Contract No. 1074629 from the FDA. Dr. Normand serves as Vice Chair, Methodology Committee of the Patient Centered Outcomes Research Institute (PCORI). The views expressed by Dr. Normand do not necessarily reflect those of the PCORI. NR 11 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 3062 EP 3065 DI 10.1002/sim.5482 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200016 PM 22806612 ER PT J AU Albasanz-Puig, A Murray, J Namekata, M Wijelath, ES AF Albasanz-Puig, Adaia Murray, Jacqueline Namekata, Mayumi Wijelath, Errol S. TI Opposing roles of STAT-1 and STAT-3 in regulating vascular endothelial growth factor expression in vascular smooth muscle cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE VEGF; STAT-3; STAT-1; HIF-1 alpha; Oncostatin-M; Smooth muscle cell ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ONCOSTATIN-M; VEGF EXPRESSION; PLAQUE NEOVASCULARIZATION; SIGNALING PATHWAY; EPITHELIAL-CELLS; CARCINOMA CELLS; CAROTID PLAQUE; COLON-CANCER; IN-VIVO AB Increased microvessel density in atherosclerotic plaques plays a major role in promoting plaque destabilization resulting in increased risk of stroke and myocardial infarction. Previously we have shown that expression of the inflammatory cytokine, Oncostatin-M (OSM), in human atherosclerotic plaques correlated with increased microvessel density, indicating a role for OSM in promoting plaque angiogenesis. The purpose of this study was to determine the mechanism by which OSM regulates Vascular Endothelial Growth Factor (VEGF) expression in human coronary artery smooth muscle cells. Using shRNA and overexpression studies, we have shown that the transcription factor, STAT-1 inhibited VEGF expression, while STAT-3 promoted the expression of VEGF. We further show that the mechanism by which STAT-1 and STAT-3 regulates VEGF expression is through modulation of Hypoxia Inducible Factor-1 alpha (HIF-1 alpha). STAT-1 suppresses HIF-1 alpha expression, whereas STAT-3 positively regulates HIF-1 alpha expression. These results provide evidence that activated STAT-1 and STAT-3 regulate VEGF expression indirectly, by modulating HIF-1 alpha activity. Published by Elsevier Inc. C1 VA Puget Sound Hlth Care Syst, Div Vasc Surg, Dept Surg, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. RP Wijelath, ES (reprint author), Dept Vet Affairs Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM errolw@u.washington.edu FU US Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program FX This study was supported by the US Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program. NR 45 TC 12 Z9 13 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 9 PY 2012 VL 428 IS 1 BP 179 EP 184 DI 10.1016/j.bbrc.2012.10.037 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 043DN UT WOS:000311523200031 PM 23068100 ER PT J AU Grapov, D Adams, SH Pedersen, TL Garvey, WT Newman, JW AF Grapov, Dmitry Adams, Sean H. Pedersen, Theresa L. Garvey, W. Timothy Newman, John W. TI Type 2 Diabetes Associated Changes in the Plasma Non-Esterified Fatty Acids, Oxylipins and Endocannabinoids SO PLOS ONE LA English DT Article ID NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; GLUCOSE-PRODUCTION; PULSATILE INSULIN; BETA-OXIDATION; METABOLISM; PATHOGENESIS; ACTIVATION; DELIVERY; HUMANS AB Type 2 diabetes has profound effects on metabolism that can be detected in plasma. While increases in circulating non-esterified fatty acids (NEFA) are well-described in diabetes, effects on signaling lipids have received little attention. Oxylipins and endocannabinoids are classes of bioactive fatty acid metabolites with many structural members that influence insulin signaling, adipose function and inflammation through autocrine, paracrine and endocrine mechanisms. To link diabetes-associated changes in plasma NEFA and signaling lipids, we quantitatively targeted >150 plasma lipidome components in age- and body mass index-matched, overweight to obese, non-diabetic (n = 12) and type 2 diabetic (n = 43) African-American women. Diabetes related NEFA patterns indicated similar to 60% increase in steroyl-CoA desaturase activity and similar to 40% decrease in very long chain polyunsaturated fatty acid chain shortening, patterns previously associated with the development of nonalcoholic fatty liver disease. Further, epoxides and ketones of eighteen carbon polyunsaturated fatty acids were elevated >80% in diabetes and strongly correlated with changes in NEFA, consistent with their liberation during adipose lipolysis. Endocannabinoid behavior differed by class with diabetes increasing an array of N-acylethanolamides which were positively correlated with pro-inflammatory 5-lipooxygenase-derived metabolites, while monoacylglycerols were negatively correlated with body mass. These results clearly show that diabetes not only results in an increase in plasma NEFA, but shifts the plasma lipidomic profiles in ways that reflect the biochemical and physiological changes of this pathological state which are independent of obesity associated changes. Citation: Grapov D, Adams SH, Pedersen TL, Garvey WT, Newman JW (2012) Type 2 Diabetes Associated Changes in the Plasma Non-Esterified Fatty Acids, Oxylipins and Endocannabinoids. PLoS ONE 7(11): e48852. doi: 10.1371/journal.pone.0048852 C1 [Grapov, Dmitry; Adams, Sean H.; Newman, John W.] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. [Grapov, Dmitry; Adams, Sean H.; Pedersen, Theresa L.; Newman, John W.] USDA, Obes & Metab Res Unit, ARS, Western Human Nutr Res Ctr, Davis, CA USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. RP Newman, JW (reprint author), Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. EM john.newman@ars.usda.gov FU National Institute of General Medical Sciences-National Institutes of Health (NIGMS-NIH) [T32-GM008799]; intramural United States Department of Agriculture-Agricultural Research Service (USDA-ARS) [5306-51530-019-00D]; National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NIDDK) [R01DK078328-01]; NIH [DK-038764, DK-083562, P01 HL-055782]; Merit Review program of the Department of Veterans Affairs; University of Alabama (UAB) Center for Clinical and Translational Science [UL1 RR025777]; UAB Nutrition and Obesity Research Center [P30-DK56336]; UAB Diabetes Research and Training Center [P60 DK079626] FX This work was funded in part by the following: National Institute of General Medical Sciences-National Institutes of Health (NIGMS-NIH) T32-GM008799 (D.G.); intramural United States Department of Agriculture-Agricultural Research Service (USDA-ARS) Project 5306-51530-019-00D (J.W.N. and S.H.A.); National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NIDDK) R01DK078328-01 (S.H.A.); NIH grants DK-038764, DK-083562, and P01 HL-055782 and the Merit Review program of the Department of Veterans Affairs (W.T.G.). The authors also acknowledge support from the research core facilities of the University of Alabama (UAB) Center for Clinical and Translational Science (UL1 RR025777), the UAB Nutrition and Obesity Research Center (P30-DK56336), and the UAB Diabetes Research and Training Center (P60 DK079626). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 32 Z9 32 U1 1 U2 31 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 NOV 8 PY 2012 VL 7 IS 11 AR e48852 DI 10.1371/journal.pone.0048852 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053KE UT WOS:000312269500039 PM 23144998 ER PT J AU Haile, CN De La Garza, R Mahoney, JJ Nielsen, DA Kosten, TR Newton, TF AF Haile, Colin N. De La Garza, Richard, II Mahoney, James J., III Nielsen, David A. Kosten, Thomas R. Newton, Thomas F. TI The Impact of Disulfiram Treatment on the Reinforcing Effects of Cocaine: A Randomized Clinical Trial SO PLOS ONE LA English DT Article ID DOPAMINE-BETA-HYDROXYLASE; PLACEBO-CONTROLLED TRIAL; ALTERNATIVE REINFORCERS; ALCOHOL DEPENDENCE; FOLLOW-UP; HUMANS; INHIBITION; SEEKING; NOREPINEPHRINE; PSYCHOTHERAPY AB Background: Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users. Methods: Seventeen non-treatment seeking, cocaine-dependent volunteers participated in this double-blind, placebo-controlled, laboratory-based study. A cross-over design was utilized in which participants received placebo in one phase and disulfiram (250 mg/d) in the other. Following three days of study medication participants completed two choice sessions. In one they made 10 choices between receiving an intravenous infusion of saline or money that increased in value (US$ 0.05-16) and in the other cocaine (20 mg) or money. Results: Participants chose cocaine more than saline under both disulfiram and placebo conditions (p<0.05). Unexpectedly, disulfiram increased both the number of cocaine and saline infusion choices (p<0.05). We next examined the relationship between disulfiram dose and cocaine choices. Disulfiram dose (mg/kg bodyweight) was negatively correlated with number of choices for cocaine (p<0.05). Disulfiram also enhanced cocaine-induced increases in cardiovascular measures (p's<0.05-0.01). Conclusions: Disulfiram's impact on the reinforcing effects of cocaine depends on dose relative to body weight. Our results suggest that the use of weight-based medication doses would produce more reliable effects, consistent with weight-based dosing used in pediatrics and in preclinical research. C1 [Haile, Colin N.; De La Garza, Richard, II; Mahoney, James J., III; Nielsen, David A.; Kosten, Thomas R.; Newton, Thomas F.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Newton, TF (reprint author), Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM tnewton@bcm.edu RI De La Garza, Richard/B-2489-2014; Mahoney, James/I-2753-2014; OI De La Garza, Richard/0000-0003-1943-4469; Mahoney, James/0000-0003-0824-1776; Haile, Colin/0000-0001-8293-7291; newton, thomas/0000-0002-3198-5901 FU National Institutes of Health [R01 DA017705, K24 DA017754, M01 RR00188] FX This study was funded by research grants from the National Institutes of Health (R01 DA017705, K24 DA017754, and M01 RR00188). Sterile cocaine HCl for human use was provided by a contractor for National Institute on Drug Abuse's Drug Supply Program (RTI International, North Carolina). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 13 Z9 13 U1 3 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 8 PY 2012 VL 7 IS 11 AR e47702 DI 10.1371/journal.pone.0047702 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053KE UT WOS:000312269500010 PM 23144826 ER PT J AU Radich, JP Kopecky, KJ Appelbaum, FR Kamel-Reid, S Stock, W Malnassy, G Paietta, E Wadleigh, M Larson, RA Emanuel, P Tallman, M Lipton, J Turner, AR Deininger, M Druker, BJ AF Radich, Jerald P. Kopecky, Kenneth J. Appelbaum, Frederick R. Kamel-Reid, Suzanne Stock, Wendy Malnassy, Greg Paietta, Elisabeth Wadleigh, Martha Larson, Richard A. Emanuel, Peter Tallman, Martin Lipton, Jeff Turner, A. Robert Deininger, Michael Druker, Brian J. TI A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia SO BLOOD LA English DT Article ID CYTOGENETIC RESPONSES; INTERFERON-ALPHA; FOLLOW-UP; NILOTINIB; RESISTANT; THERAPY AB Tyrosine kinase inhibitor therapy with imatinib (IM), dasatinib (DAS), or nilotinib is very effective in chronic-phase chronic myeloid leukemia. Two hundred fifty-three patients with newly diagnosed chronic-phase chronic myeloid leukemia were randomized to IM 400 mg/day or DAS 100 mg/day. The proportion of patients achieving a complete cytogenetic remission rate was superior with DAS (84% vs 69%), as was the 12-month molecular response by the proportions of patients achieving > 3-log, > 4-log, and > 4.5-log reduction in BCR-ABL transcript levels. Overall and progression-free survival was similar in the 2 arms. Among patients who achieved hematologic CR, 3-year relapse-free survival was 91% with DAS and 88% with IM 400 mg. Grade 3 and 4 toxicities were most commonly hematologic, including thrombocytopenia in 18% and 8% of DAS and IM patients, respectively. DAS induced more complete cytogenetic response and deeper molecular responses after 12 months, compared with IM 400 mg, and with a median follow-up of 3.0 years there have been very few deaths, relapses, or progressions in the 2 arms. In summary, DAS compared with IM appeared to have more short-term cytogenetic and molecular response, more hematologic toxicity, and similar overall survival. This trial is registered at www.clinicaltrials.gov as NCT00070499. (Blood. 2012;120(19):3898-3905) C1 [Radich, Jerald P.; Kopecky, Kenneth J.; Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Kopecky, Kenneth J.] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Kamel-Reid, Suzanne] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Stock, Wendy; Malnassy, Greg; Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emanuel, Peter] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Tallman, Martin] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lipton, Jeff] Univ Toronto, Toronto, ON, Canada. [Turner, A. Robert] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Deininger, Michael] Univ Utah, Salt Lake City, UT USA. [Druker, Brian J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Radich, JP (reprint author), Fred Hutchinson Canc Res Ctr, 1400 Fairview Ave N,C2-023, Seattle, WA 98109 USA. EM jradich@fhcrc.org OI Emanuel, Peter/0000-0002-9764-2434; Larson, Richard/0000-0001-9168-3203 FU Public Health Service from the National Institutes of Health [CA32102-31, CA38926-25, CA31946, CA41287, CA32291, CA077202]; Canadian Cancer Society Research Institute [21039]; Novartis; BMS; Pfizer FX This work was supported in part by Public Health Service Cooperative Agreement grant numbers CA32102-31, CA38926-25; CA31946, CA41287, CA32291, and CA077202 from the National Institutes of Health; and Canadian Cancer Society Research Institute Grant 21039.; J.P.R. received honoraria (consulting) from Novartis, Bristol-Myers Squibb (BMS), Pfizer, and Ariad, and research support from Novartis and BMS. K.J.K. received salary support for this trial from BMS as did the SWOG Statistical Center. R. A. L. received honoraria for consulting from Novartis, BMS, and Pfizer. W. S. received research support from Novartis and BMS. M. D. received honorarium (consulting) from BMS and Novartis, and research support from Novartis. B.J.D.'s institution received clinical trial support from Novartis and BMS. Oregon Health & Science University (OHSU) and B.J.D. have a financial interest in MolecularMD. OHSU has licensed technology used in some of these clinical trials to MolecularMD. This potential individual and institutional conflict of interest has been reviewed and managed by OHSU. J.L. received consulting fees from BMS, Novartis, and Pfizer, and research support from BMS and Novartis. A. R. T. received honoraria and research support form BMS and Novartis. The remaining authors declare no competing financial interests. NR 17 TC 66 Z9 67 U1 0 U2 11 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 8 PY 2012 VL 120 IS 19 BP 3898 EP 3905 DI 10.1182/blood-2012-02-410688 PG 8 WC Hematology SC Hematology GA 044OL UT WOS:000311629600011 PM 22915637 ER PT J AU Tian, Z Zhao, JJ Tai, YT Amin, SB Hu, YG Berger, AJ Richardson, P Chauhan, D Anderson, KC AF Tian, Ze Zhao, Jian-jun Tai, Yu-Tzu Amin, Samir B. Hu, Yiguo Berger, Allison J. Richardson, Paul Chauhan, Dharminder Anderson, Kenneth C. TI Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells SO BLOOD LA English DT Article ID PIM SERINE/THREONINE KINASES; PROTEASOME INHIBITOR MLN9708; MULTIPLE-MYELOMA CELLS; MICRORNA EXPRESSION; IN-VIVO; BREAST-CANCER; GROWTH; TUMORIGENESIS; APOPTOSIS; SURVIVAL AB miRs play a critical role in tumor pathogenesis as either oncogenes or tumor-suppressor genes. However, the role of miRs and their regulation in response to proteasome inhibitors in multiple myeloma (MM) is unclear. In the current study, miR profiling in proteasome inhibitor MLN2238-treated MM.1S MM cells shows up-regulation of miR33b. Mechanistic studies indicate that the induction of miR33b is predominantly via transcriptional regulation. Examination of miR33b in patient MM cells showed a constitutively low expression. Overexpression of miR33b decreased MM cell viability, migration, colony formation, and increased apoptosis and sensitivity of MM cells to MLN2238 treatment. In addition, overexpression of miR33b or MLN2238 exposure negatively regulated oncogene PIM-1 and blocked PIM-1 wild-type, but not PIM-1 mutant, luciferase activity. Moreover, PIM-1 overexpression led to significant abrogation of miR33b- or MLN2238-induced cell death. SGI-1776, a biochemical inhibitor of PIM-1, triggered apoptosis in MM. Finally, overexpression of miR33b inhibited tumor growth and prolonged survival in both subcutaneous and disseminated human MM xenograft models. Our results show that miR33b is a tumor suppressor that plays a role during MLN2238-induced apoptotic signaling in MM cells, and these data provide the basis for novel therapeutic strategies targeting miR33b in MM. (Blood. 2012;120(19):3958-3967) C1 [Tian, Ze; Zhao, Jian-jun; Tai, Yu-Tzu; Amin, Samir B.; Hu, Yiguo; Richardson, Paul; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Tian, Ze; Zhao, Jian-jun; Tai, Yu-Tzu; Amin, Samir B.; Hu, Yiguo; Richardson, Paul; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Berger, Allison J.] Takeda Oncol Co, Millenium, Boston, MA USA. RP Chauhan, D (reprint author), Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Mayer 561,450 Brookline Ave, Boston, MA 02115 USA. EM Dharminder_Chauhan@dfci.harvard.edu; Kenneth_Anderson@dfci.harvard.edu OI Amin, Samir/0000-0002-3207-9505 FU National Institutes of Health [P50100707, PO1-CA078378, RO1 CA050947] FX This investigation was supported by National Institutes of Health Specialized Programs of Research Excellence (SPORE) grants P50100707, PO1-CA078378, and RO1 CA050947. K. C. A. is an American Cancer Society Clinical Research Professor. J. H. Lin at Dana-Farber Cancer Institute provided normal plasma cells. NR 43 TC 30 Z9 34 U1 2 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 8 PY 2012 VL 120 IS 19 BP 3958 EP 3967 DI 10.1182/blood-2012-01-401794 PG 10 WC Hematology SC Hematology GA 044OL UT WOS:000311629600018 PM 22983447 ER PT J AU Matsuura, S Komeno, Y Stevenson, KE Biggs, JR Lam, K Tang, TD Lo, MC Cong, XL Yan, M Neuberg, DS Zhang, DE AF Matsuura, Shinobu Komeno, Yukiko Stevenson, Kristen E. Biggs, Joseph R. Lam, Kentson Tang, Tingdong Lo, Miao-Chia Cong, Xiuli Yan, Ming Neuberg, Donna S. Zhang, Dong-Er TI Expression of the runt homology domain of RUNX1 disrupts homeostasis of hematopoietic stem cells and induces progression to myelodysplastic syndrome SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; GENE-EXPRESSION; BONE-MARROW; AML1/PEBP2-ALPHA-B GENE; ADULT HEMATOPOIESIS; POINT MUTATIONS; CD34(+) CELLS; CBF-BETA; MICE AB Mutations of RUNX1 are detected in patients with myelodysplastic syndrome (MDS). In particular, C-terminal truncation mutations lack a transcription regulatory domain and have increased DNA binding through the runt homology domain. The expression of the runt homology domain, RUNX1(41-214), in mouse hematopoietic cells induced progression to MDS and acute myeloid leukemia. Analysis of premyelodysplastic animals found expansion of c-Kit(+)Sca-1(+)Lin(-) cells and skewed differentiation to myeloid at the expense of the lymphoid lineage. These abnormalities correlate with the phenotype of Runx1-deficient animals, as expected given the reported dominant-negative role of C-terminal mutations over the full-length RUNX1. However, MDS is not observed in Runx1-deficient animals. Gene expression profiling found that RUNX1(41214) c-Kit(+)Sca-1(+)Lin(-) cells have an overlapping yet distinct gene expression profile from Runx1-deficient animals. Moreover, an unexpected parallel was observed between the hematopoietic phenotype of RUNX1(41-214) and aged animals. Genes deregulated in RUNX1(41-214), but not in Runx1-deficient animals, were inversely correlated with the aging gene signature of HSCs, suggesting that disruption of the expression of genes related to normal aging by RUNX1 mutations contributes to development of MDS. The data presented here provide insights into the mechanisms of development of MDS in HSCs by C-terminal mutations of RUNX1. (Blood. 2012;120(19):4028-4037) C1 [Matsuura, Shinobu; Komeno, Yukiko; Biggs, Joseph R.; Lam, Kentson; Tang, Tingdong; Lo, Miao-Chia; Cong, Xiuli; Yan, Ming; Zhang, Dong-Er] Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Stevenson, Kristen E.; Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zhang, Dong-Er] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Zhang, Dong-Er] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. RP Zhang, DE (reprint author), Univ Calif San Diego, Moores UCSD Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM d7zhang@ucsd.edu FU National Institutes of Health [P01DK080665, R01CA096735]; Ruth L. Kirschstein National Research Service Award [F32HL091641] FX This work was supported by funding from the National Institutes of Health (P01DK080665 and R01CA096735). S. M. is a recipient of the Ruth L. Kirschstein National Research Service Award (F32HL091641). NR 50 TC 8 Z9 8 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 8 PY 2012 VL 120 IS 19 BP 4028 EP 4037 DI 10.1182/blood-2012-01-404533 PG 10 WC Hematology SC Hematology GA 044OL UT WOS:000311629600025 PM 22919028 ER PT J AU Verma, S Miles, D Gianni, L Krop, IE Welslau, M Baselga, J Pegram, M Oh, DY Dieras, V Guardino, E Fang, L Lu, MW Olsen, S Blackwell, K AF Verma, Sunil Miles, David Gianni, Luca Krop, Ian E. Welslau, Manfred Baselga, Jose Pegram, Mark Oh, Do-Youn Dieras, Veronique Guardino, Ellie Fang, Liang Lu, Michael W. Olsen, Steven Blackwell, Kim CA EMILIA Study Grp TI Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PHASE-II; CAPECITABINE; LAPATINIB; ANTIBODY; RECEPTOR; THERAPY; PLUS AB Background Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker. Methods We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane, to T-DM1 or lapatinib plus capecitabine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. Secondary end points included progression-free survival (investigator-assessed), the objective response rate, and the time to symptom progression. Two interim analyses of overall survival were conducted. Results Among 991 randomly assigned patients, median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001), and median overall survival at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001). The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with lapatinib plus capecitabine; P<0.001); results for all additional secondary end points favored T-DM1. Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine. Conclusions T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane. (Funded by F. Hoffmann-La Roche/Genentech; EMILIA ClinicalTrials.gov number, NCT00829166.) C1 [Verma, Sunil] Sunnybrook Odette Canc Ctr, Toronto, ON M4N 3M5, Canada. [Miles, David] Mt Vernon Canc Ctr, Northwood, Middx, England. [Gianni, Luca] Hosp San Raffaele, I-20132 Milan, Italy. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baselga, Jose] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Welslau, Manfred] Med Off Hematol, Aschaffenburg, Germany. [Pegram, Mark] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Oh, Do-Youn] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Guardino, Ellie; Fang, Liang; Lu, Michael W.; Olsen, Steven] Genentech Inc, San Francisco, CA 94080 USA. [Dieras, Veronique] Inst Curie, Paris, France. [Blackwell, Kim] Duke Univ, Med Ctr, Durham, NC USA. RP Verma, S (reprint author), Sunnybrook Odette Canc Ctr, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM sunil.verma@sunnybrook.ca FU F. Hoffmann-La Roche/Genentech FX Funded by F. Hoffmann-La Roche/Genentech; EMILIA ClinicalTrials.gov number, NCT00829166. NR 15 TC 856 Z9 887 U1 19 U2 162 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 NOV 8 PY 2012 VL 367 IS 19 BP 1783 EP 1791 DI 10.1056/NEJMoa1209124 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 033DG UT WOS:000310773200005 PM 23020162 ER PT J AU Getahun, BS Yeshi, MM Roberts, DJ AF Getahun, Birhanu Sendek Yeshi, Melisachew M. Roberts, Drucilla J. TI Case 34-2012: A 27-Year-Old Woman in Ethiopia with Severe Pain, Bleeding, and Shock during Labor SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MATERNAL MORTALITY; RUPTURED UTERUS; UTERINE RUPTURE; ABDOMINAL-PAIN; RISK-FACTORS; TERM LABOR; 3 DELAYS; PREGNANCY; DELIVERY; MANAGEMENT C1 [Getahun, Birhanu Sendek] Univ Gondar, Dept Obstet & Gynecol, Gondar Coll Med & Hlth Sci, Gondar, Ethiopia. [Yeshi, Melisachew M.] Mekelle Univ, Ayder Referral Hosp, Dept Pathol, Mekelle, Ethiopia. [Roberts, Drucilla J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Getahun, BS (reprint author), Univ Gondar, Dept Obstet & Gynecol, Gondar Coll Med & Hlth Sci, Gondar, Ethiopia. NR 33 TC 1 Z9 1 U1 0 U2 2 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 NOV 8 PY 2012 VL 367 IS 19 BP 1839 EP 1845 DI 10.1056/NEJMcpc1209508 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 033DG UT WOS:000310773200014 PM 23134385 ER PT J AU Clark, J Silvaggi, JM Kiselak, T Zheng, KN Clore, EL Dai, Y Bass, CE Simon, DK AF Clark, Joanne Silvaggi, Jessica M. Kiselak, Tomas Zheng, Kangni Clore, Elizabeth L. Dai, Ying Bass, Caroline E. Simon, David K. TI Pgc-1 alpha Overexpression Downregulates Pitx3 and Increases Susceptibility to MPTP Toxicity Associated with Decreased Bdnf SO PLOS ONE LA English DT Article ID COACTIVATOR 1-ALPHA PGC-1-ALPHA; TYROSINE-HYDROXYLASE EXPRESSION; AMYOTROPHIC-LATERAL-SCLEROSIS; AGE-OF-ONSET; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; TRANSCRIPTIONAL COACTIVATOR; SUBSTANTIA-NIGRA; SKELETAL-MUSCLE AB Multiple mechanisms likely contribute to neuronal death in Parkinson's disease (PD), including mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) positively regulates the expression of genes required for mitochondrial biogenesis and the cell's antioxidant responses. Also, expression of PGC-1 alpha-regulated genes is low in substantia nigra (SN) neurons in early PD. Thus upregulation of PGC-1 alpha is a candidate neuroprotective strategy in PD. Here, an adeno-associated virus (AAV) was used to induce unilateral overexpression of Pgc-1 alpha, or a control gene, in the SN of wild-type C57BL/6CR mice. Three weeks after AAV administration, mice were treated with saline or MPTP. Overexpression of Pgc-1 alpha in the SN induced expression of target genes, but unexpectedly it also greatly reduced the expression of tyrosine hydroxylase (Th) and other markers of the dopaminergic phenotype with resultant severe loss of striatal dopamine. Reduced Th expression was associated with loss of Pitx3, a transcription factor that is critical for the development and maintenance of dopaminergic cells. Expression of the neurotrophic factor Bdnf, which also is regulated by Pitx3, similarly was reduced. Overexpression of Pgc-1 alpha also led to increased sensitivity to MPTP-induced death of Th+ neurons. Pgc-1 alpha overexpression alone, in the absence of MPTP treatment, did not lead to cell loss in the SN or to loss of dopaminergic terminals. These data demonstrate that overexpression of Pgc-1 alpha results in dopamine depletion associated with lower levels of Pitx3 and enhances susceptibility to MPTP. These data may have ramifications for neuroprotective strategies targeting overexpression of PGC-1 alpha in PD. C1 [Clark, Joanne; Kiselak, Tomas; Zheng, Kangni; Clore, Elizabeth L.; Dai, Ying; Simon, David K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Silvaggi, Jessica M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bass, Caroline E.] SUNY Buffalo, Sch Med & Biosci, Dept Pharmacol & Toxicol, Buffalo, NY 14260 USA. RP Clark, J (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. EM jclark3@bidmc.harvard.edu FU National Parkinson Foundation; National Research Service Award [F32DK075253-02]; Michael J. Fox Foundation; Mentored Research Scientist Development Award [K01DA024763] FX This work was funded by a National Parkinson Foundation "Mega-Research Project" Award (DKS), a National Research Service Award (F32DK075253-02, JMS), a Target Validation award from the Michael J. Fox Foundation (DKS) and a Mentored Research Scientist Development Award (K01DA024763, CEB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 27 Z9 27 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 NOV 7 PY 2012 VL 7 IS 11 AR e48925 DI 10.1371/journal.pone.0048925 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800172 PM 23145024 ER PT J AU Kim, SK Gignoux, CR Wall, JD Lum-Jones, A Wang, HS Haiman, CA Chen, GK Henderson, BE Kolonel, LN Le Marchand, L Stram, DO Saxena, R Cheng, I AF Kim, Sung K. Gignoux, Christopher R. Wall, Jeffrey D. Lum-Jones, Annette Wang, Hansong Haiman, Christopher A. Chen, Gary K. Henderson, Brian E. Kolonel, Laurence N. Le Marchand, Loic Stram, Daniel O. Saxena, Richa Cheng, Iona TI Population Genetic Structure and Origins of Native Hawaiians in the Multiethnic Cohort Study SO PLOS ONE LA English DT Article ID SOUTHEAST-ASIAN POPULATIONS; PACIFIC ISLANDERS; MITOCHONDRIAL DNAS; AFRICAN-AMERICANS; SPEAKING PEOPLES; TIME DEPENDENCY; UNITED-STATES; EXPRESS-TRAIN; DISEASE GENES; LOS-ANGELES AB The population genetic structure of Native Hawaiians has yet to be comprehensively studied, and the ancestral origins of Polynesians remain in question. In this study, we utilized high-resolution genome-wide SNP data and mitochondrial genomes of 148 and 160 Native Hawaiians, respectively, to characterize their population structure of the nuclear and mitochondrial genomes, ancestral origins, and population expansion. Native Hawaiians, who self-reported full Native Hawaiian heritage, demonstrated 78% Native Hawaiian, 11.5% European, and 7.8% Asian ancestry with 99% belonging to the B4 mitochondrial haplogroup. The estimated proportions of Native Hawaiian ancestry for those who reported mixed ancestry (i.e. 75% and 50% Native Hawaiian heritage) were found to be consistent with their self-reported heritage. A significant proportion of Melanesian ancestry (mean = 32%) was estimated in 100% self-reported Native Hawaiians in an ADMIXTURE analysis of Asian, Melanesian, and Native Hawaiian populations of K = 2, where K denotes the number of ancestral populations. This notable proportion of Melanesian admixture supports the "Slow-Boat" model of migration of ancestral Polynesian populations from East Asia to the Pacific Islands. In addition, approximately 1,300 years ago a single, strong expansion of the Native Hawaiian population was estimated. By providing important insight into the underlying population structure of Native Hawaiians, this study lays the foundation for future genetic association studies of this U. S. minority population. C1 [Lum-Jones, Annette; Wang, Hansong; Kolonel, Laurence N.; Le Marchand, Loic; Cheng, Iona] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Kim, Sung K.; Gignoux, Christopher R.; Wall, Jeffrey D.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Kim, Sung K.] Sequenom Inc, San Diego, CA USA. [Haiman, Christopher A.; Chen, Gary K.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Cheng, I (reprint author), Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. EM icheng@cc.hawaii.edu FU National Institute of Health [CA140636, CA063464, CA54281, HG004049-01A2] FX This work was supported by the National Institute of Health grants (CA140636, CA063464, CA54281, and HG004049-01A2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 82 TC 4 Z9 4 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e47881 DI 10.1371/journal.pone.0047881 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800029 PM 23144833 ER PT J AU McKeon, S Pace-Schott, EF Spencer, RMC AF McKeon, Shannon Pace-Schott, Edward F. Spencer, Rebecca M. C. TI Interaction of Sleep and Emotional Content on the Production of False Memories SO PLOS ONE LA English DT Article ID COGNITIVE NEUROSCIENCE; DECLARATIVE MEMORY; ENHANCES MEMORY; CONSOLIDATION; RECALL; WORDS; LISTS AB Sleep benefits veridical memories, resulting in superior recall relative to off-line intervals spent awake. Sleep also increases false memory recall in the Deese-Roediger-McDermott (DRM) paradigm. Given the suggestion that emotional veridical memories are prioritized for consolidation over sleep, here we examined whether emotion modulates sleep's effect on false memory formation. Participants listened to semantically related word lists lacking a critical lure representing each list's "gist.'' Free recall was tested after 12 hours containing sleep or wake. The Sleep group recalled more studied words than the Wake group but only for emotionally neutral lists. False memories of both negative and neutral critical lures were greater following sleep relative to wake. Morning and Evening control groups (20-minute delay) did not differ ruling out circadian accounts for these differences. These results support the adaptive function of sleep in both promoting the consolidation of veridical declarative memories and in extracting unifying aspects from memory details. C1 [McKeon, Shannon; Pace-Schott, Edward F.; Spencer, Rebecca M. C.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pace-Schott, Edward F.; Spencer, Rebecca M. C.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Pace-Schott, Edward F.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Spencer, RMC (reprint author), Univ Massachusetts, Dept Psychol, Tobin Hall, Amherst, MA 01003 USA. EM rspencer@psych.umass.edu OI Spencer, Rebecca/0000-0002-8674-2384 FU Commonwealth College Honors Research Grant at the University of Massachusetts, Amherst [NIH R00 AG029710, NIH 1R21MH090357] FX Commonwealth College Honors Research Grant at the University of Massachusetts, Amherst, NIH R00 AG029710, and NIH 1R21MH090357. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 8 Z9 8 U1 7 U2 41 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 NOV 7 PY 2012 VL 7 IS 11 AR e49353 DI 10.1371/journal.pone.0049353 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800250 PM 23145159 ER PT J AU Nesterenko, I Wanningen, S Bagci-Onder, T Anderegg, M Shah, K AF Nesterenko, Irina Wanningen, Simone Bagci-Onder, Tugba Anderegg, Maarten Shah, Khalid TI Evaluating the Effect of Therapeutic Stem Cells on TRAIL Resistant and Sensitive Medulloblastomas SO PLOS ONE LA English DT Article ID APOPTOSIS-INDUCING LIGAND; HISTONE DEACETYLASE INHIBITORS; GLIOBLASTOMA-MULTIFORME CELLS; HUMAN GLIOMA-CELLS; CANCER-THERAPY; ANTITUMOR-ACTIVITY; TUMOR-THERAPY; BRAIN-TUMORS; GENE-THERAPY; IN-VIVO AB Mesenchymal stem cells (MSC) are emerging as novel cell-based delivery agents; however, a thorough investigation addressing their therapeutic potential in medulloblastomas (MB) has not been explored to date. In this study, we engineered human MSC to express a potent and secretable variant of a tumor specific agent, tumor necrosis factor-apoptosis-inducing ligand (S-TRAIL) and assessed the ability of MSC-S-TRAIL mediated MB killing alone or in combination with a small molecule inhibitor of histone-deacetylase, MS-275, in TRAIL-sensitive and -resistant MB in vitro and in vivo. We show that TRAIL sensitivity/resistance correlates with the expression of its cognate death receptor (DR) 5 and MSC-S-TRAIL induces caspase-3 mediated apoptosis in TRAIL-sensitive MB lines. In TRAIL-resistant MB, we show upregulation of DR4/5 levels when pre-treated with MS-275 and a subsequent sensitization to MSC-S-TRAIL mediated apoptosis. Using intracranially implanted MB and MSC lines engineered with different combinations of fluorescent and bioluminescent proteins, we show that MSC-S-TRAIL has significant anti-tumor effects in mice bearing TRAIL-sensitive and MS-275 pretreated TRAIL-resistant MBs. To our knowledge, this is the first study that explores the use of human MSC as MB-targeting therapeutic-vehicles in vivo in TRAIL-sensitive and resistant tumors, and has implications for developing effective therapies for patients with medulloblastomas. C1 [Nesterenko, Irina; Wanningen, Simone; Bagci-Onder, Tugba; Anderegg, Maarten; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. [Nesterenko, Irina; Wanningen, Simone; Bagci-Onder, Tugba; Anderegg, Maarten; Shah, Khalid] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. EM kshah@mgh.harvard.edu FU American Cancer Society [NIH-CA138922, NIH-NS071197]; James McDonnell Foundation FX This work was supported by American Cancer Society (K.S.), NIH-CA138922, NIH-NS071197 (K.S.) and the James McDonnell Foundation (K.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 9 Z9 9 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e49219 DI 10.1371/journal.pone.0049219 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800233 PM 23145127 ER PT J AU Shindoh, N Yoda, A Yoda, Y Sullivan, TJ Weigert, O Lane, AA Kopp, N Bird, L Rodig, SJ Fox, EA Weinstock, DM AF Shindoh, Nobuaki Yoda, Akinori Yoda, Yuka Sullivan, Timothy J. Weigert, Oliver Lane, Andrew A. Kopp, Nadja Bird, Liat Rodig, Scott J. Fox, Edward A. Weinstock, David M. TI Next-Generation cDNA Screening for Oncogene and Resistance Phenotypes SO PLOS ONE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EML4-ALK FUSION GENE; LUNG-CANCER; EXPRESSION; CRLF2; ALK; LIBRARIES; MELANOMA; CELLS AB There is a pressing need for methods to define the functional relevance of genetic alterations identified by next-generation sequencing of cancer specimens. We developed new approaches to efficiently construct full-length cDNA libraries from small amounts of total RNA, screen for transforming and resistance phenotypes, and deconvolute by next-generation sequencing. Using this platform, we screened a panel of cDNA libraries from primary specimens and cell lines in cytokine-dependent murine Ba/F3 cells. We demonstrate that cDNA library-based screening can efficiently identify DNA and RNA alterations that confer either cytokine-independent proliferation or resistance to targeted inhibitors, including RNA alterations and intergenic fusions. Using barcoded next-generation sequencing, we simultaneously deconvoluted cytokinein-dependent clones recovered after transduction of 21 cDNA libraries. This approach identified multiple gain-of-function alleles, including KRAS G12D, NRAS Q61K and an activating splice variant of ERBB2. This approach has broad applicability for identifying transcripts that confer proliferation, resistance and other phenotypes in vitro and potentially in vivo. C1 [Shindoh, Nobuaki; Yoda, Akinori; Yoda, Yuka; Weigert, Oliver; Lane, Andrew A.; Kopp, Nadja; Bird, Liat; Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sullivan, Timothy J.; Fox, Edward A.] Dana Farber Canc Inst, Microarray Core, Boston, MA 02115 USA. [Rodig, Scott J.; Fox, Edward A.; Weinstock, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Shindoh, Nobuaki] Astellas Pharma Inc, Drug Discovery Res, Tsukuba, Ibaraki, Japan. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM dweinstock@partners.org FU Stand Up to Cancer Innovative Research Grant [SU2C-AACR-IRG0409]; American Cancer Society Research Scholar Grant [RSG-10-181-01-RMC]; Astellas Pharma Inc.; Deutsche Forschungsgemeinschaft FX This work was supported by Stand Up to Cancer Innovative Research Grant SU2C-AACR-IRG0409 and American Cancer Society Research Scholar Grant RSG-10-181-01-RMC to DMW. NS was partially supported by Astellas Pharma Inc. OW was partially supported by the Deutsche Forschungsgemeinschaft. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 18 TC 5 Z9 5 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 NOV 7 PY 2012 VL 7 IS 11 AR e49201 DI 10.1371/journal.pone.0049201 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800229 PM 23145123 ER PT J AU Buijze, GA Jorgsholm, P Thomsen, NOB Bjorkman, A Besjakov, J Ring, D AF Buijze, Geert A. Jorgsholm, Peter Thomsen, Niels O. B. Bjorkman, Anders Besjakov, Jack Ring, David TI Diagnostic Performance of Radiographs and Computed Tomography for Displacement and Instability of Acute Scaphoid Waist Fractures SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PERCUTANEOUS SCREW FIXATION; NONUNION; IMMOBILIZATION; REDUCTION; DEFORMITY; INJURIES; PATTERNS; LIGAMENT; WRIST; BONE AB Background: Fracture displacement is the most important factor associated with nonunion of a scaphoid waist fracture. We evaluated the performance characteristics of radiographs and computed tomography (CT) in the diagnosis of intraoperative displacement and instability of scaphoid waist fractures using wrist arthroscopy as the reference standard. Methods: During a six-year period (2004 to 2010) at two institutions, forty-four adult patients with a scaphoid waist fracture underwent arthroscopy-assisted operative fracture treatment at a mean of nine days (range, two to twenty-two days) after injury. Subjects included all of those with a displaced scaphoid fracture seen on radiographs and a selection of patients with a nondisplaced scaphoid fracture. All patients had preoperative radiographs and CT. Arthroscopy with up to 5 kg of traction was the reference standard for fracture displacement and instability. Results: The reference standard (arthroscopy) led to a diagnosis of twenty-two displaced fractures (all unstable) and twenty-two nondisplaced fractures (seven unstable). Displacement was diagnosed in eleven patients (25%) with the use of radiographs and in twenty (45%) with CT. The sensitivity, specificity, and accuracy for diagnosing intraoperative displacement were 45%, 95%, and 70%, respectively, with the use of radiographs and 77%, 86%, and 82%, respectively, with CT. The sensitivity, specificity, and accuracy for diagnosing intraoperative instability were 34%, 93%, and 55%, respectively, with the use of radiographs and 62%, 87%, and 70%, respectively, with CT. Assuming a 10% prevalence of fracture displacement and instability among all scaphoid waist fractures, the positive and negative predictive values for displacement were 53% and 94%, respectively, with the use of radiographs and 39% and 97% with CT whereas the positive and negative predictive values for instability were 36% and 93%, respectively, with radiographs and 34% and 95% with CT. Conclusions: Radiographs and CT scans cannot be relied on to accurately diagnose intraoperative scaphoid fracture displacement or instability compared with arthroscopic examination. The influence, with regard to the risk of nonunion, of intraoperative instability of a scaphoid fracture that is seen to be nondisplaced on radiographs or CT is currently unknown. C1 [Buijze, Geert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. [Jorgsholm, Peter; Thomsen, Niels O. B.; Bjorkman, Anders] Lund Univ, Skane Univ Hosp, Dept Hand Surg, SE-20502 Malmo, Sweden. [Besjakov, Jack] Lund Univ, Skane Univ Hosp, Dept Radiol, SE-20502 Malmo, Sweden. RP Buijze, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 33 TC 11 Z9 11 U1 0 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV 7 PY 2012 VL 94A IS 21 BP 1967 EP 1974 DI 10.2106/JBJS.K.00993 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 032ZI UT WOS:000310761400007 PM 23014795 ER PT J AU Ghose, K Maunsell, JHR AF Ghose, Kaushik Maunsell, John H. R. TI A Strong Constraint to the Joint Processing of Pairs of Cortical Signals SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PRIMARY VISUAL-CORTEX; WINNER-TAKE-ALL; INTRACORTICAL MICROSTIMULATION; ELECTRICAL MICROSTIMULATION; INFEROTEMPORAL CORTEX; SPATIAL SUMMATION; MOTION DIRECTION; STRIATE CORTEX; MACAQUE MONKEY; HUMAN VISION AB An important question in neuroscience is how the activity from spatially distributed cortical representations is integrated and processed together. In this study, we used a new approach to investigate the integration of distributed cortical activity. We used microstimulation to directly activate pairs of sites in primary visual cortex of rhesus monkeys. The sites were activated either singly or jointly, and the monkeys were trained to behaviorally report detection of the activation of either cortical site. We compared the detection performance with predictions from two different mathematical models of signal combination. Our data show that, at cortical separations <1 mm, signal integration is well described as a linear combination (d' summation) of individual site activity. At larger separations, signal integration is better described as a maximum operation on the site signals. We compare our neurophysiological findings to existing psychophysical data and suggest the intriguing possibility that cortical activity originating at spatial separations greater than similar to 1 mm is processed as if by parallel, independent circuits whose signals can be compared against each other but not summed. This in turn implies that there is a strong constraint to the kinds of computations the brain can perform with spatially distributed cortical activity. C1 [Ghose, Kaushik; Maunsell, John H. R.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Ghose, K (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM kaushik.ghose@gmail.com RI Maunsell, John/G-5702-2010 OI Maunsell, John/0000-0003-0018-4439 FU Howard Hughes Medical Institute; National Institutes of Health [R01EY005911] FX This work was supported by the Howard Hughes Medical Institute and National Institutes of Health Grant R01EY005911. We thank David Averbukh for constructing the optically isolated current monitors. NR 55 TC 4 Z9 4 U1 0 U2 11 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 NOV 7 PY 2012 VL 32 IS 45 BP 15922 EP 15933 DI 10.1523/JNEUROSCI.2186-12.2012 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 034AH UT WOS:000310842000026 PM 23136430 ER PT J AU Clasie, BM Sharp, GC Seco, J Flanz, JB Kooy, HM AF Clasie, Benjamin M. Sharp, Gregory C. Seco, Joao Flanz, Jacob B. Kooy, Hanne M. TI Numerical solutions of the gamma-index in two and three dimensions SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DOSE DISTRIBUTIONS; QUANTITATIVE-EVALUATION; INTERPOLATION AB The gamma-index is used routinely to establish correspondence between two dose distributions. The definition of the gamma-index can be written with a single equation but solving this equation at millions of points is computationally expensive, especially in three dimensions. Our goal is to extend the vector-equation method in Bakai et al (2003 Phys. Med. Biol. 48 3543-53) to higher order for better accuracy and, as important, to determine the magnitude of accuracy in a higher order solution. We construct a numerical framework for calculating the gamma-index in two and three dimensions and present an efficient method for calculating the gamma-index with zeroth-, first-and second-order methods using tricubic spline interpolation. For an intensity-modulated radiation therapy example with 1.78 x 10(6) voxels, the zeroth-order, first-order, first-order iterations and semi-second-order methods calculate the three-dimensional gamma-index in 1.5, 4.7, 34.7 and 35.6 s with 36.7%, 1.1%, 0.2% and 0.8% accuracy, respectively. The accuracy of linear interpolation with this example is 1.0%. We present efficient numerical methods for calculating the three-dimensional gamma-index with tricubic spline interpolation. The first-order method with iterations is the most accurate and fastest choice of the numerical methods if the dose distributions may have large second-order gradients. Furthermore, the difference between iterations can be used to determine the accuracy of the method. C1 [Clasie, Benjamin M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Clasie, BM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM bclasie@partners.org RI Seco, Joao/J-4451-2012 FU Massachusetts General Hospital FX This work was funded in part through the Massachusetts General Hospital managed National Cancer Institute federal share program. NR 12 TC 16 Z9 16 U1 0 U2 3 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 NOV 7 PY 2012 VL 57 IS 21 BP 6981 EP 6997 DI 10.1088/0031-9155/57/21/6981 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 029WT UT WOS:000310528700019 PM 23044713 ER PT J AU Clasie, BM Flanz, JB Kooy, HM AF Clasie, Benjamin M. Flanz, Jacob B. Kooy, Hanne M. TI Interpolation of tabulated proton Bragg peaks SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BEAMS AB Treatment planning databases for pencil beam scanning can be large, difficult to manage and problematic for quality assurance when they contain tabulated Bragg peaks at small range resolution. Smaller range resolution, in the absence of an accurate interpolation method, improves the accuracy in dose calculations. In this work, we derive an approximate scaling function to interpolate between tabulated Bragg peaks, and determine the accuracy of this interpolation technique and the minimum number of tabulated peaks in a treatment planning database. With the new interpolation technique, three tabulated mono-energetic Bragg peaks (N = 3) are a suitable lower limit for N to achieve interpolation accuracy better than +/- 1% of the maximum dose in pristine and spread out Bragg peaks for ranges between 6.8 and 32.1 cm of water. C1 [Clasie, Benjamin M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Clasie, BM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM bclasie@partners.org FU Massachusetts General Hospital FX Funded in part through the Massachusetts General Hospital managed National Cancer Institute federal share program. NR 5 TC 0 Z9 0 U1 0 U2 2 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 NOV 7 PY 2012 VL 57 IS 21 BP N405 EP N409 DI 10.1088/0031-9155/57/21/N405 PG 5 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 029WT UT WOS:000310528700004 PM 23073269 ER PT J AU Rothfuchs, AG Roffe, E Gibson, A Cheever, AW Ezekowitz, RAB Takahashi, K Steindel, M Sher, A Bafica, A AF Rothfuchs, Antonio Gigliotti Roffe, Ester Gibson, Amanda Cheever, Allen W. Ezekowitz, R. Alan B. Takahashi, Kazue Steindel, Mario Sher, Alan Bafica, Andre TI Mannose-Binding Lectin Regulates Host Resistance and Pathology during Experimental Infection with Trypanosoma cruzi SO PLOS ONE LA English DT Article ID CHAGAS-DISEASE; MAMMALIAN-CELLS; DEFICIENT MICE; PROTEIN; TISSUE; SERUM; SUSCEPTIBILITY; AMASTIGOTES; CARDIOMYOPATHY; RECOGNITION AB Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important for host defense. Although recent genetic studies suggest an involvement of MBL/MASP2-associated pathways in Chagas' disease, it is currently unknown whether MBL plays a role in host resistance to the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas' disease. In this study we employed MBL-/- mice to assess the role of MBL in resistance to experimental infection with T. cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and protein level. Similarly, symptomatic acute Chagas' disease patients displayed increased serum concentrations of MBL compared to patients with indeterminate, asymptomatic forms of the disease. Furthermore, increased parasite loads in the blood and/or tissue were observed in MBL-/- mice compared to WT controls. This was associated with reduced systemic levels of IL-12/23p40 in MBL-/- mice. Importantly, MBL-/- mice infected with a cardiotropic strain of T. cruzi displayed increased myocarditis and cardiac fibrosis compared to WT controls. The latter was accompanied by elevated hydroxyproline content and mRNA levels of collagen-1 and -6 in the heart. These observations point to a previously unappreciated role for MBL in regulating host resistance and cardiac inflammation during infection with a major human pathogen. C1 [Rothfuchs, Antonio Gigliotti; Gibson, Amanda; Cheever, Allen W.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Roffe, Ester] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA. [Ezekowitz, R. Alan B.; Takahashi, Kazue] Harvard Univ, Sch Med, Dept Pediat, Lab Dev Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rothfuchs, Antonio Gigliotti] Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden. [Steindel, Mario; Bafica, Andre] Univ Fed Santa Catarina, Dept Microbiol Immunol & Parasitol, Florianopolis, SC, Brazil. RP Rothfuchs, AG (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM antonio.rothfuchs@ki.se; andre.bafica@ufsc.br RI Rothfuchs, Antonio/F-5981-2013; Vacinas, Inct/J-9431-2013; Roffe, Ester/H-4688-2012 OI Rothfuchs, Antonio/0000-0001-6001-7240; FU Intramural Research Program of the NIAID; EU [FP7-MC-IRG-247684]; Swedish Society for Medicine FX This work was supported by the Intramural Research Program of the NIAID. AB and MS are CNPq senior research fellows. AGR is a recipient of a Marie Curie International Reintegration grant from the EU (FP7-MC-IRG-247684) and a project grant from the Swedish Society for Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 7 Z9 8 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 6 PY 2012 VL 7 IS 11 AR e47835 DI 10.1371/journal.pone.0047835 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040IE UT WOS:000311315300012 PM 23139754 ER PT J AU Papak, J Kansagara, D AF Papak, Joel Kansagara, Devan TI Management of Hyperglycemia in a Hospitalized Patient with Diabetes Mellitus and Cardiovascular Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL PATIENTS; GLUCOSE-INSULIN-POTASSIUM; RANDOMIZED CONTROLLED-TRIAL; TIGHT GLYCEMIC CONTROL; CARE-UNIT PATIENTS; INTENSIVE-CARE; WOUND-INFECTION; FATTY-ACIDS; MORTALITY AB Hyperglycemia in patients with and without known diabetes is a common finding in patients hospitalized with cardiovascular disease, and is associated with poor outcomes. Investigators have been examining the role of insulin to treat patients with acute myocardial infarction since the 1960's. Until the 1990's most studies evaluated fixed doses of glucose-insulin-potassium (GIK) infusions. The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial, published in 1995, evaluated the role of adjustable-dose insulin infusion to lower blood glucose. Its promising results spurred further interest and a number of trials evaluating the use of insulin to lower blood glucose in hospitalized patients - many of which included patients with cardiovascular disease - have been conducted over the last two decades with conflicting results. This manuscript reviews the epidemiology and pathophysiology of hyperglycemia in hospitalized patients, summarizes the evidence for benefits and harms of using insulin to treat hyperglycemic patients hospitalized with cardiovascular disease, and offers some practical management considerations. Published by Elsevier Inc. (Am J Cardiol 2012;110[suppl]:24B-31B) C1 [Kansagara, Devan] Portland VA Med Ctr, Evidence Based Synth Program, Portland, OR USA. [Kansagara, Devan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Kansagara, D (reprint author), 3710 SW US Vet Hosp Rd,P3 Med, Portland, OR 97239 USA. EM kansagar@ohsu.edu FU Novo Nordisk Inc. FX Funding for publication and medical writing assistance were provided by Novo Nordisk Inc. We thank Ruth Kleinpell, PhD, RN, and Mary Lou Briglio (Executive Administrative Assistant to Michael H. Davidson, MD) for assistance in the preparation of this supplement. NR 50 TC 7 Z9 8 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 6 PY 2012 VL 110 IS 9 SU S BP 24B EP 31B DI 10.1016/j.amjcard.2012.08.034 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 036FM UT WOS:000311011800004 PM 23062564 ER PT J AU Wang, CCL Reusch, JEB AF Wang, Cecilia C. Low Reusch, Jane E. B. TI Diabetes and Cardiovascular Disease: Changing the Focus from Glycemic Control to Improving Long-Term Survival SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIAL; IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; BLOOD-PRESSURE CONTROL; RISK-FACTORS; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; FOLLOW-UP; ACCORD TRIAL AB Diabetes mellitus (DM) is the fifth-leading cause of death worldwide and contributes to leading causes of death, cancer and cardiovascular disease, including CAD, stroke, peripheral vascular disease, and other vascular disease. While glycemic management remains a cornerstone of DM care, the co-management of hypertension, atherosclerosis, cardiovascular risk reduction, and prevention of long-term consequences associated with DM are now well recognized as essential to improve long-term survival. Clinical trial evidence substantiates the importance of glycemic control, low-density cholesterol lowering therapy, blood pressure lowering, control of albuminuria, and comprehensive approaches targeting multiple risk factors to reduce cardiovascular risk. This article presents a review of the role of DM in the pathogenesis of atherosclerosis and cardiac dysfunction, recent evidence on the degree of glycemic control and mortality, and available evidence for a multifaceted approach to improve long-term outcomes for patients. Published by Elsevier Inc. (Am J Cardiol 2012;110[suppl]:58B-68B) C1 [Wang, Cecilia C. Low] Univ Colorado, Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Aurora, CO 80045 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Wang, CCL (reprint author), Univ Colorado, Sch Med, Div Endocrinol Diabet & Metab, Dept Med, MS 8106,Bldg RC-1 S,Room 7103, Aurora, CO 80045 USA. EM cecilia.wang@ucdenver.edu FU Novo Nordisk Inc.; Bristol-Meyers Squibb/Amylin; GlaxoSmithKline FX Funding for publication and medical writing assistance were provided by Novo Nordisk Inc. We thank Ruth Kleinpell, PhD, RN, and Mary Lou Briglio (Executive Administrative Assistant to Michael H. Davidson, MD) for assistance in the preparation of this supplement.; The authors who contributed to this article have disclosed the following industry relationships:; Jane EB Reusch, MD, has received funding from Bristol-Meyers Squibb/Amylin for investigator-initiated trial and GlaxoSmithKline. Dr. Reusch also serves on the advisory board for GlaxoSmithKline. NR 84 TC 28 Z9 30 U1 2 U2 13 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 NOV 6 PY 2012 VL 110 IS 9 SU S BP 58B EP 68B DI 10.1016/j.amjcard.2012.08.036 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 036FM UT WOS:000311011800008 PM 23062569 ER PT J AU Solt, K AF Solt, Ken TI General Anesthesia: Activating a Sleep Switch? SO CURRENT BIOLOGY LA English DT Editorial Material ID AROUSAL; RECEPTORS; EMERGENCE; SYSTEMS C1 [Solt, Ken] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. [Solt, Ken] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Solt, K (reprint author), Harvard Univ, Sch Med, Dept Anesthesia, 55 Fruit St,GRB-444, Boston, MA 02114 USA. EM ksolt@partners.org OI Solt, Ken/0000-0001-5328-2062 NR 20 TC 2 Z9 2 U1 0 U2 6 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 NOV 6 PY 2012 VL 22 IS 21 BP R918 EP R919 DI 10.1016/j.cub.2012.09.033 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 036VK UT WOS:000311060200012 PM 23137688 ER PT J AU Knudsen, AB Hur, C Gazelle, GS Schrag, D McFarland, EG Kuntz, KM AF Knudsen, Amy B. Hur, Chin Gazelle, G. Scott Schrag, Deborah McFarland, Elizabeth G. Kuntz, Karen M. TI Rescreening of Persons With a Negative Colonoscopy Result: Results From a Microsimulation Model SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID FECAL OCCULT-BLOOD; AMERICAN-CANCER-SOCIETY; RANDOMIZED CONTROLLED-TRIAL; ON-COLORECTAL-CANCER; SERVICES TASK-FORCE; CT COLONOGRAPHY; SCREENING COLONOSCOPY; MEDICARE POPULATION; LARGE-INTESTINE; LARGE-BOWEL AB Background: Persons with a negative result on screening colonoscopy are recommended to repeat the procedure in 10 years. Objective: To assess the effectiveness and costs of colonoscopy versus other rescreening strategies after an initial negative colonoscopy result. Design: Microsimulation model. Data Sources: Literature and data from the Surveillance, Epidemiology, and End Results program. Target Population: Persons aged 50 years who had no adenomas or cancer detected on screening colonoscopy. Time Horizon: Lifetime. Perspective: Societal. Intervention: No further screening or rescreening starting at age 60 years with colonoscopy every 10 years, annual highly sensitive guaiac fecal occult blood testing (HSFOBT), annual fecal immuno-chemical testing (FIT), or computed tomographic colonography (CTC) every 5 years. Outcome Measures: Lifetime cases of colorectal cancer, life expectancy, and lifetime costs per 1000 persons, assuming either perfect or imperfect adherence. Results of Base-Case Analysis: Rescreening with any method substantially reduced the risk for colorectal cancer compared with no further screening (range, 7.7 to 12.6 lifetime cases per 1000 persons [perfect adherence] and 17.7 to 20.9 lifetime cases per 1000 persons [imperfect adherence] vs. 31.3 lifetime cases per 1000 persons with no further screening). In both adherence scenarios, the differences in life-years across rescreening strategies were small (range, 30 893 to 30 902 life-years per 1000 persons [perfect adherence] vs. 30 865 to 30 869 life-years per 1000 persons [imperfect adherence]). Rescreening with HSFOBT, FIT, or CTC had fewer complications and was less costly than continuing colonoscopy. Results of Sensitivity Analysis: Results were sensitive to test-specific adherence rates. Limitation: Data on adherence to rescreening were limited. Conclusion: Compared with the currently recommended strategy of continuing colonoscopy every 10 years after an initial negative examination, rescreening at age 60 years with annual HSFOBT, annual FIT, or CTC every 5 years provides approximately the same benefit in life-years with fewer complications at a lower cost. Therefore, it is reasonable to use other methods to rescreen persons with negative colonoscopy results. C1 [Knudsen, Amy B.] Harvard Univ, Massachusetts Gen Hosp, Sch Publ Hlth, Inst Technol Assessment, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. SSM St Joseph Hosp, St Charles, MO USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Knudsen, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Publ Hlth, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM aknudsen@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 FU National Cancer Institute, National Institutes of Health [RC1CA147256, U01CA088204, U01CA152959]; National Cancer Institute FX By award RC1CA147256 and grants U01CA088204 and U01CA152959 from the National Cancer Institute, National Institutes of Health.; Primary Funding Source: National Cancer Institute. NR 64 TC 9 Z9 9 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 6 PY 2012 VL 157 IS 9 BP 611 EP + DI 10.7326/0003-4819-157-9-201211060-00005 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 033GX UT WOS:000310783300002 PM 23128861 ER PT J AU Blumenthal, D AF Blumenthal, David TI The 2012 Presidential Election: It's Health Care, Stupid! SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Blumenthal, David] Partners HealthCare Syst, Massachusetts Gen Hosp, Boston, MA USA. [Blumenthal, David] Harvard Univ, Sch Med, Boston, MA USA. RP Blumenthal, D (reprint author), Partners HealthCare Syst, Massachusetts Gen Hosp, Boston, MA USA. EM dblumenthal@partners.org NR 2 TC 0 Z9 0 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 6 PY 2012 VL 157 IS 9 BP 665 EP + DI 10.7326/0003-4819-157-9-201211060-00546 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 033GX UT WOS:000310783300008 PM 23405386 ER PT J AU Dong, XC Mi, LZ Zhu, JH Wang, W Hu, P Luo, BH Springer, TA AF Dong, Xianchi Mi, Li-Zhi Zhu, Jianghai Wang, Wei Hu, Ping Luo, Bing-Hao Springer, Timothy A. TI alpha(v)beta(3) Integrin Crystal Structures and Their Functional Implications SO BIOCHEMISTRY LA English DT Article ID EXTRACELLULAR SEGMENT; PROTEIN STABILITY; HYBRID DOMAIN; BETA-SUBUNIT; COILED-COIL; OUTSIDE-IN; ACTIVATION; AFFINITY; COMPLEX; LIGAND AB Many questions about the significance of structural features of integrin alpha(v)beta(3) with respect to its mechanism of activation remain. We have determined and re-refined crystal structures of the alpha(v)beta(3) ectodomain linked to C-terminal coiled coils (alpha(v)beta(3)-AB) and four transmembrane (TM) residues in each subunit (alpha(v)beta(3)-1TM), respectively. The alpha(v) and beta(3) subunits with four and eight extracellular domains, respectively, are bent at knees between the integrin headpiece and lower legs, and the headpiece has the closed, low affinity conformation. The structures differ in the occupancy of three metal-binding sites in the beta I domain. Occupancy appears to be related to the pH of crystallization, rather than to the physiologic regulation of ligand binding at the central, metal ion dependent adhesion site No electron density was observed for TM residues and much of the alpha(v) linker alpha(v)beta(3)-AB and alpha(v)beta(3)-1TM demonstrate flexibility in the linker between their extracellular and TM domains, rather than the previously proposed rigid linkage. A previously postulated interface between the alpha(v) and beta(3) subunits at their knees was also not supported, because it lacks high-quality density, required rebuilding in alpha(v)beta(3)-1TM, and differed markedly between alpha(v)beta(3)-1TM and alpha(v)beta(3)-AB. Together with the variation in domain-domain orientation within their bent ectodomains between alpha(v)beta(3)-AB and alpha(v)beta(3)-1TM, these findings are compatible with the requirement for large structural changes, such as extension at the knees and headpiece opening, in conveying activation signals between the extracellular ligand-binding site and the cytoplasm. C1 [Dong, Xianchi; Mi, Li-Zhi; Zhu, Jianghai; Luo, Bing-Hao; Springer, Timothy A.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Dong, Xianchi; Mi, Li-Zhi; Zhu, Jianghai; Luo, Bing-Hao; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wang, Wei; Hu, Ping; Luo, Bing-Hao] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. RP Springer, TA (reprint author), 3 Blackfan Circle,Rm 3100, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Zhu, Jianghai/B-7339-2014; Dong, Xianchi/C-1393-2015; Mi, Li-Zhi/B-1371-2016 OI Dong, Xianchi/0000-0001-5121-1236; Mi, Li-Zhi/0000-0001-9907-5245 FU National Institutes of Health [HL103526] FX Supported by National Institutes of Health Grant HL103526. NR 58 TC 20 Z9 20 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 6 PY 2012 VL 51 IS 44 BP 8814 EP 8828 DI 10.1021/bi300734n PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 031TC UT WOS:000310664200012 PM 23106217 ER PT J AU Sauer, AJ Newton-Cheh, C AF Sauer, Andrew J. Newton-Cheh, Christopher TI Response to Letter Regarding Article, "Clinical and Genetic Determinants of Torsade de Pointes Risk" SO CIRCULATION LA English DT Letter ID DISPERSION C1 [Sauer, Andrew J.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. RP Sauer, AJ (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. OI Sauer, Andrew/0000-0002-9268-2795 NR 5 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 NOV 6 PY 2012 VL 126 IS 19 BP E310 EP E310 DI 10.1161/CIRCULATIONAHA.112.133520 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 032UH UT WOS:000310744100004 ER PT J AU Weinrauch, LA Desai, AS Lewis, EF D'Elia, JA AF Weinrauch, Larry A. Desai, Akshay S. Lewis, Eldrin F. D'Elia, John A. TI Ultrafiltration in End-Stage Heart Failure Too Little, Too Late? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE acute decompensated heart failure; cordiorenal syndrome; prognosis; slow continuous ultrafiltration ID WORSENING RENAL-FUNCTION; AMBULATORY PERITONEAL-DIALYSIS; INTRAVENOUS MILRINONE; TRIAL; DIURETICS; OUTCOMES; CHF C1 [Weinrauch, Larry A.; D'Elia, John A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Weinrauch, Larry A.; Desai, Akshay S.; Lewis, Eldrin F.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Weinrauch, LA (reprint author), Harvard Univ, Sch Med, 521 Mt Auburn St, Watertown, MA 02472 USA. EM lweinrauch@hms.harvard.edu OI D'Elia, John/0000-0001-9482-581X; Weinrauch, Larry/0000-0003-1357-9528 NR 25 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 6 PY 2012 VL 60 IS 19 BP 1913 EP 1915 DI 10.1016/j.jacc.2012.06.052 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 027LB UT WOS:000310352600010 PM 23062536 ER PT J AU Beshiri, ML Holmes, KB Richter, WF Hess, S Islam, ABMMK Yan, Q Plante, L Litovchick, L Gevry, N Lopez-Bigas, N Kaelin, WG Benevolenskaya, EV AF Beshiri, Michael L. Holmes, Katherine B. Richter, William F. Hess, Samuel Islam, Abul B. M. M. K. Yan, Qin Plante, Lydia Litovchick, Larisa Gevry, Nicolas Lopez-Bigas, Nuria Kaelin, William G., Jr. Benevolenskaya, Elizaveta V. TI Coordinated repression of cell cycle genes by KDM5A and E2F4 during differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromatin; histone demethylase; whole; genome sequencing; histone methylation ID TRANSCRIPTIONAL REPRESSION; MOLECULAR-MECHANISMS; EMBRYONIC STEM; RBP2; METHYLATION; DEMETHYLASE; COMPLEX; BINDING; BIOCONDUCTOR; STATE AB Epigenetic regulation underlies the robust changes in gene expression that occur during development. How precisely epigenetic enzymes contribute to development and differentiation processes is largely unclear. Here we show that one of the enzymes that removes the activating epigenetic mark of trimethylated lysine 4 on histone H3, lysine (K)-specific demethylase 5A (KDM5A), reinforces the effects of the retinoblastoma (RB) family of transcriptional repressors on differentiation. Global location analysis showed that KDM5A cooccupies a substantial portion of target genes with the E2F4 transcription factor. During ES cell differentiation, knockout of KDM5A resulted in derepression of multiple genomic loci that are targets of KDM5A, denoting a direct regulatory function. In terminally differentiated cells, common KDM5A and E2F4 gene targets were bound by the pRB-related protein p130, a DREAM complex component. KDM5A was recruited to the transcription start site regions independently of E2F4; however, it cooperated with E2F4 to promote a state of deepened repression at cell cycle genes during differentiation. These findings reveal a critical role of H3K4 demethylation by KDM5Ain the transcriptional silencing of genes that are suppressed by RB family members in differentiated cells. C1 [Litovchick, Larisa; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Litovchick, Larisa; Kaelin, William G., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Beshiri, Michael L.; Holmes, Katherine B.; Richter, William F.; Hess, Samuel; Islam, Abul B. M. M. K.; Benevolenskaya, Elizaveta V.] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. [Islam, Abul B. M. M. K.; Lopez-Bigas, Nuria] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Res Unit Biomed Informat, Barcelona 08003, Spain. [Plante, Lydia; Gevry, Nicolas] Univ Sherbrooke, Fac Sci, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada. [Yan, Qin] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. [Lopez-Bigas, Nuria] Passeig Lluis Co, ICREA, Barcelona 08010, Spain. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu; evb@uic.edu RI Yan, Qin/E-8893-2012; Lopez-Bigas, Nuria/F-6193-2011; Gasull, Martina/A-6630-2013 OI Yan, Qin/0000-0003-4077-453X; Lopez-Bigas, Nuria/0000-0003-4925-8988; FU National Institutes of Health [R01 CA138631, R01 CA076120]; Spanish Ministry of Science [SAF2009-06954]; Fonds de la recherche en sante du Quebec; Clinical and Translational Science Award [UL1 RR024139]; V Scholar Award; Autonomous Government of Catalonia, Spain FX We thank Ms. Alexandra Vilkova for technical assistance. The project was supported by Grants R01 CA138631 (to E. V. B.) and R01 CA076120 (to W. G. K.) from the National Institutes of Health; Education Grant SAF2009-06954 (to N.L.-B.) from the Spanish Ministry of Science; a Chercheur boursier (junior 1) award from the Fonds de la recherche en sante du Quebec (to N.G.); Clinical and Translational Science Award Grant UL1 RR024139 and a V Scholar Award (to Q.Y.); and a fellowship from the Autonomous Government of Catalonia, Spain (to A. B. M. M. K. I.). W. G. K. is a Howard Hughes Medical Institute Investigator and a Doris Duke Distinguished Scientist. NR 32 TC 21 Z9 22 U1 0 U2 13 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 NOV 6 PY 2012 VL 109 IS 45 BP 18499 EP 18504 DI 10.1073/pnas.1216724109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038DZ UT WOS:000311156700059 PM 23093672 ER PT J AU Kodack, DP Chung, E Yamashita, H Incio, J Duyverman, AMMJ Song, Y Farrar, CT Huang, YH Ager, E Kamoun, W Goel, S Snuderl, M Lussiez, A Hiddingh, L Mahmood, S Tannous, BA Eichler, AF Fukumura, D Engelman, JA Jain, RK AF Kodack, David P. Chung, Euiheon Yamashita, Hiroshi Incio, Joao Duyverman, Annique M. M. J. Song, Youngchul Farrar, Christian T. Huang, Yuhui Ager, Eleanor Kamoun, Walid Goel, Shom Snuderl, Matija Lussiez, Alisha Hiddingh, Lotte Mahmood, Sidra Tannous, Bakhos A. Eichler, April F. Fukumura, Dai Engelman, Jeffrey A. Jain, Rakesh K. TI Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE treatment resistance; tumor-stroma interaction; targeted therapy; tumor microenvironment; antiangiogenesis ID NERVOUS-SYSTEM METASTASES; ENDOTHELIAL GROWTH-FACTOR; PHASE-II; LAPATINIB GW572016; TRASTUZUMAB; CELLS; ANGIOGENESIS; BEVACIZUMAB; CAPECITABINE; COMBINATION AB Brain metastases are a serious obstacle in the treatment of patients with human epidermal growth factor receptor-2 (HER2)-amplified breast cancer. Although extracranial disease is controlled with HER2 inhibitors in the majority of patients, brain metastases often develop. Because these brain metastases do not respond to therapy, they are frequently the reason for treatment failure. We developed a mouse model of HER2-amplified breast cancer brain metastasis using an orthotopic xenograft of BT474 cells. As seen in patients, the HER2 inhibitors trastuzumab and lapatinib controlled tumor progression in the breast but failed to contain tumor growth in the brain. We observed that the combination of a HER2 inhibitor with an anti-VEGF receptor-2 (VEGFR2) antibody significantly slows tumor growth in the brain, resulting in a striking survival benefit. This benefit appears largely due to an enhanced antiangiogenic effect: Combination therapy reduced both the total and functional microvascular density in the brain xenografts. In addition, the combination therapy led to a marked increase in necrosis of the brain lesions. Moreover, we observed even better antitumor activity after combining both trastuzumab and lapatinib with the anti-VEGFR2 antibody. This triple-drug combination prolonged the median overall survival fivefold compared with the control-treated group and twofold compared with either two-drug regimen. These findings support the clinical development of this three-drug regimen for the treatment of HER2-amplified breast cancer brain metastases. C1 [Kodack, David P.; Chung, Euiheon; Yamashita, Hiroshi; Incio, Joao; Duyverman, Annique M. M. J.; Huang, Yuhui; Ager, Eleanor; Kamoun, Walid; Goel, Shom; Snuderl, Matija; Lussiez, Alisha; Hiddingh, Lotte; Mahmood, Sidra; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Song, Youngchul; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Farrar, Christian T.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Snuderl, Matija] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eichler, April F.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Eichler, April F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chung, Euiheon] Gwangju Inst Sci & Technol, Dept Med Syst Engn, Kwangju 500712, South Korea. [Chung, Euiheon] Gwangju Inst Sci & Technol, Sch Mechatron, Kwangju 500712, South Korea. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu; jengelman@partners.org; jain@steele.mgh.harvard.edu OI Ager, Eleanor/0000-0002-7849-9206; Huang, Yuhui/0000-0003-1985-3575; Incio, Joao/0000-0002-0259-1356; Snuderl, Matija/0000-0003-0752-0917 FU Dyax; MedImmune; Roche; US Department of Defense [W81XWH-10-1-0016]; US National Cancer Institute [R01-CA126642, P01-CA080124, R01-CA096915]; Federal Share Proton Beam Program Income; Basic Research Projects in High-tech Industrial Technology at Gwangju Institute of Science and Technology; Institute of Medical System Engineering at Gwangju Institute of Science and Technology; National Research Foundation of Korea [2011-0019619, 2012R1A1A1012853]; Massachusetts General Hospital; US National Institutes of Health [K25AG029415]; [T32-CA073479]; [R21CA155862] FX J.A.E. serves as a consultant for GlaxoSmithKline and Genentech (Roche). R.K.J. has research grants from Dyax, MedImmune, and Roche; serves as a consultant to Noxxon Pharmaceuticals; serves on the Scientific Advisory Board of Enlight and SynDevRx; serves on the Board of Directors of XTuit; serves on the Board of Trustees of H&Q Healthcare Investors and H&Q Life Sciences Investors; and has equity in Enlight, SynDevRx, and XTuit Pharmaceuticals. No funds or reagents from any of these organizations were used in the current study.; We thank S. Roberge, J. Kahn, C. Smith, N. Kirkpatrick, R. Ramjiawan, and P. Huang for help with experiments and interpretation of data, and D. Duda, B. Seed, and I. Kuter for useful suggestions and clinical insight. We also thank ImClone Systems/Eli Lilly and Company for the generous gift of DC101. This work was supported, in part, by US Department of Defense Breast Cancer Research Innovator Award W81XWH-10-1-0016 (to R.K.J.); US National Cancer Institute Grants R01-CA126642 (to R.K.J.), P01-CA080124 (to R.K.J. and D.F.), and R01-CA096915 (to D.F.); Federal Share Proton Beam Program Income (to R.K.J.); Grant T32-CA073479 (to D.P.K.); Basic Research Projects in High-tech Industrial Technology at Gwangju Institute of Science and Technology (E.C.); the Institute of Medical System Engineering at Gwangju Institute of Science and Technology (E.C.); the Bio & Medical Technology Development Program and Basic Science Program through the National Research Foundation of Korea Grants 2011-0019619 and 2012R1A1A1012853 (to E.C.) a Tosteson postdoctoral fellowship at the Massachusetts General Hospital (to E.C.); Grant R21CA155862 (to C.T.F.); and US National Institutes of Health Grant K25AG029415 (to C.T.F.). NR 37 TC 47 Z9 49 U1 0 U2 17 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 NOV 6 PY 2012 VL 109 IS 45 BP E3119 EP E3127 DI 10.1073/pnas.1216078109 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038DZ UT WOS:000311156700013 PM 23071298 ER PT J AU Hakimelahi, R Yoo, AJ He, JL Schwamm, LH Lev, MH Schaefer, PW Gonzalez, RG AF Hakimelahi, Reza Yoo, Albert J. He, Julian Schwamm, Lee H. Lev, Michael H. Schaefer, Pamela W. Gonzalez, Ramon Gilberto TI Rapid identification of a major diffusion/perfusion mismatch in distal internal carotid artery or middle cerebral artery ischemic stroke SO BMC NEUROLOGY LA English DT Article ID LESION VOLUME; PERFUSION MRI; IMAGING SCALE; DIFFUSION; THROMBOLYSIS; SELECTION; DESMOTEPLASE; TOMOGRAPHY; DIAGNOSIS; OCCLUSION AB Background: We tested the hypothesis that in patients with occlusion of the terminal internal carotid artery and/or the proximal middle cerebral artery, a diffusion abnormality of 70 ml or less is accompanied by a diffusion/perfusion mismatch of at least 100%. Methods: Sixty-eight consecutive patients with terminal ICA and/or proximal MCA occlusions and who underwent diffusion/perfusion MRI within 24 hours of stroke onset were retrospectively identified. DWI and mean transit time (MTT) volumes were measured. Prospectively, 48 consecutive patients were identified with the same inclusion criteria. DWI and time to peak (TTP) lesion volumes were measured. A large mismatch volume was defined as an MTT or TTP abnormality at least twice the DWI lesion volume. Results: In the retrospective study, 49 of 68 patients had a DWI lesion volume <= 70 ml (mean 20.2 ml; SEM 2.9 ml). A DWI/MTT mismatch of > 100% was observed in all 49 patients (P < .0001). In the prospective study, there were 35/48 patients with DWI volumes <= 70 ml (mean 18.7 ml; SEM 3.0 ml). A mismatch > 100% was present in all 35 (P < .0001). Conclusions: Acute stroke patients with major anterior circulation artery occlusion are exceedingly likely to have a major diffusion/perfusion mismatch if the diffusion lesion volume is 70 ml or less. This suggests that physiology-based patient assessments may be made using only vessel imaging and diffusion MRI as a simple alternative to perfusion imaging. C1 [Hakimelahi, Reza; Yoo, Albert J.; He, Julian; Lev, Michael H.; Schaefer, Pamela W.; Gonzalez, Ramon Gilberto] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Gonzalez, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. EM rggonzalez@partners.org OI Schwamm, Lee/0000-0003-0592-9145 FU National Institute of Neurological Disorders and Stroke [NS050041] FX Supported in part by a grant from the National Institute of Neurological Disorders and Stroke NS050041 (R. G. G). A preliminary version of this work was presented in at the 2009 Annual Meeting of the ASNR, Vancouver. The authors wish to acknowledge significant contributions by William A. Copen, MD. NR 26 TC 10 Z9 10 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD NOV 5 PY 2012 VL 12 AR 132 DI 10.1186/1471-2377-12-132 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 052NE UT WOS:000312203800001 PM 23121836 ER PT J AU Parmar, K D'Andrea, AD AF Parmar, Kalindi D'Andrea, Alan D. TI Stressed Out: Endogenous Aldehydes Damage Hematopoietic Stem Cells SO CELL STEM CELL LA English DT Editorial Material ID FANCONI-ANEMIA; MICE; DEFECTS; REPAIR; FANCD2 AB Despite a well-defined role for the Fanconi anemia (FA) pathway in mediating DNA repair, the mechanisms underlying the bone marrow failure in FA patients are poorly defined. Recently in Nature, Garaycoechea et al. (2012), identify aldehyde-mediated genotoxicity of hematopoietic stem cells as a cause for bone marrow failure. C1 [Parmar, Kalindi; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL048546, R37 HL052725]; NIDDK NIH HHS [R01 DK043889] NR 9 TC 3 Z9 3 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD NOV 2 PY 2012 VL 11 IS 5 BP 583 EP 584 DI 10.1016/j.stem.2012.10.007 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 042LE UT WOS:000311471900002 PM 23122283 ER PT J AU Weir, GC AF Weir, Gordon C. TI Cellular Transplantation into Lymph Nodes May Not Be Such a Crazy Idea SO CELL STEM CELL LA English DT Editorial Material ID ISLET TRANSPLANTATION; PANCREATIC-ISLETS; CELLS AB A study published in Nature Biotechnology by Komori and colleagues (Komori et al., 2012) has identified the surprising potential of lymph nodes as sites for cellular transplants. C1 [Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Weir, Gordon C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu NR 8 TC 2 Z9 2 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD NOV 2 PY 2012 VL 11 IS 5 BP 587 EP 588 DI 10.1016/j.stem.2012.10.004 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 042LE UT WOS:000311471900004 PM 23122285 ER PT J AU Zhang, J Nuebel, E Daley, GQ Koehler, CM Teitell, MA AF Zhang, Jin Nuebel, Esther Daley, George Q. Koehler, Carla M. Teitell, Michael A. TI Metabolic Regulation in Pluripotent Stem Cells during Reprogramming and Self-Renewal SO CELL STEM CELL LA English DT Review ID DIFFERENTIATION; CANCER; STRESS; GROWTH; PROLIFERATION; TRANSITION; EXPRESSION; GLUCOSE; ACETYLATION; CONSUMPTION AB Small, rapidly dividing pluripotent stem cells (PSCs) have unique energetic and biosynthetic demands compared with typically larger, quiescent differentiated cells. Shifts between glycolysis and oxidative phosphorylation with PSC differentiation or reprogramming to pluripotency are accompanied by changes in cell cycle, biomass, metabolite levels, and redox state. PSC and cancer cell metabolism are overtly similar, with metabolite levels influencing epigenetic/genetic programs. Here, we discuss the emerging roles for metabolism in PSC self-renewal, differentiation, and reprogramming. C1 [Zhang, Jin; Teitell, Michael A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Nuebel, Esther; Koehler, Carla M.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Koehler, Carla M.; Teitell, Michael A.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Teitell, Michael A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Broad Stem Cell Res Ctr, Los Angeles, CA 90095 USA. [Teitell, Michael A.] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA. [Daley, George Q.] Childrens Hosp, Manton Ctr Orphan Dis Res, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Broad Inst, Cambridge, MA 02142 USA. [Zhang, Jin; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Teitell, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. EM mteitell@ucla.edu FU CIRM [RS1-00313, RB1-01397, TB1-01183, TG2-01169]; Broad Stem Cell Research Center at UCLA; NIH [GM061721, GM073981, PNEY018228, P01GM081621, CA156674, CA90571, R24DK092760, RC4-DK090913, UO1-HL100001]; Alex's Lemonade Stand; Doris Duke Medical Foundation; Ellison Medical Foundation FX This work was supported by grants from CIRM (RS1-00313, RB1-01397, TB1-01183, and TG2-01169), a training grant from the Broad Stem Cell Research Center at UCLA, and grants from the NIH (GM061721, GM073981, PNEY018228, P01GM081621, CA156674, and CA90571). C.M.K. is an Established Investigator of the American Heart Association and M.A.T. was a Scholar of the Leukemia and Lymphoma Society. G.Q.D. is supported by grants from the NIH (R24DK092760, RC4-DK090913, and UO1-HL100001), Alex's Lemonade Stand, Doris Duke Medical Foundation, and Ellison Medical Foundation. G.Q.D. is an affiliate member of the Broad Institute and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. Many original articles were omitted due to space limitations; for this, we apologize. NR 55 TC 114 Z9 118 U1 3 U2 48 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD NOV 2 PY 2012 VL 11 IS 5 BP 589 EP 595 DI 10.1016/j.stem.2012.10.005 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 042LE UT WOS:000311471900005 PM 23122286 ER PT J AU McKinney-Freeman, S Cahan, P Li, H Lacadie, SA Huang, HT Curran, M Loewer, S Naveiras, O Kathrein, KL Konantz, M Langdon, EM Lengerke, C Zon, LI Collins, JJ Daley, GQ AF McKinney-Freeman, Shannon Cahan, Patrick Li, Hu Lacadie, Scott A. Huang, Hsuan-Ting Curran, Matthew Loewer, Sabine Naveiras, Olaia Kathrein, Katie L. Konantz, Martina Langdon, Erin M. Lengerke, Claudia Zon, Leonard I. Collins, James J. Daley, George Q. TI The Transcriptional Landscape of Hematopoietic Stem Cell Ontogeny SO CELL STEM CELL LA English DT Article ID DEFINITIVE HEMATOPOIESIS; HAEMOGENIC ENDOTHELIUM; REGULATORY NETWORKS; AGM REGION; YOLK-SAC; EXPRESSION; GENE; DIFFERENTIATION; PROGENITORS; LEUKEMIA AB Transcriptome analysis of adult hematopoietic stem cells (HSCs) and their progeny has revealed mechanisms of blood differentiation and leukemogenesis, but a similar analysis of HSC development is lacking. Here, we acquired the transcriptomes of developing HSCs purified from >2,500 murine embryos and adult mice. We found that embryonic hematopoietic elements clustered into three distinct transcriptional states characteristic of the definitive yolk sac, HSCs undergoing specification, and definitive HSCs. We applied a network-biology-based analysis to reconstruct the gene regulatory networks of sequential stages of HSC development and functionally validated candidate transcriptional regulators of HSC ontogeny by morpholino-mediated knockdown in zebrafish embryos. Moreover, we found that HSCs from in vitro differentiated embryonic stem cells closely resemble definitive HSCs, yet lack a Notch-signaling signature, likely accounting for their defective lymphopoiesis. Our analysis and web resource will enhance efforts to identify regulators of HSC ontogeny and facilitate the engineering of hematopoietic specification. C1 [McKinney-Freeman, Shannon; Cahan, Patrick; Lacadie, Scott A.; Huang, Hsuan-Ting; Curran, Matthew; Loewer, Sabine; Naveiras, Olaia; Kathrein, Katie L.; Langdon, Erin M.; Zon, Leonard I.; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [McKinney-Freeman, Shannon; Cahan, Patrick; Lacadie, Scott A.; Huang, Hsuan-Ting; Curran, Matthew; Loewer, Sabine; Naveiras, Olaia; Kathrein, Katie L.; Langdon, Erin M.; Zon, Leonard I.; Daley, George Q.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [McKinney-Freeman, Shannon] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. [Li, Hu; Collins, James J.] Boston Univ, Dept Biomed Engn, Ctr BioDynam, Boston, MA 02215 USA. [Li, Hu; Collins, James J.] Boston Univ, Ctr Adv Biotechnol, Boston, MA 02215 USA. [Li, Hu; Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Konantz, Martina; Lengerke, Claudia] Univ Tubingen, Div Hematol & Oncol, Med Ctr 2, D-72076 Tubingen, Germany. [Konantz, Martina] Max Planck Inst Dev Biol, Dept Genet 3, D-72076 Tubingen, Germany. [Zon, Leonard I.; Collins, James J.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Zon, Leonard I.; Daley, George Q.] Stem Cell Transplantat Program, Boston, MA 02115 USA. [Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Broad Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu OI Cahan, Patrick/0000-0003-3652-2540; Lengerke, Claudia/0000-0001-5442-2805 FU NIH [K01 DK080846, RO1-DK70055, RO1-DK59279, UO1-HL100001, RL1DE019021, R24-DK092760]; ARRA stimulus package [RC2-HL102815]; Roche Foundation for Anemia Research; Alex's Lemonade Stand; Harvard Stem Cell Institute; Burroughs Wellcome Fund; Leukemia and Lymphoma Society; NHLBI [T32HL007623, 2T32HL66987-11]; HHMI; NIH NIDDK [1R24DK092760-01]; Howard Hughes Medical Institute; SysCODE (Systems-based Consortium for Organ Design Engineering); Boston University Clinical and Translational Science Institute (CTSI) [UL1-TR000157]; Deutsche Krebshilfe (Max Eder Program); Deutsche Forschungsgemeinschaft [SFB773]; [NIH-P50-NS40828]; [NIH-P30-HD18655] FX We thank M.W. Lensch for helpful discussions and critical review of the manuscript, N. Gerry for assistance with gene expression arrays, and J. Daley and S. Lazo-Kallanian of the Dana Farber Cancer Institute (Boston, MA) and Richard Ashman and Jim Houston of St. Jude Children's Research Hospital (Memphis, TN) for expertise in cell sorting and flow cytometry. Fluidigm experiments were performed by the Molecular Genetics Core Facility at Children's Hospital Boston supported by NIH-P50-NS40828 and NIH-P30-HD18655. S.M.F. was supported by NIH grant K01 DK080846. G.Q.D. is supported by grants from the NIH (RO1-DK70055, RO1-DK59279, UO1-HL100001, Progenitor cell biology consortium, R24-DK092760, and special funds from the ARRA stimulus package RC2-HL102815), the Roche Foundation for Anemia Research, Alex's Lemonade Stand, and the Harvard Stem Cell Institute. G.Q.D. is an affiliate member of the Broad Institute, a recipient of Clinical Scientist Awards in Translational Research from the Burroughs Wellcome Fund and the Leukemia and Lymphoma Society, and an investigator of the Manton Center for Orphan Disease Research. P.C. is supported by grants T32HL007623 and 2T32HL66987-11 from the NHLBI. G.Q.D., LIZ., and J.J.C. are investigators of the Howard Hughes Medical Institute. L.I.Z. is supported by HHMI and NIH NIDDK 1R24DK092760-01. J.J.C. and H.L. are supported by Howard Hughes Medical Institute, SysCODE (Systems-based Consortium for Organ Design & Engineering), and NIH grant # RL1DE019021, and H.L. is supported by Boston University Clinical and Translational Science Institute (CTSI) grant # UL1-TR000157. C.L. was supported by grants from the Deutsche Krebshilfe (Max Eder Program) and the Deutsche Forschungsgemeinschaft (SFB773). L.I.Z. is a founder and stock holder of Fate, Inc. and a scientific advisor for Stemgent. NR 66 TC 73 Z9 75 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD NOV 2 PY 2012 VL 11 IS 5 BP 701 EP 714 DI 10.1016/j.stem.2012.07.018 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 042LE UT WOS:000311471900015 PM 23122293 ER PT J AU Asselbergs, FW Guo, YR van Iperen, EPA Sivapalaratnam, S Tragante, V Lanktree, MB Lange, LA Almoguera, B Appelman, YE Barnard, J Baumert, J Beitelshees, AL Bhangale, TR Chen, YDI Gaunt, TR Gong, Y Hopewell, JC Johnson, T Kleber, ME Langaee, TY Li, MY Li, YR Liu, KA McDonough, CW Meijs, ME Middelberg, RPS Musunuru, K Nelson, CP O'Connell, JR Padmanabhan, S Pankow, JS Pankratz, N Rafelt, S Rajagopalan, R Romaine, SPR Schork, NJ Shaffer, J Shen, HQ Smith, EN Tischfield, SE van der Most, PJ van Vliet-Ostaptchouk, JV Verweij, N Volcik, KA Zhang, L Bailey, KR Bailey, KM Bauer, F Boer, JMA Braund, PS Burt, A Burton, PR Buxbaum, SG Chen, W Cooper-DeHoff, RM Cupples, LA deJong, JS Delles, C Duggan, D Fornage, M Furlong, CE Glazer, N Gums, JG Hastie, C Holmes, MV Illig, T Kirkland, SA Kivimaki, M Klein, R Klein, BE Kooperberg, C Kottke-Marchant, K Kumari, M LaCroix, AZ Mallela, L Murugesan, G Ordovas, J Ouwehand, WH Post, WS Saxena, R Scharnagl, H Schreiner, PJ Shah, T Shields, DC Shimbo, D Srinivasan, SR Stolk, RP Swerdlow, DI Taylor, HA Topo, EJ Toskala, E van Pelt, JL van Setten, J Yusuf, S Whittaker, JC Zwinderman, AH Anand, SS Balmforth, AJ Berenson, GS Bezzina, CR Boehm, BO Boerwinkle, E Casas, JP Caulfield, MJ Clarke, R Connell, JM Cruickshanks, KJ Davidson, KW Day, INM de Bakker, PIW Doevendans, PA Dominiczak, AE Hall, AS Hartman, CA Hengstenberg, C Hillege, HL Hofker, MH Humphries, SE Jarvik, GP Johnson, JA Kaess, BM Kathiresan, S Koenig, W Lawlor, DA Maerz, W Melander, O Mitchell, BD Montgomery, GW Munroe, PB Murray, SS Newhouse, SJ Onland-Moret, NC Poulter, N Psaty, B Redline, S Rich, SS Rotter, JI Schunkert, H Sever, P Shuldiner, AR Silverstein, RL Stanton, A Thorand, B Trip, MD Tsai, MY van der Harst, P van der Schoot, E van der Schouw, YT Verschuren, WMM Watkins, H Wilde, AAM Wolffenbuttel, BHR Whitfield, JB Hovingh, GK Ballantyne, CM Wijmenga, C Reilly, MP Martin, NG Wilson, JG Rader, DJ Samani, NJ Reiner, AP Hegele, RA Kastelein, JJP Hingorani, AD Talmud, PJ Hakonarson, H Elbers, CC Keating, BJ Drenos, F AF Asselbergs, Folkert W. Guo, Yiran van Iperen, Erik P. A. Sivapalaratnam, Suthesh Tragante, Vinicius Lanktree, Matthew B. Lange, Leslie A. Almoguera, Berta Appelman, Yolande E. Barnard, John Baumert, Jens Beitelshees, Amber L. Bhangale, Tushar R. Chen, Yii-Der Ida Gaunt, Tom R. Gong, Yan Hopewell, Jemma C. Johnson, Toby Kleber, Marcus E. Langaee, Taimour Y. Li, Mingyao Li, Yun R. Liu, Kiang McDonough, Caitrin W. Meijs, Matthijs El. Middelberg, Rita P. S. Musunuru, Kiran Nelson, Christopher P. O'Connell, Jeffery R. Padmanabhan, Sandosh Pankow, James S. Pankratz, Nathan Rafelt, Suzanne Rajagopalan, Ramakrishnan Romaine, Simon P. R. Schork, Nicholas J. Shaffer, Jonathan Shen, Haiqing Smith, Erin N. Tischfield, Sam E. van der Most, Peter J. van Vliet-Ostaptchouk, Jana V. Verweij, Niek Volcik, Kelly A. Zhang, Li Bailey, Kent R. Bailey, Kristian M. Bauer, Florianne Boer, Jolanda M. A. Braund, Peter S. Burt, Amber Burton, Paul R. Buxbaum, Sarah G. Chen, Wei Cooper-DeHoff, Rhonda M. Cupples, L. Adrienne deJong, Jonas S. Delles, Christian Duggan, David Fornage, Myriam Furlong, Clement E. Glazer, Nicole Gums, John G. Hastie, Claire Holmes, Michael V. Illig, Thomas Kirkland, Susan A. Kivimaki, Mika Klein, Ronald Klein, Barbara E. Kooperberg, Charles Kottke-Marchant, Kandice Kumari, Meena LaCroix, Andrea Z. Mallela, Laya Murugesan, Gurunathan Ordovas, Jose Ouwehand, Willem H. Post, Wendy S. Saxena, Richa Scharnagl, Hubert Schreiner, Pamela J. Shah, Tina Shields, Denis C. Shimbo, Daichi Srinivasan, Sathanur R. Stolk, Ronald P. Swerdlow, Daniel I. Taylor, Herman A., Jr. Topo, Eric J. Toskala, Elina van Pelt, Joost L. van Setten, Jessica Yusuf, Salim Whittaker, John C. Zwinderman, A. H. Anand, Sonia S. Balmforth, Anthony J. Berenson, Gerald S. Bezzina, Connie R. Boehm, Bernhard O. Boerwinkle, Eric Casas, Juan P. Caulfield, Mark J. Clarke, Robert Connell, John M. Cruickshanks, Karen J. Davidson, Karina W. Day, Ian N. M. de Bakker, Paul I. W. Doevendans, Pieter A. Dominiczak, Anna E. Hall, Alistair S. Hartman, Catharina A. Hengstenberg, Christian Hillege, Hans L. Hofker, Marten H. Humphries, Steve E. Jarvik, Gail P. Johnson, Julie A. Kaess, Bernhard M. Kathiresan, Sekar Koenig, Wolfgang Lawlor, Debbie A. Maerz, Winfried Melander, Olle Mitchell, Braxton D. Montgomery, Grant W. Munroe, Patricia B. Murray, Sarah S. Newhouse, Stephen J. Onland-Moret, N. Charlotte Poulter, Neil Psaty, Bruce Redline, Susan Rich, Stephen S. Rotter, Jerome I. Schunkert, Heribert Sever, Peter Shuldiner, Alan R. Silverstein, Roy L. Stanton, Alice Thorand, Barbara Trip, Mieke D. Tsai, Michael Y. van der Harst, Pim van der Schoot, Ellen van der Schouw, Yvonne T. Verschuren, W. M. Monique Watkins, Hugh Wilde, Arthur A. M. Wolffenbuttel, Bruce H. R. Whitfield, John B. Hovingh, G. Kees Ballantyne, Christie M. Wijmenga, Cisca Reilly, Muredach P. Martin, Nicholas G. Wilson, James G. Rader, Daniel J. Samani, Nilesh J. Reiner, Alex P. Hegele, Robert A. Kastelein, John J. P. Hingorani, Aroon D. Talmud, Philippa J. Hakonarson, Hakon Elbers, Clara C. Keating, Brendan J. Drenos, Fotios CA LifeLines Cohort Study TI Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; APOLIPOPROTEIN B-100; MISSING HERITABILITY; PLASMA TRIGLYCERIDES; QUANTITATIVE TRAITS; STATISTICAL-MODEL; COMPLEX TRAITS AB Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids. C1 [Guo, Yiran; Almoguera, Berta; Li, Yun R.; Mallela, Laya; Toskala, Elina; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Asselbergs, Folkert W.; Tragante, Vinicius; Meijs, Matthijs El.; Doevendans, Pieter A.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, NL-3508 GA Utrecht, Netherlands. [Asselbergs, Folkert W.; Bauer, Florianne; de Bakker, Paul I. W.; Onland-Moret, N. 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[Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Samani, Nilesh J.] Glenfield Gen Hosp, Natl Inst Hlth, Res Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England. [Hegele, Robert A.] Univ Western Ontario, Robarts Res Inst, London, ON N6A 5K8, Canada. [Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. RP Keating, BJ (reprint author), Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA. EM bkeating@mail.med.upenn.edu; f.drenos@ucl.ac.uk RI Wolffenbuttel, Bruce/A-8419-2011; Stanton, Alice/F-4697-2012; de Bakker, Paul/B-8730-2009; Wijmenga, Cisca/D-2173-2009; van der Schouw, Yvonne/F-8327-2014; Thorand, Barbara/B-5349-2014; Jarvik, Gail/N-6476-2014; Gaunt, Tom/O-3918-2014; Boehm, Bernhard/F-8750-2015; Onland-Moret, N. Charlotte/G-9185-2011; Guo, Yiran/H-4120-2011; Stolk, Ronald/B-2341-2013; Montgomery, Grant/B-7148-2008; Hegele, Robert/G-3301-2011; Newhouse, Stephen/C-9330-2011; Padmanabhan, Sandosh/S-3963-2016; Verweij, Niek/A-4499-2017; Buxbaum, Sarah/E-1970-2013; OI van Iperen, Erik/0000-0001-7107-3168; Topol, Eric/0000-0002-1478-4729; Mitchell, Braxton/0000-0003-4920-4744; Ouwehand, Willem/0000-0002-7744-1790; Lawlor, Debbie A/0000-0002-6793-2262; Pankow, James/0000-0001-7076-483X; Kleber, Marcus/0000-0003-0663-7275; Martin, Nicholas/0000-0003-4069-8020; Wolffenbuttel, Bruce/0000-0001-9262-6921; de Bakker, Paul/0000-0001-7735-7858; van der Schouw, Yvonne/0000-0002-4605-435X; Thorand, Barbara/0000-0002-8416-6440; Jarvik, Gail/0000-0002-6710-8708; Gaunt, Tom/0000-0003-0924-3247; Guo, Yiran/0000-0002-6549-8589; Stolk, Ronald/0000-0002-0518-1205; Montgomery, Grant/0000-0002-4140-8139; Newhouse, Stephen/0000-0002-1843-9842; Shah, Tina/0000-0001-7724-7210; Franke, Lude/0000-0002-5159-8802; Cupples, L. Adrienne/0000-0003-0273-7965; Lanktree, Matthew/0000-0002-5750-6286; Stanton, Alice/0000-0002-4961-165X; van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Kivimaki, Mika/0000-0002-4699-5627; Buxbaum, Sarah/0000-0002-4886-3564; Talmud, Philippa/0000-0002-5560-1933; Johnson, Toby/0000-0002-5998-3270; Swerdlow, Daniel/0000-0002-7946-3459; Padmanabhan, Sandosh/0000-0003-3869-5808; Humphries, Stephen E/0000-0002-8221-6547; Wijmenga, Cisca/0000-0002-5635-1614; Kumari, Meena/0000-0001-9716-1035; Verweij, Niek/0000-0002-4303-7685; Klein, Ronald/0000-0002-4428-6237; Watkins, Hugh/0000-0002-5287-9016 FU AHRQ HHS [HS06516]; British Heart Foundation [CH/03/001, CH/98001, PG/02/128, PG/07/131/24254, PG/07/132/24256, PG/07/133/24260, RG/07/005/23633, RG/08/008, RG/08/008/25291, RG/10/12/28456, RG/2001004, SP/07/007/23671, SP/08/005/25115]; Department of Health; Intramural NIH HHS; Medical Research Council [G0802432, G9521010, G9521010D, MC_U137686857]; NCATS NIH HHS [UL1 TR000064, UL1 TR000124, UL1 TR000135, UL1 TR000454]; NCI NIH HHS [P30 CA015704]; NCRR NIH HHS [UL1 RR025774, UL1RR025005]; NEI NIH HHS [U10EY06594]; NHGRI NIH HHS [U01HG004402]; NHLBI NIH HHS [HL36310, K24 HL084034, N01-HC-05187, N01-HC-15103, N01-HC-25195, N01-HC-35129, N01-HC-45134, N01-HC-45204, N01-HC-45205, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-55222, N01-HC-75150, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-95095, N01-HC-95100, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, P01 HL088117, P50HL81011, R01 HL088119, R01 HL091099, R01 HL105756, R01 HL67406, R01-HL-071205, R01-HL-076784, R01-HL-092577, R01HL086694, R01HL087641, R01HL59367, U01 HL72515, U01-HL-080295]; NIA NIH HHS [AG-16592, AG13196, R01 AG011099, R01 AG016592, R01 AG021917, R01 AG18728, R01-AG-028321, R01AG021917, R37 AG011099, R37AG11099]; NICHD NIH HHS [HD-061437, HD-062783]; NIDDK NIH HHS [P30 DK063491, P30 DK072488]; NIGMS NIH HHS [U01 GM074492, U01-GM074492]; NIMHD NIH HHS [P20 MD006899]; Wellcome Trust [, 090532] NR 76 TC 95 Z9 95 U1 4 U2 41 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 NOV 2 PY 2012 VL 91 IS 5 BP 823 EP 838 DI 10.1016/j.ajhg.2012.08.032 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 036FI UT WOS:000311011400005 PM 23063622 ER PT J AU Yariz, KO Duman, D Seco, CZ Dallman, J Huang, MQ Peters, TA Sirmaci, A Lu, N Schraders, M Skromne, I Oostrik, J Diaz-Horta, O Young, JI Tokgoz-Yilmaz, S Konukseven, O Shahin, H Hetterschijt, L Kanaan, M Oonk, AMM Edwards, YJK Li, HW Atalay, S Blanton, S DeSmidt, AA Liu, XZ Pennings, RJE Lu, ZM Chen, ZY Kremer, H Tekin, M AF Yariz, Kemal O. Duman, Duygu Seco, Celia Zazo Dallman, Julia Huang, Mingqian Peters, Theo A. Sirmaci, Asli Lu, Na Schraders, Margit Skromne, Isaac Oostrik, Jaap Diaz-Horta, Oscar Young, Juan I. Tokgoz-Yilmaz, Suna Konukseven, Ozlem Shahin, Hashem Hetterschijt, Lisette Kanaan, Moien Oonk, Anne M. M. Edwards, Yvonne J. K. Li, Huawei Atalay, Semra Blanton, Susan DeSmidt, Alexandra A. Liu, Xue-Zhong Pennings, Ronald J. E. Lu, Zhongmin Chen, Zheng-Yi Kremer, Hannie Tekin, Mustafa TI Mutations in OTOGL, Encoding the Inner Ear Protein Otogelin-like, Cause Moderate Sensorineural Hearing Loss SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HAIR-CELLS; EXPRESSION; ZEBRAFISH; GENE AB Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Here we present OTOGL mutations, a homozygous one base pair deletion (c.1430 delT) causing a frameshift (p.Val477Glufs*25) in a large consanguineous family and two compound heterozygous mutations, c.547C>T (p.Arg183*) and c.5238+5G>A, in a nonconsanguineous family with moderate nonsyndromic sensorineural hearing loss. OTOGL maps to the DFNB84 locus at 12q21.31 and encodes otogelin-like, which has structural similarities to the epithelial-secreted mucin protein family. We demonstrate that Otogl is expressed in the inner ear of vertebrates with a transcription level that is high in embryonic, lower in neonatal, and much lower in adult stages. Otogelin-like is localized to the acellular membranes of the cochlea and the vestibular system and to a variety of inner ear cells located underneath these membranes. Knocking down of otogl with morpholinos in zebrafish leads to sensorineural hearing loss and anatomical changes in the inner ear, supporting that otogelin-like is essential for normal inner ear function. We propose that OTOGL mutations affect the production and/or function of acellular structures of the inner ear, which ultimately leads to sensorineural hearing loss. C1 [Yariz, Kemal O.; Sirmaci, Asli; Diaz-Horta, Oscar; Young, Juan I.; Edwards, Yvonne J. K.; Blanton, Susan; Liu, Xue-Zhong; Tekin, Mustafa] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Yariz, Kemal O.; Sirmaci, Asli; Diaz-Horta, Oscar; Young, Juan I.; Edwards, Yvonne J. K.; Blanton, Susan; Tekin, Mustafa] Univ Miami, Miller Sch Med, Dr John T Macdonald Dept Human Genet, Miami, FL 33136 USA. [Liu, Xue-Zhong] Univ Miami, Miller Sch Med, Dept Otolaryngol, Miami, FL 33136 USA. [Duman, Duygu; Tokgoz-Yilmaz, Suna; Atalay, Semra; Tekin, Mustafa] Ankara Univ, Sch Med, Div Pediat Genet, TR-06100 Ankara, Turkey. [Seco, Celia Zazo; Peters, Theo A.; Schraders, Margit; Oostrik, Jaap; Oonk, Anne M. M.; Pennings, Ronald J. E.; Kremer, Hannie] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands. [Seco, Celia Zazo; Peters, Theo A.; Schraders, Margit; Oostrik, Jaap; Oonk, Anne M. M.; Pennings, Ronald J. E.; Kremer, Hannie] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Seco, Celia Zazo; Peters, Theo A.; Schraders, Margit; Oostrik, Jaap; Hetterschijt, Lisette; Kremer, Hannie] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands. [Hetterschijt, Lisette; Kremer, Hannie] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Dallman, Julia; Skromne, Isaac; DeSmidt, Alexandra A.; Lu, Zhongmin] Univ Miami, Dept Biol, Miami, FL 33146 USA. [Huang, Mingqian; Lu, Na; Chen, Zheng-Yi] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Eaton Peabody Lab, Boston, MA 02114 USA. [Lu, Na; Li, Huawei] Fudan Univ, Affiliated Eye & ENT Hosp, Dept Otol & Skull Base Surg, Shanghai 200031, Peoples R China. [Konukseven, Ozlem] Ataturk Training & Res Hosp, Hearing & Balance Disorders Diag & Rehabil Ctr, TR-06800 Ankara, Turkey. [Shahin, Hashem; Kanaan, Moien] Bethlehem Univ, Dept Life Sci, Bethlehem, Israel. [Liu, Xue-Zhong] Cent S Univ, Xiangya Hosp 2, Dept Otolaryngol Head & Neck Surg, Changsha 410011, Hunan, Peoples R China. RP Tekin, M (reprint author), Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. EM mtekin@med.miami.edu RI Kremer, Hannie/F-5126-2010; Pennings, Ronald/J-6651-2012; Peters, T.A./L-4571-2015; Schraders, Margit/A-1607-2016; Oostrik, Jaap/A-1703-2016; Oonk, Anne/G-3935-2016 OI Kremer, Hannie/0000-0002-0841-8693; FU National Institutes of Health [R01DC009645, R01 DC006908, R21 DC009879, RO1DC05575]; Fredrick and Ines Yeatts Inner Ear Hair Cell Regeneration Fellowship; Heinsius Houbolt Foundation; Oticon Foundation [09-3742]; ZonMW [40-00812-98-09047, 90700388]; RNID [GR36]; China Scholarship Council, P.R. China; Hurong Scholar Award in Hunan, China; University of Miami Provost Research Award and College of Arts; Sciences Gabelli Fellowship; National Science Foundation [IOS-0920449]; University of Miami Provost Research Award FX We want to acknowledge the families for their participation in the study. This work was supported by National Institutes of Health grants R01DC009645 to M.T., R01 DC006908 to Z.-Y.C, R21 DC009879 to Z. L., RO1DC05575 to X.-Z.L., the Fredrick and Ines Yeatts Inner Ear Hair Cell Regeneration Fellowship to M.H. and N.L., the Heinsius Houbolt Foundation to H.K., the Oticon Foundation (09-3742) to H.K., ZonMW to H.K. (40-00812-98-09047) and R.J.E.P. (90700388), and the RNID (GR36) to H.K. N.L. was supported by a grant from the China Scholarship Council, P.R. China. X.Z.L. was supported by Hurong Scholar Award in Hunan, China. Z.L. and J.D. were supported by the University of Miami Provost Research Award and College of Arts. Z.L. was supported by Sciences Gabelli Fellowship. I.S. was supported by National Science Foundation grant IOS-0920449 and by the University of Miami Provost Research Award. We are grateful to Atlas Antibodies for providing the OTOGL immunogenic peptide. NR 31 TC 38 Z9 43 U1 0 U2 17 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 NOV 2 PY 2012 VL 91 IS 5 BP 872 EP 882 DI 10.1016/j.ajhg.2012.09.011 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 036FI UT WOS:000311011400009 PM 23122586 ER PT J AU Xu, C Xu, Y Gursoy-Yuzugullu, O Price, BD AF Xu, Chang Xu, Ye Gursoy-Yuzugullu, Ozge Price, Brendan D. TI The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1 SO FEBS LETTERS LA English DT Article DE DNA repair; MacroH2A1; Ionizing radiation; 53BP1; Nucleosome ID DOUBLE-STRAND BREAKS; DNA-DAMAGE; CHROMATIN; 53BP1; ACTIVATION; REPAIR; PROTEINS; MAINTENANCE; METHYLATION; CHECKPOINT AB The repair of DNA double-strand breaks (DSBs) requires remodeling of the local chromatin architecture to allow the repair machinery to access sites of damage. Here, we report that the histone variant macroH2A1.1 is recruited to DSBs. Cells lacking macroH2A1 have defective recruitment of 53BP1, defective activation of chk2 kinase and increased radiosensitivity. Importantly, macroH2A1.1 is not incorporated into nucleosomes at DSBs, but instead associates with the chromatin through a mechanism which requires PARP1 activity. These results reveal an unusual mechanism involving a direct association of macroH2A1.1 with PARylated chromatin which is critical for retaining 53BP1 at sites of damage. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved. C1 [Xu, Chang; Xu, Ye; Gursoy-Yuzugullu, Ozge; Price, Brendan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Xu, Chang] Chinese Acad Med Sci, Inst Radiat Med, Tianjin 300192, Peoples R China. [Xu, Chang] Peking Union Med Coll, Tianjin Key Lab Mol Nucl Med, Tianjin 300192, Peoples R China. RP Xu, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM 2008xucchang@gmail.com; brendan_price@dfci.harvard.edu FU NCI [CA64585, CA93602] FX We thank J. Stark for NHEJ reporter cells and B. Chadwick for mH2A1.1 and mH2A1.2 plasmids. Supported by Grants from the NCI (CA64585 and CA93602) to BDP. NR 26 TC 19 Z9 20 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 2 PY 2012 VL 586 IS 21 BP 3920 EP 3925 DI 10.1016/j.febslet.2012.09.030 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 029WV UT WOS:000310529000025 PM 23031826 ER PT J AU Lu, CF Mi, LZ Schurpf, T Walz, T Springer, TA AF Lu, Chafen Mi, Li-Zhi Schuerpf, Thomas Walz, Thomas Springer, Timothy A. TI Mechanisms for Kinase-mediated Dimerization of the Epidermal Growth Factor Receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; LUNG-CANCER; ACTIVATION; EGFR; DOMAIN; INHIBITOR; CELLS; VISUALIZATION; SENSITIVITY; COMPLEXES AB We study a mechanism by which dimerization of the EGF receptor (EGFR) cytoplasmic domain is transmitted to the ectodomain. Therapeutic and other small molecule antagonists to the kinase domain that stabilize its active conformation, but not those that stabilize an inactive conformation, stabilize ectodomain dimerization. Inhibitor-induced dimerization requires an asymmetric kinase domain interface associated with activation. EGF and kinase inhibitors stimulate formation of identical dimer interfaces in the EGFR transmembrane domain, as shown by disulfide cross-linking. Disulfide cross-linking at an interface in domain IV in the ectodomain was also stimulated similarly; however, EGF but not inhibitors stimulated cross-linking in domain II. Inhibitors similarly induced noncovalent dimerization in nearly full-length, detergent-solubilized EGFR as shown by gel filtration. EGFR ectodomain deletion resulted in spontaneous dimerization, whereas deletion of exons 2-7, in which extracellular domains III and IV are retained, did not. In EM, kinase inhibitor-induced dimers lacked any well defined orientation between the ectodomain monomers. Fab of the therapeutic antibody cetuximab to domain III confirmed a variable position and orientation of this domain in inhibitor-induced dimers but suggested that the C termini of domain IV of the two monomers were in close proximity, consistent with dimerization in the transmembrane domains. The results provide insights into the relative energetics of intracellular and extracellular dimerization in EGFR and have significance for physiologic dimerization through the asymmetric kinase interface, bidirectional signal transmission in EGFR, and mechanism of action of therapeutics. C1 [Lu, Chafen; Mi, Li-Zhi; Schuerpf, Thomas; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Lu, Chafen; Mi, Li-Zhi; Schuerpf, Thomas; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Walz, Thomas] Howard Hughes Med Inst, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Mi, Li-Zhi/B-1371-2016 OI Mi, Li-Zhi/0000-0001-9907-5245 FU National Institutes of Health [HL-103526]; Howard Hughes Medical Institute FX This work was supported, in whole or in part, by National Institutes of Health Grant HL-103526. This work was also supported by the Howard Hughes Medical Institute (to T. W.). NR 32 TC 17 Z9 17 U1 0 U2 16 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 2 PY 2012 VL 287 IS 45 DI 10.1074/jbc.M112.414391 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 031LP UT WOS:000310642200057 PM 22988250 ER PT J AU Derr, ND Goodman, BS Jungmann, R Leschziner, AE Shih, WM Reck-Peterson, SL AF Derr, N. D. Goodman, B. S. Jungmann, R. Leschziner, A. E. Shih, W. M. Reck-Peterson, S. L. TI Tug-of-War in Motor Protein Ensembles Revealed with a Programmable DNA Origami Scaffold SO SCIENCE LA English DT Article ID CYTOPLASMIC DYNEIN; INTRACELLULAR-TRANSPORT; BIDIRECTIONAL TRANSPORT; ORGANELLE TRANSPORT; TRANSIENT BINDING; STEPPING BEHAVIOR; MOLECULAR MOTORS; CARGO TRANSPORT; KINESIN; MICROTUBULES AB Cytoplasmic dynein and kinesin-1 are microtubule-based motors with opposite polarity that transport a wide variety of cargo in eukaryotic cells. Many cellular cargos demonstrate bidirectional movement due to the presence of ensembles of dynein and kinesin, but are ultimately sorted with spatial and temporal precision. To investigate the mechanisms that coordinate motor ensemble behavior, we built a programmable synthetic cargo using three-dimensional DNA origami to which varying numbers of DNA oligonucleotide-linked motors could be attached, allowing for control of motor type, number, spacing, and orientation in vitro. In ensembles of one to seven identical-polarity motors, motor number had minimal affect on directional velocity, whereas ensembles of opposite-polarity motors engaged in a tug-of-war resolvable by disengaging one motor species. C1 [Derr, N. D.; Goodman, B. S.; Reck-Peterson, S. L.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Derr, N. D.; Shih, W. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Derr, N. D.; Shih, W. M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Jungmann, R.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Jungmann, R.; Shih, W. M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Leschziner, A. E.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Reck-Peterson, SL (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM reck-peterson@hms.harvard.edu RI Jungmann, Ralf/A-6357-2015 OI Jungmann, Ralf/0000-0003-4607-3312 FU Alexander von Humboldt Foundation; Rita Allen Foundation; Harvard Armenise Foundation; NIH [1 DP2 OD004268-1, 1U54GM094608, 1DP2OD004641]; ONR [N000014091118, N000141010241] FX We thank C. Lin for assistance with electron microscopy; F. Aguet for assistance with data analysis; J. Huang, W. Qiu, W. B. Redwine, and A. Roberts for helpful advice and critical reading of the manuscript; members of the Reck-Peterson and Shih labs for advice and helpful discussions; and J. Iwasa for illustrations. EM data were collected at the Center for Nanoscale Systems, Harvard University. DNA-PAINT data were collected at the Nikon Imaging Center, Harvard Medical School. R. J. is supported from the Alexander von Humboldt Foundation through a Feodor Lynen fellowship. S.L.R.-P. is funded by the Rita Allen Foundation, the Harvard Armenise Foundation, and a NIH New Innovator award (1 DP2 OD004268-1). W. M. S. is funded by NIH awards (1U54GM094608 and 1DP2OD004641) and ONR awards (N000014091118 and N000141010241). NR 38 TC 129 Z9 130 U1 14 U2 124 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 2 PY 2012 VL 338 IS 6107 BP 662 EP 665 DI 10.1126/science.1226734 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 029SM UT WOS:000310516000052 PM 23065903 ER PT J AU Kreindler, JL Chen, B Kreitman, Y Kofonow, J Adams, KM Cohen, NA AF Kreindler, James L. Chen, Bei Kreitman, Yael Kofonow, Jennifer Adams, Kelly M. Cohen, Noam A. TI The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CHRONIC RHINOSINUSITIS; BICARBONATE SECRETION; CHRONIC SINUSITIS; CELLS; INHIBITION; DIAGNOSIS; CHANNEL; AIRWAYS; NASAL AB Background: Herbal remedies predate written history and continue to be used more frequently than conventional pharmaceutical medications. The novel dry extract BNO 1011 is based on a combination of five herbs that is used to treat acute and chronic rhinosinusitis. We evaluated the pharmacologic effects of the novel dry extract BNO 1011 on human respiratory epithelial cultures specifically addressing electrolyte transport and cilia beat frequency (CBF). Methods: Well-differentiated human bronchial epithelial cultures grown at an air-liquid interface were treated on the apical or basolateral surface with varying concentrations of dry extract BNO 1011. Changes in transepithelial sodium and chloride transport were determined in Ussing chambers under voltage-clamped conditions. Changes in CBF were determined using the Sissons-Ammons Video Analysis system (Ammons Engineering, Mt. Morris, MI). Results: When applied to the apical surface, dry extract BNO 1011 activated forskolin-stimulated chloride secretion and ciliary beat in a dose-dependent fashion. Basolateral application of dry extract BNO 1011 did not alter the measured physiological properties. Conclusion: Apical application of dry extract BNO 1011 stimulates both chloride secretion and CBF and therefore may augment mucociliary clearance. C1 [Kreindler, James L.; Adams, Kelly M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Kreindler, James L.; Adams, Kelly M.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Chen, Bei; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Kreitman, Yael] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Kofonow, Jennifer; Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg 5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 FU Bionorica SE, Neumarkt, Germany FX Funded by Bionorica SE, Neumarkt, Germany. The company had no role in collecting or analyzing data for inclusion in this article but did participate in its generation. Evaluation of raw data and data interpretation were performed independently by the investigators NR 30 TC 3 Z9 3 U1 0 U2 2 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 NOV-DEC PY 2012 VL 26 IS 6 BP 439 EP 443 DI 10.2500/ajra.2012.26.3821 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 193FK UT WOS:000322543600005 PM 23232192 ER PT J AU Menzies, NA Cohen, T Lin, HH Murray, M Salomon, JA AF Menzies, Nicolas A. Cohen, Ted Lin, Hsien-Ho Murray, Megan Salomon, Joshua A. TI Population Health Impact and Cost-Effectiveness of Tuberculosis Diagnosis with Xpert MTB/RIF: A Dynamic Simulation and Economic Evaluation SO PLOS MEDICINE LA English DT Article ID MULTIDRUG-RESISTANT TUBERCULOSIS; NEGATIVE PULMONARY TUBERCULOSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; CARE FACILITY INVOLVEMENT; HIGH HIV PREVALENCE; SHORT-TERM RISK; SOUTH-AFRICA; ANTIRETROVIRAL THERAPY; HIV-1-INFECTED PATIENTS; COLLABORATIVE ANALYSIS AB Background: The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert. Methods and Findings: We evaluated potential health and economic consequences of implementing Xpert in five southern African countries-Botswana, Lesotho, Namibia, South Africa, and Swaziland-where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000-284,000) TB cases and 182,000 (97,000-302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%-40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$ 460 million (294-699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$ 959 (633-1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$ 792 (482-1,785) in Swaziland to US$ 1,257 (767-2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values. Conclusions: Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence. C1 [Menzies, Nicolas A.; Salomon, Joshua A.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Menzies, Nicolas A.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Cohen, Ted; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cohen, Ted] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Lin, Hsien-Ho] Natl Taiwan Univ, Grad Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan. [Salomon, Joshua A.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. RP Menzies, NA (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM nmenzies@fas.harvard.edu RI Salomon, Joshua/D-3898-2009; OI Salomon, Joshua/0000-0003-3929-5515; LIN, HSIEN-HO/0000-0002-7481-6016 FU UNITAID; Massachusetts General Hospital's Program in Cancer Outcomes and Training (NIH Grant) [R25 CA092203] FX NAM and JAS were supported in part by funding from UNITAID. NAM was also supported by a training grant from the Massachusetts General Hospital's Program in Cancer Outcomes and Training (NIH Grant No. R25 CA092203). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 105 TC 81 Z9 83 U1 0 U2 14 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 NOV PY 2012 VL 9 IS 11 AR e1001347 DI 10.1371/journal.pmed.1001347 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 048CW UT WOS:000311888800013 PM 23185139 ER PT J AU Orrell, C Levison, J Ciaranello, A Bekker, L Kuritzkes, D Freedberg, K Wood, R AF Orrell, C. Levison, J. Ciaranello, A. Bekker, L. Kuritzkes, D. Freedberg, K. Wood, R. TI Evolution of resistance in paediatric patients with failure on antiretroviral therapy SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY LA English DT Meeting Abstract C1 [Orrell, C.; Bekker, L.; Wood, R.] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Levison, J.; Ciaranello, A.; Freedberg, K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kuritzkes, D.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU INT AIDS SOCIETY PI GENEVA PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND SN 1758-2652 J9 J INT AIDS SOC JI J. Int. AIDS Soc. PD NOV PY 2012 VL 15 SU 4 BP 7 EP 7 DI 10.7448/IAS.15.6.18086 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 167SH UT WOS:000320654200021 ER PT J AU McMillin, DW Mitsiades, CS AF McMillin, Douglas W. Mitsiades, Constantine S. TI High-throughput approaches to discover novel immunomodulatory agents for cancer SO ONCOIMMUNOLOGY LA English DT Article DE pharmacological immunomodulators; high-throughput screening; cancer; immune effector cells; tumor heterogeneity ID MULTIPLE-MYELOMA; THERAPY; LENALIDOMIDE AB The clinical success of immunomodulatory thalidomide derivatives has renewed the general interest in immunomodulatory anticancer compounds and prompted us to develop a high-throughput system to quantify immune effector-cell activity. We documented that the interaction between cancer cells, their stroma, anticancer agents and cells from the innate system are critical for determining the response of tumors to immunomodulatory strategies. C1 [Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Constantine_Mitsiades@dfci.harvard.edu NR 10 TC 5 Z9 5 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 J9 ONCOIMMUNOLOGY JI OncoImmunology PD NOV PY 2012 VL 1 IS 8 BP 1406 EP 1408 DI 10.4161/onci.21058 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 108GR UT WOS:000316280700025 ER PT J AU Boudreaux, ED Bedek, KL Byrne, NJ Baumann, BM Lord, SA Grissom, G AF Boudreaux, Edwin D. Bedek, Kristyna L. Byrne, Nelson J. Baumann, Brigitte M. Lord, Sherrill A. Grissom, Grant TI The Computer-Assisted Brief Intervention for Tobacco (CABIT) Program: A Pilot Study SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE technology; tobacco use cessation; smoking cessation; referrals ID EMERGENCY-DEPARTMENT PATIENTS; PROMOTING SMOKING-CESSATION; RANDOMIZED-CONTROLLED-TRIAL; NICOTINE DEPENDENCE; PRIMARY-CARE; INTEGRATIVE MODEL; FAGERSTROM TEST; RISK-REDUCTION; HEALTH; PHYSICIANS AB Background: Health care providers do not routinely carry out brief counseling for tobacco cessation despite the evidence for its effectiveness. For this intervention to be routinely used, it must be brief, be convenient, require little investment of resources, require little specialized training, and be perceived as efficacious by providers. Technological advances hold much potential for addressing the barriers preventing the integration of brief interventions for tobacco cessation into the health care setting. Objective: This paper describes the development and initial evaluation of the Computer-Assisted Brief Intervention for Tobacco (CABIT) program, a web-based, multimedia tobacco intervention for use in opportunistic settings. Methods: The CABIT uses a self-administered, computerized assessment to produce personalized health care provider and patient reports, and cue a stage-matched video intervention. Respondents interested in changing their tobacco use are offered a faxed referral to a "best matched" tobacco treatment provider (ie, dynamic referral). During 2008, the CABIT program was evaluated in an emergency department, an employee assistance program, and a tobacco dependence program in New Jersey. Participants and health care providers completed semistructured interviews and satisfaction ratings of the assessment, reports, video intervention, and referrals using a 5-point scale. Results: Mean patient satisfaction scores (n = 67) for all domains ranged from 4.00 (Good) to 5.00 (Excellent; Mean = 4.48). Health care providers completed satisfaction forms for 39 patients. Of these 39 patients, 34 (87%) received tobacco resources and referrals they would not have received under standard care. Of the 45 participants offered a dynamic referral, 28 (62%) accepted. Conclusions: The CABIT program provided a user-friendly, desirable service for tobacco users and their health care providers. Further development and clinical trial testing is warranted to establish its effectiveness in promoting treatment engagement and tobacco cessation. (J Med Internet Res 2012; 14(6): e163) doi: 10.2196/jmir.2074 C1 [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. [Bedek, Kristyna L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Byrne, Nelson J.] Credit Valley Hosp, Mississauga, ON, Canada. [Byrne, Nelson J.] Trillium Hlth Ctr, Mississauga, ON, Canada. [Baumann, Brigitte M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. [Baumann, Brigitte M.] Cooper Univ Hosp, Dept Emergency Med, Camden, NJ USA. [Lord, Sherrill A.; Grissom, Grant] Polaris Hlth Direct Inc, Langhorne, PA USA. RP Boudreaux, ED (reprint author), Univ Massachusetts, Sch Med, LA 189,55 Lake Ave North, Worcester, MA 01655 USA. EM Edwin.Boudreaux@umassmed.edu OI Boudreaux, Edwin/0000-0002-3223-6371 FU National Institute on Drug Abuse [R41DA019718] FX The study was performed while Edwin Boudreaux, Ph.D., was employed by Cooper Health System and faculty with Robert Wood Johnson Medical School in Camden, NJ. He is currently employed by the University of Massachusetts Medical School. This research was supported by a Small Business Technology Grant from the National Institute on Drug Abuse (R41DA019718) to Polaris Health Directions, Inc. NR 49 TC 2 Z9 2 U1 0 U2 8 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 NOV-DEC PY 2012 VL 14 IS 6 BP 72 EP 87 AR e163 DI 10.2196/jmir.2074 PG 16 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 099TV UT WOS:000315646000006 PM 23208070 ER PT J AU Emani, S Yamin, CK Peters, E Karson, AS Lipsitz, SR Wald, JS Williams, DH Bates, DW AF Emani, Srinivas Yamin, Cyrus K. Peters, Ellen Karson, Andrew S. Lipsitz, Stuart R. Wald, Jonathan S. Williams, Deborah H. Bates, David W. TI Patient Perceptions of a Personal Health Record: A Test of the Diffusion of Innovation Model SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Personal health record (PHR); perceptions; innovation; electronic health records (EHRs); meaningful use ID TECHNOLOGY ACCEPTANCE MODEL; INFORMATION-TECHNOLOGY; MEDICAL-RECORDS; DIGITAL DIVIDE; RECOMMENDATIONS; COMMUNICATION; SATISFACTION; EXPERIENCES; SERVICES; MESSAGE AB Background: Personal health records (PHRs) have emerged as an important tool with which patients can electronically communicate with their doctors and doctor's offices. However, there is a lack of theoretical and empirical research on how patients perceive the PHR and the differences in perceptions between users and non-users of the PHR. Objective: To apply a theoretical model, the diffusion of innovation model, to the study of PHRs and conduct an exploratory empirical study on the applicability of the model to the study of perceptions of PHRs. A secondary objective was to assess whether perceptions of PHRs predict the perceived value of the PHR for communicating with the doctor's office. Methods: We first developed a survey capturing perceptions of PHR use and other factors such as sociodemographic characteristics, access and use of technology, perceived innovativeness in the domain of information technology, and perceptions of privacy and security. We then conducted a cross-sectional survey (N = 1500). Patients were grouped into five groups of 300: PHR users (innovators, other users, and laggards), rejecters, and non-adopters. We applied univariate statistical analysis (Pearson chi-square and one-way ANOVA) to assess differences among groups and used multivariate statistical techniques (factor analysis and multiple regression analysis) to assess the presence of factors identified by the diffusion of innovation model and the predictors of our dependent variable (value of PHR for communicating with the doctor's office). Results: Of the 1500 surveys, 760 surveys were returned for an overall response rate of 51%. Computer use among non-adopters (75%) was lower than that among PHR users (99%) and rejecters (92%) (P<.001). Non-adopters also reported a lower score on personal innovativeness in information technology (mean = 2.8) compared to 3.6 and 3.1, respectively, for users and rejecters (P<.001). Four factors identified by the diffusion of innovation model emerged in the factor analysis: ease of use, relative advantage, observability, and trialability. PHR users perceived greater ease of use and relative advantage of the PHR than rejecters and non-adopters (P<.001). Multiple regression analysis showed the following factors as significant positive predictors of the value of PHR for communicating with the doctor's office: relative advantage, ease of use, trialability, perceptions of privacy and security, age, and computer use. Conclusion: Our study found that the diffusion of innovation model fits the study of perceptions of the PHR and provides a suitable theoretical and empirical framework to identify the factors that distinguish PHR users from non-users. The ease of use and relative advantage offered by the PHR emerged as the most important domains among perceptions of PHR use and in predicting the value of the PHR. Efforts to improve uptake and use of PHRs should focus on strategies that enhance the ease of use of PHRs and that highlight the relative advantages of PHRs. (J Med Internet Res 2012; 14(6): e150) doi: 10.2196/jmir.2278 C1 [Emani, Srinivas; Lipsitz, Stuart R.; Williams, Deborah H.; Bates, David W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gen Internal Med,Dept Med, Boston, MA 02120 USA. [Yamin, Cyrus K.] Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH USA. [Peters, Ellen] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Karson, Andrew S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Decis Support Unit,Dept Med, Boston, MA 02120 USA. [Wald, Jonathan S.] RTI Int, Waltham, MA USA. [Wald, Jonathan S.] Harvard Univ, Sch Med, Boston, MA 02120 USA. [Bates, David W.] Harvard Univ, Sch Publ Hlth, Dept Healthcare Policy & Management, Boston, MA 02120 USA. RP Emani, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gen Internal Med,Dept Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM semani1@partners.org FU Partners-Siemens Research Council; Agency for Health Care Research and Quality (AHRQ) [R18 HS 018656] FX Funding for this study was provided by the Partners-Siemens Research Council and the Agency for Health Care Research and Quality (AHRQ) under Grant # R18 HS 018656 (Improving uptake and use of personal health records). We thank the three anonymous reviewers for their valuable comments on the paper. NR 36 TC 31 Z9 32 U1 3 U2 40 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 NOV-DEC PY 2012 VL 14 IS 6 BP 310 EP 324 AR e150 DI 10.2196/jmir.2278 PG 15 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 099TV UT WOS:000315646000024 PM 23128775 ER PT J AU Lee, PH Perlis, RH Jung, JY Byrne, EM Rueckert, E Siburian, R Haddad, S Mayerfeld, CE Heath, AC Pergadia, ML Madden, PAF Boomsma, DI Penninx, BW Sklar, P Martin, NG Wray, NR Purcell, SM Smoller, JW AF Lee, P. H. Perlis, R. H. Jung, J-Y Byrne, E. M. Rueckert, E. Siburian, R. Haddad, S. Mayerfeld, C. E. Heath, A. C. Pergadia, M. L. Madden, P. A. F. Boomsma, D. I. Penninx, B. W. Sklar, P. Martin, N. G. Wray, N. R. Purcell, S. M. Smoller, J. W. TI Multi-locus genome-wide association analysis supports the role of glutamatergic synaptic transmission in the etiology of major depressive disorder SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE Genome-wide association study; glutamatergic synaptic neurotransmission; major depressive disorder; pathway analysis ID MOOD DISORDERS; MGLU8 RECEPTOR; NMDA RECEPTOR; CHROMOSOME 3; LINKAGE; POPULATION; IMPUTATION; GENETICS; ANXIETY; SYSTEM AB Major depressive disorder (MDD) is a common psychiatric illness characterized by low mood and loss of interest in pleasurable activities. Despite years of effort, recent genome-wide association studies (GWAS) have identified few susceptibility variants or genes that are robustly associated with MDD. Standard single-SNP (single nucleotide polymorphism)-based GWAS analysis typically has limited power to deal with the extensive heterogeneity and substantial polygenic contribution of individually weak genetic effects underlying the pathogenesis of MDD. Here, we report an alternative, gene-set-based association analysis of MDD in an effort to identify groups of biologically related genetic variants that are involved in the same molecular function or cellular processes and exhibit a significant level of aggregated association with MDD. In particular, we used a text-mining-based data analysis to prioritize candidate gene sets implicated in MDD and conducted a multi-locus association analysis to look for enriched signals of nominally associated MDD susceptibility loci within each of the gene sets. Our primary analysis is based on the meta-analysis of three large MDD GWAS data sets (total N = 4346 cases and 4430 controls). After correction for multiple testing, we found that genes involved in glutamatergic synaptic neurotransmission were significantly associated with MDD (set-based association P = 6.9 X 10(-4)). This result is consistent with previous studies that support a role of the glutamatergic system in synaptic plasticity and MDD and support the potential utility of targeting glutamatergic neurotransmission in the treatment of MDD. C1 [Lee, P. H.; Perlis, R. H.; Siburian, R.; Haddad, S.; Mayerfeld, C. E.; Purcell, S. M.; Smoller, J. W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Lee, P. H.; Purcell, S. M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lee, P. H.; Perlis, R. H.; Rueckert, E.; Purcell, S. M.; Smoller, J. W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lee, P. H.; Perlis, R. H.; Rueckert, E.; Purcell, S. M.; Smoller, J. W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lee, P. H.; Perlis, R. H.; Rueckert, E.; Purcell, S. M.; Smoller, J. W.] Broad Inst & MIT Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Perlis, R. H.; Smoller, J. W.] Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. [Jung, J-Y] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Byrne, E. M.; Martin, N. G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Byrne, E. M.; Wray, N. R.] Univ Queensland, Brisbane St Lucia, Qld, Australia. [Heath, A. C.; Pergadia, M. L.; Madden, P. A. F.] Washington Univ, Dept Psychiat, St Louis, MO USA. [Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Penninx, B. W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Sklar, P.; Purcell, S. M.] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu RI Wray, Naomi/C-8639-2015; Byrne, Enda/J-6068-2014; OI Wray, Naomi/0000-0001-7421-3357; Byrne, Enda/0000-0002-9491-7797; Martin, Nicholas/0000-0003-4069-8020 FU NIAAA NIH HHS [K05 AA017688, AA10248, AA13320, AA13321, AA13326, AA14041, R01 AA007535, R01 AA013320, R01 AA013321, R01 AA013326, R01 AA014041]; NIMH NIH HHS [K24 MH094614, MH-079799, MH-094614, MH66206, N01 MH-90003, N01 MH090003, R01 MH-072802, R01 MH066206, R01 MH072802, R01 MH079799, R01 MH086026]; PHS HHS [NIMH MH086026] NR 59 TC 24 Z9 24 U1 0 U2 15 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 NOV PY 2012 VL 2 AR e184 DI 10.1038/tp.2012.95 PG 9 WC Psychiatry SC Psychiatry GA 104JL UT WOS:000315988700004 PM 23149448 ER PT J AU Sachs, GS Vanderburg, DG Karayal, ON Kolluri, S Bachinsky, M Cavus, I AF Sachs, Gary S. Vanderburg, Douglas G. Karayal, Onur N. Kolluri, Sheela Bachinsky, Mary Cavus, Idil TI Adjunctive Oral Ziprasidone in Patients With Acute Mania Treated With Lithium or Divalproex, Part 1: Results of a Randomized, Double-Blind, Placebo-Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; ACUTE BIPOLAR MANIA; RATING-SCALE; DSM-IV; DISORDER; MONOTHERAPY; EFFICACY; MINI AB Objective: To assess the efficacy and safety of adjunctive ziprasidone in subjects with acute mania treated with lithium or divalproex, with an inadequate response to the mood stabilizer. Method: The study enrolled subjects aged 18-65 years who had a primary DSM-IV diagnosis of bipolar I disorder, with the most recent episode manic or mixed, with or without rapid cycling, and a Young Mania Rating Scale (YMRS) score >= 18. Subjects were randomized under double-blind conditions to receive ziprasidone, 20 to 40 mg (n = 226) or 60 to 80 mg (n = 232), or placebo (n = 222) twice a day for 3 weeks in addition to their mood stabilizer. The primary efficacy variable was change in YMRS scores from baseline to 3 weeks. Secondary efficacy measures included the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity of Illness and -Improvement scales, and Global Assessment of Functioning. Computer-administered YMRS was included for quality control and to evaluate study performance. The study was conducted between April 2006 and December 2008. Results: Least-squares mean +/- standard error changes in YMRS scores from baseline to week 3 were -10.2 +/- 0.80 in the mood stabilizer + ziprasidone 60- to 80-mg group, -11.0 +/- 0.80 in the mood stabilizer + ziprasidone 20- to 40-mg group, and -9.5 +/- 0.80 in the mood stabilizer + placebo group. Mean treatment differences between adjunctive ziprasidone groups and placebo were not statistically significant on primary or secondary efficacy measures. Ziprasidone was well tolerated. Conclusions: Adjunctive ziprasidone treatment failed to separate from mood stabilizer (lithium or divalproex) treatment on primary and secondary end points. C1 [Sachs, Gary S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, Gary S.] Concordant Rater Syst, Boston, MA USA. [Vanderburg, Douglas G.] Pfizer Inc, Med Dev Grp, New York, NY USA. [Karayal, Onur N.] Pfizer Inc, Specialty Neurosci, New York, NY USA. [Kolluri, Sheela] Pfizer Inc, Stat Specialty Care, New York, NY USA. [Bachinsky, Mary] Pfizer Inc, Specialty Care Neurosci, Groton, CT 06340 USA. [Cavus, Idil] Pfizer Inc, Med Dev Grp, Groton, CT 06340 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM SachsG@aol.com FU Repligen; Pfizer Inc, New York, New York; Pfizer FX Dr Sachs is an employee of Concordant Rater Systems (Bracket) and Massachusetts General Hospital; is a consultant to Astellas, AstraZeneca, Bristol-Myers Squibb, DSP, Otsuka, Pfizer, Sepracor, Takeda and Wyeth; has received grant/research support from Repligen; has served on speakers or advisory boards of Astellas, Bristol-Myers Squibb, GlaxoSmithKline, Sanofi, Pfizer, Sepracor, Takeda, and Wyeth; and is a stock shareholder in Concordant Rater Systems. Drs Vanderburg, Karayal, Kolluri, and Cavus are employees of and stock shareholders in Pfizer Inc. Ms Bachinsky is an employee of Pfizer.; This study was sponsored by Pfizer Inc, New York, New York. The manuscript was written by the authors with editorial assistance from J. Stamford, PhD, and Hajira Koeller, PhD, of PAREXEL, which was funded by Pfizer. NR 22 TC 13 Z9 14 U1 3 U2 6 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 NOV PY 2012 VL 73 IS 11 BP 1412 EP 1419 DI 10.4088/JCP.11m07388 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SQ UT WOS:000315000700004 PM 23218157 ER PT J AU Sachs, GS Vanderburg, DG Edman, S Karayal, ON Kolluri, S Bachinsky, M Cavus, I AF Sachs, Gary S. Vanderburg, Douglas G. Edman, Suzanne Karayal, Onur N. Kolluri, Sheela Bachinsky, Mary Cavus, Idil TI Adjunctive Oral Ziprasidone in Patients With Acute Mania Treated With Lithium or Divalproex, Part 2: Influence of Protocol-Specific Eligibility Criteria on Signal Detection SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ACUTE BIPOLAR MANIA; CLINICAL-TRIALS; ANTIDEPRESSANT DRUGS; PLACEBO-RESPONSE; DOUBLE-BLIND AB Objectives: High failure rates of randomized controlled trials (RCTs) are well recognized but poorly understood. We report exploratory analyses from an adjunctive ziprasidone double-blind RCT in adults with bipolar I disorder (reported in part 1 of this article). Data collected by computer interviews and by site-based raters were analyzed to examine the impact of eligibility criteria on signal detection. Method: Clinical assessments and a remote monitoring system, including a computer-administered Young Mania Rating Scale (YMRSComp) were used to categorize subjects as eligible or ineligible on 3 key protocol-specified eligibility criteria. Data analyses compared treatment efficacy for eligible versus ineligible subgroups. All statistical analyses reported here are exploratory. Criteria were considered "impactful" if the difference between eligible and ineligible subjects on the YMRS change scores was >= 1 point. Results: 504 subjects had baseline and >= 1 post-randomization computer-administered assessments but only 180 (35.7%) met all 3 eligibility criteria based on computer assessments. There were no statistically significant differences between treatment groups in change from baseline YMRS score on the basis of site-based rater or computer assessments. All criteria tested improved signal detection except the entry criteria excluding subjects with >= 25% improvement from screen to baseline. Conclusions: On the basis of computer assessments, nearly two-thirds of randomized subjects did not meet at least 1 protocol-specified eligibility criterion. These results suggest enrollment of ineligible subjects is likely to contribute to failure of acute efficacy studies. C1 [Sachs, Gary S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, Gary S.; Edman, Suzanne] Concordant Rater Syst, Boston, MA USA. [Vanderburg, Douglas G.] Pfizer Inc, Med Dev Grp, New York, NY USA. [Karayal, Onur N.] Pfizer Inc, Specialty Neurosci, New York, NY USA. [Kolluri, Sheela] Pfizer Inc, Stat Specialty Care, New York, NY USA. [Cavus, Idil] Pfizer Inc, Specialty Care Neurosci, Groton, CT 06340 USA. [Bachinsky, Mary] Pfizer Inc, Med Dev Grp, Groton, CT 06340 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM SachsG@aol.com FU Repligen; Pfizer; Pfizer Inc FX Dr Sachs is an employee of Concordant Rater Systems (Bracket) and Massachusetts General Hospital; is a consultant to Astellas, AstraZeneca, Bristol-Myers Squibb, DSP, Otsuka, Pfizer, Sepracor, Takeda and Wyeth; has received grant/research support from Repligen; has served on speakers or advisory boards of Astellas, Bristol-Myers Squibb, GlaxoSmithKline, Sanofi, Pfizer, Sepracor, Takeda, and Wyeth; and is a stock shareholder in Concordant Rater Systems. Drs Vanderburg, Karayal, Kolluri, and Cavus are employees of and stock shareholders in Pfizer Inc. Ms Edman is an employee of Concordant Rater Systems. Ms Bachinsky is an employee of Pfizer.; This study was sponsored by Pfizer. The article was written by the authors with editorial assistance from Hilary Bennett, MSc, Karen Vondy, PhD, and Hajira Koeller, PhD, of PAREXEL, which was funded by Pfizer Inc. NR 11 TC 8 Z9 8 U1 1 U2 3 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 NOV PY 2012 VL 73 IS 11 BP 1420 EP 1425 DI 10.4088/JCP.11m07389 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SQ UT WOS:000315000700005 PM 23218158 ER PT J AU Perlis, RH Uher, R Perroud, N Fava, M AF Perlis, Roy H. Uher, Rudolf Perroud, Nader Fava, Maurizio TI Do Suicidal Thoughts or Behaviors Recur During a Second Antidepressant Treatment Trial? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; CLINICAL-TRIAL; DEPRESSION; IDEATION; RISK; CITALOPRAM; GENDEP AB Objective: A subset of patients undergoing initial antidepressant treatment experience worsening of symptoms, including thoughts of suicide or suicidal behavior, The present study explores whether this subset of patients is also more likely to experience recurrence or worsening of these symptoms during a second treatment trial with a different antidepressant. Method: We examined data collected between July 2001 and September 2006 from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter effectiveness study of outpatients with major depressive disorder diagnosed by a DSM-IV checklist. In that study, subjects who did not remit with citalopram treatment were randomized among next-step treatment options. The main outcome measure for this post hoc analysis, presence of suicidal thoughts and behaviors, was assessed using the suicide item on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated. Logistic regression was used to examine association between emergence or worsening of these symptoms with the first-step (level 1) citalopram treatment and emergence or worsening with next-step (level 2) pharmacologic or psychosocial treatment, including augmentation with bupropion or buspirone; switch to sertraline, venlafaxine, or bupropion; or addition of or switch to cognitive therapy. Results: Of 1,240 subjects entering level 2 with a score less than 3 on the suicide item, 102 (8.2%) experienced emergence or worsening of suicidal thoughts or behaviors. Emergence or worsening at level 1 was strongly associated with reemergence or worsening at level 2 (crude OR = 4.00 [95% CI, 2.45-6.51], adjusted OR = 2.95 [95% CI, 1.76-4.96]). Overall magnitude of risk was similar among next-step pharmacologic augmentation versus switching. Conclusions: These results suggest that individuals who experience emergence or worsening of suicidal thoughts or behaviors with one antidepressant treatment may warrant closer follow-up during the next-step treatment, as these symptoms may recur regardless of which modality is selected. J Clin Psychiatry 2012;73(11):1439-1442 (c) Copyright 2012 Physicians Postgraduate Press, Inc. C1 [Perlis, Roy H.; Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perlis, Roy H.; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Uher, Rudolf] Kings Coll London, Inst Psychiat, London, England. [Uher, Rudolf] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. [Perroud, Nader] Univ Hosp Geneva, Dept Psychiat, Geneva, Switzerland. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM rperlis@partners.org RI Uher, Rudolf/A-5477-2008 OI Uher, Rudolf/0000-0002-2998-0546 FU Genomind LLC; Proteus Biomedical; RIDVentures; Abbott; Alkermes; Aspect Medical Systems; AstraZeneca; Bristol-Myers Squibb; Cephalon; Eli Lilly; Forest; GlaxoSmithKline; Johnson Johnson; Lichtwer Pharma GmbH; Lorex; Novartis; Organon; PamLab; Pfizer; Pharmavite; Roche; Sanofi/Synthelabo; Solvay; Wyeth-Ayerst; Bayer AG; Biovail; BrainCells; Compellis; Cypress; Dov; EPIX; Fabre-Kramer; Grunenthal GmBH; Janssen; Jazz; Knoll; Lundbeck; MedAvante; Neuronetics; Nutrition 21; PharmaStar; Sepracor; Somaxon; Somerset; Boehringer-Ingelheim; National Institute of Mental Health [N01 MH-90003]; NIMH [MH086026] FX Dr Perlis has received consulting fees from Genomind LLC, Proteus Biomedical, and RIDVentures and royalty/patents from Concordant Rater Systems. Dr Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma GmbH, Lorex, Novartis, Organon, PamLab, Pfizer, Pharmavite, Roche, Sanofi/Synthelabo, Solvay, and Wyeth-Ayerst; advisory/consulting fees from Aspect Medical Systems, AstraZeneca, Bayer AG, Biovail, BrainCells, Bristol-Myers Squibb, Cephalon, Compellis, Cypress, Dov, Eli Lilly, EPIX, Fabre-Kramer, Forest, GlaxoSmithKline, Grunenthal GmBH, Janssen, Jazz, Johnson & Johnson, Knoll, Lundbeck, MedAvante, Neuronetics, Novartis, Nutrition 21, Organon, PamLab, Pfizer, PharmaStar, Pharmavite, Roche, Sanofi/Synthelabo, Sepracor, Solvay, Somaxon, Somerset, and Wyeth-Ayerst; and speaking fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Novartis, Organon, Pfizer, PharmaStar, and Wyeth-Ayerst. Drs Uher and Perroud report no competing interests.; The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study was supported by federal funds from the National Institute of Mental Health under contract N01 MH-90003 to the University of Texas-Southwestern Medical Center at Dallas (A. J. Rush, MD, Principal Investigator). Dr Perlis is supported by NIMH MH086026. NR 17 TC 5 Z9 5 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2012 VL 73 IS 11 BP 1439 EP 1442 DI 10.4088/JCP.12m07777 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SQ UT WOS:000315000700009 PM 23059018 ER PT J AU Evins, AE Green, AI Kane, JM Murray, RM AF Evins, A. Eden Green, Alan I. Kane, John M. Murray, Robin M. TI The Effect of Marijuana Use on the Risk for Schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID ADOLESCENT CANNABIS USE; SUBSTANCE USE; ENVIRONMENT INTERACTION; PSYCHOTIC DISORDERS; ADULT PSYCHOSIS; ONSET; SYMPTOMS; GENE; DELTA-9-TETRAHYDROCANNABINOL; ABNORMALITIES C1 [Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. [Green, Alan I.] Dartmouth, Geisel Sch Med, Dept Psychiat, Hanover, NH USA. Dartmouth, Geisel Sch Med, Dept Pharmacol & Toxicol, Hanover, NH USA. [Green, Alan I.] Dartmouth Ctr Clin & Translat, Hanover, NH USA. [Kane, John M.] Hofstra N Shore Long Isl Jewish Sch Med, Dept Psychiat, Uniondale, NY USA. [Kane, John M.] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA. [Kane, John M.] N Shore Long Isl Jewish Hlth Syst, Behav Hlth Serv, New Hyde Pk, NY USA. [Murray, Robin M.] Kings Coll London, Dept Psychosis, Inst Psychiat, London WC2R 2LS, England. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. RI Murray, Robin/F-8658-2012 OI Murray, Robin/0000-0003-0829-0519 NR 49 TC 9 Z9 9 U1 6 U2 40 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 NOV PY 2012 VL 73 IS 11 BP 1463 EP 1468 DI 10.4088/JCP.12012co1c PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SQ UT WOS:000315000700013 PM 23218162 ER PT J AU Vodovotz, Y Prelich, J Lagoa, C Barclay, D Zamora, R Murase, N Gandhi, CR AF Vodovotz, Yoram Prelich, John Lagoa, Claudio Barclay, Derek Zamora, Ruben Murase, Noriko Gandhi, Chandrashekhar R. TI Augmenter of Liver Regeneration (ALR) Is a Novel Biomarker of Hepatocellular Stress/Inflammation: In Vitro, In Vivo and In Silico Studies SO MOLECULAR MEDICINE LA English DT Article ID HEPATIC STELLATE CELLS; SULFHYDRYL OXIDASE; HEPATOTROPHIC FACTOR; HUMAN HEPATOCYTES; PORTACAVAL-SHUNT; GROWTH-FACTORS; DNA-SYNTHESIS; CYTOCHROME-C; EXPRESSION; ENDOTOXIN AB The liver is a central organ involved in inflammatory processes, including the elaboration of acute-phase proteins. Augmenter of liver regeneration (ALR) protein, expressed and secreted by hepatocytes, promotes liver regeneration and maintains viability of hepatocytes. ALR also stimulates secretion of inflammatory cytokines (tumor necrosis factor (TNF)-alpha and interleukin (IL)-6) and nitric oxide from Kupffer cells. We hypothesized that ALR may be involved in modulating inflammation induced by various stimuli. We found that hepatic ALR levels are elevated at 24 h, before or about the same time as an increase in the mRNA expression of TNF-alpha and IL-6, after portacaval shunt surgery in rats. Serum ALR also increased, but significantly only on d 4 when pathological changes in the liver become apparent. In rats, serum ALR was elevated after intraperitoneal administration of lipopolysaccharide alone and in a model of gram-negative sepsis. Serum ALP increased before alanine aminotransferase (ALT) in endotoxemia and in the same general time frame as TNF-alpha and IL-6 in the bacterial sepsis model. Furthermore, mathematical prediction of tissue damage correlated strongly with alterations in serum ALP in a mouse model of hemorrhagic shock. In vitro, monomethyl sulfonate. TNF-alpha, actinomycin D and lipopolysaccharide all caused increased release of ALR from rat hepatocytes, which preceded the loss of cell viability and/or inhibition of DNA synthesis. ALR may thus serve as a potential diagnostic marker of hepatocellular stress and/or acute inflammatory conditions. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00183 C1 [Vodovotz, Yoram; Lagoa, Claudio; Barclay, Derek; Zamora, Ruben; Murase, Noriko; Gandhi, Chandrashekhar R.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Gandhi, Chandrashekhar R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Murase, Noriko; Gandhi, Chandrashekhar R.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. [Vodovotz, Yoram; Zamora, Ruben] McGowan Inst Regenerat Med, Ctr Inflammat & Regenerat Modeling, Pittsburgh, PA USA. [Prelich, John] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Gandhi, CR (reprint author), Univ Cincinnati, Dept Surg, ML0558,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM gandhicr@ucmail.uc.edu FU VA Merit Review [1I1BX001174]; NIH [R01-DK54411, R21AA020846] FX This work was supported by VA Merit Review 1I1BX001174 and NIH grants R01-DK54411 and R21AA020846 (CR Gandhi). We thank Adam Kichler for technical assistance. NR 49 TC 6 Z9 7 U1 2 U2 4 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV PY 2012 VL 18 IS 11 BP 1421 EP 1429 DI 10.2119/molmed.2012.00183 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 087WE UT WOS:000314794300001 ER PT J AU Zaitlen, N Lindstrom, S Pasaniuc, B Cornelis, M Genovese, G Pollack, S Barton, A Bickeboller, H Bowden, DW Eyre, S Freedman, BI Friedman, DJ Field, JK Groop, L Haugen, A Heinrich, J Henderson, BE Hicks, PJ Hocking, LJ Kolonel, LN Landi, MT Langefeld, CD Le Marchand, L Meister, M Morgan, AW Raji, OY Risch, A Rosenberger, A Scherf, D Steer, S Walshaw, M Waters, KM Wilson, AG Wordsworth, P Zienolddiny, S Tchetgen, ET Haiman, C Hunter, DJ Plenge, RM Worthington, J Christiani, DC Schaumberg, DA Chasman, DI Altshuler, D Voight, B Kraft, P Patterson, N Price, AL AF Zaitlen, Noah Lindstroem, Sara Pasaniuc, Bogdan Cornelis, Marilyn Genovese, Giulio Pollack, Samuela Barton, Anne Bickeboeller, Heike Bowden, Donald W. Eyre, Steve Freedman, Barry I. Friedman, David J. Field, John K. Groop, Leif Haugen, Aage Heinrich, Joachim Henderson, Brian E. Hicks, Pamela J. Hocking, Lynne J. Kolonel, Laurence N. Landi, Maria Teresa Langefeld, Carl D. Le Marchand, Loic Meister, Michael Morgan, Ann W. Raji, Olaide Y. Risch, Angela Rosenberger, Albert Scherf, David Steer, Sophia Walshaw, Martin Waters, Kevin M. Wilson, Anthony G. Wordsworth, Paul Zienolddiny, Shanbeh Tchetgen, Eric Tchetgen Haiman, Christopher Hunter, David J. Plenge, Robert M. Worthington, Jane Christiani, David C. Schaumberg, Debra A. Chasman, Daniel I. Altshuler, David Voight, Benjamin Kraft, Peter Patterson, Nick Price, Alkes L. TI Informed Conditioning on Clinical Covariates Increases Power in Case-Control Association Studies SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; QUANTITATIVE-TRAIT LOCI; CANCER SUSCEPTIBILITY LOCI; DISCORDANT SIB PAIRS; GENETIC-VARIANTS; LUNG-CANCER; MACULAR DEGENERATION; CHINESE POPULATION; COMMON VARIANT; RISK-FACTORS AB Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low-BMI cases are larger than those estimated from high-BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-controlcovariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled falsepositive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1x10(-9)). The improvement varied across diseases with a 16% median increase in chi(2) test statistics and a commensurate increase in power. This suggests that applying our method to existing and future association studies of these diseases may identify novel disease loci. C1 [Zaitlen, Noah; Lindstroem, Sara; Pasaniuc, Bogdan; Pollack, Samuela; Tchetgen, Eric Tchetgen; Hunter, David J.; Christiani, David C.; Schaumberg, Debra A.; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Zaitlen, Noah; Pasaniuc, Bogdan; Pollack, Samuela; Tchetgen, Eric Tchetgen; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Zaitlen, Noah; Pasaniuc, Bogdan; Pollack, Samuela; Hunter, David J.; Plenge, Robert M.; Altshuler, David; Voight, Benjamin; Kraft, Peter; Patterson, Nick; Price, Alkes L.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Zaitlen, Noah; Lindstroem, Sara; Pasaniuc, Bogdan; Pollack, Samuela; Hunter, David J.; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Cornelis, Marilyn; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Schaumberg, Debra A.; Chasman, Daniel I.] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA USA. [Genovese, Giulio; Friedman, David J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Barton, Anne; Eyre, Steve; Worthington, Jane] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester, Lancs, England. [Bickeboeller, Heike; Rosenberger, Albert] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, Gottingen, Germany. [Bowden, Donald W.] Wake Forest Sch Med, Ctr Human Genom, Winston Salem, NC USA. [Freedman, Barry I.] Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA. [Field, John K.; Raji, Olaide Y.] Univ Liverpool, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England. [Groop, Leif] Lund Univ, Scania Univ Hosp, Diabet & Endocrinol Res Unit, Dept Clin Sci, Malmo, Sweden. [Haugen, Aage; Zienolddiny, Shanbeh] Natl Inst Occupat Hlth, Sect Toxicol, Oslo, Norway. [Heinrich, Joachim] German Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany. [Henderson, Brian E.; Waters, Kevin M.; Haiman, Christopher] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hicks, Pamela J.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27103 USA. [Hocking, Lynne J.] Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen, Scotland. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Langefeld, Carl D.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Meister, Michael] Univ Klinikum, Thoraxklin, Heidelberg, Germany. [Meister, Michael; Risch, Angela] German Ctr Lung Res, Translat Lung Res Ctr Heidelberg, Heidelberg, Germany. [Morgan, Ann W.] NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [Risch, Angela; Scherf, David] DKFZ German Canc Res Ctr, Heidelberg, Germany. [Steer, Sophia] Kings Coll Hosp, Natl Hlth Serv Fdn Trust, London, England. [Walshaw, Martin] Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England. [Wilson, Anthony G.] Univ Sheffield, Deptartment Infect & Immun, Sheffield, S Yorkshire, England. [Wordsworth, Paul] Nuffield Orthopaed Ctr, NIHR Oxford Musculoskeletal Biomed Res Unit, Oxford OX3 7LD, England. [Plenge, Robert M.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Schaumberg, Debra A.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Altshuler, David; Voight, Benjamin] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David; Voight, Benjamin] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Altshuler, David; Voight, Benjamin] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David; Voight, Benjamin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Zaitlen, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM nzaitlen@hsph.harvard.edu; aprice@hsph.harvard.edu RI Altshuler, David/A-4476-2009; Worthington, Jane/M-9770-2014; Barton, Anne/N-2053-2014; Zienolddiny, Shanbeh/O-7392-2015; Risch, Angela/H-2669-2013; OI Altshuler, David/0000-0002-7250-4107; Worthington, Jane/0000-0003-0544-042X; Eyre, Stephen/0000-0002-1251-6974; Barton, Anne/0000-0003-3316-2527; Risch, Angela/0000-0002-8026-5505; Hocking, Lynne J/0000-0002-2414-2826; Field, John/0000-0003-3951-6365 FU National Heart, Lung, and Blood Institute [HL043851, HL69757]; National Cancer Institute [CA 047988]; Donald W. Reynolds Foundation; Fondation Leducq; Amgen; NIH [R01 HG006399, R21 ES020754, 5T32ES007142-27]; U.S. National Institutes of Health, National Cancer Institute [U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07]; Manchester Biomedical Research Centre; Arthritis Research Campaign FX The WGHS is supported by HL043851 and HL69757 from the National Heart, Lung, and Blood Institute and CA 047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. This work was funded by NIH grants R01 HG006399 (B Pasaniuc, S Pollack, N Patterson, AL Price) and R21 ES020754 (N Zaitlen, M Cornelis, N Patterson, AL Price) and NIH fellowship 5T32ES007142-27 (N Zaitlen). This work was supported by the U.S. National Institutes of Health, National Cancer Institute [cooperative agreements U01-CA98233-07 to DJ Hunter, U01-CA98710-06 to S Gapstur, U01-CA98216-06 to E Riboli and R Kaaks, and U01-CA98758-07 to BE Henderson, and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics]. A Barton, S Eyre, and J Worthington were supported by Manchester Biomedical Research Centre and the Arthritis Research Campaign. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 33 Z9 33 U1 2 U2 15 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 NOV PY 2012 VL 8 IS 11 AR e1003032 DI 10.1371/journal.pgen.1003032 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 048DY UT WOS:000311891600020 PM 23144628 ER PT J AU Kural, C Tacheva-Grigorova, SK Boulant, S Cocucci, E Baust, T Duarte, D Kirchhausen, T AF Kural, Comert Tacheva-Grigorova, Silvia K. Boulant, Steeve Cocucci, Emanuele Baust, Thorsten Duarte, Delfim Kirchhausen, Tom TI Dynamics of Intracellular Clathrin/AP1-and Clathrin/AP3-Containing Carriers SO CELL REPORTS LA English DT Article ID TRANS-GOLGI NETWORK; MEDIATED ENDOCYTOSIS; MAMMALIAN-CELLS; COATED PITS; DISTINCT FUNCTIONS; MEMBRANE FISSION; MUTANT DYNAMIN; RECRUITMENT; VESICLES; PROTEINS AB Clathrin/AP1- and clathrin/AP3-coated vesicular carriers originate from endosomes and the trans-Golgi network. Here, we report the real-time visualization of these structures in living cells reliably tracked by rapid, three-dimensional imaging with the use of a spinning-disk confocal microscope. We imaged relatively sparse, diffraction-limited, fluorescent objects containing chimeric fluorescent protein (clathrin light chain, sigma adaptor subunits, or dynamin2) with a spatial precision of up to similar to 30 nm and a temporal resolution of similar to 1 s. The dynamic characteristics of the intracellular clathrin/AP1 and clathrin/AP3 carriers are similar to those of endocytic clathrin/AP2 pits and vesicles; the clathrin/AP1 coats are, on average, slightly shorter-lived than their AP2 and AP3 counterparts. We confirmed that although dynamin2 is recruited as a burst to clathrin/AP2 pits immediately before their budding from the plasma membrane, we found no evidence supporting a similar association of dynamin2 with clathrin/AP1 or clathrin/AP3 carriers at any stage during their lifetime. We found no effects of chemical inhibitors of dynamin function or the K44A dominant-negative mutant of dynamin on AP1 and AP3 dynamics. This observation suggests that an alternative budding mechanism, yet to be discovered, is responsible for the scission step of clathrin/AP1 and clathrin/AP3 carriers. C1 [Kural, Comert; Tacheva-Grigorova, Silvia K.; Boulant, Steeve; Cocucci, Emanuele; Baust, Thorsten; Duarte, Delfim; Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kural, Comert; Tacheva-Grigorova, Silvia K.; Boulant, Steeve; Cocucci, Emanuele; Baust, Thorsten; Duarte, Delfim; Kirchhausen, Tom] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Duarte, Delfim] Univ Porto, Dept Biochem, Fac Med, U38, P-4200319 Oporto, Portugal. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu OI Duarte, Delfim/0000-0003-3476-0211 FU Harvard Medical School-Portugal Program in Translational Research and Information; summer travel fellowship from the Fundacao Luso-Americana para o Desenvolvimento (FLAD); NIH grant [GM-075252, U54 AI057159] FX We thank Lei Lu for preparing the sample and the data used to generate Figure S1, Eric Marino for maintaining the Imaging Resource used in this study, Frances Brodsky for the clathrin light chain antibody, Marcel Mettlen and Sandy Schmid for the adenovirus encoding WT and dynamin2K44A and Pietro DeCamilli, Marc McNiven, Sandy Schmid and members of our laboratory for helpful discussions. Comert Kural is a recipient of a Helen Hay Whitney Foundation Fellowship. Delfim Duarte was supported by the Harvard Medical School-Portugal Program in Translational Research and Information and by a summer travel fellowship from the Fundacao Luso-Americana para o Desenvolvimento (FLAD). This work was supported in part by NIH grant GM-075252 (T.K.) and U54 AI057159 (New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility). NR 50 TC 25 Z9 26 U1 0 U2 10 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 NOV PY 2012 VL 2 IS 5 BP 1111 EP 1119 DI 10.1016/j.celrep.2012.09.025 PG 9 WC Cell Biology SC Cell Biology GA 083IU UT WOS:000314457700007 PM 23103167 ER PT J AU Feng, Q Hato, SV Langereis, MA Zoll, J Virgen-Slane, R Peisley, A Hur, S Semler, BL van Rij, RP van Kuppeveld, FJM AF Feng, Qian Hato, Stanleyson V. Langereis, Martijn A. Zoll, Jan Virgen-Slane, Richard Peisley, Alys Hur, Sun Semler, Bert L. van Rij, Ronald P. van Kuppeveld, Frank J. M. TI MDA5 Detects the Double-Stranded RNA Replicative Form in Picornavirus-Infected Cells SO CELL REPORTS LA English DT Article ID RECOGNITION; PROTEIN; INITIATION; SELF; ACID AB RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C), a synthetic dsRNA mimic. Here, we dissected the IFN-alpha/beta-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-alpha/beta response. IFN-alpha/beta production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions. C1 [Feng, Qian; Hato, Stanleyson V.; Langereis, Martijn A.; Zoll, Jan; van Rij, Ronald P.; van Kuppeveld, Frank J. M.] Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, NL-6500 HB Nijmegen, Netherlands. [Virgen-Slane, Richard; Semler, Bert L.] Univ Calif Irvine, Sch Med, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. [Peisley, Alys; Hur, Sun] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. RP van Kuppeveld, FJM (reprint author), Univ Utrecht, Div Virol, Dept Infect Dis & Immunol, Fac Vet Med, Yalelaan 1, NL-3584 CL Utrecht, Netherlands. EM f.j.m.vankuppeveld@uu.nl RI Langereis, Martijn/D-3532-2013; Langereis, martijn/K-2965-2012; Van Rij, Ronald/I-7073-2012; Zoll, G.J./L-4776-2015; OI Langereis, Martijn/0000-0003-4950-961X; Van Rij, Ronald/0000-0003-0221-4689; Virgen-Slane, Richard/0000-0002-0011-3844 FU Mosaic grants from the Netherlands Organisation for Scientific Research (NWO) [NWO-017.002.025, NWO-017.006.043]; Rubicon grant from the Netherlands Organisation for Scientific Research (NWO) [NWO-825.11.022]; ECHO grant from the Netherlands Organisation for Scientific Research (NWO) [NWO-CW-700.59.007] FX We wish to thank Drs. Shizuo Akira and James Chen for the gifts of MEFs, Thomas Michiels and Robert Silverman for the gift of HeLa-M cells, and Toby Tuthill and Dave Rowlands for the gift of ERAV. S.H. and Q.F. are supported by Mosaic grants (NWO-017.002.025 and NWO-017.006.043, respectively), M.L. by a Rubicon grant (NWO-825.11.022), and F.K. by an ECHO grant (NWO-CW-700.59.007), all from the Netherlands Organisation for Scientific Research (NWO). B.L.S. is a Senior Fellow of the American Asthma Foundation. NR 18 TC 58 Z9 59 U1 3 U2 14 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 NOV PY 2012 VL 2 IS 5 BP 1187 EP 1196 DI 10.1016/j.celrep.2012.10.005 PG 10 WC Cell Biology SC Cell Biology GA 083IU UT WOS:000314457700016 PM 23142662 ER PT J AU Maturo, S Silver, A Nimkin, K Sagar, P Ashland, J van der Kouwe, AJW Hartnick, C AF Maturo, Stephen Silver, Amanda Nimkin, Katherine Sagar, Pallavi Ashland, Jean van der Kouwe, Andre J. W. Hartnick, Christopher TI MRI With Synchronized Audio to Evaluate Velopharyngeal Insufficiency SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article DE cleft palate; magnetic resonance imaging; pediatrics; speech; velopharyngeal insufficiency ID VELI-PALATINI MUSCLE; CLEFT-PALATE; MECHANISM; SPEECH; MOVIE AB Objective: To demonstrate the feasibility of simultaneous-acquired magnetic resonance imaging (MRI) and high-quality synchronized audio recording for evaluating velopharyngeal closure. Design: Institutional Review Board-approved case series. Setting: Tertiary care hospital. Patients: Three healthy adult volunteers with a normal speech pattern. Interventions: MRI with simultaneous recorded audio files evaluating velopharyngeal closure. Main outcome measure: Precise imaging and audio coordination of specific phonatory tasks. Results: Synchronization of MRI and audio in all three adults. Conclusion: Our novel imaging and audio protocol provides simultaneous acquired MRI with synchronized high quality audio for evaluating velopharyngeal closure. This technique may provide the opportunity to improve diagnosis and surgical planning in patients with velopharyngeal insufficiency. C1 [Maturo, Stephen; Silver, Amanda; Hartnick, Christopher] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. [Sagar, Pallavi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Ashland, Jean] Massachusetts Gen Hosp, Speech Commun Grp, Dept Speech & Language Pathol, Boston, MA 02114 USA. [van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr, Boston, MA 02114 USA. RP Hartnick, C (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 15 TC 7 Z9 7 U1 0 U2 4 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1545-1569 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD NOV PY 2012 VL 49 IS 6 BP 761 EP 763 DI 10.1597/10-255 PG 3 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 084BA UT WOS:000314509600020 PM 21740179 ER PT J AU Kennelty, KA Thorpe, JM Chewning, B Mott, DA AF Kennelty, Korey A. Thorpe, Joshua M. Chewning, Betty Mott, David A. TI Use of pharmacists or pharmacies as Medicare Part D information sources SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE Medicare Part D; community pharmacies; pharmacists; information sources; rural setting; prescription costs ID BENEFICIARIES; HEALTH AB Objective: To characterize beneficiaries who used a pharmacy or pharmacist as a Medicare Part D information source. Methods: This cross-sectional descriptive study involved 4,724 Medicare Part D beneficiaries who graduated from Wisconsin high schools in 1957. The main outcome measure was beneficiary self-reported use of a pharmacy or pharmacist as a Medicare Part D information source. Results: Only 13% of the total sample and 15% of those with three or more medications used a pharmacy or pharmacist for Medicare Part D information. Adjusted logistic regression revealed that beneficiaries living in rural communities, compared with metropolitan areas, and with higher out-of-pocket prescription costs were more likely to use a pharmacy or pharmacist for Medicare Part D information. Beneficiaries with lower educational attainment were less likely to use a pharmacy or pharmacist for Medicare Part D information. Conclusion: Pharmacists have the knowledge and are in the position in the community to effectively educate beneficiaries about the Medicare Part D program. However, this study suggests that few beneficiaries are using pharmacists or pharmacies for Medicare Part D information. C1 [Kennelty, Korey A.; Thorpe, Joshua M.] Univ Wisconsin, Sch Pharm, Div Social & Adm Sci, Madison, WI 53705 USA. [Thorpe, Joshua M.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kennelty, Korey A.; Chewning, Betty; Mott, David A.] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. [Chewning, Betty] Univ Wisconsin, Sch Pharm, Sonderegger Res Ctr, Madison, WI 53705 USA. RP Kennelty, KA (reprint author), Univ Wisconsin, Sch Pharm, Rennebohm Hall 2506,777 Highland Ave, Madison, WI 53705 USA. EM kennelty@wisc.edu FU Clinical and Translational Science Award program, National Center for Research Resources, National Institutes of Health [1UL1RR025011]; National Institute on Aging [R01 AG09775, R01 AG033285]; Vilas Estate Trust; National Science Foundation; Spencer Foundation; Graduate School of the University of Wisconsin-Madison FX Clinical and Translational Science Award program, National Center for Research Resources, National Institutes of Health (grant no. 1UL1RR025011).; This research uses data from the Wisconsin Longitudinal Study (WLS) of the University of Wisconsin-Madison. Since 1991, the WLS has been supported principally by the National Institute on Aging (R01 AG09775, R01 AG033285), with additional support from the Vilas Estate Trust, the National Science Foundation, the Spencer Foundation, and the Graduate School of the University of Wisconsin-Madison. A public use file of data from the Wisconsin Longitudinal Study is available from the Wisconsin Longitudinal Study, University of Wisconsin-Madison, 1180 Observatory Drive, Madison, WI 53706 and at www.ssc.wisc.edu/wlsresearch/data. The opinions expressed herein are those of the authors. NR 14 TC 0 Z9 0 U1 0 U2 2 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD NOV-DEC PY 2012 VL 52 IS 6 BP E205 EP E209 DI 10.1331/JAPhA.2012.11199 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 082OM UT WOS:000314401500010 PM 23229982 ER PT J AU Tager, AM AF Tager, Andrew M. TI Autotaxin Emerges as a Therapeutic Target for Idiopathic Pulmonary Fibrosis Limiting Fibrosis by Limiting Lysophosphatidic Acid Synthesis SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material ID LYSOPHOSPHOLIPASE-D ACTIVITY; LUNG INJURY; RECEPTOR; ACTIVATION; INFLAMMATION; MOTILITY; PROTEIN; LPA2 C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Tager, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL095732, R01 HL108975] NR 17 TC 14 Z9 14 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 2012 VL 47 IS 5 BP 563 EP 565 DI 10.1165/rcmb.2012-0235ED PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 082QE UT WOS:000314406400001 PM 23125419 ER PT J AU Mendez, MF AF Mendez, Mario F. TI Early-onset Alzheimer's Disease: Nonamnestic Subtypes and Type 2 AD SO ARCHIVES OF MEDICAL RESEARCH LA English DT Review DE Alzheimer's disease; Dementia; Apolipoprotein; Presenilin; Amnestic ID POSTERIOR CORTICAL ATROPHY; MILD COGNITIVE IMPAIRMENT; CEREBRAL GLUCOSE-METABOLISM; APOLIPOPROTEIN-E EPSILON-4; CLINICAL CHARACTERISTICS; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; CORTICOBASAL SYNDROME; PROGRESSIVE APHASIA; NATIONAL INSTITUTE AB Patients with Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, similar to 4-5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer's research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22-64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein E epsilon 4 (APOE epsilon 4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. (c) 2012 IMSS. Published by Elsevier Inc. C1 [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu FU NIA NIH HHS [R01 AG034499] NR 102 TC 26 Z9 28 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0188-4409 J9 ARCH MED RES JI Arch. Med. Res. PD NOV PY 2012 VL 43 IS 8 SI SI BP 677 EP 685 DI 10.1016/j.arcmed.2012.11.009 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 082FP UT WOS:000314378000013 PM 23178565 ER PT J AU Guinan, JJ Salt, A Cheatham, MA AF Guinan, John J., Jr. Salt, Alec Cheatham, Mary Ann TI Progress in cochlear physiology after Bekesy SO HEARING RESEARCH LA English DT Review ID OUTER HAIR-CELLS; GUINEA-PIG COCHLEA; CROSSED OLIVOCOCHLEAR BUNDLE; AUDITORY-NERVE RESPONSES; BASILAR-MEMBRANE; OTOACOUSTIC EMISSIONS; TECTORIAL MEMBRANE; MAMMALIAN COCHLEA; TRAVELING-WAVES; ION-TRANSPORT AB In the fifty years since Bekesy was awarded the Nobel Prize, cochlear physiology has blossomed. Many topics that are now current are things Bekesy could not have imagined. In this review we start by describing progress in understanding the origin of cochlear gross potentials, particularly the cochlear microphonic, an area in which Bekesy had extensive experience. We then review progress in areas of cochlear physiology that were mostly unknown to Bekesy, including: (1) stereocilia mechano-electrical transduction, force production, and response amplification, (2) outer hair cell (OHC) somatic motility and its molecular basis in prestin, (3) cochlear amplification and related micromechanics, including the evidence that prestin is the main motor for cochlear amplification, (4) the influence of the tectorial membrane, (5) cochlear micromechanics and the mechanical drives to inner hair cell stereocilia, (6) otoacoustic emissions, and (7) olivocochlear efferents and their influence on cochlear physiology. We then return to a subject that Bekesy knew well: cochlear fluids and standing currents, as well as our present understanding of energy dependence on the lateral wall of the cochlea. Finally, we touch on cochlear pathologies including noise damage and aging, with an emphasis on where the field might go in the future. (C) 2012 Elsevier B.V. All rights reserved. C1 [Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Labs, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Salt, Alec] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. [Cheatham, Mary Ann] Northwestern Univ, Dept Commun Sci & Disorders, Hugh Knowles Ctr, Evanston, IL 60208 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu; salta@ent.wustl.edu; m-cheatham@northwestern.edu FU NIH [RO1 DC000235, RO1 DC005977, P30 DC005209, RO1 DC01368, R01 DC00089] FX We thank Dr. Wei Zhao for comments on the manuscript. Supported by NIH RO1 DC000235, RO1 DC005977, P30 DC005209, RO1 DC01368, R01 DC00089. NR 93 TC 8 Z9 8 U1 0 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD NOV PY 2012 VL 293 IS 1-2 BP 12 EP 20 DI 10.1016/j.heares.2012.05.005 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 081OM UT WOS:000314331500003 PM 22633944 ER PT J AU Puria, S Rosowski, JJ AF Puria, Sunil Rosowski, John J. TI Bekesy's contributions to our present understanding of sound conduction to the inner ear SO HEARING RESEARCH LA English DT Review ID HUMAN MIDDLE-EAR; TYMPANIC-MEMBRANE PERFORATIONS; TIME-AVERAGED HOLOGRAPHY; COCHLEAR INPUT IMPEDANCE; ANCHORED HEARING-AID; HUMAN TEMPORAL BONES; OTOACOUSTIC EMISSIONS; SURGICAL IMPLICATIONS; PRESSURE MEASUREMENTS; HIGH-FREQUENCIES AB In our daily lives we hear airborne sounds that travel primarily through the external and middle ear to the cochlear sensory epithelium. We also hear sounds that travel to the cochlea via a second sound-conduction route, bone conduction. This second pathway is excited by vibrations of the head and body that result from substrate vibrations, direct application of vibrational stimuli to the head or body, or vibrations induced by airborne sound. The sensation of bone-conducted sound is affected by the presence of the external and middle ear, but is not completely dependent upon their function. Measurements of the differential sensitivity of patients to airborne sound and direct vibration of the head are part of the routine battery of clinical tests used to separate conductive and sensorineural hearing losses. Georg von Bekesy designed a careful set of experiments and pioneered many measurement techniques on human cadaver temporal bones, in physical models, and in human subjects to elucidate the basic mechanisms of air- and bone-conducted sound. Looking back one marvels at the sheer number of experiments he performed on sound conduction, mostly by himself without the aid of students or research associates. Bekesy's work had a profound impact on the field of middle-ear mechanics and bone conduction fifty years ago when he received his Nobel Prize. Today many of Bekesy's ideas continue to be investigated and extended, some have been supported by new evidence, some have been refuted, while others remain to be tested. (C) 2012 Elsevier B.V. All rights reserved. C1 [Puria, Sunil] Stanford Univ, Dept Mech Engn, Stanford, CA 94305 USA. [Puria, Sunil] Stanford Univ, Dept Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA. [Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu FU NIDCD of NIH [R01 DC05960, R01 DC00194] FX This work supported by NIDCD of NIH grants R01 DC05960 (SP) and R01 DC00194 (JJR). We thank Kevin N. O'Connor for editing help. NR 93 TC 2 Z9 2 U1 2 U2 31 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD NOV PY 2012 VL 293 IS 1-2 BP 21 EP 30 DI 10.1016/j.heares.2012.05.004 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 081OM UT WOS:000314331500004 PM 22617841 ER PT J AU Karaosmanoglu, D Erol, B Karcaaltincaba, M AF Karaosmanoglu, D. Erol, B. Karcaaltincaba, M. TI MULTIDETECTOR CT OF HEPATIC ARTERY PATHOLOGIES SO JBR-BTR LA English DT Article DE Aneurysm; hepatic - Hepatic artery; CT - dissection ID DONOR LIVER-TRANSPLANTATION; CELIAC ARTERY; ANEURYSM; COMPLICATIONS; DISSECTION AB The hepatic artery can be involved by a variety of pathology and diseases. Today MDCT enables high quality imaging of the hepatic artery using axial, MIP and volume rendered images. We illustrate MDCT findings of anatomical variations, aneurysm, dilatation, dissection, arteriovenous fistula, thrombosis and stenosis. Aneurysms can be saccular, fusiform and multiple and may develop due to atherosclerosis, vasculitis, trauma and biopsy. Dilatation of hepatic,artery can be seen in portal hypertension, Osler-Weber-Rendu disease and hemangiomatosis. Hepatic artery can be occluded after trauma and transplantation. Dissection develops due to atherosclerosis, Marfan and Ehler Danlos syndromes and during pregnancy. Arteriovenous fistula can be congenital and acquired. We conclude that various hepatic artery pathologies can be confidently diagnosed by MDCT. C1 [Karaosmanoglu, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Erol, B.] Antalya Educ & Res Hosp, Dept Radiol, Antalya, Turkey. [Karcaaltincaba, M.] Hacettepe Univ, Fac Med, Dept Radiol, TR-06100 Ankara, Turkey. RP Karcaaltincaba, M (reprint author), Hacettepe Univ, Sch Med, Dept Radiol, Liver Imaging Team, TR-06100 Ankara, Turkey. EM musturayk@yahoo.com RI Karcaaltincaba, Musturay/A-3866-2016 OI Karcaaltincaba, Musturay/0000-0002-3384-0909 NR 18 TC 1 Z9 1 U1 0 U2 2 PU ASSOC ROYAL SOC SCIENTIFIQUES MEDICALES BELGES PI BRUSSELS PA AVE W CHURCHILL 11-30, BRUSSELS, B-1180, BELGIUM SN 1780-2393 J9 JBR-BTR JI JBR-BTR PD NOV-DEC PY 2012 VL 95 IS 6 BP 345 EP 349 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 081NB UT WOS:000314327800001 PM 23405484 ER PT J AU Antunes, MB Chi, JJ Liu, Z Goldstein-Daruech, N Palmer, JN Zhu, J Cohen, NA AF Antunes, Marcelo B. Chi, John J. Liu, Zhi Goldstein-Daruech, Natalia Palmer, James N. Zhu, Jun Cohen, Noam A. TI Molecular Basis of Tobacco-Induced Bacterial Biofilms: An In Vitro Study SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE chronic rhinosinusitis; biofilm; tobacco; oxidative stress; quorum sensing; virulence factor ID ENDOSCOPIC SINUS SURGERY; ENTEROPATHOGENIC ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA VIRULENCE; BRONCHIAL EPITHELIAL-CELLS; ALGINATE GENE-EXPRESSION; TOXIN-COREGULATED PILI; LUXR-LUXI FAMILY; CHRONIC RHINOSINUSITIS; CYSTIC-FIBROSIS; TWITCHING MOTILITY AB Objective. To evaluate changes in the expression of biofilm-related genes when exposed to tobacco smoke and oxidative stress. Study Design. Experimental, in vitro. Setting. Laboratories of Rhinology and Microbiology, University of Pennsylvania. Subjects and Methods. Bacterial biofilm mass was measured using crystal violet staining and measurement of the optical density. Biofilm-related genes of the Pseudomonas aeruginosa PAO1 strain (pilF, flgK, lasI, lasB, rhlA, and algC) were studied following repetitive exposure to exogenous tobacco smoke and hydrogen peroxide. This was done using a reporter plasmid. Results. After I exposure to smoke, there was no change in biofilm formation. However, after 2 and 3 exposures, the biofilm formed had an increased mass (P < .05). With respect to oxidative stress in the form of H2O2, bacterial cultures demonstrated a dose- and time-dependent induction of biofilm formation compared with control conditions. Gene expression following repetitive smoke exposure demonstrated an increase in expression of pilF, flgK, algC, and lasI genes (P < .05); a decrease in rhlA (P < .05); and no significant change in the lasB gene (P = 0.1). Gene expression following H2O2 exposure demonstrated an increase in pilF (P < .05), whereas the other genes failed to demonstrate a statistical change. Conclusions. Repetitive tobacco smoke exposure leads to molecular changes in biofilm-related genes, and exposure to oxidative stress in the form of H2O2 induces biofilm growth in PAO1. This could represent adaptative changes due to oxidative stress or chemically mediated through any of the several chemicals encountered in tobacco smoke and may explain increased biofilm formation in microbes isolated from smokers. C1 [Antunes, Marcelo B.; Chi, John J.; Palmer, James N.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Liu, Zhi; Zhu, Jun] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Goldstein-Daruech, Natalia] Pontificia Univ Catolica Chile, Escuela Med, Dept Otorhinolaryngol Head & Neck Surg, Santiago, Chile. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, 3400 Spruce St,5th Floor,Silverstein Bldg, Philadelphia, PA 19104 USA. EM noam.cohen@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 FU AAOHNS Foundation Resident Research Grant FX AAOHNS Foundation Resident Research Grant. The funding source had no role in study design and conduct; collection, analysis, and interpretation of the data; and writing or approval of the manuscript. NR 79 TC 7 Z9 9 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2012 VL 147 IS 5 BP 876 EP 884 DI 10.1177/0194599812447263 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 081AF UT WOS:000314285800012 PM 22597576 ER PT J AU Falco, FJE Manchikanti, L Datta, S Sehgal, N Geffert, S Onyewu, O Singh, V Bryce, DA Benyamin, RM Simopoulos, TT Vallejo, R Gupta, S Ward, SP Hirsch, JA AF Falco, Frank J. E. Manchikanti, Laxmaiah Datta, Sukdeb Sehgal, Nalini Geffert, Stephanie Onyewu, Obi Singh, Vijay Bryce, David A. Benyamin, Ramsin M. Simopoulos, Thomas T. Vallejo, Ricardo Gupta, Sanjeeva Ward, Stephen P. Hirsch, Joshua A. TI An Update of the Systematic Assessment of the Diagnostic Accuracy of Lumbar Facet Joint Nerve Blocks SO PAIN PHYSICIAN LA English DT Review DE Chronic low back pain; lumbar facet or zygapophysial joint pain; facet joint nerve blocks; medial branch blocks; controlled comparative local anesthetic blocks ID LOW-BACK-PAIN; MEDIAL BRANCH BLOCKS; INTERLAMINAR EPIDURAL INJECTIONS; EMISSION COMPUTED-TOMOGRAPHY; ACTIVE-CONTROLLED-TRIAL; CHRONIC SPINAL PAIN; OF-THE-LITERATURE; RANDOMIZED CLINICAL-TRIAL; LOCAL-ANESTHETIC BLOCKS; 2-YEAR FOLLOW-UP AB Background: Lumbar facet joints are a well recognized source of low back pain and referred pain in the lower extremity in patients with chronic low back pain. Conventional clinical features and other non-invasive diagnostic modalities are unreliable in diagnosing lumbar zygapophysial joint pain. Controlled diagnostic studies with at least 80% pain relief as the criterion standard have shown the prevalence of lumbar facet joint pain to be 16% to 41% of patients with chronic low back pain without disc displacement or radiculitis, with a false-positive rate of 17% to 49% with a single diagnostic block. Study Design: A systematic review of the diagnostic accuracy of lumbar facet joint nerve blocks. Objective: To determine and update the diagnostic accuracy of lumbar facet joint nerve blocks in the assessment of chronic low back pain. Methods: A methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. Studies scoring less than 50% are presented descriptively and analyzed critically. The level of evidence was classified as good, fair, and limited or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to June 2012, and manual searches of the bibliographies of known primary and review articles. Outcome Measures: Studies must have been performed utilizing controlled local anesthetic blocks. Pain relief was categorized as at least 50% pain relief from baseline pain and the ability to perform previously painful movements. Results: A total of 25 diagnostic accuracy studies were included. Of these, one study evaluated 50% to 74% relief as criterion standard with a single block with prevalence of 48%, 4 studies evaluated 75% to 100% relief as the criterion standard with a single block with a prevalence of 31% to 61%, 5 studies evaluated 50% to 74% relief as the criterion standard with controlled blocks with a prevalence of 15% to 61%, and 13 studies evaluated 75% to 100% relief as the criterion standard with controlled blocks with a prevalence of 25% to 45% in heterogenous populations. False-positive rates ranged from 17% to 66% in the 50% to 74% pain relief group and 27% to 49% with at least 75% relief as the criterion standard. Based on this evaluation, the evidence showed that there is good evidence for diagnostic facet joint nerve blocks with 75% to 100% pain relief as the criterion standard with dual blocks and fair evidence with 50% to 74% pain relief as the criterion standard with controlled diagnostic blocks; however, the evidence is poor with single diagnostic blocks of 50% to 74%, and limited for 75% or more pain relief as the criterion standard. Limitations: The shortcomings of this systematic review of the accuracy of diagnostic lumbar facet joint nerve blocks include a paucity of literature and continued debate on an appropriate gold standard. Conclusion: There is good evidence for diagnostic facet joint nerve blocks with 75% to 100% pain relief as the criterion standard with dual blocks, with fair evidence with 50% to 74% pain relief. C1 [Falco, Frank J. E.; Geffert, Stephanie; Onyewu, Obi] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.; Onyewu, Obi] Temple Univ Hosp & Med Sch, Pain Med Fellowship Program, Philadelphia, PA 19140 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Datta, Sukdeb] Laser Spine & Pain Inst, New York, NY USA. [Sehgal, Nalini] Univ Wisconsin, Sch Med & Publ Hlth, Intervent Pain Program, Madison, WI USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Bryce, David A.] Adv Pain Management, Madison, WI USA. [Benyamin, Ramsin M.; Vallejo, Ricardo] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Urbana, IL 61801 USA. [Simopoulos, Thomas T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Vallejo, Ricardo] Illinois State Univ, Normal, IL 61761 USA. [Gupta, Sanjeeva] Bradford Teaching Hosp NHS Fdn Trust, Bradford Royal Infirm, Bradford, W Yorkshire, England. [Ward, Stephen P.] Nhs Trust, Brighton Univ Hosp, Brighton, E Sussex, England. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Falco, FJE (reprint author), 139 E Chestnut Hill Rd, Newark, DE 19713 USA. EM cssm01@aol.com FU Sucampo Pharmaceuticals; Alfred Mann Foundation; Teknon Foundation; Spinal Restoration, Inc.; Bioness; Boston Scientific; Vertos Medical; Medtronic; Kimberly Clarke; Epimed; BioDelivery Sciences International, Inc.; Theravance; Mundipharma Research; Cephalon/Teva; AstraZeneca; Purdue Pharma, LP; Mundipharma Research GmbH Co.; CareFusion FX Dr. Datta receives research support from Sucampo Pharmaceuticals and an honorarium from Smith and Nephew.; Dr. Benyamin is a consultant with Bioness and Nevro, serves on the advisory boards of Vertos Medical and Nuvo Pharma, teaches/lectures for Vertos Medical, Boston Scientific, Neurotherm, and Bioness, and receives research/grants from Alfred Mann Foundation, Teknon Foundation, Spinal Restoration, Inc., Bioness, Boston Scientific, Vertos Medical, Medtronic, Kimberly Clarke, Epimed, BioDelivery Sciences International, Inc., Theravance, Mundipharma Research, Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP.; Dr. Vallejo receives research support from Cephalon/Teva, BioDelivery Sciences International, Inc., Mundipharma Research GmbH & Co., AstraZeneca, Purdue Pharma, LP, and Theravance.; Dr. Hirsch has received fees from CareFusion in the past 12 months. He participated in an Aetrium focus group and received compensation. NR 365 TC 18 Z9 18 U1 0 U2 9 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 NOV-DEC PY 2012 VL 15 IS 6 BP E869 EP E907 PG 39 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 075JD UT WOS:000313880400005 PM 23159979 ER PT J AU Manchikanti, L Falco, FJE Singh, V Pampati, V Parr, AT Benyamin, RM Fellows, B Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Singh, Vijay Pampati, Vidyasagar Parr, Allan T. Benyamin, Ramsin M. Fellows, Bert Hirsch, Joshua A. TI Utilization of Interventional Techniques in Managing Chronic Pain in the Medicare Population: Analysis of Growth Patterns from 2000 to 2011 SO PAIN PHYSICIAN LA English DT Review DE Interventional techniques; interventional pain management; facet joint injections; epidural steroid injections; sacroiliac joint injections; chronic pain; chronic spinal pain ID LOW-BACK-PAIN; INTERLAMINAR EPIDURAL INJECTIONS; ACTIVE-CONTROLLED-TRIAL; SPINAL-CORD STIMULATION; CHRONIC NONCANCER PAIN; CLINICAL-PRACTICE GUIDELINES; LUMBAR DISC HERNIATION; DOUBLE-BLIND TRIAL; UNITED-STATES; NECK PAIN AB Background: Reports from the United States Government Accountability Office (GAO), the Institute of Medicine (IOM), the Medicare Payment Advisory Commission (MedPAC), and the Office of Inspector General (OIG) continue to express significant concern with the overall fiscal sustainability of Medicare and the exponential increase in costs for chronic pain management. Study Design: The study is an analysis of the growth of interventional techniques in managing chronic pain in Medicare beneficiaries from 2000 to 2011. Objective: To evaluate the use of all interventional techniques in chronic pain management. Methods: The study was performed utilizing the Centers for Medicare and Medicaid Services (CMS) Physician Supplier Procedure Summary Master Data from 2000 to 2011. Results: Interventional techniques for chronic pain have increased dramatically from 2000 to 2011. Overall, the increase of interventional pain management (IPM) procedures from 2000 to 2011 went up 228%, with 177% per 100,000 Medicare beneficiaries. The increases were highest for facet joint interventions and sacroiliac joint blocks with a total increase of 386% and 310% per 100,000 Medicare beneficiaries, followed by 168% and 127% for epidural and adhesiolysis procedures, 150% and 111% for other types of nerve blocks and finally, 28% and 8% increases for percutaneous disc procedures. The geometric average of annual increases was 9.7% overall with 13.7% for facet joint interventions and sacroiliac joint blocks and 7.7% for epidural and adhesiolysis procedures. Limitations: The limitations of this study included a lack of inclusion of Medicare participants in Medicare Advantage plans, as well as potential documentation, coding, and billing errors. Conclusion: Interventional techniques increased significantly in Medicare beneficiaries from 2000 to 2011. Overall, there was an increase of 177% in the utilization of IPM services per 100,000 Medicare beneficiaries, with an annual geometric average increase of 9.7%. The study also showed an exponential increase in facet joint interventions and sacroiliac joint blocks. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar; Fellows, Bert] 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. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Parr, Allan T.] Premier Pain Ctr, Covington, LA USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Urbana, IL 61801 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, 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 American Society of Interventional Pain Physicians (ASIPP); Alfred Mann Foundation; Teknon Foundation; Spinal Restoration, Inc.; Bioness; Boston Scientific; Vertos Medical; Medtronic; Kimberly Clarke; Epimed; BioDelivery Sciences International, Inc.; Theravance; Mundipharma Research; Cephalon/Teva; AstraZeneca; Purdue Pharma, LP FX The data from the Centers for Medicare and Medicaid Services (CMS) were purchased for $1,000 by the American Society of Interventional Pain Physicians (ASIPP). There was no other funding. Internal resources were utilized in preparing this manuscript.; Dr. Benyamin is a consultant with Bioness and Nevro; serves on the advisory boards of Vertos Medical and Nuvo Pharma; teaches/lectures for Vertos Medical, Boston Scientific, Neurotherm, and Bioness; and receives research/grants from Alfred Mann Foundation, Teknon Foundation, Spinal Restoration, Inc., Bioness, Boston Scientific, Vertos Medical, Medtronic, Kimberly Clarke, Epimed, BioDelivery Sciences International, Inc., Theravance, Mundipharma Research, Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP. NR 97 TC 58 Z9 58 U1 1 U2 5 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 NOV-DEC PY 2012 VL 15 IS 6 BP E969 EP E982 PG 14 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 075JD UT WOS:000313880400008 PM 23159982 ER PT J AU Manchikanti, L Benyamin, RM Swicegood, JR Falco, FJE Datta, S Pampati, V Fellows, B Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin M. Swicegood, John R. Falco, Frank J. E. Datta, Sukdeb Pampati, Vidyasagar Fellows, Bert Hirsch, Joshua A. TI Assessment of Practice Patterns of Perioperative Management of Antiplatelet and Anticoagulant Therapy in Interventional Pain Management SO PAIN PHYSICIAN LA English DT Review DE Interventional pain management; interventional techniques; hemostasis; anticoagulants; antiplatelet therapy; thromboembolic events; bleeding; complications; aspirin; clopidogrel (Plavix); warfarin (Coumadin) ID INTERLAMINAR EPIDURAL INJECTIONS; ACTIVE-CONTROLLED-TRIAL; CLINICAL-PRACTICE GUIDELINES; LUMBAR SPINAL STENOSIS; CHRONIC NONCANCER PAIN; CHRONIC THORACIC PAIN; MEDIAL BRANCH BLOCKS; 2-YEAR FOLLOW-UP; DOUBLE-BLIND; REGIONAL-ANESTHESIA AB Background: The role of antithrombotic therapy is well known for its primary and secondary prevention of cardiovascular disease by decreasing the incidence of acute cerebral, cardiovascular, peripheral vascular, and other thrombotic events. The overwhelming data show that the risk of thrombotic events is significantly higher than that of bleeding during surgery after antiplatelet drug discontinuation. It has been assumed that discontinuing antiplatelet therapy prior to performing interventional pain management techniques is a common practice, even though doing so may potentially increase the risk of acute cerebral and cardiovascular events. There are no data available concerning these events, specifically in relation to the occurrence of thromboembolic events, even though some data are available concerning bleeding complications. Even then, interventionalists seem to routinely discontinue all antithrombotic therapy prior to all interventional pain management techniques. Objective: To assess the perioperative antiplatelet and anticoagulant practice patterns of US interventional pain management physicians as well as adverse events in patients on antithrombotic therapy who undergo interventional pain management techniques when that therapy is continued or stopped. Study Design: An online survey of interventional pain management physicians. Study Setting: Interventional pain management practices in the United States. Methods: An online survey was commissioned among 2,300 members of the American Society of Interventional Pain Physicians. The survey was designed to assess practice patterns and complications encountered. Results: Of the 2,300 members surveyed, 325 responded. These results showed that all physicians discontinued warfarin therapy; whereas, 97% discontinued clopidogrel; 96% ticlopidine; 95% Aggrastat (tirofiban); 93% cilostazol, 85% dipyridamole, 60% aspirin 350 mg; 39% aspirin 81 mg; and 39% other nonsteroidal anti-inflammatory drugs (NSAIDs) prior to performing interventional pain management techniques. The majority of physicians accepted an international normalized ratio of 1.5 or less as a safe level. An assessment of serious complications showed thromboembolic events were 3 times more frequent than bleeding complications: 162 thromboembolic events and 55 serious bleeding complications from epidural hematomas. Thromboembolic complications were severe and higher when antiplatelet therapy was discontinued. Bleeding complications from epidural hematomas were similar whether antiplatelet therapy was continued or discontinued (26 versus 29). Limitations: This study was limited by its being an online survey of the membership of one organization in one country and that there was a 14% response rate. Underreporting in surveys is common. Further, the incidence of thromboembolic events or epidural hematomas may be misrepresented as a percentage since these drugs were continued in a very small percentage of patients. Consequently, the incidences described in this manuscript may not show appropriate percentages. Conclusion: The results illustrate an overwhelming pattern of discontinuing antiplatelet and warfarin therapy as well as aspirin and other NSAIDs prior to performing interventional pain management techniques. However, thromboembolism complications may be 3 times more prevalent than epidural hematomas (162 versus 55 events). It is concluded that clinicians must balance the risks of thromboembolism and bleeding in each patient prior to the routine discontinuation of antiplatelet therapy. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar; Fellows, Bert] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Urbana, IL 61801 USA. [Swicegood, John R.] Adv Intervent Pain & Diagnost Western Arkansas, Ft Smith, AR 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. [Datta, Sukdeb] Laser Spine & Pain Inst, New York, NY USA. [Datta, Sukdeb] Mt Sinai Sch Med, Dept Anesthesiol, New York, NY USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, 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 Alfred Mann Foundation; Teknon Foundation; Spinal Restoration, Inc.; Bioness; Boston Scientific; Vertos Medical; Medtronic; Kimberly Clarke; Epimed; BioDelivery Sciences International, Inc.; Theravance; Mundipharma Research; Cephalon/Teva; AstraZeneca; Purdue Pharma, LP; Sucampo Pharmaceuticals; CareFusion FX Dr. Benyamin is a consultant with Bioness and Nevro, serves on the advisory boards of Vertos Medical and Nuvo Pharma, teaches/lectures for Vertos Medical, Boston Scientific, Neurotherm, and Bioness, and receives research/grants from Alfred Mann Foundation, Teknon Foundation, Spinal Restoration, Inc., Bioness, Boston Scientific, Vertos Medical, Medtronic, Kimberly Clarke, Epimed, BioDelivery Sciences International, Inc., Theravance, Mundipharma Research, Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP.; Dr. Falco is a consultant for St. Jude Medical Inc. and Joimax Inc. Dr. Datta receives research support from Sucampo Pharmaceuticals and an honorarium from Smith and Nephew. Dr. Hirsch has received fees from CareFusion in the past 12 months. He participated in an Aetrium focus group and received compensation. NR 100 TC 18 Z9 19 U1 0 U2 4 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 NOV-DEC PY 2012 VL 15 IS 6 BP E955 EP E968 PG 14 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 075JD UT WOS:000313880400007 PM 23159981 ER PT J AU Onyewu, O Manchikanti, L Falco, FJE Singh, V Geffert, S Helm, S Cohen, SP Hirsch, JA AF Onyewu, Obi Manchikanti, Laxmaiah Falco, Frank J. E. Singh, Vijay Geffert, Stephanie Helm, Standiford, II Cohen, Steven P. Hirsch, Joshua A. TI An Update of the Appraisal of the Accuracy and Utility of Cervical Discography in Chronic Neck Pain SO PAIN PHYSICIAN LA English DT Review DE Chronic cervical pain; cervical intervertebral disc; cervical discography; provocation discography; analgesic discography; pain generator; false-positives; diagnostic accuracy; sensitivity; specificity; outcomes ID LOW-BACK-PAIN; INTERLAMINAR EPIDURAL INJECTIONS; 2000-2010 TASK-FORCE; CHRONIC SPINAL PAIN; PRESSURE-CONTROLLED DISCOGRAPHY; ZYGAPOPHYSIAL JOINT PAIN; INTERVERTEBRAL DISC DEGENERATION; LUMBAR PROVOCATION DISCOGRAPHY; WHIPLASH-ASSOCIATED DISORDERS; MYOFASCIAL TRIGGER POINTS AB Background: Chronic neck pain represents a significant public health problem. Despite high prevalence rates, there is a lack of consensus regarding the causes or treatments for this condition. Based on controlled evaluations, the cervical intervertebral discs, facet joints, and atlantoaxial joints have all been implicated as pain generators. Cervical provocation discography, which includes disc stimulation and morphological evaluation, is occasionally used to distinguish a painful disc from other potential sources of pain. Yet in the absence of validation and controlled outcome studies, the procedure remains mired in controversy. Study Design: A systematic review of the diagnostic accuracy of cervical discography. Objective: To systematically evaluate and update the diagnostic accuracy of cervical discography. Methods: The available literature on cervical discography was reviewed. Methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. However, studies scoring less than 50% are presented descriptively and analyzed critically. The level of evidence was classified as good, fair, and limited or poor based on the quality of evidence developed by the U. S. Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to June 2012, and manual searches of the bibliographies of known primary and review articles. Results: A total of 41 manuscripts were considered for accuracy and utility of cervical discography in chronic neck pain. There were 23 studies evaluating accuracy of discography. There were 3 studies meeting inclusion criteria for assessing the accuracy and prevalence of discography, with a prevalence of 16% to 53%. Based on modified Agency for Healthcare Research and Quality (AHRQ) accuracy evaluation and United States Preventive Services Task Force (USPSTF) level of evidence criteria, this systematic review indicates the strength of evidence is limited for the diagnostic accuracy of cervical discography. Limitations: Limitations include a paucity of literature, poor methodological quality, and very few studies performed utilizing International Association for the Study of Pain (IASP) criteria. Conclusion: There is limited evidence for the diagnostic accuracy of cervical discography. Nevertheless, in the absence of any other means to establish a relationship between pathology and symptoms, cervical provocation discography may be an important evaluation tool in certain contexts to identify a subset of patients with chronic neck pain secondary to intervertebral disc disorders. Based on the current systematic review, cervical provocation discography performed according to the IASP criteria with control disc(s), and a minimum provoked pain intensity of 7 of 10, or at least 70% reproduction of worst pain (i.e. worst spontaneous pain of 7 = 7 x 70% = 5), may be a useful tool for evaluating chronic pain and cervical disc abnormalities in a small proportion of patients. C1 [Onyewu, Obi; Falco, Frank J. E.; Geffert, Stephanie] Mid Atlantic Spine & Pain Phys Newark, Newark, DE USA. [Onyewu, Obi; Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Pain Med Fellowship Program, Philadelphia, PA 19140 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Hills, CA USA. [Cohen, Steven P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Cohen, Steven P.] Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Onyewu, O (reprint author), Mid Atlantic Spine, 139 E Chestnut Hill Rd, Newark, DE 19713 USA. EM obionyewu@aol.com FU Cephalon/Teva; AstraZeneca; Purdue Pharma, LP; CareFusion 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.; Dr. Hirsch has received fees from CareFusion in the past 12 months. He participated in an Aetrium focus group and received compensation.. NR 274 TC 14 Z9 14 U1 0 U2 8 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 NOV-DEC PY 2012 VL 15 IS 6 BP E777 EP E806 PG 30 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 075JD UT WOS:000313880400002 PM 23159976 ER PT J AU Li, MY Verdijk, LB Sakamoto, K Ely, B van Loon, LJC Musi, N AF Li, Mengyao Verdijk, Lex B. Sakamoto, Kei Ely, Brian van Loon, Luc J. C. Musi, Nicolas TI Reduced AMPK-ACC and mTOR signaling in muscle from older men, and effect of resistance exercise SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Aging; Skeletal muscle; AMPK; mTOR; Resistance exercise ID ACTIVATED PROTEIN-KINASE; HUMAN SKELETAL-MUSCLE; GLUCOSE-UPTAKE; ELDERLY-MEN; MAMMALIAN TARGET; DOSE-RESPONSE; CELL-GROWTH; AMINO-ACID; YOUNG; HYPERTROPHY AB AMP-activated protein kinase (AMPK) is a key energy-sensitive enzyme that controls numerous metabolic and cellular processes. Mammalian target of rapamycin (mTOR) is another energy/nutrient-sensitive kinase that controls protein synthesis and cell growth. In this study we determined whether older versus younger men have alterations in the AMPK and mTOR pathways in skeletal muscle, and examined the effect of a long term resistance type exercise training program on these signaling intermediaries. Older men had decreased AMPK alpha 2 activity and lower phosphorylation of AMPK and its downstream signaling substrate acetyl-CoA carboxylase (ACC). mTOR phosphylation also was reduced in muscle from older men. Exercise training increased AMPK alpha 1 activity in older men, however, AMPK alpha 2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not affected. In conclusion, older men have alterations in the AMPK-ACC and mTOR pathways in muscle. In addition, prolonged resistance type exercise training induces an isoform-selective up regulation of AMPK activity. Published by Elsevier Ireland Ltd. C1 [Li, Mengyao; Ely, Brian; Musi, Nicolas] Audie L Murphy Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Li, Mengyao; Ely, Brian; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Ctr Hlth Aging, San Antonio, TX 78229 USA. [Li, Mengyao; Ely, Brian; Musi, Nicolas] Texas Diabet Inst, San Antonio, TX 78207 USA. [Verdijk, Lex B.; van Loon, Luc J. C.] Maastricht Univ, Med Ctr, NUIRIM Sch Nutr Toxicol & Metab, Dept Human Movement Sci, NL-6200 MD Maastricht, Netherlands. [Sakamoto, Kei] Nestle Inst Hlth Sci SA, CH-1015 Lausanne, Switzerland. RP Musi, N (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM musi@uthscsa.edu RI Verdijk, Lex/H-4468-2016; OI van Loon, Luc J.C./0000-0002-6768-9231 FU National Institutes of Health [RO1-DK80157, RO1-DK089229]; Paul B. Beeson Career Development Award from the American Federation for Aging Research and the National Institute on Aging [K23-AG030979]; Anna Foundation (Leiden, the Netherlands); U.K. Medical Research Council FX This work was supported by grants from the National Institutes of Health (RO1-DK80157 and RO1-DK089229 to N.M). N.M. was the recipient of a Paul B. Beeson Career Development Award (K23-AG030979) from the American Federation for Aging Research and the National Institute on Aging. L.V. received support from the Anna Foundation (Leiden, the Netherlands) and K.S. from U.K. Medical Research Council. NR 57 TC 16 Z9 17 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV-DEC PY 2012 VL 133 IS 11-12 BP 655 EP 664 DI 10.1016/j.mad.2012.09.001 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 077FC UT WOS:000314012300003 PM 23000302 ER PT J AU Klein, OJ Bhayana, B Park, YJ Evans, CL AF Klein, Oliver J. Bhayana, Brijesh Park, Yong Jin Evans, Conor L. TI In Vitro Optimization of EtNBS-PDT against Hypoxic Tumor Environments with a Tiered, High-Content, 3D Model Optical Screening Platform SO MOLECULAR PHARMACEUTICS LA English DT Article DE hypoxia; acidosis; 3D cancer culture models; photodynamic therapy; high-content screening; microscopy ID PHOTODYNAMIC THERAPY; OVARIAN-CANCER; CHEMOTHERAPEUTIC-AGENTS; CLONOGENIC-ASSAY; DRUG-RESISTANCE; MTT ASSAY; EFFICACY; CELLS; VIVO; CISPLATIN AB Hypoxia and acidosis are widely recognized as major contributors to the development of treatment resistant cancer. For patients with disseminated metastatic lesions, such as most women with ovarian cancer (OvCa), the progression to treatment resistant disease is almost always fatal. Numerous therapeutic approaches have been developed to eliminate treatment resistant carcinoma, including novel biologic, chemo, radiation, and photodynamic therapy (PDT) regimens. Recently, PDT using the cationic photosensitizer EtNBS was found to be highly effective against therapeutically unresponsive hypoxic and acidic OvCa cellular populations in vitro. To optimize this treatment regimen, we developed a tiered, high-content, image-based screening approach utilizing a biologically relevant OvCa 3D culture model to investigate a small library of side-chain modified EtNBS derivatives. The uptake, localization, and photocytotoxicity of these compounds on both the cellular and nodular levels were observed to be largely mediated by their respective ethyl side chain chemical alterations. In particular, EtNBS and its hydroxyl-terminated derivative (EtNBS-OH) were found to have similar pharmacological parameters, such as their nodular localization patterns and uptake kinetics. Interestingly, these two molecules were found to induce dramatically different therapeutic outcomes: EtNBS was found to be more effective in killing the hypoxic, nodule core cells with superior selectivity, while EtNBS-OH was observed to trigger widespread structural degradation of nodules. This breakdown of the tumor architecture can improve the therapeutic outcome and is known to synergistically enhance the antitumor effects of front-line chemotherapeutic regimens. These results, which would not have been predicted or observed using traditional monolayer or in vivo animal screening techniques, demonstrate the powerful capabilities of 3D in vitro screening approaches for the selection and optimization of therapeutic agents for the targeted destruction of specific cellular subpopulations. C1 [Klein, Oliver J.; Bhayana, Brijesh; Evans, Conor L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02215 USA. [Park, Yong Jin] Korea Adv Inst Sci & Technol, Dept Chem & Biomol Engn, Taejon 335, South Korea. RP Evans, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,BAR410, Boston, MA 02215 USA. EM Evans.Conor@mgh.harvard.edu FU National Institutes of Health [NIH R21 CA155535]; NIH Director's New Innovator Award Program [1 DP2 0D007096] FX We would like to thank Tayyaba Hasan for the use of the 670 nm fiber coupled diode laser. Y.J.P. was supported by the KAIST HST summer intern program and the Gwanjung scholarship foundation. We thank Adnan Abu-Yousif for his help with the MTT assay. This work was funded by the National Institutes of Health through NIH R21 CA155535 and the NIH Director's New Innovator Award Program, Grant No. 1 DP2 0D007096. Information on the New Innovator Award Program is at http://nihroadmap.nih.gov/newinnovator/. NR 50 TC 15 Z9 15 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD NOV PY 2012 VL 9 IS 11 BP 3171 EP 3182 DI 10.1021/mp300262x PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 073US UT WOS:000313769200019 PM 22946843 ER PT J AU Akgoz, A Mukundan, S Lee, TC AF Akgoz, Ayca Mukundan, Srini Lee, Thomas C. TI Imaging of Rickettsial, Spirochetal, and Parasitic Infections SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Rickettsial Infections; Neurosyphilis; Lyme disease; CNS Toxoplasmosis ID CENTRAL-NERVOUS-SYSTEM; GRANULOMATOUS AMEBIC ENCEPHALITIS; BONE-MARROW-TRANSPLANTATION; ACUTE TRANSVERSE MYELITIS; DIFFUSION-WEIGHTED MRI; MOUNTAIN-SPOTTED-FEVER; LYME-DISEASE; BRAIN-STEM; NEUROIMAGING FINDINGS; HYDATID-DISEASE AB Imaging of Rickettsial, Spirochetal, and Parasitic Infections Ayca Akgoz, Srini Mukundan, and Thomas C. Lee This article is an update and literature review of the clinical and neuroimaging findings of the commonly known rickettsial, spirochetal, and eukaryotic parasitic infections. Being familiar with clinical presentation and imaging findings of these infections is crucial for early diagnosis and treatment especially in patients who live in or have a travel history to endemic regions or are immunocompromised. C1 [Lee, Thomas C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiol, Boston, MA 02115 USA. RP Lee, TC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM tclee@post.harvard.edu NR 113 TC 3 Z9 3 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 EI 1557-9867 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2012 VL 22 IS 4 BP 633 EP + DI 10.1016/j.nic.2012.05.015 PG 26 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 058EH UT WOS:000312616400007 PM 23122260 ER PT J AU Shah, RV Holmes, D Anderson, M Wang, TY Kontos, MC Wiviott, SD Scirica, BM AF Shah, Ravi V. Holmes, DaJuanicia Anderson, Monique Wang, Tracy Y. Kontos, Michael C. Wiviott, Stephen D. Scirica, Benjamin M. TI Risk of Heart Failure Complication During Hospitalization for Acute Myocardial Infarction in a Contemporary Population Insights From the National Cardiovascular Data ACTION Registry SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; myocardial infarction; outcomes ID ACUTE CORONARY SYNDROMES; INTERVENTION OUTCOMES NETWORK; CHRONIC KIDNEY-DISEASE; SYSTOLIC DYSFUNCTION; GLOBAL REGISTRY; EVENTS GRACE; PREDICTORS; MANAGEMENT; FREQUENCY; VALIANT AB Background-Patients with acute myocardial infarction (MI) complicated by heart failure (HF) are subject to higher mortality during the index hospitalization. Early risk prediction and intervention may help prevent HF-related morbidity and mortality. Methods and Results-We examined 77 675 ST-elevation MI and 110 128 non-ST-elevation patients with MI without cardiogenic shock or HF at presentation treated at 609 hospitals in Acute Coronary Treatment and Intervention Outcomes Network Registry (ACTION) Registry-Get With The Guidelines between January 1, 2007, and March 31, 2011. Logistic regression identified patient characteristics associated with development of in-hospital HF. Overall, 3.8% of patients with MI developed in-hospital HF, which was associated with higher mortality in both ST-elevation MI and non-ST elevation MI. In multivariable logistic regression, left ventricular ejection fraction <= 30%, prior HF, diabetes mellitus, female sex, ST-elevation MI, and hypertension (all P<0.005) were independently associated with in-hospital HF. Patients who developed HF during non-ST-elevation MI were more likely to be medically managed without catheterization (30% versus 13% with HF, P<0.0001) or had longer delays to surgical or percutaneous revascularization. Patients with ST-elevation MI and HF were less likely to receive primary percutaneous coronary revascularization (84% versus 79% with HF, P<0.0001), and more likely to receive thrombolytic therapy (14% versus 11%; P=0.0001). Conclusions-Patients with MI who develop HF during hospitalization have a higher risk clinical profile and greater mortality, but may be less likely to receive revascularization in a timely fashion. Targeting these highest risk patients may improve outcome post-MI. (Circ Heart Fail. 2012;5:693-702.) C1 [Shah, Ravi V.] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA USA. [Holmes, DaJuanicia; Anderson, Monique; Wang, Tracy Y.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Kontos, Michael C.] Virginia Commonwealth Univ, Dept Cardiol, Richmond, VA USA. [Wiviott, Stephen D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI, Boston, MA 02115 USA. [Scirica, Benjamin M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. RP Scirica, BM (reprint author), 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM bscirica@partners.org FU American Heart Association [11POST000002]; Heart Failure National Institutes for Health - National Heart, Lung and Blood Institute Clinical Research Network [U01-HL084877]; Bristol-Myers Squibb/Sanofi Aventis Partnership; Schering Plough/Merck Co., Inc; The Medicines Co; Heartscape Technologies, Inc.; Canyon Pharmaceuticals; Eli Lilly/Daiichi Sankyo Alliance; Merck; AstraZeneca; Johnson and Johnson; Bayer Healthcare; Daiichi Sankyo; Bristol-Myers Squibb; Gilead Sciences; Novartis; Eli Lilly FX R.V.S. is supported by an American Heart Association Post-Doctoral Fellowship Award (11POST000002) and a training grant from the Heart Failure National Institutes for Health - National Heart, Lung and Blood Institute Clinical Research Network (U01-HL084877). T.Y.W reports research grants to the Duke Clinical Research Institute from Bristol-Myers Squibb/Sanofi Aventis Partnership; Schering Plough/Merck & Co., Inc, The Medicines Co, Heartscape Technologies, Inc., Canyon Pharmaceuticals, and Eli Lilly/Daiichi Sankyo Alliance, as well as consulting or honoraria from Medco Health Solutions, Inc., Astra Zeneca, and the American College of Cardiology Foundation (all conflicts of interest are listed at www.dcri.org.). B. M. S. reports research grants from Merck, AstraZeneca, Johnson and Johnson, Bayer Healthcare, Daiichi Sankyo, Bristol-Myers Squibb, Gilead Sciences, Novartis; Consultant: Gilead Sciences, Arena Pharmaceuticals, Lexicon. M. C. K reports speaker's bureau and consultancy from Astellas and AstraZeneca. S. D. W reports research grants from AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, and consultancy from AstraZeneca, Bayer, Arena, Ortho McNeil, Johnson and Johnson, Norvartis, Merck Schering Plough. R. V. S., M. A., and D. H. have no disclosures to report. The authors would like to acknowledge the support of the Duke Clinical Research Institute and ACTION Registry-Get With The Guidelines for statistical support and critical review of this article. ACTION Registry-GWTG is an initiative of the American College of Cardiology Foundation and the American Heart Association with partnering support from the Society of Chest Pain Centers, the American College of Emergency Physicians, and the Society of Hospital Medicine. The registry is funded in part by an independent grant from Merck and by Bristol-Myers Squibb. NR 25 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2012 VL 5 IS 6 BP 693 EP 702 DI 10.1161/CIRCHEARTFAILURE.112.968180 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071GZ UT WOS:000313580100015 PM 23051950 ER PT J AU Mohammed, SF Borlaug, BA Roger, VL Mirzoyev, SA Rodeheffer, RJ Chirinos, JA Redfield, MM AF Mohammed, Selma F. Borlaug, Barry A. Roger, Veronique L. Mirzoyev, Sultan A. Rodeheffer, Richard J. Chirinos, Julio A. Redfield, Margaret M. TI Comorbidity and Ventricular and Vascular Structure and Function in Heart Failure With Preserved Ejection Fraction A Community-Based Study SO CIRCULATION-HEART FAILURE LA English DT Article DE anemia; heart failure with preserved ejection fraction; hypertension; diabetes mellitus; renal dysfunction; obesity ID BODY-SIZE; SYSTOLIC HYPERTENSION; REVERSE EPIDEMIOLOGY; DIABETES-MELLITUS; AORTIC DIAMETER; IRON-DEFICIENCY; ANEMIA; OBESITY; IMPACT; DYSFUNCTION AB Background-Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Methods and Results-Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive. Conclusions-Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease. (Circ Heart Fail. 2012;5:710-719.) C1 [Mohammed, Selma F.; Borlaug, Barry A.; Roger, Veronique L.; Rodeheffer, Richard J.; Redfield, Margaret M.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. [Roger, Veronique L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Mirzoyev, Sultan A.] Mayo Clin, Mayo Med Sch, Rochester, MN 55905 USA. [Chirinos, Julio A.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Redfield, MM (reprint author), Mayo Clin, Div Cardiovasc Dis, Guggenheim 9,200 1st St SW, Rochester, MN 55905 USA. EM redfield.margaret@mayo.edu OI Mirzoyev, Sultan/0000-0003-4819-6658 FU National Institutes of Health [HL72435, HL 55502, U01HL 84907, PO1HL 76611, HL080076, T32-HL0711]; American Heart Association [AHA 0885031N]; Mayo Clinic FX This study (HL72435 and HL 55502) and the investigators (Margaret M. Redfield, U01HL 84907, and PO1HL 76611; Julio A. Chirinos, HL080076 and AHA 0885031N; Selma F. Mohammed T32-HL0711) were supported by the National Institutes of Health, American Heart Association, and Mayo Clinic. NR 43 TC 71 Z9 72 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2012 VL 5 IS 6 BP 710 EP 719 DI 10.1161/CIRCHEARTFAILURE.112.968594 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071GZ UT WOS:000313580100017 PM 23076838 ER PT J AU Vaduganathan, M Ambrosy, AP Greene, SJ Mentz, RJ Subacius, HP Maggioni, AP Swedberg, K Nodari, S Zannad, F Konstam, MA Butler, J Gheorghiade, M AF Vaduganathan, Muthiah Ambrosy, Andrew P. Greene, Stephen J. Mentz, Robert J. Subacius, Haris P. Maggioni, Aldo P. Swedberg, Karl Nodari, Savina Zannad, Faiez Konstam, Marvin A. Butler, Javed Gheorghiade, Mihai CA EVEREST Trial Investigators TI Predictive Value of Low Relative Lymphocyte Count in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction Insights from the EVEREST Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; immune system; lymphocytes; prognosis ID INITIATE LIFESAVING TREATMENT; BLOOD-CELL COUNT; OPTIMIZE-HF; ORGANIZED PROGRAM; DOUBLE-BLIND; MORTALITY; TOLVAPTAN; ENDOTOXIN; REGISTRY; THERAPY AB Background-Low lymphocyte count has been shown to be an independent prognostic marker in heart failure (HF) in the outpatient setting. Limited data exist regarding whether relative lymphocyte count correlates with postdischarge outcomes in patients hospitalized for HF. Methods and Results-We performed a post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, which randomized 4133 patients hospitalized for worsening HF with an ejection fraction <= 40% within 48 hours of admission to tolvaptan or placebo for a median follow-up of 9.9 months. The primary end points of all-cause mortality and cardiovascular mortality or HF hospitalization were analyzed in patients with available baseline complete blood counts (n=3717). Lymphocyte percentage was analyzed as a continuous variable. Times to events were compared using log-rank tests and multivariable Cox regression models. Patients with low lymphocyte percentage tended to be older and had higher rates of comorbid disease (diabetes mellitus, atrial fibrillation, and renal insufficiency). Low lymphocyte counts were associated with wide QRS duration, high natriuretic peptides, and low ejection fraction, blood pressure, and serum sodium. These patients were less likely to receive evidence-based HF medications. After adjusting for 22 known clinical risk factors, a 10% decrease in lymphocytes was associated with an increased hazard of all-cause mortality (adjusted hazard ratio 1.31 [95% CI: 1.14-1.150], P<0.001) and cardiovascular mortality or HF hospitalization (adjusted hazard ratio 1.14 [95% CI: 1.04-1.25], P=0.007) in the first 100 days postdischarge. Lymphopenia during hospitalization normalizes in majority of patients in the early postdischarge period. Conclusions-Low relative lymphocyte count during hospitalization for HF is an independent predictor of poor outcomes in the early postdischarge period, beyond traditional prognostic indicators. (Circ Heart Fail. 2012;5:750-758.) C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Ambrosy, Andrew P.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Subacius, Haris P.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Dept Med, Chicago, IL 60611 USA. [Mentz, Robert J.] Duke Univ, Med Ctr, Durham, NC USA. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Swedberg, Karl] Univ Gothenburg, Gothenburg, Sweden. [Nodari, Savina] Univ Brescia, Dept Cardiol, Brescia, Italy. [Zannad, Faiez] Nancy Univ, Dept Cardiol, Nancy, France. [Konstam, Marvin A.] Tufts Med Ctr, Boston, MA USA. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Subacius, Haris/0000-0003-4061-1220; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Center for Cardiovascular Innovation (Northwestern University Feinberg School of Medicine, Chicago, IL); Otsuka Inc. (Rockville, MD) FX Haris P. Subacius conducted all final analyses for this article with funding from the Center for Cardiovascular Innovation (Northwestern University Feinberg School of Medicine, Chicago, IL). The authors had full access to the data, take responsibility for its integrity, and had complete control and authority over article preparation and the decision to publish. Otherwise, the authors have no potential conflicts of interest to disclose.; Otsuka Inc. (Rockville, MD) provided financial and material support for the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. Database management was performed by the sponsor. NR 34 TC 20 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2012 VL 5 IS 6 BP 750 EP 758 DI 10.1161/CIRCHEARTFAILURE.112.970525 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071GZ UT WOS:000313580100022 PM 23051949 ER PT J AU Lecker, SH Zavin, A Cao, PR Arena, R Allsup, K Daniels, KM Joseph, J Schulze, PC Forman, DE AF Lecker, Stewart H. Zavin, Alexandra Cao, Peirang Arena, Ross Allsup, Kelly Daniels, Karla M. Joseph, Jacob Schulze, P. Christian Forman, Daniel E. TI Expression of the Irisin Precursor FNDC5 in Skeletal Muscle Correlates With Aerobic Exercise Performance in Patients With Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; genes; physiology; biopsy ID VENTILATORY RESPONSE; SCIENTIFIC STATEMENT; OXYGEN-CONSUMPTION; VE/VCO2 SLOPE; PEAK VO2; INTOLERANCE; ASSOCIATION; METABOLISM; MECHANISMS; LIMITATION AB Background-Exercise-induced increase in peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) expression has been shown to increase the expression of the fibronectin type III domain containing 5 (FNDC5) gene and thereby its product, irisin, in mice. Given that exercise intolerance is a hallmark characteristic of heart failure (HF), and because PGC-1 alpha and irisin promote exercise benefits in animals, we hypothesized that expression of these genes relates to aerobic performance in patients with HF. Methods and Results-Systolic HF (left ventricular ejection fraction <= 40%) patients underwent cardiopulmonary exercise testing to evaluate aerobic performance. High versus low aerobic performance was assessed using oxygen consumption (peak Vo(2) [>14 versus <= 14 mL O-2.kg(-1).min(-1)]) and ventilatory efficiency (VE/Vco(2) slope [<34 versus >= 34]). Muscle biopsies of the vastus lateralis and real-time polymerase chain reaction were used to quantify muscle gene expression.. Twenty-four patients were studied. FNDC5 (5.7 +/- 3.5 versus 3.1 +/- 1.2, P< 0.05) and PGC-1 alpha (9.9 +/- 5.9 versus 4.5 +/- 1.9, P<0.01) gene expressions were greater in the high-peak Vo(2) group; correlation between FNDC5 and PGC-1 alpha was significant (r=0.56, P<0.05) only in the high-peak Vo(2) group. Similarly, FNDC5 and PGC-1 alpha gene expression was greater in the high-performance group based on lower VE/Vco(2) slopes (5.8 +/- 3.6 versus 3.3 +/- 1.4, P<0.05 and 9.7 +/- 6 versus 5.3 +/- 3.4, P<0.05); FNDC5 also correlated with PGC-1 alpha (r=0.55, P<0.05) only in the low VE/Vco(2) slope group. Conclusions-This is the first study to show that FNDC5 expression relates to functional capacity in a human HF population. Lower FNDC5 expression may underlie reduced aerobic performance in HF patients. (Circ Heart Fail. 2012;5:812-818.) C1 [Lecker, Stewart H.; Cao, Peirang] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Nephrol,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Daniels, Karla M.; Forman, Daniel E.] Harvard Univ, Div Cardiovasc Med, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Zavin, Alexandra; Allsup, Kelly; Joseph, Jacob; Forman, Daniel E.] VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Joseph, Jacob; Forman, Daniel E.] VA Boston Healthcare Syst, Div Cardiovasc Med, Boston, MA USA. [Arena, Ross] Univ New Mexico, Dept Orthopaed & Rehabil, Div Phys Therapy, Sch Med, Albuquerque, NM 87131 USA. [Arena, Ross] Univ New Mexico, Sch Med, Div Cardiol, Dept Internal Med, Albuquerque, NM 87131 USA. [Schulze, P. Christian] Columbia Univ, Med Ctr, Div Cardiol, New York, NY USA. RP Forman, DE (reprint author), Harvard Univ, Div Cardiovasc Med, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM deforman@partners.org RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 FU Veterans Affairs Merit Award [F4726R] FX This work was supported by the Veterans Affairs Merit Award (F4726R). NR 33 TC 68 Z9 78 U1 2 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2012 VL 5 IS 6 BP 812 EP 818 DI 10.1161/CIRCHEARTFAILURE.112.969543 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071GZ UT WOS:000313580100029 PM 23001918 ER PT J AU Mitchell, DM Henao, MP Finkelstein, JS Burnett-Bowie, SAM AF Mitchell, Deborah M. Henao, Maria P. Finkelstein, Joel S. Burnett-Bowie, Sherri-Ann M. TI PREVALENCE AND PREDICTORS OF VITAMIN D DEFICIENCY IN HEALTHY ADULTS SO ENDOCRINE PRACTICE LA English DT Article ID 25-HYDROXYVITAMIN D; D INSUFFICIENCY; SERUM 25-HYDROXYVITAMIN-D; HYPOVITAMINOSIS-D; US POPULATION; YOUNG-ADULTS; WHITE WOMEN; BONE; AMERICAN; CALCIUM AB Objective: Vitamin D deficiency is highly prevalent in high-risk patient populations, but the prevalence among otherwise healthy adults is less well-defined. The goal of this study was to determine the prevalence and predictors of low 25-hydroxyvitamin D [25(OH)D] levels in healthy younger adults. Methods: This was a cross-sectional study of 634 healthy volunteers aged 18-50 years performed between January, 2006 and May, 2008. We measured serum 25(OH) D and parathyroid hormone and recorded demographic variables including age, sex, race, and use of multivitamin supplements. Results: Thirty-nine percent of subjects had 25(OH)D <= 20 ng/mL and 64% had 25(OH)D <= 30 ng/mL. Predictors of lower 25(OH)D levels included male sex, black or Asian race, and lack of multivitamin use (P<0.001 for each predictor). Seasonal variation in 25(OH)D levels was present in the overall cohort but was not observed in multivitamin users. Lower 25(OH)D levels were associated with increased risk of elevated parathyroid hormone. Regression models predicted 25(OH)D levels <= 20 or <= 30 ng/mL with areas under the receiver operating characteristic curves of 0.76 and 0.80, respectively. Conclusion: Low 25(OH)D levels are prevalent in healthy adults and may confer risk of skeletal disease. Black and Asian adults are at increased risk of deficiency and multivitamin use appears partially protective. Our models predicting low 25(OH)D levels may guide decision-making regarding whom to screen for vitamin D deficiency. (Endocr Pract. 2012;18:914-923) C1 [Mitchell, Deborah M.; Henao, Maria P.; Finkelstein, Joel S.; Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. RP Mitchell, DM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM dmmitchell@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X; Mitchell, Deborah/0000-0003-0364-9107 FU National Institutes of Health [K23DK073356, R01AG030545, K24DK02759, M01RR01066]; Solvay Pharmaceuticals, Inc., Brussels, Belgium; Massachusetts General Hospital Physician-Scientist Development Award; Boston Area Diabetes and Endocrinology Research Center Grant; Claflin Distinguished Scholar Award FX This work was supported by the following grants: National Institutes of Health grants K23DK073356 (to Dr. Sherri-Ann M. Burnett-Bowie), R01AG030545 (to Dr. Joel S. Finkelstein), K24DK02759 (to Dr. Joel S. Finkelstein), and M01RR01066 (to the Harvard Clinical and Translational Science Center, Boston, Massachusetts); an investigator-initiated grant from Solvay Pharmaceuticals, Inc., Brussels, Belgium (to Dr. Joel S. Finkelstein); a Massachusetts General Hospital Physician-Scientist Development Award, a Boston Area Diabetes and Endocrinology Research Center Grant, and a Claflin Distinguished Scholar Award (to Dr. Sherri-Ann M. Burnett-Bowie). NR 42 TC 26 Z9 28 U1 1 U2 8 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 NOV-DEC PY 2012 VL 18 IS 6 BP 914 EP 923 DI 10.4158/EP12072.OR PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 069US UT WOS:000313463200014 PM 22982792 ER PT J AU Song, LG Liu, ML Ono, N Bringhurst, FR Kronenberg, HM Guo, J AF Song, Lige Liu, Minlin Ono, Noriaki Bringhurst, F. Richard Kronenberg, Henry M. Guo, Jun TI Loss of Wnt/beta-Catenin Signaling Causes Cell Fate Shift of Preosteoblasts From Osteoblasts to Adipocytes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ADIPOGENESIS; CANONICAL WNT SIGNALING; OSTEOGENESIS; beta-CATENIN ID ACTIVATED RECEPTOR-GAMMA; GLYCOGEN-SYNTHASE KINASE-3-BETA; BONE-MARROW; BETA-CATENIN; MESENCHYMAL PROGENITORS; STEM-CELLS; IN-VIVO; DIFFERENTIATION; ADIPOGENESIS; OSTEOPOROSIS AB Wnt signaling is essential for osteogenesis and also functions as an adipogenic switch, but it is not known if interrupting wnt signaling via knockout of beta-catenin from osteoblasts would cause bone marrow adiposity. Here, we determined whether postnatal deletion of beta-catenin in preosteoblasts, through conditional cre expression driven by the osterix promoter, causes bone marrow adiposity. Postnatal disruption of beta-catenin in the preosteoblasts led to extensive bone marrow adiposity and low bone mass in adult mice. In cultured bone marrow-derived cells isolated from the knockout mice, adipogenic differentiation was dramatically increased, whereas osteogenic differentiation was significantly decreased. As myoblasts, in the absence of wnt/beta-catenin signaling, can be reprogrammed into the adipocyte lineage, we sought to determine whether the increased adipogenesis we observed partly resulted from a cell-fate shift of preosteoblasts that had to express osterix (lineage-committed early osteoblasts), from the osteoblastic to the adipocyte lineage. Using lineage tracing both in vivo and in vitro we showed that the loss of beta-catenin from preosteoblasts caused a cell-fate shift of these cells from osteoblasts to adipocytes, a shift that may at least partly contribute to the bone marrow adiposity and low bone mass in the knockout mice. These novel findings indicate that wnt/beta-catenin signaling exerts control over the fate of lineage-committed early osteoblasts, with respect to their differentiation into osteoblastic versus adipocytic populations in bone, and thus offers potential insight into the origin of bone marrow adiposity. (C) 2012 American Society for Bone and Mineral Research. C1 [Guo, Jun] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Guo, J (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM jguo2@partners.org FU MGH-Department of Medicine; National Institutes of Health [PO1 DK11794] FX We thank Andrew P. McMahon (Harvard University) for generously providing osx-cre mice, Mary L Bouxsein for mu CT analysis of bone phenotype, and Jie Zhao (MGH-Core Center for Photomedicine) for expert assistance in confocal microscopy. This work was supported by the MGH-Department of Medicine (FRB and JG), and by a grant (PO1 DK11794 to HMK) from the National Institutes of Health. NR 41 TC 58 Z9 64 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2012 VL 27 IS 11 BP 2344 EP 2358 DI 10.1002/jbmr.1694 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 073FS UT WOS:000313729500016 PM 22729939 ER PT J AU Altshuler, DM Durbin, RM Abecasis, GR Bentley, DR Chakravarti, A Clark, AG Donnelly, P Eichler, EE Flicek, P Gabriel, SB Gibbs, RA Green, ED Hurles, ME Knoppers, BM Korbel, JO Lander, ES Lee, C Lehrach, H Mardis, ER Marth, GT McVean, GA Nickerson, DA Schmidt, JP Sherry, ST Wang, J Wilson, RK Gibbs, RA Dinh, H Kovar, C Lee, S Lewis, L Muzny, D Reid, J Wang, M Wang, J Fang, XD Guo, XS Jian, M Jiang, H Jin, X Li, GQ Li, JX Li, YR Li, Z Liu, X Lu, Y Ma, XD Su, Z Tai, SS Tang, MF Wang, B Wang, GB Wu, HL Wu, RH Yin, Y Zhang, WW Zhao, J Zhao, MR Zheng, XL Zhou, Y Lander, ES Altshuler, DM Gabriel, SB Gupta, N Flicek, P Clarke, L Leinonen, R Smith, RE Zheng-Bradley, X Bentley, DR Grocock, R Humphray, S James, T Kingsbury, Z Lehrach, H Sudbrak, R Albrecht, MW Amstislavskiy, VS Borodina, TA Lienhard, M Mertes, F Sultan, M Timmermann, B Yaspo, ML Sherry, ST McVean, GA Mardis, ER Wilson, RK Fulton, L Fulton, R Weinstock, GM Durbin, RM Balasubramaniam, S Burton, J Danecek, P Keane, TM Kolb-Kokocinski, A McCarthy, S Stalker, J Quail, M Schmidt, JP Davies, CJ Gollub, J Webster, T Wong, B Zhan, YP Auton, A Gibbs, RA Yu, F Bainbridge, M Challis, D Evani, US Lu, J Muzny, D Nagaswamy, U Reid, J Sabo, A Wang, Y Yu, J Wang, J Coin, LJM Fang, L Guo, XS Jin, X Li, GQ Li, QB Li, YR Li, ZY Lin, HX Liu, BH Luo, RB Qin, N Shao, HJ Wang, BQ Xie, YL Ye, C Yu, C Zhang, F Zheng, HC Zhu, HM Marth, GT Garrison, EP Kural, D Lee, WP Leong, WF Ward, AN Wu, JT Zhang, MY Lee, C Griffin, L Hsieh, CH Mills, RE Shi, XH von Grotthuss, M Zhang, CS Daly, MJ DePristo, MA Altshuler, DM Banks, E Bhatia, G Carneiro, MO del Angel, G Gabriel, SB Genovese, G Gupta, N Handsaker, RE Hartl, C Lander, ES McCarroll, SA Nemesh, JC Poplin, RE Schaffner, SF Shakir, K Yoon, SC Lihm, J Makarov, V Jin, HJ Kim, W Kim, KC Korbel, JO Rausch, T Flicek, P Beal, K Clarke, L Cunningham, F Herrero, J McLaren, WM Ritchie, GRS Smith, RE Zheng-Bradley, X Clark, AG Gottipati, S Keinan, A Rodriguez-Flores, JL Sabeti, PC Grossman, SR Tabrizi, S Tariyal, R Cooper, DN Ball, EV Stenson, PD Bentley, DR Barnes, B Bauer, M Cheetham, RK Cox, T Eberle, M Humphray, S Kahn, S Murray, L Peden, J Shaw, R Ye, K Batzer, MA Konkel, MK Walker, JA MacArthur, DG Lek, M Sudbrak, R Amstislavskiy, VS Herwig, R Shriver, MD Bustamante, CD Byrnes, JK De la Vega, FM Gravel, S Kenny, EE Kidd, JM Lacroute, P Maples, BK Moreno-Estrada, A Zakharia, F Halperin, E Baran, Y Craig, DW Christoforides, A Homer, N Izatt, T Kurdoglu, AA Sinari, SA Squire, K Sherry, ST Xiao, CL Sebat, J Bafna, V Ye, K Burchard, EG Hernandez, RD Gignoux, CR Haussler, D Katzman, SJ Kent, WJ Howie, B Ruiz-Linares, A Dermitzakis, ET Lappalainen, T Devine, SE Liu, XY Maroo, A Tallon, LJ Rosenfeld, JA Michelson, LP Abecasis, GR Kang, HM Anderson, P Angius, A Bigham, A Blackwell, T Busonero, F Cucca, F Fuchsberger, C Jones, C Jun, G Li, Y Lyons, R Maschio, A Porcu, E Reinier, F Sanna, S Schlessinger, D Sidore, C Tan, A Trost, MK Awadalla, P Hodgkinson, A Lunter, G McVean, GA Marchini, JL Myers, S Churchhouse, C Delaneau, O Gupta-Hinch, A Iqbal, Z Mathieson, I Rimmer, A Xifara, DK Oleksyk, TK Fu, YX Liu, XM Xiong, MM Jorde, L Witherspoon, D Xing, JC Eichler, EE Browning, BL Alkan, C Hajirasouliha, I Hormozdiari, F Ko, A Sudmant, PH Mardis, ER Chen, K Chinwalla, A Ding, L Dooling, D Koboldt, DC McLellan, MD Wallis, JW Wendl, MC Zhang, QY Durbin, RM Hurles, ME Tyler-Smith, C Albers, CA Ayub, Q Balasubramaniam, S Chen, Y Coffey, AJ Colonna, V Danecek, P Huang, N Jostins, L Keane, TM Li, H McCarthy, S Scally, A Stalker, J Walter, K Xue, YL Zhang, YJ Gerstein, MB Abyzov, A Balasubramanian, S Chen, JM Clarke, D Fu, Y Habegger, L Harmanci, AO Jin, MK Khurana, E Mu, XJ Sisu, C Li, YR Luo, RB Zhu, HM Lee, C Griffin, L Hsieh, CH Mills, RE Shi, XH von Grotthuss, M Zhang, CS Marth, GT Garrison, EP Kural, D Lee, WP Ward, AN Wu, JT Zhang, MY McCarroll, SA Altshuler, DM Banks, E del Angel, G Genovese, G Handsaker, RE Hartl, C Nemesh, JC Shakir, K Yoon, SC Lihm, J Makarov, V Degenhardt, J Flicek, P Clarke, L Smith, RE Zheng-Bradley, X Korbel, JO Rausch, T Stutz, AM Bentley, DR Barnes, B Cheetham, RK Eberle, M Humphray, S Kahn, S Murray, L Shaw, R Ye, K Batzer, MA Konkel, MK Walker, JA Lacroute, P Craig, DW Homer, N Church, D Xiao, CL Sebat, J Bafna, V Michaelson, JJ Ye, K Devine, SE Liu, XY Maroo, A Tallon, LJ Lunter, G McVean, GA Iqbal, Z Witherspoon, D Xing, JC Eichler, EE Alkan, C Hajirasouliha, I Hormozdiari, F Ko, A Sudmant, PH Chen, K Chinwalla, A Ding, L McLellan, MD Wallis, JW Hurles, ME Ben Blackburne Li, H Lindsay, SJ Ning, ZM Scally, A Walter, K Zhang, YJ Gerstein, MB Abyzov, A Chen, JM Clarke, D Khurana, E Mu, XJ Sisu, C Gibbs, RA Yu, FL Bainbridge, M Challis, D Evani, US Kovar, C Lewis, L Lu, J Muzny, D Nagaswamy, U Reid, J Sabo, A Yu, J Guo, XS Li, YR Wu, RH Marth, GT Garrison, EP Leong, WF Ward, AN del Angel, G DePristo, MA Gabriel, SB Gupta, N Hartl, C Poplin, RE Clark, AG Rodriguez-Flores, JL Flicek, P Clarke, L Smith, RE Zheng-Bradley, X MacArthur, DG Bustamante, CD Gravel, S Craig, DW Christoforides, A Homer, N Izatt, T Sherry, ST Xiao, CL Dermitzakis, ET Abecasis, GR Kang, HM McVean, GA Mardis, ER Dooling, D Fulton, L Fulton, R Koboldt, DC Durbin, RM Balasubramaniam, S Keane, TM McCarthy, S Stalker, J Gerstein, MB Balasubramanian, S Habegger, L Garrison, EP Gibbs, RA Bainbridge, M Muzny, D Yu, FL Yu, J del Angel, G Handsaker, RE Makarov, V Rodriguez-Flores, JL Jin, HJ Kim, W Kim, KC Flicek, P Beal, K Clarke, L Cunningham, F Herrero, J McLaren, WM Ritchie, GRS Zheng-Bradley, X Tabrizi, S MacArthur, DG Lek, M Bustamante, CD De la Vega, FM Craig, DW Kurdoglu, AA Lappalainen, T Rosenfeld, JA Michelson, LP Awadalla, P Hodgkinson, A McVean, GA Chen, K Tyler-Smith, C Chen, Y Colonna, V Frankish, A Harrow, J Xue, YL Gerstein, MB Abyzov, A Balasubramanian, S Chen, JM Clarke, D Fu, Y Harmanci, AO Jin, MK Khurana, E Mu, XJ Sisu, C Gibbs, RA Fowler, G Hale, W Kalra, D Kovar, C Muzny, D Reid, J Wang, J Guo, X Li, G Li, Y Zheng, X Altshuler, DM Flicek, P Clarke, L Barker, J Kelman, G Kulesha, E Leinonen, R McLaren, WM Radhakrishnan, R Roa, A Smirnov, D Smith, RE Streeter, I Toneva, I Vaughan, B Zheng-Bradley, X Bentley, DR Cox, T Humphray, S Kahn, S Sudbrak, R Albrecht, MW Lienhard, M Craig, DW Izatt, T Kurdoglu, AA Sherry, ST Ananiev, V Belaia, Z Beloslyudtsev, D Bouk, N Chen, C Church, D Cohen, R Cook, C Garner, J Hefferon, T Kimelman, M Liu, C Lopez, J Meric, P O'Sullivan, C Ostapchuk, Y Phan, L Ponomarov, S Schneider, V Shekhtman, E Sirotkin, K Slotta, D Xiao, CL Zhang, H Haussler, D Abecasis, GR McVean, GA Alkan, C Ko, A Dooling, D Durbin, RM Balasubramaniam, S Keane, TM McCarthy, S Stalker, J Chakravarti, A Knoppers, BM Abecasis, GR Barnes, KC Beiswanger, C Burchard, EG Bustamante, CD Cai, HY Cao, HZ Durbin, RM Gharani, N Gibbs, RA Gignoux, CR Gravel, S Henn, B Jones, D Jorde, L Kaye, JS Keinan, A Kent, A Kerasidou, A Li, YR Mathias, R McVean, GA Moreno-Estrada, A Ossorio, PN Parker, M Reich, D Rotimi, CN Royal, CD Sandoval, K Su, YY Sudbrak, R Tian, ZM Timmermann, B Tishkoff, S Toji, LH Tyler-Smith, C Via, M Wang, YH Yang, HM Yang, L Zhu, JY Bodmer, W Bedoya, G Ruiz-Linares, A Ming, CZ Yang, G You, CJ Peltonen, L Garcia-Montero, A Orfao, A Dutil, J Martinez-Cruzado, JC Oleksyk, TK Brooks, LD Felsenfeld, AL McEwen, JE Clemm, NC Duncanson, A Dunn, M Green, ED Guyer, MS Peterson, JL Abecasis, GR Auton, A Brooks, LD DePristo, MA Durbin, RM Handsaker, RE Kang, HM Marth, GT McVean, GA AF Altshuler, David M. Durbin, Richard M. Abecasis, Goncalo R. Bentley, David R. Chakravarti, Aravinda Clark, Andrew G. Donnelly, Peter Eichler, Evan E. Flicek, Paul Gabriel, Stacey B. Gibbs, Richard A. Green, Eric D. Hurles, Matthew E. Knoppers, Bartha M. Korbel, Jan O. Lander, Eric S. Lee, Charles Lehrach, Hans Mardis, Elaine R. Marth, Gabor T. McVean, Gil A. Nickerson, Deborah A. Schmidt, Jeanette P. Sherry, Stephen T. Wang, Jun Wilson, Richard K. Gibbs, Richard A. Dinh, Huyen Kovar, Christie Lee, Sandra Lewis, Lora Muzny, Donna Reid, Jeff Wang, Min Wang, Jun Fang, Xiaodong Guo, Xiaosen Jian, Min Jiang, Hui Jin, Xin Li, Guoqing Li, Jingxiang Li, Yingrui Li, Zhuo Liu, Xiao Lu, Yao Ma, Xuedi Su, Zhe Tai, Shuaishuai Tang, Meifang Wang, Bo Wang, Guangbiao Wu, Honglong Wu, Renhua Yin, Ye Zhang, Wenwei Zhao, Jiao Zhao, Meiru Zheng, Xiaole Zhou, Yan Lander, Eric S. Altshuler, David M. Gabriel, Stacey B. Gupta, Namrata Flicek, Paul Clarke, Laura Leinonen, Rasko Smith, Richard E. Zheng-Bradley, Xiangqun Bentley, David R. Grocock, Russell Humphray, Sean James, Terena Kingsbury, Zoya Lehrach, Hans Sudbrak, Ralf Albrecht, Marcus W. Amstislavskiy, Vyacheslav S. Borodina, Tatiana A. Lienhard, Matthias Mertes, Florian Sultan, Marc Timmermann, Bernd Yaspo, Marie-Laure Sherry, Stephen T. McVean, Gil A. Mardis, Elaine R. Wilson, Richard K. Fulton, Lucinda Fulton, Robert Weinstock, George M. Durbin, Richard M. Balasubramaniam, Senduran Burton, John Danecek, Petr Keane, Thomas M. Kolb-Kokocinski, Anja McCarthy, Shane Stalker, James Quail, Michael Schmidt, Jeanette P. Davies, Christopher J. Gollub, Jeremy Webster, Teresa Wong, Brant Zhan, Yiping Auton, Adam Gibbs, Richard A. Yu, Fuli Bainbridge, Matthew Challis, Danny Evani, Uday S. Lu, James Muzny, Donna Nagaswamy, Uma Reid, Jeff Sabo, Aniko Wang, Yi Yu, Jin Wang, Jun Coin, Lachlan J. M. Fang, Lin Guo, Xiaosen Jin, Xin Li, Guoqing Li, Qibin Li, Yingrui Li, Zhenyu Lin, Haoxiang Liu, Binghang Luo, Ruibang Qin, Nan Shao, Haojing Wang, Bingqiang Xie, Yinlong Ye, Chen Yu, Chang Zhang, Fan Zheng, Hancheng Zhu, Hongmei Marth, Gabor T. Garrison, Erik P. Kural, Deniz Lee, Wan-Ping Leong, Wen Fung Ward, Alistair N. Wu, Jiantao Zhang, Mengyao Lee, Charles Griffin, Lauren Hsieh, Chih-Heng Mills, Ryan E. Shi, Xinghua von Grotthuss, Marcin Zhang, Chengsheng Daly, Mark J. DePristo, Mark A. Altshuler, David M. Banks, Eric Bhatia, Gaurav Carneiro, Mauricio O. del Angel, Guillermo Gabriel, Stacey B. Genovese, Giulio Gupta, Namrata Handsaker, Robert E. Hartl, Chris Lander, Eric S. McCarroll, Steven A. Nemesh, James C. Poplin, Ryan E. Schaffner, Stephen F. Shakir, Khalid Yoon, Seungtai C. Lihm, Jayon Makarov, Vladimir Jin, Hanjun Kim, Wook Kim, Ki Cheol Korbel, Jan O. Rausch, Tobias Flicek, Paul Beal, Kathryn Clarke, Laura Cunningham, Fiona Herrero, Javier McLaren, William M. Ritchie, Graham R. S. Smith, Richard E. Zheng-Bradley, Xiangqun Clark, Andrew G. Gottipati, Srikanth Keinan, Alon Rodriguez-Flores, Juan L. Sabeti, Pardis C. Grossman, Sharon R. Tabrizi, Shervin Tariyal, Ridhi Cooper, David N. Ball, Edward V. Stenson, Peter D. Bentley, David R. Barnes, Bret Bauer, Markus Cheetham, R. Keira Cox, Tony Eberle, Michael Humphray, Sean Kahn, Scott Murray, Lisa Peden, John Shaw, Richard Ye, Kai Batzer, Mark A. Konkel, Miriam K. Walker, Jerilyn A. MacArthur, Daniel G. Lek, Monkol Sudbrak, Ralf Amstislavskiy, Vyacheslav S. Herwig, Ralf Shriver, Mark D. Bustamante, Carlos D. Byrnes, Jake K. De la Vega, Francisco M. Gravel, Simon Kenny, Eimear E. Kidd, Jeffrey M. Lacroute, Phil Maples, Brian K. Moreno-Estrada, Andres Zakharia, Fouad Halperin, Eran Baran, Yael Craig, David W. Christoforides, Alexis Homer, Nils Izatt, Tyler Kurdoglu, Ahmet A. Sinari, Shripad A. Squire, Kevin Sherry, Stephen T. Xiao, Chunlin Sebat, Jonathan Bafna, Vineet Ye, Kenny Burchard, Esteban G. Hernandez, Ryan D. Gignoux, Christopher R. Haussler, David Katzman, Sol J. Kent, W. James Howie, Bryan Ruiz-Linares, Andres Dermitzakis, Emmanouil T. Lappalainen, Tuuli Devine, Scott E. Liu, Xinyue Maroo, Ankit Tallon, Luke J. Rosenfeld, Jeffrey A. Michelson, Leslie P. Abecasis, Goncalo R. Kang, Hyun Min Anderson, Paul Angius, Andrea Bigham, Abigail Blackwell, Tom Busonero, Fabio Cucca, Francesco Fuchsberger, Christian Jones, Chris Jun, Goo Li, Yun Lyons, Robert Maschio, Andrea Porcu, Eleonora Reinier, Fred Sanna, Serena Schlessinger, David Sidore, Carlo Tan, Adrian Trost, Mary Kate Awadalla, Philip Hodgkinson, Alan Lunter, Gerton McVean, Gil A. Marchini, Jonathan L. Myers, Simon Churchhouse, Claire Delaneau, Olivier Gupta-Hinch, Anjali Iqbal, Zamin Mathieson, Iain Rimmer, Andy Xifara, Dionysia K. Oleksyk, Taras K. Fu, Yunxin Liu, Xiaoming Xiong, Momiao Jorde, Lynn Witherspoon, David Xing, Jinchuan Eichler, Evan E. Browning, Brian L. Alkan, Can Hajirasouliha, Iman Hormozdiari, Fereydoun Ko, Arthur Sudmant, Peter H. Mardis, Elaine R. Chen, Ken Chinwalla, Asif Ding, Li Dooling, David Koboldt, Daniel C. McLellan, Michael D. Wallis, John W. Wendl, Michael C. Zhang, Qunyuan Durbin, Richard M. Hurles, Matthew E. Tyler-Smith, Chris Albers, Cornelis A. Ayub, Qasim Balasubramaniam, Senduran Chen, Yuan Coffey, Alison J. Colonna, Vincenza Danecek, Petr Huang, Ni Jostins, Luke Keane, Thomas M. Li, Heng McCarthy, Shane Scally, Aylwyn Stalker, James Walter, Klaudia Xue, Yali Zhang, Yujun Gerstein, Mark B. Abyzov, Alexej Balasubramanian, Suganthi Chen, Jieming Clarke, Declan Fu, Yao Habegger, Lukas Harmanci, Arif O. Jin, Mike Khurana, Ekta Mu, Xinmeng Jasmine Sisu, Cristina Li, Yingrui Luo, Ruibang Zhu, Hongmei Lee, Charles Griffin, Lauren Hsieh, Chih-Heng Mills, Ryan E. Shi, Xinghua von Grotthuss, Marcin Zhang, Chengsheng Marth, Gabor T. Garrison, Erik P. Kural, Deniz Lee, Wan-Ping Ward, Alistair N. Wu, Jiantao Zhang, Mengyao McCarroll, Steven A. Altshuler, David M. Banks, Eric del Angel, Guillermo Genovese, Giulio Handsaker, Robert E. Hartl, Chris Nemesh, James C. Shakir, Khalid Yoon, Seungtai C. Lihm, Jayon Makarov, Vladimir Degenhardt, Jeremiah Flicek, Paul Clarke, Laura Smith, Richard E. Zheng-Bradley, Xiangqun Korbel, Jan O. Rausch, Tobias Stuetz, Adrian M. Bentley, David R. Barnes, Bret Cheetham, R. Keira Eberle, Michael Humphray, Sean Kahn, Scott Murray, Lisa Shaw, Richard Ye, Kai Batzer, Mark A. Konkel, Miriam K. Walker, Jerilyn A. Lacroute, Phil Craig, David W. Homer, Nils Church, Deanna Xiao, Chunlin Sebat, Jonathan Bafna, Vineet Michaelson, Jacob J. Ye, Kenny Devine, Scott E. Liu, Xinyue Maroo, Ankit Tallon, Luke J. Lunter, Gerton McVean, Gil A. Iqbal, Zamin Witherspoon, David Xing, Jinchuan Eichler, Evan E. Alkan, Can Hajirasouliha, Iman Hormozdiari, Fereydoun Ko, Arthur Sudmant, Peter H. Chen, Ken Chinwalla, Asif Ding, Li McLellan, Michael D. Wallis, John W. Hurles, Matthew E. Ben Blackburne Li, Heng Lindsay, Sarah J. Ning, Zemin Scally, Aylwyn Walter, Klaudia Zhang, Yujun Gerstein, Mark B. Abyzov, Alexej Chen, Jieming Clarke, Declan Khurana, Ekta Mu, Xinmeng Jasmine Sisu, Cristina Gibbs, Richard A. Yu, Fuli Bainbridge, Matthew Challis, Danny Evani, Uday S. Kovar, Christie Lewis, Lora Lu, James Muzny, Donna Nagaswamy, Uma Reid, Jeff Sabo, Aniko Yu, Jin Guo, Xiaosen Li, Yingrui Wu, Renhua Marth, Gabor T. Garrison, Erik P. Leong, Wen Fung Ward, Alistair N. del Angel, Guillermo DePristo, Mark A. Gabriel, Stacey B. Gupta, Namrata Hartl, Chris Poplin, Ryan E. Clark, Andrew G. Rodriguez-Flores, Juan L. Flicek, Paul Clarke, Laura Smith, Richard E. Zheng-Bradley, Xiangqun MacArthur, Daniel G. Bustamante, Carlos D. Gravel, Simon Craig, David W. Christoforides, Alexis Homer, Nils Izatt, Tyler Sherry, Stephen T. Xiao, Chunlin Dermitzakis, Emmanouil T. Abecasis, Goncalo R. Kang, Hyun Min McVean, Gil A. Mardis, Elaine R. Dooling, David Fulton, Lucinda Fulton, Robert Koboldt, Daniel C. Durbin, Richard M. Balasubramaniam, Senduran Keane, Thomas M. McCarthy, Shane Stalker, James Gerstein, Mark B. Balasubramanian, Suganthi Habegger, Lukas Garrison, Erik P. Gibbs, Richard A. Bainbridge, Matthew Muzny, Donna Yu, Fuli Yu, Jin del Angel, Guillermo Handsaker, Robert E. Makarov, Vladimir Rodriguez-Flores, Juan L. Jin, Hanjun Kim, Wook Kim, Ki Cheol Flicek, Paul Beal, Kathryn Clarke, Laura Cunningham, Fiona Herrero, Javier McLaren, William M. Ritchie, Graham R. S. Zheng-Bradley, Xiangqun Tabrizi, Shervin MacArthur, Daniel G. Lek, Monkol Bustamante, Carlos D. De la Vega, Francisco M. Craig, David W. Kurdoglu, Ahmet A. Lappalainen, Tuuli Rosenfeld, Jeffrey A. Michelson, Leslie P. Awadalla, Philip Hodgkinson, Alan McVean, Gil A. Chen, Ken Tyler-Smith, Chris Chen, Yuan Colonna, Vincenza Frankish, Adam Harrow, Jennifer Xue, Yali Gerstein, Mark B. Abyzov, Alexej Balasubramanian, Suganthi Chen, Jieming Clarke, Declan Fu, Yao Harmanci, Arif O. Jin, Mike Khurana, Ekta Mu, Xinmeng Jasmine Sisu, Cristina Gibbs, Richard A. Fowler, Gerald Hale, Walker Kalra, Divya Kovar, Christie Muzny, Donna Reid, Jeff Wang, Jun Guo, Xiaosen Li, Guoqing Li, Yingrui Zheng, Xiaole Altshuler, David M. Flicek, Paul Clarke, Laura Barker, Jonathan Kelman, Gavin Kulesha, Eugene Leinonen, Rasko McLaren, William M. Radhakrishnan, Rajesh Roa, Asier Smirnov, Dmitriy Smith, Richard E. Streeter, Ian Toneva, Iliana Vaughan, Brendan Zheng-Bradley, Xiangqun Bentley, David R. Cox, Tony Humphray, Sean Kahn, Scott Sudbrak, Ralf Albrecht, Marcus W. Lienhard, Matthias Craig, David W. Izatt, Tyler Kurdoglu, Ahmet A. Sherry, Stephen T. Ananiev, Victor Belaia, Zinaida Beloslyudtsev, Dimitriy Bouk, Nathan Chen, Chao Church, Deanna Cohen, Robert Cook, Charles Garner, John Hefferon, Timothy Kimelman, Mikhail Liu, Chunlei Lopez, John Meric, Peter O'Sullivan, Chris Ostapchuk, Yuri Phan, Lon Ponomarov, Sergiy Schneider, Valerie Shekhtman, Eugene Sirotkin, Karl Slotta, Douglas Xiao, Chunlin Zhang, Hua Haussler, David Abecasis, Goncalo R. McVean, Gil A. Alkan, Can Ko, Arthur Dooling, David Durbin, Richard M. Balasubramaniam, Senduran Keane, Thomas M. McCarthy, Shane Stalker, James Chakravarti, Aravinda Knoppers, Bartha M. Abecasis, Goncalo R. Barnes, Kathleen C. Beiswanger, Christine Burchard, Esteban G. Bustamante, Carlos D. Cai, Hongyu Cao, Hongzhi Durbin, Richard M. Gharani, Neda Gibbs, Richard A. Gignoux, Christopher R. Gravel, Simon Henn, Brenna Jones, Danielle Jorde, Lynn Kaye, Jane S. Keinan, Alon Kent, Alastair Kerasidou, Angeliki Li, Yingrui Mathias, Rasika McVean, Gil A. Moreno-Estrada, Andres Ossorio, Pilar N. Parker, Michael Reich, David Rotimi, Charles N. Royal, Charmaine D. Sandoval, Karla Su, Yeyang Sudbrak, Ralf Tian, Zhongming Timmermann, Bernd Tishkoff, Sarah Toji, Lorraine H. Tyler-Smith, Chris Via, Marc Wang, Yuhong Yang, Huanming Yang, Ling Zhu, Jiayong Bodmer, Walter Bedoya, Gabriel Ruiz-Linares, Andres Ming, Cai Zhi Yang, Gao You, Chu Jia Peltonen, Leena Garcia-Montero, Andres Orfao, Alberto Dutil, Julie Martinez-Cruzado, Juan C. Oleksyk, Taras K. Brooks, Lisa D. Felsenfeld, Adam L. McEwen, Jean E. Clemm, Nicholas C. Duncanson, Audrey Dunn, Michael Green, Eric D. Guyer, Mark S. Peterson, Jane L. Abecasis, Goncalo R. Auton, Adam Brooks, Lisa D. DePristo, Mark A. Durbin, Richard M. Handsaker, Robert E. Kang, Hyun Min Marth, Gabor T. McVean, Gil A. CA 1000 Genomes Project Consortium TI An integrated map of genetic variation from 1,092 human genomes SO NATURE LA English DT Article ID COPY NUMBER VARIATION; POPULATION-SCALE; WIDE ASSOCIATION; CODING VARIATION; RARE; VARIANTS; DISEASE; LOCI; DISCOVERY; HISTORY AB By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations. C1 [Donnelly, Peter; McVean, Gil A.; Lunter, Gerton; Marchini, Jonathan L.; Myers, Simon; Gupta-Hinch, Anjali; Iqbal, Zamin; Mathieson, Iain; Rimmer, Andy; Xifara, Dionysia K.; Kerasidou, Angeliki] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Donnelly, Peter; Marchini, Jonathan L.; Myers, Simon; Churchhouse, Claire; Delaneau, Olivier; Xifara, Dionysia K.; Garrison, Erik P.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Altshuler, David M.; Gabriel, Stacey B.; Gupta, Namrata; Daly, Mark J.; DePristo, Mark A.; Banks, Eric; Bhatia, Gaurav; Carneiro, Mauricio O.; del Angel, Guillermo; Genovese, Giulio; Handsaker, Robert E.; Hartl, Chris; McCarroll, Steven A.; Nemesh, James C.; Poplin, Ryan E.; Schaffner, Stephen F.; Shakir, Khalid; Sabeti, Pardis C.; Grossman, Sharon R.; Tabrizi, Shervin; Tariyal, Ridhi; Li, Heng] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Reich, David] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02142 USA. [Durbin, Richard M.; Hurles, Matthew E.; Balasubramaniam, Senduran; Burton, John; Danecek, Petr; Keane, Thomas M.; Kolb-Kokocinski, Anja; McCarthy, Shane; Stalker, James; Quail, Michael; Tyler-Smith, Chris; Ayub, Qasim; Chen, Yuan; Coffey, Alison J.; Colonna, Vincenza; Huang, Ni; Jostins, Luke; Scally, Aylwyn; Walter, Klaudia; Xue, Yali; Zhang, Yujun; Ben Blackburne; Lindsay, Sarah J.; Ning, Zemin; Frankish, Adam; Harrow, Jennifer] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Abecasis, Goncalo R.; Kang, Hyun Min; Anderson, Paul; Blackwell, Tom; Busonero, Fabio; Fuchsberger, Christian; Jun, Goo; Maschio, Andrea; Porcu, Eleonora; Sidore, Carlo; Tan, Adrian; Trost, Mary Kate] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Bentley, David R.; Grocock, Russell; Humphray, Sean; James, Terena; Kingsbury, Zoya; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; Murray, Lisa; Peden, John; Shaw, Richard] Illumina United Kingdom, Near Saffron Walden CB10 1XL, Essex, England. [Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Clark, Andrew G.; Keinan, Alon; Rodriguez-Flores, Juan L.; De la Vega, Francisco M.; Degenhardt, Jeremiah] Cornell Univ, Ctr Comparat & Populat Genom, Ithaca, NY 14850 USA. [Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA. [Flicek, Paul; Clarke, Laura; Leinonen, Rasko; Smith, Richard E.; Zheng-Bradley, Xiangqun; Beal, Kathryn; Cunningham, Fiona; Herrero, Javier; McLaren, William M.; Ritchie, Graham R. S.; Clarke, Laura; Barker, Jonathan; Kelman, Gavin; Kulesha, Eugene; Leinonen, Rasko; Radhakrishnan, Rajesh; Roa, Asier; Smirnov, Dmitriy; Streeter, Ian; Toneva, Iliana; Vaughan, Brendan] European Bioinformat Inst, Cambridge CB10 1SD, England. [Gibbs, Richard A.; Dinh, Huyen; Kovar, Christie; Lee, Sandra; Lewis, Lora; Muzny, Donna; Reid, Jeff; Wang, Min; Yu, Fuli; Bainbridge, Matthew; Challis, Danny; Evani, Uday S.; Lu, James; Nagaswamy, Uma; Sabo, Aniko; Wang, Yi; Yu, Jin; Fowler, Gerald; Hale, Walker; Kalra, Divya] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Knoppers, Bartha M.] McGill Univ, Ctr Genom & Policy, Montreal, PQ H3A 1A4, Canada. [Korbel, Jan O.; Rausch, Tobias; Stuetz, Adrian M.] European Mol Biol Lab, Genome Biol Res Unit, D-69117 Heidelberg, Germany. [Lee, Charles; Griffin, Lauren; Hsieh, Chih-Heng; Mills, Ryan E.; Shi, Xinghua; von Grotthuss, Marcin; Zhang, Chengsheng] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lehrach, Hans; Sudbrak, Ralf; Amstislavskiy, Vyacheslav S.; Lienhard, Matthias; Mertes, Florian; Sultan, Marc; Timmermann, Bernd; Yaspo, Marie-Laure; Herwig, Ralf] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. Dahlem Ctr Genome Res & Med Syst Biol, D-14195 Berlin, Germany. [Mardis, Elaine R.; Wilson, Richard K.; Fulton, Lucinda; Fulton, Robert; Weinstock, George M.; Chinwalla, Asif; Ding, Li; Dooling, David; Koboldt, Daniel C.; McLellan, Michael D.; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA. [Marth, Gabor T.; Garrison, Erik P.; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Ward, Alistair N.; Wu, Jiantao; Zhang, Mengyao; Garrison, Erik P.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Nickerson, Deborah A.; Alkan, Can; Hormozdiari, Fereydoun; Ko, Arthur; Sudmant, Peter H.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Schmidt, Jeanette P.; Davies, Christopher J.; Gollub, Jeremy; Webster, Teresa; Wong, Brant; Zhan, Yiping] Affymetrix Inc, Santa Clara, CA 95051 USA. [Sherry, Stephen T.; Xiao, Chunlin; Church, Deanna; Ananiev, Victor; Belaia, Zinaida; Beloslyudtsev, Dimitriy; Bouk, Nathan; Chen, Chao; Cohen, Robert; Cook, Charles; Garner, John; Hefferon, Timothy; Kimelman, Mikhail; Liu, Chunlei; Lopez, John; Meric, Peter; Ostapchuk, Yuri; Phan, Lon; Ponomarov, Sergiy; Schneider, Valerie; Shekhtman, Eugene; Sirotkin, Karl; Slotta, Douglas; Zhang, Hua] US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Wang, Jun; Fang, Xiaodong; Guo, Xiaosen; Jian, Min; Jiang, Hui; Jin, Xin; Li, Guoqing; Li, Jingxiang; Li, Yingrui; Li, Zhuo; Liu, Xiao; Lu, Yao; Ma, Xuedi; Su, Zhe; Tai, Shuaishuai; Tang, Meifang; Wang, Bo; Wang, Guangbiao; Wu, Honglong; Wu, Renhua; Yin, Ye; Zhang, Wenwei; Zhao, Jiao; Zhao, Meiru; Zheng, Xiaole; Zhou, Yan; Coin, Lachlan J. 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[Jin, Hanjun] Dankook Univ, Dept Nanobiomed Sci, Cheonan 330714, South Korea. [Kim, Wook; Kim, Ki Cheol] Dankook Univ, Dept Biol Sci, Cheonan 330714, South Korea. [Gottipati, Srikanth; Jones, Danielle] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. [Sabeti, Pardis C.; Grossman, Sharon R.; Tariyal, Ridhi] Harvard Univ, Ctr Syst Biol, Cambridge, MA 02138 USA. [Sabeti, Pardis C.; Grossman, Sharon R.; Tariyal, Ridhi] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Cooper, David N.; Ball, Edward V.; Stenson, Peter D.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales. [Barnes, Bret; Kahn, Scott] Illumina Inc, San Diego, CA 92122 USA. [Ye, Kai] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Mol Epidemiol Sect, NL-2333 ZA Leiden, Netherlands. [Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [MacArthur, Daniel G.; Lek, Monkol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Shriver, Mark D.] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. [Bustamante, Carlos D.; Gravel, Simon; Kenny, Eimear E.; Kidd, Jeffrey M.; Lacroute, Phil; Maples, Brian K.; Moreno-Estrada, Andres; Zakharia, Fouad; Henn, Brenna; Sandoval, Karla] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Byrnes, Jake K.] Ancestry Com, San Francisco, CA 94107 USA. [Halperin, Eran; Baran, Yael] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Tel Aviv Univ, Dept Microbiol, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. [Craig, David W.; Christoforides, Alexis; Izatt, Tyler; Kurdoglu, Ahmet A.; Sinari, Shripad A.] Translat Genom Res Inst, Phoenix, AZ 85004 USA. [Homer, Nils] Life Technol, Beverly, MA 01915 USA. [Squire, Kevin] Univ Calif Los Angeles, David Geffen Sch ofMedicine, Dept Human Genet, Los Angeles, CA 90024 USA. [Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Sebat, Jonathan] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Bafna, Vineet] Univ Calif San Diego, Dept Comp Sci, La Jolla, CA 92093 USA. [Ye, Kenny] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Burchard, Esteban G.; Hernandez, Ryan D.; Gignoux, Christopher R.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci & Med, San Francisco, CA 94158 USA. [Haussler, David; Katzman, Sol J.; Kent, W. James] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. [Howie, Bryan] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Ruiz-Linares, Andres] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England. [Dermitzakis, Emmanouil T.; Lappalainen, Tuuli] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Lappalainen, Tuuli] Univ Geneva, Inst Genet & Genom Geneva iGE3, CH-1211 Geneva, Switzerland. Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. [Devine, Scott E.; Liu, Xinyue; Maroo, Ankit; Tallon, Luke J.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Rosenfeld, Jeffrey A.; Michelson, Leslie P.; Michelson, Leslie P.] Univ Med & Dent New Jersey, IST High Performance & Res Comp, Newark, NJ 07107 USA. [Michelson, Leslie P.] Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA. [Angius, Andrea; Busonero, Fabio; Cucca, Francesco; Maschio, Andrea; Porcu, Eleonora; Sanna, Serena; Sidore, Carlo] CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy. [Bigham, Abigail] Univ Michigan, Dept Anthropol, Ann Arbor, MI 48109 USA. [Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy. [Jones, Chris; Reinier, Fred] Ctr Adv Studies Res & Dev Sardinia CRS4, AGCT Program, I-09010 Pula, Italy. [Li, Yun] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Lyons, Robert] Univ Michigan, Sequencing Core, Ann Arbor, MI 48109 USA. [Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA. [Awadalla, Philip; Hodgkinson, Alan] Univ Montreal, Ste Justine Hosp, Res Ctr, Dept Pediat, Montreal, PQ H3T 1C5, Canada. [Oleksyk, Taras K.; Martinez-Cruzado, Juan C.] Univ Puerto Rico, Dept Biol, Mayaguez, PR 00680 USA. [Fu, Yunxin; Liu, Xiaoming; Xiong, Momiao] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Jorde, Lynn; Witherspoon, David] Univ Utah, Sch Med, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. [Xing, Jinchuan] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. [Browning, Brian L.] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA. Bilkent Univ, Dept Comp Engn, TR-06800 Bilkent, Turkey. [Hajirasouliha, Iman] Simon Fraser Univ, Dept Comp Sci, Burnaby, BC V5A 1S6, Canada. [Chen, Ken] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77230 USA. [Albers, Cornelis A.] Univ Cambridge, Dept Haematol, Cambridge CB2 1TN, England. [Albers, Cornelis A.] Natl Hlth Serv Blood & Transplant, Cambridge CB2 1TN, England. Natl Res Council CNR, Inst Genet & Biophys, I-80125 Naples, Italy. [Gerstein, Mark B.; Abyzov, Alexej; Chen, Jieming; Fu, Yao; Habegger, Lukas; Harmanci, Arif O.; Mu, Xinmeng Jasmine; Sisu, Cristina] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. [Balasubramanian, Suganthi; Jin, Mike; Khurana, Ekta] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Clarke, Declan] Yale Univ, Dept Chem, New Haven, CT 06520 USA. [Michaelson, Jacob J.] Univ Calif San Diego, Beyster Ctr Genom Psychiat Dis, La Jolla, CA 92093 USA. [Rotimi, Charles N.] NHGRI, US Natl Inst Hlth, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Barnes, Kathleen C.] Johns Hopkins Univ, Sch Med, Div Allergy & Clinical Immunol, Baltimore, MD 21205 USA. [Beiswanger, Christine; Gharani, Neda; Toji, Lorraine H.] Coriell Inst Med Res, Camden, NJ 08103 USA. [Kaye, Jane S.] Univ Oxford, Ctr Hlth Law & Emerging Technol, Oxford OX3 7LF, England. [Kent, Alastair] Genet Alliance, London N1 3QP, England. [Mathias, Rasika] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Ossorio, Pilar N.] Univ Wisconsin Madison, Morgridge Inst Res, Dept Med Hist & Bioeth, Madison, WI 53706 USA. [Ossorio, Pilar N.] Univ Wisconsin, Sch Law, Madison, WI 53706 USA. [Parker, Michael] Univ Oxford, Dept Publ Hlth, Ethox Ctr, Oxford OX3 7LF, England. [Royal, Charmaine D.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. [Tishkoff, Sarah] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Via, Marc] Univ Barcelona, Dept Anim Biol, Unit Anthropol, E-08028 Barcelona, Spain. [Bodmer, Walter] Univ Oxford, John Radcliffe Hosp, Canc & Immunogenet Lab, Oxford OX3 9DS, England. [Bedoya, Gabriel] Univ Antioquia, Inst Biol, Mol Genet Lab, Medellin, Colombia. [Yang, Gao] Peking Univ, Shenzhen Hosp, Shenzhen 518036, Peoples R China. [You, Chu Jia] Chinese Acad Med Sci, Inst Med Biol, Kunming 650118, Peoples R China. [You, Chu Jia] Peking Union Med Coll, Kunming 650118, Peoples R China. [Garcia-Montero, Andres; Orfao, Alberto] Univ Salamanca, Inst Biomed Res Salamanca IBSAL, Ctr Invest Canc IBMCC CSIC USAL, Inst Biol Mol & Celular Canc, Salamanca 37007, Spain. [Garcia-Montero, Andres] Univ Salamanca, Banco Nacl ADN Carlos 3, Salamanca 37007, Spain. [Orfao, Alberto] Univ Salamanca, Cytometry Serv, Salamanca 37007, Spain. [Orfao, Alberto] Univ Salamanca, Dept Med, Salamanca 37007, Spain. [Dutil, Julie] Ponce Sch Med & Hlth Sci, Ponce, PR 00716 USA. [Duncanson, Audrey; Dunn, Michael] Wellcome Trust Res Labs, London NW1 2BE, England. RP McVean, GA (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. EM mcvean@well.ox.ac.uk RI Colonna, Vincenza/H-2021-2014; Wang, Jun/B-9503-2016; Coin, Lachlan/A-9001-2014; Mu, Xinmeng/P-2562-2016; Mills, Ryan/A-1979-2011; Shao, Haojing/C-5429-2017; Jun, Goo/F-1941-2017; chen, chao/D-2665-2014; Via, Marc/L-6511-2014; Schaffner, Stephen/D-1189-2011; Ye, Kai/B-3640-2012; Kalra, Divya/N-5453-2014; Albers, Kees/A-4170-2015; Myers, Simon/A-6792-2015; Angius, Andrea/B-8966-2015; Li, Yingrui/K-1064-2015; Angius, Andrea/P-9549-2015; Wang, Jun/C-8434-2016; Lunter, Gerton/H-4939-2016; Jun, Goo/M-5235-2016; Dermitzakis, Emmanouil/B-7687-2013; Abyzov, Alexej/M-4284-2013; Altshuler, David/A-4476-2009; Alkan, Can/D-2982-2009; Khurana, Ekta/C-4933-2013; Weinstock, George/C-6314-2013; Ning, Zemin/D-2411-2013; Li, Heng/D-9344-2011; Abecasis, Goncalo/B-7840-2010; Liu, Xiaoming/C-2743-2008; Xing, Jinchuan/A-2489-2012; Korbel, Jan/G-6470-2012; Taras, Oleksyk/J-8805-2013; Browning, Brian/A-1178-2010 OI Cooper, David N./0000-0002-8943-8484; Flicek, Paul/0000-0002-3897-7955; McLaren, William/0000-0001-6218-1116; Walter, Klaudia/0000-0003-4448-0301; McCarthy, Shane/0000-0002-2715-4187; Iqbal, Zamin/0000-0001-8466-7547; Keane, Thomas/0000-0001-7532-6898; Rausch, Tobias/0000-0001-5773-5620; Lappalainen, Tuuli/0000-0002-7746-8109; Abecasis, Goncalo/0000-0003-1509-1825; Ayub, Qasim/0000-0003-3291-0917; Ning, Zemin/0000-0003-4359-776X; Colonna, Vincenza/0000-0002-3966-0474; Herrero, Javier/0000-0001-7313-717X; Clarke, Laura/0000-0002-5989-6898; Kim, Kicheol/0000-0003-3667-9900; Sudmant, Peter/0000-0002-9573-8248; Kidd, Jeffrey/0000-0002-9631-1465; Sidore, Carlo/0000-0001-7504-7477; Rodriguez-Flores, Juan L/0000-0002-0394-8062; Wang, Jun/0000-0002-2113-5874; Yu, Jin/0000-0002-2990-6602; sanna, serena/0000-0002-3768-1749; liu, bh/0000-0002-4948-2835; Ritchie, Graham/0000-0002-6456-9736; McVean, Gil/0000-0002-5012-4162; Durbin, Richard/0000-0002-9130-1006; Zheng Bradley, Xiangqun/0000-0002-9324-2708; Fuchsberger, Christian/0000-0002-5918-8947; Sebat, Jonathan/0000-0002-9087-526X; Lindsay, Sarah/0000-0002-0965-3070; Leinonen, Rasko/0000-0002-2639-7187; Lunter, Gerton/0000-0002-3798-2058; Chen, Jieming/0000-0003-3767-9486; Abyzov, Alexej/0000-0001-5405-6729; Bodmer, Walter/0000-0001-6244-9792; Coin, Lachlan/0000-0002-4300-455X; Mu, Xinmeng/0000-0002-8079-0828; Mills, Ryan/0000-0003-3425-6998; Shao, Haojing/0000-0002-8806-197X; Jun, Goo/0000-0003-0891-0204; Streeter, Ian/0000-0003-4024-3552; Stuetz, Adrian/0000-0001-7650-3470; Angius, Andrea/0000-0001-9372-1162; Kulesha, Eugene/0000-0002-4285-6232; Radhakrishnan, Rajesh/0000-0001-7170-699X; Sisu, Cristina/0000-0001-9371-0797; Vaughan, Brendan/0000-0002-2199-1267; Via, Marc/0000-0002-9966-9921; Albers, Kees/0000-0003-4115-3727; Myers, Simon/0000-0002-2585-9626; Angius, Andrea/0000-0003-2596-6461; Wang, Jun/0000-0002-8540-8931; Jun, Goo/0000-0003-0891-0204; Altshuler, David/0000-0002-7250-4107; Alkan, Can/0000-0002-5443-0706; Weinstock, George/0000-0002-2997-4592; Li, Heng/0000-0003-4874-2874; Liu, Xiaoming/0000-0001-8285-5528; Korbel, Jan/0000-0002-2798-3794; Taras, Oleksyk/0000-0002-8148-3918; Browning, Brian/0000-0001-6454-6633 FU Wellcome Trust [WT098051, WT090532/Z/09/Z, WT085475/Z/08/Z, WT095552/Z/11/Z, WT086084/Z/08/Z, WT089250/Z/09/Z, WT085532AIA]; Medical Research Council [G0900747(91070)]; British Heart Foundation [RG/09/12/28096]; National Basic Research Program of China (973 program) [2011CB809201, 2011CB809202, 2011CB809203]; Chinese 863 program [2012AA02A201]; National Natural Science Foundation of China [30890032, 31161130357]; Shenzhen Key Laboratory of Transomics Biotechnologies [CXB201108250096A]; Shenzhen Municipal Government of China [ZYC200903240080A, ZYC201105170397A]; Guangdong Innovative Research Team Program [2009010016]; BMBF [01GS08201, 0315428A]; Max Planck Society; Swiss National Science Foundation [31003A_130342]; Swiss National Science Foundation NCCR 'Frontiers in Genetics' grant; Louis Jeantet Foundation; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/I021213/1]; German Research Foundation [KO 4037/1-1]; Netherlands Organization for Scientific Research VENI [639.021.125]; Beatriu de Pinos Program [2006BP-A 10144, 2009BP-B 00274]; Israeli Science Foundation [04514831]; Genome Quebec and the Ministry of Economic Development, Innovation and Trade [PSR-SIIRI-195]; National Institutes of Health (NIH) [UO1HG5214, RC2HG5581, RO1MH84698, R01HG4719, R01HG3698, RC2HG5552, UO1HG6513, R01HG4960, R01HG5701, U01HG5715, T32GM8283, U01HG5208, U01HG6569, R01HG2898, R01CA166661, UO1HG5209, UO1HG5725, P41HG4221, P01HG4120, U01HG5728]; BAA-NIAID-DAIT-NIHAI [2009061, T32GM7748, U54HG3079, UL1RR024131, HHSN268201100040C] FX We thank many people who contributed to this project: A. Naranjo, M. V. Parra and C. Duque for help with the collection of the Colombian samples; N. Kalin and F. Laplace for discussions; A. Schlattl and T. Zichner for assistance in managing data sets; E. Appelbaum, H. Arbery, E. Birney, S. Bumpstead, J. Camarata, J. Carey, G. Cochrane, M. DaSilva, S. Dokel, E. Drury, C. Duque, K. Gyaltsen, P. Jokinen, B. Lenz, S. Lewis, D. Lu, A. Naranjo, S. Ott, I. Padioleau, M. V. Parra, N. Patterson, A. Price, L. Sadzewicz, S. Schrinner, N. Sengamalay, J. Sullivan, F. Ta, Y. Vaydylevich, O. Venn, K. Watkins and A. Yurovsky for assistance, discussion and advice. We thank the people who generously contributed their samples, from these populations: Yoruba in Ibadan, Nigeria; the Han Chinese in Beijing, China; the Japanese in Tokyo, Japan; the Utah CEPH community; the Luhya in Webuye, Kenya; people with African ancestry in the Southwest United States; the Toscani in Italia; people with Mexican ancestry in Los Angeles, California; the Southern Han Chinese in China; the British in England and Scotland; the Finnish in Finland; the Iberian Populations in Spain; the Colombians in Medellin, Colombia; and the Puerto Ricans in Puerto Rico. This research was supported in part by Wellcome Trust grants WT098051 to R. M. D., M. E. H. and C. T. S.; WT090532/Z/09/Z, WT085475/Z/08/Z and WT095552/Z/11/Z to P. Do.; WT086084/Z/08/Z and WT090532/Z/09/Z to G. A. M.; WT089250/Z/09/Z to I. M.; WT085532AIA to P. F.; Medical Research Council grant G0900747(91070) to G. A. M.; British Heart Foundation grant RG/09/12/28096 to C. A. A.; the National Basic Research Program of China (973 program no. 2011CB809201, 2011CB809202 and 2011CB809203); the Chinese 863 program (2012AA02A201); the National Natural Science Foundation of China (30890032, 31161130357); the Shenzhen Key Laboratory of Transomics Biotechnologies (CXB201108250096A); the Shenzhen Municipal Government of China (grants ZYC200903240080A and ZYC201105170397A); Guangdong Innovative Research Team Program (no. 2009010016); BMBF grant 01GS08201 to H. Le.; BMBF grant 0315428A to R. H.; the Max Planck Society; Swiss National Science Foundation 31003A_130342 to E. T. D.; Swiss National Science Foundation NCCR 'Frontiers in Genetics' grant to E. T. D.; Louis Jeantet Foundation grant to E. T. D.; Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/I021213/1 to A. R.-L.; German Research Foundation (Emmy Noether Fellowship KO 4037/1-1) to J. O. K.; Netherlands Organization for Scientific Research VENI grant 639.021.125 to K. Y.; Beatriu de Pinos Program grants 2006BP-A 10144 and 2009BP-B 00274 to M. V.; Israeli Science Foundation grant 04514831 to E. H.; Genome Quebec and the Ministry of Economic Development, Innovation and Trade grant PSR-SIIRI-195 to P.Aw.; National Institutes of Health (NIH) grants UO1HG5214, RC2HG5581 and RO1MH84698 to G. R. A.; R01HG4719 and R01HG3698 to G. T. M; RC2HG5552 and UO1HG6513 to G. R. A. and G. T. M.; R01HG4960 and R01HG5701 to B. L. B.; U01HG5715 to C. D. B. and A. G. C.; T32GM8283 to D. Cl.; U01HG5208 to M. J. D.; U01HG6569 to M. A. D.; R01HG2898 and R01CA166661 to S. E. D.; UO1HG5209, UO1HG5725 and P41HG4221 to C. Le.; P01HG4120 to E. E. E.; U01HG5728 to Yu.F.; U54HG3273 and U01HG5211 to R.A.G.; R01HL95045 to S. B. G.; U41HG4568 to S.J.K.; P41HG2371 to W.J.K.; ES015794, AI077439, HL088133 and HL078885 to E. G. B.; RC2HL102925 to S. B. G. and D. M. A.; R01GM59290 to L.B.J. and M. A. B.; U54HG3067 to E. S. L. and S. B. G.; T15LM7033 to B. K. M.; T32HL94284 to J.L.R.-F.; ; DP2OD6514 and BAA-NIAID-DAIT-NIHAI 2009061 to P. C. S.; T32GM7748 to X. S.; U54HG3079 to R. K. W.; UL1RR024131 to R. D. H.; HHSN268201100040C to the Coriell Institute for Medical Research; a Sandler Foundation award and an American Asthma Foundation award to E. G. B.; an IBMOpen Collaborative Research Program award to Y.B.; an A.G. Leventis Foundation scholarship to D. K. X.; a Wolfson Royal Society Merit Award to P. Do.; a Howard Hughes Medical Institute International Fellowship award to P. H. S.; a grant from T. and V. Stanley to S.C.Y.; and a Mary Beryl Patch Turnbull Scholar Program award to K. C. B. E. H. is a faculty fellow of the Edmond J. Safra Bioinformatics program at Tel-Aviv University. E. E. E. and D. H. are investigators of the Howard Hughes Medical Institute. M. V. G. is a long-term fellow of EMBO. NR 47 TC 3036 Z9 3066 U1 74 U2 569 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 1 PY 2012 VL 491 IS 7422 BP 56 EP 65 DI 10.1038/nature11632 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028PM UT WOS:000310434500030 ER PT J AU Jostins, L Ripke, S Weersma, RK Duerr, RH McGovern, DP Hui, KY Lee, JC Schumm, LP Sharma, Y Anderson, CA Essers, J Mitrovic, M Ning, K Cleynen, I Theatre, E Spain, SL Raychaudhuri, S Goyette, P Wei, Z Abraham, C Achkar, JP Ahmad, T Amininejad, L Ananthakrishnan, AN Andersen, V Andrews, JM Baidoo, L Balschun, T Bampton, PA Bitton, A Boucher, G Brand, S Buning, C Cohain, A Cichon, S D'Amato, M De Jong, D Devaney, KL Dubinsky, M Edwards, C Ellinghaus, D Ferguson, LR Franchimont, D Fransen, K Gearry, R Georges, M Gieger, C Glas, J Haritunians, T Hart, A Hawkey, C Hedl, M Hu, XL Karlsen, TH Kupcinskas, L Kugathasan, S Latiano, A Laukens, D Lawrance, IC Lees, CW Louis, E Mahy, G Mansfield, J Morgan, AR Mowat, C Newman, W Palmieri, O Ponsioen, CY Potocnik, U Prescott, NJ Regueiro, M Rotter, JI Russell, RK Sanderson, JD Sans, M Satsangi, J Schreiber, S Simms, LA Sventoraityte, J Targan, SR Taylor, KD Tremelling, M Verspaget, HW De Vos, M Wijmenga, C Wilson, DC Winkelmann, J Xavier, RJ Zeissig, S Zhang, B Zhang, CK Zhao, HY Silverberg, MS Annese, V Hakonarson, H Brant, SR Radford-Smith, G Mathew, CG Rioux, JD Schadt, EE Daly, MJ Franke, A Parkes, M Vermeire, S Barrett, JC Cho, JH AF Jostins, Luke Ripke, Stephan Weersma, Rinse K. Duerr, Richard H. McGovern, Dermot P. Hui, Ken Y. Lee, James C. Schumm, L. Philip Sharma, Yashoda Anderson, Carl A. Essers, Jonah Mitrovic, Mitja Ning, Kaida Cleynen, Isabelle Theatre, Emilie Spain, Sarah L. Raychaudhuri, Soumya Goyette, Philippe Wei, Zhi Abraham, Clara Achkar, Jean-Paul Ahmad, Tariq Amininejad, Leila Ananthakrishnan, Ashwin N. Andersen, Vibeke Andrews, Jane M. Baidoo, Leonard Balschun, Tobias Bampton, Peter A. Bitton, Alain Boucher, Gabrielle Brand, Stephan Buening, Carsten Cohain, Ariella Cichon, Sven D'Amato, Mauro De Jong, Dirk Devaney, Kathy L. Dubinsky, Marla Edwards, Cathryn Ellinghaus, David Ferguson, Lynnette R. Franchimont, Denis Fransen, Karin Gearry, Richard Georges, Michel Gieger, Christian Glas, Juergen Haritunians, Talin Hart, Ailsa Hawkey, Chris Hedl, Matija Hu, Xinli Karlsen, Tom H. Kupcinskas, Limas Kugathasan, Subra Latiano, Anna Laukens, Debby Lawrance, Ian C. Lees, Charlie W. Louis, Edouard Mahy, Gillian Mansfield, John Morgan, Angharad R. Mowat, Craig Newman, William Palmieri, Orazio Ponsioen, Cyriel Y. Potocnik, Uros Prescott, Natalie J. Regueiro, Miguel Rotter, Jerome I. Russell, Richard K. Sanderson, Jeremy D. Sans, Miquel Satsangi, Jack Schreiber, Stefan Simms, Lisa A. Sventoraityte, Jurgita Targan, Stephan R. Taylor, Kent D. Tremelling, Mark Verspaget, Hein W. De Vos, Martine Wijmenga, Cisca Wilson, David C. Winkelmann, Juliane Xavier, Ramnik J. Zeissig, Sebastian Zhang, Bin Zhang, Clarence K. Zhao, Hongyu Silverberg, Mark S. Annese, Vito Hakonarson, Hakon Brant, Steven R. Radford-Smith, Graham Mathew, Christopher G. Rioux, John D. Schadt, Eric E. Daly, Mark J. Franke, Andre Parkes, Miles Vermeire, Severine Barrett, Jeffrey C. Cho, Judy H. CA Int IBD Genetics Consortium IIBDGC TI Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease SO NATURE LA English DT Article ID HYPER-IGE SYNDROME; RISK LOCI; SUSCEPTIBILITY; EXPRESSION; METAANALYSIS; TUBERCULOSIS; MUTATIONS; NETWORK; NUMBER AB Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD. C1 [Hui, Ken Y.; Cho, Judy H.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. [Jostins, Luke; Anderson, Carl A.; Barrett, Jeffrey C.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Ripke, Stephan; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Weersma, Rinse K.; De Jong, Dirk] Univ Groningen, Dept Gastroenterol & Hepatol, NL-9700 RB Groningen, Netherlands. [Mitrovic, Mitja] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Duerr, Richard H.; Baidoo, Leonard; Fransen, Karin; Regueiro, Miguel] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15261 USA. [Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [McGovern, Dermot P.; Targan, Stephan R.; Taylor, Kent D.] F Widjaja Fdn Inflammatory Bowel, Los Angeles, CA 90048 USA. [McGovern, Dermot P.; Targan, Stephan R.; Taylor, Kent D.] Immunobiol Res Inst, Los Angeles, CA 90048 USA. [McGovern, Dermot P.; Haritunians, Talin; Rotter, Jerome I.; Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Lee, James C.; Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Inflammatory Bowel Dis Res Grp, Cambridge CB2 0QQ, England. [Schumm, L. Philip] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Sharma, Yashoda; Ning, Kaida; Abraham, Clara; Hedl, Matija; Cho, Judy H.] Yale Univ, Sch Med, Dept Internal Med, Sect Digest Dis, New Haven, CT 06520 USA. [Essers, Jonah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mitrovic, Mitja; Potocnik, Uros] Univ Maribor, Fac Med, Ctr Human Mol Genet & Pharmacogen, SLO-2000 Maribor, Slovenia. [Cleynen, Isabelle; Vermeire, Severine] Katholieke Univ Leuven, Gastroenterol Sect, Dept Clin & Expt Med, B-3000 Louvain, Belgium. [Theatre, Emilie; Georges, Michel] Univ Liege, Grp Interdisciplinaire Genoprote Appl GIGA R, Unit Anim Genom, B-4000 Liege, Belgium. [Theatre, Emilie; Georges, Michel] Univ Liege, Fac Vet Med, B-4000 Liege, Belgium. [Theatre, Emilie; Louis, Edouard] Univ Liege, Ctr Hosp Univ, Div Gastroenterol, B-4000 Liege, Belgium. [Spain, Sarah L.; Prescott, Natalie J.; Mathew, Christopher G.] Kings Coll London, Dept Med & Mol Genet, Div Genet & Mol Med, Sch Med,Guys Hosp, London SE1 9RT, England. [Raychaudhuri, Soumya; Hu, Xinli] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Goyette, Philippe; Boucher, Gabrielle; Rioux, John D.] Univ Montreal, Montreal, PQ H1T 1C8, Canada. [Goyette, Philippe; Boucher, Gabrielle; Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Wei, Zhi] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA. [Achkar, Jean-Paul] Cleveland Clin, Dept Gastroenterol & Hepatol, Inst Digest Dis, Cleveland, OH 44195 USA. [Achkar, Jean-Paul] Cleveland Clin, Lerner Res Inst, Dept Pathobiol, Cleveland, OH 44195 USA. [Ahmad, Tariq] Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England. [Amininejad, Leila; Franchimont, Denis] Univ Libre Brussels, Erasmus Hosp, Dept Gastroenterol, B-1070 Brussels, Belgium. [Ananthakrishnan, Ashwin N.; Devaney, Kathy L.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Andersen, Vibeke] Viborg Reg Hosp, Dept Med, DK-8800 Viborg, Denmark. [Andrews, Jane M.] Royal Adelaide Hosp, Dept Gastroenterol & Hepatol, Inflammatory Bowel Dis Serv, Adelaide, SA 5000, Australia. [Andrews, Jane M.] Univ Adelaide, Sch Med, Adelaide, SA 5000, Australia. [Balschun, Tobias; Ellinghaus, David; Schreiber, Stefan; Franke, Andre] Univ Kiel, Inst Clin Chem, D-24105 Kiel, Germany. [Bampton, Peter A.] Flinders Med Ctr, Dept Gastroenterol & Hepatol, Adelaide, SA 5000, Australia. [Bampton, Peter A.] Flinders Univ S Australia, Sch Med, Adelaide, SA 5000, Australia. [Bitton, Alain; Glas, Juergen] McGill Univ, Ctr Hlth, Div Gastroenterol, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. [Brand, Stephan] Univ Munich, Univ Hosp Munich Grosshadern, Dept Med 2, D-80336 Munich, Germany. [Buening, Carsten] Univ Med Berlin, Charite, Dept Gastroenterol, D-10117 Berlin, Germany. [Cohain, Ariella; Zhang, Bin; Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Cichon, Sven] Univ Hosp Bonn, Life & Brain Ctr, Dept Genom, D-53012 Bonn, Germany. [D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, S-14183 Stockholm, Sweden. [Dubinsky, Marla] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA. [Edwards, Cathryn] Torbay Hosp, Dept Gastroenterol, Torquay TQ2 7AA, Devon, England. [Ferguson, Lynnette R.; Morgan, Angharad R.] Univ Auckland, Fac Med & Hlth Sci, Sch Med Sci, Auckland 1142, New Zealand. [Fransen, Karin; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen T, Netherlands. [Gearry, Richard] Univ Otago, Dept Med, Christchurch 8140, New Zealand. [Gearry, Richard] Christchurch Hosp, Dept Gastroenterol, Christchurch 8011, New Zealand. [Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany. [Hart, Ailsa] St Marks Hosp, Harrow HA1 3UJ, Middx, England. [Hawkey, Chris] QueensMed Ctr, Nottingham Digest Dis Ctr, Nottingham NG7 1AW, England. [Karlsen, Tom H.] Natl Hosp Norway, Oslo Univ Hosp, Internal Med Res Inst, N-0424 Oslo, Norway. [Kupcinskas, Limas; Sventoraityte, Jurgita] Kaunas Univ Med, Dept Gastroenterol, LT-44307 Kaunas, Lithuania. [Kugathasan, Subra] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. [Latiano, Anna; Palmieri, Orazio; Annese, Vito] Ist Ricovero & Cura Carattere Sci Casa Sollievo S, Gastroenterol Unit, I-71013 San Giovanni Rotondo, Italy. [Laukens, Debby; De Vos, Martine] Ghent Univ Hosp, Dept Gastroenterol & Hepatol, B-9000 Ghent, Belgium. [Lawrance, Ian C.] Univ Western Australia, Sch Med & Pharmacol, Fremantle, WA 6009, Australia. [Lees, Charlie W.; Satsangi, Jack] Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Mahy, Gillian] Townsville Hosp, Dept Gastroenterol, Townsville, Qld 4810, Australia. [Mansfield, John] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Mowat, Craig] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med, Dundee DD1 9SY, Scotland. [Newman, William] Univ Manchester, MAHSC, Manchester M13 9PL, Lancs, England. [Ponsioen, Cyriel Y.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands. [Potocnik, Uros] Univ Maribor, Fac Chem & Chem Engn, SLO-2000 Maribor, Slovenia. [Russell, Richard K.; Wilson, David C.] Royal Hosp Sick Children, Glasgow G3 8SJ, Lanark, Scotland. [Sanderson, Jeremy D.] Guys & St Thomas NHS Fdn Trust, St Thomas Hosp, Dept Gastroenterol, London SE1 7EH, England. [Sans, Miquel] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Dept Gastroenterol, Barcelona, Spain. [Sans, Miquel] CIBER EHD, Barcelona 08036, Spain. [Schreiber, Stefan; Zeissig, Sebastian] Univ Kiel, Dept Gen Internal Med, D-24118 Kiel, Germany. [Simms, Lisa A.; Radford-Smith, Graham] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Tremelling, Mark] Norfolk & Norwich Univ Hosp, Norwich NR4 7UY, Norfolk, England. [Verspaget, Hein W.] Leiden Univ, Med Ctr, Dept Gastroenterol, NL-2333 ZA Leiden, Netherlands. [Wilson, David C.] Univ Edinburgh, Edinburgh EH9 1UW, Midlothian, Scotland. [Winkelmann, Juliane] Tech Univ Munich, Inst Human Genet, D-80336 Munich, Germany. [Winkelmann, Juliane] Tech Univ Munich, Dept Neurol, D-80336 Munich, Germany. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Zhang, Clarence K.; Zhao, Hongyu] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06520 USA. [Silverberg, Mark S.] Univ Toronto, Mt Sinai Hosp, Ctr Inflammatory Bowel Dis, Toronto, ON M5G 1X5, Canada. [Annese, Vito] Azienda Osped Univ AOU Careggi, Unit Gastroenterol SOD2, I-50134 Florence, Italy. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Pediat Inflammatory Bowel Dis, Dept Pediat, Philadelphia, PA 19104 USA. [Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Meyerhoff Inflammatory Bowel Dis Ctr, Baltimore, MD 21205 USA. [Brant, Steven R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Radford-Smith, Graham] Royal Brisbane & Womens Hosp, Dept Gastroenterol, Brisbane, Qld 4029, Australia. [Radford-Smith, Graham] Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia. [Vermeire, Severine] Univ Hosp Leuven, Dept Gastroenterol, B-3000 Louvain, Belgium. RP Cho, JH (reprint author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. EM judy.cho@yale.edu RI Palmieri, Orazio/J-7697-2012; Croitoru, Kenneth/C-4604-2015; Latiano, Anna/R-1965-2016; Franke, Andre/B-2151-2010; Spain, Sarah/G-1968-2010; Anderson, Carl/B-8327-2013; Ellinghaus, David/G-4467-2012; Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015; Mathew, Christopher/G-3434-2015; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Schreiber, Stefan/B-6748-2008; Wijmenga, Cisca/D-2173-2009; Zeissig, Sebastian/B-6297-2012; Prescott, Natalie/F-6490-2011; Jankowski, Janusz/H-2706-2012; Blackwell, Jenefer/H-3015-2015 OI Ouwehand, Willem/0000-0002-7744-1790; Hattersley, Andrew/0000-0001-5620-473X; Andersen, Vibeke/0000-0002-0127-2863; Newman, William/0000-0002-6382-4678; Wain, Louise/0000-0003-4951-1867; D'Amato, Mauro/0000-0003-2743-5197; Lee, James/0000-0001-5711-9385; Wallace, Chris/0000-0001-9755-1703; Eyre, Stephen/0000-0002-1251-6974; Gearry, Richard/0000-0002-2298-5141; Halfvarson, Jonas/0000-0003-0122-7234; Potocnik, Uros/0000-0003-1624-9428; Henderson, Paul/0000-0003-3634-6428; Zeggini, Eleftheria/0000-0003-4238-659X; Winkelmann, Juliane/0000-0003-2667-9691; Kennedy, Nicholas/0000-0003-4368-1961; Gillman, Matthew/0000-0002-2340-6930; Plomin, Robert/0000-0002-0756-3629; Plagnol, Vincent/0000-0002-5597-9215; Gieger, Christian/0000-0001-6986-9554; Wijmenga, Cisca/0000-0002-5635-1614; Barrett, Jeffrey/0000-0002-1152-370X; Palmieri, Orazio/0000-0002-0019-7929; Croitoru, Kenneth/0000-0003-1231-0180; Latiano, Anna/0000-0003-3719-2061; Franke, Andre/0000-0003-1530-5811; Lango Allen, Hana/0000-0002-7803-8688; Burren, Oliver/0000-0002-3388-5760; Laukens, Debby/0000-0002-1984-5850; Hocking, Lynne J/0000-0002-2414-2826; Spain, Sarah/0000-0002-7591-8364; Duerr, Richard/0000-0001-6586-3905; Vermeire, Severine/0000-0001-9942-3019; Anderson, Carl/0000-0003-1719-7009; Rioux, John/0000-0001-7560-8326; Mathew, Christopher/0000-0003-4178-1838; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Schreiber, Stefan/0000-0003-2254-7771; Prescott, Natalie/0000-0002-5901-7371; Jankowski, Janusz/0000-0003-2130-9181; FU National Association for Colitis and Crohn's disease; Wellcome Trust [098051, 083948/Z/07/Z, 085475/B/08/Z, 085475/Z/08/Z]; Medical Research Council UK; Catherine McEwan Foundation; NHS Research Scotland career fellowship; Peninsula College of Medicine and Dentistry, Exeter; National Institute for Health Research, through the Comprehensive Local Research Network; Biomedical ResearchCentre; Saint Thomas' NationalHealth Service Trust; King's College London; Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine; University of Manchester; Central Manchester Foundation Trust; Medical Research Council [G0000934]; Wellcome Trust grant [068545/Z/02]; UK National Blood Service; National Institute of Diabetes, Digestive and Kidney diseases (NIDDK) IBD Genetics Consortium; National Institutes of Health (NIH) [MSTP TG T32GM07205]; USPHS [PO1DK046763]; Cedars-Sinai F. Widjaja Inflammatory Bowel and Immunobiology Research Institute Research Funds; National Center for Research Resources (NCRR) [M01-RR00425]; UCLA/Cedars-Sinai/Harbor/Drew Clinical and Translational Science Institute (CTSI) [UL1 TR000124-01]; Southern California Diabetes and Endocrinology Research Grant (DERC) [DK063491]; Helmsley Foundation; Crohn's and Colitis Foundation of America; Netherlands Organization for Scientific Research [90.700.281, 918.66.620]; Celiac Disease Consortium [BSIK03009]; German Ministry of Education and Research through the National Genome Research Network; Popgen biobank, through the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ` Inflammation at Interfaces'; DFG [FR 2821/2-1, BR 1912/6-1]; Else Kroner-Fresenius-Stiftung (Else Kroner-Exzellenzstipendium); Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition; Italian Ministry of Health [GR-2008-1144485]; Swedish Society of Medicine; Ihre Foundation; Orebro University Hospital Research Foundation; Karolinska Institutet; Swedish National Program for IBD Genetics; Swedish Organization for IBD; Swedish Medical Research Council; Royal Brisbane and Women's Hospital Foundation; National Health and Medical Research Council, Australia; European Community (5th PCRDT); NIDDK, National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation (JDRF); Helmholtz Zentrum Munchen-German Research Center for Environmental Health; German Federal Ministry of Education and Research (BMBF); State of Bavaria; [DK062431]; [DK062422]; [DK062420]; [DK062432]; [DK062423]; [DK062413]; [DK076984]; [DK084554]; [DK062429]; [DK062429-S1]; [CA141743]; [DK83756]; [AI062773]; [DK043351]; [U01 DK062418] FX We thank all the subjects who contributed samples and the physicians and nursing staff who helped with recruitment globally. UK case collections were supported by the National Association for Colitis and Crohn's disease; Wellcome Trust grant 098051 (L. J., C. A. A., J. C. B.); Medical Research Council UK; the Catherine McEwan Foundation; an NHS Research Scotland career fellowship (R. K. R.); Peninsula College of Medicine and Dentistry, Exeter; the National Institute for Health Research, through the Comprehensive Local Research Network, and through Biomedical ResearchCentreawards toGuy's& Saint Thomas' NationalHealth Service Trust, King's College London, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine and to the University of Manchester and Central Manchester Foundation Trust. The British 1958 Birth Cohort DNA collection was funded by Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02, and the UK National Blood Service controls by the Wellcome Trust. The Wellcome Trust Case Control Consortiumprojects were supported by Wellcome Trust grants 083948/Z/07/Z, 085475/B/08/Z and 085475/Z/08/Z. North American collections and data processing were supported by funds to the National Institute of Diabetes, Digestive and Kidney diseases (NIDDK) IBD Genetics Consortium, which is funded by the following grants: DK062431 (S. R. B.), DK062422 (J. H. C.), DK062420 (R. H. D.), DK062432 (J. D. R.), DK062423 (M. S. S.), DK062413 (D. P. M.), DK076984 (M. J. D.), DK084554 (M. J. D. and D. P. M.) and DK062429 (J. H. C.). Additional funds were provided by funding to J. H. C. (DK062429-S1 and Crohn's & Colitis Foundation of America, Senior Investigator Award (5-2229)) and R.H.D. (CA141743). K. Y. H. is supported by the National Institutes of Health (NIH) MSTP TG T32GM07205 training award. Cedars-Sinai is supported by USPHS grant PO1DK046763 and the Cedars-Sinai F. Widjaja Inflammatory Bowel and Immunobiology Research Institute Research Funds, National Center for Research Resources (NCRR) grant M01-RR00425, UCLA/Cedars-Sinai/Harbor/Drew Clinical and Translational Science Institute (CTSI) Grant (UL1 TR000124-01), the Southern California Diabetes and Endocrinology Research Grant (DERC) (DK063491), The Helmsley Foundation (D. P. M.) and the Crohn's and Colitis Foundation of America (D. P. M.). R. J. X. and A. N. A. are funded by DK83756, AI062773, DK043351 and the Helmsley Foundation. The Netherlands Organization for Scientific Research supported R. K. W. with a clinical fellowship grant (90.700.281) and C. W. (VICI grant 918.66.620). C. W. is also supported by the Celiac Disease Consortium (BSIK03009). This study was also supported by the German Ministry of Education and Research through the National Genome Research Network, the Popgen biobank, through the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ` Inflammation at Interfaces' and DFG grant no. FR 2821/2-1. S. B. was supported by DFG BR 1912/6-1 and the Else Kroner-Fresenius-Stiftung (Else Kroner-Exzellenzstipendium 2010_EKES.32). Italian case collections were supported by the Italian Group for IBD and the Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition and funded by the Italian Ministry of Health GR-2008-1144485. Activities in Sweden were supported by the Swedish Society of Medicine, Ihre Foundation, Orebro University Hospital Research Foundation, Karolinska Institutet, the Swedish National Program for IBD Genetics, the Swedish Organization for IBD, and the Swedish Medical Research Council. D. F. and S. V.; are senior clinical investigators for the Funds for Scientific Research (FWO/FNRS) Belgium. We acknowledge a grant from Viborg Regional Hospital, Denmark. V. Andersen was supported by SHS Aabenraa, Denmark. We acknowledge funding provided by the Royal Brisbane and Women's Hospital Foundation, National Health and Medical Research Council, Australia and by the European Community (5th PCRDT). We acknowledge the following groups that provided biological samples or data for this study: the Inflammatory Bowel in South Eastern Norway (IBSEN) study group, the Norwegian Bone Marrow Donor Registry (NMBDR), the Avon Longitudinal Study of Parents and Children, the Human Biological Data Interchange and Diabetes UK, and Banco Nacional de ADN, Salamanca. This research also uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the NIDDK, National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation (JDRF) and supported by U01 DK062418. The KORA study was initiated and financed by the Helmholtz Zentrum Munchen-German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. KORAresearch was supported within the Munich Center of Health Sciences (MC Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ. NR 30 TC 1287 Z9 1307 U1 46 U2 300 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 1 PY 2012 VL 491 IS 7422 BP 119 EP 124 DI 10.1038/nature11582 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028PM UT WOS:000310434500042 PM 23128233 ER PT J AU Leung, J Nguyen-Traxler, A Lee, EM Yip, JS Weinstock, JV Chan, WW Ngo, P Weinstein, BJ Bonis, PA AF Leung, John Nguyen-Traxler, Ann Lee, Erika M. Yip, Jason S. Weinstock, Joel V. Chan, Walter W. Ngo, Peter Weinstein, Barbara J. Bonis, Peter A. TI Assessment of fractionated exhaled nitric oxide as a biomarker for the treatment of eosinophilic esophagitis SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; CROHNS-DISEASE; SYNTHASE ACTIVITY; ATOPIC-DERMATITIS; ASTHMA; CHILDREN; ADULTS; POPULATION; EXPRESSION AB Diagnosis of eosinophilic esophagitis (EoE) and determination of response to therapy is based on histological assessment of the esophagus, which requires upper endoscopy. In children, in whom a dietary approach is commonly used, multiple endoscopies are needed, because foods are eliminated and then gradually reintroduced. Ideally, noninvasive methods could supplement or replace upper endoscopy to facilitate management. Fractionated exhaled nitric oxide (FeNO) has been proposed as a useful measure for monitoring disease activity in studies of patients with eosinophil-predominant asthma and in other atopic disorders. Thus, we should evaluate whether FeNO levels could be a useful biomarker to assess response to therapy in EoE patients. This study was designed to determine whether there is a change in FeNO levels during treatment with topical corticosteroids and whether changes correlated with clinical response. This was a prospective, multicenter study that enrolled nonasthmatic patients with established EoE. FeNO level and symptom scores were measured at baseline, biweekly during 6-week swallowed fluticasone treatment, and 4 weeks posttreatment. Twelve patients completed the trial. We found a statistically significant difference between median pre- and posttreatment FeNO levels; a change of FeNO level after 2 weeks of treatment or FeNO level at the end of treatment confidently predicted a clinical or histological response. Although our findings suggest nitric oxide possibly has a physiological role in EoE, our observations do not support a role of FeNo determination for management of EoE. (Allergy Asthma Proc 33:519-524, 2012; doi: 10.2500/aap.2012.33.3606) C1 [Leung, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02114 USA. [Nguyen-Traxler, Ann; Lee, Erika M.; Yip, Jason S.; Weinstock, Joel V.; Bonis, Peter A.] Tufts Med Ctr, Div Gastroenterol, Boston, MA USA. [Chan, Walter W.] Harvard Univ, Sch Med, Dept Med, Div Gastroenterol Hepatol & Endoscopy,Brigham & W, Boston, MA 02114 USA. [Ngo, Peter] Floating Hosp Children, Tufts Med Ctr, Div Pediat Gastroenterol, Boston, MA USA. [Weinstein, Barbara J.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. RP Leung, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Immunol & Allergy, 55 Fruit St, Boston, MA 02114 USA. EM jleung7@partners.org FU Tufts CTSI's Pilot Studies Program (i.e., Catalyst, Planning, or Methods Development); National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health [UL1 RR025752]; International Gastrointestinal Eosinophil Researchers (TIGERS) Concept Award; National Institutes of Health Ruth L. Kirschstein Institutional Research Training Grant (T32 NIH) [T32DK007542] FX Funded by Tufts CTSI's Pilot Studies Program (i.e., Catalyst, Planning, or Methods Development); the project was funded by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1 RR025752. P.A. Bonis and J. Leung are funded by The International Gastrointestinal Eosinophil Researchers (TIGERS) Concept Award. J. Leung (post-doctoral) was funded in part by National Institutes of Health Ruth L. Kirschstein Institutional Research Training Grant (T32 NIH) T32DK007542. The remaining authors have no conflicts of interest to declare pertaining to this article NR 29 TC 5 Z9 5 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD NOV-DEC PY 2012 VL 33 IS 6 BP 519 EP 524 DI 10.2500/aap.2012.33.3606 PG 6 WC Allergy SC Allergy GA 066LP UT WOS:000313222600013 PM 23394511 ER PT J AU Leung, CW Ding, EL Catalano, PJ Villamor, E Rimm, EB Willett, WC AF Leung, Cindy W. Ding, Eric L. Catalano, Paul J. Villamor, Eduardo Rimm, Eric B. Willett, Walter C. TI Dietary intake and dietary quality of low-income adults in the Supplemental Nutrition Assistance Program SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FOOD STAMP PARTICIPATION; CORONARY-HEART-DISEASE; WEIGHT-GAIN; WOMEN; RISK; OBESITY; HEALTH; MEN; EXPENDITURES; PATTERNS AB Background: The Supplemental Nutrition Assistance Program (SNAP) aims to alleviate hunger among its beneficiaries by providing benefits to purchase nutritious foods. Objective: We conducted a comprehensive dietary analysis of low-income adults and examined differences in dietary intake between SNAP participants and nonparticipants. Design: The study population comprised 3835 nonelderly adults with a household income <= 130% of the federal poverty level from the 1999-2008 NHANES. The National Cancer Institute method was used to estimate the distributions of usual intake for dietary outcomes. Relative differences in dietary intake by SNAP participation were estimated with adjustment for sociodemographic characteristics and household food security. Results: Few low-income adults consumed recommended amounts of whole grains, fruit, vegetables, fish, and nuts/seeds/legumes. Conversely, many low-income adults exceeded recommended limits for processed meats, sweets, and bakery desserts and sugar-sweetened beverages. Approximately 13-22% of low-income adults did not meet any food and nutrient guidelines; virtually no adults met all of the guidelines. Compared with nonparticipants, SNAP participants consumed 39% fewer whole grains (95% CI: -57%, -15%), 44% more 100% fruit juice (95% CI: 0%, 107%), 56% more potatoes (95% CI: 18%, 106%), 46% more red meat (95% CI: 4%, 106%), and, in women, 61% more sugar-sweetened beverages (95% CI: 3%, 152%). SNAP participants also had lower dietary quality scores than did nonparticipants, as measured by a modified Alternate Healthy Eating Index. Conclusion: Although the diets of all low-income adults need major improvement, SNAP participants in particular had lower-quality diets than did income-eligible nonparticipants. Am J Clin Nutr 2012;96:977-88. C1 [Leung, Cindy W.; Ding, Eric L.; Villamor, Eduardo; Rimm, Eric B.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Leung, Cindy W.; Rimm, Eric B.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ding, Eric L.; Rimm, Eric B.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ding, Eric L.; Rimm, Eric B.; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Villamor, Eduardo] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Leung, CW (reprint author), Univ Calif San Francisco, Sch Med, Ctr Hlth & Community, 3333 Calif St,Suite 465, San Francisco, CA 94118 USA. EM cindy-leung@post.harvard.edu OI Ding, Eric/0000-0002-5881-8097 FU NIH [5 T32 CA009001-35]; American Diabetes Association FX CWL was supported by NIH training grant 5 T32 CA009001-35. ELD was supported by a fellowship from the American Diabetes Association. NR 47 TC 55 Z9 56 U1 4 U2 75 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2012 VL 96 IS 5 BP 977 EP 988 DI 10.3945/ajcn.112.040014 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 062UX UT WOS:000312949600006 PM 23034960 ER PT J AU Aronis, KN Khan, SM Mantzoros, CS AF Aronis, Konstantinos N. Khan, Sami M. Mantzoros, Christos S. TI Effects of trans fatty acids on glucose homeostasis: a meta-analysis of randomized, placebo-controlled clinical trials SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID INSULIN SENSITIVITY; SERUM-LIPIDS; METABOLIC SYNDROME; VEGETABLE-OILS; HEART-DISEASE; STEARIC-ACID; RISK-FACTORS; HEALTHY-MEN; DIETARY-FAT; LIFE-STYLE AB Background: Although evidence from cohort studies has suggested that trans fatty acid (TFA) consumption may be associated with insulin resistance and diabetes, randomized placebo-controlled trials (RCTs) have yielded conflicting results. Objective: In a meta-analysis, we combined all available RCTs that examined the role of TFA intake on glucose homeostasis. Design: A systematic review of PubMed was performed, and a total of 7 RCTs were included in the meta-analysis. Primary outcomes were glucose and insulin concentrations. Secondary outcomes were total, LDL-, and HDL-cholesterol and triglyceride concentrations. The pooled effect size (ES) was calculated through fixed- and random-effects meta-analyses. The potential existence of publication bias was evaluated by using funnel-plot analysis. Metaregression analysis was performed to evaluate for potential dose-response relations between the ES of outcomes and TFA intake. Results: Increased TFA intake did not result in significant changes in glucose or insulin concentrations. Increased TFA intake led to a significant increase in total and LDL- cholesterol [ES (95% CI): 0.28 (0.04, 0.51) and 0.36 (0.13, 0.60), respectively] and a significant decrease in HDL-cholesterol concentrations [ES (95% CI): -0.25 (-0.48, -0.01)]. Our analysis also showed the absence of publication bias and any dose-response relations between the ES and TFA intake. Conclusions: Increased TFA intake does not result in changes in glucose, insulin, or triglyceride concentrations but leads to an increase in total and LDL- cholesterol and a decrease in HDL-cholesterol concentrations. There is no evidence to support a potential benefit of the reduction of dietary TFA intake on glucose homeostasis. Am J Clin Nutr 2012;96:1093-9. C1 [Aronis, Konstantinos N.; Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Endocrinol Sect,Dept Internal Med, Boston, MA 02215 USA. [Aronis, Konstantinos N.; Khan, Sami M.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med,Dept Internal Med, Boston, MA 02215 USA. [Aronis, Konstantinos N.] Boston Univ, Dept Internal Med, Boston Med Ctr, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med,Dept Internal Med, 330 Brookline Ave,Stoneman 816, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 FU National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants 58785, 79929, and 81913) and the Clinical Science Research and Development Service of the VA Office of Research and Development (award 1I01CX000422-01A1). NR 34 TC 17 Z9 18 U1 0 U2 12 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2012 VL 96 IS 5 BP 1093 EP 1099 DI 10.3945/ajcn.112.040576 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 062UX UT WOS:000312949600019 PM 23053553 ER PT J AU Look, AT AF Look, A. T. TI T-ALL and T-lymphoblastic lymphoma (T-LBL) the same or different diseases? SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 4th International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkins Lymphoma CY NOV 01-03, 2012 CL New York, NY C1 [Look, A. T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2012 VL 159 SU 1 SI SI MA 65 BP 36 EP 36 PG 1 WC Hematology SC Hematology GA 061ZV UT WOS:000312889800065 ER PT J AU Carrion, IV Nedjat-Haiem, F Marquez, DX AF Carrion, I. V. Nedjat-Haiem, F. Marquez, D. X. TI OLDER LATINO MEN WITH CANCER: A STUDY OF THEIR TREATMENT DECISIONS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Carrion, I. V.] Univ S Florida, Tampa, FL USA. [Nedjat-Haiem, F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Marquez, D. X.] Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 24 EP 24 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201127 ER PT J AU Bonner, L Lanto, A Bolkan, C Watson, G Campbell, DG Zivin, K Rubenstein, L AF Bonner, L. Lanto, A. Bolkan, C. Watson, G. Campbell, D. G. Zivin, K. Rubenstein, L. TI POSTTRAUMATIC STRESS DISORDER AND HELP-SEEKING FROM CLERGY AMONG VETERANS WITH DEPRESSION IN PRIMARY CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bonner, L.; Watson, G.] Vet Affairs Puget Sound, Seattle, WA USA. [Bolkan, C.] Washington State Univ, Vancouver, WA USA. [Campbell, D. G.] Univ Montana, Missoula, MT 59812 USA. [Lanto, A.; Rubenstein, L.] Vet Affairs Greater Los Angeles, Los Angeles, CA USA. [Zivin, K.] Vet Affairs Ann Arbor, Ann Arbor, MI USA. [Zivin, K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Rubenstein, L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Bonner, L.; Watson, G.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 41 EP 41 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201206 ER PT J AU Hartmann, CW Meterko, M Zhao, S Palmer, JA Berlowitz, D AF Hartmann, C. W. Meterko, M. Zhao, S. Palmer, J. A. Berlowitz, D. TI A NEW INSTRUMENT FOR ASSESSING SAFETY CLIMATE IN VA NURSING HOMES: YOU CAN'T IMPROVE WHAT YOU CAN'T MEASURE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hartmann, C. W.; Zhao, S.; Palmer, J. A.; Berlowitz, D.] Bedford VA Med Ctr, CHQOER, Bedford, MA USA. [Hartmann, C. W.; Meterko, M.; Palmer, J. A.; Berlowitz, D.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Meterko, M.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 41 EP 41 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201208 ER PT J AU Palmer, J Meterko, M Zhao, S Berlowitz, D Hartmann, CW AF Palmer, J. Meterko, M. Zhao, S. Berlowitz, D. Hartmann, C. W. TI COMFORT LEVELS WITH CULTURE CHANGE: A SURVEY OF VA NURSING HOME STAFF SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Palmer, J.; Zhao, S.; Berlowitz, D.; Hartmann, C. W.] MA VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Palmer, J.; Meterko, M.; Berlowitz, D.; Hartmann, C. W.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Meterko, M.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 42 EP 42 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201210 ER PT J AU Rivero, T Hughes, J Martin, JL Kramer, B AF Rivero, T. Hughes, J. Martin, J. L. Kramer, B. TI VETERANS HEALTH ADMINISTRATION ADULT DAY HEALTH CARE PROGRAMS: VARIATIONS AND COMMON FEATURES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rivero, T.; Hughes, J.; Martin, J. L.; Kramer, B.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, North Hills, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 42 EP 42 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201212 ER PT J AU Stripling, A Dautovich, ND Heesacker, M AF Stripling, A. Dautovich, N. D. Heesacker, M. TI AS DAYS GO BY: AN EXAMINATION OF INTRA-INDIVIDUAL VARIABILITY IN SUBJECTIVE AGING AND SELECT CORRELATES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Stripling, A.] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Dautovich, N. D.] Univ Alabama, Tuscaloosa, AL USA. [Heesacker, M.] Univ Florida, Gainesville, FL USA. RI Stripling, Ashley/D-8421-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 47 EP 47 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201234 ER PT J AU Tomko, J Lloyd, A Hennon, JG Hall, SB Husted, J Zana, K Sykes, D AF Tomko, J. Lloyd, A. Hennon, J. G. Hall, S. B. Husted, J. Zana, K. Sykes, D. TI IN-HOME CARE COORDINATION AND INTENSIVE CAREGIVER SUPPORT FOR CAREGIVERS OF VETERANS WITH DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tomko, J.; Lloyd, A.; Hennon, J. G.; Hall, S. B.; Husted, J.; Zana, K.; Sykes, D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 52 EP 52 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201255 ER PT J AU Haley, PP Allen, RS AF Haley, P. P. Allen, R. S. TI LONGITUDINAL CHANGES IN EXPECTATIONS FOR NURSING HOME USE IN THE HEALTH AND RETIREMENT STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Haley, P. P.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Haley, P. P.; Allen, R. S.] Univ Alabama, Dept Psychol, Ctr Mental Hlth & Aging, Tuscaloosa, AL 35487 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 76 EP 77 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201359 ER PT J AU Santos-Modesitt, W Yaffe, K Byers, AL Simonsick, EM Satterfield, S Cauley, JA Harris, TB Barnes, DE AF Santos-Modesitt, W. Yaffe, K. Byers, A. L. Simonsick, E. M. Satterfield, S. Cauley, J. A. Harris, T. B. Barnes, D. E. TI BRAIN-DERIVED NEUROTROPHIC FACTOR AND DEPRESSIVE SYMPTOMS IN THE HEALTH ABC STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Santos-Modesitt, W.; Yaffe, K.; Byers, A. L.; Barnes, D. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Santos-Modesitt, W.; Yaffe, K.; Byers, A. L.; Barnes, D. E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Simonsick, E. M.; Harris, T. B.] NIA, NIH, Bethesda, MD 20892 USA. [Satterfield, S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Cauley, J. A.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 97 EP 97 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201445 ER PT J AU Barnes, DE Santos-Modesitt, W Byers, AL Poelke, G Goodson, W Middleton, LE Yaffe, K AF Barnes, D. E. Santos-Modesitt, W. Byers, A. L. Poelke, G. Goodson, W. Middleton, L. E. Yaffe, K. TI THE MENTAL ACTIVITY AND EXERCISE (MAX) TRIAL SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Barnes, D. E.; Santos-Modesitt, W.; Byers, A. L.; Goodson, W.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnes, D. E.; Santos-Modesitt, W.; Byers, A. L.; Poelke, G.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Middleton, L. E.] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 101 EP 101 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201462 ER PT J AU Barnes, DE Chesney, MA Yaffe, K Flores, C Wu, E Mehling, WE AF Barnes, D. E. Chesney, M. A. Yaffe, K. Flores, C. Wu, E. Mehling, W. E. TI PREVENTING LOSS OF INDEPENDENCE THROUGH EXERCISE (PLIE) FOR OLDER ADULTS WITH DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Chesney, M. A.; Wu, E.; Mehling, W. E.] Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. [Barnes, D. E.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Flores, C.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Flores, C.] Inst Aging, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 102 EP 103 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201467 ER PT J AU Tilly, JL AF Tilly, J. L. TI OVARIAN AGING AND THE MENOPAUSE: CAN WE REWIND THE FEMALE BIOLOGICAL CLOCK THROUGH STEM CELL-BASED TECHNOLOGIES? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tilly, J. L.] Massachusetts Gen Hosp, MGH Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Tilly, J. L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 124 EP 124 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201558 ER PT J AU Roiland, R Heidrich, SM AF Roiland, R. Heidrich, S. M. TI A CROSS-TIME EXPLORATION OF INFLAMMATION, PSYCHOLOGICAL WELL - BEING AND FRAILTY IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Roiland, R.] Univ Wisconsin, Sch Nursing, Madison, WI USA. [Heidrich, S. M.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 181 EP 181 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201815 ER PT J AU Jeong, Y Igarashi, H Aldwin, CM Spiro, A AF Jeong, Y. Igarashi, H. Aldwin, C. M. Spiro, A. TI TRAJECTORIES OF HASSLES AND UPLIFTS IN RELATION TO MORTALITY: THE VA NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Jeong, Y.; Igarashi, H.; Aldwin, C. M.] Oregon State Univ, Sch Social & Behav Sci, Corvallis, OR 97331 USA. [Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, A.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 182 EP 182 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888201818 ER PT J AU Mavandadi, S Miller, B Sorkin, D Oslin, D AF Mavandadi, S. Miller, B. Sorkin, D. Oslin, D. TI THE RELATIONSHIP BETWEEN CULTURAL PREFERENCES AND CLINICAL OUTCOMES AMONG OLDER ADULTS RECEIVING MENTAL HEALTH CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mavandadi, S.; Miller, B.; Oslin, D.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Mavandadi, S.; Oslin, D.] Univ Penn, Philadelphia, PA 19104 USA. [Sorkin, D.] Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 186 EP 186 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202014 ER PT J AU Lee, L Spiro, A AF Lee, L. Spiro, A. TI PSYCHOLOGICAL PROFILES OF MEN IN THE VA NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Lee, L.; Spiro, A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Spiro, A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Lee, L.; Spiro, A.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 193 EP 193 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202046 ER PT J AU Gross, AL Johnson, JK Pa, J McLaren, DG Park, LQ Manly, JJ AF Gross, A. L. Johnson, J. K. Pa, J. McLaren, D. G. Park, L. Q. Manly, J. J. TI LONGITUDINAL CHANGE IN NEUROPSYCHOLOGICAL PERFORMANCE USING LATENT GROWTH MODELS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Gross, A. L.] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, J. K.; Pa, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McLaren, D. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Park, L. Q.] Univ Calif Davis, Davis, CA 95616 USA. [Manly, J. J.] Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 265 EP 265 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202371 ER PT J AU Johnson, MD Apesoa-Varano, E Hay, J Unutzer, J Hinton, L AF Johnson, M. D. Apesoa-Varano, E. Hay, J. Unutzer, J. Hinton, L. TI DEPRESSION TREATMENT PREFERENCES OF OLDER WHITE AND MEXICAN AMERICAN MEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Johnson, M. D.] Univ Calif Los Angeles, W Los Angeles VA, Los Angeles, CA USA. [Apesoa-Varano, E.; Hinton, L.] Univ Calif Davis, Davis, CA USA. [Hay, J.] Univ So Calif, Los Angeles, CA USA. [Unutzer, J.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 272 EP 272 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202410 ER PT J AU Barnes, DE Palmer, RM Fortinsky, RH Boscardin, J Kirby, K Mehta, K Counsell, SR Landefeld, C AF Barnes, D. E. Palmer, R. M. Fortinsky, R. H. Boscardin, J. Kirby, K. Mehta, K. Counsell, S. R. Landefeld, C. TI A TOOL TO PREDICT RECOVERY, DEPENDENCE OR DEATH IN OLDER ADULTS WHO BECOME DISABLED DURING HOSPITALIZATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Barnes, D. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnes, D. E.; Boscardin, J.; Kirby, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Palmer, R. M.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Fortinsky, R. H.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Boscardin, J.; Kirby, K.; Mehta, K.; Landefeld, C.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Mehta, K.] Stanford Univ, Stanford, CA 94305 USA. [Counsell, S. R.] Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 282 EP 282 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202460 ER PT J AU Hung, WW Morano, B Boockvar, K AF Hung, W. W. Morano, B. Boockvar, K. TI USE OF HEALTH INFORMATION TECHNOLOGY DURING CARE TRANSITIONS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hung, W. W.; Morano, B.; Boockvar, K.] James J Peters VA Med Ctr, Bronx, NY USA. [Hung, W. W.; Morano, B.; Boockvar, K.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 310 EP 310 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202605 ER PT J AU Csiszar, A Sosnowska, D Tucsek, Z Toth, P Colman, R Weindruch, R Anderson, R Ungvari, Z AF Csiszar, A. Sosnowska, D. Tucsek, Z. Toth, P. Colman, R. Weindruch, R. Anderson, R. Ungvari, Z. TI CIRCULATING FACTORS INDUCED BY CALORIC RESTRICTION IN THE NON-HUMAN PRIMATE MACACA MULATTA ACTIVATE ANGIOGENIC PROCESSES IN ENDOTHELIAL CELLS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Csiszar, A.; Sosnowska, D.; Tucsek, Z.; Toth, P.; Ungvari, Z.] Univ Oklahoma, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, Hlth Sci Ctr, Oklahoma City, OK USA. [Colman, R.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA. [Weindruch, R.; Anderson, R.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Weindruch, R.; Anderson, R.] Univ Wisconsin, Geriatr Res Educ & Clin Ctr, William S Middleton Mem Vet Hosp, Madison, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 316 EP 317 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202634 ER PT J AU Hashmi, AZ AF Hashmi, A. Z. TI FROM THE CONGO TO THE MGH: REDISCOVERING CNS AMYLOID ANGIOPATHY AS A CAUSE OF ICH IN THE SILVER GENERATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hashmi, A. Z.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 318 EP 318 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202639 ER PT J AU Mair, CA Quinones, AR AF Mair, C. A. Quinones, A. R. TI FAMILY AVAILABILITY, NATIONAL HEALTHCARE INFRASTRUCTURE, AND SUPPORT PREFERENCES FOR OLDER ADULTS WITH CHRONIC DISEASE IN EUROPE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mair, C. A.] Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, Baltimore, MD 21228 USA. [Quinones, A. R.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 322 EP 322 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202656 ER PT J AU Chiu, C Lu, F Wray, LA Beverly, EA AF Chiu, C. Lu, F. Wray, L. A. Beverly, E. A. TI HOW DOES CHANGE IN DEPRESSIVE SYMPTOMATOLOGY INFLUENCE TRAJECTORIES IN WEIGHT, COGNITIVE FUNCTION AND BEHAVIORS IN PATIENTS WITH DIABETES? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Chiu, C.; Lu, F.] Natl Cheng Kung Univ, Coll Med, Inst Gerontol, Tainan 70101, Taiwan. [Lu, F.] Natl Cheng Kung Univ, Coll Med, Dept Family Med, Tainan 70101, Taiwan. [Beverly, E. A.] Harvard Univ, Sch Med, Joslin Diabet Med Ctr, Boston, MA USA. [Wray, L. A.] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 324 EP 325 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202667 ER PT J AU Proulx, J Nath, R Igarashi, H Jeong, Y Aldwin, CM Spiro, A AF Proulx, J. Nath, R. Igarashi, H. Jeong, Y. Aldwin, C. M. Spiro, A. TI CROSS-LAGGED EXAMINATION OF TOTAL CHOLESTEROL AND DEPRESSIVE SYMPTOMS: FINDINGS FROM THE NAS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Proulx, J.; Nath, R.; Igarashi, H.; Jeong, Y.; Aldwin, C. M.] Oregon State Univ, Corvallis, OR 97331 USA. [Spiro, A.] VA Boston Hlth Care Syst, Boston, MA USA. [Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 326 EP 326 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202673 ER PT J AU Lee, L Aldwin, CM Jeong, Y Levenson, M Spiro, A AF Lee, L. Aldwin, C. M. Jeong, Y. Levenson, M. Spiro, A. TI CHOLESTEROL TRAJECTORIES AND MORTALITY: FINDINGS FROM THE NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Lee, L.; Spiro, A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Spiro, A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Lee, L.; Spiro, A.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Behav Sci Div, Boston, MA USA. [Aldwin, C. M.; Jeong, Y.; Levenson, M.] Oregon State Univ, Sch Social & Behav Hlth Sci, Corvallis, OR 97331 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 329 EP 329 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202686 ER PT J AU Shrestha, S Armento, M Zeno, D Stanley, M Wilson, NL AF Shrestha, S. Armento, M. Zeno, D. Stanley, M. Wilson, N. L. TI ENGAGING AFRICAN-AMERICAN ELDERS IN LATE-LIFE ANXIETY TREATMENT RESEARCH SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Shrestha, S.; Armento, M.; Stanley, M.; Wilson, N. L.] Baylor Coll Med, Houston, TX 77030 USA. [Shrestha, S.; Armento, M.; Zeno, D.; Stanley, M.] Michael E DeBakey Vet Affair Med Ctr, Houston, TX USA. [Stanley, M.] S Cent Mental Illness Res Educ & Clin Care, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 345 EP 345 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202753 ER PT J AU Canio, WC Connor, KI Vassar, SD Lee, ML Vickrey, BG Chodosh, J AF Canio, W. C. Connor, K. I. Vassar, S. D. Lee, M. L. Vickrey, B. G. Chodosh, J. TI THE IMPACT OF SOCIAL WORK CONSULTATION ON THE QUALITY OF DEMENTIA CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Canio, W. C.; Vassar, S. D.; Lee, M. L.; Vickrey, B. G.; Chodosh, J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Canio, W. C.; Connor, K. I.; Vassar, S. D.; Lee, M. L.; Vickrey, B. G.; Chodosh, J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Vickrey, B. G.; Chodosh, J.] RAND Hlth, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 351 EP 351 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202776 ER PT J AU Thielke, SM Kaye, J Hayes, T Mattek, NC Quinones, AR AF Thielke, S. M. Kaye, J. Hayes, T. Mattek, N. C. Quinones, A. R. TI DAILY OBSERVED WALKING SPEED AND SELF-REPORTED LOW MOOD IN COMMUNITY-DWELLING OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Thielke, S. M.] Univ Washington, Seattle, WA 98195 USA. [Thielke, S. M.] Puget Sound VA Med Ctr, Seattle, WA USA. [Kaye, J.; Hayes, T.; Mattek, N. C.; Quinones, A. R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kaye, J.] Portland VA Med Ctr, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 352 EP 352 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888202780 ER PT J AU Huang, DL Chan, KC Young, BA AF Huang, D. L. Chan, K. C. Young, B. A. TI DENTAL CARE AND DENTITION STATUS ARE ASSOCIATED WITH QUALITY OF LIFE IN OLDER VETERANS WITH DIABETES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Huang, D. L.; Young, B. A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Huang, D. L.; Chan, K. C.; Young, B. A.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 378 EP 378 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203053 ER PT J AU Mori, T Crandall, CJ Merkin, S Seeman, T Binkley, N Greendale, GA Karlamangla, AS AF Mori, T. Crandall, C. J. Merkin, S. Seeman, T. Binkley, N. Greendale, G. A. Karlamangla, A. S. TI CHILDHOOD SOCIOECONOMIC STATUS AND ADULT BONE STRENGTH: FINDINGS FROM THE MIDLIFE IN THE US STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mori, T.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Mori, T.] UCLA Fielding Sch Publ Hlth, Los Angeles, CA USA. [Crandall, C. J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. [Merkin, S.; Seeman, T.; Greendale, G. A.; Karlamangla, A. S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Binkley, N.] Univ Wisconsin, Osteoporosis Clin Ctr, Madison, WI USA. [Binkley, N.] Univ Wisconsin, Res Program, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 378 EP 378 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203054 ER PT J AU Brown, RT Steinman, M AF Brown, R. T. Steinman, M. TI CHARACTERISTICS OF US EMERGENCY DEPARTMENT VISITS BY OLDER HOMELESS ADULTS: RESULTS FROM A NATIONALLY REPRESENTATIVE SURVEY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Brown, R. T.; Steinman, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brown, R. T.; Steinman, M.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 385 EP 385 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203085 ER PT J AU Boockvar, K Hung, WW Morano, B AF Boockvar, K. Hung, W. W. Morano, B. TI A RHIO ENHANCED CARE TRANSITIONS INTERVENTION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Boockvar, K.; Hung, W. W.; Morano, B.] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 426 EP 426 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203279 ER PT J AU Kind, A Jensen, LL Barczi, S Bridges, AJ Kordahl, B Smith, MA Asthana, S AF Kind, A. Jensen, L. L. Barczi, S. Bridges, A. J. Kordahl, B. Smith, M. A. Asthana, S. TI THE VA COORDINATED-TRANSITIONAL CARE (C-TRAC) PROGRAM: A REGISTERED NURSE TELEPHONE-BASED INITIATIVE TO IMPROVE TRANSITIONS FOR HOSPITALIZED VETERANS WITH DEMENTIA AND OTHER HIGH-RISK CONDITIONS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kind, A.; Barczi, S.; Asthana, S.] Univ Wisconsin, Dept Med, Div Geriatr, Sch Med & Publ Hlth, Madison, WI USA. [Kind, A.; Barczi, S.; Asthana, S.] US Dept Vet Affairs, GRECC, William S Middleton Hosp, Madison, WI USA. [Smith, M. A.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. [Smith, M. A.] Univ Wisconsin, Dept Family Med, Sch Med & Publ Hlth, Madison, WI USA. [Smith, M. A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 426 EP 426 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203278 ER PT J AU Carrion, IV Nedjat-Haiem, F AF Carrion, I. V. Nedjat-Haiem, F. TI CONDUCTING A QUALITATIVE STUDY WITH OLDER LATINO MEN WITH CANCER SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Carrion, I. V.] Univ S Florida, Tampa, FL USA. [Nedjat-Haiem, F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 439 EP 440 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203346 ER PT J AU Byers, AL Neylan, TC Covinsky, K Yaffe, K AF Byers, A. L. Neylan, T. C. Covinsky, K. Yaffe, K. TI CHRONICITY OF PTSD AND RISK OF DISABILITY IN OLDER AMERICANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Byers, A. L.; Neylan, T. C.; Covinsky, K.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Byers, A. L.; Neylan, T. C.; Covinsky, K.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 476 EP 476 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203527 ER PT J AU Nocera, J Yaffe, K Simonsick, EM Williamson, J Newman, AB Caserotti, P Harris, T Shorr, RI AF Nocera, J. Yaffe, K. Simonsick, E. M. Williamson, J. Newman, A. B. Caserotti, P. Harris, T. Shorr, R. I. TI EVALUATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND PHYSICAL FUNCTION IN OLDER ADULTS FROM THE HEALTH ABC STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Nocera, J.; Shorr, R. I.] US Dept Vet Affairs, Gainesville, FL USA. [Nocera, J.; Shorr, R. I.] Univ Florida, Gainesville, FL USA. [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Simonsick, E. M.; Harris, T.] NIH, Bethesda, MD 20892 USA. [Williamson, J.] Wake Forest Baptist Med Ctr, Winston Salem, NC USA. [Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Caserotti, P.] Univ So Denmark, Odense, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 508 EP 508 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203688 ER PT J AU Edes, T AF Edes, T. TI HOME BASED PRIMARY CARE: FROM VA EXPERIENCE TO EMERGENCE IN MEDICARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Edes, T.] US Dept Vet Affairs, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 509 EP 509 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203693 ER PT J AU Karel, MJ Karlin, B AF Karel, M. J. Karlin, B. TI THE VA HBPC MENTAL HEALTH INITIATIVE: PROGRAM IMPLEMENTATION AND PRELIMINARY OUTCOMES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Karel, M. J.; Karlin, B.] VA Cent Off, Off Mental Hlth Serv, Washington, DC USA. [Karel, M. J.] VA Boston Healthcare Syst, Mental Hlth, Brockton, MA USA. [Karel, M. J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 509 EP 509 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203691 ER PT J AU Ramsey, JL Neupert, SD Mroczek, D Spiro, A AF Ramsey, J. L. Neupert, S. D. Mroczek, D. Spiro, A. TI DAILY CO-OCCURRENCE OF AFFECT AND STRESS RESIDUE IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ramsey, J. L.; Neupert, S. D.] N Carolina State Univ, Raleigh, NC 27695 USA. [Mroczek, D.] Purdue Univ, W Lafayette, IN 47907 USA. [Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 524 EP 524 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203761 ER PT J AU Mulligan, EA Jahn, AL Naik, AD Gosian, J June, A Herman, L Moye, J AF Mulligan, E. A. Jahn, A. L. Naik, A. D. Gosian, J. June, A. Herman, L. Moye, J. TI SUCCESSFUL NAVIGATION OF PREVIOUS LIFE EXPERIENCES MAY MITIGATE CANCER DISTRESS IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mulligan, E. A.; Jahn, A. L.; Gosian, J.; June, A.; Moye, J.] VA Boston Healthcare Syst, Brockton, MA USA. [Mulligan, E. A.; Jahn, A. L.; June, A.; Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. [Naik, A. D.; Herman, L.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Naik, A. D.; Herman, L.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 529 EP 529 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203783 ER PT J AU June, A Moye, J Mulligan, EA Jahn, AL Gosian, J Herman, L Naik, AD AF June, A. Moye, J. Mulligan, E. A. Jahn, A. L. Gosian, J. Herman, L. Naik, A. D. TI PROVIDING SUPPORTIVE CARE ACROSS THE CANCER CONTINUUM SO GERONTOLOGIST LA English DT Meeting Abstract C1 [June, A.; Moye, J.; Mulligan, E. A.; Jahn, A. L.; Gosian, J.] VA Boston Healthcare Syst, Brockton, MA USA. [Herman, L.; Naik, A. D.] Baylor Coll Med, Houston, TX 77030 USA. [Herman, L.; Naik, A. D.] Michael E DeBakey Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 530 EP 530 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203786 ER PT J AU King, BJ Mahoney, JE Pecanac, KE Yoon, J Brown, RL AF King, B. J. Mahoney, J. E. Pecanac, K. E. Yoon, J. Brown, R. L. TI FREQUENCY AND DURATION OF NURSE-ASSISTED OLDER PATIENT AMBULATION IN A HOSPITAL SETTING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [King, B. J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Mahoney, J. E.; Pecanac, K. E.; Yoon, J.; Brown, R. L.] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 569 EP 569 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204096 ER PT J AU Espinoza, SE Hazuda, HP AF Espinoza, S. E. Hazuda, H. P. TI NUMBER OF FRAILTY CHARACTERISTICS IS ASSOCIATED WITH HOSPITALIZATION IN OLDER MEXICAN AMERICANS AND EUROPEAN AMERICANS INDEPENDENTLY OF SOCIODEMOGRAPHIC FACTORS AND DISEASE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Espinoza, S. E.; Hazuda, H. P.] UT Hlth Sci Ctr, San Antonio, TX USA. [Espinoza, S. E.; Hazuda, H. P.] S Texas Vet Healthcare Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 570 EP 570 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204101 ER PT J AU Pecanac, KE King, B Yoon, J Brown, RL Schiefelbein, T Bowers, B AF Pecanac, K. E. King, B. Yoon, J. Brown, R. L. Schiefelbein, T. Bowers, B. TI USE OF HAND HELD COMPUTERS TO DOCUMENT PHASES OF AMBULATION OF OLDER ADULTS IN A HOSPITAL SETTING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Pecanac, K. E.; Yoon, J.; Brown, R. L.; Schiefelbein, T.; Bowers, B.] Univ Wisconsin, Madison, WI USA. [King, B.] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 571 EP 571 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204105 ER PT J AU Yoon, J King, BJ Pecanac, KE Bowers, B Brown, RL Schiefelbein, T AF Yoon, J. King, B. J. Pecanac, K. E. Bowers, B. Brown, R. L. Schiefelbein, T. TI A COMPARISON OF TIME-AND-MOTION OBSERVATION AND SELF-REPORT OF NURSE ASSISTED OLDER PATIENT AMBULATION IN HOSPITAL SETTINGS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Yoon, J.; Pecanac, K. E.; Bowers, B.; Brown, R. L.; Schiefelbein, T.] Univ Wisconsin, Sch Nursing, Madison, WI USA. [King, B. J.] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 571 EP 571 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204104 ER PT J AU Engle, RL Sullivan, JL Tyler, D Parker, V Lukas, CV AF Engle, R. L. Sullivan, J. L. Tyler, D. Parker, V. Lukas, C. VanDeusen TI TRAINING AND COACHING TO PROMOTE HIGH PERFORMANCE IN VA NURSING HOME CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Engle, R. L.; Sullivan, J. L.; Tyler, D.; Parker, V.; Lukas, C. VanDeusen] VA Boston Healthcare Syst, Boston, MA USA. [Sullivan, J. L.; Parker, V.; Lukas, C. VanDeusen] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Tyler, D.] Brown Univ, Ctr Gerontol & Hlth Care Res, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 576 EP 576 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204127 ER PT J AU Damron-Rodriguez, J Frank, J Fassbinder, J Kramer, B AF Damron-Rodriguez, J. Frank, J. Fassbinder, J. Kramer, B. TI COMPETENCY-BASED POST-GRADUATE EDUCATION: MEASUREMENT DEVELOPMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Frank, J.; Fassbinder, J.; Kramer, B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Damron-Rodriguez, J.] Univ Calif Los Angeles, Luskin Sch Publ Affairs, Los Angeles, CA USA. [Fassbinder, J.] Calif Council Gerontol & Geriatr, Los Angeles, CA USA. [Kramer, B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 605 EP 606 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204248 ER PT J AU Quinn, LS Wolden-Hanson, T AF Quinn, L. S. Wolden-Hanson, T. TI ROLE OF INTERLEUKIN-15 IN EXERCISE ENDURANCE, ENERGY METABOLISM, AND BODY COMPOSITION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Quinn, L. S.; Wolden-Hanson, T.] VA Puget Sound Hlth Care Syst, GRECC S182, Seattle, WA USA. [Quinn, L. S.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 608 EP 608 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204261 ER PT J AU Mintzer, J Rosenberg, P Drye, L Scherer, R Herrmann, N Lanctot, K AF Mintzer, J. Rosenberg, P. Drye, L. Scherer, R. Herrmann, N. Lanctot, K. TI APATHY IN DEMENTIA METHYLPHENIDATE TRIAL (ADMET)- PRELIMINARY EFFICACY REPORT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mintzer, J.] Med Univ S Carolina, Alzheimers Res Program, N Charleston, SC USA. [Mintzer, J.] Med Univ S Carolina, Alzheimers Clin Program, N Charleston, SC USA. [Mintzer, J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Herrmann, N.; Lanctot, K.] Univ Toronto, Toronto, ON, Canada. [Herrmann, N.; Lanctot, K.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Rosenberg, P.; Drye, L.; Scherer, R.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 625 EP 625 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204343 ER PT J AU Hughes, J Jouldjian, S Alessi, C Washginton, DL Martin, JL AF Hughes, J. Jouldjian, S. Alessi, C. Washginton, D. L. Martin, J. L. TI SLEEP PROBLEMS AND PROBABLE PTSD AMONGST OLDER FEMALE VETERANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hughes, J.; Jouldjian, S.; Alessi, C.; Martin, J. L.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, North Hills, CA USA. [Alessi, C.; Washginton, D. L.; Martin, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 645 EP 646 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204441 ER PT J AU Settersten, RA Day, J Waldinger, RJ Elder, GH AF Settersten, R. A. Day, J. Waldinger, R. J. Elder, G. H. TI THE LEGACIES OF MILITARY SERVICE IN WORLD WAR II ON MEN'S HEALTH AND WELLBEING IN LATE LIFE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Settersten, R. A.; Day, J.] Oregon State Univ, Corvallis, OR 97331 USA. [Waldinger, R. J.] Univ N Carolina, Chapel Hill, NC USA. [Elder, G. H.] Harvard Univ, Boston, MA 02115 USA. [Elder, G. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 645 EP 645 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204440 ER PT J AU Vuckovic, NH Edes, T Nichols, LO AF Vuckovic, N. H. Edes, T. Nichols, L. O. TI PATIENT EXPERIENCES OF INTERDISCIPLINARY SYMPTOM MANAGEMENT IN VA HOME BASED PRIMARY CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Vuckovic, N. H.] Intel Corp, Beaverton, OR USA. [Edes, T.] US Dept Vet Affairs, Washington, DC USA. [Nichols, L. O.] Vet Affairs Med Ctr, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 655 EP 655 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204490 ER PT J AU Park, M Huang, DL AF Park, M. Huang, D. L. TI FINANCIAL SUPPORT AND DEPRESSION OUTCOMES AMONG OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Park, M.] Univ Washington, Seattle, WA 98195 USA. [Huang, D. L.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 659 EP 659 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204509 ER PT J AU Allison, TA AF Allison, T. A. TI HOW ELDERS CREATE MEANING THROUGH SONG AND SELF-PRESENTATION IN A NURSING HOME SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Allison, T. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Allison, T. A.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 668 EP 668 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204550 ER PT J AU Puterman, E Epel, E Lin, J Blackburn, E Gross, J Whooley, M Cohen, B AF Puterman, E. Epel, E. Lin, J. Blackburn, E. Gross, J. Whooley, M. Cohen, B. TI A MULTISYSTEM PROTECTIVE PROFILE MODERATES THE DEPRESSION - LEUKOCYTE TELOMERE LENGTH ASSOCIATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Puterman, E.; Epel, E.; Lin, J.; Blackburn, E.; Whooley, M.; Cohen, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Whooley, M.; Cohen, B.] San Francisco VA Med Ctr, San Francisco, CA USA. [Gross, J.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 670 EP 670 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204565 ER PT J AU Howe, JL Griffith, JL AF Howe, J. L. Griffith, J. L. TI RURAL INTERDISCIPLINARY TEAM TRAINING FOR RURAL HEALTHCARE PROVIDERS: ENHANCING TEAM SKILLS TO IMPROVE CARE FOR OLDER VETERANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Howe, J. L.; Griffith, J. L.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Howe, J. L.; Griffith, J. L.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 680 EP 680 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204617 ER PT J AU Chernoff, R Howe, JL AF Chernoff, R. Howe, J. L. TI WEBINARS: A NEW APPROACH TO PROFESSIONAL EDUCATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Chernoff, R.] Cent Arkansas Vet Healthcare Syst, GRECC, Little Rock, AR USA. [Howe, J. L.] VISN 3 GRECC Mt Sinai Sch Med, James J Peters VAMC, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 681 EP 681 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204618 ER PT J AU Stephens, C Sackett, N Schopfer, DW Schmajuk, G Moy, N Pierce, R Wallhagen, MI Lee, S AF Stephens, C. Sackett, N. Schopfer, D. W. Schmajuk, G. Moy, N. Pierce, R. Wallhagen, M. I. Lee, S. TI PATIENT AND PROVIDER PERSPECTIVES OF THE UNIQUE TRANSITIONAL CARE NEEDS OF REHOSPITALIZED VETERANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Stephens, C.; Schopfer, D. W.; Schmajuk, G.; Moy, N.; Pierce, R.; Lee, S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Stephens, C.; Sackett, N.; Schmajuk, G.; Pierce, R.; Wallhagen, M. I.; Lee, S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 683 EP 684 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204633 ER PT J AU Bean, JF Latham, N Ni, P Holt, NE Percac-Lima, S Leveille, SG Jette, A AF Bean, J. F. Latham, N. Ni, P. Holt, N. E. Percac-Lima, S. Leveille, S. G. Jette, A. TI WHICH REHABILITATIVE IMPAIRMENTS ARE ASSOCIATED WITH FUNCTIONAL STATUS AMONG OLDER PRIMARY CARE PATIENTS? RESULTS FROM THE BOSTON REHABILITATIVE IMPAIRMENT STUDY OF THE ELDERLY (BOSTON RISE) SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bean, J. F.; Holt, N. E.] Spaulding Rehabil Hosp, Boston, MA USA. [Bean, J. F.] Harvard Univ, Sch Med, Boston, MA USA. [Latham, N.; Ni, P.; Jette, A.] Boston Univ, Boston, MA 02215 USA. [Percac-Lima, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leveille, S. G.] Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 686 EP 686 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204644 ER PT J AU Jacobson, KK AF Jacobson, K. K. TI WORKING TOGETHER IN A SKILLED NURSING FACILITY? THE IMPORTANCE OF A SPECIALIZED INTERDISCIPLINARY TEAM APPROACH WHEN CARING FOR RESIDENTS WHO ARE BEHAVIORALLY CHALLENGING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Jacobson, K. K.] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Jacobson, K. K.] John F Kennedy Univ, Pleasant Hill, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 696 EP 696 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204694 ER PT J AU Stripling, A AF Stripling, A. TI QUALITY OF LIFE IN A SKILLED NURSING FACILITY? IMPLEMENTING AND SUSTAINING A NON-PHARMACOLOGICAL INTERVENTION FOR RESIDENTS WHO ARE BEHAVIORALLY CHALLENGING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Stripling, A.] San Francisco VA Med Ctr, Dept Geropsychiat, San Francisco, CA USA. RI Stripling, Ashley/D-8421-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 696 EP 696 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204693 ER PT J AU Sutherland, ES AF Sutherland, E. S. TI RAISING THE GAF WITH THE SOCIAL FOCUS COHORT: AN INNOVATIVE CLINICAL PRACTICE TO IMPROVE THE OVERALL QUALITY OF LIFE FOR RESIDENTS IN LONG-TERM CARE WHO ARE BEHAVIORALLY CHALLENGING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sutherland, E. S.] San Francisco VA Med Ctr, Dept Geropsychiat, San Francisco, CA USA. [Sutherland, E. S.] UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 696 EP 696 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204691 ER PT J AU Sutherland, ES AF Sutherland, E. S. TI BEHAVIORAL ISSUES IN A SKILLED NURSING FACILITY? DEVELOPING AND IMPLEMENTING AN INNOVATIVE CLINICAL PROGRAM FOR RESIDENTS WHO ARE BEHAVIORALLY CHALLENGING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sutherland, E. S.] San Francisco VA Med Ctr, Dept Geropsychiat, San Francisco, CA USA. [Sutherland, E. S.] UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 696 EP 696 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204692 ER PT J AU Davison, EH Kaiser, AP Wang, J Stellman, JM AF Davison, E. H. Kaiser, A. Pless Wang, J. Stellman, J. M. TI PSYCHOLOGICAL OUTCOMES AMONG OLDER WOMEN LINKED TO STRESSFUL AND POSITIVE NURSING EXPERIENCES IN VIETNAM SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Davison, E. H.; Wang, J.] VA Boston, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Kaiser, A. Pless] VA Boston, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Davison, E. H.; Kaiser, A. Pless] Boston Univ, Sch Med, Boston, MA 02118 USA. [Stellman, J. M.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Stellman, J. M.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 697 EP 697 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204698 ER PT J AU Cigolle, C Quinones, AR Bennett, JM Blaum, C Liang, J AF Cigolle, C. Quinones, A. R. Bennett, J. M. Blaum, C. Liang, J. TI ARE RESPONDENTS IN PANEL SURVEYS CONSISTENT IN THEIR SELF-REPORT OF CHRONIC DISEASES? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Cigolle, C.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. [Cigolle, C.; Blaum, C.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Cigolle, C.; Blaum, C.] VA Ann Arbor Geriatr Res Educ & Clin Ctr GRECC, Ann Arbor, MI USA. [Quinones, A. R.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Quinones, A. R.] Portland VA Med Ctr, Portland, OR USA. [Bennett, J. M.; Liang, J.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 704 EP 704 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204732 ER PT J AU Dodge, HH Bowman, G Katsumata, Y Ohya, Y Yasura, S Kaye, J Todoriki, H AF Dodge, H. H. Bowman, G. Katsumata, Y. Ohya, Y. Yasura, S. Kaye, J. Todoriki, H. TI THE ASSOCIATION BETWEEN SERUM OMEGA-3 FATTY ACIDS AND COGNITIVE FUNCTIONS AMONG THE OLDEST OLD IN OKINAWA, JAPAN: KOCOA PROJECT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Dodge, H. H.; Bowman, G.; Katsumata, Y.; Kaye, J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Dodge, H. H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Ohya, Y.; Todoriki, H.] Univ Ryukyus, Nishihara, Okinawa 90301, Japan. [Yasura, S.] Okinawa Int Univ, Okinawa, Japan. [Kaye, J.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 725 EP 725 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204833 ER PT J AU Chuang, ML Gona, P Hautvast, GLTF Salton, CJ Blease, SJ Yeon, SB Breeuwer, M O'Donnell, CJ Manning, WJ AF Chuang, Michael L. Gona, Philimon Hautvast, Gilion L. T. F. Salton, Carol J. Blease, Susan J. Yeon, Susan B. Breeuwer, Marcel O'Donnell, Christopher J. Manning, Warren J. TI Correlation of Trabeculae and Papillary Muscles With Clinical and Cardiac Characteristics and Impact on CMR Measures of LV Anatomy and Function SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac magnetic resonance; left ventricular ejection fraction; papillary muscle; population study; trabeculae ID VENTRICULAR NON-COMPACTION; MAGNETIC-RESONANCE; SYSTOLIC DYSFUNCTION; MASS; HYPERTRABECULATION/NONCOMPACTION; REPRODUCIBILITY; CARDIOMYOPATHY; NONCOMPACTION; DIAGNOSIS; FLASH AB OBJECTIVES The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF). BACKGROUND Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized. METHODS Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension. RESULTS In the referent group (mean age 61 +/- 9 years; 262 men and 423 women), mean TPM was 23 +/- 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool. CONCLUSIONS Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity. (J Am Coll Cardiol Img 2012;5:1115-23) (C) 2012 by the American College of Cardiology Foundation C1 [Chuang, Michael L.; Gona, Philimon; Blease, Susan J.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Chuang, Michael L.; Salton, Carol J.; Yeon, Susan B.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med, Boston, MA 02215 USA. [Chuang, Michael L.; O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA. [Gona, Philimon] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Hautvast, Gilion L. T. F.; Breeuwer, Marcel] Philips Healthcare, Best, Netherlands. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Manning, WJ (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM wmanning@bidmc.harvard.edu FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01 HC 25195]; National Institutes of Health [RO1 HL70279]; Philips Healthcare; Philips Medical Systems FX This research was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01 HC 25195), a subcontract from the National Institutes of Health (RO1 HL70279), and by an unrestricted grant from Philips Healthcare. Drs. Hautvast and Breeuwer are employees of Philips Healthcare. Dr. Manning has received research support from Philips Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 20 TC 24 Z9 25 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 NOV PY 2012 VL 5 IS 11 BP 1115 EP 1123 DI 10.1016/j.jcmg.2012.05.015 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 066VG UT WOS:000313248600006 PM 23153911 ER PT J AU Su, XL Ohi, R Pellman, D AF Su, Xiaolei Ohi, Ryoma Pellman, David TI Move in for the kill: motile microtubule regulators SO TRENDS IN CELL BIOLOGY LA English DT Review DE kinesin-8; kinesin-13; kinesin-4; microtubule dynamics; microtubule depolymerase ID KINESIN-RELATED PROTEIN; PLUS-END-TRACKING; FISSION YEAST; MITOTIC SPINDLE; PROMOTES MICROTUBULE; MOTOR PROTEINS; SACCHAROMYCES-CEREVISIAE; CHROMOSOME CONGRESSION; DROSOPHILA KLP67A; DIRECTED MOTOR AB The stereotypical function of kinesin superfamily motors is to transport cargo along microtubules. However, some kinesins also shape the microtubule track by regulating microtubule assembly and disassembly. Recent work has shown that the kinesin-8 family of motors emerge as key regulators of cellular microtubule length. The studied kinesin-8s are highly processive motors that walk towards the microtubule plus-end. Once at plus-ends, they have complex effects on polymer dynamics; kinesin-8s. either destabilize or stabilize microtubules, depending on the context. This review focuses on the mechanisms underlying kinesin-8-microtubule interactions and microtubule length control. We compare and contrast kinesin-8s with the other major microtubule-regulating kinesins (kinesin-4 and kinesin-13), to survey the current understanding of the diverse ways that kinesins control microtubule dynamics. C1 [Su, Xiaolei; Pellman, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Su, Xiaolei; Pellman, David] Harvard Univ, Dept Pediat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Su, Xiaolei; Pellman, David] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Su, Xiaolei; Pellman, David] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. [Ohi, Ryoma] Vanderbilt Univ, Dept Cell & Dev Biol, Med Ctr, Nashville, TN 37232 USA. RP Pellman, D (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM David_Pellman@dfci.harvard.edu FU Howard Hughes Medical Institute; National Institute of Health [GM61345, GM086610] FX We thank H. Arellano-Santoyo for helpful comments on the manuscript. D.P. was supported by the Howard Hughes Medical Institute and a National Institute of Health grant (GM61345). R.O. was supported by National Institute of Health Grant GM086610. NR 89 TC 27 Z9 28 U1 2 U2 26 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD NOV PY 2012 VL 22 IS 11 BP 567 EP 575 DI 10.1016/j.tcb.2012.08.003 PG 9 WC Cell Biology SC Cell Biology GA 068SB UT WOS:000313385400003 PM 22959403 ER PT J AU Vyas, JM AF Vyas, Jatin M. TI The dendritic cell The general of the army SO VIRULENCE LA English DT Editorial Material ID CROSS-PRESENTATION; DYNAMICS; SUBSETS C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Vyas, JM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU NIAID NIH HHS [R01 AI092084] NR 27 TC 1 Z9 2 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD NOV PY 2012 VL 3 IS 7 BP 601 EP 602 DI 10.4161/viru.22975 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 067HU UT WOS:000313285700012 PM 23221475 ER PT J AU Ramirez-Ortiz, ZG Means, TK AF Ramirez-Ortiz, Zaida G. Means, Terry K. TI The role of dendritic cells in the innate recognition of pathogenic fungi (A. fumigatus, C. neoformans and C. albicans) SO VIRULENCE LA English DT Article DE plasmacytoid dendritic cells; conventional dendritic cells; fungi; Toll-like receptors; scavenger receptors ID CRYPTOCOCCUS-NEOFORMANS; ASPERGILLUS-FUMIGATUS; CANDIDA-ALBICANS; HOST-DEFENSE; IMMUNE-RESPONSES; ANTIFUNGAL IMMUNITY; INVASIVE ASPERGILLOSIS; DEOXYNUCLEIC ACIDS; ADAPTIVE IMMUNITY; RECEPTOR GENES AB Dendritic cells (DCs) are the bridge between the innate and adaptive immune system. DCs are responsible for sensing and patrolling the environment, initiating a host response and instructing the proper adaptive immune response against pathogens. Recent advances in medical treatments have led to increased use of immunosuppressive drugs, leading to the emergence of fungal species that cause life-threatening infections in humans. Three of these opportunistic fungal pathogens: Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans pose the biggest concern for the immune-compromised host. Here we will review the interactions between DCs and these fungal pathogens, the receptors expressed on DCs that mediate these responses and the signaling mechanisms that shape the adaptive host response. C1 [Means, Terry K.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Means, TK (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. EM means.terry@mgh.harvard.edu FU NIAID NIH HHS [R01 AI084884, T32 AI007061] NR 96 TC 22 Z9 27 U1 2 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD NOV PY 2012 VL 3 IS 7 BP 635 EP 646 DI 10.4161/viru.22295 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 067HU UT WOS:000313285700016 PM 23076328 ER PT J AU Vyas, JM AF Vyas, Jatin M. TI Insights into dendritic cell function using advanced imaging modalities SO VIRULENCE LA English DT Article DE microscopy; TIRF; spinning disk; two photon microscopy; optical traps; optical tweezer ID II MHC COMPARTMENTS; TOLL-LIKE RECEPTORS; IMMUNE-SYSTEM; INNATE IMMUNITY; ANTIGEN PRESENTATION; OPTICAL TWEEZERS; LYMPH-NODES; SINGLE-CELL; T-CELLS; MICROSCOPY AB The application of advanced imaging techniques to fundamental questions in immunology has provided insight into dendritic cell function and has challenged dogma created using static imaging of lymphoid tissue. The history of dendritic cell biology has a storied past and is tightly linked to imaging. The development of imaging techniques that emphasize live cell imaging in situ has provided not only breath-taking movies, but also novel insights into the importance of spatiotemporal relationships between antigen presenting cells and T cells. This review serves to provide a primer on two-photon microscopy, TIRF microscopy, spinning disk confocal microscopy and optical trapping and provides selective examples of insights gained from these tools on dendritic cell biology. C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Vyas, JM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU NIH [R01 AI092084, T32AI007061] FX J.M.V. is supported by NIH grant R01 AI092084. Post-doctoral fellows in the lab are supported by NIH grant T32AI007061. The author thanks all of the current and former members of the laboratory. NR 55 TC 1 Z9 2 U1 0 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PD NOV PY 2012 VL 3 IS 7 BP 690 EP 694 DI 10.4161/viru.22981 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 067HU UT WOS:000313285700022 PM 23221474 ER PT J AU Lin, MT Cantuti-Castelvetri, I Lees, AJ Beal, MF Simon, DK AF Lin, Michael T. Cantuti-Castelvetri, Ippolita Lees, Andrew J. Beal, M. Flint Simon, David K. TI Somatic Mitochondrial DNA Mutations and Parkinsonism Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 [Lin, Michael T.; Beal, M. Flint] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. [Cantuti-Castelvetri, Ippolita] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cantuti-Castelvetri, Ippolita; Simon, David K.] Harvard Univ, Sch Med, Boston, MA USA. [Lees, Andrew J.] UCL, Inst Neurol, Reta Lila Weston Inst Neurol Studies, London, England. [Simon, David K.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Lin, MT (reprint author), Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. NR 3 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2012 VL 72 IS 5 BP 823 EP 824 DI 10.1002/ana.23739 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 062RV UT WOS:000312940300024 ER PT J AU Seligowski, AV Kaiser, AP King, LA King, DW Potter, C Spiro, A AF Seligowski, Antonia V. Kaiser, Anica Pless King, Lynda A. King, Daniel W. Potter, Carrie Spiro, Avron, III TI Correlates of Life Satisfaction among Aging Veterans SO APPLIED PSYCHOLOGY-HEALTH AND WELL BEING LA English DT Article ID QUALITY-OF-LIFE; ONSET STRESS SYMPTOMATOLOGY; OLDER-ADULTS; POSTTRAUMATIC GROWTH; COMBAT VETERANS; PERCEIVED CONTROL; WAR VETERANS; HEALTH; TRAUMA; RESILIENCE AB Background: The purpose of this study was to document the associations of stressors (combat exposure, retirement concerns, and late-life stressful events), personal resources (social support, sense of mastery, and positive appraisal of military experiences), and functional health (both physical and mental) with life satisfaction in older veterans. Methods: Participants were 562 male combat veterans (mean age = 70). Self-report questionnaires were administered via mail survey. A hierarchical multiple regression analysis was performed. Results: Each step of the regression analysis demonstrated a significant contribution to variance in life satisfaction (48% in total). Although stressors were significant when entered as a set, their influence dissipated in the presence of personal resources and functional health. For the full model, seven of 11 independent variables were unique and significant predictors, including all personal resource factors and both functional health indices. Sense of mastery was most potent. Conclusions: Even in the presence of stressors, personal resources and functional health appear to serve protective roles in explaining levels of life satisfaction among aging veterans. C1 [Seligowski, Antonia V.; Kaiser, Anica Pless; King, Lynda A.; King, Daniel W.; Potter, Carrie; Spiro, Avron, III] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Kaiser, Anica Pless; King, Lynda A.; King, Daniel W.; Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Seligowski, AV (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B-2, Boston, MA 02130 USA. EM avic858@gmail.com FU NIA NIH HHS [R01-AG18436] NR 39 TC 3 Z9 3 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1758-0846 J9 APPL PSYCHOL-HLTH WE JI Appl. Psychol.-Health Well Being PD NOV PY 2012 VL 4 IS 3 BP 261 EP 275 DI 10.1111/j.1758-0854.2012.01073.x PG 15 WC Psychology, Applied SC Psychology GA 061UR UT WOS:000312874400001 PM 23081763 ER PT J AU Bessa, TF Cordeiro, CA Goncalves, RM Young, LH Campos, WR Orefice, F Teixeira, AL AF Bessa, Thais Fontes Cordeiro, Cynthia Azeredo Goncalves, Roberto Martins Young, Lucy H. Campos, Wesley R. Orefice, Fernando Teixeira, Antonio L. TI Increased serum levels of soluble tumor necrosis factor receptor-2 (sTNFR2) in patients with active toxoplasmic retinochoroiditis SO BRAZILIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Toxoplasmosis; Uveitis; TNF-alpha; Soluble TNF receptors ID NITRIC-OXIDE SYNTHASE; OCULAR TOXOPLASMOSIS; TNF RECEPTOR; PROTECTIVE ROLE; MESSENGER-RNA; IN-VIVO; UVEITIS; ALPHA; ACTIVATION; EXPRESSION AB This study aimed to investigate the serum levels of the cytokine TNF-alpha and its soluble receptors (sTNFR1 and sTNFR2) in patients with toxoplasmosis retinochoroidits (TR) and controls. 37 patients with TR and 30 subjects with positive serology for toxoplasmosis but without history and signs of uveitis were included in this study. Serum concentrations of TNF-alpha, sTNFR1, and sTNFR2 were determined by ELISA. Serum concentrations of TNF-alpha and sTNFR1 were similar in controls (mean +/- SD median values; 56.57 +/- 141.96 and 504.37 +/- 163.87, respectively) and TR patients (mean +/- SD values, 121.62 +/- 217.56 and 511.15 +/- 189.30, respectively). Serum concentrations of sTNFR2 were higher in the uveitis group when compared to the control group (respectively, mean +/- SD values, 1734.84 +/- 379.32 and 1442.75 +/- 309.47; p=0.002). There was no association between the serum levels of the molecules and the time of first symptoms, severity of vitreous haze, size or localization of active lesions, levels of visual acuity, and presence of vasculitis. These results suggest that TR is associated with changes in the circulating levels of inflammatory biomarkers, but they are not correlated with local/ocular signs. (C) 2012 Elsevier Editora Ltda. All rights reserved. C1 [Teixeira, Antonio L.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Lab Imunofarmacol, BR-31270901 Belo Horizonte, MG, Brazil. [Bessa, Thais Fontes; Cordeiro, Cynthia Azeredo; Goncalves, Roberto Martins; Campos, Wesley R.; Orefice, Fernando] Univ Fed Minas Gerais, Dept Ophthalmol, Uveitis Sect, BR-31270901 Belo Horizonte, MG, Brazil. [Cordeiro, Cynthia Azeredo; Young, Lucy H.] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Teixeira, AL (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Lab Imunofarmacol, Av Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil. EM altexr@gmail.com FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil); Fundacao de Amparo a Pesquisa de Minas Gerais (Fapemig, Brazil) FX This work was funded by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil) and the Fundacao de Amparo a Pesquisa de Minas Gerais (Fapemig, Brazil). These funding agencies had no role in the study design, collection, analysis, and interpretation of data; nor in the writing of the report; nor in the decision to submit the article for publication. NR 32 TC 2 Z9 2 U1 0 U2 2 PU CONTEXTO PI SALVADOR PA RUA ALFREDO MAGALHAES, 04-BARRA, SALVADOR, BAHIA 40140-140, BRAZIL SN 1413-8670 J9 BRAZ J INFECT DIS JI Braz. J. Infect. Dis. PD NOV-DEC PY 2012 VL 16 IS 6 BP 540 EP 544 DI 10.1016/j.bjid.2012.07.009 PG 5 WC Infectious Diseases SC Infectious Diseases GA 059BW UT WOS:000312680400007 PM 23141990 ER PT J AU Hoshida, Y Fuchs, BC Tanabe, KK AF Hoshida, Yujin Fuchs, Bryan C. Tanabe, Kenneth K. TI Prevention of Hepatocellular Carcinoma: Potential Targets, Experimental Models, and Clinical Challenges SO CURRENT CANCER DRUG TARGETS LA English DT Review DE Animal model; chemoprevention; clinical trial; hepatocellular carcinoma; liver cirrhosis; prevention ID CHRONIC HEPATITIS-C; STELLATE CELL ACTIVATION; ACID-DEFINED DIET; PRIMARY BILIARY-CIRRHOSIS; TRANSGENIC MOUSE MODEL; FATTY LIVER-DISEASE; NF-KAPPA-B; INTRAARTERIAL IODINE-131-LABELED LIPIODOL; PROSPECTIVE RANDOMIZED-TRIAL; ADJUVANT INTERFERON THERAPY AB Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. C1 [Hoshida, Yujin] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, Tisch Canc Inst, Div Liver Dis,Dept Med, New York, NY 10029 USA. [Fuchs, Bryan C.; Tanabe, Kenneth K.] Harvard Univ, Div Surg Oncol, Massachusetts Gen Hosp, Canc Ctr,Med Sch, Boston, MA 02114 USA. RP Hoshida, Y (reprint author), Mt Sinai Sch Med, Mt Sinai Liver Canc Program, Tisch Canc Inst, Div Liver Dis,Dept Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM yujin.hoshida@mssm.edu FU European Comission; NCI [5 K01CA140861] FX Yujin Hoshida is supported by European Comission's 7th Framework Programme (FPT-Health 2010, Heptromic). Bryan C. Fuchs is supported by a K-award from NCI (5 K01CA140861). NR 403 TC 25 Z9 25 U1 1 U2 21 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD NOV PY 2012 VL 12 IS 9 BP 1129 EP 1159 PG 31 WC Oncology SC Oncology GA 064DV UT WOS:000313052200008 PM 22873223 ER PT J AU Reyna, D Bellairs, J Walensky, L Gavathiotis, E AF Reyna, D. Bellairs, J. Walensky, L. Gavathiotis, E. TI Direct Targeting of Pro-apoptotic BAX for Cancer Therapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Reyna, D.; Gavathiotis, E.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Med, Dept Biochem, Bronx, NY 10467 USA. [Bellairs, J.; Walensky, L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Dept Pediat Oncol 2, Boston, MA 02115 USA. [Bellairs, J.; Walensky, L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Program Canc Chem Biol,Childrens Hosp Boston, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 20 BP 10 EP 10 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000019 ER PT J AU Weber, J Daud, A Infante, J Sosman, J Flaherty, K Kefford, R Hamid, O Schuchter, L Patel, K Gonzalez, R AF Weber, J. Daud, A. Infante, J. Sosman, J. Flaherty, K. Kefford, R. Hamid, O. Schuchter, L. Patel, K. Gonzalez, R. TI Clinical Status of RAF/MEK Inhibitors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Weber, J.] Univ S Florida, H Lee Moffitt Canc Ctr, Melanoma Res Ctr, Tampa, FL 33682 USA. [Daud, A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Infante, J.] Sarah Cannon Res Inst, Nashville, TN USA. [Sosman, J.] Vanderbilt Univ, Ingram Canc Ctr, Nashville, TN USA. [Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kefford, R.] Westmead Hosp, Melanoma Inst Australia, Sydney, NSW, Australia. [Hamid, O.] Angeles Clin, Los Angeles, CA USA. [Schuchter, L.] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. 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TI Synergistic Interaction Between P-glycoprotein Inhibitors and APO866 in Primary Leukemic Cells SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Soncini, D.; Cagnetta, A.; Caffa, I.; Ballestrero, A.; Patrone, F.; Nencioni, A.] Univ Genoa, DI MI, Genoa, Italy. [Bruzzone, S.] Univ Genoa, DI MES, Genoa, Italy. [Cea, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Bruzzone, Santina/A-4264-2015 OI Bruzzone, Santina/0000-0003-2034-3716 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 74 BP 24 EP 24 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000070 ER PT J AU Ong, Q Hochberg, FH Cima, MJ AF Ong, Q. Hochberg, F. H. Cima, M. J. TI Device for Treatment of Brain Tumor Associated Edema SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Ong, Q.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hochberg, F. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 113 BP 35 EP 35 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000109 ER PT J AU Corcoran, R Cheng, K Hata, A Faber, A Singh, A Settleman, J Benes, C Mino-Kenudson, M Wong, K Engelman, J AF Corcoran, R. Cheng, K. Hata, A. Faber, A. Singh, A. Settleman, J. Benes, C. Mino-Kenudson, M. Wong, K. Engelman, J. TI Synthetic Lethal Interaction of Combined BCL-XL and MEK Inhibition Promotes Tumor Regressions in KRAS-mutant Cancer Models SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Corcoran, R.; Hata, A.; Faber, A.; Benes, C.; Engelman, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Cheng, K.; Wong, K.] Dana Farber Canc Inst, Ctr Canc, Boston, MA 02115 USA. [Singh, A.] Boston Univ, Ctr Canc, Boston, MA 02215 USA. [Settleman, J.] Genentech Inc, Discovery Oncol, San Francisco, CA 94080 USA. [Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 149 BP 46 EP 46 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000145 ER PT J AU Moroco, JA Craigo, JK Gray, NS Smithgall, TE AF Moroco, J. A. Craigo, J. K. Gray, N. S. Smithgall, T. E. TI Diversity in Individual Src-family Kinase Regulation: Opportunities for Selective Inhibitor Discovery SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Moroco, J. A.; Craigo, J. K.; Smithgall, T. E.] Univ Pittsburgh, Sch Med Microbiol & Mol Genet, Pittsburgh, PA USA. [Gray, N. S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol,Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 225 BP 68 EP 68 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000221 ER PT J AU Verdine, GL AF Verdine, G. L. TI Next-Generation Therapeutics for Unconventional Targets SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Verdine, G. L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Verdine, G. L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Verdine, G. L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Verdine, G. L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Verdine, G. L.] Dana Farber Canc Inst, Chem Biol Initiat, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 242 BP 74 EP 75 PG 2 WC Oncology SC Oncology GA 060FX UT WOS:000312763000236 ER PT J AU Petrylak, D Kantoff, P Mega, A Stephenson, J Vogelzang, N Fleming, M Blattman, S Stambler, N D'Ambrosio, P Israel, RJ AF Petrylak, D. Kantoff, P. Mega, A. Stephenson, J. Vogelzang, N. Fleming, M. Blattman, S. Stambler, N. D'Ambrosio, P. Israel, R. J. TI Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC): a Phase 1 Trial in Castration-Resistant Metastatic Prostate Cancer (mCRPC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Petrylak, D.] Columbia Univ Med Ctr, Genitourinary Oncol Sect, New York, NY USA. [Kantoff, P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Solid Tumor Oncol, Boston, MA 02115 USA. [Mega, A.] Brown Univ, Providence, RI 02912 USA. [Stephenson, J.] Canc Ctr Carolinas, Greenville, SC USA. [Vogelzang, N.] Comprehens Canc Ctr Nevada US Oncol Res, Las Vegas, NV USA. [Fleming, M.] Virginia Oncol Associates, Norfolk, VA USA. [Blattman, S.; Stambler, N.; D'Ambrosio, P.] Progen Pharmaceut Inc, Clin Res, Tarrytown, NY USA. [Israel, R. J.] Progen Pharmaceut Inc, Med Affairs & Clin Res, Tarrytown, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 244 BP 75 EP 75 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000238 ER PT J AU Fournel, M Wang, J Beaulieu, N Bonfils, C Hurwitz, H Shapiro, G Kollmannsberger, CK Juretic, M Besterman, JM Maroun, CR AF Fournel, M. Wang, J. Beaulieu, N. Bonfils, C. Hurwitz, H. Shapiro, G. Kollmannsberger, C. K. Juretic, M. Besterman, J. M. Maroun, C. R. TI A Novel Assay for the Met Inhibitory Activity of MGCD265 in Plasma From Solid Tumor Patients in a Dose Escalating Phase I Study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Fournel, M.; Wang, J.; Beaulieu, N.; Bonfils, C.; Besterman, J. M.; Maroun, C. R.] Methy Gene Inc, Translat Sci, Montreal, PQ, Canada. [Hurwitz, H.] Duke Univ, Med Ctr, Durham, NC USA. [Shapiro, G.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. [Kollmannsberger, C. K.] British Columbia Canc Agcy, Med, Vancouver, BC V5Z 4E6, Canada. [Juretic, M.] Methy Gene Inc, Clin Dev, Montreal, PQ, Canada. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 312 BP 95 EP 96 PG 2 WC Oncology SC Oncology GA 060FX UT WOS:000312763000305 ER PT J AU Zhang, T Ebbinghaus, S Loboda, A Nebozhyn, M Lunceford, J Haines, B Rivera, V Sant, C Demetris, G Blay, JY AF Zhang, T. Ebbinghaus, S. Loboda, A. Nebozhyn, M. Lunceford, J. Haines, B. Rivera, V. Sant, C. Demetris, G. Blay, J. Y. TI Gene Expression Analysis of Human Sarcoma Tissues to Explore Clinical Outcomes of mTOR Inhibition with Ridaforolimus: Correlative Science From the Phase III SUCCEED Trial Testing Maintenance Therapy for Metastatic Disease SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Zhang, T.] Merck Res Labs, Informat & Anal, Boston, MA USA. [Ebbinghaus, S.] Merck Res Labs, Clin Res, N Wales, PA USA. [Loboda, A.; Nebozhyn, M.] Merck Res Labs, Informat & Anal, N Wales, PA USA. [Lunceford, J.] Merck Res Labs, Early Dev Stat, N Wales, PA USA. [Haines, B.] Merck Res Labs, In Vivo Pharmacol, Boston, MA USA. 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TI Tumor Pharmacodynamic Assessments by Reverse Phase Protein Array Reveal Broad Pathway Inhibition in Patients Treated with an AKT Kinase Inhibitor SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Yan, Y.; Lackner, M. R.] Genentech Inc, Oncol Biomarker Dev, San Francisco, CA 94080 USA. [Tabernero, J.] Vall dHebron Univ Hosp, Med Oncol Serv, Barcelona, Spain. [Scaltriti, M.; Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Cervantes, A.] Univ Valencia, Valencia, Spain. [Patel, P.] Genentech Inc, Exploratory Clin Dev, San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 359 BP 110 EP 110 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000352 ER PT J AU Ahnert, JR Burris, HA Schellens, JHM Schuler, M Goodman, O Britten, C Richards, D Demanse, D Silva, A Baselga, J AF Rodon Ahnert, J. Burris, H. A. Schellens, J. H. M. Schuler, M. Goodman, O. Britten, C. Richards, D. Demanse, D. Silva, A. Baselga, J. TI Phase I Dose-escalation Study of the Oral Dual MTOR/PI3K Inhibitor BEZ235, Solid Dispersion System (SDS) Sachet Formulation, in Patients with Advanced Solid Tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Rodon Ahnert, J.] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain. [Burris, H. A.] Sarah Cannon Res Inst, Drug Dev Program, Nashville, TN USA. [Schellens, J. H. M.] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands. [Schuler, M.] W Deutsch Tumorzentrum Univ Klinikum Essen Univ D, Dept Med Oncol, Essen, Germany. [Goodman, O.] UC San Diego Nevada Canc Inst, Las Vegas, NV USA. [Britten, C.] UCLA Jonsson Canc Ctr, Dept Med Hematol Oncol, Los Angeles, CA USA. [Richards, D.] Texas Oncol Tyler, Med Oncol, Tyler, TX USA. [Demanse, D.] Novartis Pharma AG, Stat, Basel, Switzerland. [Silva, A.] Novartis Pharma AG, Clin Oncol, Basel, Switzerland. [Baselga, J.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 366 BP 112 EP 112 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000359 ER PT J AU Chandarlapaty, S Rodrik-Outmezguine, V Scaltriti, MM Sakr, R Will, M Giri, D Hudis, C Baselga, J King, T Rosen, N AF Chandarlapaty, S. Rodrik-Outmezguine, V. Scaltriti, M. Maurizio Sakr, R. Will, M. Giri, D. Hudis, C. Baselga, J. King, T. Rosen, N. TI A Mechanistic Logic for Dual Targeting of HER2 and PI3K/AKT/mTOR Signaling in HER2 Amplified Breast Cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Chandarlapaty, S.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Scaltriti, M. Maurizio; Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 417 BP 127 EP 127 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000410 ER PT J AU Letai, A Kutuk, O Vo, T Ryan, J Deng, J Sarosiek, K Chonghaile, TN AF Letai, A. Kutuk, O. Vo, T. Ryan, J. Deng, J. Sarosiek, K. Chonghaile, T. Ni TI The mitochondrial basis of resistance to BCL-2 antagonists and conventional chemotherapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Letai, A.; Kutuk, O.; Vo, T.; Ryan, J.; Deng, J.; Sarosiek, K.; Chonghaile, T. Ni] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Ni Chonghaile, Triona/L-9418-2015 OI Ni Chonghaile, Triona/0000-0002-3041-4031 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 427 BP 133 EP 133 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000420 ER PT J AU Shao, H Chung, J Balaj, L Charest, A Bigner, DD Carter, BS Hochberg, FH Breakefield, XO Weissleder, R Lee, H AF Shao, H. Chung, J. Balaj, L. Charest, A. Bigner, D. D. Carter, B. S. Hochberg, F. H. Breakefield, X. O. Weissleder, R. Lee, H. TI Protein Typing of Circulating Microvesicles Allows Real-time Monitoring of Glioblastoma Therapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Shao, H.; Chung, J.; Weissleder, R.; Lee, H.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Balaj, L.; Breakefield, X. O.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Charest, A.] Tufts Univ, Sch Med, Mol Oncol Res Inst, Boston, MA 02111 USA. [Bigner, D. D.] Duke Univ, Med Ctr, Brain Tumor Ctr, Durham, NC USA. [Carter, B. S.] UCSD Sch Med, Div Neurol Surg, San Diego, CA USA. [Hochberg, F. H.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 443 BP 137 EP 138 PG 2 WC Oncology SC Oncology GA 060FX UT WOS:000312763000436 ER PT J AU Ostroff, R Mehan, M Brody, E Stewart, A Williams, S Baron, A Feser, W Franklin, W Wolf, H Miller, Y AF Ostroff, R. Mehan, M. Brody, E. Stewart, A. Williams, S. Baron, A. Feser, W. Franklin, W. Wolf, H. Miller, Y. TI Proteomic Insights in Oncology: What Have We Learned From Measuring Millions of Proteins? SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Ostroff, R.; Brody, E.; Williams, S.] SomaLogic Inc, Med, Boulder, CO USA. [Mehan, M.; Stewart, A.] SomaLogic Inc, Bioinformat, Boulder, CO USA. [Baron, A.; Feser, W.; Franklin, W.; Wolf, H.; Miller, Y.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Miller, Y.] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 460 BP 142 EP 142 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000453 ER PT J AU Sullivan, R Montaser, L Sepehr, A Buchbinder, E Gunturi, A Simonson, R Mier, JW Flaherty, KT Iafrate, AJ Panka, DJ AF Sullivan, R. Montaser, L. Sepehr, A. Buchbinder, E. Gunturi, A. Simonson, R. Mier, J. W. Flaherty, K. T. Iafrate, A. J. Panka, D. J. TI Clinical Utility of a Highly Sensitive Blood BRAF Assay in Patients with Stage II and III Malignant Melanoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Sullivan, R.; Flaherty, K. T.; Iafrate, A. J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Montaser, L.; Sepehr, A.; Buchbinder, E.; Gunturi, A.; Simonson, R.; Mier, J. W.; Panka, D. J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 462 BP 143 EP 143 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000455 ER PT J AU Zahir, H Rodig, S Sequist, LV Rimassa, L Eng, C Halim, AB Wang, Y von Roemeling, R Chen, Y Schwartz, B AF Zahir, H. Rodig, S. Sequist, L. V. Rimassa, L. Eng, C. Halim, A. B. Wang, Y. von Roemeling, R. Chen, Y. Schwartz, B. TI Relationship Between Tumor MET Expression and Clinical Outcomes in Cancer Patients Treated with Tivantinib SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Zahir, H.] Daiichi Sankyo Inc, Clin Pharmacol, Edison, NJ USA. [Rodig, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rodig, S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sequist, L. V.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sequist, L. V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rimassa, L.] Ist Clin Humanitas IRCCS, Humanitas Canc Ctr, Med Oncol Unit, Milan, Italy. [Eng, C.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Halim, A. B.] Daiichi Sankyo Inc, Clin Biomarkers, Edison, NJ USA. [Wang, Y.] Daiichi Sankyo Inc, Clin Dev, Edison, NJ USA. [von Roemeling, R.] Daiichi Sankyo Inc, Clin Dev Oncol, Edison, NJ USA. [Chen, Y.; Schwartz, B.] ArQule Inc, Clin Dev, Woburn, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 482 BP 149 EP 149 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000475 ER PT J AU Ott, C Kopp, N Bird, L Paranal, R Qi, J Bowman, T Rodig, S Kung, A Weinstock, D Bradner, J AF Ott, C. Kopp, N. Bird, L. Paranal, R. Qi, J. Bowman, T. Rodig, S. Kung, A. Weinstock, D. Bradner, J. TI BET Bromodomain Inhibition Targets Both c-Myc and IL7R in Acute Lymphoblastic Leukemia SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Ott, C.; Kopp, N.; Bird, L.; Paranal, R.; Qi, J.; Weinstock, D.; Bradner, J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bowman, T.; Rodig, S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kung, A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 539 BP 166 EP 166 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000531 ER PT J AU Messersmiths, WA LoRusso, PM Cleary, JM Dasaris, A Huang, B Shaik, NM Cesari, R McLachlan, K Kern, KA Shapiro, GI AF Messersmiths, W. A. LoRusso, P. M. Cleary, J. M. Dasaris, A. Huang, B. Shaik, N. M. Cesari, R. McLachlan, Kr. Kern, K. A. Shapiro, G. I. TI A First-in-patient Phase I Study of the Novel Gamma Secretase Inhibitor PF-03084014 in Patients with Advanced Solid Tumor Malignancies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Messersmiths, W. A.; Dasaris, A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [LoRusso, P. M.] Karmanos Canc Inst, Res Adm, Detroit, MI USA. [Cleary, J. M.; Shapiro, G. I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. [Huang, B.; Shaik, N. M.; McLachlan, Kr.; Kern, K. A.] Pfizer, Oncol Business Unit, San Diego, CA USA. [Cesari, R.] Pfizer, Oncol Business Unit, Milan, Italy. NR 0 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 588 BP 180 EP 180 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000580 ER PT J AU Wagner, A Messersmith, W Shaik, N Zheng, X McLachlan, K Cesari, R Courtney, R Levin, W El-Khoueiry, A AF Wagner, A. Messersmith, W. Shaik, N. Zheng, X. McLachlan, K. Cesari, R. Courtney, R. Levin, W. El-Khoueiry, A. TI Phase 1 Dose-escalation Study of PF-04449913, an Oral Hedgehog Inhibitor in Patients with Select Solid Tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Wagner, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Messersmith, W.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Shaik, N.] Pfizer Oncol, Clin Pharmacol, San Diego, CA USA. [Zheng, X.] Pfizer Oncol, Translat Med, San Diego, CA USA. [McLachlan, K.] Pfizer Oncol, Translat Oncol, San Diego, CA USA. [Cesari, R.] Pfizer Oncol, Clin Dev, Milan, Italy. [Courtney, R.; Levin, W.] Pfizer Oncol, Clin Dev, San Diego, CA USA. [El-Khoueiry, A.] Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 587 BP 180 EP 180 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000579 ER PT J AU Haluska, P Menefee, ME Plimack, ER Rosenberg, JE Northfelt, DW LaVallee, T Huang, W Yu, XQ Viner, JL LoRusso, P AF Haluska, P. Menefee, M. E. Plimack, E. R. Rosenberg, J. E. Northfelt, D. W. LaVallee, T. Huang, W. Yu, X. Q. Viner, J. L. LoRusso, P. TI A Phase 1 Study of MEDI-573, an Investigational Monoclonal Antibody That Targets IGF-I and IGF-II: Safety, Pharmacokinetics, and Antitumor Activity in Adults with Advanced Solid Tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Haluska, P.] Mayo Clin, Rochester, MN USA. [Menefee, M. E.] Mayo Clin, Jacksonville, FL 32224 USA. [Plimack, E. R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Rosenberg, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Northfelt, D. W.] Mayo Clin, Scottsdale, AZ USA. [LaVallee, T.] MedImmune LLC, R&D TS Oncol, Gaithersburg, MD USA. [Huang, W.] MedImmune LLC, Stat, Gaithersburg, MD USA. [LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 609 BP 187 EP 188 PG 2 WC Oncology SC Oncology GA 060FX UT WOS:000312763000601 ER PT J AU Zolak, JS de Andrade, JA AF Zolak, Jason S. de Andrade, Joao A. TI Idiopathic Pulmonary Fibrosis SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article DE Idiopathic pulmonary fibrosis; Pathogenesis; Diagnosis; Management ID ENDOPLASMIC-RETICULUM STRESS; INTERSTITIAL LUNG-DISEASE; PLACEBO-CONTROLLED TRIAL; ACID GASTROESOPHAGEAL-REFLUX; OXIDATIVE STRESS; ARTERIAL-HYPERTENSION; PREMATURE SENESCENCE; EPITHELIAL-CELLS; PREVALENCE; THERAPY AB Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause characterized by progressive scarring of the lung parenchyma and relentless loss of lung function. The diagnosis depends on close collaboration between clinicians, radiologists, and pathologists. No therapies approved by the Food and Drug Administration are available for IPF, and an analysis of completed clinical trials has demonstrated that the clinical course of IPF is largely unpredictable. Until therapies that improve survival become available, measures to preserve function and quality of life should be considered, and gastroesophageal reflux should be treated aggressively. C1 [de Andrade, Joao A.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Interstitial Lung Dis Program, Birmingham, AL 35294 USA. [de Andrade, Joao A.] Birmingham VA Med Ctr, Med Intens Care Unit, Birmingham, AL USA. RP de Andrade, JA (reprint author), Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Interstitial Lung Dis Program, 1900 Univ Blvd,THT 422, Birmingham, AL 35294 USA. EM joao@uab.edu FU NIH/NHLBI (IPFnet); Intermune; Actelion; Fibrogen; Centocor; Immuneworks; Gilead; Boehringer-Ingelheim; Celgene FX Funding sources: Dr Zolak: nil; Dr de Andrade: NIH/NHLBI (IPFnet), Intermune, Actelion, Fibrogen, Centocor, Immuneworks, Gilead, Boehringer-Ingelheim, and Celgene. NR 83 TC 1 Z9 2 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD NOV PY 2012 VL 32 IS 4 BP 473 EP + DI 10.1016/j.iac.2012.08.006 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 058FM UT WOS:000312619500004 PM 23102062 ER PT J AU Sedaghat, AR Bhattacharyya, N AF Sedaghat, Ahmad R. Bhattacharyya, Neil TI Radiographic density profiles link frontal and anterior ethmoid sinuses behavior in chronic rhinosinusitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE sinusitis; computed tomography; paranasal sinuses; paranasal sinus diseases; opacity; density; Hounsfield units ID SINUSITIS; SURGERY AB Background: Chronic rhinosinusitis (CRS) may occur through heterogeneous disease processes. It is possible that more than 1 inflammatory process underlies CRS in any given patient. If so, heterogeneity in processes may be a function of the spatial organization of the paranasal sinuses. Density characteristics of sinus opacities on computed tomography (CT) scans offer insight into the nature of sinus opacities and disease, in general, and may thus be used to detect spatial heterogeneity of sinus disease within a given patient. Methods: The study was a retrospective chart review of CRS patients with available sinus CT scans. Radiographic density profiles of sinus opacities were assessed by raw measures of densities (in Hounsfield units [HU]). Radiographic density profiles of the different affected sinuses were compared to each other, checked for correlation, and finally, checked for evidence of clustering using a principal component analysis. Results: Frontal sinus opacities appear to be more heterogeneous, with both higher and lower density components than other sinuses. There was strong correlation between the radiographic density profiles of opacities in the frontal, anterior ethmoid, and sphenoid sinuses (p < 0.001). However, on principal component analysis the radiographic density characteristics of the opacities of the frontal and anterior ethmoid sinuses appeared to cluster together more than the other sinuses. Conclusion: Radiographic properties of sinus opacities suggest the nature of sinus opacities are related not only to some common underlying pathology but also to factors related to the specific sinus as well as other spatially close affected sinuses. This suggests an anatomic orientation for sinus pathophysiology in CRS. C1 [Sedaghat, Ahmad R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Sedaghat, Ahmad R.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Divison Otolaryngol, Boston, MA 02115 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 14 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD NOV-DEC PY 2012 VL 2 IS 6 BP 496 EP 500 DI 10.1002/alr.21063 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 051QN UT WOS:000312142200010 PM 22736637 ER PT J AU Brody, A Sullivan-Marx, EM AF Brody, Abraham Sullivan-Marx, Eileen M. TI The Patient Protection and Affordable Care Act Implications for Geriatric Nurses and Patients SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Editorial Material C1 [Brody, Abraham; Sullivan-Marx, Eileen M.] NYU, Coll Nursing, New York, NY USA. [Brody, Abraham] James J Peters Bronx Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Brody, A (reprint author), NYU, Coll Nursing, New York, NY USA. OI Brody, Abraham/0000-0002-3405-7043 NR 10 TC 2 Z9 2 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD NOV PY 2012 VL 38 IS 11 BP 3 EP 5 DI 10.3928/00989134-20121008-01 PG 3 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 064AF UT WOS:000313042600001 PM 23126510 ER PT J AU Miller, M Chen, ALC Stokes, SD Silverman, S Bowirrat, A Manka, M Manka, D Miller, DK Perrine, K Chen, TJH Bailey, JA Downs, W Waite, RL Madigan, MA Braverman, ER Damle, U Kerner, M Giordano, J Morse, S Oscar-Berman, M Barh, D Blum, K AF Miller, Merlene Chen, Amanda L. C. Stokes, Stan D. Silverman, Susan Bowirrat, Abdalla Manka, Matthew Manka, Debra Miller, David K. Perrine, Kenneth Chen, Thomas J. H. Bailey, John A. Downs, William Waite, Roger L. Madigan, Margaret A. Braverman, Eric R. Damle, Uma Kerner, Mallory Giordano, John Morse, Siobhan Oscar-Berman, Marlene Barh, Debmalya Blum, Kenneth TI Early Intervention of Intravenous KB220IV-Neuroadaptagen Amino-Acid Therapy (NAAT)(TM) Improves Behavioral Outcomes in a Residential Addiction Treatment Program: A Pilot Study SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE Chronic Abstinence Symptom Severity (CASS) Scale; dopamine; KB220IV-neuroadaptagen amino-acid therapy (NAAT); reward deficiency syndrome (RDS) ID REWARD DEFICIENCY SYNDROME; DOPAMINE-RECEPTOR GENE; A1 ALLELE; ENKEPHALINASE INHIBITION; PROTRACTED ABSTINENCE; NUCLEUS-ACCUMBENS; POLYDRUG ABUSERS; ALCOHOL; BROMOCRIPTINE; ACTIVATION AB Substance use disorders (SUD) are inheritable and the culprit is hypodopaminergic function regulated by reward genes. We evaluated a natural dopaminergic agonist; KB220 intravenous (IV) and oral variants, to improve dopaminergic function in SUD. Our pilot experiment found a significant reduction of chronic symptoms, measured by the Chronic Abstinence Symptom Severity (CASS) Scale. The combined group (IV and oral) did significantly better than the oral-only group over the first week and 30-day follow-up period. Next, the combination was given to 129 subjects and three factors; Emotion, Somatic, and Impaired Cognition, with eigenvalues greater than one were extracted for baseline CASS-Revised (CASS-R) variables. Paired sample t-tests for pre and post-treatment scales showed significant declines (p = .00001) from pre- to post-treatment: t = 19.1 for Emotion, t = 16.1 for Somatic, and: = 14.9 for Impaired Cognition. In a two-year follow-up of 23 subjects who underwent KB220IV therapy (at least five IV treatments over seven days) plus orals for 30+ days: 21 (91%) were sober at six months, 19 (82%) having no relapse; 19 (82%) were sober at one year, 18 (78%) having no relapse; and 21(91%) were sober two-years post-treatment, 16(70%) having no relapse. We await additional research and advise caution in interpreting these encouraging results. C1 [Bailey, John A.; Blum, Kenneth] Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA. [Miller, Merlene; Manka, Matthew; Manka, Debra; Miller, David K.] AminoStream Inc, Indianapolis, IN USA. [Bailey, John A.; Blum, Kenneth] Univ Florida, McKnight Brain Inst, Gainesville, FL 32610 USA. [Chen, Amanda L. C.] Chang Jung Christian Univ, Dept Engn & Management Adv Technol, Tainan, Taiwan. [Stokes, Stan D.] Lee Clin, Winchester, VA USA. [Perrine, Kenneth; Braverman, Eric R.] Weill Cornell Coll Med, Dept Neurol Surg, New York, NY USA. [Chen, Thomas J. H.] Chang Jung Christian Univ, Dept Occupat Safety & Hlth, Tainan, Taiwan. [Miller, Merlene; Miller, David K.; Downs, William; Waite, Roger L.; Madigan, Margaret A.; Blum, Kenneth] Reward Deficiency Solut LLC, Dept Nutrigen & Personalized Med, San Diego, CA USA. [Miller, Merlene; Miller, David K.; Downs, William; Waite, Roger L.; Madigan, Margaret A.; Blum, Kenneth] LifeGen Inc, San Diego, CA USA. [Braverman, Eric R.; Damle, Uma; Kerner, Mallory; Blum, Kenneth] PATH Fdn, New York, NY USA. [Giordano, John; Morse, Siobhan; Blum, Kenneth] G&G Holist Addict Treatment Ctr, N Miami Beach, FL USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston VA Healthcare Syst, Boston, MA USA. [Barh, Debmalya; Blum, Kenneth] IIOAB, Ctr Genom & Appl Gene Technol, Purba Medinipur, W Bengal, India. [Blum, Kenneth] Domin Diagnost LLC, N Kingstown, RI USA. [Blum, Kenneth] Malibu Beach Recovery Ctr, Malibu Beach, CA USA. [Blum, Kenneth] Univ Vermont, Coll Med, Ctr Clin & Translat Sci, Global Integrated Serv Unit, Burlington, VT USA. RP Blum, K (reprint author), Univ Florida, Dept Psychiat, POB 103424, Gainesville, FL 32610 USA. EM tjhchen@yahoo.com.tw; drd2gene@aol.com RI Barh, Debmalya/O-4246-2015 OI Barh, Debmalya/0000-0002-2557-7768 FU NIAAA NIH HHS [K05 AA000219, K05-AA00219, R01 AA007112, R01-AA07112] NR 47 TC 4 Z9 4 U1 9 U2 14 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD NOV-DEC PY 2012 VL 44 IS 5 BP 398 EP 409 DI 10.1080/02791072.2012.737727 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 060AJ UT WOS:000312747100007 PM 23457891 ER PT J AU Gray, AN Henderson-Frost, JM Boyd, D Sharafi, S Niki, H Goldberg, MB AF Gray, Andrew N. Henderson-Frost, Josephine M. Boyd, Dana Sharafi, Shirin Niki, Hironori Goldberg, Marcia B. TI Unbalanced Charge Distribution as a Determinant for Dependence of a Subset of Escherichia coli Membrane Proteins on the Membrane Insertase YidC (vol 2, e00238, 2011) SO MBIO LA English DT Correction C1 [Gray, Andrew N.; Boyd, Dana; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Henderson-Frost, Josephine M.; Sharafi, Shirin; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA USA. [Niki, Hironori] Natl Inst Genet, Ctr Genet Resource Informat, Mishima, Shizuoka 411, Japan. RP Gray, AN (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD NOV-DEC PY 2012 VL 3 IS 6 AR e00500-12 DI 10.1128/mBio.00500-12 PG 1 WC Microbiology SC Microbiology GA 064UK UT WOS:000313100700034 ER PT J AU Hartmann, AS Becker, AE Hampton, C Bryant-Waugh, R AF Hartmann, Andrea S. Becker, Anne E. Hampton, Claire Bryant-Waugh, Rachel TI Pica and Rumination Disorder in DSM-5 SO PSYCHIATRIC ANNALS LA English DT Article ID PREGNANT-WOMEN; EATING-DISORDERS; CHILDREN; GEOPHAGY; SCHOOLCHILDREN; ANEMIA; IRON; ASSOCIATION; POPULATION; DIAGNOSIS C1 [Hartmann, Andrea S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Becker, Anne E.; Hampton, Claire] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02114 USA. [Bryant-Waugh, Rachel] Great Ormond St Hosp Children NHS Fdn Trust, Dept Child & Adolescent Mental Hlth, London, England. RP Hartmann, AS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM ahartmann1@partners.org NR 35 TC 4 Z9 4 U1 3 U2 19 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2012 VL 42 IS 11 BP 426 EP 430 DI 10.3928/00485713-20121105-09 PG 5 WC Psychiatry SC Psychiatry GA 065TG UT WOS:000313171500009 ER PT J AU Jhaveri, KS Harisinghani, MG AF Jhaveri, Kartik S. Harisinghani, Mukesh G. TI Male Pelvic Imaging SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Jhaveri, Kartik S.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Jhaveri, Kartik S.] Univ Hlth Network, Mt Sinai Hosp, Joint Dept Med Imaging, Toronto, ON, Canada. [Jhaveri, Kartik S.] Womens Coll Hosp, Toronto, ON, Canada. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harisinghani, Mukesh G.] Harvard Univ, Med School, Cambridge, MA 02138 USA. RP Jhaveri, KS (reprint author), Univ Toronto, Toronto, ON M5S 1A1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 2012 VL 50 IS 6 BP XI EP XI DI 10.1016/j.rcl.2012.10.006 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058EI UT WOS:000312616500001 ER PT J AU Talab, SS Preston, MA Elmi, A Tabatabaei, S AF Talab, Saman Shafaat Preston, Mark A. Elmi, Azadeh Tabatabaei, Shahin TI Prostate Cancer Imaging What the Urologist Wants to Know SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Prostate cancer; Transrectal ultrasonography; Magnetic resonance imaging; Diagnosis; Staging; Follow-up ID RADICAL RETROPUBIC PROSTATECTOMY; CONTRAST-ENHANCED MRI; EXTERNAL-BEAM RADIOTHERAPY; DIFFUSION-WEIGHTED MRI; CONVENTIONAL SYSTEMATIC BIOPSY; POSITIVE SURGICAL MARGINS; DOPPLER TARGETED BIOPSY; REAL-TIME ELASTOGRAPHY; LYMPH-NODE METASTASES; LOCAL RECURRENCE AB No consensus exists at present regarding the use of imaging for the evaluation of prostate cancer. Ultrasonography is mainly used for biopsy guidance and magnetic resonance imaging is the mainstay in evaluating the extent of local tumor. Computed tomography and radionuclide bone scanning are mainly reserved for assessment of advanced disease. Positron emission tomography is gaining acceptance in the evaluation of treatment response and recurrence. The combination of anatomic, functional, and metabolic imaging modalities has promise to improve treatment. This article reviews current imaging techniques and touches on the evolving technologies being used for detection and follow-up of prostate cancer. C1 [Talab, Saman Shafaat; Preston, Mark A.; Tabatabaei, Shahin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Elmi, Azadeh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Tabatabaei, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM stabatabaei@partners.org NR 178 TC 13 Z9 13 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 2012 VL 50 IS 6 BP 1015 EP + DI 10.1016/j.rcl.2012.08.004 PG 28 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058EI UT WOS:000312616500002 PM 23122036 ER PT J AU Hedgire, SS Pargaonkar, VK Elmi, A Harisinghani, AM Harisinghani, MG AF Hedgire, Sandeep S. Pargaonkar, Vivek K. Elmi, Azadeh Harisinghani, Alpana M. Harisinghani, Mukesh G. TI Pelvic Nodal Imaging SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Lymph node; Metastasis; Testicular cancer; Prostate cancer; Penile cancer; Bladder cancer ID SUPERPARAMAGNETIC IRON-OXIDE; MULTICENTER CLINICAL-TRIAL; SQUAMOUS-CELL CARCINOMA; LYMPH-NODE; PROSTATE-CANCER; BLADDER-CANCER; COMPUTED-TOMOGRAPHY; HISTOPATHOLOGIC FINDINGS; RADICAL PROSTATECTOMY; CERVICAL-CANCER AB Detection of nodal metastases in men with pelvic urogenital malignancies is important for accurate staging and has therapeutic and prognostic implications. Knowledge of clinical anatomy of these nodes and the lymphatic pathways is critical for assigning the correct N or M staging and to assess the treatment response. Both computed tomography and magnetic resonance imaging use size and morphologic criteria for nodal characterization. The limitations of these criteria have formed basis newer functional imaging tools. This article focuses on the clinical anatomy, pathways of lymphatic spread of malignancies, current criteria, and newer advances in imaging of male pelvic nodes. C1 [Hedgire, Sandeep S.; Pargaonkar, Vivek K.; Elmi, Azadeh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Harisinghani, Alpana M.] Percept Informat, Billerica, MA 01821 USA. RP Hedgire, SS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM hedgire.sandeep@mgh.harvard.edu NR 70 TC 6 Z9 6 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 2012 VL 50 IS 6 BP 1111 EP + DI 10.1016/j.rcl.2012.08.002 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058EI UT WOS:000312616500007 PM 23122041 ER PT J AU Shenoy-Bhangle, A Perez-Johnston, R Singh, A AF Shenoy-Bhangle, Anuradha Perez-Johnston, Rocio Singh, Ajay TI Penile Imaging SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Penile imaging; Peyronie; Penile fracture; Penile malignancy; Implants ID PEYRONIES-DISEASE; ERECTILE DYSFUNCTION; DOPPLER EVALUATION; SURGICAL-TREATMENT; FOLLOW-UP; CANCER; CARCINOMA; MALIGNANCIES; ULTRASOUND; DIAGNOSIS AB In Peyronie disease, magnetic resonance (MR) imaging is better than ultrasound in detecting impalpable plaques and plaque dimensions, whereas calcified plaques are better visualized on ultrasound. Ultrasound with color Doppler technique is superior to MR imaging in evaluating vascular causes of erectile dysfunction. In penile fractures, MR imaging should be performed with the patient in the erect position to avoid kinking between the pendulous and fixed parts and thus enable better demonstration of the site of tunica albuginea disruption for surgical planning. MR imaging is better than ultrasound in delineating primary penile malignancies and demonstrating lymph nodal involvement. C1 [Shenoy-Bhangle, Anuradha; Singh, Ajay] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Night Imaging Serv, Boston, MA 02115 USA. RP Shenoy-Bhangle, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Night Imaging Serv, White 280,55 Fruit St, Boston, MA 02115 USA. EM ashenoy-bhangle@partners.org NR 49 TC 2 Z9 2 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 2012 VL 50 IS 6 BP 1167 EP + DI 10.1016/j.rcl.2012.08.009 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058EI UT WOS:000312616500010 PM 23122044 ER PT J AU Avery, LL Scheinfeld, MH AF Avery, Laura L. Scheinfeld, Meir H. TI Imaging of Male Pelvic Trauma SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Bladder trauma; Testicular trauma; Testicular rupture; Penile trauma; Penile fracture ID RADIOLOGIC-PATHOLOGICAL CORRELATION; BLUNT SCROTAL TRAUMA; MAJOR BLADDER TRAUMA; URETHRAL INJURY; CT CYSTOGRAPHY; CONVENTIONAL CYSTOGRAPHY; COMPUTED-TOMOGRAPHY; VASCULAR INJURIES; EXTERNAL FIXATION; PENILE FRACTURE AB Prompt imaging plays an important role in the evaluation of male pelvic soft tissue trauma. Using appropriate imaging modalities, with optimization of contrast administration when appropriate, is essential for accurate diagnosis. Traumatic bladder rupture, either extraperitoneal or intraperitoneal, is diagnosed with high accuracy using computed tomography cystography. Suspicion of urethral injury warrants evaluation with retrograde urethrography to evaluate for the presence of injury and injury location. Early identification of laceration of the testicular tunica albuginea is essential. Understanding both normal penile anatomy and the imaging appearance of corpus rupture (as opposed to a hematoma) is imperative for proper diagnosis and management. C1 [Avery, Laura L.] Harvard Univ, Massachusetts Gen Hosp, Div Emergency Radiol, Sch Med,Dept Radiol, Boston, MA 02114 USA. [Scheinfeld, Meir H.] Montefiore Med Ctr, Albert Einstein Coll Med, Div Emergency Radiol, Bronx, NY 10467 USA. RP Avery, LL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Emergency Radiol, Sch Med,Dept Radiol, 55 Fruit St,FHD 210, Boston, MA 02114 USA. EM lavery@partners.org OI Scheinfeld, Meir H/0000-0001-8880-4318 NR 76 TC 4 Z9 4 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 2012 VL 50 IS 6 BP 1201 EP + DI 10.1016/j.rcl.2012.08.010 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058EI UT WOS:000312616500012 PM 23122046 ER PT J AU Choueiri, TK McDermott, D Duh, MS Sarda, SP Neary, MP Oh, WK AF Choueiri, Toni K. McDermott, David Duh, Mei Sheng Sarda, Sujata P. Neary, Maureen P. Oh, William K. TI Costs associated with angiogenesis inhibitor therapies for metastatic renal cell carcinoma in clinical practice: Results from a medical chart review study SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Renal cell carcinoma; Angiogenesis; Cost; Sunitinib; Sorafenib; Bevacizumab ID ECONOMIC-EVALUATION; 2ND-LINE TREATMENT; SUNITINIB MALATE; TRIAL; SORAFENIB; SAFETY; BURDEN AB Objective: To estimate costs for treatment of mRCC patients receiving angiogenesis inhibitors (AI) using resource utilization data from medical charts. Materials and methods: A retrospective chart review was performed in two U.S. tertiary oncology centers. Non-trial mRCC patients treated from 04/2003 to 06/2008, >= 18 years old, and with >= 1 prescription for sunitinib (SU; n = 57), sorafenib (SOR; n = 62), or >= 1 intravenous (i.v.) administration bevacizumab (BEV; n = 25) as first AI were included. Per-patient-per-month (PPPM) costs ($2008) were estimated for drug, i.v. administration, office visits, procedures, and AE treatments. AI drug costs were estimated by applying Average Wholesale Price to treatment course. Office visit and procedure costs were based on private insurance reimbursement. Hospitalization costs were based on HCUP National Inpatient Sample charges for AEs and were converted to costs. ER visit cost was based on national average from Medical Expenditure Panel Survey. Results: Median treatment duration (mo) was 10.5 (SU), 8.1 (SOR), 7.9 (BEV). Average daily oral dosage was 32 mg (SU), 690 mg (SOR); average dose per i.v. administration was 871 mg (BEV). Total PPPM costs were $7,945 (SU), $6,990 (SOR), $15,189 (BEV). AI drugs accounted for the majority of PPPM costs ($5,639 [SU], $5,214 [SOR], $13,664 [BEV]), followed by procedures ($1,420 [SU], $1,004 [SOR], $749 [BEV]), and AE treatments ($729 [SU], $636 [SOR], $291 [BEV]). Conclusions: BEV patients incurred about twice the cost of SU patients and more than twice the cost of SOR patients, mainly due to higher drug and i.v. administration costs. Patients who received SU incurred the highest cost for AE management. (C) 2012 Elsevier Inc. All rights reserved. C1 [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02118 USA. [Duh, Mei Sheng; Sarda, Sujata P.] Anal Grp Inc, Boston, MA 02118 USA. [Neary, Maureen P.] GlaxoSmithKline, Collegeville, PA 19426 USA. [Oh, William K.] Mt Sinai Sch Med, New York, NY 10001 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu FU GlaxoSmithKline, Collegeville, PA; GlaxoSmithKline FX This study was funded by GlaxoSmithKline, Collegeville, PA. The funding from GlaxoSmithKline was not contingent upon the study results. GlaxoSmithKline participated in the study design, results interpretation, and manuscript preparation. The study drugs sunitinib, sorafenib, and bevacizumab are manufactured by Pfizer, Bayer Healthcare Pharmaceuticals, and Genentech, respectively. A similar molecule developed by GlaxoSmithKline (pazopanib) was recently approved by the United States Food and Drug Administration for treatment of patients with advanced renal cell carcinoma. NR 21 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2012 VL 30 IS 6 BP 848 EP 855 DI 10.1016/j.urolonc.2010.07.009 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 056SI UT WOS:000312511300015 PM 20926319 ER PT J AU Flavin, R Finn, SP Choueiri, TK Ingoldsby, H Ring, M Barrett, C Rogers, M Smyth, P O'Regan, E Gaffney, E O'Leary, JJ Loda, M Signoretti, S Sheils, O AF Flavin, Richard Finn, Stephen P. Choueiri, Toni K. Ingoldsby, Helen Ring, Martina Barrett, Ciara Rogers, Miranda Smyth, Paul O'Regan, Esther Gaffney, Eoin O'Leary, John J. Loda, Massimo Signoretti, Sabina Sheils, Orla TI RET protein expression in papillary renal cell carcinoma SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE RET; Papillary renal cell carcinoma; GDNF ID THYROID-CARCINOMA; TYROSINE KINASE; HUMAN CANCER; ONCOGENE; PROTOONCOGENE; MUTATIONS; TUMORS; CLASSIFICATION; RECEPTOR; REARRANGEMENTS AB Objective: To examine the role of RET in renal malignancy, in particular papillary renal cell carcinoma (RCC). Materials and methods: A cohort of 111 archival renal samples was used consisting of 94 renal cancers (66 papillary RCC, 18 conventional clear cell carcinoma, 10 chromophobe RCC), 4 benign oncocytomas, and 13 normal kidney tissues. RET protein expression was examined by immunohistochemistry and expression levels were correlated with clinicopathologic and patient survival data. Results: Positive RET staining was seen in 34/66 (52%) papillary RCCs, 4/10 (40%) chromophobe carcinomas, 4/4 (100%) oncocytomas, and 11/13 (85%) normal kidney samples. All 18 cases of conventional clear cell carcinoma had negative RET staining. RET expression was associated with low Fuhrman nuclear grade. Conclusions: RET protein may be contributing in part to an adaptation of a papillary growth pattern in certain renal malignancies. Given the possible therapeutic benefit of small molecule inhibitors of RET activation, further work needs to be done to highlight the functional relevance of RET protein expression in papillary RCC. (C) 2012 Elsevier Inc. All rights reserved. C1 [Flavin, Richard; Ingoldsby, Helen] Natl Univ Ireland, Dept Pathol, Galway, Ireland. [Flavin, Richard; Finn, Stephen P.; Barrett, Ciara; Smyth, Paul; O'Regan, Esther; Gaffney, Eoin; O'Leary, John J.; Sheils, Orla] St James Hosp, Dept Histopathol, Dublin, Ireland. [Ring, Martina; O'Leary, John J.] Coombe Womens Hosp, Trinity Coll, Dept Histopathol, Dublin, Ireland. [Flavin, Richard; Finn, Stephen P.; Choueiri, Toni K.; Rogers, Miranda; Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Loda, Massimo; Signoretti, Sabina] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ingoldsby, H (reprint author), Natl Univ Ireland, Dept Pathol, Galway, Ireland. EM helen.ingoldsby@nuigalway.ie RI Sheils, Orla Sheils/B-8461-2015; OI Sheils, Orla Sheils/0000-0002-4493-9496; Finn, Stephen/0000-0002-8628-5814 FU HRB [CRT/2006/010] FX R.F. was sponsored by a HRB Clinical Research Fellow Ireland grant number CRT/2006/010. NR 40 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2012 VL 30 IS 6 BP 900 EP 905 DI 10.1016/j.urolonc.2010.08.025 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 056SI UT WOS:000312511300022 PM 21396847 ER PT J AU Eastham, JA Carroll, P Pisters, L Nguyen, PT Touijer, K AF Eastham, James A. Carroll, Peter Pisters, Louis Nguyen, Paul T. Touijer, Karim TI Salvage therapies after radiation therapy SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate cancer; Radiation therapy C1 [Eastham, James A.; Touijer, Karim] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. [Carroll, Peter] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94115 USA. [Carroll, Peter] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA. [Pisters, Louis] Univ Texas MD Anderson Canc Ctr, Dept Urol Oncol, Houston, TX 77030 USA. [Nguyen, Paul T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Eastham, JA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. EM easthamj@mskcc.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2012 VL 30 IS 6 BP 940 EP 941 DI 10.1016/j.urolonc.2012.09.007 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 056SI UT WOS:000312511300029 PM 23218071 ER PT J AU Wiler, JL Handel, DA Ginde, AA Aronsky, D Genes, NG Hackman, JL Hilton, JA Hwang, U Kamali, M Pines, JM Powell, E Sattarian, M Fu, RW AF Wiler, Jennifer L. Handel, Daniel A. Ginde, Adit A. Aronsky, Dominik Genes, Nicholas G. Hackman, Jeffrey L. Hilton, Joshua A. Hwang, Ula Kamali, Michael Pines, Jesse M. Powell, Emilie Sattarian, Medhi Fu, Rongwei TI Predictors of patient length of stay in 9 emergency departments SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID AMBULANCE DIVERSION; VARIABLES; TRIAGE; TIME; CARE AB Objectives: Prolonged emergency department (ED) length of stay (LOS) is linked to adverse outcomes, decreased patient satisfaction, and ED crowding. This multicenter study identified factors associated with increased LOS. Methods: This retrospective study included 9 EDs from across the United States. Emergency department daily operational metrics were collected from calendar year 2009. A multivariable linear population average model was used with log-transformed LOS as the dependent variable to identify which ED operational variables are predictors of LOS for ED discharged, admitted, and overall ED patient categories. Results: Annual ED census ranged from 43 000 to 101 000 patients. The number of ED treatment beds ranged from 27 to 95. Median overall LOS for all sites was 5.4 hours. Daily percentage of admitted patients was found to be a significant predictor of discharged and admitted patient LOS. Higher daily percentage of discharged and eloped patients, more hours on ambulance diversion, and weekday (vs weekend) of patient presentation were significantly associated with prolonged LOS for discharged and admitted patients (P < .05). For each percentage of increase in discharged patients, there was a 1% associated decrease in overall LOS, whereas each percentage of increase in eloped patients was associated with a 1.2% increase in LOS. Conclusions: Length of stay was increased on days with higher percentage daily admissions, higher elopements, higher periods of ambulance diversion, and during weekdays, whereas LOS was decreased on days with higher numbers of discharges and weekends. This is the first study to demonstrate this association across a broad group of hospitals. (C) 2012 Elsevier Inc. All rights reserved. C1 [Wiler, Jennifer L.; Ginde, Adit A.] Univ Colorado Denver SOM, Dept Emergency Med, Aurora, CO 80045 USA. [Wiler, Jennifer L.] Washington Univ, Sch Med, Div Emergency Med, St Louis, MO 63110 USA. [Handel, Daniel A.] Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, Portland, OR 97239 USA. [Aronsky, Dominik] Vanderbilt Univ, Dept Biomed Informat & Emergency Med, Nashville, TN 37232 USA. [Genes, Nicholas G.; Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Hackman, Jeffrey L.] Univ Missouri, Truman Med Ctr, Dept Emergency Med, Kansas City, MO 64139 USA. [Hilton, Joshua A.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Hwang, Ula] James J Peters VAMC, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Kamali, Michael] Univ Rochester, Dept Emergency Med, Rochester, NY 14642 USA. [Pines, Jesse M.] George Washington Univ, Sch Med, Dept Emergency Med, Washington, DC 20037 USA. [Pines, Jesse M.] George Washington Sch Publ Hlth, Dept Hlth Policy, Washington, DC 20037 USA. [Powell, Emilie] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. [Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Emergency Med & Publ Hlth & Prevent Med, Portland, OR 97239 USA. RP Wiler, JL (reprint author), Univ Colorado Denver SOM, Dept Emergency Med, Aurora, CO 80045 USA. EM jennifer.wiler@ucdenver.edu RI Wiler, Jennifer/G-7676-2016; bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017; OI Genes, Nicholas/0000-0002-9836-2477 FU NIA NIH HHS [K24 AG022345] NR 25 TC 11 Z9 11 U1 1 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2012 VL 30 IS 9 BP 1860 EP 1864 DI 10.1016/j.ajem.2012.03.028 PG 5 WC Emergency Medicine SC Emergency Medicine GA 049QD UT WOS:000311997600029 PM 22633732 ER PT J AU Marill, KA AF Marill, Keith A. TI Diagnostic testing and the average absolute likelihood ratio: application to diagnosing wide QRS complex tachycardia and other ED diseases SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID VENTRICULAR-TACHYCARDIA; CONFIDENCE AB The Bayesian approach to disease diagnosis in the emergency department is facilitated by the use of likelihood ratios (LRs) to evaluate diagnostic tests. The use of dichotomous, interval, and joint LRs for single and multiple tests is reviewed, and comparison is made to regression modeling. The clinical motivation for a single statistic to describe the average change in the odds of disease associated with the use of a particular test or series of tests is described. This new extension of the LR concept is termed the average absolute LR (AALR). Illustrative examples include the use of elevated electrocardiogram ST segment and troponin to diagnose acute myocardial infarction, and serum D-dimer and computed tomographic angiography to diagnose pulmonary embolism. Finally, a detailed example with original data demonstrating the use of the AALR to compare QRS duration, QRS axis, and the 2 tests combined to diagnose ventricular tachycardia in patients with stable sustained regular wide QRS tachycardia is provided. Application of both tests together to patients with wide QRS complex tachycardia changes the odds of ventricular tachycardia, on average, by a factor of 3.5 (95% confidence interval, 2.4-6.2). Challenges are described, and methods are provided to estimate the 95% confidence interval of the LR and AALR using bootstrapping techniques. The AALR is a test statistic that may be helpful for clinicians and researchers in evaluating and comparing diagnostic testing approaches. (C) 2012 Elsevier Inc. All rights reserved. C1 [Marill, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Marill, KA (reprint author), Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM kmarill@partners.org NR 16 TC 2 Z9 3 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2012 VL 30 IS 9 BP 1895 EP 1906 DI 10.1016/j.ajem.2012.04.002 PG 12 WC Emergency Medicine SC Emergency Medicine GA 049QD UT WOS:000311997600034 PM 22858576 ER PT J AU Tsai, CL Sullivan, AF Gordon, JA Kaushal, R Magid, DJ Blumenthal, D Camargo, CA AF Tsai, Chu-Lin Sullivan, Ashley F. Gordon, James A. Kaushal, Rainu Magid, David J. Blumenthal, David Camargo, Carlos A., Jr. TI Racial/ethnic differences in emergency care for joint dislocation in 53 US EDs SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID QUALITY-OF-CARE; ACUTE MYOCARDIAL-INFARCTION; LONG-BONE FRACTURES; PROCEDURAL SEDATION; PAIN MANAGEMENT; DEPARTMENT ANALGESIA; RACIAL DISPARITIES; CLINICAL POLICY; HEALTH-CARE; ETHNICITY AB Objective: The aim of the study was to investigate racial/ethnic differences in emergency care for patients with joint dislocation. Methods: We performed a secondary analysis of the dislocation component of the National Emergency Department Safety Study. Using a principal diagnosis of dislocation, we identified emergency department (ED) visits for joint dislocations in 53 urban EDs across 19 US states between 2003 and 2005. Quality of care was evaluated based on 9 guideline-concordant care measures. Results: Of the 1945 patients included in this analysis, 1124 (58%) were white; 561 (29%), black, and 260 (13%), Hispanic. One-third of the 53 EDs cared for 51% of minority patients. After multivariable adjustment, black patients were less likely to receive any analgesic treatment (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.51-0.90) or opioid treatment (OR, 0.64; 95% CI, 0.41-0.997), waited longer to receive analgesia (mean difference in time to analgesic treatment, 32 minutes; 95% CI, 16-52 minutes), and were less likely to receive reassessments of pain (OR, 0.49; 95% CI, 0.34-0.70) compared with white patients. There were no ethnic disparities in most of the care measures between Hispanic and white patients. There were no disparities in initial pain assessment, pre- and postprocedural neurovascular assessment, procedural monitoring, or success of joint reduction across the racial/ethnic groups. Conclusions: Black patients presenting to the ED with joint dislocations received lower quality of care in some, but not all, areas compared with white patients. Future interventions should target these areas to eliminate racial disparities in dislocation care. (C) 2012 Elsevier Inc. All rights reserved. C1 [Tsai, Chu-Lin; Sullivan, Ashley F.; Gordon, James A.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Gordon, James A.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Kaushal, Rainu] Weill Cornell Med Coll, New York, NY 10065 USA. [Kaushal, Rainu] New York Presbyterian Hosp, New York, NY 10065 USA. [Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Aurora, CO 80231 USA. [Magid, David J.] Univ Colorado Denver, Dept Emergency Med, Aurora, CO 80231 USA. [Magid, David J.] Univ Colorado Denver, Dept Prevent Med & Biometr, Aurora, CO 80231 USA. [Blumenthal, David] US Dept HHS, Off Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA. RP Tsai, CL (reprint author), Univ Texas Sch Publ Hlth, Div Epidemiol & Dis Control, Houston, TX 77030 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality (Rockville, MD) [R01 HS013099] FX This study was supported by grant R01 HS013099 from the Agency for Healthcare Research and Quality (Rockville, MD). NR 58 TC 10 Z9 10 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2012 VL 30 IS 9 BP 1970 EP 1980 DI 10.1016/j.ajem.2012.04.023 PG 11 WC Emergency Medicine SC Emergency Medicine GA 049QD UT WOS:000311997600044 PM 22795991 ER PT J AU Dale, S Olds, J AF Dale, Sarah Olds, Jacqueline TI Maintaining professionalism in the face of burnout SO BRITISH JOURNAL OF GENERAL PRACTICE LA English DT Article C1 [Dale, Sarah] Creating Focus, Nottingham, England. [Olds, Jacqueline] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Dale, S (reprint author), Creating Focus, Nottingham, England. EM sarah@creatingfocus.org NR 10 TC 2 Z9 2 U1 0 U2 5 PU ROYAL COLL GENERAL PRACTITIONERS PI LONDON PA 14 PRINCES GATE, HYDE PARK, LONDON SW7 1PU, ENGLAND SN 0960-1643 J9 BRIT J GEN PRACT JI Br. J. Gen. Pract. PD NOV PY 2012 VL 62 IS 604 BP 605 EP 607 DI 10.3399/bjgp12X658449 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 056TQ UT WOS:000312514700031 PM 23211174 ER PT J AU Hivert, MF Dusseault-Belanger, F Cohen, A Courteau, J Vanasse, A AF Hivert, Marie-France Dusseault-Belanger, Francis Cohen, Alan Courteau, Josiane Vanasse, Alain TI Modified Metabolic Syndrome Criteria for Identification of Patients at Risk of Developing Diabetes and Coronary Heart Diseases: Longitudinal Assessment via Electronic Health Records SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ADOLESCENTS; DISPARITIES; MANAGEMENT; DIAGNOSIS; EDUCATION; CANADA AB Background: Metabolic syndrome has been shown to predict type 2 diabetes mellitus and cardiovascular events in well-studied cohorts, but lack of appropriate measures in real-life populations has limited its use in clinical settings. We developed and tested an algorithm to identify patients at risk for future diabetes or coronary heart disease (CHD) events using electronic health records (EHRs) at the Centre Hospitalier Universitaire de Sherbrooke (CHUS). Methods: Patients older than 18 years who had at least 1 visit (outpatient or inpatient) at the CHUS in 2002 or 2003 were included. We excluded patients with diabetes or CHD at baseline. Patients with at least 3 relevant measurements were classified as no metabolic syndrome (zero criteria met), at-risk for metabolic syndrome (1-2 criteria met), or having metabolic syndrome (>= 3 criteria met). Incidence of diabetes and CHD were assessed through 2008. Results: Data from 31,823 patients were included at baseline: 2997 (9.4%) were classified as having metabolic syndrome, while 18,686 (59%) were classified as at risk for metabolic syndrome. During the 5-year follow-up, having metabolic syndrome was associated with a 20.0% risk of developing diabetes (age-and sex-adjusted odds ratio = 5.12 [95% confidence interval, 4.57-5.74]; P < 0.0001) and a 14.7% CHD event incidence (age-and sex-adjusted odds ratio = 1.83 [95% confidence interval, 1.62-2.07]; P < 0.0001). Conclusions: An algorithm based on clinically available EHRs could identify patients at high cardiometabolic risk of future diabetes and CHD in the population receiving care at the CHUS. C1 [Hivert, Marie-France; Dusseault-Belanger, Francis; Cohen, Alan; Courteau, Josiane; Vanasse, Alain] Univ Sherbrooke, Fac Med, Ctr Hosp Univ Sherbrooke, Ctr Rech Clin Etienne Lebel, Sherbrooke, PQ J1H 5N4, Canada. [Hivert, Marie-France] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Univ Sherbrooke, Fac Med, Ctr Hosp Univ Sherbrooke, Ctr Rech Clin Etienne Lebel, 3001 12E Ave Nord, Sherbrooke, PQ J1H 5N4, Canada. EM marie-france.hivert@usherbrooke.ca FU Fonds de Recherche en Sante du Quebec (FRSQ); FRSQ; Canadian Diabetes Association FX The Centre de Recherche Clinique Etienne-LeBel is a clinical research centre supported by the Fonds de Recherche en Sante du Quebec (FRSQ). M.F.H. is supported by an FRSQ Scholar Award (junior 1 level) and a Canadian Diabetes Association Clinical Scientist Award. A.V. receives a career award form the FRSQ as a senior clinician scholar. NR 27 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD NOV-DEC PY 2012 VL 28 IS 6 BP 744 EP 749 DI 10.1016/j.cjca.2012.02.009 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 053GW UT WOS:000312260400021 PM 22552176 ER PT J AU Simonato, M Loscher, W Cole, AJ Dudek, FE Engel, J Kaminski, RM Loeb, JA Scharfman, H Staley, KJ Velisek, L Klitgaard, H AF Simonato, Michele Loescher, Wolfgang Cole, Andrew J. Dudek, F. Edward Engel, Jerome, Jr. Kaminski, Rafal M. Loeb, Jeffrey A. Scharfman, Helen Staley, Kevin J. Velisek, Libor Klitgaard, Henrik TI Finding a better drug for epilepsy: Preclinical screening strategies and experimental trial design SO EPILEPSIA LA English DT Review DE Drug development; Antiseizure drug; Epileptogenesis; Disease modification; Comorbidities; Biomarkers ID INDUCED STATUS EPILEPTICUS; RAT MODEL; INTERICTAL SPIKES; INFANTILE SPASMS; ANIMAL-MODELS; EPILEPTOGENESIS; SEIZURES; IDENTIFICATION; BIOMARKERS; RELEVANCE AB The antiepileptic drugs (AEDs) introduced during the past two decades have provided several benefits: they offered new treatment options for symptomatic treatment of seizures, improved ease of use and tolerability, and lowered risk for hypersensitivity reactions and detrimental drugdrug interactions. These drugs, however, neither attenuated the problem of drug-refractory epilepsy nor proved capable of preventing or curing the disease. Therefore, new preclinical screening strategies are needed to identify AEDs that target these unmet medical needs. New therapies may derive from novel targets identified on the basis of existing hypotheses for drug-refractory epilepsy and the biology of epileptogenesis; from research on genetics, transcriptomics, and epigenetics; and from mechanisms relevant for other therapy areas. Novel targets should be explored using new preclinical screening strategies, and new technologies should be used to develop medium- to high-throughput screening models. In vivo testing of novel drugs should be performed in models mimicking relevant aspects of drug refractory epilepsy and/or epileptogenesis. To minimize the high attrition rate associated with drug development, which arises mainly from a failure to demonstrate sufficient clinical efficacy of new treatments, it is important to define integrated strategies for preclinical screening and experimental trial design. An important tool will be the discovery and implementation of relevant biomarkers that will facilitate a continuum of proof-of-concept approaches during early clinical testing to rapidly confirm or reject preclinical findings, and thereby lower the risk of the overall development effort. In this review, we overview some of the issues related to these topics and provide examples of new approaches that we hope will be more successful than those used in the past. C1 [Simonato, Michele] Univ Ferrara, Ctr Neurosci, Dept Clin & Expt Med, Pharmacol Sect, I-44100 Ferrara, Italy. [Simonato, Michele] Natl Inst Neurosci, Ferrara, Italy. [Loescher, Wolfgang] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Hannover, Germany. [Loescher, Wolfgang] Ctr Syst Neurosci, Hannover, Germany. [Cole, Andrew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Serv, Boston, MA USA. [Dudek, F. Edward] Univ Utah, Dept Physiol, Salk Sch Med, Salt Lake City, UT 84112 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Kaminski, Rafal M.; Klitgaard, Henrik] UCB Pharma, CNS Res, Braine Lalleud, Belgium. [Loeb, Jeffrey A.] Wayne State Univ, Detroit, MI USA. [Scharfman, Helen] NYU, Langone Med Ctr, New York, NY USA. [Scharfman, Helen] Colombia Univ, New York, NY USA. [Staley, Kevin J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Velisek, Libor] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA. [Velisek, Libor] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. RP Simonato, M (reprint author), Univ Ferrara, Ctr Neurosci, Dept Clin & Expt Med, Pharmacol Sect, Via Fossato Mortara 17-19, I-44100 Ferrara, Italy. EM michele.simonato@unife.it FU NINDS NIH HHS [P01 NS002808, R37 NS033310] NR 35 TC 33 Z9 34 U1 2 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2012 VL 53 IS 11 BP 1860 EP 1867 DI 10.1111/j.1528-1167.2012.03541.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 035UM UT WOS:000310975400005 PM 22708847 ER PT J AU Kato, K Yonetsu, T Kim, SJ Xing, L Lee, H McNulty, I Yeh, RW Sakhuja, R Zhang, SS Uemura, S Yu, B Mizuno, K Jang, IK AF Kato, Koji Yonetsu, Taishi Kim, Soo-Joong Xing, Lei Lee, Hang McNulty, Iris Yeh, Robert W. Sakhuja, Rahul Zhang, Shaosong Uemura, Shiro Yu, Bo Mizuno, Kyoichi Jang, Ik-Kyung TI Comparison of Nonculprit Coronary Plaque Characteristics Between Patients With and Without Diabetes A 3-Vessel Optical Coherence Tomography Study SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE diabetes mellitus; optical coherence tomography; plaque ID ACUTE MYOCARDIAL-INFARCTION; INTRAVASCULAR ULTRASOUND ANALYSIS; CARDIOVASCULAR RISK-FACTORS; BEAM COMPUTED-TOMOGRAPHY; THIN-CAP FIBROATHEROMA; ARTERY-DISEASE; ATHEROSCLEROTIC PLAQUES; STENT IMPLANTATION; METABOLIC SYNDROME; MORTALITY AB Objectives The aim of the present study was to compare the characteristics of nonculprit coronary plaques between diabetes mellitus (DM) and non-DM patients using 3-vessel optical coherence tomography (OCT) imaging. Background DM patients have a higher recurrent cardiovascular event rate. Methods Patients who had undergone 3-vessel OCT imaging were identified from the Massachusetts General Hospital OCT Registry. Characteristics of nonculprit plaques were compared between DM and non-DM patients. Results A total of 230 nonculprit plaques were identified in 98 patients. Compared with non-DM patients, DM patients had a larger lipid index (LI) (averaged lipid arc x lipid length; 778.6 +/- 596.1 vs. 1358.3 +/- 939.2, p < 0.001) and higher prevalence of calcification (48.4% vs. 72.2%, p = 0.034) and thrombus (0% vs. 8.3%, p = 0.047). DM patients were divided into 2 groups based on glycated hemoglobin (A(1C)) levels of <= 7.9% and >= 8.0%. LI was significantly correlated with diabetic status (778.6 +/- 596.1 [non-DM] vs. 1,171.5 +/- 708.1 [A(1C) <= 7.9%] vs. 1,638.5 +/- 1,173.8 [A(1C) >= 8%], p value for linear trend = 0.005), and fibrous cap thickness was inversely correlated with the A(1C) level (99.4 +/- 46.7 mu m [non-DM] vs. 91.7 +/- 29.6 mu m [A(1C) <= 7.9%] vs. 72.9 +/- 22.7 mu m [A(1C) >= 8%], p value for linear trend = 0.014). Patients with A(1C) >= 8% also had the highest prevalence of thin-cap fibroatheroma (TCFA) and macrophage infiltration. Conclusions Compared with non-DM patients, DM patients have a larger LI and a higher prevalence of calcification and thrombus. The LI was larger and TCFA and macrophage infiltration were frequent in patients with A(1C) >= 8%. (J Am Coll Cardiol Intv 2012;5:1150-8) (C) 2012 by the American College of Cardiology Foundation C1 [Kato, Koji; Yonetsu, Taishi; Kim, Soo-Joong; Xing, Lei; McNulty, Iris; Yeh, Robert W.; Mizuno, Kyoichi; Jang, Ik-Kyung] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Kim, Soo-Joong] Kyung Hee Univ, Dept Cardiol, Coll Med, Seoul, South Korea. [Sakhuja, Rahul] Wellmont CVA Heart Inst, Kingsport, TN USA. [Zhang, Shaosong] LightLab Imaging St Jude Med, Westford, MA USA. [Zhang, Shaosong] Harbin Med Univ, Harbin, Peoples R China. [Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. Nippon Med Sch, Dept Med, Div Cardiol Hepatol Geriatr & Integrated Med, Tokyo 113, Japan. [Yu, Bo] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2,Key Lab, Educ Minist Myocardial Ischemia Mech & Treatment, Harbin, Peoples R China. RP Jang, IK (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St GRB 800, Boston, MA 02114 USA. EM ijang@partners.org FU St. Jude Medical; Cardiology Division of Massachusetts General Hospital; Dr. John Nam fellowship grant; Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad; LightLab Imaging/St. Jude Medical FX This study was supported by research grants from St. Jude Medical, the Cardiology Division of Massachusetts General Hospital, and a Dr. John Nam fellowship grant. Dr. Kato received a grant from Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad. Dr. Zhang is an employee of LightLab Imaging/St Jude Medical. Dr. Jang received a research grant and consulting fee from LightLab Imaging/St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 43 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD NOV PY 2012 VL 5 IS 11 BP 1150 EP 1158 DI 10.1016/j.jcin.2012.06.019 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 055SV UT WOS:000312438700011 PM 23174639 ER PT J AU Jena, AB Romley, JA Newton-Cheh, C Noseworthy, P AF Jena, Anupam B. Romley, John A. Newton-Cheh, Christopher Noseworthy, Peter TI Therapeutic hypothermia for cardiac arrest: Real-world utilization trends and hospital mortality SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CLINICAL COMORBIDITY INDEX; ADMINISTRATIVE DATA; COMATOSE SURVIVORS; RESUSCITATION; RECOMMENDATIONS; IMPLEMENTATION; ACCURACY AB BACKGROUND: Therapeutic hypothermia (TH) improves outcomes following cardiac arrest in small clinical trials. OBJECTIVE: To study real-world utilization and outcomes in US hospitals. DESIGN: Retrospective cohort study. SETTING: California hospitals. PATIENTS: Patients eligible for therapeutic hypothermia after cardiac arrest. INTERVENTIONS: We analyzed all discharges from California (19992008) to identify patients eligible for TH after cardiac arrest. Patients were considered eligible for TH if both cardiac arrest and anoxic brain injury were among the administrative diagnoses (n = 46,833). Patients undergoing TH (n = 204) were identified through billing codes. MEASUREMENTS: TH utilization and in-hospital mortality. RESULTS: Use of TH increased over the study period with 87.3% (178/204) of TH occurring between 2006 and 2008. Few hospitals appeared to perform TH over the study period (47/419, 11.2%). Utilization of TH was concentrated in a few centers, with the top 3 of 419 centers accounting for 31.4% (64/204) of cases. Patients undergoing TH were younger, less likely to be male, more likely to be treated at teaching centers, and had similar comorbidities compared to eligible individuals who did not undergo TH. The adjusted odds ratio for hospital mortality among patients undergoing TH was 0.80 (95% confidence interval [CI] 0.601.06, P = 0.11). CONCLUSIONS: TH utilization appears low, but implementation is increasing. Case selection and referral biases limit the analysis of the relationship between center TH volume and in-hospital mortality. Journal of Hospital Medicine 2012. (c) 2012 Society of Hospital Medicine. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Romley, John A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Newton-Cheh, Christopher; Noseworthy, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Cardiovasc Res Ctr, Boston, MA USA. [Newton-Cheh, Christopher; Noseworthy, Peter] Ctr Human Genet Res, Boston, MA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU NIH [R03AG031990-A1]; Heart Rhythm Society; Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology FX Disclosures: Dr Romley received support from NIH grant R03AG031990-A1. Dr Noseworthy received support from the Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology granted by the Heart Rhythm Society. The design, conduct, analysis, interpretation, and presentation of the data are the responsibility of the investigators, with no involvement from the funding sources. The contents of this article have not been published in any other peer-reviewed media, and the manuscript is not under review elsewhere. All authors listed have contributed sufficiently to this project to be included as authors. The authors have no conflict of interest, financial or otherwise. NR 32 TC 10 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD NOV-DEC PY 2012 VL 7 IS 9 BP 684 EP 689 DI 10.1002/jhm.1974 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 053AK UT WOS:000312241600004 PM 23023977 ER PT J AU Vazirani, S Lankarani-Fard, A Liang, LJ Stelzner, M Asch, SM AF Vazirani, Sondra Lankarani-Fard, Azadeh Liang, Li-Jung Stelzner, Matthias Asch, Steven M. TI Perioperative processes and outcomes after implementation of a hospitalist-run preoperative clinic SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID NONCARDIAC SURGERY; CARDIOVASCULAR EVALUATION; MEDICAL CONSULTATION; BETA-BLOCKERS; CARE; GUIDELINES; MANAGEMENT; INPATIENTS; ISSUES; TRIAL AB BACKGROUND: A structured, medical preoperative evaluation may positively impact the perioperative course of medically complex patients. Hospitalists are in a unique position to assist in preoperative evaluations, given their expertise with inpatient medicine and postoperative surgical consultation. OBJECTIVE: To evaluate specific outcomes after addition of a Hospitalist-run, medical Preoperative clinic to the standard Anesthesia preoperative evaluation. DESIGN, SETTING, PATIENTS: A pre/post retrospective, comparative review of outcomes of 5223 noncardiac surgical patients at a tertiary care Veterans Administration (VA) medical center. RESULTS: Length of stay was reduced for inpatients with an American Society of Anesthesia (ASA) score of 3 or higher (P < 0.0001). There was a trend towards a reduction in same-day, medically avoidable surgical cancellations (8.5% vs 4.9%, P = 0.065). More perioperative beta blockers were used (P < 0.0001) and more stress tests were ordered (P = 0.012). Inpatient mortality rates were reduced (1.27% vs 0.36%, P = 0.0158). CONCLUSION: A structured medical preoperative evaluation may benefit medically complex patients and improve perioperative processes and outcomes. Journal of Hospital Medicine 2012. (c) 2012 Society of Hospital Medicine C1 [Vazirani, Sondra; Lankarani-Fard, Azadeh] Univ Calif Los Angeles, David Geffen Sch Med, Hospitalist Div, VA Greater Los Angeles Healthcare Syst,Dept Med, Los Angeles, CA 90073 USA. [Liang, Li-Jung] Univ Calif Los Angeles, Dept Med, Stat Core, Los Angeles, CA 90073 USA. [Stelzner, Matthias] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA. [Asch, Steven M.] VA Palo Alto, Hlth Serv Res, Palo Alto, CA USA. RP Vazirani, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Hospitalist Div, VA Greater Los Angeles Healthcare Syst,Dept Med, 11301 Wilshire Blvd,Mail Code 10H1-111, Los Angeles, CA 90073 USA. EM Sondra.vazirani@va.gov NR 19 TC 9 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD NOV-DEC PY 2012 VL 7 IS 9 BP 697 EP 701 DI 10.1002/jhm.1968 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 053AK UT WOS:000312241600006 PM 22961756 ER PT J AU Kangovi, S Grande, D Meehan, P Mitra, N Shannon, R Long, JA AF Kangovi, Shreya Grande, David Meehan, Patricia Mitra, Nandita Shannon, Richard Long, Judith A. TI Perceptions of readmitted patients on the transition from hospital to home SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID SOCIOECONOMIC-STATUS; READMISSIONS; QUALITY; RISK; CARE; REHOSPITALIZATION; MANAGEMENT; DISCHARGE; COVERAGE AB BACKGROUND: Hospital leaders have had mixed success reducing readmissions Little is known about the readmitted patient's perspective. METHODS: A cross-sectional 36-item survey was administered to 1084 readmitted inpatients of The Hospital of the University of Pennsylvania (an urban academic medical center) and Penn Presbyterian Medical Center (an urban community hospital) between November 10, 2010 and July 5, 2011. The survey response rate was 32.9%. RESULTS: The most commonly reported issues contributing to readmission were: 1) feeling unprepared for discharge (11.8%); 2) difficulty performing activities of daily living (ADLs) (10.6%); 3) trouble adhering to discharge medications (5.7%); 4) difficulty accessing discharge medications (5.0%); and 5) lack of social support (4.7%). Low-socioeconomic status (SES) (defined as uninsured or Medicaid) patients were more likely than high-SES patients to report difficulty understanding (odds ratio [OR] 2.7; 95% confidence interval [CI] 1.1, 6.6) and executing (OR 2.2; 95% CI 1.1, 4.4) discharge instructions, difficulty adhering to medications (OR 1.8; 95% CI 1.2, 3.0), lack of social support (OR 2.0; 95% CI 1.2, 3.6), lack of basic resources (OR 2.6; 95% CI 1.1, 6.1), and substance abuse (OR 6.7; 95% CI 2.3, 19.2). CONCLUSIONS: Patients reported transition challenges which they believe contribute to illness relapse and readmission. Interventions designed to address these challenges, and tailored for patient characteristics such as SES, may better address the root causes of readmission. Journal of Hospital Medicine 2012. (c) 2012 Society of Hospital Medicine C1 [Kangovi, Shreya] Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. [Kangovi, Shreya; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Grande, David; Shannon, Richard; Long, Judith A.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Kangovi, Shreya; Grande, David; Long, Judith A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Meehan, Patricia] Univ Penn Hlth Syst, Dept Social Work, Philadelphia, PA USA. [Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Long, Judith A.] Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Kangovi, S (reprint author), Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, 423 Guardian Dr,13th Floor,Blockley Hall, Philadelphia, PA 19104 USA. EM kangovi@mail.med.upenn.edu FU Leonard Davis Institute of Health Economics; HealthWell Foundation; National Human Genome Research Institute; Agency for Healthcare Research and Quality FX Disclosures: Support for this study was provided by a grant from the Leonard Davis Institute of Health Economics. Dr Grande has received honoraria from the Johns Hopkins University CME Program; has a consultancy with the National Nursing Centers Consortium; and has received grant support from, or has grants pending with, the HealthWell Foundation, the National Human Genome Research Institute, and the Agency for Healthcare Research and Quality. Dr Shannon is the founder of a biotech company, Ventrigen, LLC; is a senior fellow at IHI; is on the scientific advisory boards for Glasgow Smith Klein, Pfizer, Merck, and Value Capture; and is a member of the Board of Directors of the ABIM. NR 17 TC 24 Z9 24 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD NOV-DEC PY 2012 VL 7 IS 9 BP 709 EP 712 DI 10.1002/jhm.1966 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 053AK UT WOS:000312241600009 PM 23212980 ER PT J AU Kang, S Akerblad, P Kiviranta, R Gupta, RK Kajimura, S Griffin, MJ Min, J Baron, R Rosen, ED AF Kang, Sona Akerblad, Peter Kiviranta, Riku Gupta, Rana K. Kajimura, Shingo Griffin, Michael J. Min, Jie Baron, Roland Rosen, Evan D. TI Regulation of Early Adipose Commitment by Zfp521 SO PLOS BIOLOGY LA English DT Article ID B-CELL FACTOR; ADIPOCYTE DIFFERENTIATION; OSTEOBLAST DIFFERENTIATION; GENE-EXPRESSION; BONE-FORMATION; PPAR-GAMMA; STEM-CELLS; IN-VIVO; ADIPOGENESIS; ZFP423 AB While there has been significant progress in determining the transcriptional cascade involved in terminal adipocyte differentiation, less is known about early events leading to lineage commitment and cell fate choice. It has been recently discovered that zinc finger protein 423 (Zfp423) is an early actor in adipose determination. Here, we show that a close paralog of Zfp423, Zfp521, acts as a key regulator of adipose commitment and differentiation in vitro and in vivo. Zfp521 exerts its actions by binding to early B cell factor 1 (Ebf1), a transcription factor required for the generation of adipocyte progenitors, and inhibiting the expression of Zfp423. Overexpression of Zfp521 in cells greatly inhibits adipogenic potential, whereas RNAi-mediated knock-down or genetic ablation of Zfp521 enhances differentiation. In addition, Zfp521(-/-) embryos exhibit increased mass of interscapular brown adipose tissue and subcutaneous white adipocytes, a cell autonomous effect. Finally, Ebf1 participates in a negative feedback loop to repress Zfp521 as differentiation proceeds. Because Zfp521 is known to promote bone development, our results suggest that it acts as a critical switch in the commitment decision between the adipogenic and osteogenic lineages. C1 [Kang, Sona; Akerblad, Peter; Griffin, Michael J.; Min, Jie; Rosen, Evan D.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. [Kang, Sona; Akerblad, Peter; Gupta, Rana K.; Kajimura, Shingo; Griffin, Michael J.; Min, Jie; Rosen, Evan D.] Harvard Univ, Sch Med, Boston, MA USA. [Akerblad, Peter] AstraZeneca R&D, Molndal, Sweden. [Kiviranta, Riku; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Kiviranta, Riku; Baron, Roland] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Gupta, Rana K.; Kajimura, Shingo] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Gupta, Rana K.; Kajimura, Shingo] Dana Farber Canc Inst, Div Metab & Chron Dis, Boston, MA 02115 USA. RP Kang, S (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. EM erosen@bidmc.harvard.edu FU NIH [AR48218, AR 57769]; [NIHDK078061] FX This work was supported by NIHDK078061 to EDR and by NIH AR48218 and AR 57769 to RB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 36 Z9 38 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2012 VL 10 IS 11 AR e1001433 DI 10.1371/journal.pbio.1001433 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 048CR UT WOS:000311888300016 PM 23209378 ER PT J AU Mathias, SD Chren, MM Yim, YM Colwell, HH Reyes, C Chen, DM Fosko, SW AF Mathias, S. D. Chren, M. M. Yim, Y. M. Colwell, H. H. Reyes, C. Chen, D. M. Fosko, S. W. TI ASSESSING HEALTH-RELATED QUALITY OF LIFE (HRQOL) FOR ADVANCED BASAL CELL CARCINOMA (ABCC) AND BASAL CELL CARCINOMA NEVUS SYNDROME (BCCNS): DEVELOPMENT OF THE FIRST DISEASE-SPECIFIC PATIENT-REPORTED OUTCOME (PRO) QUESTIONNAIRE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Mathias, S. D.; Colwell, H. H.] Hlth Outcomes Solut, Winter Pk, FL USA. [Chren, M. M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Yim, Y. M.; Reyes, C.; Chen, D. M.] Genentech Inc, San Francisco, CA 94080 USA. [Fosko, S. W.] St Louis Univ, Sch Med, St Louis, MO 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 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2012 VL 15 IS 7 BP A430 EP A430 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 055JF UT WOS:000312411100807 ER PT J AU Pietzsch, JB Geisler, BP Jaff, MR AF Pietzsch, J. B. Geisler, B. P. Jaff, M. R. TI BUDGET IMPACT OF DRUG ELUTING BALLOONS FOR INTERMITTENT CLAUDICATION FROM SUPERFICIAL FEMORAL ARTERY DISEASE IN THE UNITED STATES HEALTH CARE SYSTEM SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Pietzsch, J. B.; Geisler, B. P.] Wing Tech Inc, Menlo Pk, CA USA. [Jaff, M. R.] Mass Gen Hosp, Boston, MA USA. RI Geisler, Benjamin/A-9244-2010 OI Geisler, Benjamin/0000-0003-1704-6067 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 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2012 VL 15 IS 7 BP A348 EP A348 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 055JF UT WOS:000312411100378 ER PT J AU Schlosser, RJ AF Schlosser, Rodney J. TI To Balloon or Not to Balloon? SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article C1 [Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Dept Surg Otolaryngol, Charleston, SC USA. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Ste 1130,POB 250550, Charleston, SC 29425 USA. EM schlossr@musc.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2012 VL 138 IS 11 BP 1080 EP 1081 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 055FH UT WOS:000312400100013 PM 23165384 ER PT J AU Sethi, R Kozin, E Lin, HW Faquin, WC Randolph, GW AF Sethi, Roshan Kozin, Elliott Lin, Harrison W. Faquin, William C. Randolph, Gregory W. TI Pathology Quiz Case 2 Papillary Thryoid Carcinoma Arising in the Setting of Black Thyroid SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID MINOCYCLINE; PIGMENTATION; GLAND C1 [Sethi, Roshan; Kozin, Elliott; Lin, Harrison W.; Randolph, Gregory W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kozin, Elliott; Lin, Harrison W.; Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sethi, R (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2012 VL 138 IS 11 BP 1093 EP 1095 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 055FH UT WOS:000312400100018 PM 23165392 ER PT J AU Merkow, RP Bilimoria, KY McCarter, MD Phillips, JD DeCamp, MM Sherman, KL Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. McCarter, Martin D. Phillips, Joseph D. DeCamp, Malcolm M. Sherman, Karen L. Ko, Clifford Y. Bentrem, David J. TI Short-term Outcomes After Esophagectomy at 164 American College of Surgeons National Surgical Quality Improvement Program Hospitals Effect of Operative Approach and Hospital-Level Variation SO ARCHIVES OF SURGERY LA English DT Article ID LIMITED TRANSHIATAL RESECTION; ESOPHAGUS; ADENOCARCINOMA; CARCINOMA; SURVIVAL; CANCER; IMPACT AB Hypothesis: When assessing the effect of operative approach on outcomes, it may be less relevant whether a transhiatal or an Ivor Lewis esophagectomy was performed and may be more important to focus on patient selection and the quality of the hospital performing the operation. Design: Observational study. Setting: Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program. Patients: Individuals undergoing esophagectomy were identified from January 1, 2005, to December 31, 2010. The following 4 groups were created based on operative approach: transhiatal, Ivor Lewis, 3-field, and any approach with an intestinal conduit. Main Outcome Measures: Risk-adjusted 30-day outcomes and hospital-level variation in performance. Results: At 164 hospitals, 1738 patients underwent an esophageal resection: 710 (40.9%) were transhiatal, 497 (28.6%) were Ivor Lewis, 361 (20.8%) were 3-field, and 170 (9.8%) were intestinal conduits. Compared with the transhiatal approach, Ivor Lewis esophagectomy was not associated with increased risk for postoperative complications; however, 3-field esophagectomy was associated with increased likelihood of postoperative pneumonia (odds ratio [OR], 1.88; 95% CI, 1.28-2.77) and prolonged ventilation exceeding 48 hours (OR, 1.68; 95% CI, 1.16-2.42). Intestinal conduit use was associated with increased 30-day mortality (OR, 2.65; 95% CI, 1.08-6.47), prolonged ventilation exceeding 48 hours (OR, 1.61; 95% CI, 1.01-2.54), and return to the operating room for any indication (OR, 1.85; 95% CI, 1.16-2.96). Patient characteristics were the strongest predictive factors for 30-day mortality and serious morbidity. After case-mix adjustment, hospital performance varied by 161% for 30-day mortality and by 84% for serious morbidity. Conclusions: Compared with transhiatal dissection, Ivor Lewis esophagectomy did not result in worse postoperative complications. After controlling for case-mix, hospital performance varied widely for all outcomes assessed, indicating that reductions in short-term outcomes will likely result from expanding other aspects of hospital quality beyond a focus on specific technical maneuvers. Arch Surg. 2012;147(11):1009-1016 C1 [Merkow, Ryan P.; Bilimoria, Karl Y.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bilimoria, Karl Y.; Phillips, Joseph D.; DeCamp, Malcolm M.; Sherman, Karen L.; Bentrem, David J.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA. [Merkow, Ryan P.; McCarter, Martin D.] Univ Colorado Denver Anschutz Med Campus, Dept Surg, Aurora, CO USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Merkow, RP (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM rmerkow@facs.org FU American College of Surgeons Clinical Scholars in Residence Program; Career Development Award from the Health Services Research Division, Department of Veterans Affairs FX Dr Merkow is supported by the American College of Surgeons Clinical Scholars in Residence Program. Dr Bentrem is supported by a Career Development Award from the Health Services Research Division, Department of Veterans Affairs. NR 22 TC 19 Z9 19 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD NOV PY 2012 VL 147 IS 11 BP 1009 EP 1016 PG 8 WC Surgery SC Surgery GA 055EG UT WOS:000312397400006 PM 23165615 ER PT J AU Lin, M Zhao, Y Wang, SQ Liu, M Duan, ZF Chen, YM Li, F Xu, F Lu, TJ AF Lin, Min Zhao, Ying Wang, ShuQi Liu, Ming Duan, ZhenFeng Chen, YongMei Li, Fei Xu, Feng Lu, TianJian TI Recent advances in synthesis and surface modification of lanthanide-doped upconversion nanoparticles for biomedical applications SO BIOTECHNOLOGY ADVANCES LA English DT Review DE Lanthanide-doped upconversion nanoparticles; Synthesis; Surface modification; Biomedical applications ID CONVERTING PHOSPHOR TECHNOLOGY; CATIONIC IRIDIUM(III) COMPLEXES; EARTH FLUORIDE NANOCRYSTALS; IN-VIVO; FLUORESCENT NANOPARTICLES; PHOTODYNAMIC THERAPY; NAYF4 NANOCRYSTALS; QUANTUM DOTS; LATERAL-FLOW; UPCONVERTING NANOPARTICLES AB Lanthanide (Ln)-doped upconversion nanoparticles (UCNPs) with appropriate surface modification can be used for a wide range of biomedical applications such as bio-detection, cancer therapy, bio-labeling, fluorescence imaging, magnetic resonance imaging and drug delivery The upconversion phenomenon exhibited by Ln-doped UCNPs renders them tremendous advantages in biological applications over other types of fluorescent materials (e.g.. organic dyes, fluorescent proteins, gold nanoparticles, quantum dots, and luminescent transition metal complexes) for: (i) enhanced tissue penetration depths achieved by near-infrared (NIR) excitation; (ii) improved stability against photobleaching, photoblinking and photochemical degradation; (iii) non-photodamaging to DNA/RNA due to lower excitation light energy; (iv) lower cytotoxicity; and (v) higher detection sensitivity. Ln-doped UCNPs are therefore attracting increasing attentions in recent years. In this review, we present recent advances in the synthesis of Ln-doped UCNPs and their surface modification, as well as their emerging applications in biomedicine. The future prospects of Ln-doped UCNPs for biomedical applications are also discussed. (c) 2012 Elsevier Inc. All rights reserved. C1 [Lin, Min; Xu, Feng] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. [Lin, Min; Zhao, Ying; Chen, YongMei; Li, Fei; Xu, Feng; Lu, TianJian] Xi An Jiao Tong Univ, Biomed Engn & Biomech Ctr, Xian 710049, Peoples R China. [Wang, ShuQi] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Liu, Ming] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Duan, ZhenFeng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Cambridge, MA 02138 USA. [Chen, YongMei; Li, Fei] Xi An Jiao Tong Univ, Sch Sci, Dept Chem, Xian 710049, Peoples R China. RP Xu, F (reprint author), Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. EM fengxu@mail.xjtu.edu.cn; tjlu@xjtu.edu.cn RI Liu, Ming/B-4143-2009; Xu, Feng/C-7430-2011; Lu, Tian Jian/E-6063-2016; Xu, Feng/H-4468-2011; OI Liu, Ming/0000-0002-6310-948X; Xu, Feng/0000-0003-4351-0222; Duan, Zhenfeng/0000-0002-8543-083X FU Major International (Regional) Joint Research Program of China [11120101002]; National Natural Science Foundation of China [10825210]; National 111 Project of China [B06024] FX This work was supported by the Major International (Regional) Joint Research Program of China (11120101002); the National Natural Science Foundation of China (10825210); and the National 111 Project of China (B06024). NR 153 TC 102 Z9 109 U1 34 U2 470 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0734-9750 EI 1873-1899 J9 BIOTECHNOL ADV JI Biotechnol. Adv. PD NOV-DEC PY 2012 VL 30 IS 6 BP 1551 EP 1561 DI 10.1016/j.biotechadv.2012.04.009 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 047RQ UT WOS:000311859100032 PM 22561011 ER PT J AU Garber, JE AF Garber, J. E. TI Cancer risk-reducing measures for high risk women SO BREAST LA English DT Meeting Abstract C1 [Garber, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD NOV PY 2012 VL 21 SU 1 BP S2 EP S2 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 054QB UT WOS:000312357200006 ER PT J AU Partridge, AH AF Partridge, A. H. TI Management of early menopause associated symptoms SO BREAST LA English DT Meeting Abstract C1 [Partridge, A. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD NOV PY 2012 VL 21 SU 1 BP S6 EP S6 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 054QB UT WOS:000312357200019 ER PT J AU Rosenberg, S Tamimi, R Gelber, S Ruddy, K Kereakoglow, S Borges, V Come, S Schapira, L Winer, E Partridge, A AF Rosenberg, S. Tamimi, R. Gelber, S. Ruddy, K. Kereakoglow, S. Borges, V. Come, S. Schapira, L. Winer, E. Partridge, A. TI Sexual functioning in young women with breast cancer SO BREAST LA English DT Meeting Abstract C1 [Rosenberg, S.; Tamimi, R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gelber, S.; Ruddy, K.; Kereakoglow, S.; Partridge, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Borges, V.] Univ Colorado, Dept Med Oncol, Denver, CO 80202 USA. [Come, S.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Schapira, L.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD NOV PY 2012 VL 21 SU 1 BP S13 EP S13 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 054QB UT WOS:000312357200034 ER PT J AU Harris, WH AF Harris, William H. TI Edge Loading Has a Paradoxical Effect on Wear in Metal-on-Polyethylene Total Hip Arthroplasties SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ACETABULAR COMPONENT; CERAMIC BEARINGS; IMPINGEMENT; SQUEAKING; ALUMINA; MICROSEPARATION; REPLACEMENTS; ORIENTATION; LINERS; CUPS AB Background Edge wear is an adverse factor that can negatively impact certain THAs. In some metal-on-metal THAs, it can lead to adverse tissue reactions including aseptic lymphocytic vasculitis-associated lesions and even to pseudotumor formation. In some ceramic-on-ceramic THAs, it can lead to squeaking and/or stripe wear. Edge wear in metal-on-metal and ceramic-on-ceramic THAs can also be associated with accelerated wear across the articulation of these joints. Questions/purposes I asked: Does edge wear occur in metal-on-polyethylene (MOP) articulations? And if so, does it increase joint wear? Methods I examined the evidence in the literature for edge wear occurring in MOP THA and then assessed the evidence in the literature for data supporting the concept that edge wear in MOP hips could accelerate wear across the articulation over time. Results Extensive data in the literature confirm edge wear is common in MOP THA. Surprisingly, the evidence does not support that it accelerates wear across the articulation. In fact, substantial data support the concept that it does not. Conclusions These observations suggest, in terms of edge wear accelerating overall wear, MOP articulation may have a privileged position compared to hard-on-hard THA articulations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harris, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ1126, Boston, MA 02114 USA. EM wharrishm@hotmail.com FU Biomet, Inc (Warsaw, IN, USA); Zimmer, Inc (Warsaw, IN, USA); DePuy Orthopaedics, Inc (Warsaw, IN, USA); Zimmer, Inc FX Massachusetts General Hospital has received, in any 1 year, funding from Biomet, Inc (Warsaw, IN, USA), Zimmer, Inc (Warsaw, IN, USA), and DePuy Orthopaedics, Inc (Warsaw, IN, USA). The author certifies that he has or may receive payments or benefits, in any 1 year, an amount in excess of $100,000 from Zimmer, Inc, related to this work. The author certifies that he has a patent planned or pending or issued that has been assigned to the Massachusetts General Hospital, which has licensed it to Zimmer, Inc. NR 33 TC 18 Z9 18 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2012 VL 470 IS 11 BP 3077 EP 3082 DI 10.1007/s11999-012-2330-7 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 054TX UT WOS:000312368200017 PM 22644421 ER PT J AU Bot, AGJ Vranceanu, AM Herndon, JH Ring, DC AF Bot, Arjan G. J. Vranceanu, Ana-Maria Herndon, James H. Ring, David C. TI Correspondence of Patient Word Choice with Psychologic Factors in Patients With Upper Extremity Illness SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID LOW-BACK-PAIN; INTERACTION ANALYSIS SYSTEM; QUALITY-OF-LIFE; CANCER-PATIENTS; PRIMARY-CARE; PROVIDER COMMUNICATION; MEDICAL OUTPATIENTS; ORTHOPEDIC TRAUMA; MISSING DATA; SATISFACTION AB Background Studies of patients with back pain, cancer, and in a general medical practice note that the use of certain phrases by a patient when communicating with their health provider can indicate greater disability and distress than expected for patients with a given disorder. However, it is unclear whether such phrases apply to patients with hand and arm disorders. Questions/purposes We assessed whether specific patient phrases are associated with symptoms, disability, and psychologic factors in patients with hand and arm disorders. Methods We recorded and coded 61 interviews of new patients. Specific expressions of patients were listed and categorized into six phrase categories: "I can't'', "Find it and fix it'', "Something is wrong'', "It's serious'', "Deemphasis (hoping)'', and "Protective mindset''. Patients completed questionnaires for arm-specific disability (DASH), depression (Patient Health Questionnaire [PHQ-9]), pain catastrophizing (Pain Catastrophizing Scale [PCS]), and heightened illness concern (Whiteley Index). Results Patients who endorsed phrases in the category "I can't'' had higher scores on the PCS, Whiteley, DASH, and pain; they also had longer visits. Patients expressing "Something is wrong'' had higher scores for the PCS, pain, and duration of visit. Patients using "It's serious'' had a higher score for pain. Finally, patients using "Protective mindset'' had lower PHQ-9 scores and younger age. Conclusions Patient word choice may indicate underlying distress or ineffective coping strategies that represent important opportunities for empathy and support, including evidence-based cognitive and behavioral interventions. C1 [Herndon, James H.; Ring, David C.] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Vranceanu, Ana-Maria] Massachusetts Gen Hosp, Dept Psychiat, Benson Henry Mind Body Inst, Boston, MA 02114 USA. [Vranceanu, Ana-Maria] Massachusetts Gen Hosp, Dept Behav Med, Benson Henry Mind Body Inst, Boston, MA 02114 USA. [Herndon, James H.; Ring, David C.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Wiser Together Inc, Washington, DC, USA; Skeletal Dynamics LLC (Miami, FL, USA); Wright Medical Technology, Inc (Arlington, TN, USA); Biomet, Inc (Warsaw, IN, USA); AO North America (Paoli, PA, USA); AO International (Davos, Switzerland); Illuminos (Providence, RI, USA) FX One of the authors (JHH) certifies that he has or may receive payments or benefits, during the study period, less than $10,000) from wisertogether.com (Wiser Together Inc, Washington, DC, USA). One of the authors (DCR) certifies that he has or may receive payments or benefits, during the study period, greater than $10,000 from Skeletal Dynamics LLC (Miami, FL, USA), Wright Medical Technology, Inc (Arlington, TN, USA), Biomet, Inc (Warsaw, IN, USA), AO North America (Paoli, PA, USA), AO International (Davos, Switzerland), and Illuminos (Providence, RI, USA). NR 38 TC 2 Z9 2 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2012 VL 470 IS 11 BP 3180 EP 3186 DI 10.1007/s11999-012-2436-y PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 054TX UT WOS:000312368200030 PM 22707072 ER PT J AU Conners, EE Hagedorn, HJ Butler, JN Felmet, K Hoang, T Wilson, P Klima, G Sudzina, E Anaya, HD AF Conners, E. E. Hagedorn, H. J. Butler, J. N. Felmet, K. Hoang, T. Wilson, P. Klima, G. Sudzina, E. Anaya, H. D. TI Evaluating the implementation of nurse-initiated HIV rapid testing in three Veterans Health Administration substance use disorder clinics SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE HIV; AIDS; screening; nurse initiated; rapid test; Veterans Health Administration; substance use disorder ID CARE SETTINGS; PHYSICIANS AB Individuals with substance use disorders (SUDs) are at higher risk of HIV infection, yet recent studies show rates of HIV testing are low among this population. We implemented and evaluated a nurse-initiated HIV oral rapid testing (NRT) strategy at three Veterans Health Administration SUD clinics. Implementation of NRT includes streamlined nurse training and a computerized clinical reminder. The evaluation employed qualitative interviews with staff and a quantitative evaluation of HIV testing rates. Barriers to testing included lack of laboratory support and SUD nursing resistance to performing medical procedures. Facilitators included the ease of NAT integration into workflow, engaged management and an existing culture of disease prevention. Six-months post intervention, rapid testing rates at SUD clinics in sites 1, 2, and 3 were 5.0%, 1.1% and 24.0%, respectively. Findings indicate that NAT can be successfully incorporated into some types of SUD subclinics with minimal perceived impact on workflow and time. C1 [Conners, E. E.; Butler, J. N.; Hoang, T.; Anaya, H. D.] VA Greater Los Angeles Healthcare Syst, Vet Affairs Qual Enhancement Res Initiat QUERI HI, Los Angeles, CA USA. [Conners, E. E.; Butler, J. N.; Hoang, T.; Anaya, H. D.] Ctr Excellence Study Healthcare Provider Behav, VA Hlth Serv Res & Dev HSR&D, Los Angeles, CA USA. [Hagedorn, H. J.] Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Hagedorn, H. J.] Minneapolis VA Healthcare Syst, VA QUERI Subst Use Disorders, Minneapolis, MN USA. [Felmet, K.] Georgia State Univ, Atlanta, GA 30303 USA. [Felmet, K.; Wilson, P.; Klima, G.; Sudzina, E.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. [Anaya, H. D.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. [Anaya, H. D.] VA Chicago Healthcare Syst, VA Ctr Management Complex Chron Condit CMC3, Chicago, IL USA. [Anaya, H. D.] VA Chicago Healthcare Syst, Qual Enhancement Res Initiat Spinal Cord Injury S, Chicago, IL USA. RP Conners, EE (reprint author), 9500 Gilman Dr,MC 0507, La Jolla, CA 92093 USA. EM conners84@gmail.com FU VA Quality Enhancement Research Initiative (QUERI) [RRP 09-122]; Department of Veterans Affairs, Veterans Health Administration (VHA), Health Services Research and Development Service (HSRD) FX The authors would like to thank Dr Matthew Goetz, Dr Herschel Knapp, Dr Gretchen Haas, Dr Dmitriy Gutkin, and Helen Bonanomi for their invaluable assistance on this project. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. This research was funded by VA Quality Enhancement Research Initiative (QUERI) grant RRP 09-122 awarded to the last author and supported by the Department of Veterans Affairs, Veterans Health Administration (VHA), Health Services Research and Development Service (HSR&D). This study was reviewed and sanctioned by a US Department of Veterans Affairs Institutional Review Board (IRB) process. The last author owns stock in a company that develops biotechnological products, one of which is a RT for diagnosing HIV and is also principal investigator on an external HIV linkage to care grant. NR 17 TC 6 Z9 6 U1 0 U2 6 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD NOV PY 2012 VL 23 IS 11 BP 799 EP 805 DI 10.1258/ijsa.2012.012050 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 054OD UT WOS:000312352200008 PM 23155100 ER PT J AU Liu, XH Yao, S Levine, AC Kirschenbaum, A Pan, JP Wu, Y Qin, WP Collier, L Bauman, WA Cardozo, CP AF Liu, Xin-Hua Yao, Shen Levine, Alice C. Kirschenbaum, Alexander Pan, Jiangping Wu, Yong Qin, Weiping Collier, Lauren Bauman, William A. Cardozo, Christopher P. TI Nandrolone, an Anabolic Steroid, Stabilizes Numb Protein Through Inhibition of mdm2 in C2C12 Myoblasts SO JOURNAL OF ANDROLOGY LA English DT Article DE Androgen receptor; skeleton muscle; notch signaling ID POSTNATAL MYOGENESIS; UBIQUITIN LIGASE; SKELETAL-MUSCLE; CELL ACTIVATION; MAMMALIAN NUMB; NOTCH; DIFFERENTIATION; TESTOSTERONE; HYPERTROPHY; ANDROGENS AB Nandrolone, an anabolic steroid, slows denervation atrophy of rat muscle, prevents denervation-induced nuclear accumulation of intracellular domain of the Notch receptor, and elevates expression of Numb. Numb acts as an inhibitor of Notch signaling and promotes myogenic differentiation of satellite cells. Turnover of Numb is regulated by mdm2, an E3 ubiquitin ligase. With these considerations in mind, we investigated the effects of nandrolone on the expression of Numb and mdm2 proteins and determined the effect of mdm2 on nandrolone-induced alterations in Numb protein in C2C12 myoblasts. When C2C12 cells were cultured in a medium favoring differentiation (Dulbecco modified Eagle medium containing 2% horse serum), nandrolone up-regulated Numb protein levels in a time-dependent manner and prolonged Numb protein half-life from 10 to 18 hours. In contrast, nandrolone reduced the expression of mdm2 protein. To determine whether the decreased mdm2 expression induced by nandrolone was responsible for the increased levels and prolonged half-life of Numb protein in this cell line, mdm2 small interfering RNA (siRNA) was employed to inhibit mdm2 expression. Compared to cells transfected with scrambled siRNA (negative control), transfection with mdm2-siRNA increased basal Numb protein expression but abolished the further increase in Numb protein levels by nandrolone. In addition, transfection of mdm2-siRNA mimicked the effect of nandrolone to prolong the half-life of Numb protein. Moreover, when C2C12 cells were forced to overexpress mdm2, there was a significant decline in the expression of both basal and inducible Numb protein. Our data suggest that nandrolone, by a novel mechanism for this agent in a muscle cell type, increases Numb protein levels in C2C12 myoblasts by stabilizing Numb protein against degradation, at least in part, via suppression of mdm2 expression. C1 [Liu, Xin-Hua; Pan, Jiangping; Wu, Yong; Qin, Weiping; Collier, Lauren; Bauman, William A.; Cardozo, Christopher P.] James J Peter VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY 10468 USA. [Liu, Xin-Hua; Yao, Shen; Levine, Alice C.; Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Levine, Alice C.; Kirschenbaum, Alexander] Mt Sinai Sch Med, Dept Urol, New York, NY USA. [Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Cardozo, CP (reprint author), James J Peter VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM chris.cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, F7756R, F6997R] FX Supported by the Veterans Health Administration, Rehabilitation Research and Development Service (grants B4162C, F7756R, and F6997R). NR 29 TC 3 Z9 3 U1 1 U2 5 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 EI 1939-4640 J9 J ANDROL JI J. Androl. PD NOV-DEC PY 2012 VL 33 IS 6 BP 1216 EP 1223 DI 10.2164/jandrol.112.016428 PG 8 WC Andrology SC Endocrinology & Metabolism GA 051GC UT WOS:000312113200021 PM 22700758 ER PT J AU Singh, JA Sperling, JW Schleck, C Harmsen, WS Cofield, RH AF Singh, Jasvinder A. Sperling, John W. Schleck, Cathy Harmsen, William S. Cofield, Robert H. TI Periprosthetic infections after total shoulder arthroplasty: a 33-year perspective SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Total shoulder arthroplasty; periprosthetic infections ID QUALITY-OF-LIFE; HIP-ARTHROPLASTY; REIMPLANTATION; COMPLICATIONS; MORBIDITY AB Background: To examine the rates and predictors of deep periprosthetic infections after primary total shoulder arthroplasty (TSA). Methods: We used prospectively collected data on all primary TSA patients from 1976-2008 at Mayo Clinic Medical Center. We estimated survival free of deep periprosthetic infections after primary TSA using Kaplan-Meier survival. Univariate and multivariable Cox regression was used to assess the association of patient-related factors (age, gender, body mass index), comorbidity (Deyo-Charlson index), American Society of Anesthesiologists class, implant fixation, and underlying diagnosis with risk of infection. Results: A total of 2,207 patients, with a mean age of 65 years (SD, 12 years), 53% of whom were women, underwent 2,588 primary TSAs. Mean follow-up was 7 years (SD, 6 years), and the mean body mass index was 30 kg/m(2) (SD, 6 kg/m(2)). The American Society of Anesthesiologists class was 1 or 2 in 61% of cases. Thirty-two confirmed deep periprosthetic infections occurred during follow-up. In earlier years, Staphylococcus predominated; in recent years, Propionibacterium acnes was almost as common. The 5-, 10-, and 20-year prosthetic infection-free rates were 99.3% (95% confidence interval [CI], 98.9-99.6), 98.5% (95% CI, 97.8-99.1), and 97.2% (95% CI, 96.0-98.4), respectively. On multivariable analysis, a male patient had a significantly higher risk of deep periprosthetic infection (hazard ratio, 2.67 [95% CI, 1.22-5.87]; P = .01) and older age was associated with lower risk (hazard ratio, 0.97 [95% CI, 0.95-1.00] per year; P = .05). Conclusions: The periprosthetic infection rate was low at 20-year follow-up. Male gender and younger age were significant risk factors for deep periprosthetic infections after TSA. Future studies should investigate whether differences in bone morphology, medical comorbidity, or other factors are underlying these associations. Level of evidence: Level IV, Case Series, Treatment Study. (C) 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Sperling, John W.; Cofield, Robert H.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institutes of Health Clinical Translational Science Award (Mayo Clinic Center for Clinical and Translational Research) [1 KL2 RR024151-01]; Allergan; Takeda; Savient; Wyeth; Amgen; Tornier; URL Pharmaceuticals; Novartis FX This material is the result of work supported by National Institutes of Health Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and the use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA.; There are no financial conflicts related to this work. J.A.S. has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. J.W.S. has received royalties from Aircast and Biomet and consultant fees from Tornier and owns stock in Tornier. R.H.C. has received royalties from Smith & Nephew. NR 17 TC 52 Z9 53 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD NOV PY 2012 VL 21 IS 11 BP 1534 EP 1541 DI 10.1016/j.jse.2012.01.006 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 049RH UT WOS:000312000600019 PM 22516570 ER PT J AU Bandyopadhaya, A Kesarwani, M Que, YA He, JX Padfield, K Tompkins, R Rahme, LG AF Bandyopadhaya, Arunava Kesarwani, Meenu Que, Yok-Ai He, Jianxin Padfield, Katie Tompkins, Ronald Rahme, Laurence G. TI The Quorum Sensing Volatile Molecule 2-Amino Acetophenon Modulates Host Immune Responses in a Manner that Promotes Life with Unwanted Guests SO PLOS PATHOGENS LA English DT Article ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; N-3-OXODODECANOYL HOMOSERINE LACTONE; TOLL-LIKE-RECEPTORS; PSEUDOMONAS-AERUGINOSA; INNATE IMMUNITY; ENDOTOXIN TOLERANCE; BACTERIAL VIRULENCE; GENE-EXPRESSION; N-(3-OXODODECANOYL)-L-HOMOSERINE LACTONE AB Increasing evidence indicates that bacterial quorum sensing (QS) signals are important mediators of immunomodulation. However, whether microbes utilize these immunomodulatory signals to maintain infection remain unclear. Here, we show that the Pseudomonas aeruginosa QS-regulated molecule 2-amino acetophenone (2-AA) modulates host immune responses in a manner that increases host ability to cope with this pathogen. Mice treated with 2-AA prior to infection had a 90% survival compared to 10% survival rate observed in the non-pretreated infected mice. Whilst 2-AA stimulation activates key innate immune response pathways involving mitogen-activated protein kinases (MAPKs), nuclear factor (NF)-kappa B, and pro-inflammatory cytokines, it attenuates immune response activation upon pretreatment, most likely by upregulating anti-inflammatory cytokines. 2-AA host pretreatment is characterized by a transcriptionally regulated block of c-JUN N-terminal kinase (JNK) and NF-kappa B activation, with relatively preserved activation of extracellular regulated kinase (ERK) 1/2. These kinase changes lead to CCAAT/enhancer-binding protein-beta (c/EBP beta) activation and formation of the c/EBP beta-p65 complex that prevents NF-kappa B activation. 2-AA's aptitude for dampening the inflammatory processes while increasing host survival and pathogen persistence concurs with its ability to signal bacteria to switch to a chronic infection mode. Our results reveal a QS immunomodulatory signal that promotes original aspects of interkingdom communication. We propose that this communication facilitates pathogen persistence, while enabling host tolerance to infection. C1 [Bandyopadhaya, Arunava; Kesarwani, Meenu; Que, Yok-Ai; He, Jianxin; Padfield, Katie; Tompkins, Ronald; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Bandyopadhaya, Arunava; Kesarwani, Meenu; Que, Yok-Ai; He, Jianxin; Padfield, Katie; Tompkins, Ronald; Rahme, Laurence G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bandyopadhaya, Arunava; Kesarwani, Meenu; Que, Yok-Ai; He, Jianxin; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Bandyopadhaya, Arunava; Kesarwani, Meenu; Que, Yok-Ai; He, Jianxin; Padfield, Katie; Tompkins, Ronald; Rahme, Laurence G.] Shriners Hosp Children Boston, Boston, MA USA. RP Bandyopadhaya, A (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. EM rahme@molbio.mgh.harvard.edu FU Shriners research grant [87100] FX This work was supported by Shriners research grant #87100 to LGR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 18 Z9 18 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2012 VL 8 IS 11 AR e1003024 DI 10.1371/journal.ppat.1003024 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 049PY UT WOS:000311997100041 PM 23166496 ER PT J AU Fogelman, D Zafonte, R AF Fogelman, David Zafonte, Ross TI Exercise to Enhance Neurocognitive Function After Traumatic Brain Injury SO PM&R LA English DT Article ID PLASTICITY-RELATED PROTEINS; SPORT-RELATED CONCUSSION; VOLUNTARY EXERCISE; HIPPOCAMPAL NEUROGENESIS; SYNAPTIC PLASTICITY; PHYSICAL-ACTIVITY; DENTATE GYRUS; UP-REGULATION; IN-VIVO; TRIAL AB Vigorous exercise has long been associated with improved health in many domains. Results of clinical observation have suggested that neurocognitive performance also is improved by vigorous exercise. Data derived from animal model based research have been emerging that show molecular and neuroanatomic mechanisms that may explain how exercise improves cognition, particularly after traumatic brain injury. This article will summarize the current state of the basic science and clinical literature regarding exercise as an intervention, both independently and in conjunction with other modalities, for brain injury rehabilitation. A key principle is the factor of timing of the initiation of exercise after mild traumatic brain injury, balancing potentially favorable and detrimental effects on recovery. PM R 2012;4:908-913 C1 [Zafonte, Ross] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Massachusetts Gen Hosp,Dept Phys Med & Rehabil, Cambridge, MA 02138 USA. RP Fogelman, D (reprint author), 125 Nashua St, Boston, MA 02114 USA. EM rzafonte@partners.org NR 40 TC 8 Z9 8 U1 0 U2 29 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 NOV PY 2012 VL 4 IS 11 BP 908 EP 913 DI 10.1016/j.pmrj.2012.09.028 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 048AU UT WOS:000311883400019 PM 23174558 ER PT J AU Wallis, J Lipp, OV Vanman, EJ AF Wallis, Jennifer Lipp, Ottmar V. Vanman, Eric J. TI Face age and sex modulate the other-race effect in face recognition SO ATTENTION PERCEPTION & PSYCHOPHYSICS LA English DT Article DE Face perception; Recognition; Age; Race; Sex; Other-race effect ID OWN-AGE; ERP EVIDENCE; BIAS; GENDER; MEMORY; CATEGORIZATION; PERCEPTION; DISTINCTIVENESS; IDENTIFICATION; INDIVIDUATION AB Faces convey a variety of socially relevant cues that have been shown to affect recognition, such as age, sex, and race, but few studies have examined the interactive effect of these cues. White participants of two distinct age groups were presented with faces that differed in race, age, and sex in a face recognition paradigm. Replicating the other-race effect, young participants recognized young own-race faces better than young other-race faces. However, recognition performance did not differ across old faces of different races (Experiments 1, 2A). In addition, participants showed an other-age effect, recognizing White young faces better than White old faces. Sex affected recognition performance only when age was not varied (Experiment 2B). Overall, older participants showed a similar recognition pattern (Experiment 3) as young participants, displaying an other-race effect for young, but not old, faces. However, they recognized young and old White faces on a similar level. These findings indicate that face cues interact to affect recognition performance such that age and sex information reliably modulate the effect of race cues. These results extend accounts of face recognition that explain recognition biases (such as the other-race effect) as a function of dichotomous ingroup/outgroup categorization, in that outgroup characteristics are not simply additive but interactively determine recognition performance. C1 [Wallis, Jennifer; Lipp, Ottmar V.; Vanman, Eric J.] Univ Queensland, Sch Psychol, Brisbane, Qld, Australia. [Wallis, Jennifer] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Wallis, J (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM jennifer_wallis@meei.harvard.edu RI Lipp, Ottmar/A-1254-2007 OI Lipp, Ottmar/0000-0001-6734-8608 FU Australian Research Council [DP110100460]; UQRS/UQIRTA fellowship FX This research was supported under the Australian Research Council's Discovery Projects funding scheme (project number DP110100460) and by an UQRS/UQIRTA fellowship to Jennifer Wallis. NR 40 TC 9 Z9 9 U1 4 U2 46 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1943-3921 J9 ATTEN PERCEPT PSYCHO JI Atten. Percept. Psychophys. PD NOV PY 2012 VL 74 IS 8 BP 1712 EP 1721 DI 10.3758/s13414-012-0359-z PG 10 WC Psychology; Psychology, Experimental SC Psychology GA 051PV UT WOS:000312140400015 PM 22933042 ER PT J AU Fong, ZV Winter, JM AF Fong, Zhi Ven Winter, Jordan M. TI Biomarkers in Pancreatic Cancer Diagnostic, Prognostic, and Predictive SO CANCER JOURNAL LA English DT Review DE Pancreatic cancer; biomarker; diagnostic; predictive; prognostic ID CIRCULATING TUMOR-CELLS; DIFFERENTIALLY EXPRESSED GENES; GEMCITABINE-BASED CHEMOTHERAPY; SINGLE-INSTITUTION EXPERIENCE; MITOXANTRONE PLUS PREDNISONE; RANDOMIZED CONTROLLED-TRIAL; CARBOHYDRATE ANTIGEN 19-9; POLYMERASE CHAIN-REACTION; ADVANCED PROSTATE-CANCER; DISEASE-FREE SURVIVAL AB Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. There has been minimal progress with regard to cancer-specific outcomes in recent decades. Although effective therapies will undoubtedly change the natural history of the disease, effective biomarkers are a promising tool that will likely have a positive impact and will undoubtedly have an important role in the management of patients with pancreatic ductal adenocarcinoma (PDA) in the future. At present, serum CA-19-9 (carbohydrate antigen 19-9) is the only Food and Drug Administration-approved biomarker for PDA, and it has utility as a prognostic marker and as a marker of disease recurrence. There has been a recent explosion in the pancreatic cancer biomarker field with more than 2000 biomarker studies implicating thousands of informative genes as candidate biomarkers. In this review, we summarize the literature on CA-19-9 in PDA and highlight the most promising investigational biomarkers. Distinctions are made between diagnostic biomarkers (detection of disease), prognostic biomarkers (provide information on prognosis and recurrence pattern), and predictive biomarkers (predict treatment response). C1 [Fong, Zhi Ven] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Winter, Jordan M.] Thomas Jefferson Univ, Dept Surg, Philadelphia, PA 19107 USA. RP Fong, ZV (reprint author), Massachusetts Gen Hosp, Dept Surg, Grb 425,55 Fruit St, Boston, MA 02114 USA. EM zfong@partners.org NR 122 TC 53 Z9 54 U1 2 U2 20 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 NOV-DEC PY 2012 VL 18 IS 6 BP 530 EP 538 DI 10.1097/PPO.0b013e31827654ea PG 9 WC Oncology SC Oncology GA 047IN UT WOS:000311833400008 PM 23187839 ER PT J AU Conrad, C Lillemoe, KD AF Conrad, Claudius Lillemoe, Keith D. TI Surgical Palliation of Pancreatic Cancer SO CANCER JOURNAL LA English DT Review DE Pancreatic cancer; surgical palliation; obstructive jaundice; gastric outlet obstruction; tumor-associated pain ID CELIAC PLEXUS BLOCK; GASTRIC OUTLET OBSTRUCTION; QUALITY-OF-LIFE; LAPAROSCOPIC DISTAL PANCREATECTOMY; UNRESECTABLE PERIAMPULLARY CANCER; PROSPECTIVE RANDOMIZED-TRIAL; PROPHYLACTIC GASTROJEJUNOSTOMY; BILIARY OBSTRUCTION; PROGNOSTIC-FACTORS; BYPASS AB The surgical palliation of pancreatic cancer remains an important component of the treatment of this disease. The introduction of a new aggressive and effective chemotherapy regimen (FOLFIRINOX), interdisciplinary palliative care, and minimally invasive approaches for providing palliation are all factors that expand the role of the surgeon in the care of patients with unresectable disease. Currently, the role of the surgeon in the palliation of pancreatic cancer is (1) to identify patients with incurable disease (either preoperatively or intraoperatively), (2) to determine the optimal palliative technique to optimize results and preserve resources, and (3) to perform palliation of symptoms with low morbidity and mortality. The 3 most common symptoms of pancreatic cancer requiring surgical palliation are obstructive jaundice, gastric outlet obstruction, and tumor-associated pain. It is important that the surgeon recognizes the full range of surgical and nonoperative techniques available and contributes to the decision making as to the most appropriate method for each individual patient. C1 [Conrad, Claudius; Lillemoe, Keith D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Lillemoe, KD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,WHT 5-506, Boston, MA 02114 USA. EM cconrad@partners.org; klillemoe@partners.org NR 52 TC 3 Z9 3 U1 0 U2 4 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 NOV-DEC PY 2012 VL 18 IS 6 BP 577 EP 583 DI 10.1097/PPO.0b013e3182797dfe PG 7 WC Oncology SC Oncology GA 047IN UT WOS:000311833400014 PM 23187845 ER PT J AU Balderas-Munoz, K Castillo-Martinez, L Orea-Tejeda, A Infante-Vazquez, O Utrera-Lagunas, M Martinez-Memije, R Keirns-Davis, C Becerra-Luna, B Sanchez-Vidal, G AF Balderas-Munoz, Karla Castillo-Martinez, Lilia Orea-Tejeda, Arturo Infante-Vazquez, Oscar Utrera-Lagunas, Marcelo Martinez-Memije, Raul Keirns-Davis, Candace Becerra-Luna, Bryan Sanchez-Vidal, Gabriela TI Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation SO CARDIOLOGY JOURNAL LA English DT Article DE citrulline; systolic heart failure; endothelial function ID L-ARGININE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; HUMANS; METABOLISM; SYNTHASE AB Background: The utility of L-arginine and L-citrulline in treatment of arterial hypertension by increasing vascular oxide nitric availability has been demonstrated. Photoplethysmography, a simple and low-cost optical technique, makes it possible to assess vascular function and to detect changes in blood flow, pulse and swelling of the microvascular tissular space. The aim of the study was to evaluate the effect of L-citrulline supplementation on functional class, ejection fraction and peripheral blood flow in patients with systolic heart failure. Methods: Thirty-five stable outpatients attending the Heart Failure Clinic at the INCMNSZ underwent clinical evaluation, radioisotopic ventriculography and photoplethysmography before and at the end of 4 months. They were randomized into two groups: experimental group, with oral L-citrulline supplementation (3 g/day, n = 20) and control group, without supplementation (n = 15). Results: In the experimental group the left ventricular ejection fraction (LVEF) increased 20.3% at rest and 12.7% with stress, as well as the right ventricular ejection fraction at rest of 15.10% and 14.88% with stress. In addition, functional class improved in 35%, and the maximum amplitude time/total time (MAT/TT) index decreased 23.1%. These changes were statistically significant compared with the control group. Conclusions: Citrulline supplementation significantly improved the LVEF, the endothelial function (MAT/TT index) and functional class. Citrulline can be an important co-adjuvant in the treatment of stable and stable systolic heart failure patients. (Cardiol J 2012; 19, 6: 612-617) C1 [Balderas-Munoz, Karla; Castillo-Martinez, Lilia; Orea-Tejeda, Arturo; Utrera-Lagunas, Marcelo; Sanchez-Vidal, Gabriela] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Heart Failure Clin, Mexico City, DF, Mexico. [Infante-Vazquez, Oscar; Martinez-Memije, Raul; Becerra-Luna, Bryan] Inst Nacl Cardiol ICh, Instrumentat Dept, Mexico City, DF, Mexico. [Keirns-Davis, Candace] Massachusetts Gen Hosp, Interpreter Serv, Boston, MA 02114 USA. RP Orea-Tejeda, A (reprint author), Providencia 1218 A Int 402, Mexico City 03100, DF, Mexico. EM oreatart@gmail.com RI Castillo-Martinez, Lilia/H-3750-2013 NR 30 TC 8 Z9 8 U1 1 U2 5 PU VIA MEDICA PI GDANSK PA UL SWIETOKRZYSKA 73, 80-180 GDANSK, POLAND SN 1897-5593 EI 1898-018X J9 CARDIOL J JI Cardiol. J. PD NOV PY 2012 VL 19 IS 6 BP 612 EP 617 DI 10.5603/CJ.2012.0113 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 049XP UT WOS:000312017000009 PM 23224924 ER PT J AU Potash, J Anderson, KC AF Potash, Jesse Anderson, Kenneth C. TI Gauging Progress in a Decades-Old Fight SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 [Potash, Jesse; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2012 VL 18 IS 21 BP 5833 EP 5833 DI 10.1158/1078-0432.CCR-12-2802 PG 1 WC Oncology SC Oncology GA 049YV UT WOS:000312020400001 PM 22977189 ER PT J AU Janeway, KA Maki, RG AF Janeway, Katherine A. Maki, Robert G. TI New Strategies in Sarcoma Therapy: Linking Biology and Novel Agents SO CLINICAL CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMOR; INFLAMMATORY MYOFIBROBLASTIC TUMOR; FACTOR-KAPPA-B; REFRACTORY EWING SARCOMA; HUMAN OSTEOSARCOMA CELLS; CHILDRENS ONCOLOGY GROUP; SYNOVIAL SARCOMA; RECEPTOR ACTIVATOR; MONOCLONAL-ANTIBODY; ANTI-GD2 ANTIBODY AB The ability to better interrogate the genetic state of a given cancer is giving rise to a new paradigm in cancer therapeutics in which the specific genetic alterations that give rise to the cancer inform the therapeutic decision-making for that specific patient. Sarcomas of soft tissue and bone represent model diseases that underscore this paradigm. However, many barriers prevent linkage of one of the 75 or more different types of sarcoma to novel therapeutic agents. In the present perspective, the authors outline key therapeutic opportunities and hurdles in clinical sarcoma research, focusing on specific examples of sarcomas that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations. Focused clinical trial design, ideally with several biomarker or histology-specific arms, is one means to be simultaneously parsimonious and inclusive. Clin Cancer Res; 18(21); 5837-44. (C) 2012 AACR. C1 [Maki, Robert G.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Maki, Robert G.] Mt Sinai Sch Med, Jack Martin Fund Div Pediat Hematol Oncol, New York, NY 10029 USA. [Janeway, Katherine A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Maki, RG (reprint author), Mt Sinai Sch Med, Dept Med, 1 Gustave Levy Pl,Box 1208, New York, NY 10029 USA. EM bobmakimd@gmail.com FU Timothy O'Brien Fund; St. Baldrick's Foundation; Hyundai Hope on Wheels; GlaxoSmithKline; Hoffman-LaRoche; Lilly; Pfizer; Merck; Eisai; Ziopharm FX This study is supported by the Timothy O'Brien Fund (to K.A. Janeway), the St. Baldrick's Foundation (to K.A. Janeway), and Hyundai Hope on Wheels (to R.G. Maki).; R.G. Maki has consulting fees from GlaxoSmithKline, Hoffman-LaRoche, Lilly, Pfizer, Merck, and Eisai; honoraria from Novartis and Ziopharm; commercial research support from Eisai and Ziopharm; is a consultant/advisory board member of Eisai, Novartis, Pfizer, Merck, GlaxoSmithKline, Morphotek, 23 & me, n-of-one, Foundation Medicine, and Bayer; and has expert testimony from Pfizer: ODAC Meeting. No potential conflicts of interest were disclosed by K.A. Janeway. NR 55 TC 6 Z9 6 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2012 VL 18 IS 21 BP 5837 EP 5844 DI 10.1158/1078-0432.CCR-12-0875 PG 8 WC Oncology SC Oncology GA 049YV UT WOS:000312020400003 PM 22929804 ER PT J AU Kong, S Sengupta, S Tyler, B Bais, AJ Ma, QZ Doucette, S Zhou, JY Sahin, A Carter, BS Brem, H Junghans, RP Sampath, P AF Kong, Seogkyoung Sengupta, Sadhak Tyler, Betty Bais, Anthony J. Ma, Qiangzhong Doucette, Saryn Zhou, Jinyuan Sahin, Ayguen Carter, Bob S. Brem, Henry Junghans, Richard P. Sampath, Prakash TI Suppression of Human Glioma Xenografts with Second-Generation IL13R-Specific Chimeric Antigen Receptor-Modified T Cells SO CLINICAL CANCER RESEARCH LA English DT Article ID INTERLEUKIN-13 RECEPTOR; MALIGNANT GLIOMA; BRAIN-TUMORS; RECOGNITION; LYMPHOCYTES; REJECTION; COMPONENT; THERAPY; CLONING; CHAIN AB Purpose: Glioblastoma multiforme (GBM) remains highly incurable, with frequent recurrences after standard therapies of maximal surgical resection, radiation, and chemotherapy. To address the need for new treatments, we have undertaken a chimeric antigen receptor (CAR) "designer T cell" (dTc) immunotherapeutic strategy by exploiting interleukin (IL) 13 receptor alpha-2 (IL13R alpha 2) as a GBM-selective target. Experimental Design: We tested a second-generation IL13 "zetakine" CAR composed of a mutated IL13 extracellular domain linked to intracellular signaling elements of the CD28 costimulatory molecule and CD3 zeta. The aim of the mutation (IL13.E13K.R109K) was to enhance selectivity of the CAR for recognition and killing of IL13R alpha 2(+) GBMs while sparing normal cells bearing the composite IL13R alpha 1/IL4R alpha receptor. Results: Our aim was partially realized with improved recognition of tumor and reduced but persisting activity against normal tissue IL13R alpha 1(+) cells by the IL13.E13K.R109K CAR. We show that these IL13 dTcs were efficient in killing IL13R alpha 2(+) glioma cell targets with abundant secretion of cytokines IL2 and IFN gamma, and they displayed enhanced tumor-induced expansion versus control unmodified T cells in vitro. In an in vivo test with a human glioma xenograft model, single intracranial injections of IL13 dTc into tumor sites resulted in marked increases in animal survivals. Conclusions: These data raise the possibility of immune targeting of diffusely invasive GBM cells either via dTc infusion into resection cavities to prevent GBM recurrence or via direct stereotactic injection of dTcs to suppress inoperable or recurrent tumors. Systemic administration of these IL13 dTc could be complicated by reaction against normal tissues expressing IL13Ra1. Clin Cancer Res; 18(21); 5949-60. (C) 2012 AACR. C1 [Bais, Anthony J.; Ma, Qiangzhong; Junghans, Richard P.] Boston Univ, Sch Med, Roger Williams Med Ctr, Biotherapeut Dev Lab,Dept Med, Providence, RI 02908 USA. [Doucette, Saryn] Boston Univ, Sch Med, Roger Williams Med Ctr, Dept Pathol, Providence, RI 02908 USA. [Kong, Seogkyoung; Sengupta, Sadhak; Sampath, Prakash] Boston Univ, Sch Med, Roger Williams Med Ctr, Brain Tumor Lab,Dept Neurosurg, Providence, RI 02908 USA. [Tyler, Betty; Brem, Henry] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Hunterian Neurosurg Res Lab, Baltimore, MD 21205 USA. [Zhou, Jinyuan] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Sahin, Ayguen; Carter, Bob S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Junghans, RP (reprint author), Boston Univ, Sch Med, Roger Williams Med Ctr, Biotherapeut Dev Lab,Dept Med, 825 Chalkstone Ave,NC 143, Providence, RI 02908 USA. EM rpj@bu.edu FU Roger Williams Hospital Brain Tumor Fund; Rhode Island Brain and Spine Tumor Foundation FX This work was supported by the Roger Williams Hospital Brain Tumor Fund and an award from the Rhode Island Brain and Spine Tumor Foundation. NR 37 TC 41 Z9 42 U1 1 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2012 VL 18 IS 21 BP 5949 EP 5960 DI 10.1158/1078-0432.CCR-12-0319 PG 12 WC Oncology SC Oncology GA 049YV UT WOS:000312020400014 PM 22966020 ER PT J AU Lee, EQ Puduvalli, VK Reid, JM Kuhn, JG Lamborn, KR Cloughesy, TF Chang, SM Drappatz, J Yung, WKA Gilbert, MR Robins, HI Lieberman, FS Lassman, AB McGovern, RM Xu, JH Desideri, S Ye, XB Ames, MM Espinoza-Delgado, I Prados, MD Wen, PY AF Lee, Eudocia Q. Puduvalli, Vinay K. Reid, Joel M. Kuhn, John G. Lamborn, Kathleen R. Cloughesy, Timothy F. Chang, Susan M. Drappatz, Jan Yung, W. K. Alfred Gilbert, Mark R. Robins, H. Ian Lieberman, Frank S. Lassman, Andrew B. McGovern, Renee M. Xu, Jihong Desideri, Serena Ye, Xiabu Ames, Matthew M. Espinoza-Delgado, Igor Prados, Michael D. Wen, Patrick Y. TI Phase I Study of Vorinostat in Combination with Temozolomide in Patients with High-Grade Gliomas: North American Brain Tumor Consortium Study 04-03 SO CLINICAL CANCER RESEARCH LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; ADJUVANT TEMOZOLOMIDE; TRIAL; GLIOBLASTOMA; SAHA; RADIOTHERAPY; CONCOMITANT; GROWTH; CANCER AB Purpose: A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG). Experimental Design: This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days of the first cycle and 200 mg/m(2)/day for 5 days of the subsequent 28-day cycles. Results: In part 1, the MTD of vorinostat administered on days 1 to 7 and 15 to 21 of every 28-day cycle, in combination with TMZ, was 500 mg daily. Dose-limiting toxicities (DLT) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In part 2, the MTD of vorinostat on days 1 to 7 and 15 to 21 of every 28-day cycle, combined with TMZ, was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells. Conclusion: Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway. Clin Cancer Res; 18(21); 6032-9. (C) 2012 AACR. C1 [Lee, Eudocia Q.; Drappatz, Jan; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Puduvalli, Vinay K.; Yung, W. K. Alfred; Gilbert, Mark R.; Xu, Jihong] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Reid, Joel M.; McGovern, Renee M.; Ames, Matthew M.] Mayo Clin, Ctr Comprehens Canc, Rochester, MN USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Drappatz, Jan; Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Ctr Canc, Pittsburgh, PA USA. [Robins, H. Ian] Univ Wisconsin, Madison, WI USA. [Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Desideri, Serena; Ye, Xiabu] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,SW 430, Boston, MA 02215 USA. EM pwen@partners.org RI Puduvalli, Vinay/A-2411-2016; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU NIH [U01 CA062399]; Merck; UpToDate; DEMOS Publishers; Genentech; Celgene; Schering; Abbott; Campus Bio; Eisai; GSK; Merck/Schering-Plough; Novartis; Kyowa Hakko Kirin Pharma; Keryx; Sigma Tau; Amgen; AstraZeneca; Esai; Sanofi-Aventis; Genzyme; Medimmune; Vascular Biogenics FX E. Q. Lee is on advisory board for Novartis and has royalties from UpToDate and DEMOS Publishers. Vinay K. Puduvalli has a research grant support from Merck, Genentech, and Celgene and is on advisory board for Novartis. Joel M. Reid has a funding from Merck for PK analysis. T. F. Cloughesy is a consultant/advisory member of Merck, Roche, Merck Sorano, Celgene, and Novartis, has honoraria from speakers bureau from Merck, and honoraria from ad board from Genentech and Roche. Susan M. Chang has a research support from Schering. Mark R. Gilbert is on advisory boards of Merck, Genentech and Abbott and has honoraria from Merck, Genentech and Abbott. H. Ian Robins is a consultant/advisory board member of Genentech and Abbott. Andrew B. Lassman is a consultant/advisory board member, is a Speaker, and has research funding from Abbott, Campus Bio, Eisai, Genentech, GSK, Merck/Schering-Plough, Novartis, Kyowa Hakko Kirin Pharma, Keryx, Sigma Tau. R. M. McGovern and Matthew M. Ames have funding from Merck for PK analysis. Patrick Y. Wen is a consultant/ advisory board member of Novartis and Merck, is a paid speaker for Merck, has research support from Amgen, AstraZeneca, Esai, Sanofi-Aventis, Genentech, Genzyme, Novartis, Medimmune, Vascular Biogenics, and has royalties from UpToDate and DEMOS Publishers. No potential conflicts of interest were disclosed by other authors.; This study was sponsored by NIH Grant number U01 CA062399. Funding for pharmacokinetic analysis was provided by Merck. NR 14 TC 20 Z9 22 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2012 VL 18 IS 21 BP 6032 EP 6039 DI 10.1158/1078-0432.CCR-12-1841 PG 8 WC Oncology SC Oncology GA 049YV UT WOS:000312020400022 PM 22923449 ER PT J AU Sun, HY Wagener, M Cacciarelli, TV Singh, N AF Sun, Hsin-Yun Wagener, Marilyn Cacciarelli, Thomas V. Singh, Nina TI Impact of rifaximin use for hepatic encephalopathy on the risk of early post-transplant infections in liver transplant recipients SO CLINICAL TRANSPLANTATION LA English DT Article DE early post-transplant Infections; hepatic encephalopathy; liver transplant; multidrug-resistant bacteria; rifaximin ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MULTICENTER; EFFICACY; DIARRHEA AB Background: Whether the use of rifaximin for hepatic encephalopathy during liver transplant candidacy has an impact on post-transplant infections is not known. Methods: We compared the frequency and spectrum of infections within 90 d post-transplant in liver transplant recipients who did and did not receive rifaximin for hepatic encephalopathy during transplant candidacy. Results: Of 110 consecutive liver transplant recipients, 30 (27%) received rifaximin. Rifaximin users were more severely ill based on higher Model for End-Stage Liver Disease (MELD) score (p = 0.005). When controlled for MELD (stratified by MELD < 30, MELD >= 30), the risk of infections was significantly lower in rifaximin vs. no rifaximin recipients (OR = 0.269, 95% CI 0.078-0.0.934, p = 0.026). Rifaximin use was not associated with a higher risk of multidrug resistant bacterial infections (OR = 1.8, 95% CI 0.42-8.35, p = 0.40). The probability of post-transplant survival at 90 d did not differ for patients with or without rifaximin use (0.90 for both groups, p = 0.56). Conclusions: Rifaximin appeared to have a protective effect against early post-transplant infections in more severely ill liver transplant recipients. Rifaximin use did not select for multidrug resistant bacteria in these patients. C1 [Sun, Hsin-Yun; Wagener, Marilyn; Cacciarelli, Thomas V.; Singh, Nina] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Dept Internal Med, Natl Taiwan Univ Hosp, Taipei, Taiwan. [Wagener, Marilyn; Cacciarelli, Thomas V.; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. RP Singh, N (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu OI SUN, HSIN-YUN/0000-0003-0074-7721 NR 17 TC 6 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD NOV-DEC PY 2012 VL 26 IS 6 BP 849 EP 852 DI 10.1111/j.1399-0012.2012.01619.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 051LS UT WOS:000312129100016 PM 22432742 ER PT J AU Pehmoller, C Brandt, N Birk, JB Hoeg, LD Sjoberg, KA Goodyear, LJ Kiens, B Richter, EA Wojtaszewski, JFP AF Pehmoller, Christian Brandt, Nina Birk, Jesper B. Hoeg, Louise D. Sjoberg, Kim A. Goodyear, Laurie J. Kiens, Bente Richter, Erik A. Wojtaszewski, Jorgen F. P. TI Exercise Alleviates Lipid-Induced Insulin Resistance in Human Skeletal Muscle-Signaling Interaction at the Level of TBC1 Domain Family Member 4 SO DIABETES LA English DT Article ID GTPASE-ACTIVATING PROTEIN; FREE FATTY-ACIDS; STIMULATED GLUCOSE-UPTAKE; AS160 PHOSPHORYLATION; GLUT4 TRANSLOCATION; KINASE-C; 14-3-3 BINDING; POTENTIAL ROLE; AKT SUBSTRATE; SENSITIVITY AB Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation. Diabetes 61:2743-2752, 2012 C1 [Pehmoller, Christian; Brandt, Nina; Birk, Jesper B.; Hoeg, Louise D.; Sjoberg, Kim A.; Kiens, Bente; Richter, Erik A.; Wojtaszewski, Jorgen F. P.] Univ Copenhagen, Mol Physiol Grp, Dept Exercise & Sport Sci, Copenhagen, Denmark. [Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect, Boston, MA 02115 USA. RP Wojtaszewski, JFP (reprint author), Univ Copenhagen, Mol Physiol Grp, Dept Exercise & Sport Sci, Copenhagen, Denmark. EM jwojtaszewki@ifl.ku.dk RI Wojtaszewski, Jorgen /P-6583-2014; Birk, Jesper/D-3523-2015; Sjoberg, Kim/D-7612-2015 OI Wojtaszewski, Jorgen /0000-0001-9785-6830; Birk, Jesper/0000-0001-9775-4789; Sjoberg, Kim/0000-0001-6880-4804 FU Danish Medical Research Council; Lundbeck Research Foundation; Novo Nordisk Research Foundation; Danish Ministry of Food, Agriculture and Fisheries; European Union [LSHMCT-2004-005272]; Danish Ministry of Science, Technology and Innovation FX This study was supported by grants from the Danish Medical Research Council (J.F.P.W.); The Lundbeck Research Foundation (J.F.P.W.); the Novo Nordisk Research Foundation (J.F.P.W.); Danish Ministry of Food, Agriculture and Fisheries (B.K.); and an integrated project funded by the European Union (LSHMCT-2004-005272) (E.A.R., B.K., J.F.P.W.). This work was carried out as part of the research program of the UNIK: Food, Fitness and Pharma for Health and Disease (see www.foodfitnesspharma.ku.dk) (E.A.R., B. K., J.F.P.W.). The UNIK project is supported by the Danish Ministry of Science, Technology and Innovation. NR 49 TC 26 Z9 26 U1 0 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2012 VL 61 IS 11 BP 2743 EP 2752 DI 10.2337/db11-1572 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GQ UT WOS:000312041600012 PM 22851577 ER PT J AU Liu, ML Xiang, RH Wilk, SA Zhang, N Sloane, LB Azarnoush, K Zhou, LJ Chen, HZ Xiang, GD Walter, CA Austad, SN Musi, N DeFronzo, RA Asmis, R Scherer, PE Dong, LQ Liu, F AF Liu, Meilian Xiang, Ruihua Wilk, Sarah Ann Zhang, Ning Sloane, Lauren B. Azarnoush, Kian Zhou, Lijun Chen, Hongzhi Xiang, Guangda Walter, Christi A. Austad, Steven N. Musi, Nicolas DeFronzo, Ralph A. Asmis, Reto Scherer, Philipp E. Dong, Lily Q. Liu, Feng TI Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance SO DIABETES LA English DT Article ID COMPLEMENT-RELATED PROTEIN; ADIPOSE-SPECIFIC PROTEIN; COLLAGENOUS DOMAIN; POSTTRANSLATIONAL MODIFICATIONS; METABOLIC SYNDROME; ENDOCRINE ORGAN; ACID OXIDATION; SENSITIVITY; TISSUE; GLUCOSE AB The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the other hand, a significant correlation between adiponectin multimerization and its insulin-sensitizing effects has been demonstrated, suggesting a promising alternative therapeutic strategy. Here we show that transgenic mice overexpressing disulfide bond A oxidoreductase-like protein in fat (fDsbA-L) exhibited increased levels of total and the high-molecular-weight form of adiponectin compared with wild-type (WT) littermates. The fDsbA-L mice also displayed resistance to diet-induced obesity, insulin resistance, and hepatic steatosis compared with WT control mice. The protective effects of DsbA-L overexpression on diet-induced insulin resistance, but not increased body weight and fat cell size, were significantly decreased in adiponectin-deficient fDsbA-L mice (fDsbA-L/Ad(-/-)). In addition, the fDsbA-L/Ad(-/-) mice displayed greater activity and energy expenditure compared with adiponectin knockout mice under a high-fat diet. Taken together, our results demonstrate that DsbA-L protects mice from diet-induced obesity and insulin resistance through adiponectin-dependent and independent mechanisms. In addition, upregulation of DsbA-L could be an effective therapeutic approach for the treatment of obesity and its associated metabolic disorders. Diabetes 61:2776-2786, 2012 C1 [Liu, Meilian; Liu, Feng] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Xiang, Ruihua; Wilk, Sarah Ann; Sloane, Lauren B.; Azarnoush, Kian; Zhou, Lijun; Xiang, Guangda; Walter, Christi A.; Austad, Steven N.; Dong, Lily Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Zhang, Ning; Musi, Nicolas; DeFronzo, Ralph A.; Liu, Feng] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Chen, Hongzhi; Asmis, Reto; Liu, Feng] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Walter, Christi A.; Austad, Steven N.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Walter, Christi A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Scherer, Philipp E.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Touchstone Diabet Ctr, Dallas, TX 75390 USA. [Scherer, Philipp E.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. RP Liu, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. EM liuf@uthscsa.edu FU American Diabetes Association Research Award [1-12-BS-115]; National Institutes of Health [DK-76902, DK-69930, P30-AG-13319-1SSI, DK-80157, DK-89229, HL-70963, R01-DK-55758, R01-CA-112023, RC1-DK-86629, P01-DK-88761] FX This work was supported by an American Diabetes Association Research Award (1-12-BS-115 to F.L.) and by National Institutes of Health RO1 grants DK-76902 (to F.L.), DK-69930 (to L.Q.D.), P30-AG-13319-1SSI (to S.N.A.), DK-80157 and DK-89229 (to N.M.), HL-70963 (to R.A.), and R01-DK-55758, R01-CA-112023, RC1-DK-86629, and P01-DK-88761 (to P.E.S.). NR 50 TC 25 Z9 28 U1 3 U2 32 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2012 VL 61 IS 11 BP 2776 EP 2786 DI 10.2337/db12-0169 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GQ UT WOS:000312041600015 PM 22807031 ER PT J AU Dinh, T Tecilazich, F Kafanas, A Doupis, J Gnardellis, C Leal, E Tellechea, A Pradhan, L Lyons, TE Giurini, JE Veves, A AF Thanh Dinh Tecilazich, Francesco Kafanas, Antonios Doupis, John Gnardellis, Charalambos Leal, Ermelindo Tellechea, Ana Pradhan, Leena Lyons, Thomas E. Giurini, John E. Veves, Aristidis TI Mechanisms Involved in the Development and Healing of Diabetic Foot Ulceration SO DIABETES LA English DT Article ID ENDOTHELIAL DYSFUNCTION; INFLAMMATORY CYTOKINES; ADIPOSE-TISSUE; HIGH-RISK; EXPRESSION; REACTIVITY; OBESITY; NEUROPATHY; ENHANCE; DISEASE AB We examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 +/- 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-a, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs. Diabetes 61:2937-2947, 2012 C1 [Thanh Dinh; Tecilazich, Francesco; Kafanas, Antonios; Doupis, John; Leal, Ermelindo; Tellechea, Ana; Pradhan, Leena; Lyons, Thomas E.; Giurini, John E.; Veves, Aristidis] Harvard Univ, Microcirculat Lab, Sch Med, Boston, MA 02115 USA. [Thanh Dinh; Tecilazich, Francesco; Kafanas, Antonios; Doupis, John; Leal, Ermelindo; Tellechea, Ana; Pradhan, Leena; Lyons, Thomas E.; Giurini, John E.; Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Joslin Beth Israel Deaconess Foot Ctr, Sch Med, Boston, MA 02215 USA. [Gnardellis, Charalambos] Technol Educ Inst Messolonghi, Mesolongion, Greece. RP Veves, A (reprint author), Harvard Univ, Microcirculat Lab, Sch Med, Boston, MA 02115 USA. EM aveves@bidmc.harvard.edu RI Tellechea, Ana/C-4900-2013; Leal, Ermelindo/G-3051-2010; OI Leal, Ermelindo/0000-0003-1748-9861; Tellechea, Ana/0000-0001-9387-7706 FU National Institutes of Health [R01-HL-075678, R01-DK-076937, R01-NS-066205]; National Center for Research Resources [UL1RR025758] FX This work was supported by National Institutes of Health Grants R01-HL-075678, R01-DK-076937, and R01-NS-066205 (to A.V.). The project described was supported by the Clinical Translational Science Award (UL1RR025758) to Harvard University and Beth Israel Deaconess Medical Center from the National Center for Research Resources. NR 28 TC 65 Z9 74 U1 0 U2 18 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2012 VL 61 IS 11 BP 2937 EP 2947 DI 10.2337/db12-0227 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GQ UT WOS:000312041600032 PM 22688339 ER PT J AU Mima, A Hiraoka-Yamomoto, J Li, Q Kitada, M Li, CZ Geraldes, P Matsumoto, M Mizutani, K Park, K Cahill, C Nishikawa, SI Rask-Madsen, C King, GL AF Mima, Akira Hiraoka-Yamomoto, Junko Li, Qian Kitada, Munehiro Li, Chenzhong Geraldes, Pedro Matsumoto, Motonobu Mizutani, Koji Park, Kyoungmin Cahill, Christopher Nishikawa, Shin-Ichi Rask-Madsen, Christian King, George L. TI Protective Effects of GLP-1 on Glomerular Endothelium and Its Inhibition by PKC beta Activation in Diabetes SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; NF-KAPPA-B; INSULIN-RESISTANCE; GENE-EXPRESSION; NEPHROPATHY; RECEPTOR; MICE; DYSFUNCTION; OBESITY; INJURY AB To characterize glucagon-like peptide (GLP)-1 signaling and its effect on renal endothelial dysfunction and glomerulopathy. We studied the expression and signaling of GLP-1 receptor (GLP-1R) on glomerular endothelial cells and the novel finding of protein kinase A-dependent phosphorylation of c-Raf at Ser259 and its inhibition of angiotensin 11 (Ang II) phospho-c-Raf(Ser338) and Erk1/2 phosphorylation. Mice overexpressing protein kinase C (PKC)beta 2 in endothelial cells (EC-PKC beta 2Tg) were established. Ang H and GLP-1 actions in glomenilar endothelial cells were analyzed with small interfering RNA of GLP-1R. PKC beta isoform activation induced by diabetes decreased GLP-1R expression and protective action on the renal endothelium by increasing its degradation via ubiquitination and enhancing phospho-c-Raf(Ser338) and Ang II activation of phospho-Erk1/2. EC-PKC beta 2Tg mice exhibited decreased GLP-1R expression and increased phospho-c-Raf(Ser338), leading to enhanced effects of Ang H. Diabetic EC-PKC beta 2Tg mice exhibited greater loss of endothelial GLP-1R expression and exendin-4-protective actions and exhibited more albuminuria and mesangial expansion than diabetic controls. These results showed that the renal protective effects of GLP-1 were mediated via the inhibition of Ang II actions on cRaf (Ser259) and diminished by diabetes because of PKC beta activation and the increased degradation of GLP-1R in the glomerular endothelial cells. Diabetes 61:2967-2979, 2012 C1 [Mima, Akira; Hiraoka-Yamomoto, Junko; Li, Qian; Kitada, Munehiro; Li, Chenzhong; Matsumoto, Motonobu; Mizutani, Koji; Park, Kyoungmin; Cahill, Christopher; Rask-Madsen, Christian; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Geraldes, Pedro] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Nishikawa, Shin-Ichi] RIKEN Ctr Dev Biol, Lab Stem Cell Biol, Kobe, Hyogo, Japan. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. EM george.king@joslin.harvard.edu FU National Institutes of Health/National Eye Institute [EY016150]; Diabetes and Endocrinology Research Center [P30DK036836]; Manpei Suzuki Diabetes Foundation; Kanzawa Medical Research Foundation; NOVARTIS Foundation FX This work was supported by National Institutes of Health/National Eye Institute (EY016150) and the Diabetes and Endocrinology Research Center (P30DK036836). A.M. is the recipient of a Research Fellowship (Manpei Suzuki Diabetes Foundation, Kanzawa Medical Research Foundation, and the NOVARTIS Foundation) (Japan) for the Promotion of Science. NR 30 TC 58 Z9 67 U1 1 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2012 VL 61 IS 11 BP 2967 EP 2979 DI 10.2337/db11-1824 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GQ UT WOS:000312041600035 PM 22826029 ER PT J AU Wexler, DJ Beauharnais, CC Regan, S Nathan, DM Cagliero, E Larkin, ME AF Wexler, Deborah J. Beauharnais, Catherine C. Regan, Susan Nathan, David M. Cagliero, Enrico Larkin, Mary E. TI Impact of inpatient diabetes management, education, and improved discharge transition on glycemic control 12 months after discharge SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Inpatient diabetes management; Diabetes care management strategy; Inpatient to outpatient transitions in care ID INSULIN THERAPY; HOSPITALIZED-PATIENTS; OLDER PATIENTS; HEART-FAILURE; FOLLOW-UP; CARE; TRIAL; INITIATION; MELLITUS; COSTS AB Aim: To determine whether inpatient diabetes management and education with improved transition to outpatient care (IDMET) improves glycemic control after hospital discharge in patients with uncontrolled type 2 diabetes (T2DM). Methods: Adult inpatients with T2DM and HbA1c > 7.5% (58 mmol/mol) admitted for reasons other than diabetes to an academic medical center were randomly assigned to either IDMET or usual care (UC). Linear mixed models estimated treatment-dependent differences in the change in HbA1c (measured at 3, 6, and 12 months) from baseline to 1-year follow-up. Results: Thirty-one subjects had mean age 55 +/- 12.6 years, with mean HbA1c of 9.7 +/- 1.6% (82 +/- 18 mmol/mol). Mean inpatient glucose was lower in the IDMET than in the UC group (176 +/- 66 versus 195 +/- 74 mg/dl [9.7 versus 10.8 mmol/l], P = 0.001). In the year after discharge, the average HbA1c reduction was greater in the IDMET group compared with the UC group by 0.6% (SE 0.5%, [7 (SE 5) mmol/mol], P = 0.3). Among patients newly discharged on insulin, the average HbA1c reduction was greater in the in the IDMET group than in the UC group by 2.4% (SE 1.0%, [25 (SE 11) mmol/mol], P = 0.04). Conclusions: Inpatient diabetes management (IDMET) substantially improved glycemic control 1 year after discharge in patients newly discharged on insulin; patients previously treated with insulin did not benefit. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Wexler, Deborah J.] Massachusetts Gen Hosp, MGH Diabet Unit, Ctr Diabet, Boston, MA 02114 USA. [Wexler, Deborah J.; Regan, Susan; Nathan, David M.; Cagliero, Enrico; Larkin, Mary E.] Harvard Univ, Sch Med, Boston, MA USA. [Beauharnais, Catherine C.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Regan, Susan] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, MGH Diabet Unit, Ctr Diabet, Bulfinch 408A,55 Fruit St, Boston, MA 02114 USA. EM dwexler@partners.org OI Regan, Susan/0000-0003-0940-2017 FU NIDDK Career Development Award [K23 DK 080 228]; Charlton Fund for Innovative Diabetes Research FX This study was funded by and DJW is supported by an NIDDK Career Development Award (K23 DK 080 228). DMN is funded by the Charlton Fund for Innovative Diabetes Research. NR 30 TC 14 Z9 14 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD NOV PY 2012 VL 98 IS 2 BP 249 EP 256 DI 10.1016/j.diabres.2012.09.016 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049CA UT WOS:000311958400012 PM 23036785 ER PT J AU Shin, J Padmanabhan, A de Groh, ED Lee, JS Haidar, S Dahlberg, S Guo, F He, SN Wolman, MA Granato, M Lawson, ND Wolfe, SA Kim, SH Solnica-Krezel, L Kanki, JP Ligon, KL Epstein, JA Look, AT AF Shin, Jimann Padmanabhan, Arun de Groh, Eric D. Lee, Jeong-Soo Haidar, Sam Dahlberg, Suzanne Guo, Feng He, Shuning Wolman, Marc A. Granato, Michael Lawson, Nathan D. Wolfe, Scot A. Kim, Seok-Hyung Solnica-Krezel, Lilianna Kanki, John P. Ligon, Keith L. Epstein, Jonathan A. Look, A. Thomas TI Zebrafish neurofibromatosis type 1 genes have redundant functions in tumorigenesis and embryonic development SO DISEASE MODELS & MECHANISMS LA English DT Article ID TUMOR-SUPPRESSOR GENE; NERVE SHEATH TUMORS; ZINC-FINGER NUCLEASES; LARVAL ZEBRAFISH; NF1 GENE; RAS; P53; PROLIFERATION; INACTIVATION; PROTEIN AB Neurofibromatosis type 1 (NF1) is a common, dominantly inherited genetic disorder that results from mutations in the neurofibromin 1 (NF1) gene. Affected individuals demonstrate abnormalities in neural-crest-derived tissues that include hyperpigmented skin lesions and benign peripheral nerve sheath tumors. NF1 patients also have a predisposition to malignancies including juvenile myelomonocytic leukemia (JMML), optic glioma, glioblastoma, schwannoma and malignant peripheral nerve sheath tumors (MPNSTs). In an effort to better define the molecular and cellular determinants of NF1 disease pathogenesis in vivo, we employed targeted mutagenesis strategies to generate zebrafish harboring stable germline mutations in nf1a and nf1b, orthologues of NF1. Animals homozygous for loss-of-funcion alleles of nf1a or nf1b alone are phenotypically normal and viable. Homozygous loss of both alleles in combination generates larval phenotypes that resemble aspects of the human disease and results in larval lethality between 7 and 10 days post fertilization. nf1-null larvae demonstrate significant central and peripheral nervous system defects. These include aberrant proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), dysmorphic myelin sheaths and hyperplasia of Schwann cells. Loss of nf1 contributes to tumorigenesis as demonstrated by an accelerated onset and increased penetrance of high-grade gliomas and MPNSTs in adult nf1a(+/-); nf1b(-/-); p53(e7/e7) animals. nf1-null larvae also demonstrate significant motor and learning defects. Importantly, we identify and quantitatively analyze a novel melanophore phenotype in nf1-null larvae, providing the first animal model of the pathognomonic pigmentation lesions of NF1. Together, these findings support a role for nf1a and nf1b as potent tumor suppressor genes that also function in the development of both central and peripheral glial cells as well as melanophores in zebrafish. C1 [Padmanabhan, Arun; de Groh, Eric D.; Wolman, Marc A.; Granato, Michael; Epstein, Jonathan A.] Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Padmanabhan, Arun; de Groh, Eric D.; Wolman, Marc A.; Granato, Michael; Epstein, Jonathan A.] Univ Penn, Perelman Sch Med, Inst Regenerat Med, Philadelphia, PA 19104 USA. [Shin, Jimann; Lee, Jeong-Soo; Dahlberg, Suzanne; Guo, Feng; He, Shuning; Kanki, John P.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Shin, Jimann; Lee, Jeong-Soo; Dahlberg, Suzanne; Guo, Feng; He, Shuning; Kanki, John P.; Look, A. Thomas] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Haidar, Sam; Ligon, Keith L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Lawson, Nathan D.; Wolfe, Scot A.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. [Kim, Seok-Hyung] Vanderbilt Univ, Sch Med, Dept Neurol, Nashville, TN 37232 USA. [Solnica-Krezel, Lilianna] Washington Univ, Sch Med St Louis, Dept Dev Biol, St Louis, MO 63110 USA. RP Epstein, JA (reprint author), Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. EM epsteinj@mail.med.upenn.edu; thomas_look@dfci.harvard.edu FU Department of Defense [W81XWH-07-1-0228, W81XWH-12-1-0125]; National Institutes of Health [R01 HL062974, R01 HL093766, T32 HL007843-15, R01 HG002995]; Alex's Lemonade Stand Foundation; Sarnoff Cardiovascular Research Foundation; Dana-Farber Cancer Institute (DFCI) Pediatric Low-Grade Astrocytoma Program; Children's Tumor Foundation; Vanderbilt University Academic Venture Capital Fund; Spain Fund for Regenerative Medicine; W.W. Smith Endowed Chair FX This work was supported by the Department of Defense [grant numbers W81XWH-07-1-0228 and W81XWH-12-1-0125 to J.A.E. and A.T.L.] and the National Institutes of Health [grant numbers R01 HL062974 to J.A.E.; R01 HL093766 to N.D.L. and S.A.W.; T32 HL007843-15 to E.D.D.; and R01 HG002995 to L.S.-K.). A.T.L. was supported by an Innovator Award from Alex's Lemonade Stand Foundation. A.P. was supported by a fellowship from the Sarnoff Cardiovascular Research Foundation, J.S. was supported by a fellowship from the Dana-Farber Cancer Institute (DFCI) Pediatric Low-Grade Astrocytoma Program, and J.-S.L. was supported by a Young Investigator Award from the Children's Tumor Foundation. This work was also supported by the Vanderbilt University Academic Venture Capital Fund to L.S.-K. as well as the Spain Fund for Regenerative Medicine and the W.W. Smith Endowed Chair to J.A.E. NR 67 TC 18 Z9 18 U1 0 U2 13 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD NOV PY 2012 VL 5 IS 6 BP 881 EP 894 DI 10.1242/dmm.009779 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 047RT UT WOS:000311859700020 PM 22773753 ER PT J AU Shtasel, D Viron, M Freudenreich, O AF Shtasel, Derri Viron, Mark Freudenreich, Oliver TI Community Psychiatry: What Should Future Psychiatrists Learn? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE delivery of health care; dual diagnosis; homeless persons; integrated health care systems; internship and residency; mentally ill persons ID SERIOUS MENTAL-ILLNESS; HEALTH-CARE; HOMELESS; RECOVERY; QUALITY; ADULTS; MODEL AB Community psychiatry training is required by all adult psychiatry residency training programs. Unlike other core elements of training, the specific content is not clearly articulated, leaving program design and content up to individual programs. At the same time, the meaning of "community psychiatry" is increasingly in the eye of the beholder; traditional structures and systems have lost funding, services are more diffuse, and the traditional medical model is becoming less valued. In this column we describe an approach to training in community psychiatry that is intended to prepare future psychiatrists for the clinical and systems challenges they will undoubtedly face and that achieves this goal through trainees' caring for an especially vulnerable subpopulation-homeless individuals with severe and persistent mental illness. We describe how this model teaches residents to think simultaneously at both the individual and the systems levels and enables them to understand the critical need to use nontraditional treatment approaches in order to provide comprehensive care for this marginalized population. We believe that this clinical and training paradigm can be replicated and might guide other residency training programs in their approach to teaching community psychiatry. (HARV REV PSYCHIATRY 2012;20:318-323.) C1 [Shtasel, Derri; Freudenreich, Oliver] Harvard Univ, Sch Med, Boston, MA USA. [Shtasel, Derri; Freudenreich, Oliver] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Viron, Mark] Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. [Viron, Mark] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Shtasel, D (reprint author), Massachusetts Gen Hosp Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM dshtasel@partners.org NR 29 TC 0 Z9 0 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 2012 VL 20 IS 6 BP 318 EP 323 DI 10.3109/10673229.2012.747799 PG 6 WC Psychiatry SC Psychiatry GA 051KQ UT WOS:000312125800004 PM 23216069 ER PT J AU Lenehan, G AF Lenehan, Gail TI POSITIONING ENA FOR THE FUTURE SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Lenehan, Gail] Emergency Nurses Assoc, Boston, MA USA. [Lenehan, Gail] Massachusetts Gen Hosp, Emergency Dept, Boston, MA 02114 USA. RP Lenehan, G (reprint author), Emergency Nurses Assoc, Boston, MA USA. EM gail.lenehan@gmail.com 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 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD NOV PY 2012 VL 38 IS 6 BP 507 EP 507 DI 10.1016/j.jen.2012.10.003 PG 1 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 049QG UT WOS:000311997900001 PM 23122193 ER PT J AU Li, H Cai, Q Wu, H Vathipadiekal, V Dobbin, ZC Li, TY Hua, X Landen, CN Birrer, MJ Sanchez-Beato, M Zhang, RG AF Li, Hua Cai, Qi Wu, Hong Vathipadiekal, Vinod Dobbin, Zachary C. Li, Tianyu Hua, Xiang Landen, Charles N. Birrer, Michael J. Sanchez-Beato, Margarita Zhang, Rugang TI SUZ12 Promotes Human Epithelial Ovarian Cancer by Suppressing Apoptosis via Silencing HRK SO MOLECULAR CANCER RESEARCH LA English DT Article ID HISTONE METHYLTRANSFERASE ACTIVITY; PROSTATE-CANCER; GENOMIC ANALYSES; CELL-DEATH; EZH2; PROTEIN; GENE; METHYLATION; PROLIFERATION; EXPRESSION AB Epithelial ovarian cancer (EOC) ranks first as the cause of death for gynecological cancers in the United States. SUZ12 is a component of the polycomb repressive complex 2 (PRC2) and is essential for PRC2-mediated gene silencing by generating trimethylation on lysine 27 residue of histone H3 (H3K27Me3). The role of SUZ12 in EOC has never been investigated. Here, we show that SUZ12 is expressed at significantly higher levels in human EOC (n = 117) compared with either normal human ovarian surface epithelium (n = 35, P < 0.001) or fallopian tube epithelium (n 15, P < 0.001). There is a positive correlation between expression of SUZ12 and EZH2 in human EOC (P < 0.001). In addition, expression of SUZ12 positively correlates with Ki67, a marker of cell proliferation (P < 0.001), and predicts shorter overall survival (P = 0.0078). Notably, knockdown of SUZ12 suppresses the growth of human EOC cells in vitro and in vivo in both orthotopic and subcutaneous xenograft EOC models. In addition, SUZ12 knockdown decreases the levels of H3K27Me3 and triggers apoptosis of human EOC cells. Mechanistically, we identified Harakiri (HRK), a proapoptotic gene, as a novel SUZ12 target gene, and showed that HRK upregulation mediates apoptosis induced by SUZ12 knockdown in human EOC cells. In summary, we show that SUZ12 promotes the proliferation of human EOC cells by inhibiting apoptosis and HRK is a novel SUZ12 target gene whose upregulation contributes to apoptosis induced by SUZ12 knockdown. Mol Cancer Res; 10(11); 1462-72. (C) 2012 AACR. C1 [Li, Hua; Zhang, Rugang] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA. [Cai, Qi] Fox Chase Canc Ctr, Histopathol Facil, Philadelphia, PA 19111 USA. [Wu, Hong] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. [Li, Tianyu] Fox Chase Canc Ctr, Biostat & Bioinformat Facil, Philadelphia, PA 19111 USA. [Hua, Xiang] Fox Chase Canc Ctr, Transgen Facil, Philadelphia, PA 19111 USA. [Zhang, Rugang] Fox Chase Canc Ctr, Womens Canc Program, Philadelphia, PA 19111 USA. [Vathipadiekal, Vinod; Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Dobbin, Zachary C.; Landen, Charles N.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Sanchez-Beato, Margarita] Spanish Natl Canc Res Ctr CNIO, Human Genet Programme, Madrid, Spain. [Sanchez-Beato, Margarita] Hosp Univ Puerta de Hierro Majadahonda, Madrid, Spain. RP Zhang, RG (reprint author), Wistar Inst Anat & Biol, Gene Express & Regulat Program, Room 308,3601 Spruce St, Philadelphia, PA 19104 USA. EM rzhang@wistar.org OI Vathipadiekal, Vinod/0000-0002-8181-6890 FU NIH/NCI [R01 CA163377]; DOD ovarian cancer academy award [OC093420]; Cancer Center Support Grant (CCSG) [CA010815] FX R. Zhang is an Ovarian Cancer Research Fund (OCRF) Liz Tilberis Scholar. This work was supported by an NIH/NCI R01 CA163377 in part by a DOD ovarian cancer academy award (OC093420 to R. Zhang). Support of Core Facilities used in this study was provided by Cancer Center Support Grant (CCSG) CA010815 to The Wistar Institute. NR 41 TC 18 Z9 20 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2012 VL 10 IS 11 BP 1462 EP 1472 DI 10.1158/1541-7786.MCR-12-0335 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 049YO UT WOS:000312019600006 PM 22964433 ER PT J AU Chang, DK Sui, JH Geng, SS Muvaffak, A Bai, M Fuhlbrigge, RC Lo, A Yammanuru, A Hubbard, L Sheehan, J Campbell, JJ Zhu, Q Kupper, TS Marasco, WA AF Chang, De-Kuan Sui, Jianhua Geng, Shusheng Muvaffak, Asli Bai, Mei Fuhlbrigge, Robert C. Lo, Agnes Yammanuru, Anuradha Hubbard, Luke Sheehan, Jared Campbell, James J. Zhu, Quan Kupper, Thomas S. Marasco, Wayne A. TI Humanization of an Anti-CCR4 Antibody That Kills Cutaneous T-Cell Lymphoma Cells and Abrogates Suppression by T-Regulatory Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CHEMOKINE RECEPTOR CCR4; MONOCLONAL-ANTIBODY; SEZARY-SYNDROME; MYCOSIS-FUNGOIDES; LEUKEMIA-LYMPHOMA; MOLECULAR TARGET; IN-VIVO; IMMUNOTHERAPY; EXPRESSION; ASSOCIATION AB Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of neoplastic disorders characterized by clonally derived and skin-homing malignant T cells that express high level of chemokine receptor CCR4, which is associated with their skin-homing capacity. CCR4 is also highly expressed on T-regulatory cells (Tregs) that can migrate to several different types of chemotactic ligand CCL17- and CCL22-secreting tumors to facilitate tumor cell evasion from immune surveillance. Thus, its high-level expression on CTCL cells and Tregs makes CCR4 a potential ideal target for antibody-based immunotherapy for CTCL and other types of solid tumors. Here, we conducted humanization and affinity optimization of a murine anti-CCR4 monoclonal antibody (mAb), mAb1567, that recognizes both the N-terminal and extracellular domains of CCR4 with high affinity and inhibits chemotaxis of CCR4(+) CTCL cells. In a mouse CTCL tumor model, mAb1567 exhibited a potent antitumor effect and in vitro mechanistic studies showed that both complement-dependent cytotoxicity (CDC) and neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) likely mediated this effect. mAb1567 also exerts human NK cell-mediated ADCC activity in vitro. Moreover, mAb1567 also effectively inhibits chemotaxis of CD4(+)CD25(high) Tregs via CCL22 and abrogates Treg suppression activity in vitro. An affinity-optimized variant of humanized mAb1567, mAb2-3, was selected for further preclinical development based on its higher binding affinity and more potent ADCC and CDC activities. Taken together, this high-affinity humanized mAb2-3 with potent antitumor effect and a broad range of mechanisms of action may provide a novel immunotherapy for CTCL and other solid tumors. Mol Cancer Ther; 11(11); 2451-61. (C) 2012 AACR. C1 [Chang, De-Kuan; Sui, Jianhua; Geng, Shusheng; Muvaffak, Asli; Lo, Agnes; Yammanuru, Anuradha; Hubbard, Luke; Sheehan, Jared; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Chang, De-Kuan; Sui, Jianhua; Geng, Shusheng; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02215 USA. [Bai, Mei; Fuhlbrigge, Robert C.; Campbell, James J.; Kupper, Thomas S.] Harvard Univ, Dept Dermatol, Harvard Skin Dis Res Ctr, Brigham & Womens Hosp,Med Sch, Boston, MA 02215 USA. RP Marasco, WA (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & AIDS, 450 Brookline Ave, Boston, MA 02215 USA. EM quan_zhu@dfci.harvard.edu; tkupper@partners.org; wayne_marasco@dfci.harvard.edu OI SUI, JIANHUA/0000-0002-1272-9662 FU Skin Cancer Score [2P50CA093683]; NIH [AI058804] FX This work was funded by Skin Cancer Score project 2P50CA093683 to T. S. Kupper, J. Campbell, and W. A. Marasco and NIH AI058804 to Q. Zhu. NR 49 TC 27 Z9 29 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD NOV PY 2012 VL 11 IS 11 BP 2451 EP 2461 DI 10.1158/1535-7163.MCT-12-0278 PG 11 WC Oncology SC Oncology GA 049VN UT WOS:000312011600015 PM 22869555 ER PT J AU Chen, YX Melton, DW Gelfond, JAL McManus, LM Shireman, PK AF Chen, Yongxin Melton, David W. Gelfond, Jonathan A. L. McManus, Linda M. Shireman, Paula K. TI MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation SO PHYSIOLOGICAL GENOMICS LA English DT Article DE microRNA; myogenic progenitor cell; muscle regeneration; muscle differentiation ID SKELETAL-MUSCLE; MUSCULAR-DYSTROPHY; CYCLE PROGRESSION; SATELLITE CELLS; MICROARRAY DATA; GENE-REGULATION; MICRORNA; EXPRESSION; E2F; MYOGENESIS AB Chen Y, Melton DW, Gelfond JAL, McManus LM, Shireman PK. MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation. Physiol Genomics 44: 1042-1051, 2012. First published September 11, 2012; doi: 10.1152/physiolgenomics.00052.2012.-Micro-RNAs (miRNAs) regulate many biological processes including muscle development. However, little is known regarding miRNA regulation of muscle regeneration. Murine tibialis anterior muscle was evaluated after cardiotoxin-induced injury and used for global miRNA expression analysis. From day 1 through day 21 following injury, 298 miRNAs were significantly changed at least at one time point, including 86 miRNAs that were altered >10-fold compared with uninjured skeletal muscle. Temporal miRNA expression patterns included inflammation-related miRNAs (miR-223 and -147) that increased immediately after injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, -133a, and -499) that abruptly decreased following injury followed by upregulation in later regenerative events. Another cluster of miRNAs were transiently increased in the early days of muscle regeneration including miR-351, a miRNA that was also transiently expressed during myogenic progenitor cell (MPC) differentiation in vitro. Based on computational predictions, further studies demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown of miR-351 expression inhibited MPC proliferation and promoted apoptosis during MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis during differentiation. Collectively, these observations suggest that miR-351 is involved in both the maintenance of MPC proliferation and the transition into differentiated myotubes. Thus, a novel, time-dependent sequence of molecular events during muscle regeneration has been identified; miR-351 inhibits E2f3 expression, a key regulator of cell cycle progression and proliferation, and promotes MPC proliferation and protects early differentiating MPC from apoptosis, important events in the hostile tissue environment after acute muscle injury. C1 [Chen, Yongxin; McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Melton, David W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Melton, David W.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Gelfond, Jonathan A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Melton, David W.; McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shireman, PK (reprint author), 7703 Floyd Curl Dr,MC 7741, San Antonio, TX 78229 USA. EM shireman@uthscsa.edu FU National Institutes of Health (NIH) [K01-AR-059096, KL2-R025766, R01-HL-074236, T32-HL-007446, F30-HL-110743]; Veterans Administration Merit Review; University of Texas Health Science Center at San Antonio; NIH-NCI [P30 CA-054174] FX These studies were supported, in part, by National Institutes of Health (NIH) Grants K01-AR-059096, KL2-R025766, R01-HL-074236, T32-HL-007446, and F30-HL-110743 and by Veterans Administration Merit Review. Data were generated in the Core Flow Cytometry Facility, which is supported by the University of Texas Health Science Center at San Antonio and NIH-NCI P30 CA-054174 (Cancer Therapy & Research Center). NR 70 TC 24 Z9 24 U1 0 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD NOV PY 2012 VL 44 IS 21 BP 1042 EP 1051 DI 10.1152/physiolgenomics.00052.2012 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 032FU UT WOS:000310699800004 PM 22968638 ER PT J AU Megargel, E Broder-Fingert, S AF Megargel, Eve Broder-Fingert, Sarabeth TI Autism and Hospitals: A Difficult Match SO ACADEMIC PEDIATRICS LA English DT Editorial Material AB As a resident, you always have that one patient who sticks out in your mind-the one who had some profound impact on your practice of medicine and your life outside of medicine. For me, though, it wasn't just one patient. It was one patient after another with the same challenge: autism. Having worked in the school system before medical school, I immediately recognized what was missing in the way physicians and the medical establishment approached children with autism. The hospital staff had no real understanding of these children and how their worlds worked. I first met Billy's mother on a crisp spring afternoon. I had been thinking about and searching for a way to provide the best care for children with autism when in the hospital. I wanted to hear what Eve, the mother of a ywung man with autism, thought about the issue. The following is Eve's story, in her own words. C1 [Broder-Fingert, Sarabeth] MassGen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. RP Broder-Fingert, S (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Fl, Boston, MA 02114 USA. EM sbroderfingert@gmail.com NR 0 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD NOV-DEC PY 2012 VL 12 IS 6 BP 469 EP 470 PG 2 WC Pediatrics SC Pediatrics GA 048OA UT WOS:000311920600001 PM 23159035 ER PT J AU Pulcini, CD Kotelchuck, M Kuhlthau, KA Nozzolillo, AA Perrin, JM AF Pulcini, Christian D. Kotelchuck, Milton Kuhlthau, Karen A. Nozzolillo, Alixandra A. Perrin, James M. TI Potential Savings From Redetermining Disability Among Children Receiving Supplemental Security Income Benefits SO ACADEMIC PEDIATRICS LA English DT Article DE children; costs; disability; savings; SSI ID HEALTH-CARE AB OBJECTIVE: To compare the costs of redetermining disability to potential savings in Supplemental Security Income payments associated with different strategies for implementing Continuing Disability Reviews (CDRs) among children potentially enrolled in SSI from 2012 to 2021. METHODS: We reviewed publicly available reports from the Social Security Administration and Government Accountability Office to estimate costs and savings. We considered CDRs for children ages 1-17 years, excluding mandated low-birth weight and age 18 redeterminations that SSA routinely has performed. RESULTS: If in 2012 the Social Security Administration performs the same number of CDRs for children as in 2010 (16,677, 1% of eligibles) at a cessation rate of 15%, the agency would experience net savings of approximately $145 million in benefit payments. If CDR numbers increased to the greatest level ever (183,211, 22% of eligibles, in 1999) at the same cessation rate, the agency would save approximately $1.6 billion in benefit payments. DISCUSSION: Increasing the numbers of CDRs for children represents a considerable opportunity for savings. Recognizing the dynamic nature of disability, the agency could reassess the persistence of disability systematically; doing so could free up resources from children who are no longer eligible and help the agency better direct its benefits to recipients with ongoing disability and whose families need support to meet the extra costs associated with raising a child with a major disability. C1 [Perrin, James M.] MassGen Hosp Children, Div Gen Pediat, MGH Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Pulcini, Christian D.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Kotelchuck, Milton; Kuhlthau, Karen A.; Perrin, James M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Perrin, JM (reprint author), MassGen Hosp Children, Div Gen Pediat, MGH Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,Room 1542, Boston, MA 02114 USA. EM jperrin@partners.org FU American Pediatric Society/Society for Pediatric Research [T35 HD 7446] FX Preparation of this work was supported by a grant to the American Pediatric Society/Society for Pediatric Research (grant T35 HD 7446). This work is solely the responsibility of the authors and does not represent the official views of the American Pediatric Society/Society for Pediatric Research. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review or approval of the manuscript. Mr. Christian Pulcini had full access to all of the data in the study, and he takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 17 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD NOV-DEC PY 2012 VL 12 IS 6 BP 489 EP 494 PG 6 WC Pediatrics SC Pediatrics GA 048OA UT WOS:000311920600005 PM 22989732 ER PT J AU Boxerman, JL Jayaraman, MV Mehan, WA Rogg, JM Haas, RA AF Boxerman, J. L. Jayaraman, M. V. Mehan, W. A. Rogg, J. M. Haas, R. A. TI Clinical Stroke Penumbra: Use of National Institutes of Health Stroke Scale as a Surrogate for CT Perfusion in Patient Triage for Infra-Arterial Middle Cerebral Artery Stroke Therapy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; COOPERATIVE ACUTE STROKE; ACUTE HEMISPHERIC STROKE; COMPUTED-TOMOGRAPHY; SOURCE IMAGES; INFARCT CORE; DWI MISMATCH; THROMBOLYSIS; SCORE AB BACKGROUND AND PURPOSE: CTP may help triage acute stroke patients for IAT, but requires additional contrast agent, radiation, and imaging time. Our aim was to determine whether clinical examination (NIHSS) with NCCT and CTA can substitute for CTP without significantly affecting IAT triage of patients with acute MCA stroke. MATERIALS AND METHODS: We reviewed NCCT, CTA, and CTP imaging performed within 8 hours of symptom onset in 36 patients presenting with MCA territory stroke (September 2007 October 2009). Two neuroradiologists reviewed, independently and by consensus, NCCT, CTA, and CTP (CTP group), and 2 different neuroradiologists blinded to CTP reviewed NCCT, CTA, and NIHSS (stroke scale group) to determine IAT eligibility: M1 or proximal M2 occlusion; infarct core <1/3 MCA territory; and ischemic penumbra >20% infarct core. The stroke scale group estimated infarct core from NCCT and CTA source images and ischemic penumbra from core size relative to NIHSS score and re-evaluated patients after unblinding to CTP. We computed intragroup and intergroup K scores for IAT treatment recommendation and used the McNemar test to determine whether CTP significantly affected the stroke scale group's decisions. RESULTS: IAT was recommended in 16/36 (44%) and 17/36 (47%) patients by the CTP and stroke scale groups, respectively, with intragroup kappa scores of 0.78 +/- 0.11 versus 0.83 +/- 0.09. The intergroup kappa score was 0.83 +/- 0.09. When unblinded to CTP, the stroke scale group revised 2/36 (5.6%) decisions, which was insignificant (P = .48, McNemar test). CONCLUSIONS: NIHSS interpreted with NCCT and CTA may be an effective substitute for CTP-derived measures in the IAT triage of patients with acute MCA stroke. Replacing CTP may potentially reduce radiation and contrast dose and time to treatment. C1 [Boxerman, J. L.; Jayaraman, M. V.; Rogg, J. M.; Haas, R. A.] Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI 02903 USA. [Boxerman, J. L.; Jayaraman, M. V.; Rogg, J. M.; Haas, R. A.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Mehan, W. A.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Boxerman, JL (reprint author), Rhode Isl Hosp, Dept Diagnost Imaging, 593 Eddy St, Providence, RI 02903 USA. EM jboxerman@lifespan.org NR 36 TC 3 Z9 4 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV PY 2012 VL 33 IS 10 BP 1893 EP 1900 DI 10.3174/ajnr.A3102 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 045QH UT WOS:000311711400011 PM 22627795 ER PT J AU Kougias, P Tiwari, V Orcutt, S Chen, A Pisimisis, G Barshes, NR Bechara, CF Berger, DH AF Kougias, Panagiotis Tiwari, Vikram Orcutt, Sonia Chen, Amber Pisimisis, George Barshes, Neal R. Bechara, Carlos F. Berger, David H. TI Derivation and out-of-sample validation of a modeling system to predict length of surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Modeling; Regression; Operative length; Precision ID TIMES; DURATION; THEATER; EXPENDITURES; VARIABILITY AB BACKGROUND: We performed a retrospective study to compare the precision of a regression model (RM) system with the precision of the standard method of surgical length prediction using historical means (HM). METHODS: Data were collected on patients who underwent carotid endarterectomy and lower-extremity bypass. Multiple linear regression was used to model the operative time length (OTL). The precision of the RM versus HM in predicting case length then was compared in a validation dataset. RESULTS: With respect to carotid endarterectomy, surgeon, surgical experience, and cardiac surgical risk were significant predictors of OTL. For lower-extremity bypass, surgeon, use of prosthetic conduit, and performance of a sequential bypass or hybrid procedure were significant predictors of OTL. The precision of out-of-sample prediction was greater for the RM system compared with HM for both procedures. CONCLUSIONS: A regression methodology to predict case length appears promising in decreasing uncertainty about surgical case length. Published by Elsevier Inc. C1 [Kougias, Panagiotis; Orcutt, Sonia; Chen, Amber; Pisimisis, George; Barshes, Neal R.; Bechara, Carlos F.; Berger, David H.] Baylor Coll Med, Houston Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Tiwari, Vikram] Vanderbilt Univ, Nashville, TN USA. RP Kougias, P (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM pkougias@bcm.edu FU Houston VAMC Health Services Research and Development Center of Excellence FX The authors would like to acknowledge the Houston VAMC Health Services Research and Development Center of Excellence for support provided in this project. NR 20 TC 5 Z9 5 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2012 VL 204 IS 5 BP 563 EP 568 DI 10.1016/j.amjsurg.2012.07.013 PG 6 WC Surgery SC Surgery GA 045YZ UT WOS:000311734000008 PM 23140826 ER PT J AU Stewart, L Griffiss, JM Jarvis, GA Way, LW AF Stewart, Lygia Griffiss, J. McLeod Jarvis, Gary A. Way, Lawrence W. TI The association between body mass index and severe biliary infections: a multivariate analysis SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-of-VA-Surgeons CY APR 01-03, 2012 CL Miami Beach, FL SP Assoc VA Surg DE Biliary infections; Gallstones; Bactibilia; Bacteremia; Cholangitis; Cholecystitis; Obesity; Body mass index (BMI) ID NECROSIS-FACTOR-ALPHA; GALLSTONE DISEASE; PIGMENT GALLSTONES; OBESITY; BACTERIA; PANCREATITIS; MANIFESTATIONS; LIPOPROTEINS; PATHOGENESIS; COMPLEMENT AB BACKGROUND: Obesity has been associated with worse infectious disease outcomes. It is a risk factor for cholesterol gallstones, but little is known about associations between body mass index (BMI) and biliary infections. We studied this using factors associated with biliary infections. METHODS: A total of 427 patients with gallstones were studied. Gallstones, bile, and blood (as applicable) were cultured. Illness severity was classified as follows: none (no infection or inflammation), systemic inflammatory response syndrome (fever, leukocytosis), severe (abscess, cholangitis, empyema), or multi-organ dysfunction syndrome (bacteremia, hypotension, organ failure). Associations between BMI and biliary bacteria, bacteremia, gallstone type, and illness severity were examined using bivariate and multivariate analysis. RESULTS: BMI inversely correlated with pigment stones, biliary bacteria, bacteremia, and increased illness severity on bivariate and multivariate analysis. CONCLUSIONS: Obesity correlated with less severe biliary infections. BMI inversely correlated with pigment stones and biliary bacteria; multivariate analysis showed an independent correlation between lower BMI and illness severity. Most patients with severe biliary infections had a normal BMI, suggesting that obesity may be protective in biliary infections. This study examined the correlation between BMI and biliary infection severity. Published by Elsevier Inc. C1 [Stewart, Lygia; Way, Lawrence W.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA. [Stewart, Lygia] San Francisco VA Med Ctr, Dept Surg 112, San Francisco, CA USA. [Griffiss, J. McLeod; Jarvis, Gary A.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Immunochem, San Francisco, CA 94121 USA. [Griffiss, J. McLeod; Jarvis, Gary A.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94121 USA. RP Stewart, L (reprint author), Univ Calif San Francisco, Dept Surg, 112,4150 Clement St, San Francisco, CA 94121 USA. EM lygia.stewart@med.va.gov NR 29 TC 4 Z9 5 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2012 VL 204 IS 5 BP 574 EP 579 DI 10.1016/j.amjsurg.2012.07.002 PG 6 WC Surgery SC Surgery GA 045YZ UT WOS:000311734000010 PM 22892201 ER PT J AU Altom, LK Deierhoi, RJ Grams, J Richman, JS Vick, CC Henderson, WG Itani, KMF Hawn, MT AF Altom, Laura K. Deierhoi, Rhiannon J. Grams, Jayleen Richman, Joshua S. Vick, Catherine C. Henderson, William G. Itani, Kamal M. F. Hawn, Mary T. TI Association between Surgical Care Improvement Program venous thromboembolism measures and postoperative events SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Surgical Care Improvement Program; SCIP measures; Postoperative outcomes; Venous thromboembolism; VTE; Deep venous thrombosis; DVT; Pulmonary embolism; PE; SCIP measure; Adherence; VTE risk factors ID DEEP-VEIN THROMBOSIS; COLORECTAL SURGERY; PROJECT MEASURES; SITE INFECTION; PROPHYLAXIS; PREVENTION; OUTCOMES; RISK; ADHERENCE; PATIENT AB BACKGROUND: In 2006, the Surgical Care Improvement Program (SCIP) implemented measures to reduce venous thromboembolism (VTE). There are little data on whether these measures reduce VTE rates. This study proposed to examine associations between SCIP-VTE adherence and VTE rates. METHODS: SCIP-VTE adherence for 30,531 surgeries from 2006 to 2009 was linked with VA Surgical Quality Improvement Program data. Patient demographics, comorbidities, and surgical characteristics associated with VTE were summarized. VTE rates were compared by SCIP-VTE adherence. Multivariable logistic regression was used to model VTE by adherence, adjusting for multiple associated factors. RESULTS: Of 30,531 surgeries, 89.9% adhered to SCIP-VTE; 1.4% experienced VTE. Logistic regression identified obesity, smoking, functional status, weight loss, emergent status, age older than 64 years, and surgical time as associated with VTE. SCIP-VTE was not associated with VTE (1.4% vs 1.33%; P = .3), even after adjustment. CONCLUSIONS: This study identified several important risk factors for VTE but found no association with SCIP-VTE adherence. Published by Elsevier Inc. C1 [Altom, Laura K.; Deierhoi, Rhiannon J.; Richman, Joshua S.; Vick, Catherine C.; Hawn, Mary T.] Birmingham Vet Adm Hosp, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL 35294 USA. [Altom, Laura K.; Grams, Jayleen; Richman, Joshua S.; Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL 35294 USA. [Altom, Laura K.] Univ Alabama Birmingham, Hlth Serv Comparat Effectiveness Res Training Pro, Birmingham, AL USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. [Henderson, William G.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Itani, Kamal M. F.] Boston Univ, Dept Surg, VA Boston Hlth Care Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Hawn, MT (reprint author), Birmingham Vet Adm Hosp, Ctr Surg Med Acute Care Res & Transit, 1530 3rd Ave S,KB 428, Birmingham, AL 35294 USA. EM mhawn@uabmc.edu FU HSRD [PPO 10-296, CDA 09-014]; AHRQ [T32HS013852] FX Supported by HSRD PPO 10-296, CDA 09-014, and AHRQ T32HS013852. NR 23 TC 20 Z9 20 U1 1 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2012 VL 204 IS 5 BP 591 EP 597 DI 10.1016/j.amjsurg.2012.07.006 PG 7 WC Surgery SC Surgery GA 045YZ UT WOS:000311734000013 PM 22906249 ER PT J AU Cajipe, MD Chu, D Bakaeen, FG Casal, RF LeMaire, SA Coselli, JS Cornwell, LD AF Cajipe, Miguel D. Chu, Danny Bakaeen, Faisal G. Casal, Roberto F. LeMaire, Scott A. Coselli, Joseph S. Cornwell, Lorraine D. TI Video-assisted thoracoscopic lobectomy is associated with better perioperative outcomes than open lobectomy in a veteran population SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-of-VA-Surgeons CY APR 01-03, 2012 CL Miami Beach, FL SP Assoc VA Surg DE Lung cancer; Veterans; Veterans Affairs; Lobectomy; Video-assisted thoracoscopic surgery; Outcomes; VATS; Complications ID CELL LUNG-CANCER; THORACIC-SURGERY LOBECTOMY; THORACOTOMY; TUMORS AB BACKGROUND: We sought to establish the feasibility and efficacy of video-assisted thoracoscopic (VATS) lobectomy in treating lung cancer in a veteran population. METHODS: We retrospectively analyzed preoperative, intraoperative, and postoperative parameters in 46 VATS versus 45 open lobectomy patients at a single center. RESULTS: The 2 groups were similar in preoperative and intraoperative variables. Although surgical mortality was not significantly different after lobectomy performed with VATS (0 of 46) compared with open lobectomy (2 of 45, 4%; P = .2), there were fewer complications in VATS patients (14 of 46, 30%) than their open counterparts (26 of 45, 58%; P = .009). VATS patients also had a shorter chest tube duration and length of stay. In multivariate analysis, VATS was associated independently with a reduced risk of complications (odds ratio,.359; P = .04). CONCLUSIONS: VATS lobectomy in a veteran population is feasible and safe and may lead to better perioperative outcomes than open thoracotomy without compromising oncologic principles. Published by Elsevier Inc. C1 [Cajipe, Miguel D.; Chu, Danny; Bakaeen, Faisal G.; Casal, Roberto F.; LeMaire, Scott A.; Coselli, Joseph S.; Cornwell, Lorraine D.] Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Chu, Danny; Bakaeen, Faisal G.; LeMaire, Scott A.; Coselli, Joseph S.] St Lukes Episcopal Hosp, Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX USA. RP Cornwell, LD (reprint author), Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM cornwell@bcm.edu NR 22 TC 12 Z9 14 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2012 VL 204 IS 5 BP 607 EP 612 DI 10.1016/j.amjsurg.2012.07.022 PG 6 WC Surgery SC Surgery GA 045YZ UT WOS:000311734000016 PM 22959921 ER PT J AU Hall, DE Morrison, P Nikolajski, C Fine, M Arnold, R Zickmund, SL AF Hall, Daniel E. Morrison, Penelope Nikolajski, Cara Fine, Michael Arnold, Robert Zickmund, Susan L. TI Informed consent for inguinal herniorrhaphy and cholecystectomy: describing how patients make decisions to have surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-of-VA-Surgeons CY APR 01-03, 2012 CL Miami Beach, FL SP Assoc VA Surg DE Informed consent; Informed decision making; Decision making; iMed consent; Decision aid; Herniorrhaphy; Cholecystectomy ID CLINICAL ANESTHESIA; BACK; COMMUNICATION; PERSPECTIVE; UNDERSTAND; QUALITY; IMPACT; TRIAL; VIDEO AB BACKGROUND: We describe how patients perceive the process of informed consent and its influence on decision making for elective surgery. METHODS: A cohort of 38 patients documented consent for cholecystectomy or inguinal herniorrhaphy using the Veterans Affair's computer-based tool for documenting informed consent for clinical treatment. Participants completed semistructured telephone interviews exploring their attitudes about informed consent, iMed, and the decision-making process. We used qualitative methods to code and analyze the data. RESULTS: Sixty-nine percent of patients decided to have surgery before meeting their surgeon, and 47% stated that the surgeon did not influence their decision. Although the surgeon was an important source of information for most patients (81%), patients frequently described using information gathered before meeting the surgeon, such as other health care providers (81%) or family members (58%). Most (68%) patients perceived iMed as a legal formality with little influence on decision making. CONCLUSIONS: Future research should examine whether patient decision making regarding elective surgery becomes better informed if nonsurgeon clinicians connect patients to educational resources such as iMed closer to the time of initial diagnosis and before meeting the surgeon. Published by Elsevier Inc. C1 [Hall, Daniel E.; Nikolajski, Cara; Fine, Michael; Zickmund, Susan L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Morrison, Penelope] Univ Pittsburgh, RAND Univ Pittsburgh Hlth Inst, Pittsburgh, PA USA. [Nikolajski, Cara] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Fine, Michael; Arnold, Robert] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Zickmund, Susan L.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. RP Hall, DE (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151 C-H, Pittsburgh, PA 15206 USA. EM hallde@upmc.edu RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 35 TC 1 Z9 1 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2012 VL 204 IS 5 BP 619 EP 625 DI 10.1016/j.amjsurg.2012.07.020 PG 7 WC Surgery SC Surgery GA 045YZ UT WOS:000311734000018 PM 22944389 ER PT J AU Hayman, AV Tarpley, JL Berger, DH Wilson, MA Livingston, EH Kibbe, MR AF Hayman, Amanda V. Tarpley, John L. Berger, David H. Wilson, Mark A. Livingston, Edward H. Kibbe, Melina R. CA Assoc VA Surg TI How is the Department of Veterans Affairs addressing the new Accreditation Council for Graduate Medical Education intern work hour limitations? Solutions from the Association of Veterans Affairs Surgeons SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Intern; Work-hour limitation; ACGME; Veterans Affairs ID COMMUNICATION AB BACKGROUND: The Accreditation Council for Graduate Medical Education implemented new intern work-hour regulations in July 2011 that have unique implications for surgical training at Veterans Affairs (VA) medical centers. Implementation of these new regulations required profound restructuring of trainee night coverage systems at many VA medical centers. This article offers approaches and potential solutions to the Accreditation Council for Graduate Medical Education regulations used by different surgery programs throughout the country that are applicable to the VA training environment. METHODS: The information contained in this article was derived from the opinion of a panel of academic surgical leaders in the VA system and responses to a survey that was sent to national VA surgical leaders. RESULTS: The most common solution chosen by the VA centers was hiring physician extenders (37%). The most common type of extender was a nonphysician extender, that is, nurse practitioner or physician assistant (70%), followed by a surgical hospitalist (33%), and surgical resident moonlighter (24%). Other common solutions included the following: night float for residents (22%) or interns (19%), establishing early versus late shifts (19%), or establishing cross-institutional or disciplinary coverage (19%). CONCLUSIONS: The public expects the medical community to produce safe, experienced surgeons, while demanding they are well rested and directly supervised at all times. The ability to meet these expectations can be challenging. Published by Elsevier Inc. C1 [Hayman, Amanda V.; Kibbe, Melina R.] Jesse Brown VA Med Ctr, Chicago, IL 60611 USA. [Tarpley, John L.] VA Tennessee Valley Hlth Care Syst, Nashville, TN USA. [Berger, David H.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Wilson, Mark A.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Livingston, Edward H.] Univ Texas SW Sch Med, Dallas, TX USA. RP Kibbe, MR (reprint author), Jesse Brown VA Med Ctr, 676 N St Clair,650, Chicago, IL 60611 USA. EM mkibbe@nmh.org NR 6 TC 2 Z9 2 U1 2 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2012 VL 204 IS 5 BP 655 EP 662 DI 10.1016/j.amjsurg.2012.07.009 PG 8 WC Surgery SC Surgery GA 045YZ UT WOS:000311734000024 PM 22906248 ER PT J AU Saul, D Stephens, D Hofstatter, RD Ahmed, L Langhoff, E Heimann, TM AF Saul, Daniel Stephens, Daniel Hofstaetter, Rita de Cassia Ahmed, Leaque Langhoff, Erik Heimann, Tomas M. TI Preliminary outcomes of laparoscopic sleeve gastrectomy in a Veterans Affairs medical center SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-of-VA-Surgeons CY APR 01-03, 2012 CL Miami Beach, FL SP Assoc VA Surg DE Bariatric surgery; Morbid obesity; Laparoscopic sleeve gastrectomy; Vertical gastrectomy; Staple line reinforcement; Diabetes; Veterans Affairs ID Y GASTRIC BYPASS; TYPE-2 DIABETES-MELLITUS; MORBIDLY OBESE-PATIENTS; HEALTH-CARE-SYSTEM; HIGH-RISK PATIENTS; BARIATRIC SURGERY; REINFORCEMENT; OPERATION; GHRELIN AB BACKGROUND: Preliminary results of a new bariatric surgery program in a VA Medical Center using laparoscopic sleeve gastrectomy (LSG). METHODS: Prospective review of the first 50 patients who underwent LSG. Percentage change in body mass index (BMI), comorbidities, serum glucose, glycosylated hemoglobin (HbA1c), lipid profiles, and medications were recorded. RESULTS: Mean age was 52 years. Average BMI was 46 kg/m(2). There were no mortalities or staple line leaks. The percentage excess BMI loss was 47% and 54% at 6 and 12 months, respectively. After 6 months, fasting glucose level decreased from 127 to 93 mg/dL, and mean glycosylated hemoglobin decreased from 6.8% to 5.7%. At 1-year follow-up evaluation, serum cholesterol decreased from 182 to 168 mg/dL, mean triglycerides from 179 to 93 mg/dL, low-density lipoprotein from 110 to 94 mg/dL, and high-density lipoprotein increased from 42 to 50 mg/dL. CONCLUSIONS: Laparoscopic sleeve gastrectomy is safe and effective for morbidly obese VA patients and resulted in significant discontinuation of medication for hypertension, diabetes and hyperlipidemia. Published by Elsevier Inc. C1 [Stephens, Daniel] James J Peters VA Med Ctr, Dept Surg, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Stephens, D (reprint author), James J Peters VA Med Ctr, Dept Surg, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM djs979@yahoo.com NR 38 TC 3 Z9 3 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2012 VL 204 IS 5 BP E1 EP E6 DI 10.1016/j.amjsurg.2012.07.005 PG 6 WC Surgery SC Surgery GA 045YZ UT WOS:000311734000001 PM 22902102 ER PT J AU Freeman, JS Horton, ES AF Freeman, Jeffrey S. Horton, Edward S. TI What Have We Learned About the Treatment of Type 2 Diabetes? The Evolving Paradigms SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Review DE type 2 diabetes; management; efficacy; safety ID ADD-ON THERAPY; INADEQUATE GLYCEMIC CONTROL; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; INCRETIN-BASED THERAPIES; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; PROTAMINE HAGEDORN INSULIN; TWICE-DAILY EXENATIDE; OPEN-LABEL TRIAL; TO-TARGET TRIAL AB Insulin, the first treatment for diabetes, was discovered >90 years ago. Since then, many new types of insulin have become available, including analogs that more closely mimic the characteristics of endogenous insulin. In addition, oral antidiabetes drugs and other types of injectable therapies have been approved for the treatment of patients with type 2 diabetes. As newer treatments are approved for type 2 diabetes, the choice and-paradoxically-the complexity of treatment increases. The potential benefits of all treatment options must be carefully balanced against potential adverse events to truly analyze the overall efficacy, safety, tolerability, and potential long-term effects. The manner in which outcomes are assessed and the methods employed to make such assessments have changed over time. This review will address these issues as they are related to therapies for type 2 diabetes, including insulin, oral antidiabetes drugs, and incretin-based agents. C1 [Freeman, Jeffrey S.] Philadelphia Coll Osteopath Med, Div Endocrinol & Metab, Philadelphia, PA 19131 USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Freeman, JS (reprint author), Philadelphia Coll Osteopath Med, Div Endocrinol & Metab, 4190 City Ave, Philadelphia, PA 19131 USA. EM jeffreyfreemando@aol.com FU Good Publication Practice for Communicating Company; Novo Nordisk Inc. FX The authors wish to thank Beatriz Mitryzk, PharmD, and Aric Fader, PhD, of MedVal Scientific Information Services, LLC, for providing medical writing and editorial assistance. This article was prepared according to the International Society for Medical Publication Professionals' Good Publication Practice for Communicating Company-Sponsored Medical Research: the GPP2 Guidelines. Funding to support the preparation of this article was provided by Novo Nordisk Inc. NR 126 TC 1 Z9 1 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD NOV-DEC PY 2012 VL 19 IS 6 BP 449 EP 464 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 042JO UT WOS:000311467700011 PM 23154228 ER PT J AU Abbott, AL Adelman, MA Alexandrov, AV Barnett, HJM Beard, J Bell, P Bjorck, M Blacker, D Buckley, CJ Cambria, RP Comerota, AJ Connolly, ES Davies, AH Eckstein, HH Faruqi, R Fraedrich, G Gloviczki, P Hankey, GJ Harbaugh, RE Heldenberg, E Kittner, SJ Kleinig, TJ Mikhailidis, DP Moore, WS Naylor, R Nicolaides, A Paraskevas, KI Pelz, DM Prichard, JW Purdie, G Ricco, JB Riles, T Rothwell, P Sandercock, P Sillesen, H Spence, JD Spinelli, F Tan, A Thapar, A Veith, FJ Zhou, W AF Abbott, Anne L. Adelman, Mark A. Alexandrov, Andrei V. Barnett, Henry J. M. Beard, Jonathan Bell, Peter Bjorck, Martin Blacker, David Buckley, Clifford J. Cambria, Richard P. Comerota, Anthony J. Connolly, E. Sander, Jr. Davies, Alun H. Eckstein, Hans-Henning Faruqi, Rishad Fraedrich, Gustav Gloviczki, Peter Hankey, Graeme J. Harbaugh, Robert E. Heldenberg, Eitan Kittner, Steven J. Kleinig, Timothy J. Mikhailidis, Dimitri P. Moore, Wesley S. Naylor, Ross Nicolaides, Andrew Paraskevas, Kosmas I. Pelz, David M. Prichard, James W. Purdie, Grant Ricco, Jean-Baptiste Riles, Thomas Rothwell, Peter Sandercock, Peter Sillesen, Henrik Spence, J. David Spinelli, Francesco Tan, Aaron Thapar, Ankur Veith, Frank J. Zhou, Wei TI Why the US Center for Medicare and Medicaid Services Should Not Extend Reimbursement Indications for Carotid Artery Angioplasty/Stenting SO ANGIOLOGY LA English DT Letter ID RANDOMIZED CONTROLLED-TRIAL; STROKE PREVENTION; ENDARTERECTOMY; STENOSIS; RISK; DISEASE; REVASCULARIZATION; PROFESSIONALS; ASSOCIATION; GUIDELINES C1 [Abbott, Anne L.] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia. [Abbott, Anne L.] Florey Neurosci Inst, Melbourne, Vic, Australia. [Adelman, Mark A.] NYU, Langone Med Ctr, New York, NY USA. [Alexandrov, Andrei V.] Univ Alabama Hosp & Clin, Comprehens Stroke Ctr, Birmingham, AL USA. [Barnett, Henry J. M.] Univ Western Ontario, Toronto, ON, Canada. [Beard, Jonathan] No Gen Hosp, Sheffield Vasc Inst, Sheffield S5 7AU, S Yorkshire, England. [Bell, Peter] Univ Leicester, Leicester, Leics, England. [Bell, Peter] Univ Leicester Hosp, Leicester, Leics, England. [Bjorck, Martin] Uppsala Univ, Dept Surg Sci, Vasc Surg Sect, Uppsala, Sweden. [Blacker, David] Sir Charles Gairdner Hosp, Dept Neurol, Nedlands, WA 6009, Australia. [Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Cambria, Richard P.] Harvard Univ, Sch Med, Boston, MA USA. [Comerota, Anthony J.] Toledo Hosp, Jobst Vasc Inst, Toledo, OH USA. [Connolly, E. Sander, Jr.] Columbia Univ, Dept Neurol Surg, New York, NY USA. [Davies, Alun H.] Imperial Coll Sch Med, London, England. [Eckstein, Hans-Henning] Tech Univ Munich, D-8000 Munich, Germany. [Eckstein, Hans-Henning] Tech Univ Munich, Klinikum Rechts Isar, Dept Vasc & Endovasc Surg, D-8000 Munich, Germany. [Faruqi, Rishad] Stanford Univ, Dept Surg, Stanford, CA 94305 USA. [Faruqi, Rishad] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Faruqi, Rishad] Kaiser Permanente Med Ctr, Dept Vasc & Endovasc Surg, Santa Clara, CA USA. [Fraedrich, Gustav] Med Univ, Dept Vasc Surg, Innsbruck, Austria. [Gloviczki, Peter] Mayo Clin, Div Vasc & Endovasc Surg, Rochester, MN USA. [Harbaugh, Robert E.] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA. [Harbaugh, Robert E.] Penn State Univ, Milton S Hershey Med Ctr, Dept Engn Sci & Mech, Hershey, PA 17033 USA. [Heldenberg, Eitan] Tel Aviv Univ, Assaf Harofeh Med Ctr, Zerifin, Israel. [Kittner, Steven J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Kleinig, Timothy J.; Tan, Aaron] Royal Adelaide Hosp, Dept Neurol, Adelaide, SA 5000, Australia. [Kleinig, Timothy J.; Tan, Aaron] Lyell McEwin Hosp, Dept Neurol, Adelaide, SA, Australia. [Kleinig, Timothy J.] Univ Adelaide, Adelaide, SA 5005, Australia. [Mikhailidis, Dimitri P.] UCL, Univ Coll London Med Sch, Dept Clin Biochem, Vasc Dis Prevent Clin, London, England. [Moore, Wesley S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Vasc Surg, Los Angeles, CA 90095 USA. [Naylor, Ross] Leicester Royal Infirm, Leicester, Leics, England. [Nicolaides, Andrew] Univ London Imperial Coll Sci Technol & Med, Vasc Diagnost Ctr, London, England. [Pelz, David M.] Univ Western Ontario, Dept Med Imaging, London, ON, Canada. [Pelz, David M.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. [Prichard, James W.] Yale Univ, Sch Med, New Haven, CT USA. [Purdie, Grant] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Ricco, Jean-Baptiste] Univ Poitiers, Vasc Surg Serv, Poitiers, France. [Riles, Thomas; Veith, Frank J.] NYU, Dept Surg, Sch Med, New York, NY 10016 USA. [Rothwell, Peter] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci Clin Neurol, Oxford OX3 9DU, England. [Sandercock, Peter] Western Gen Hosp, Dept Clin Neurosci, Edinburgh EH4 2XU, Midlothian, Scotland. [Sillesen, Henrik] Univ Copenhagen, Rigshosp, Dept Vasc Surg, DK-1168 Copenhagen, Denmark. [Spence, J. David] Univ Western Ontario, London, ON N6A 3K7, Canada. [Spence, J. David] Robarts Res Inst, Stroke Prevent & Atherosclerosis Res Ctr, London, ON N6A 5C1, Canada. [Spinelli, Francesco] Univ Messina, Dept Cardiovasc & Thorac Surg, Messina, Italy. [Thapar, Ankur] Charing Cross Hosp, Royal Coll Surg, London, England. [Veith, Frank J.] Cleveland Clin, Cleveland, OH 44106 USA. [Veith, Frank J.] Case Western Reserve Univ, Lerner Sch Med, Cleveland, OH 44106 USA. [Veith, Frank J.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Surg, Bethesda, MD 20814 USA. [Zhou, Wei] Palo Alto VA Hlth Care Syst, Vasc Sect, Div Vasc & Endovasc Surg, Stanford, CA USA. RP Abbott, AL (reprint author), Baker IDI Heart & Diabet Inst, 75 Commercial Rd, Melbourne, Vic 3004, Australia. EM anne.l.abbott@gmail.com RI Mikhailidis, Dimitri/A-1869-2013; Abbott, Anne/G-6604-2013; Spence, J. David/K-6396-2013; Hankey, Graeme /H-4968-2014; OI Spence, J. David/0000-0001-7478-1098; Hankey, Graeme /0000-0002-6044-7328; Eckstein, Hans-Henning/0000-0002-0743-1642; Spinelli, Francesco/0000-0001-6527-1993; Sandercock, Peter/0000-0001-8484-0135; Alexandrov, Andrei V/0000-0001-8871-1023; Adelman, Mark/0000-0001-9276-6131 FU The Dunhill Medical Trust [RCS/DMT 3RD ROUND (3)] NR 56 TC 1 Z9 1 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-3197 J9 ANGIOLOGY JI Angiology PD NOV PY 2012 VL 63 IS 8 BP 639 EP 644 DI 10.1177/0003319711436076 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 045GQ UT WOS:000311683800015 PM 22495879 ER PT J AU Rao, SY Lee, SY Gutierrez, A Perrigoue, J Thapa, RJ Tu, ZG Jeffers, JR Rhodes, M Anderson, S Oravecz, T Hunger, SP Timakhov, RA Zhang, RG Balachandran, S Zambetti, GP Testa, JR Look, AT Wiest, DL AF Rao, Shuyun Lee, Sang-Yun Gutierrez, Alejandro Perrigoue, Jacqueline Thapa, Roshan J. Tu, Zhigang Jeffers, John R. Rhodes, Michele Anderson, Stephen Oravecz, Tamas Hunger, Stephen P. Timakhov, Roman A. Zhang, Rugang Balachandran, Siddharth Zambetti, Gerard P. Testa, Joseph R. Look, A. Thomas Wiest, David L. TI Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NF-KAPPA-B; T-CELL DEVELOPMENT; TRANSLATIONAL CONTROL; EXPRESSION; GENE; INHIBITION; P53; ACTIVATION; LYMPHOMA AB Ribosomal protein (RP) mutations in diseases such as 5q- syndrome both disrupt hematopoiesis and increase the risk of developing hematologic malignancy. However, the mechanism by which RP mutations increase cancer risk has remained an important unanswered question. We show here that monoallelic, germline inactivation of the ribosomal protein L22 (Rpl22) predisposes T-lineage progenitors to transformation. Indeed, RPL22 was found to be inactivated in similar to 10% of human T-acute lymphoblastic lweukemias. Moreover, monoallelic loss of Rpl22 accelerates development of thymic lymphoma in both a mouse model of T-cell malignancy and in acute transformation assays in vitro. We show that Rpl22 inactivation enhances transformation potential through induction of the stemness factor, Lin28B. Our finding that Rpl22 inactivation promotes transformation by inducing expression of Lin28B provides the first insight into the mechanistic basis by which mutations in Rpl22, and perhaps some other RP genes, increases cancer risk. (Blood.2012;120(18):3764-3773) C1 [Rao, Shuyun; Lee, Sang-Yun; Perrigoue, Jacqueline; Thapa, Roshan J.; Rhodes, Michele; Balachandran, Siddharth; Wiest, David L.] Fox Chase Canc Ctr, Immune Cell Dev & Host Def Program, Philadelphia, PA 19111 USA. [Gutierrez, Alejandro; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gutierrez, Alejandro; Look, A. Thomas] Childrens Hosp Boston, Boston, MA USA. [Tu, Zhigang; Zhang, Rugang] Fox Chase Canc Ctr, Womens Canc Program, Philadelphia, PA 19111 USA. [Jeffers, John R.; Zambetti, Gerard P.] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. [Anderson, Stephen; Oravecz, Tamas] Lexicon Pharmaceut Inc, Dept Immunol, The Woodlands, TX USA. [Hunger, Stephen P.] Univ Colorado, Denver Sch Med, Sect Pediat Hematol Oncol Bone Marrow Transplanta, Aurora, CO USA. [Timakhov, Roman A.; Testa, Joseph R.] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA. RP Wiest, DL (reprint author), Fox Chase Canc Ctr, Immune Cell Dev & Host Def Program, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM david.wiest@fccc.edu OI Gutierrez, Alejandro/0000-0002-0249-9007; Wiest, David/0000-0002-0792-3188; Tu, Zhigang/0000-0001-9844-3245 FU National Institutes of Health [R01-AI073920, R01-CA77429, R21-CA141194, P01CA06927, T32 CA009035, 5K08CA133103]; Center grant [P30-DK-50306]; Commonwealth of Pennsylvania; Blood Cell Development and Cancer Keystone; Greenwald and Plain & Fancy Fellowships; American Society of Hematology-Amos Faculty Development Program; [U10 CA98543]; [U10 CA98413]; [U24 CA114766]; [5P01CA068484] FX This work was supported by National Institutes of Health grants R01-AI073920, R01-CA77429, and R21-CA141194; National Institutes of Health core grant P01CA06927; Center grant P30-DK-50306; an appropriation from the Commonwealth of Pennsylvania; and support from the Blood Cell Development and Cancer Keystone. This work was supported in part by grants to the COG, including U10 CA98543 (COG Chair's grant), U10 CA98413 (COG Statistical Center), and U24 CA114766 (COG Specimen Banking), as well as by grant 5P01CA068484 (to the Dana-Farber Cancer Institute and A. T. L.). S.Y.L. was supported by both the Greenwald and Plain & Fancy Fellowships. J.P. is a Merck fellow of the Life Sciences Research Fellowship and was a fellow of the National Institutes of HealthT32 CA009035 training grant. A. G. is a scholar of the American Society of Hematology-Amos Faculty Development Program and is supported by National Institutes of Health grant 5K08CA133103. NR 50 TC 38 Z9 39 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2012 VL 120 IS 18 BP 3764 EP 3773 DI 10.1182/blood-2012-03-415349 PG 10 WC Hematology SC Hematology GA 044MW UT WOS:000311624800020 PM 22976955 ER PT J AU Ronchi, D Garone, C Bordoni, A Rios, PG Calvo, SE Ripolone, M Ranieri, M Rizzuti, M Villa, L Magri, F Corti, S Bresolin, N Mootha, VK Moggio, M DiMauro, S Comi, GP Sciacco, M AF Ronchi, Dario Garone, Caterina Bordoni, Andreina Rios, Purificacion Gutierrez Calvo, Sarah E. Ripolone, Michela Ranieri, Michela Rizzuti, Mafalda Villa, Luisa Magri, Francesca Corti, Stefania Bresolin, Nereo Mootha, Vamsi K. Moggio, Maurizio DiMauro, Salvatore Comi, Giacomo P. Sciacco, Monica TI Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions SO BRAIN LA English DT Article DE DGUOK; mitochondrial DNA instability; autosomal recessive progressive external ophthalmoplegia; multiple mitochondrial DNA deletions ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; HUMAN DEOXYGUANOSINE KINASE; THYMIDINE KINASE; MTDNA DELETIONS; OPTIC ATROPHY; NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY; MOLECULAR-FEATURES; GENE-MUTATIONS; HUMAN-CELLS; DEPLETION AB The molecular diagnosis of mitochondrial disorders still remains elusive in a large proportion of patients, but advances in next generation sequencing are significantly improving our chances to detect mutations even in sporadic patients. Syndromes associated with mitochondrial DNA multiple deletions are caused by different molecular defects resulting in a wide spectrum of predominantly adult-onset clinical presentations, ranging from progressive external ophthalmoplegia to multi-systemic disorders of variable severity. The mutations underlying these conditions remain undisclosed in half of the affected subjects. We applied next-generation sequencing of known mitochondrial targets (MitoExome) to probands presenting with adult-onset mitochondrial myopathy and harbouring mitochondrial DNA multiple deletions in skeletal muscle. We identified autosomal recessive mutations in the DGUOK gene (encoding mitochondrial deoxyguanosine kinase), which has previously been associated with an infantile hepatocerebral form of mitochondrial DNA depletion. Mutations in DGUOK occurred in five independent subjects, representing 5.6% of our cohort of patients with mitochondrial DNA multiple deletions, and impaired both muscle DGUOK activity and protein stability. Clinical presentations were variable, including mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis in a young female who had received a liver transplant at 9 months of age and adult-onset lower motor neuron syndrome with mild cognitive impairment. These findings reinforce the concept that mutations in genes involved in deoxyribonucleotide metabolism can cause diverse clinical phenotypes and suggest that DGUOK should be screened in patients harbouring mitochondrial DNA deletions in skeletal muscle. C1 [Ronchi, Dario; Bordoni, Andreina; Ranieri, Michela; Rizzuti, Mafalda; Magri, Francesca; Corti, Stefania; Bresolin, Nereo; Comi, Giacomo P.] Univ Milan, IRCCS Fdn Ca Granda Osped Maggiore Policlin, Dept Pathophysiol & Transplantat DEPT, Dino Ferrari Ctr,Neurosci Sect,Neurol Unit, I-20122 Milan, Italy. [Garone, Caterina; Rios, Purificacion Gutierrez; DiMauro, Salvatore] Columbia Univ Med Ctr, Dept Neurol, New York, NY 10032 USA. [Garone, Caterina] Univ Turin, Human Genet Joint PhD Programme, I-10125 Turin, Italy. [Garone, Caterina] Univ Bologna, I-40125 Bologna, Italy. [Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst Harvard & MIT, Seven Cambridge Ctr, Broad Metab Initiat, Cambridge, MA 02142 USA. [Ripolone, Michela; Villa, Luisa; Moggio, Maurizio; Sciacco, Monica] Univ Milan, IRCCS Fdn Ca Granda Osped Maggiore Policlin, Dino Ferrari Ctr, Neuromuscular Unit, I-20122 Milan, Italy. [Corti, Stefania; Bresolin, Nereo; Comi, Giacomo P.] Univ Milan, Ctr Excellence Neurodegenerat Dis, I-20122 Milan, Italy. [Bresolin, Nereo] IRCCS Eugenio Medea, I-23842 Bosisio Parini, Lecco, Italy. RP Ronchi, D (reprint author), Univ Milan, IRCCS Fdn Ca Granda Osped Maggiore Policlin, Dept Pathophysiol & Transplantat, Neurosci Sect, Via Francesco Sforza 35, I-20122 Milan, Italy. EM dario.ronchi@unimi.it RI Gutierrez Rios, Purificacion/I-4234-2015; Comi, Giacomo /K-5702-2016; Corti, Stefania/K-6034-2016; Ronchi, Dario/K-8011-2016; Magri, Francesca/K-5739-2016; OI Gutierrez Rios, Purificacion/0000-0002-4585-1912; Comi, Giacomo /0000-0002-1383-5248; Corti, Stefania/0000-0001-5425-969X; Ronchi, Dario/0000-0002-6093-9816; Magri, Francesca/0000-0001-8974-9453; Garone, Caterina/0000-0003-4928-1037 FU National Institutes of Health [GM077465, GM097136, HD32062]; Marriott Mitochondrial Disorder Clinical Research Fund; Italian Telethon [GUP09004]; Associazione Amici del Centro Dino Ferrari, University of Milan; Telethon project [GTB07001ER]; Eurobiobank project [QLTR-2001-02769]; Criobanca Automatizzata di Materiale Biologico [02.187] FX This work was supported by a grant from the National Institutes of Health (GM077465 and GM097136 to V.K.M.; HD32062 to S.D.M.), by the Marriott Mitochondrial Disorder Clinical Research Fund to S. D. M. and by a contribution of the Italian Telethon (grant GUP09004 to G.P.C.) 'Constructing a database for a nation-wide Italian collaborative network of mitochondrial diseases'. The financial support of Associazione Amici del Centro Dino Ferrari, University of Milan; the Telethon project GTB07001ER; the Eurobiobank project QLTR-2001-02769 and R. F. 02.187 Criobanca Automatizzata di Materiale Biologico is gratefully acknowledged. NR 57 TC 31 Z9 32 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2012 VL 135 BP 3404 EP 3415 DI 10.1093/brain/aws258 PN 11 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 044SV UT WOS:000311644800025 PM 23043144 ER PT J AU Pierre, JM AF Pierre, Joseph M. TI Mental Illness and Mental Health: Is the Glass Half Empty or Half Full? SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Review DE diagnostic expansion; prevalence inflation; bereavement; adjustment disorder; contextual utility; neuroenhancement; mental illness; mental health ID NATIONAL COMORBIDITY SURVEY; BEREAVEMENT-RELATED DEPRESSION; HARMFUL DYSFUNCTION ANALYSIS; DSM-IV DISORDERS; ADJUSTMENT DISORDER; DIAGNOSTIC-CRITERIA; COMPLICATED GRIEF; COGNITIVE ENHANCEMENT; PSYCHIATRIC DIAGNOSES; CLINICAL-SIGNIFICANCE AB During the past century, the scope of mental health intervention in North America has gradually expanded from an initial focus on hospitalized patients with psychoses to outpatients with neurotic disorders, including the so-called worried well. The Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, is further embracing the concept of a mental illness spectrum, such that increasing attention to the softer end of the continuum can be expected in the future. This anticipated shift rekindles important questions about how mental illness is defined, how to distinguish between mental disorders and normal reactions, whether psychiatry is guilty of prevalence inflation, and when somatic therapies should be used to treat problems of living. Such debates are aptly illustrated by the example of complicated bereavement, which is best characterized as a form of adjustment disorder. Achieving an overarching definition of mental illness is challenging, owing to the many different contexts in which DSM diagnoses are used. Careful analyses of such contextual utility must inform future decisions about what ends up in DSM, as well as how mental illness is defined by public health policy and society at large. A viable vision for the future of psychiatry should include a spectrum model of mental health (as opposed to exclusively mental illness) that incorporates graded, evidence-based interventions delivered by a range of providers at each point along its continuum. C1 [Pierre, Joseph M.] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA USA. [Pierre, Joseph M.] W Los Angeles VA Med Ctr, Schizophrenia Treatment Unit, Los Angeles, CA USA. [Pierre, Joseph M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Pierre, JM (reprint author), 11301 Wilshire Blvd,Bldg 210,Room 15, Los Angeles, CA 90073 USA. EM joseph.pierre2@va.gov NR 104 TC 4 Z9 4 U1 5 U2 21 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD NOV PY 2012 VL 57 IS 11 BP 651 EP 658 PG 8 WC Psychiatry SC Psychiatry GA 044BV UT WOS:000311595300002 PM 23149280 ER PT J AU Miyamoto, DT Lee, RJ Stott, SL Ting, DT Wittner, BS Ulman, M Smas, ME Lord, JB Brannigan, BW Trautwein, J Bander, NH Wu, CL Sequist, LV Smith, MR Ramaswamy, S Toner, M Maheswaran, S Haber, DA AF Miyamoto, David T. Lee, Richard J. Stott, Shannon L. Ting, David T. Wittner, Ben S. Ulman, Matthew Smas, Malgorzata E. Lord, Jenna B. Brannigan, Brian W. Trautwein, Julie Bander, Neil H. Wu, Chin-Lee Sequist, Lecia V. Smith, Matthew R. Ramaswamy, Sridhar Toner, Mehmet Maheswaran, Shyamala Haber, Daniel A. TI Androgen Receptor Signaling in Circulating Tumor Cells as a Marker of Hormonally Responsive Prostate Cancer SO CANCER DISCOVERY LA English DT Article ID BONE METASTASES; CASTRATION; GENE; AMPLIFICATION; TESTOSTERONE; ANTIANDROGEN; ABIRATERONE; EXPRESSION; SURVIVAL; THERAPY AB Androgen deprivation therapy (ADT) is initially effective in treating metastatic prostate cancer, and secondary hormonal therapies are being tested to suppress androgen receptor (AR) reactivation in castration-resistant prostate cancer (CRPC). Despite variable responses to AR pathway inhibitors in CRPC, there are no reliable biomarkers to guide their application. Here, we used microfluidic capture of circulating tumor cells (CTC) to measure AR signaling readouts before and after therapeutic interventions. Single-cell immunofluorescence analysis revealed predominantly "AR-on" CTC signatures in untreated patients, compared with heterogeneous ("AR-on, AR-off, and AR-mixed") CTC populations in patients with CRPC. Initiation of first-line ADT induced a profound switch from "AR-on" to "AR-off" CTCs, whereas secondary hormonal therapy in CRPC resulted in variable responses. Presence of "AR-mixed" CTCs and increasing "AR-on" cells despite treatment with abiraterone acetate were associated with an adverse treatment outcome. Measuring treatment-induced signaling responses within CTCs may help guide therapy in prostate cancer. SIGNIFICANCE: Acquired resistance to first-line hormonal therapy in prostate cancer is heterogeneous in the extent of AR pathway reactivation. Measurement of pre- and posttreatment AR signaling within CTCs may help target such treatments to patients most likely to respond to second-line therapies. Cancer Discov; 2(11); 995-1003. (C) 2012 AACR. C1 [Miyamoto, David T.; Lee, Richard J.; Ting, David T.; Wittner, Ben S.; Ulman, Matthew; Smas, Malgorzata E.; Lord, Jenna B.; Brannigan, Brian W.; Trautwein, Julie; Sequist, Lecia V.; Smith, Matthew R.; Ramaswamy, Sridhar; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Stott, Shannon L.; Toner, Mehmet] Harvard Univ, Sch Med, Ctr Bioengn Med, Charlestown, MA 02129 USA. [Miyamoto, David T.] Harvard Univ, Sch Med, Dept Radiat Oncol, Charlestown, MA 02129 USA. [Lee, Richard J.; Ting, David T.; Sequist, Lecia V.; Smith, Matthew R.; Ramaswamy, Sridhar; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Stott, Shannon L.; Toner, Mehmet; Maheswaran, Shyamala] Harvard Univ, Sch Med, Dept Surg, Charlestown, MA 02129 USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. [Bander, Neil H.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Haber, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM maheswaran@helix.mgh.harvard.edu; Haber@helix.mgh.harvard.edu OI Ting, David/0000-0002-3261-2322 FU Evans Foundation; Prostate Cancer Foundation (PCF); Program of the Entertainment Industry Foundation [SU2C-AACR-DT0309]; T.J. Martell Foundation; Starr Cancer Consortium; Susan G. Komen for the Cure [KG090412]; NCI-MGH Federal Share Program; Department of Defense Physician Research Training Awards; Mazzone-DF/HCC Career Development Award; Conquer Cancer Foundation Career Development Award; PCF Young Investigator Award; American Cancer Society; Howard Hughes Medical Institute; Stand Up To Cancer Dream Team Translational Cancer Research Grant; [NIH-NIBIB-5R01EB008047]; [NCI-CA129933]; [NCI-C06-CA-059267]; [NIH-5K12CA87723-09] FX This work was supported by a Challenge Grant from the Evans Foundation and the Prostate Cancer Foundation (PCF); a Stand Up To Cancer Dream Team Translational Cancer Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0309, to D. A. Haber, M. Toner, and S. Maheswaran); T.J. Martell Foundation (to D. A. Haber); Starr Cancer Consortium (to D. A. Haber); the Susan G. Komen for the Cure KG090412 (S. Maheswaran); NIH-NIBIB-5R01EB008047 (to M. Toner and D. A. Haber); NCI-CA129933 (to D. A. Haber); the NCI-MGH Federal Share Program (to S. Maheswaran); NCI-C06-CA-059267 (to D. T. Miyamoto); NIH-5K12CA87723-09 (to D. T. Ting); Department of Defense Physician Research Training Awards (to D. T. Miyamoto and R.J. Lee); Mazzone-DF/HCC Career Development Award (to D. T. Miyamoto); Conquer Cancer Foundation Career Development Award and PCF Young Investigator Award (to R.J. Lee); American Cancer Society (to S. L. Stott); and Howard Hughes Medical Institute (to D.A. Haber). NR 23 TC 109 Z9 111 U1 3 U2 26 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 NOV PY 2012 VL 2 IS 11 BP 995 EP 1003 DI 10.1158/2159-8290.CD-12-0222 PG 9 WC Oncology SC Oncology GA 048IU UT WOS:000311905400023 PM 23093251 ER PT J AU Geng, HM Brennan, S Milne, TA Chen, WY Li, YS Hurtz, C Kweon, SM Zickl, L Shojaee, S Neuberg, D Huang, CX Biswas, D Xin, Y Racevskis, J Ketterling, RP Luger, SM Lazarus, H Tallman, MS Rowe, JM Litzow, MR Guzman, ML Allis, CD Roeder, RG Muschen, M Paietta, E Elemento, O Melnick, AM AF Geng, Huimin Brennan, Sarah Milne, Thomas A. Chen, Wei-Yi Li, Yushan Hurtz, Christian Kweon, Soo-Mi Zickl, Lynette Shojaee, Seyedmehdi Neuberg, Donna Huang, Chuanxin Biswas, Debabrata Xin, Yuan Racevskis, Janis Ketterling, Rhett P. Luger, Selina M. Lazarus, Hillard Tallman, Martin S. Rowe, Jacob M. Litzow, Mark R. Guzman, Monica L. Allis, C. David Roeder, Robert G. Mueschen, Markus Paietta, Elisabeth Elemento, Olivier Melnick, Ari M. TI Integrative Epigenomic Analysis Identifies Biomarkers and Therapeutic Targets in Adult B-Acute Lymphoblastic Leukemia SO CANCER DISCOVERY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; PLURIPOTENT STEM-CELLS; DNA METHYLATION; HISTONE MODIFICATIONS; CYTOSINE METHYLATION; TRANSCRIPTION FACTOR; HEMATOPOIETIC STEM; MLL TRANSLOCATIONS; HODGKINS LYMPHOMA AB Genetic lesions such as BCR-ABL1, E2A-PBX1, and MLL rearrangements (MLLr) are associated with unfavorable outcomes in adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Leukemia oncoproteins may directly or indirectly disrupt cytosine methylation patterning to mediate the malignant phenotype. We postulated that DNA methylation signatures in these aggressive B-ALLs would point toward disease mechanisms and useful biomarkers and therapeutic targets. We therefore conducted DNA methylation and gene expression profiling on a cohort of 215 adult patients with B-ALL enrolled in a single phase III clinical trial (ECOG E2993) and normal control B cells. In BCR-ABL1-positive B-ALLs, aberrant cytosine methylation patterning centered around a cytokine network defined by hypomethylation and overexpression of IL2RA(CD25). The E2993 trial clinical data showed that CD25 expression was strongly associated with a poor outcome in patients with ALL regardless of BCR-ABL1 status, suggesting CD25 as a novel prognostic biomarker for risk stratification in B-ALLs. In E2A-PBX1-positive B-ALLs, aberrant DNA methylation patterning was strongly associated with direct fusion protein binding as shown by the E2A-PBX1 chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq), suggesting that E2A-PBX1 fusion protein directly remodels the epigenome to impose an aggressive B-ALL phenotype. MLLr B-ALL featured prominent cytosine hypomethylation, which was linked with MLL fusion protein binding, H3K79 dimethylation, and transcriptional upregulation, affecting a set of known and newly identified MLL fusion direct targets with oncogenic activity such as FLT3 and BCL6. Notably, BCL6 blockade or loss of function suppressed proliferation and survival of MLLr leukemia cells, suggesting BCL6-targeted therapy as a new therapeutic strategy for MLLr B-ALLs. SIGNIFICANCE: We conducted the first integrative epigenomic study in adult B-ALLs, as a correlative study to the ECOG E2993 phase III clinical trial. This study links for the first time the direct actions of oncogenic fusion proteins with disruption of epigenetic regulation mediated by cytosine methylation. We identify a novel clinically actionable biomarker in B-ALLs: IL2RA (CD25), which is linked with BCR-ABL1 and an inflammatory signaling network associated with chemotherapy resistance. We show that BCL6 is a novel MLL fusion protein target that is required to maintain the proliferation and survival of primary human adult MLLr cells and provide the basis for a clinical trial with BCL6 inhibitors for patients with MLLr. Cancer Discov; 2(11); 1004-23. (C) 2012 AACR. C1 [Geng, Huimin; Brennan, Sarah; Li, Yushan; Huang, Chuanxin; Xin, Yuan; Guzman, Monica L.; Melnick, Ari M.] Cornell Univ, Weill Med Coll, Dept Med, Div Hematol Oncol, New York, NY 10021 USA. [Geng, Huimin; Elemento, Olivier] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10021 USA. [Milne, Thomas A.; Allis, C. David] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10021 USA. [Chen, Wei-Yi; Biswas, Debabrata; Roeder, Robert G.] Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10021 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Racevskis, Janis; Paietta, Elisabeth] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Hurtz, Christian; Kweon, Soo-Mi; Shojaee, Seyedmehdi; Mueschen, Markus] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Geng, Huimin; Hurtz, Christian; Shojaee, Seyedmehdi; Mueschen, Markus] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Zickl, Lynette; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Milne, Thomas A.] Univ Oxford, Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England. [Ketterling, Rhett P.; Litzow, Mark R.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Luger, Selina M.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Rowe, Jacob M.] Rambam Med Ctr, Dept Hematol & BMT, Haifa, Israel. [Lazarus, Hillard] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Hurtz, Christian] Max Planck Inst Immunobiol, Freiburg, Germany. RP Melnick, AM (reprint author), Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, 1300 York Ave, New York, NY 10065 USA. EM epaietta@earthlink.net; ole2001@med.cornell.edu; amm2014@med.cornell.edu RI Milne, Tom/E-1872-2016 OI Milne, Tom/0000-0002-0413-4271 FU MRC [G8223452]; Chemotherapy Foundation; Burroughs Wellcome Foundation; Sackler Center for Bio-medical and Physical Sciences at the Weill Cornell Medical College; NSF CAREER grant [DBI 1054964]; LLS TRP [6097-10]; LLS SCOR [7132-08]; Medical Research Council UK; Starr Cancer Consortium; NIH0 grant; LLS fellowship [5230-09, 5089-10] FX The authors thank Dr. Peter H. Wiernik for his support of the E2993 clinical trial and correlative studies as former chair of the ECOG leukemia committee and Dr. Sue Richards and the MRC/ECOG trial management group supported by MRC grant (G8223452) for maintaining the trial database for ECOG. They also thank the assistance of the Weill Cornell Epigenomics Core Facility.; A.M. Melnick is supported by the Chemotherapy Foundation, Burroughs Wellcome Foundation, and the Sackler Center for Bio-medical and Physical Sciences at the Weill Cornell Medical College. O. Elemento is supported in part by the NSF CAREER grant DBI 1054964. A. M. Melnick and M. Muschen are supported by LLS TRP 6097-10. A. M. Melnick, R. G. Roeder, C. D. Allis, and T. A. Milne were supported by LLS SCOR 7132-08. T. A. Milne was supported by the Medical Research Council UK. R. G. Roeder was supported by Starr Cancer Consortium and NIH0 grants. W.-Y. Chen and D. Biswas were supported by LLS fellowship 5230-09 and 5089-10. NR 81 TC 31 Z9 36 U1 1 U2 9 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 NOV PY 2012 VL 2 IS 11 BP 1004 EP 1023 DI 10.1158/2159-8290.CD-12-0208 PG 20 WC Oncology SC Oncology GA 048IU UT WOS:000311905400024 PM 23107779 ER PT J AU Ibrahim, YH Garcia-Garcia, C Serra, V He, L Torres-Lockhart, K Prat, A Anton, P Cozar, P Guzman, M Grueso, J Rodriguez, O Calvo, MT Aura, C Diez, O Rubio, IT Perez, J Rodon, J Cortes, J Ellisen, LW Scaltriti, M Baselga, J AF Ibrahim, Yasir H. Garcia-Garcia, Celina Serra, Violeta He, Lei Torres-Lockhart, Kristine Prat, Aleix Anton, Pilar Cozar, Patricia Guzman, Marta Grueso, Judit Rodriguez, Olga Teresa Calvo, Maria Aura, Claudia Diez, Orland Rubio, Isabel T. Perez, Jose Rodon, Jordi Cortes, Javier Ellisen, Leif W. Scaltriti, Maurizio Baselga, Jose TI PI3K Inhibition Impairs BRCA1/2 Expression and Sensitizes BRCA-Proficient Triple-Negative Breast Cancer to PARP Inhibition SO CANCER DISCOVERY LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION; THERAPEUTIC STRATEGY; CELL APOPTOSIS; DNA-DAMAGE; REPAIR; H2AX; METASTASIS; MUTATIONS; CARCINOMA AB PARP inhibitors are active in tumors with defects in DNA homologous recombination (HR) due to BRCA1/2 mutations. The phosphoinositide 3-kinase (PI3K) signaling pathway preserves HR steady state. We hypothesized that in BRCA-proficient triple-negative breast cancer (TNBC), PI3K inhibition would result in HR impairment and subsequent sensitization to PARP inhibitors. We show in TNBC cells that PI3K inhibition leads to DNA damage, downregulation of BRCA1/2, gain in poly-ADP-ribosylation, and subsequent sensitization to PARP inhibition. In TNBC patient-derived primary tumor xenografts, dual PI3K and PARP inhibition with BKM120 and olaparib reduced the growth of tumors displaying BRCA1/2 downregulation following PI3K inhibition. PI3K-mediated BRCA downregulation was accompanied by extracellular signal-regulated kinase (ERK) phosphorylation. Overexpression of an active form of MEK1 resulted in ERK activation and downregulation of BRCA1, whereas the MEK inhibitor AZD6244 increased BRCA1/2 expression and reversed the effects of MEK1. We subsequently identified that the ETS1 transcription factor was involved in the ERK-dependent BRCA1/2 downregulation and that knockdown of ETS1 led to increased BRCA1/2 expression, limiting the sensitivity to combined BKM120 and olaparib in 3-dimensional culture. SIGNIFICANCE: Treatment options are limited for patients with TNBCs. PARP inhibitors have clinical activity restricted to a small subgroup of patients with BRCA mutations. Here, we show that PI3K blockade results in HR impairment and sensitization to PARP inhibition in TNBCs without BRCA mutations, providing a rationale to combine PI3K and PARP inhibitors in this indication. Our findings could greatly expand the number of patients with breast cancer that would benefit from therapy with PARP inhibitors. On the basis of our findings, a clinical trial with BKM120 and olaparib is being initiated in patients with TNBCs. Cancer Discov; 2(11); 1036-47. (C) 2012 AACR. C1 [He, Lei; Torres-Lockhart, Kristine; Ellisen, Leif W.; Scaltriti, Maurizio; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ibrahim, Yasir H.; Garcia-Garcia, Celina; Serra, Violeta; Anton, Pilar; Cozar, Patricia; Guzman, Marta; Grueso, Judit; Rodriguez, Olga; Teresa Calvo, Maria; Baselga, Jose] Vall dHebron Inst Oncol VHIO, Expt Therapeut Lab, Barcelona, Spain. [Prat, Aleix] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Scaltriti, Maurizio; Baselga, Jose] Harvard Univ, Sch Med, Boston, MA USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 N Grove St,LRH 1, Boston, MA 02114 USA. EM mscaltriti@partners.org; jbaselga@partners.org RI Prat, Aleix/P-8561-2014; OI Prat, Aleix/0000-0003-2377-540X; Cortes, Javier/0000-0001-7623-1583 FU Stand Up To Cancer Dream Team Translational Cancer Research Grant; Program of the Entertainment Industry Foundation [SU2C-AACR-DT0209]; Avon Foundation [AFG01-2010-019]; Tracey Davis Memorial Fund; Novartis (CIBOT); FERO Foundation supporting research grant; DOD/CDMRP postdoctoral fellowship [BC093523] FX This work was funded by a Stand Up To Cancer Dream Team Translational Cancer Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209 to J. Baselga), the Avon Foundation (AFG01-2010-019), the Tracey Davis Memorial Fund (L. W. Ellisen), a noncommercial research agreement with Novartis (CIBOT to J. Baselga), and FERO Foundation supporting research grants (J. Baselga). L. He is supported by a DOD/CDMRP postdoctoral fellowship (BC093523). NR 36 TC 154 Z9 157 U1 6 U2 54 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 NOV PY 2012 VL 2 IS 11 BP 1036 EP 1047 DI 10.1158/2159-8290.CD-11-0348 PG 12 WC Oncology SC Oncology GA 048IU UT WOS:000311905400026 PM 22915752 ER PT J AU Juvekar, A Burga, LN Hu, H Lunsford, EP Ibrahim, YH Balmana, J Rajendran, A Papa, A Spencer, K Lyssiotis, CA Nardella, C Pandolfi, PP Baselga, J Scully, R Asara, JM Cantley, LC Wulf, GM AF Juvekar, Ashish Burga, Laura N. Hu, Hai Lunsford, Elaine P. Ibrahim, Yasir H. Balmana, Judith Rajendran, Anbazhagan Papa, Antonella Spencer, Katherine Lyssiotis, Costas A. Nardella, Caterina Pandolfi, Pier Paolo Baselga, Jose Scully, Ralph Asara, John M. Cantley, Lewis C. Wulf, Gerburg M. TI Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1-Related Breast Cancer SO CANCER DISCOVERY LA English DT Article ID FACTOR RECEPTOR EXPRESSION; MAMMARY EPITHELIAL-CELLS; POLY(ADP-RIBOSE) POLYMERASE; GENETIC-VARIATION; TUMOR-SUPPRESSOR; PROGNOSTIC VALUE; BRCA2 CARRIERS; MICE RESISTANT; DNA-REPAIR; GROWTH AB There is a need to improve treatments for metastatic breast cancer. Here, we show the activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in a MMTV-CreBrca1(f/f)Trp53(+/-) mouse model of breast cancer. When treated with the pan-class IA PI3K inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, tumor cell proliferation, and angiogenesis. Resistant tumors maintained suppression of AKT phosphorylation but exhibited activation of the MAPK pathway at the "pushing margin." Surprisingly, PI3K inhibition increased indicators of DNA damage, poly-ADP-ribosylation (PAR), and gamma-H2AX, but decreased Rad51 focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. The PARP inhibitor olaparib alone attenuated tumor growth modestly; however, the combination of NVP-BKM120 and olaparib delayed tumor doubling to more than 70 days in the mouse model and more than 50 days in xenotransplants from human BRCA1-related tumors, suggesting that combined PI3K and PARP inhibition might be an effective treatment of BRCA1-related tumors. SIGNIFICANCE: Current treatment options for triple-negative breast cancer are limited to chemotherapeutic regimens that have considerable toxicity and are not curative. We report here that the combination of a PI3K inhibitor with a PARP inhibitor provides in vivo synergy for treatment of an endogenous mouse model for BRCA1-related breast cancers, making this a candidate combination to be tested in human clinical trials. Cancer Discov; 2(11); 1048-63. (C) 2012 AACR. C1 [Juvekar, Ashish; Burga, Laura N.; Hu, Hai; Lunsford, Elaine P.; Rajendran, Anbazhagan; Spencer, Katherine; Scully, Ralph; Wulf, Gerburg M.] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. [Papa, Antonella; Nardella, Caterina; Pandolfi, Pier Paolo] Beth Israel Deaconess Med Ctr, Div Canc Genet, Boston, MA 02215 USA. [Lyssiotis, Costas A.; Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baselga, Jose] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Ibrahim, Yasir H.; Balmana, Judith; Baselga, Jose] Univ Hosp Vall dHebron, Dept Med Oncol, Barcelona, Spain. RP Wulf, GM (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM gwulf@bidmc.harvard.edu RI Scully, Ralph/F-5008-2013; Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Papa, Antonella/0000-0001-8653-7121 FU Stand Up To Cancer Dream Team Translational Research Grant; Program of the Entertainment Industry Foundation [SU2C-AACR-DT0209]; Breast Cancer Research Foundation (BCRF); Susan G. Komen for the Cure grant [BCTR0601030]; NIH NCI grant [5P01CA120964-05, 5P30CA006516-46]; NIH grant [GM41890]; NCI grant [P01CA089021] FX L.C. Cantley and G. M. Wulf are supported by a Stand Up To Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209), and by the Breast Cancer Research Foundation (BCRF). G. M. Wulf was supported by a Susan G. Komen for the Cure grant BCTR0601030. J.M. Asara is supported by NIH NCI grants 5P01CA120964-05 and 5P30CA006516-46. L. C. Cantley is supported by NIH grant GM41890 and NCI grant P01CA089021. NR 50 TC 125 Z9 127 U1 2 U2 33 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 NOV PY 2012 VL 2 IS 11 BP 1048 EP 1063 DI 10.1158/2159-8290.CD-11-0336 PG 16 WC Oncology SC Oncology GA 048IU UT WOS:000311905400027 PM 22915751 ER PT J AU Amodio, N Di Martino, MT Foresta, U Leone, E Lionetti, M Leotta, M Gulla, AM Pitari, MR Conforti, F Rossi, M Agosti, V Fulciniti, M Misso, G Morabito, F Ferrarini, M Neri, A Caraglia, M Munshi, NC Anderson, KC Tagliaferri, P Tassone, P AF Amodio, N. Di Martino, M. T. Foresta, U. Leone, E. Lionetti, M. Leotta, M. Gulla, A. M. Pitari, M. R. Conforti, F. Rossi, M. Agosti, V. Fulciniti, M. Misso, G. Morabito, F. Ferrarini, M. Neri, A. Caraglia, M. Munshi, N. C. Anderson, K. C. Tagliaferri, P. Tassone, P. TI miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1 SO CELL DEATH & DISEASE LA English DT Article DE multiple myeloma; plasma cell leukemia; miR-29b; microRNA; miRNAs; Sp1; bortezomib ID IN-VIVO; THERAPEUTIC TARGETS; MICROARRAY ANALYSIS; TUMOR-SUPPRESSOR; MESSENGER-RNAS; LUNG-CANCER; MICRORNAS; GENE; EXPRESSION; LEUKEMIA AB MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells. Cell Death and Disease (2012) 3, e436; doi:10.1038/cddis.2012.175; published online 29 November 2012 C1 [Tassone, P.] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, T Campanella Canc Ctr, I-88100 Catanzaro, Italy. [Lionetti, M.; Neri, A.] Univ Milan, Dept Med Sci, IRCCS Policlin Fdn, Milan, Italy. [Conforti, F.] Magna Graecia Univ Catanzaro, Pathol Unit, Catanzaro, Italy. [Fulciniti, M.; Munshi, N. C.; Anderson, K. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fulciniti, M.; Munshi, N. C.; Anderson, K. C.] Harvard Univ, Sch Med, Boston, MA USA. [Fulciniti, M.; Munshi, N. C.] Boston Vet Adm Healthcare Syst, Boston, MA USA. [Misso, G.; Caraglia, M.] Univ Naples 2, Dept Biochem Biophys & Gen Pathol, Naples, Italy. [Morabito, F.] Azienda Osped Annunziata, Hematol Unit, Cosenza, Italy. [Ferrarini, M.] Univ Genoa, Dept Internal Med, Ist Nazl Ric Canc, Div Med Oncol C, I-16126 Genoa, Italy. [Tassone, P.] Temple Univ, Sbarro Inst Canc Res & Mol Med, Ctr Biotechnol, Coll Sci & Technol, Philadelphia, PA 19122 USA. RP Tassone, P (reprint author), Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, T Campanella Canc Ctr, Salvatore Venuta Campus, I-88100 Catanzaro, Italy. EM tassone@unicz.it RI Caraglia, Michele/N-5670-2015; OI Caraglia, Michele/0000-0003-2408-6091; AGOSTI, Valter/0000-0001-6785-093X; neri, antonino/0000-0001-9047-5912; Ferrarini, Manlio/0000-0002-6154-2570; Misso, Gabriella/0000-0002-7787-2531; ROSSI, Marco/0000-0002-7258-475X FU Italian Association for Cancer Research (AIRC) [9980] FX This work was supported by funds of Italian Association for Cancer Research (AIRC), PI: PT. 'Special Program Molecular Clinical Oncology-5 per mille' n. 9980, 2010/15. NR 58 TC 65 Z9 67 U1 1 U2 21 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 NOV PY 2012 VL 3 AR e436 DI 10.1038/cddis.2012.175 PG 11 WC Cell Biology SC Cell Biology GA 047IH UT WOS:000311832600020 PM 23190608 ER PT J AU Grinstein, J Cannon, CP AF Grinstein, Jonathan Cannon, Christopher P. TI Aspirin Resistance: Current Status and Role of Tailored Therapy SO CLINICAL CARDIOLOGY LA English DT Review ID ACUTE CORONARY SYNDROMES; LOW-DOSE ASPIRIN; ARTERY-BYPASS-SURGERY; CONGESTIVE-HEART-FAILURE; PLATELET-FUNCTION TESTS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; ANTIPLATELET THERAPY; PRIMARY PREVENTION AB Aspirin is integral in the primary and secondary prevention of coronary artery disease and acute coronary syndrome. Given the high clinical importance of aspirin in the management of coronary artery disease, much attention has been directed towards the concept of aspirin resistance. Unfortunately, the term aspirin resistance is ill-defined in the literature, leading to a large variance in the reported prevalence of this phenomenon. In this review, the current understanding of aspirin resistance is discussed. Commonly used functional and diagnostic tests of platelet function, including their strengths and weakness, are reviewed. We next discuss several proposed mechanisms of aspirin resistance and special high-risk groups at risk for aspirin treatment failure. We then discuss optimal dosing and diagnostic strategies for those populations at risk for aspirin resistance with a focus on tailored aspirin therapy for high-risk groups. Finally, future topics of interest in the field of aspirin resistance are considered. C1 [Grinstein, Jonathan; Cannon, Christopher P.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinstein, J (reprint author), Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM jgrinstein@partners.org FU Accumetrics; AstraZeneca; Essentialis; GlaxoSmithKline; Merck; Regeneron; Sanofi; Takeda; Alnylam; Bristol-Myers Squibb; Pfizer FX Jonathan Grinstein has no funding, financial relationships, or conflicts of interest to disclose. Christopher P. Cannon receives research grants/support from the following companies: Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, and Takeda. He is also on the advisory board (but funds donated to charity) for Alnylam, Bristol-Myers Squibb, and Pfizer. He is a Clinical Advisor, equity in Automedics Medical Systems. NR 79 TC 18 Z9 19 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD NOV PY 2012 VL 35 IS 11 BP 673 EP 681 DI 10.1002/clc.22031 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 037KO UT WOS:000311103200010 PM 22740110 ER PT J AU Ghoshhajra, BB Sidhu, MS El-Sherief, A Rojas, C Yeh, DD Engel, LC Liberthson, R Abbara, S Bhatt, A AF Ghoshhajra, Brian B. Sidhu, Manavjot S. El-Sherief, Ahmed Rojas, Carlos Yeh, Doreen Defaria Engel, Leif-Christopher Liberthson, Richard Abbara, Suhny Bhatt, Ami TI Adult Congenital Heart Disease Imaging with Second-generation Dual-source Computed Tomography: Initial Experiences and Findings SO CONGENITAL HEART DISEASE LA English DT Article DE Adult Congenital Heart Disease; Cardiac Computed Tomography; Dual Source ID RIGHT-VENTRICULAR-FUNCTION; GREAT-ARTERIES; HIGH-PITCH; SOURCE CT; TRANSPOSITION; REPAIR AB Adult congenital heart disease patients present a unique challenge to the cardiac imager. Patients may present with both acute and chronic manifestations of their complex congenital heart disease and also require surveillance for sequelae of their medical and surgical interventions. Multimodality imaging is often required to clarify their anatomy and physiology. Radiation dose is of particular concern in these patients with lifelong imaging needs for their chronic disease. The second-generation dual-source scanner is a recently available advanced clinical cardiac computed tomography (CT) scanner. It offers a combination of the high-spatial resolution of modern CT, the high-temporal resolution of dual-source technology, and the wide z-axis coverage of modern cone-beam geometry CT scanners. These advances in technology allow novel protocols that markedly reduce scan time, significantly reduce radiation exposure, and expand the physiologic imaging capabilities of cardiac CT. We present a case series of complicated adult congenital heart disease patients imaged by the second-generation dual-source CT scanner with extremely low-radiation doses and excellent image quality. C1 [Ghoshhajra, Brian B.; Sidhu, Manavjot S.; El-Sherief, Ahmed; Rojas, Carlos; Engel, Leif-Christopher; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Ghoshhajra, Brian B.; Yeh, Doreen Defaria; Liberthson, Richard; Abbara, Suhny; Bhatt, Ami] Massachusetts Gen Hosp, Div Cardiol, Adult Congenital Heart Dis Program, Boston, MA 02114 USA. [Ghoshhajra, Brian B.; Sidhu, Manavjot S.; El-Sherief, Ahmed; Rojas, Carlos; Engel, Leif-Christopher; Abbara, Suhny] Harvard Univ, Sch Med, Boston, MA USA. RP Sidhu, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiovasc Imaging Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM manavsidhu83@gmail.com RI Ghoshhajra, Brian/J-2114-2016 OI Ghoshhajra, Brian/0000-0002-3865-3432 NR 21 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-079X EI 1747-0803 J9 CONGENIT HEART DIS JI Congenit. Heart Dis. PD NOV-DEC PY 2012 VL 7 IS 6 BP 516 EP 525 DI 10.1111/chd.12008 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044HU UT WOS:000311611000008 PM 23075048 ER PT J AU Thurman, JM Kulik, L Mitchell, LM Hourcade, DE Hannan, JP Coughlin, B Woodell, AS Pickering, MC Rohrer, B Holers, M AF Thurman, Joshua M. Kulik, Liudmila Mitchell, Lynne M. Hourcade, Dennis E. Hannan, Jonathan P. Coughlin, Beth Woodell, Alex S. Pickering, Matthew C. Rohrer, Barbel Holers, Michael TI Novel monoclonal antibodies to C3d that target and identify in living animals sites of complement activation SO IMMUNOBIOLOGY LA English DT Meeting Abstract C1 [Thurman, Joshua M.; Kulik, Liudmila; Hannan, Jonathan P.; Holers, Michael] Univ Colorado, Sch Med, Dept Medicine, Aurora, CO USA. [Mitchell, Lynne M.; Hourcade, Dennis E.] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA. [Coughlin, Beth; Rohrer, Barbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Woodell, Alex S.; Rohrer, Barbel] Med Univ S Carolina, Div Res, Dept Neurosci, Charleston, SC 29425 USA. [Pickering, Matthew C.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Mol Genet & Rheumatol Sect, London, England. [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD NOV PY 2012 VL 217 IS 11 MA 177 BP 1191 EP 1191 DI 10.1016/j.imbio.2012.08.179 PG 1 WC Immunology SC Immunology GA 038PY UT WOS:000311187800191 ER PT J AU McMahon, GM Mendu, ML Gibbons, FK Christopher, KB AF McMahon, Gearoid M. Mendu, Mallika L. Gibbons, Fiona K. Christopher, Kenneth B. TI Association between hyperkalemia at critical care initiation and mortality SO INTENSIVE CARE MEDICINE LA English DT Article DE Potassium; Intensive care; Mortality ID HOSPITALIZED-PATIENTS; UNITED-STATES; APACHE-II; DISEASE; SYSTEM AB To investigate the association between potassium concentration at the initiation of critical care and all-cause mortality. We performed a retrospective observational study on 39,705 patients, age a parts per thousand yen18 years, who received critical care between 1997 and 2007 in two tertiary care hospitals in Boston, Massachusetts. The exposure of interest was the highest potassium concentration on the day of critical care initiation and categorized a priori as 4.0-4.5, 4.5-5.0, 5.0-5.5, 5.5-6.0, 6.0-6.5, or a parts per thousand yen6.5 mEq/l. Logistic regression examined death by days 30, 90, and 365 post-critical care initiation, and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. The potassium concentration was a strong predictor of all-cause mortality 30 days following critical care initiation with a significant risk gradient across potassium groups following multivariable adjustment: K = 4.5-5.0 mEq/l OR 1.25 (95 % CI, 1.16-1.35; P < 0.0001); K = 5.0-5.5 mEq/l OR 1.42 (95 % CI, 1.29-1.56; P < 0.0001); K = 5.5-6.0 mEq/l OR 1.67 (95 % CI, 1.47-1.89; P < 0.0001); K = 6.0-6.5 mEq/l OR 1.63 (95 % CI, 1.36-1.95; P < 0.0001); K > 6.5 mEq/l OR 1.72 (95 % CI, 1.49-1.99; P < 0.0001); all relative to patients with K = 4.0-4.5 mEq/l. Similar significant associations post multivariable adjustments are seen with in-hospital mortality and death by days 90 and 365 post-critical care initiation. In patients whose hyperkalemia decreases a parts per thousand yen1 mEq/l in 48 h post-critical care initiation, the association between high potassium levels and mortality is no longer significant. Our study demonstrates that a patient's potassium level at critical care initiation is robustly associated with the risk of death even at moderate increases above normal. C1 [Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. [Mendu, Mallika L.] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, 75 Francis St,MRB 418, Boston, MA 02115 USA. EM kbchristopher@partners.org OI McMahon, Gearoid/0000-0002-7723-2198 FU NIH [K08AI060881]; Department of Medicine at the Brigham and Women's Hospital FX This manuscript is dedicated to the memory of our dear friend and colleague, Nathan Edward Hellman, MD, PhD. We express deep appreciation to Steven M. Brunelli, MD, MSCE, for statistical expertise and analysis. Financial Support: Dr. Christopher was supported by NIH K08AI060881 and the Department of Medicine at the Brigham and Women's Hospital. NR 37 TC 23 Z9 23 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 2012 VL 38 IS 11 BP 1834 EP 1842 DI 10.1007/s00134-012-2636-7 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 026CN UT WOS:000310250500013 PM 22806439 ER PT J AU Abazeed, M Adams, D Giacomelli, A Pashtan, I Hammerman, P Meyerson, M AF Abazeed, M. Adams, D. Giacomelli, A. Pashtan, I. Hammerman, P. Meyerson, M. TI Development of a High Throughput Platform for Measuring Radiation Response SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Abazeed, M.; Pashtan, I.] Harvard Radiat Oncol Program, Boston, MA USA. [Adams, D.] Broad Inst, Cambridge, MA USA. [Giacomelli, A.] Harvard Univ, Sch Med, Boston, MA USA. [Hammerman, P.; Meyerson, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S701 EP S701 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902283 ER PT J AU Abazeed, M Hammerman, P Creighton, C Adams, D Giacomelli, A Meyerson, M AF Abazeed, M. Hammerman, P. Creighton, C. Adams, D. Giacomelli, A. Meyerson, M. TI NRF2 Pathway Activation Regulates Radiation Resistance in Lung Squamous Cell Carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Abazeed, M.] Harvard Radiat Oncol Program, Boston, MA USA. [Hammerman, P.; Meyerson, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Creighton, C.] Baylor Coll Med, Houston, TX 77030 USA. [Adams, D.] Broad Inst, Cambridge, MA USA. [Giacomelli, A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S179 EP S180 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900448 ER PT J AU Aizer, AA Paly, JJ Zietman, AL Beard, CJ Nguyen, PL Kaplan, ID Hirsch, MS Wu, C D'Amico, AV Efstathiou, JA AF Aizer, A. A. Paly, J. J. Zietman, A. L. Beard, C. J. Nguyen, P. L. Kaplan, I. D. Hirsch, M. S. Wu, C. D'Amico, A. V. Efstathiou, J. A. TI Physician Bias, Referral to a Medical Oncologist, and Active Surveillance in Low-risk Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Aizer, A. A.] Harvard Radiat Oncol Program, Boston, MA USA. [Paly, J. J.; Zietman, A. L.; Wu, C.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Beard, C. J.; Nguyen, P. L.; D'Amico, A. V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaplan, I. D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S182 EP S182 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900453 ER PT J AU Arvold, ND Pinnell, NE Mahadevan, A Connelly, S Silverman, R Weiss, SE Kelly, PJ Alexander, BM AF Arvold, N. D. Pinnell, N. E. Mahadevan, A. Connelly, S. Silverman, R. Weiss, S. E. Kelly, P. J. Alexander, B. M. TI Physician Recommendations for Steroid and Anticonvulsant Use Following Stereotactic Radiosurgery SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Arvold, N. D.] Harvard Radiat Oncol Program, Boston, MA USA. [Pinnell, N. E.; Connelly, S.; Silverman, R.; Weiss, S. E.; Alexander, B. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mahadevan, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kelly, P. J.] Cork Univ Hosp, Cork, Ireland. NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S292 EP S293 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900739 ER PT J AU Arvold, ND Niemierko, A Oh, KS Taghian, AG Lin, NU Harris, JR Alexander, BM AF Arvold, N. D. Niemierko, A. Oh, K. S. Taghian, A. G. Lin, N. U. Harris, J. R. Alexander, B. M. TI Brain Metastases After Breast-conserving Therapy for Early-stage Breast Cancer: Incidence and Characteristics by Subtype SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Arvold, N. D.] Harvard Radiat Oncol Program, Boston, MA USA. [Niemierko, A.; Oh, K. S.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lin, N. U.; Harris, J. R.; Alexander, B. M.] Dana Farber Canc Inst, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S188 EP S188 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900469 ER PT J AU Berhane, H Epperly, M Dixon, TM Cao, S Shields, D Wipf, P Li, S Gao, X Guinan, E Greenberger, JS AF Berhane, H. Epperly, M. Dixon, T. M. Cao, S. Shields, D. Wipf, P. Li, S. Gao, X. Guinan, E. Greenberger, J. S. TI Oral Delivery of Mitochondrial Targeted GS-Nitroxide JP4-039 Protects Fanconi Anemia (FA) D2-/- Mice From Irradiation Mucositis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Berhane, H.; Epperly, M.; Dixon, T. M.; Cao, S.; Shields, D.; Wipf, P.; Li, S.; Gao, X.; Greenberger, J. S.] Univ Pittsburgh, Pittsburgh, PA USA. [Guinan, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S677 EP S678 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902220 ER PT J AU Bian, S Kuban, DA Levy, LB Oh, J Choi, S McGuire, SE Pugh, TJ Nguyen, PL Lee, AK Hoffman, KE AF Bian, S. Kuban, D. A. Levy, L. B. Oh, J. Choi, S. McGuire, S. E. Pugh, T. J. Nguyen, P. L. Lee, A. K. Hoffman, K. E. TI The Influence of Age and Comorbidity on the Benefit of Adding Androgen Deprivation to Dose-escalated Radiation in Men With Intermediate-Risk Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Bian, S.; Kuban, D. A.; Levy, L. B.; Oh, J.; Choi, S.; McGuire, S. E.; Pugh, T. J.; Lee, A. K.; Hoffman, K. E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nguyen, P. L.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S370 EP S371 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901122 ER PT J AU Chan, A Adams, JA Weyman, E Parambi, R Goldsmith, T Holman, A Truong, M Busse, PM Delaney, T AF Chan, A. Adams, J. A. Weyman, E. Parambi, R. Goldsmith, T. Holman, A. Truong, M. Busse, P. M. Delaney, T. TI A Phase II Trial of Proton Radiation Therapy With Chemotherapy for Nasopharyngeal Carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Chan, A.; Adams, J. A.; Weyman, E.; Parambi, R.; Truong, M.; Busse, P. M.; Delaney, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Goldsmith, T.; Holman, A.] Massachusetts Gen Hosp, Dept Speech Swallow & Language Disorders, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S151 EP S152 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900376 ER PT J AU Chen, AB Cronin, A Weeks, J Chrischilles, E Malin, J Hayman, J Schrag, D AF Chen, A. B. Cronin, A. Weeks, J. Chrischilles, E. Malin, J. Hayman, J. Schrag, D. TI Patient Beliefs About Palliative Radiation Therapy (RT) in Incurable Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Chen, A. B.; Cronin, A.; Weeks, J.; Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chrischilles, E.] Univ Iowa, Iowa City, IA USA. [Malin, J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hayman, J.] Univ Michigan, Ann Arbor, MI 48109 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S1 EP S1 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900005 ER PT J AU Chen, Y Calkins, G Hornicek, F Harmon, D Giraud, C Nielsen, G Meltzer, P Suit, H Michaelson, J DeLaney, T AF Chen, Y. Calkins, G. Hornicek, F. Harmon, D. Giraud, C. Nielsen, G. Meltzer, P. Suit, H. Michaelson, J. DeLaney, T. TI Prognosis of Radiation Associated Bone and Soft-tissue Sarcomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Chen, Y.; Calkins, G.; Hornicek, F.; Harmon, D.; Giraud, C.; Nielsen, G.; Suit, H.; Michaelson, J.; DeLaney, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meltzer, P.] NCI, NIH, Bethesda, MD 20892 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S138 EP S138 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900342 ER PT J AU Cormack, R Nguyen, P D'Amico, AV Sridhar, S Makrigiorgos, GM AF Cormack, R. Nguyen, P. D'Amico, A. V. Sridhar, S. Makrigiorgos, G. M. TI Locally Drug Enhanced Brachytherapy: A Comparison of 2 Approaches Based on Biologically Effective Dose SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Cormack, R.; Nguyen, P.; D'Amico, A. V.; Makrigiorgos, G. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cormack, R.; Nguyen, P.; D'Amico, A. V.; Makrigiorgos, G. M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sridhar, S.] Northeastern Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S854 EP S855 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902682 ER PT J AU Craft, D Adams, J Bortfeld, T AF Craft, D. Adams, J. Bortfeld, T. TI Effective Multicriteria Optimization for Clinical IMRT Planning SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Craft, D.; Adams, J.; Bortfeld, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S792 EP S792 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902520 ER PT J AU Czerminska, M Kukluk, J Molodowitch, C Cormack, RA Killoran, JH AF Czerminska, M. Kukluk, J. Molodowitch, C. Cormack, R. A. Killoran, J. H. TI Data Integrity Verification System to Improve Safety of Radiation Therapy Treatments SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S131 EP S131 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900326 ER PT J AU Damato, A Townamchai, K Kovacs, A Cormack, R Viswanathan, A AF Damato, A. Townamchai, K. Kovacs, A. Cormack, R. Viswanathan, A. TI Dosimetric Uncertainties Associated With Interobserver Contouring Variability in Gynecologic Interstitial Brachytherapy (GIB) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Damato, A.; Townamchai, K.; Kovacs, A.; Cormack, R.; Viswanathan, A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cormack, R.; Viswanathan, A.] Harvard Univ, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S783 EP S783 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902499 ER PT J AU Damato, A Townamchai, K Kovacs, A Cormack, R Viswanathan, A AF Damato, A. Townamchai, K. Kovacs, A. Cormack, R. Viswanathan, A. TI Interfraction Uncertainties in Multifraction Gynecologic Interstitial Brachytherapy (MGIB) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Damato, A.; Townamchai, K.; Kovacs, A.; Cormack, R.; Viswanathan, A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cormack, R.; Viswanathan, A.] Harvard Univ, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S757 EP S757 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902430 ER PT J AU Duarte, C Sarkisian, N Garroutte, E Nguyen, P Hurwitz, M AF Duarte, C. Sarkisian, N. Garroutte, E. Nguyen, P. Hurwitz, M. TI Impact of Race on Prostate Cancer Treatment Selection and Cause-specific Mortality: A SEER Database Analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Duarte, C.; Sarkisian, N.; Garroutte, E.] Boston Coll, Chestnut Hill, MA 02167 USA. [Nguyen, P.; Hurwitz, M.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S374 EP S374 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901130 ER PT J AU Epstein-Peterson, Z Krishnan, M Chen, J Balboni, T AF Epstein-Peterson, Z. Krishnan, M. Chen, J. Balboni, T. TI Postoperative Radiation Therapy for Bone Metastases: The Role of Coverage of the Surgical Hardware and Dose Intensity in Treatment Outcomes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Epstein-Peterson, Z.] Harvard Univ, Sch Med, Boston, MA USA. [Krishnan, M.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, J.; Balboni, T.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, J.; Balboni, T.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S209 EP S209 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900524 ER PT J AU Gerweck, LE Lu, H Paganetti, H Zhou, Y Herrup, D Huang, P AF Gerweck, L. E. Lu, H. Paganetti, H. Zhou, Y. Herrup, D. Huang, P. TI Out of Field Cancer Risk in Mice Following Exposure to a Clinical Proton Beam SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Gerweck, L. E.; Lu, H.; Paganetti, H.; Zhou, Y.; Herrup, D.; Huang, P.] 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S683 EP S684 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902235 ER PT J AU Giantsoudi, D Grassberger, C Craft, D Niemierko, A Trofimov, AV Paganetti, H AF Giantsoudi, D. Grassberger, C. Craft, D. Niemierko, A. Trofimov, A. V. Paganetti, H. TI LET Guided Biological Optimization in IMPT: Implications on RBE Value SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S845 EP S845 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902658 ER PT J AU Goldsmith, T Holman, AS Parambi, RI Weyman, E Busse, PM Viscosi, E Wirth, LJ Clark, JR Rothenberg, SM Chan, AW AF Goldsmith, T. Holman, A. S. Parambi, R. I. Weyman, E. Busse, P. M. Viscosi, E. Wirth, L. J. Clark, J. R. Rothenberg, S. M. Chan, A. W. TI Swallowing Function After Proton Beam Therapy for Nasopharyngeal Cancer: A Prospective Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Goldsmith, T.; Holman, A. S.; Parambi, R. I.; Weyman, E.; Busse, P. M.; Viscosi, E.; Wirth, L. J.; Clark, J. R.; Rothenberg, S. M.; Chan, A. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S62 EP S63 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900156 ER PT J AU Gray, PJ Fedewa, SA Shipley, WU Virgo, KS Zietman, AL Efstathiou, JA AF Gray, P. J. Fedewa, S. A. Shipley, W. U. Virgo, K. S. Zietman, A. L. Efstathiou, J. A. TI Factors Associated With Clinical-Pathologic Stage Discrepancy in Bladder Cancer Patients Treated With Radical Cystectomy: Implications for Treatment Selection and Comparative Studies SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Gray, P. J.; Shipley, W. U.; Zietman, A. L.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gray, P. J.] Harvard Radiat Oncol Program, Boston, MA USA. [Fedewa, S. A.; Virgo, K. S.] Amer Canc Soc, Atlanta, GA 30329 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S120 EP S120 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900299 ER PT J AU Gray, PJ Fedewa, SA Shipley, WU Efstathiou, JA Zietman, AL Virgo, KS AF Gray, P. J. Fedewa, S. A. Shipley, W. U. Efstathiou, J. A. Zietman, A. L. Virgo, K. S. TI Utilization of Potentially Curative Therapies for Muscle Invasive Bladder Cancer: Results From the National Cancer Data Base SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Gray, P. J.; Shipley, W. U.; Efstathiou, J. A.; Zietman, A. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gray, P. J.] Harvard Radiat Oncol Program, Boston, MA USA. [Fedewa, S. A.; Virgo, K. S.] Amer Canc Soc, Atlanta, GA 30329 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S119 EP S119 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900297 ER PT J AU Gray, PJ Sher, DJ Cryer, SK Mak, RH Porter, J Weiss, SE Alexander, BM Jackman, DM AF Gray, P. J. Sher, D. J. Cryer, S. K. Mak, R. H. Porter, J. Weiss, S. E. Alexander, B. M. Jackman, D. M. TI Aggressive Therapy to the Thoracic Primary is Associated With Improved Survival in Patients With Non-small Cell Lung Carcinoma Presenting With Synchronous Metastases Limited to the Brain SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Gray, P. J.] Harvard Radiat Oncol Program, Boston, MA USA. [Sher, D. J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Cryer, S. K.; Mak, R. H.; Porter, J.; Weiss, S. E.; Alexander, B. M.; Jackman, D. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S102 EP S103 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900255 ER PT J AU Gray, PJ Paly, JJ Yeap, B Sanda, MG Talcott, JA Sandler, HM Michalski, JM Hamstra, DA Bekelman, JE Efstathiou, JA AF Gray, P. J. Paly, J. J. Yeap, B. Sanda, M. G. Talcott, J. A. Sandler, H. M. Michalski, J. M. Hamstra, D. A. Bekelman, J. E. Efstathiou, J. A. TI Patient-reported Quality of Life in Prostate Cancer Patients Treated With 3D Conformal Intensity Modulated or Proton Beam Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Gray, P. J.] Harvard Radiat Oncol Program, Boston, MA USA. [Paly, J. J.; Yeap, B.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sanda, M. G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sanda, M. G.] Continuum Canc Care Consortium, New York, NY USA. [Sandler, H. M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Michalski, J. M.] Washington Univ, Sch Med, St Louis, MO USA. [Hamstra, D. A.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Bekelman, J. E.] Univ Penn, Philadelphia, PA 19104 USA. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S13 EP S13 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900034 ER PT J AU Hansen, JE Chan, G Liu, Y Gera, J Sweasy, JB Sung, P Rockwell, S Nishimura, RN Weisbart, RH Glazer, PM AF Hansen, J. E. Chan, G. Liu, Y. Gera, J. Sweasy, J. B. Sung, P. Rockwell, S. Nishimura, R. N. Weisbart, R. H. Glazer, P. M. TI A Rare Cell-penetrating Anti-DNA Antibody Inhibits DNA Repair, Sensitizes Tumors To DNA-damaging Therapy, and is Synthetically Lethal to BRCA2-deficient Cancer Cells SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Hansen, J. E.; Liu, Y.; Sweasy, J. B.; Sung, P.; Rockwell, S.; Glazer, P. M.] Yale Univ, Sch Med, New Haven, CT USA. [Chan, G.; Gera, J.; Nishimura, R. N.; Weisbart, R. H.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 4 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S163 EP S163 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900406 ER PT J AU Hattangadi, JA Kuhlthau, K Szymonifka, J Yeap, B MacDonald, S Hurson, J Delahaye, J Tarbell, N Yock, T AF Hattangadi, J. A. Kuhlthau, K. Szymonifka, J. Yeap, B. MacDonald, S. Hurson, J. Delahaye, J. Tarbell, N. Yock, T. TI Health-related Quality of Life (HrQOL) in Children Treated With Proton Radiation Therapy for Extracranial Tumors: A Prospective Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Hattangadi, J. A.] Harvard Radiat Oncol Program, Boston, MA USA. [Kuhlthau, K.; Szymonifka, J.; Yeap, B.; MacDonald, S.; Hurson, J.; Delahaye, J.; Tarbell, N.; Yock, T.] 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S162 EP S162 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900403 ER PT J AU Hattangadi, JA Chapman, P Kim, D Bussiere, M Niemierko, A Rowell, A Daartz, J Ogilvy, C Loeffler, J Shih, H AF Hattangadi, J. A. Chapman, P. Kim, D. Bussiere, M. Niemierko, A. Rowell, A. Daartz, J. Ogilvy, C. Loeffler, J. Shih, H. TI Single Fraction Proton Beam Stereotactic Radiosurgery (PSRS) for Inoperable Cerebral Arteriovenous Malformations (AVMs) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Hattangadi, J. A.] Harvard Radiat Oncol Program, Boston, MA USA. [Chapman, P.; Kim, D.; Bussiere, M.; Niemierko, A.; Rowell, A.; Daartz, J.; Ogilvy, C.; Loeffler, J.; Shih, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S38 EP S38 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900097 ER PT J AU Hegde, J Chen, M Mulkern, RV Fennessy, FM Tempany, CM D'Amico, AV AF Hegde, J. Chen, M. Mulkern, R. V. Fennessy, F. M. Tempany, C. M. D'Amico, A. V. TI Preoperative 3-Tesla Multiparametric Endorectal MRI Findings and the Odds of Upgrading and Upstaging at Radical Prostatectomy in Men With Clinically Localized Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Hegde, J.] Harvard Univ, Sch Med, Boston, MA USA. [Hegde, J.; Mulkern, R. V.; Fennessy, F. M.; Tempany, C. M.; D'Amico, A. V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, M.] Univ Connecticut, Storrs, CT USA. [Mulkern, R. V.] Childrens Hosp, Boston, MA 02115 USA. [Fennessy, F. M.; D'Amico, A. V.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S359 EP S360 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901094 ER PT J AU Hurwitz, MD Iozeffi, D Gianfelice, D Kuten, A LeBlang, S Choi, J Ghanouni, P Roberts, A Pfeffer, R Kanaev, SV AF Hurwitz, M. D. Iozeffi, D. Gianfelice, D. Kuten, A. LeBlang, S. Choi, J. Ghanouni, P. Roberts, A. Pfeffer, R. Kanaev, S. V. TI Magnetic Resonance-guided Focused Ultrasound Surgery for Painful Bone Metastases is a Safe and Effective Treatment in Patients for Whom Radiation Therapy Is Contraindicated: Results of a Multicenter Phase III Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Hurwitz, M. D.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Hurwitz, M. D.] Harvard Univ, Sch Med, Boston, MA USA. [Iozeffi, D.] Rostov State Res Inst Oncol, Rostov Na Donu, Russia. [Gianfelice, D.] Univ Hlth Network Toronto, Toronto, ON, Canada. [Kuten, A.] Rambam Med Ctr, Haifa, Israel. [LeBlang, S.] Univ MRI, Boca Raton, FL USA. [Choi, J.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Ghanouni, P.] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. [Roberts, A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Pfeffer, R.] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Kanaev, S. V.] NN Petrov Oncol Res Inst, St Petersburg, Russia. 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S209 EP S209 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900523 ER PT J AU Jang, JW Parambi, RJ Goldsmith, TA Holman, AS Wirth, LJ Clark, JR Busse, PM Chan, AW AF Jang, J. W. Parambi, R. J. Goldsmith, T. A. Holman, A. S. Wirth, L. J. Clark, J. R. Busse, P. M. Chan, A. W. TI Factors Associated With Prolonged Gastrostomy Tube Usage in Patients With Oropharyngeal Cancer Treated With Chemoradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Jang, J. W.] Harvard Radiat Oncol Program, Boston, MA USA. [Parambi, R. J.; Goldsmith, T. A.; Holman, A. S.; Wirth, L. J.; Clark, J. R.; Busse, P. M.; Chan, A. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S479 EP S479 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901406 ER PT J AU Jang, JW Parambi, RJ Liliana, LS Liebsch, NJ Chan, AW AF Jang, J. W. Parambi, R. J. Liliana, L. S. Liebsch, N. J. Chan, A. W. TI Intensity Modulated Radiation Therapy and Level 1B Nodal Coverage for Oropharyngeal Carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Jang, J. W.] Harvard Radiat Oncol Program, Boston, MA USA. [Parambi, R. J.; Liliana, L. S.; Liebsch, N. J.; Chan, A. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S22 EP S23 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900058 ER PT J AU Jang, JW Paly, JJ Talcott, JA Jack, CA Ancukiewicz, M Efstathiou, JA Zietman, AL AF Jang, J. W. Paly, J. J. Talcott, J. A. Jack, C. A. Ancukiewicz, M. Efstathiou, J. A. Zietman, A. L. TI Long-term Quality of Life After Definitive Treatment for Prostate Cancer: Patient Reported Outcomes in the Second Post-treatment Decade SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Jang, J. W.] Harvard Radiat Oncol Program, Boston, MA USA. [Paly, J. J.; Ancukiewicz, M.; Efstathiou, J. A.; Zietman, A. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Talcott, J. A.] Continuum Canc Ctr New York, New York, NY USA. [Jack, C. A.] Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA 01730 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S15 EP S16 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900040 ER PT J AU Jia, X Schuemann, J Paganetti, H Jiang, S AF Jia, X. Schuemann, J. Paganetti, H. Jiang, S. TI Fast Monte Carlo Dose Calculation on GPU for Proton Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Jia, X.; Jiang, S.] UCSD, Dept Radiat Med & Appl Sci, La Jolla, CA USA. [Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S841 EP S841 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902648 ER PT J AU Jimenez, RB Yock, TI Depauw, N Adams, J Ebb, D Fullerton, B Tarbell, NJ MacDonald, SM AF Jimenez, R. B. Yock, T. I. Depauw, N. Adams, J. Ebb, D. Fullerton, B. Tarbell, N. J. MacDonald, S. M. TI Proton Radiation Therapy for High-risk Pediatric Medulloblastoma: Outcomes for Very Young Children Treated With Upfront Chemotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Jimenez, R. B.] Harvard Radiat Oncol Program, Boston, MA USA. [Yock, T. I.; Depauw, N.; Adams, J.; Fullerton, B.; Tarbell, N. J.; MacDonald, S. M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Depauw, N.] Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW, Australia. [Ebb, D.] Massachusetts Gen Hosp, Dept Pediat Hematol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S65 EP S66 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900163 ER PT J AU Jones, JC Cao, H Limaye, M Koong, A Knox, S AF Jones, J. C. Cao, H. Limaye, M. Koong, A. Knox, S. TI A New Tool for Studying Tumor- and Treatment-associated Exosomes and Microparticles SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Jones, J. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jones, J. C.; Cao, H.; Limaye, M.; Koong, A.; Knox, S.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S715 EP S716 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902322 ER PT J AU Kachnic, LA Romesser, P Mancias, JD Qureshi, MM Hartshorn, KL Willins, JD Hong, TS AF Kachnic, L. A. Romesser, P. Mancias, J. D. Qureshi, M. M. Hartshorn, K. L. Willins, J. D. Hong, T. S. TI Dose-painted Intensity Modulated Radiation Therapy for Anal Cancer: No Differences in Treatment Toxicity and Early Outcomes Between Human Immunodeficiency Virus Positive and Negative Patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Kachnic, L. A.; Romesser, P.; Qureshi, M. M.; Hartshorn, K. L.; Willins, J. D.] Boston Med Ctr, Boston, MA USA. [Mancias, J. D.] Harvard Radiat Oncol Program, Boston, MA USA. [Hong, T. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S353 EP S353 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901077 ER PT J AU Kang, J Botros, M Goldberg, S Giraud, C Nielsen, G Chen, Y Raskin, K Schwab, JH Delaney, TF Hornicek, FJ AF Kang, J. Botros, M. Goldberg, S. Giraud, C. Nielsen, G. Chen, Y. Raskin, K. Schwab, J. H. Delaney, T. F. Hornicek, F. J. TI Management of Atypical Lipomas With Radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Kang, J.] Harvard Radiat Oncol Program, Boston, MA USA. [Botros, M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Goldberg, S.; Giraud, C.; Chen, Y.; Delaney, T. F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Nielsen, G.; Raskin, K.; Schwab, J. H.; Hornicek, F. J.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Nielsen, G.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S654 EP S654 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902157 ER PT J AU Katz, LM Efstathiou, J Hoffman, KE Paly, J Opraseuth, J Killoran, J Weathers, R Stovall, M Beard, C AF Katz, L. M. Efstathiou, J. Hoffman, K. E. Paly, J. Opraseuth, J. Killoran, J. Weathers, R. Stovall, M. Beard, C. TI Impact of Radiation Field Design on Inadvertent Cardiac and Kidney Dose Delivered During Treatment for Stage I/II Seminoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Katz, L. M.; Beard, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Efstathiou, J.; Paly, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoffman, K. E.; Weathers, R.; Stovall, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Opraseuth, J.; Killoran, J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S421 EP S421 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901255 ER PT J AU Killoran, JH Gerbaudo, VH Chen, JT Killion, L Spicer, BA Mamon, HJ AF Killoran, J. H. Gerbaudo, V. H. Chen, J. T. Killion, L. Spicer, B. A. Mamon, H. J. TI Application of FLT PET to Radiation Therapy Treatment Planning of Esophageal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Killoran, J. H.; Chen, J. T.; Killion, L.; Spicer, B. A.; Mamon, H. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Killoran, J. H.; Chen, J. T.; Killion, L.; Spicer, B. A.; Mamon, H. J.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02115 USA. [Gerbaudo, V. H.] Brigham & Womens Hosp, Div Nucl Med & Mol Imaging, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S310 EP S311 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900787 ER PT J AU Korideck, H Yang, S Kimmelman, A Ngwa, W Makrigiorgos, M Berbeco, R AF Korideck, H. Yang, S. Kimmelman, A. Ngwa, W. Makrigiorgos, M. Berbeco, R. TI Preclinical Image Guided Irradiation of Pancreatic Cancer Transgenic Mouse Model SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Korideck, H.; Yang, S.; Kimmelman, A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ngwa, W.; Makrigiorgos, M.; Berbeco, R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S859 EP S859 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902693 ER PT J AU Krishnan, MS Epstein-Peterson, Z Chen, YH Catalano, PJ Chen, J Balboni, T AF Krishnan, M. S. Epstein-Peterson, Z. Chen, Y. H. Catalano, P. J. Chen, J. Balboni, T. TI Factors Predicting Life Expectancy in Patients With Metastatic Cancer Receiving Palliative Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Krishnan, M. S.] Harvard Radiat Oncol Program, Boston, MA USA. [Epstein-Peterson, Z.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Y. H.; Catalano, P. J.; Chen, J.; Balboni, T.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Y. H.; Catalano, P. J.; Chen, J.; Balboni, T.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S52 EP S52 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900132 ER EF