FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Nahas, MR Stroopinsky, D Rajabi, H Tagde, A Pyzer, AR Jain, S Coll, MD Bar-Natan, M Karp, R Luptakova, K Palmer, KA Somaiya, P Arnason, J McMasters, M Joyce, R Levine, JD Kufe, D Avigan, D Rosenblatt, J AF Nahas, Myrna Rita Stroopinsky, Dina Rajabi, Hasan Tagde, Ashujit Pyzer, Athalia Rachel Jain, Salvia Coll, Maxwell Douglas Bar-Natan, Michal Karp, Rebecca Luptakova, Katarina Palmer, Kristen Anna Somaiya, Poorvi Arnason, Jon McMasters, Malgorzata Joyce, Robin Levine, James D. Kufe, Donald Avigan, David Rosenblatt, Jacalyn TI MUC1 Inhibition Overcomes Chemotherapy Resistance in Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Nahas, Myrna Rita; Stroopinsky, Dina; Pyzer, Athalia Rachel; Coll, Maxwell Douglas; Bar-Natan, Michal; Karp, Rebecca; Luptakova, Katarina; Palmer, Kristen Anna; Somaiya, Poorvi; Arnason, Jon; McMasters, Malgorzata; Joyce, Robin; Levine, James D.; Avigan, David; Rosenblatt, Jacalyn] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Rajabi, Hasan; Tagde, Ashujit; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Jain, Salvia] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Malignant Hematol & Bone Marrow Transplantat, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020101311 ER PT J AU Nanjappa, P Kumar, S Talluri, S Ahmad, H Bajwa, A Shi, JL Gonzalez, G Magrangeas, F Minvielle, S Anderson, KC Avet-Loiseau, H Shammas, M Munshi, NC AF Nanjappa, Purushothama Kumar, Subodh Talluri, Srikanth Ahmad, Humza Bajwa, Ahsun Shi, Jialan Gonzalez, Gabriel Magrangeas, Florence Minvielle, Stephane Anderson, Kenneth C. Avet-Loiseau, Herve Shammas, Masood Munshi, Nikhil C. TI Critical Role of Split Hand/Foot Malformation Type 1 (SHFM1) in Homologous Recombination and Cell Survival in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Nanjappa, Purushothama; Kumar, Subodh; Talluri, Srikanth; Ahmad, Humza; Bajwa, Ahsun; Anderson, Kenneth C.; Shammas, Masood] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Talluri, Srikanth; Shi, Jialan; Gonzalez, Gabriel; Shammas, Masood; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Magrangeas, Florence; Minvielle, Stephane; Avet-Loiseau, Herve] CHU Nantes, Unite Mixte Genom Canc, F-44035 Nantes 01, France. [Avet-Loiseau, Herve] IUCT Oncopole, Toulouse, France. [Munshi, Nikhil C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7XY UT WOS:000368020105191 ER PT J AU Nazha, A Komrokji, RS Garcia-Manero, G Barnard, J Zell, K Zimmerman, C Al Ali, NH Roboz, GJ Steensma, DP DeZern, AE Padron, E Jabbour, EJ Greenberg, MD List, AF Kantarjian, HM Maciejewski, JP Sekeres, MA AF Nazha, Aziz Komrokji, Rami S. Garcia-Manero, Guillermo Barnard, John Zell, Katrina Zimmerman, Cassie Al Ali, Najla H. Roboz, Gail J. Steensma, David P. DeZern, Amy E. Padron, Eric Jabbour, Elias J. Greenberg, Molly Dara List, Alan F. Kantarjian, Hagop M. Maciejewski, Jaroslaw P. Sekeres, Mikkael A. TI A Novel Model to Predict Outcome of Patients with Myelodysplastic Syndromes (MDS) at the Time of Hypomethylating Agent Failure SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Nazha, Aziz] Cleveland Clin, Dept Hematol & Oncol, Leukemia Program, Taussig Canc Inst, Cleveland, OH 44106 USA. [Komrokji, Rami S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Garcia-Manero, Guillermo; Jabbour, Elias J.; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Barnard, John; Zell, Katrina; Zimmerman, Cassie; Sekeres, Mikkael A.] Cleveland Clin, Leukemia Program, Cleveland, OH 44106 USA. [Al Ali, Najla H.; Padron, Eric] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Malignant Hematol Dept, Tampa, FL 33612 USA. [Roboz, Gail J.] Weill Cornell Med Coll, Joan & Sanford I Weill Dept Med, New York, NY USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [DeZern, Amy E.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Greenberg, Molly Dara] New York Presbyterian Hosp, Weill Cornell Med Coll, Div Hematol & Oncol, New York, NY USA. [List, Alan F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol Malignancies, Tampa, FL 33612 USA. [Maciejewski, Jaroslaw P.] Cleveland Clin, Taussig Canc Inst, Taussig Canc Ctr, Expt Hematol & Hematopoiesis Sect, Cleveland, OH 44106 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 4 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103083 ER PT J AU Niesvizky, R Richardson, PG Gabrail, NY Madan, S Yee, AJ Quayle, SN Almeciga-Pinto, I Jones, SS Houston, L Hayes, D Van Duzer, J Wheeler, C Trede, NS Raje, NS AF Niesvizky, Ruben Richardson, Paul G. Gabrail, Nashat Y. Madan, Sumit Yee, Andrew J. Quayle, Steven N. Almeciga-Pinto, Ingrid Jones, Simon S. Houston, Lee Hayes, Denise Van Duzer, John Wheeler, Catherine Trede, Nikolaus S. Raje, Noopur S. TI ACY-241, a Novel, HDAC6 Selective Inhibitor: Synergy with Immunomodulatory (IMiD (R)) Drugs in Multiple Myeloma (MM) Cells and Early Clinical Results (ACE-MM-200 Study) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Niesvizky, Ruben] Weill Cornell Med Coll, Ctr Excellence Lymphoma & Myeloma, New York, NY USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancy,Dept Med Oncol,Jerome Lipp, Boston, MA 02115 USA. [Gabrail, Nashat Y.] Gabrail Canc Ctr, Canton, OH USA. [Madan, Sumit] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Hematol Oncol, San Antonio, TX 78229 USA. [Yee, Andrew J.; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Quayle, Steven N.; Almeciga-Pinto, Ingrid; Jones, Simon S.; Houston, Lee; Hayes, Denise; Van Duzer, John; Wheeler, Catherine; Trede, Nikolaus S.] Acetylon Pharmaceut Inc, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103235 ER PT J AU Nooka, AK Wang, M Yee, AJ Thomas, SK O'Donnell, EK Shah, JJ Kaufman, JL Lonial, S Richardson, PG Raje, NS AF Nooka, Ajay K. Wang, Michael Yee, Andrew J. Thomas, Sheeba K. O'Donnell, Elizabeth K. Shah, Jatin J. Kaufman, Jonathan L. Lonial, Sagar Richardson, Paul G. Raje, Noopur S. TI Updated Results of a Phase 1/2a, Dose Escalation Study of Pvx-410 Multi-Peptide Cancer Vaccine in Patients with Smoldering Multiple Myeloma (SMM) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Nooka, Ajay K.; Kaufman, Jonathan L.; Lonial, Sagar] Emory Univ, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA. [Wang, Michael; Thomas, Sheeba K.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Yee, Andrew J.; O'Donnell, Elizabeth K.; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Shah, Jatin J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801188 ER PT J AU Noort, WA de Jong-Korlaar, R Lubbers-Aalders, L Yuan, HP de Bruijn, JD Mitsiades, CS Martens, ACM Groen, RWJ AF Noort, Willy A. de Jong-Korlaar, Regina Lubbers-Aalders, Linda Yuan, Huipin de Bruijn, Joost D. Mitsiades, Constantine S. Martens, Anton C. M. Groen, Richard W. J. TI Addition of the Vascular Niche Component to the Human Bone Marrow-like Scaffold Model SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Noort, Willy A.; de Jong-Korlaar, Regina; Lubbers-Aalders, Linda; Martens, Anton C. M.; Groen, Richard W. J.] Vrije Univ Amsterdam, Med Ctr, Dept Hematol, Amsterdam, Netherlands. [Yuan, Huipin; de Bruijn, Joost D.] Xpand Biotechnol BV, Bilthoven, Netherlands. [Mitsiades, Constantine S.] Harvard Univ, Sch Med, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020101240 ER PT J AU O'Donnell, EK Laubach, JP Yee, AJ Huff, CA Basile, FG Wade, PM Paba-Prada, CE Ghobrial, IM Schlossman, RL Couture, NR Doherty, L Lyons, H English, C Munshi, NC Anderson, KC Richardson, PC Raje, NS AF O'Donnell, Elizabeth K. Laubach, Jacob P. Yee, Andrew J. Huff, Carol A. Basile, Frank G. Wade, Philip M., Jr. Paba-Prada, Claudia E. Ghobrial, Irene M. Schlossman, Robert L. Couture, Nicole R. Doherty, Lauren Lyons, Hannah English, Caroline Munshi, Nikhil C. Anderson, Kenneth C. Richardson, Paul C. Raje, Noopur S. TI A Phase II Study of Modified Lenalidomide, Bortezomib, and Dexamethasone (RVD-lite) for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [O'Donnell, Elizabeth K.; Yee, Andrew J.; Couture, Nicole R.; Doherty, Lauren; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [O'Donnell, Elizabeth K.; Laubach, Jacob P.; Yee, Andrew J.; Paba-Prada, Claudia E.; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Anderson, Kenneth C.; Richardson, Paul C.; Raje, Noopur S.] Harvard Univ, Sch Med, Boston, MA USA. [Laubach, Jacob P.; Paba-Prada, Claudia E.; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Anderson, Kenneth C.; Richardson, Paul C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yee, Andrew J.; Lyons, Hannah] Massachusetts Gen North Shore Canc Ctr, Danvers, MA USA. [Huff, Carol A.; English, Caroline] Johns Hopkins Univ, Baltimore, MD USA. [Basile, Frank G.; Wade, Philip M., Jr.] Cape Cod Healthcare, Hyannis, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801159 ER PT J AU O'Donnell, EK Kabrt, J Ezenwajiaku, N Yee, AJ Horick, N Raje, NS AF O'Donnell, Elizabeth K. Kabrt, Jessica Ezenwajiaku, Nkiruka Yee, Andrew J. Horick, Nora Raje, Noopur S. TI Early Mortality in Newly Diagnosed Multiple Myeloma in the Context of Novel Drugs SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [O'Donnell, Elizabeth K.; Kabrt, Jessica; Ezenwajiaku, Nkiruka; Yee, Andrew J.; Horick, Nora; Raje, Noopur S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Donnell, Elizabeth K.; Yee, Andrew J.; Raje, Noopur S.] Harvard Univ, Sch Med, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020104197 ER PT J AU Odejide, OO Cronin, AM Condron, NB Fletcher, SA Earle, C Abel, GA AF Odejide, Oreofe O. Cronin, Angel M. Condron, Nolan B. Fletcher, Sean A. Earle, Craig Abel, Gregory A. TI Measuring Quality of End-of-Life Care for Blood Cancers: A National Survey of Hematologic Oncologists SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Odejide, Oreofe O.; Cronin, Angel M.; Condron, Nolan B.; Fletcher, Sean A.; Abel, Gregory A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Earle, Craig] Inst Clin Evaluat Sci, Toronto, ON, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020104172 ER PT J AU Ohguchi, H Hideshima, T Bhasin, M Gorgun, G Santo, L Cea, M Mimura, N Suzuki, R Tai, YT Carrasco, RD Raje, NS Richardson, PG Harigae, H Sanda, T Anderson, KC AF Ohguchi, Hiroto Hideshima, Teru Bhasin, Manoj Gorgun, Gullu Santo, Loredana Cea, Michele Mimura, Naoya Suzuki, Rikio Tai, Yu-Tzu Carrasco, Ruben D. Raje, Noopur S. Richardson, Paul G. Harigae, Hideo Sanda, Takaomi Anderson, Kenneth C. TI The KDM3A-KLF2-IRF4 Axis Maintains Myeloma Cell Survival SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Ohguchi, Hiroto; Hideshima, Teru; Gorgun, Gullu; Cea, Michele; Mimura, Naoya; Suzuki, Rikio; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bhasin, Manoj] BIDMC Genom Prote Bioinformat & Syst Biol Ctr, Boston, MA USA. [Santo, Loredana; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Carrasco, Ruben D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Harigae, Hideo] Tohoku Univ, Grad Sch Med, Dept Hematol & Rheumatol, Sendai, Miyagi 980, Japan. [Sanda, Takaomi] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020105199 ER PT J AU Ollila, T Reagan, JL Castillo, JJ Butera, JN Winer, ES Cardin, MS AF Ollila, Thomas Reagan, John L. Castillo, Jorge J. Butera, James N. Winer, Eric S. Cardin, Michael S. TI The Role of Day 14 Bone Marrow Analysis in Determining Leukemia Free Survival and Overall Survival SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Ollila, Thomas] Brown Univ, Rhode Isl Hosp, Dept Med, Miriam Hosp, Providence, RI 02903 USA. [Reagan, John L.; Butera, James N.; Winer, Eric S.] Brown Univ, Rhode Isl Hosp, Hematol Oncol, Miriam Hosp, Providence, RI 02903 USA. [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Cardin, Michael S.] Rhode Isl Hosp, Ctr Comprehens Canc, Providence, RI 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021803277 ER PT J AU Olszewski, AJ Castillo, JJ AF Olszewski, Adam J. Castillo, Jorge J. TI Prognosis of HIV-Associated Hodgkin Lymphoma in the Antiretroviral Therapy Era: Analysis of the National Cancer Data Base (NCDB) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Olszewski, Adam J.] Brown Univ, Alpert Med Sch, Div Hematol Oncol, Providence, RI 02912 USA. [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800118 ER PT J AU Pavlasova, G Seda, V Borsky, M Cerna, K Osickova, J Mayer, J Pospisilova, S Davids, MS Brown, JR Mraz, M AF Pavlasova, Gabriela Seda, Vaclav Borsky, Marek Cerna, Katerina Osickova, Jitka Mayer, Jiri Pospisilova, Sarka Davids, Matthew S. Brown, Jennifer R. Mraz, Marek TI Microenvironmental Interactions up-Regulate CD20 Expression in CLL B Cells through the CXCR4/SDF-1 Axis: Implications for CD20-Targeting Antibodies and the Use of BCR-Inhibitors in Combination SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Pavlasova, Gabriela; Seda, Vaclav; Cerna, Katerina; Osickova, Jitka; Pospisilova, Sarka; Mraz, Marek] CEITEC MU, Mol Med, Brno, Czech Republic. [Pavlasova, Gabriela; Seda, Vaclav; Borsky, Marek; Cerna, Katerina; Osickova, Jitka; Mayer, Jiri; Pospisilova, Sarka; Mraz, Marek] Masaryk Univ, Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic. [Pavlasova, Gabriela; Seda, Vaclav; Borsky, Marek; Cerna, Katerina; Osickova, Jitka; Mayer, Jiri; Pospisilova, Sarka; Mraz, Marek] Masaryk Univ, Fac Med, Brno, Czech Republic. [Davids, Matthew S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Mraz, Marek/E-1774-2012 NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801066 ER PT J AU Perez-Ladaga, A Xie, HF Orkin, SH Sykes, DB Ebert, BL Bejar, R AF Perez-Ladaga, Albert Xie, Huafeng Orkin, Stuart H. Sykes, David B. Ebert, Benjamin L. Bejar, Rafael TI Neutrophils Derived from Ezh2-/- Progenitor Cells Demonstrate Aberrant Erythroid Lineage Gene Expression SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Perez-Ladaga, Albert; Bejar, Rafael] UCSD Moores Canc Ctr, La Jolla, CA USA. [Xie, Huafeng] Harvard Clin & Translat Sci Ctr, Boston, MA USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. [Sykes, David B.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Ebert, Benjamin L.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801054 ER PT J AU Pikman, Y Furman, A Lee, ES Place, AE Alexe, G Modiste, R Gokhale, P Kim, S Silverman, LB Stegmaier, K AF Pikman, Yana Furman, Andrew Lee, Emily S. Place, Andrew E. Alexe, Gabriela Modiste, Rebecca Gokhale, Prafulla Kim, Sunkyu Silverman, Lewis B. Stegmaier, Kimberly TI Synergistic Drug Combinations with a CDK4/6 Inhibitor in T-Cell Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Pikman, Yana; Furman, Andrew; Lee, Emily S.; Place, Andrew E.; Alexe, Gabriela; Silverman, Lewis B.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Pikman, Yana; Place, Andrew E.; Silverman, Lewis B.; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA. [Modiste, Rebecca; Gokhale, Prafulla] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Sunkyu] Novartis Inst Biomed Res, Cambridge, MA 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020101326 ER PT J AU Place, AE Pikman, Y Stevenson, K Harris, MH Cooper, TM Gore, L Hijiya, N Loh, ML Pauly, M Sulis, ML Neuberg, DS Stegmaier, K Sallan, SE Silverman, LB AF Place, Andrew E. Pikman, Yana Stevenson, Kristen Harris, Marian H. Cooper, Todd M. Gore, Lia Hijiya, Nobuko Loh, Mignon L. Pauly, Melinda Sulis, Maria Luisa Neuberg, Donna S. Stegmaier, Kimberly Sallan, Stephen E. Silverman, Lewis B. TI Phase Ib Trial of the mTOR Inhibitor Everolimus Given in Combination with Multiagent Chemotherapy in Relapsed Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Place, Andrew E.; Pikman, Yana; Stegmaier, Kimberly; Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Place, Andrew E.; Pikman, Yana; Stegmaier, Kimberly; Sallan, Stephen E.; Silverman, Lewis B.] Boston Childrens Hosp, Boston, MA USA. [Stevenson, Kristen; Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Harris, Marian H.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Cooper, Todd M.] Seattle Childrens Hosp, Dept Hematol & Oncol, Seattle, WA USA. [Gore, Lia] Univ Colorado Denver, Sect Hematol Oncol & Bone Marrow Transplantat, Pediat, Aurora, CO USA. [Hijiya, Nobuko] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp, Dept Hematol Oncol & Stem Cell Transplantat, Chicago, IL 60611 USA. [Loh, Mignon L.] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA. [Pauly, Melinda] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Dept Pediat, Atlanta, GA USA. [Sulis, Maria Luisa] Columbia Univ, Div Pediat Hematol Oncol & Stem Cell Transplant, New York, NY 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800022 ER PT J AU Puissant, A Fenouille, N Bassil, CF Ben-Sahra, I Alexe, G Benajiba, L Ramos, A Pikman, Y Burgess, MR Galinsky, I DeAngelo, DJ Stone, RM Shannon, K Hemann, MT Stegmaier, K AF Puissant, Alexandre Fenouille, Nina Bassil, Christopher F. Ben-Sahra, Issam Alexe, Gabriela Benajiba, Lina Ramos, Azucena Pikman, Yana Burgess, Michael R. Galinsky, Ilene DeAngelo, Daniel J. Stone, Richard M. Shannon, Kevin Hemann, Michael T. Stegmaier, Kimberly TI Identification of CKMT1B As a New Target in EVI1-Positive AML SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Puissant, Alexandre; Bassil, Christopher F.; Alexe, Gabriela; Benajiba, Lina; Pikman, Yana; Galinsky, Ilene; DeAngelo, Daniel J.; Stone, Richard M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Fenouille, Nina; Hemann, Michael T.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Ben-Sahra, Issam] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Ramos, Azucena] Koch Inst Integrat Canc Res, Cambridge, MA USA. [Pikman, Yana; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA. [Burgess, Michael R.] Univ Calif San Francisco, Med, San Francisco, CA 94143 USA. [Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Shannon, Kevin] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7XY UT WOS:000368020105240 ER PT J AU Qian, Y Ke, Q Wang, Z Zhang, BC AF Qian, Yu Ke, Qiang Wang, Zhe Zhang, Baochun TI Regulation of IgD Expression and Its Role in B Cell Transformation SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Qian, Yu; Ke, Qiang; Wang, Zhe; Zhang, Baochun] Dana Farber Canc Inst, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020101068 ER PT J AU Qiu, HY Sandmaier, BM Storer, BE Chauncey, T Petersen, F Pulsipher, MA Bruno, B Flowers, M Mielcarek, M Storb, R Maloney, DG AF Qiu, Huiying Sandmaier, Brenda M. Storer, Barry E. Chauncey, Thomas Petersen, Finn Pulsipher, Michael A. Bruno, Benedetto Flowers, Mary Mielcarek, Marco Storb, Rainer Maloney, David G. TI A Prospective Multicenter Study of Nonmyeloablative Conditioning with TBI or Fludarabine/TBI for HLA-Matched Related Hematopoietic Cell Transplantation for Treatment of Hematologic Malignancies with Post Grafting Immunosuppression with Tacrolimus and Mycophenolate Mofetil: 10-Year Experience SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Qiu, Huiying; Sandmaier, Brenda M.; Flowers, Mary; Mielcarek, Marco; Storb, Rainer] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sandmaier, Brenda M.; Storer, Barry E.; Chauncey, Thomas; Flowers, Mary; Mielcarek, Marco; Storb, Rainer] Univ Washington, Seattle, WA 98195 USA. [Storer, Barry E.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Chauncey, Thomas] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Petersen, Finn] LDS Hosp, Salt Lake City, UT USA. [Pulsipher, Michael A.] Univ Utah, Salt Lake City, UT USA. [Pulsipher, Michael A.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Bruno, Benedetto] Univ Turin, Turin, Italy. [Maloney, David G.] Univ Washington, Div Med Oncol, Seattle, WA 98195 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020100114 ER PT J AU Quill, TA Kumar, SK Lentzsch, S Lonial, S Roodman, GD Brady, ED Mortimer, J Obholz, KL Anderson, KC AF Quill, Timothy A. Kumar, Shaji K. Lentzsch, Suzanne Lonial, Sagar Roodman, G. David Brady, Erik D. Mortimer, Jim Obholz, Kevin L. Anderson, Kenneth C. TI Changes in Expert Recommendations and Global Practice Patterns from 2012-2015: Results from an Annually Updated Online Decision Aid for Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Quill, Timothy A.; Brady, Erik D.; Mortimer, Jim; Obholz, Kevin L.] Clin Care Opt LLC, Reston, VA USA. [Kumar, Shaji K.] Mayo Clin, Div Hematol, Rochester, MN USA. [Lentzsch, Suzanne] Columbia Univ, Div Hematol Oncol, New York, NY USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst Hematol & Med Oncol, Div BMT, Atlanta, GA 30322 USA. [Roodman, G. David] Indiana Univ, Med Hematol Oncol, Indianapolis, IN 46204 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020100270 ER PT J AU Raje, N Chau, I Hyman, DM Ribrag, V Blay, JY Tabernero, J Elez-Fernandez, ME Wolf, JS Sirzen, F Yee, A Faris, J Kaiser, M Landau, H Michot, JM Veronese, L Makrutzki, M Lasserre, SF Puzanov, I Baselga, J AF Raje, Noopur Chau, Ian Hyman, David M. Ribrag, Vincent Blay, Jean-Yves Tabernero, Josep Elena Elez-Fernandez, Maria Wolf, Juergen S. Sirzen, Florin Yee, Andrew Faris, Jason Kaiser, Martin Landau, Heather Michot, Jean-Marie Veronese, Luisa Makrutzki, Martina Lasserre, Susan Francis Puzanov, Igor Baselga, Jose TI Vemurafenib (VEM) in Relapsed Refractory Multiple Myeloma Harboring BRAF(V600) Mutations (V600m): A Cohort of the Histology-Independent VE-Basket Study SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Raje, Noopur; Yee, Andrew; Faris, Jason] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chau, Ian; Kaiser, Martin] Royal Marsden Hosp, Surrey, England. [Hyman, David M.; Landau, Heather; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ribrag, Vincent; Michot, Jean-Marie] Inst Gustave Roussy, Villejuif, France. [Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France. [Tabernero, Josep; Elena Elez-Fernandez, Maria] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, E-08193 Barcelona, Spain. [Tabernero, Josep; Elena Elez-Fernandez, Maria] Univ Autonoma Barcelona, Inst Oncol VHIO, E-08193 Barcelona, Spain. [Wolf, Juergen S.] Univ Hosp Koln, Cologne, Germany. [Sirzen, Florin; Veronese, Luisa; Makrutzki, Martina; Lasserre, Susan Francis] F Hoffmann La Roche Ltd, Basel, Switzerland. [Puzanov, Igor] Vanderbilt Univ, Med Ctr, Nashville, TN USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801205 ER PT J AU Raje, NS Bensinger, W Cole, CE Lonial, S Jagannath, S Arce-Lara, CE Valent, J Rosko, AE Harb, WA Sandhu, I Bahlis, NJ Reece, D Terpos, E Supko, J Tamang, D Jones, SS Wheeler, C Markelewicz, RJ Richardson, PG AF Raje, Noopur S. Bensinger, William Cole, Craig E. Lonial, Sagar Jagannath, Sundar Arce-Lara, Carlos E. Valent, Jason Rosko, Ashley E. Harb, Wael A. Sandhu, Irwindeep Bahlis, Nizar J. Reece, Donna Terpos, Evangelos Supko, Jeffrey Tamang, David Jones, Simon S. Wheeler, Catherine Markelewicz, Robert J., Jr. Richardson, Paul G. TI Ricolinostat (ACY-1215), the First Selective HDAC6 Inhibitor, Combines Safely with Pomalidomide and Dexamethasone and Shows Promosing Early Results in Relapsed-and-Refractory Myeloma (ACE-MM-102 Study) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bensinger, William] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cole, Craig E.] Univ Michigan, Sch Med, Dept Med, Div Hematol Oncol, Ann Arbor, MI 48104 USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA. [Jagannath, Sundar] Mt Sinai Hosp, Hematol & Med Oncol, New York, NY 10029 USA. [Arce-Lara, Carlos E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Valent, Jason] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Rosko, Ashley E.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Harb, Wael A.] Horizon Oncol Ctr, Lafayette, IN USA. [Sandhu, Irwindeep] Univ Alberta, Dept Med, Div Hematol, Edmonton, AB, Canada. [Bahlis, Nizar J.] Univ Calgary, Southern Alberta Canc Res Inst, Calgary, AB, Canada. [Reece, Donna] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Terpos, Evangelos] Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. [Supko, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tamang, David; Jones, Simon S.; Wheeler, Catherine; Markelewicz, Robert J., Jr.] Acetylon Pharmaceut Inc, Boston, MA USA. [Richardson, Paul G.] 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801170 ER PT J AU Ramachandran, J Santo, L Eda, H Chauhan, D Siu, KT Koulnis, M Huszar, D Anderson, KC Raje, NS AF Ramachandran, Janani Santo, Loredana Eda, Homare Chauhan, Dharminder Siu, Ka Tat Koulnis, Miroslav Huszar, Dennis Anderson, Kenneth C. Raje, Noopur S. TI The Biologic Relevance of PIM Kinases in the Context of Multiple Myeloma and Their Potential As Therapeutic Targets in Combination Drug Therapy SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Ramachandran, Janani; Santo, Loredana] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eda, Homare; Siu, Ka Tat; Koulnis, Miroslav; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Chauhan, Dharminder] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Huszar, Dennis] AstraZeneca, Oncol iMed, Waltham, MA USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103187 ER PT J AU Ray, A Das, DS Song, Y Chauhan, D Anderson, KC AF Ray, Arghya Das, Deepika Sharma Song, Yan Chauhan, Dharminder Anderson, Kenneth C. TI Combination of Anti-PD-L1 Antibody with IMiD (R) Immunomodulatory Drugs, HDAC Inhibitor ACY-1215, Bortezomib, or Toll-like Receptor 9 Agonist Enhances Anti-Tumor Immunity and Cytotoxicity in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Ray, Arghya; Das, Deepika Sharma; Song, Yan; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Ray, Arghya; Das, Deepika Sharma; Song, Yan; Chauhan, Dharminder] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103209 ER PT J AU Ray, A Das, DS Song, Y Macri, V Brooks, CL Rowinsky, EK Richardson, PG Chauhan, D Anderson, KC AF Ray, Arghya Das, Deepika Sharma Song, Yan Macri, Vincent Brooks, Christopher L. Rowinsky, Eric K. Richardson, Paul G. Chauhan, Dharminder Anderson, Kenneth C. TI A Novel Agent SL-401 Triggers Anti-Myeloma Activity By Targeting Plasmacytoid Dendritic Cells: Implications for a Novel Immune-Associated Mechanism SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Ray, Arghya; Das, Deepika Sharma; Song, Yan; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Ray, Arghya; Das, Deepika Sharma; Song, Yan; Chauhan, Dharminder] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Macri, Vincent; Brooks, Christopher L.; Rowinsky, Eric K.] Stemline Therapeut Inc, New York, NY USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103195 ER PT J AU Richardson, PC Hofmeister, C Raje, NS Siegel, D Lonial, S Laubach, JP Efebera, YA Vesole, DH Nooka, AK Rosenblatt, J Zaki, MH Herring, J Li, Y Shah, S Chen, MS Anderson, KC AF Richardson, Paul C. Hofmeister, Craig Raje, Noopur S. Siegel, David Lonial, Sagar Laubach, Jacob P. Efebera, Yvonne A. Vesole, David H. Nooka, Ajav K. Rosenblatt, Jacalyn Zaki, Mohamed H. Herring, Jennifer Li, Yan Shah, Sheetal Chen, Min S. Anderson, Kenneth C. TI A Phase 1, Multicenter Study of Pomalidomide, Bortezomib, and Low-Dose Dexamethasone in Patients with Proteasome Inhibitor Exposed and Lenalidomide-Refractory Myeloma (Trial MM-005) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Richardson, Paul C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancy,Dept Med Oncol,Jerome Lipp, Boston, MA 02115 USA. [Hofmeister, Craig] Ohio State Univ, Med Ctr, Div Hematol, Columbus, OH 43210 USA. [Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Siegel, David; Vesole, David H.] Hackensack Univ, John Theurer Canc Ctr, Med Ctr, Hackensack, NJ USA. [Lonial, Sagar; Nooka, Ajav K.] Emory Univ, Div BMT, Winship Canc Inst Hematol & Med Oncol, Atlanta, GA 30322 USA. [Laubach, Jacob P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Efebera, Yvonne A.] Ohio State Univ, Columbus, OH 43210 USA. [Rosenblatt, Jacalyn] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Zaki, Mohamed H.; Herring, Jennifer; Li, Yan; Shah, Sheetal; Chen, Min S.] Celgene Corp, Summit, NJ USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI Efebera, Yvonne/E-3012-2011 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103231 ER PT J AU Richardson, PG Smith, AR Triplett, BM Kernan, NA Grupp, SA Antin, JH Lehmann, LE Miloslavsky, M Hume, RL Hannah, AL Nejadnik, B Soiffer, RJ AF Richardson, Paul G. Smith, Angela R. Triplett, Brandon M. Kernan, Nancy A. Grupp, Stephan A. Antin, Joseph H. Lehmann, Leslie E. Miloslavsky, Maja Hume, Robin L. Hannah, Alison L. Nejadnik, Bijan Soiffer, Robert J. TI Early Initiation of Defibrotide in Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Following Hematopoietic Stem Cell Transplantation Improves Day+100 Survival SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancy,Dept Med Oncol,Jerome Lipp, Boston, MA 02115 USA. [Smith, Angela R.] Univ Minnesota, Div Pediat Blood & Marrow Transplantat, Minneapolis, MN USA. [Triplett, Brandon M.] St Jude Childrens Res Hosp, Bone Marrow Transplantat & Cellular Therapy, 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. [Grupp, Stephan A.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Antin, Joseph H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Antin, Joseph H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lehmann, Leslie E.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Ctr Stem Cell Transplantat,Div Hematol Malignancy, Boston, MA 02115 USA. [Miloslavsky, Maja; Hume, Robin L.; Hannah, Alison L.; Nejadnik, Bijan] Jazz Pharmaceut, Palo Alto, CA USA. [Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancy, Stem Cell Bone Marrow Transplantat Program, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801253 ER PT J AU Richez, V Luciano, F Hamouda, A Puissant, A Robert, G Jacquel, A Cluzeau, T Anderson, KC Fuzibet, JG Auberger, P AF Richez, Valentine, Jr. Luciano, Frederic Hamouda, Amine Puissant, Alexandre Robert, Guillaume Jacquel, Arnaud Cluzeau, Thomas Anderson, Kenneth C. Fuzibet, Jean-Gabriel Auberger, Patrick TI Implication of the Anti-Apoptotic Protein Bcl-B (BCL2L10) in the Pathogenesis of Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Richez, Valentine, Jr.; Robert, Guillaume] Hosp Nice, Nice, France. [Luciano, Frederic; Hamouda, Amine; Robert, Guillaume; Jacquel, Arnaud; Auberger, Patrick] Fac Med Nice, INSERM, U1065, F-06034 Nice 03, France. [Puissant, Alexandre] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Puissant, Alexandre] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Cluzeau, Thomas] St Louis Hosp, Hematol, Paris, France. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI AUBERGER, Patrick/G-1491-2013 OI AUBERGER, Patrick/0000-0002-2481-8275 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103153 ER PT J AU Rosenblatt, J Avivi, I Binyamini, N Uhl, L Somaiya, P Stroopinsky, D Palmer, KA Coll, MD Katz, T Bisharat, L Joyce, R Levine, JD Arnason, JE Luptakova, K McMasters, M Jain, S Leiba, M Sato-Dilorenzo, A Logan, E Bryant, MP Held, V Richardson, PG Laubach, JP Nagler, A Anderson, KC Munshi, NC Rowe, JM Kufe, D Avigan, D AF Rosenblatt, Jacalyn Avivi, Irit Binyamini, Noam Uhl, Lynne Somaiya, Poorvi Stroopinsky, Dina Palmer, Kristen Anna Coll, Maxwell Douglas Katz, Tami Bisharat, Lina Joyce, Robin Levine, James D. Arnason, Jon E. Luptakova, Katarina McMasters, Malgorzata Jain, Salvia Leiba, Merav Sato-Dilorenzo, Aya Logan, Emma Bryant, Mary Paty Held, Viki Richardson, Paul G. Laubach, Jacob P. Nagler, Arnon Anderson, Kenneth C. Munshi, Nikhil C. Rowe, Jacob M. Kufe, Donald Avigan, David TI Blockade of PD-1 in Combination with Dendritic Cell/Myeloma Fusion Cell Vaccination Following Autologous Stem Cell Transplantation Is Well Tolerated, Induces Anti-Tumor Immunity and May Lead to Eradication of Measureable Disease SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Rosenblatt, Jacalyn; Uhl, Lynne; Somaiya, Poorvi; Stroopinsky, Dina; Palmer, Kristen Anna; Coll, Maxwell Douglas; Levine, James D.; Arnason, Jon E.; Luptakova, Katarina; McMasters, Malgorzata; Jain, Salvia; Sato-Dilorenzo, Aya; Logan, Emma; Bryant, Mary Paty; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rosenblatt, Jacalyn; Joyce, Robin] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Avivi, Irit; Binyamini, Noam; Katz, Tami; Bisharat, Lina; Held, Viki; Rowe, Jacob M.] Rambam Hlth Care Campus, Haifa, Israel. [Jain, Salvia] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Malignant Hematol & Bone Marrow Transplantat, Boston, MA 02215 USA. [Leiba, Merav; Nagler, Arnon] Sheba Med Ctr, Ramat Gan, Israel. [Richardson, Paul G.; Laubach, Jacob P.; Munshi, Nikhil C.; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801160 ER PT J AU Rosenblatt, J Stone, RM Uhl, L Neuberg, D Somaiya, P Stroopinsky, D Joyce, R Levine, JD Arnason, JE Luptakova, K McMasters, M Jain, S Steensma, DP DeAngelo, DJ Galinsky, I Sato-Dilorenzo, A Palmer, KA Logan, E Bryant, MP Kufe, D Avigan, D AF Rosenblatt, Jacalyn Stone, Richard M. Uhl, Lynne Neuberg, Donna Somaiya, Poorvi Stroopinsky, Dina Joyce, Robin Levine, James D. Arnason, Jon E. Luptakova, Katarina McMasters, Malgorzata Jain, Salvia Steensma, David P. DeAngelo, Daniel J. Galinsky, Ilene Sato-Dilorenzo, Aya Palmer, Kristen Anna Logan, Emma Bryant, Mary Paty Kufe, Donald Avigan, David TI DC/Aml Fusion Cell Vaccination Administered to AML Patients Who Achieve a Complete Remission Potently Expands Leukemia Reactive T Cells and Is Associated with Durable Remissions SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Rosenblatt, Jacalyn; Uhl, Lynne; Somaiya, Poorvi; Stroopinsky, Dina; Levine, James D.; Arnason, Jon E.; Luptakova, Katarina; McMasters, Malgorzata; Jain, Salvia; Sato-Dilorenzo, Aya; Palmer, Kristen Anna; Logan, Emma; Bryant, Mary Paty; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rosenblatt, Jacalyn; Joyce, Robin] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Stone, Richard M.; DeAngelo, Daniel J.; Galinsky, Ilene] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Neuberg, Donna; Steensma, David P.; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jain, Salvia] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Malignant Hematol & Bone Marrow Transplantat, Boston, MA 02215 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020102061 ER PT J AU Rozic, G Lena, P Jakubikova, J Adrian, D Avigdor, A Nagler, A Leiba, M AF Rozic, Gabriela Lena, Paukov Jakubikova, Jana Adrian, Duek Avigdor, Abraham Nagler, Arnon Leiba, Merav TI STK405759 As a Novel Tubulin Active Agent for Multiple Myeloma Therapy SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Rozic, Gabriela; Lena, Paukov; Adrian, Duek; Avigdor, Abraham; Nagler, Arnon; Leiba, Merav] Chaim Sheba Med Ctr, Div Hematol & Bone Marrow Transplantat, Ramat Gan, Israel. [Jakubikova, Jana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021805001 ER PT J AU Samur, MK Minvielle, S Magrangeas, F Parmigiani, G Anderson, KC Moreau, P Attal, M Avet-Loiseau, H Munshi, NC AF Samur, Mehmet K. Minvielle, Stephane Magrangeas, Florence Parmigiani, Giovanni Anderson, Kenneth C. Moreau, Philippe Attal, Michel Avet-Loiseau, Herve Munshi, Nikhil C. TI Genomic Landscape Predictive of Minimal Residual Disease (MRD) in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Samur, Mehmet K.; Parmigiani, Giovanni] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Samur, Mehmet K.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Samur, Mehmet K.; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Minvielle, Stephane; Magrangeas, Florence] Ctr Hosp Univ Nantes, Unite Mixte Genom Canc, Nantes, France. [Moreau, Philippe] Nantes Univ Hosp, Hotel Dieu, Nantes, France. [Attal, Michel] Inst Univ Canc Toulouse Oncopole, Toulouse, France. [Avet-Loiseau, Herve] Inst Natl Sante, Ctr Rech Cancerol Toulouse, Toulouse, France. [Munshi, Nikhil C.] VA Med Hosp, Boston, MA USA. RI richard, chrystelle/K-8595-2015 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801154 ER PT J AU Samur, MK Gulla, A Cleynen, A Magrangeas, F Minvielle, S Anderson, KC Parmigiani, G Avet-Loiseau, H Munshi, NC AF Samur, Mehmet K. Gulla, Annamaria Cleynen, Alice Magrangeas, Florence Minvielle, Stephane Anderson, Kenneth C. Parmigiani, Giovanni Avet-Loiseau, Herve Munshi, Nikhil C. TI Differentially Expressed and Prognostically Significant Lincrnas May Impact Immune System and Tumor Progression in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Samur, Mehmet K.; Cleynen, Alice; Parmigiani, Giovanni] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Samur, Mehmet K.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Samur, Mehmet K.; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Gulla, Annamaria] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Gulla, Annamaria] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Magrangeas, Florence; Minvielle, Stephane] CHU Nantes, Unite Mixte Genom Canc, F-44035 Nantes 01, France. [Avet-Loiseau, Herve] Ctr Rech Cancerol Toulouse, Inst Natl Sante, Toulouse, France. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103184 ER PT J AU San Miguel, JF Hungria, VTM Yoon, SS Beksac, M Dimopoulos, MA Elghandour, A Jedrzejczak, WW Guenther, A Nakorn, TN Siritanaratkul, N Schlossman, RL Hou, J Moreau, P Lonial, S Lee, JH Einsele, H Sopala, M Bengoudifa, BR Corrado, C Binlich, F Richardson, PG AF San Miguel, Jesus F. Hungria, Vania T. M. Yoon, Sung-Soo Beksac, Meral Dimopoulos, Meletios A. Elghandour, Ashraf Jedrzejczak, Wieslaw W. Guenther, Andreas Nakorn, Thanyaphong Na Siritanaratkul, Noppadol Schlossman, Robert L. Hou, Jian Moreau, Philippe Lonial, Sagar Lee, Jae Hoon Einsele, Hermann Sopala, Monika Bengoudifa, Bourras-Rezki Corrado, Claudia Binlich, Florence Richardson, Paul G. TI Analysis of Outcomes Based on Response in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma Treated with Panobinostat or Placebo in Combination with Bortezomib and Dexamethasone in the Panorama 1 Trial: Updated Analysis Based on Prior Treatment SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [San Miguel, Jesus F.] Clin Univ Navarra CIMA, Pamplona, Spain. [Hungria, Vania T. M.] Santa Casa Misericordia Sao Paulo, Sao Paulo, Brazil. [Yoon, Sung-Soo] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Beksac, Meral] Ankara Univ, Fac Med, Dept Hematol, TR-06100 Ankara, Turkey. [Dimopoulos, Meletios A.] Univ Athens, Athens 11528, Greece. [Elghandour, Ashraf] Univ Alexandria, Qesm Bab Sharqi, Egypt. [Jedrzejczak, Wieslaw W.] Med Univ Warsaw, Hematol Oncol & Internal Dis, Warsaw, Poland. [Guenther, Andreas] Univ Kiel, Kiel, Germany. [Nakorn, Thanyaphong Na] Chulalongkorn Univ, Bangkok, Thailand. [Nakorn, Thanyaphong Na] King Chulalongkorn Mem Hosp, Bangkok, Thailand. [Siritanaratkul, Noppadol] Mahidol Univ, Siriraj Hosp, Dept Pediat & Internal Med, Bangkok 10700, Thailand. [Schlossman, Robert L.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hou, Jian] Second Mil Med Univ, Changzheng Hosp, Myeloma & Lymphoma Ctr, Dept Hematol, Shanghai, Peoples R China. [Moreau, Philippe] Nantes Univ Hosp, Dept Hematol, Nantes, France. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA. [Lee, Jae Hoon] Gachon Univ, Gil Med Ctr, Inchon, South Korea. [Einsele, Hermann] Univ Hosp Wurzburg, Dept Internal Med 2, Wurzburg, Germany. [Sopala, Monika; Bengoudifa, Bourras-Rezki; Corrado, Claudia] Novartis Pharma AG, Basel, Switzerland. [Binlich, Florence] Novartis Pharma SAS, Rueil Malmaison, France. RI richard, chrystelle/K-8595-2015 NR 0 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801172 ER PT J AU San-Miguel, JF Hungria, VTM Yoon, SS Beksac, M Dimopoulos, MA Elghandour, A Jedrzejczak, WW Guenther, A Nakorn, TN Siritanaratkul, N Schlossman, RL Hou, J Moreau, P Lonial, S Lee, JH Einsele, H Sopala, M Bengoudifa, BR Corrado, C Richardson, PG AF San-Miguel, Jesus F. Hungria, Vania T. M. Yoon, Sung-Soo Beksac, Meral Dimopoulos, Meletios A. Elghandour, Ashraf Jedrzejczak, Wieslaw W. Guenther, Andreas Nakorn, Thanyaphong Na Siritanaratkul, Noppadol Schlossman, Robert L. Hou, Jian Moreau, Philippe Lonial, Sagar Lee, Jae Hoon Einsele, Hermann Sopala, Monika Bengoudifa, Bourras-Rezki Corrado, Claudia Richardson, Paul G. TI Final Analysis of Overall Survival from the Phase 3 Panorama 1 Trial of Panobinostat Plus Bortezomib and Dexamethasone Versus Placebo Plus Bortezomib and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [San-Miguel, Jesus F.] Clin Univ Navarra CIMA, Pamplona, Spain. [Hungria, Vania T. M.] Santa Casa Med Sch, Hematol & Oncol, Sao Paulo, Brazil. [Yoon, Sung-Soo] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Beksac, Meral] Ankara Univ, Fac Med, Dept Hematol, TR-06100 Ankara, Turkey. [Dimopoulos, Meletios A.] Univ Athens, Athens 11528, Greece. [Elghandour, Ashraf] Univ Alexandria, Qesm Bab Sharqi, Egypt. [Jedrzejczak, Wieslaw W.] Med Univ Warsaw, Hematol Oncol & Internal Dis, Warsaw, Poland. [Guenther, Andreas] Univ Kiel, Kiel, Germany. [Nakorn, Thanyaphong Na] Chulalongkorn Univ, Bangkok, Thailand. [Nakorn, Thanyaphong Na] King Chulalongkorn Mem Hosp, Bangkok, Thailand. [Siritanaratkul, Noppadol] Mahidol Univ, Dept Pediat & Internal Med, Siriraj Hosp, Bangkok 10700, Thailand. [Schlossman, Robert L.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hou, Jian] Second Mil Med Univ, Changzheng Hosp, Dept Hematol, Myeloma & Lymphoma Ctr, Shanghai, Peoples R China. [Moreau, Philippe] Nantes Univ Hosp, Dept Hematol, Nantes, France. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA. [Lee, Jae Hoon] Gachon Univ, Gil Med Ctr, Inchon, South Korea. [Einsele, Hermann] Univ Hosp Wurzburg, Dept Med 2, Wurzburg, Germany. [Sopala, Monika; Bengoudifa, Bourras-Rezki; Corrado, Claudia] Novartis Pharma AG, Basel, Switzerland. RI richard, chrystelle/K-8595-2015 NR 0 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 4 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103221 ER PT J AU Schmelkin, LA Howard, MT Steensma, DP Fleming, MD Rodriguez, V Khan, S Gangat, N Wolanskyj, A Patnaik, MM AF Schmelkin, Leah Ann Howard, Matthew T. Steensma, David P. Fleming, Mark D. Rodriguez, Vilmarie Khan, Shakila Gangat, Naseema Wolanskyj, Alexandra Patnaik, Mrinal M. TI Clinico-Pathological Features and Outcomes in Patients with Congenital Sideroblastic Anemias SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Schmelkin, Leah Ann] Mayo Clin, Mayo Med Sch, Rochester, MN USA. [Howard, Matthew T.] Mayo Clin, Div Hematopathol, Rochester, MN USA. [Steensma, David P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fleming, Mark D.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Rodriguez, Vilmarie] Mayo Clin, Div Pediat Hematol & Oncol, Rochester, MN USA. [Khan, Shakila] Mayo Clin, Div Pediat Hematol Oncol, Rochester, MN USA. [Gangat, Naseema; Wolanskyj, Alexandra; Patnaik, Mrinal M.] Mayo Clin, Div Hematol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020104237 ER PT J AU Seymour, JF Silverman, LR Dohner, H Fenaux, P Mufti, GJ Santini, V Minden, MD Stone, RM Lucy, LM Songer, S Dougherty, D Hinkle, R Gambini, D Beach, CL Dombret, H AF Seymour, John F. Silverman, Lewis R. Doehner, Hartmut Fenaux, Pierre Mufti, Ghulam J. Santini, Valeria Minden, Mark D. Stone, Richard M. Lucy, Lela M. Songer, Stephen Dougherty, Donna Hinkle, Randy Gambini, Dominique Beach, C. L. Dombret, Herve TI The Safety and Tolerability of Azacitidine (AZA) Are Comparable in Patients with Acute Myeloid Leukemia (AML) or Higher-Risk Myelodysplastic Syndromes (MDS) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Seymour, John F.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Silverman, Lewis R.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Doehner, Hartmut] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany. [Fenaux, Pierre] Univ Paris 07, Hop St Louis, Paris, France. [Mufti, Ghulam J.] Kings Coll Hosp London, Dept Haematol Med, London, England. [Santini, Valeria] Univ Florence, AOU Careggi, Florence, Italy. [Minden, Mark D.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lucy, Lela M.; Songer, Stephen; Dougherty, Donna; Hinkle, Randy; Gambini, Dominique; Beach, C. L.] Celgene Corp, Summit, NJ USA. [Dombret, Herve] Hop St Louis, Hematol, Paris, France. 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 4 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800011 ER PT J AU Shammas, MA Kumar, S Nanjappa, P Samur, MK Talluri, S Lin, JH Magrangeas, F Minvielle, S Avet-Loiseau, H Munshi, NC AF Shammas, Masood A. Kumar, Subodh Nanjappa, Purushothama Samur, Mehmet K. Talluri, Srikanth Lin, Jianhong Magrangeas, Florence Minvielle, Stephane Avet-Loiseau, Herve Munshi, Nikhil C. TI Functional and Genomic Signatures of Homologous Recombination (HR) Predict for Clinical Outcome in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Shammas, Masood A.; Kumar, Subodh; Talluri, Srikanth; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Shammas, Masood A.; Kumar, Subodh; Nanjappa, Purushothama; Talluri, Srikanth; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Samur, Mehmet K.] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Lin, Jianhong] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Magrangeas, Florence; Minvielle, Stephane] CNRS 6299, Ctr Rech Cancerol Nantes Angers UMR Inserm 892, Nantes, France. [Magrangeas, Florence; Minvielle, Stephane] Univ Nantes, Inst Rech Therapeut, Nantes, France. [Avet-Loiseau, Herve] Ctr Rech Cancerol Toulouse, Inst Natl Sante, Toulouse, France. 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7XY UT WOS:000368020105192 ER PT J AU Shammas, MA Buon, L Lin, JH Samur, MK Patel, JM Vahia, A Nanjappa, P Kumar, S Bajwa, A Ahmad, H Alagpulinsa, D Parmigiani, G Magrangeas, F Minvielle, S Avet-Loiseau, H Munshi, NC AF Shammas, Masood A. Buon, Leutz Lin, Jianhong Samur, Mehmet K. Patel, Jaymin M. Vahia, Ankit Nanjappa, Purushothama Kumar, Subodh Bajwa, Ahsun Ahmad, Humza Alagpulinsa, David Parmigiani, Giovanni Magrangeas, Florence Minvielle, Stephane Avet-Loiseau, Herve Munshi, Nikhil C. TI Nuclease Activity Is Associated with Genomic Instability As Well As Survival in Myeloma; Underlying Mechanisms and Significance SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Shammas, Masood A.; Vahia, Ankit; Nanjappa, Purushothama; Kumar, Subodh; Bajwa, Ahsun; Ahmad, Humza; Alagpulinsa, David; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Shammas, Masood A.; Samur, Mehmet K.; Kumar, Subodh; Parmigiani, Giovanni] VA Boston Healthcare Syst, West Roxbury, MA USA. [Buon, Leutz] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med oncol, Boston, MA 02115 USA. [Lin, Jianhong] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Samur, Mehmet K.; Parmigiani, Giovanni] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Magrangeas, Florence; Minvielle, Stephane] Univ Nantes, Ctr Rech Cancerol Nantes, Angers UMR Inserm 892, CNRS 6299, Nantes, France. [Magrangeas, Florence; Minvielle, Stephane] Univ Nantes, Inst Rech Therapeut, Nantes, France. [Avet-Loiseau, Herve] CHU Rangueil, Unit Genom Myelome, F-31054 Toulouse, France. 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020101258 ER PT J AU Shi, C Han, LN Zhang, Q Roberts, KG Park, E Tabe, Y Jacamo, RO Mu, H Wu, SC Zhou, J Ma, H Zeng, ZH Jain, N Jabbour, EJ Muschen, M Tasian, SK Mullighan, CG Weinstock, DM Fruman, D Konopleva, M AF Shi, Ce Han, Lina Zhang, Qi Roberts, Kathryn G. Park, Eugene Tabe, Yoko Jacamo, Rodrigo Omar Mu, Hong Wu, Shuo-Chieh Zhou, Jin Ma, Helen Zeng, Zhihong Jain, Nitin Jabbour, Elias J. Muschen, Markus Tasian, Sarah K. Mullighan, Charles G. Weinstock, David M. Fruman, David Konopleva, Marina TI Combined Targeting of JAK2 with a Type II JAK2 Inhibitor and mTOR with a TOR Kinase Inhibitor Constitutes Synthetic Activity in JAK2-Driven Ph-like Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Shi, Ce; Han, Lina; Ma, Helen; Jain, Nitin; Jabbour, Elias J.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Shi, Ce] Harbin Med Univ, Affiliated Hosp 1, Dept Leukemia, Harbin, Peoples R China. [Zhang, Qi; Jacamo, Rodrigo Omar; Mu, Hong; Zeng, Zhihong; Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Sect Mol Hematol & Therapy, Houston, TX 77030 USA. [Roberts, Kathryn G.] St Jude Childrens Res Hosp, Pathol, Memphis, TN 38105 USA. [Park, Eugene] Univ Cambridge, Dept Haematol, Cambridge, England. [Tabe, Yoko] Juntendo Univ, Sch Med, Tokyo, Japan. [Wu, Shuo-Chieh] Dana Farber Canc Inst, Boston, MD USA. [Zhou, Jin] Harbin Med Univ, Affiliated Hosp 1, Dept Med, Hematol, Harbin, Peoples R China. [Muschen, Markus] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Tasian, Sarah K.] Childrens Hosp Philadelphia, Pediat Oncol, Philadelphia, PA 19104 USA. [Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Weinstock, David M.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Fruman, David] Univ Calif Irvine, Irvine, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020102041 ER PT J AU Shi, JL Lu, XG Thatte, HS AF Shi, Jialan Lu, Xiu-Gui Thatte, Hemant S. TI Novel Additive Solution "Aayusol" Significantly Preserves Platelets in Lesion-Free State during Extended Storage SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Shi, Jialan; Lu, Xiu-Gui; Thatte, Hemant S.] Harvard Univ, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cardiothorac Surg Div,Dept Surg,Med Sch, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020105124 ER PT J AU Shukla, N O'Brien, MM Silverman, LB Pauly, M Wetmore, C Loh, ML Whitlock, JA Brown, P Thomson, B Blakemore, SJ Daigle, S Pimentel, P Waters, NJ Krivstov, AV Koche, R Armstrong, SA Ho, PT Gore, L AF Shukla, Neerav O'Brien, Maureen M. Silverman, Lewis B. Pauly, Melinda Wetmore, Cynthia Loh, Mignon L. Whitlock, James A. Brown, Patrick Thomson, Blythe Blakemore, Stephen J. Daigle, Scott Pimentel, Patricia Waters, Nigel J. Krivstov, Andrei V. Koche, Richard Armstrong, Scott A. Ho, Peter T. Gore, Lia TI Preliminary Report of the Phase 1 Study of the DOT1L Inhibitor, Pinometostat, EPZ-5676, in Children with Relapsed or Refractory MLL-r Acute Leukemia: Safety, Exposure and Target Inhibition SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Shukla, Neerav] Mem Sloan Kettering, New York, NY USA. [O'Brien, Maureen M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Silverman, Lewis B.] Boston Childrens Hosp, Boston, MA USA. [Pauly, Melinda] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA. [Wetmore, Cynthia] Emory Univ, Atlanta, GA 30322 USA. [Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, San Francisco, CA USA. [Whitlock, James A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Brown, Patrick] Johns Hopkins Univ, Sch Med, Pediat Oncol, Baltimore, MD USA. [Thomson, Blythe; Blakemore, Stephen J.; Daigle, Scott; Pimentel, Patricia; Waters, Nigel J.] Epizyme Inc, Cambridge, MA USA. [Krivstov, Andrei V.; Koche, Richard; Armstrong, Scott A.; Ho, Peter T.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gore, Lia] Univ Colorado Denver, Sect Hematol Oncol & Bone Marrow Transplantat, Pediat, Aurora, CO USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800049 ER PT J AU Siegel, DS Weisel, KC Dimopoulos, MA Baz, R Richardson, PG Delforge, M Song, K San Miguel, J Moreau, P Yu, X Hong, K Sternas, L Zaki, MH Palumbo, A AF Siegel, David S. Weisel, Katja C. Dimopoulos, Meletios A. Baz, Rachid Richardson, Paul G. Delforge, Michel Song, Kevin San Miguel, Jesus Moreau, Philippe Yu, Xin Hong, Kevin Sternas, Lars Zaki, Mohamed H. Palumbo, Antonio TI Analysis of Pomalidomide Plus Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma with Vs without Moderate Renal Impairment SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Weisel, Katja C.] Univ Tubingen Hosp, Dept Med, Hematol & Oncol, Tubingen, Germany. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Athens 11528, Greece. [Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Delforge, Michel] Univ Hosp Leuven, Leuven, Belgium. [Song, Kevin] Vancouver Gen Hosp, Hematol, Vancouver, BC, Canada. [San Miguel, Jesus] Univ Navarra, Navarra, Spain. [Moreau, Philippe] Univ Nantes, Nantes, France. [Yu, Xin; Hong, Kevin; Sternas, Lars; Zaki, Mohamed H.] Celgene Corp, Summit, NJ USA. [Palumbo, Antonio] Univ Turin, Turin, Italy. RI richard, chrystelle/K-8595-2015 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103226 ER PT J AU Singh, I Samur, MK Shih-Han, L Sperling, AS Tai, YT Fulciniti, M Leslie, CS Mayr, C Munshi, NC AF Singh, Irtisha Samur, Mehmet K. Shih-Han, Lee Sperling, Adam Samuel Tai, Yu-Tzu Fulciniti, Mariateresa Leslie, Christina S. Mayr, Christine Munshi, Nikhil C. TI Global 3 ' UTR Sequencing in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Singh, Irtisha; Leslie, Christina S.] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10021 USA. [Singh, Irtisha] Triinst Training Program Computat Biol & Med, New York, NY USA. [Samur, Mehmet K.] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Samur, Mehmet K.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Samur, Mehmet K.; Tai, Yu-Tzu; Fulciniti, Mariateresa; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Shih-Han, Lee; Mayr, Christine] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. [Sperling, Adam Samuel] 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103189 ER PT J AU Siu, KT Eda, H Santo, L Ramachandran, J Koulnis, M Mertz, J Sims, RJ Cooper, M Raje, NS AF Siu, Ka Tat Eda, Homare Santo, Loredana Ramachandran, Janani Koulnis, Miroslav Mertz, Jennifer Sims, Robert J. Cooper, Michael Raje, Noopur S. TI Effect of the BET Inhibitor, Cpi-0610, Alone and in Combination with Lenalidomide in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Siu, Ka Tat; Eda, Homare; Ramachandran, Janani; Koulnis, Miroslav] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Santo, Loredana; Raje, Noopur S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mertz, Jennifer; Sims, Robert J.; Cooper, Michael] Constellat Pharmaceut, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801197 ER PT J AU Spencer, A Laubach, JP Zonder, JA Badros, AZ Harrison, S Khot, A Chauhan, D Anderson, KC Reich, SD Trikha, M Richardson, PC AF Spencer, Andrew Laubach, Jacob P. Zonder, Jeffrey A. Badros, Ashraf Z. Harrison, Simon Khot, Amit Chauhan, Dharminder Anderson, Kenneth C. Reich, Steven D. Trikha, Mohit Richardson, Paul C. TI Phase 1, Multicenter, Open-Label, Combination Study (NPI-0052-107; NCT02103335) of Pomalidomide (POM), Marizomib (MRZ, NPI-0052), and Low-Dose Dexamethasone (LD-DEX) in Patients with Relapsed and Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Spencer, Andrew] Monash Univ, Alfred Hosp, Myeloma Res Grp, Melbourne, Vic 3181, Australia. [Laubach, Jacob P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zonder, Jeffrey A.] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Badros, Ashraf Z.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Badros, Ashraf Z.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Harrison, Simon] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Khot, Amit] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic, Australia. [Chauhan, Dharminder] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Reich, Steven D.] Triphase Accelerator Corp, San Diego, CA USA. [Trikha, Mohit] Triphase Accelerator, San Diego, CA USA. [Richardson, Paul C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancy,Dept Med Oncol,Jerome Lipp, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801162 ER PT J AU Stroopinsky, D Rajabi, H Coll, MD Pyzer, AR Rosenblatt, J Jain, S Luptakova, K McMasters, M Levine, JD Joyce, R Arnason, JE Leaf, RK Nahas, MR Palmer, KA Bar-Natan, M Tagde, A Washington, A Somaiya, P Kufe, D Avigan, D AF Stroopinsky, Dina Rajabi, Hasan Coll, Maxwell Douglas Pyzer, Athalia Rachel Rosenblatt, Jacalyn Jain, Salvia Luptakova, Katarina McMasters, Malgorzata Levine, James D. Joyce, Robin Arnason, Jon E. Leaf, Rebecca Karp Nahas, Myrna Rita Palmer, Kristen Anna Bar-Natan, Michal Tagde, Ashujit Washington, Abigail Somaiya, Poorvi Kufe, Donald Avigan, David TI Immunomodulatory Effect of MUC1-C in Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Stroopinsky, Dina; Coll, Maxwell Douglas; Pyzer, Athalia Rachel; Rosenblatt, Jacalyn; Luptakova, Katarina; McMasters, Malgorzata; Levine, James D.; Arnason, Jon E.; Leaf, Rebecca Karp; Nahas, Myrna Rita; Palmer, Kristen Anna; Bar-Natan, Michal; Washington, Abigail; Somaiya, Poorvi; Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Rajabi, Hasan; Tagde, Ashujit; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Jain, Salvia] Harvard Univ, Beth Israel Deaconess Med Ctr, Malignant Hematol & Bone Marrow Transplantat, Sch Med, Boston, MA 02215 USA. [Joyce, Robin] Harvard Univ, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Joyce, Robin] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7XY UT WOS:000368020105225 ER PT J AU Sweet, KL Pemmaraju, N Lane, AA Stein, AS Vasu, S Blum, W Rizzieri, DA Wang, ES Rowinsky, EK Szarek, M Brooks, CL Disalvatore, S Liu, D Duvic, M Schwartz, JD Konopleva, M AF Sweet, Kendra L. Pemmaraju, Naveen Lane, Andrew A. Stein, Anthony S. Vasu, Sumithira Blum, William Rizzieri, David A. Wang, Eunice S. Rowinsky, Eric K. Szarek, Michael Brooks, Christopher L. Disalvatore, Sarah Liu, David Duvic, Madeleine Schwartz, Jonathan D. Konopleva, Marina TI Lead-in Stage Results of a Pivotal Trial of SL-401, an Interleukin-3 Receptor (IL-3R) Targeting Biologic, in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) or Acute Myeloid Leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Sweet, Kendra L.] Univ S Florida, H Lee Moffitt Canc Ctr, Malignant Hematol, Tampa, FL 33682 USA. [Pemmaraju, Naveen] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Lane, Andrew A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stein, Anthony S.] City Hope Natl Med Ctr, Cehr Family Ctr Leukemia Res, Duarte, CA 91010 USA. [Vasu, Sumithira] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Blum, William] Ohio State Univ, Columbus, OH 43210 USA. [Rizzieri, David A.] Duke Univ, Med Ctr, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC 27710 USA. [Wang, Eunice S.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Rowinsky, Eric K.; Szarek, Michael; Brooks, Christopher L.; Disalvatore, Sarah; Liu, David; Schwartz, Jonathan D.] Stemline Therapeut Inc, New York, NY USA. [Duvic, Madeleine] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Sect Mol Hematol & Therapy, Houston, TX 77030 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800052 ER PT J AU Szalat, R Samur, MK Cleynen, A Calkins, A Dreze, M Tai, YT Minvielle, S Avet-Loiseau, H Anderson, KC Fernand, JP Lazaro, JB Munshi, NC AF Szalat, Raphael Samur, Mehmet Kemal Cleynen, Alice Calkins, Anne Dreze, Matija Tai, Yu-Tzu Minvielle, Stephane Avet-Loiseau, Herve Anderson, Kenneth C. Fernand, Jean-Paul Lazaro, Jean-Bernard Munshi, Nikhil C. TI Dysregulated Nucleotide Excision Repair (NER) Is a New Target in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Szalat, Raphael; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Szalat, Raphael; Fernand, Jean-Paul] Hop St Louis, AP HP, Serv Immunohematol, Paris, France. [Samur, Mehmet Kemal; Cleynen, Alice] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Calkins, Anne; Dreze, Matija; Lazaro, Jean-Bernard] Dana Farber Canc Inst, Boston, MA 02115 USA. [Minvielle, Stephane] Ctr Hosp Univ Nantes, Unite Mixte Genom Canc, Nantes, France. [Avet-Loiseau, Herve] IUCT Oncopole, Toulouse, France. [Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801129 ER PT J AU van Beers, E van Vliet, M de Best, L Anderson, KC Chari, A Jagganath, S Jakubowiak, A Kumar, SK Lebovic, D Levy, J Auclair, D Lonial, S Reece, D Richardson, PG Siegel, D Stewart, AK Trudel, S Vij, R Zimmerman, T Fonseca, R AF van Beers, Erik van Vliet, Martin de Best, Leonie Anderson, Kenneth C. Chari, Ajai Jagganath, Sundar Jakubowiak, Andrzej Kumar, Shaji K. Lebovic, Daniel Levy, Joan Auclair, Daniel Lonial, Sagar Reece, Donna Richardson, Paul G. Siegel, David Stewart, A. Keith Trudel, Suzanne Vij, Ravi Zimmerman, Todd Fonseca, Rafael TI Low-Risk Multiple Myeloma By SKY92+ISS Validated in the Multiple Myeloma Genomics Initiative Study SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [van Beers, Erik; van Vliet, Martin; de Best, Leonie] SkylineDx, Rotterdam, Netherlands. [Anderson, Kenneth C.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Chari, Ajai] Icahn Sch Med Mt Sinai, Hematol & Med Oncol, New York, NY 10029 USA. [Jagganath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Jakubowiak, Andrzej] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Kumar, Shaji K.] Mayo Clin, Div Hematol, Rochester, MN USA. [Lebovic, Daniel] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Levy, Joan; Auclair, Daniel] Multiple Myeloma Res Fdn, Norwalk, CT USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA. [Reece, Donna] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Siegel, David] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Stewart, A. Keith; Fonseca, Rafael] Mayo Clin, Scottsdale, AZ USA. [Trudel, Suzanne] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Vij, Ravi] Washington Univ, St Louis, MO USA. [Zimmerman, Todd] Univ Chicago, Chicago, IL 60637 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 5 WC Hematology SC Hematology GA DA7YP UT WOS:000368021804298 ER PT J AU Verstovsek, S Talpaz, M Ritchie, E Wadleigh, M Odenike, O Jamieson, C Stein, B Uno, T Mesa, RA AF Verstovsek, Srdan Talpaz, Moshe Ritchie, Ellen Wadleigh, Martha Odenike, Olatoyosi Jamieson, Catriona Stein, Brady Uno, Tomonori Mesa, Ruben A. TI A Phase 1/2 Study of NS-018, an Oral JAK2 Inhibitor, in Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (pPV MF), or Post-Essential Thrombocythemia Myelofibrosis (pET MF) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Verstovsek, Srdan] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Talpaz, Moshe] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Ritchie, Ellen] Cornell Univ, Med, New York, NY 10021 USA. [Wadleigh, Martha] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Odenike, Olatoyosi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Jamieson, Catriona] Univ Calif San Diego, Div Regenerat Med, La Jolla, CA 92093 USA. [Stein, Brady] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. [Stein, Brady] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Uno, Tomonori] NS Pharma Inc, Paramus, NJ USA. [Mesa, Ruben A.] Mayo Clin Arizona, Hematol Oncol, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020102312 ER PT J AU Voorhees, PM Magarotto, V Sonneveld, P Plesner, T Mellqvist, UH Paba-Prada, CE Byrne, C Harmenberg, J Nordstrom, E Palumbo, A Richardson, P AF Voorhees, Peter M. Magarotto, Valeria Sonneveld, Pieter Plesner, Torben Mellqvist, Ulf-Henrik Paba-Prada, Claudia E. Byrne, Catriona Harmenberg, Johan Nordstrom, Eva Palumbo, Antonio Richardson, Paul TI Efficacy of Melflufen, a Peptidase Targeted Therapy, and Dexamethasone in an Ongoing Open-Label Phase 2a Study in Patients with Relapsed and Relapsed Refractory Multiple Myeloma (RRMM) Including an Initial Report on Progression Free Survival SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Voorhees, Peter M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Magarotto, Valeria; Palumbo, Antonio] Univ Turin, Div Hematol, Myeloma Unit, Turin, Italy. [Sonneveld, Pieter] Erasmus MC, Hematol, Rotterdam, Netherlands. [Plesner, Torben] Vejle Hosp, Dept Hematol, Vejle, Denmark. [Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Sect Hematol & Coagulat, Dept Med, Gothenburg, Sweden. [Paba-Prada, Claudia E.; Richardson, Paul] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Byrne, Catriona; Harmenberg, Johan; Nordstrom, Eva] Oncopeptides AB, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103224 ER PT J AU Vos, JM Manning, RR Meid, K Gustine, J Patterson, CJ Brodsky, P Kanan, S Kersten, MJ Treon, SP Castillo, JJ AF Vos, Josephine M. Manning, Robert R. Meid, Kirsten Gustine, Joshua Patterson, Christopher J. Brodsky, Philip Kanan, Sandra Kersten, Marie Jose Treon, Steven P. Castillo, Jorge J. TI Defining the Incidence, Pathology and Clinical Outcomes of Kidney Disease Related to Waldenstrom's Macroglobulinemia and IgM MGUS SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Vos, Josephine M.; Manning, Robert R.; Meid, Kirsten; Gustine, Joshua; Patterson, Christopher J.; Brodsky, Philip; Kanan, Sandra; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr WM, Boston, MA 02115 USA. [Vos, Josephine M.] St Antonius Hosp, Internal Med Hematol, Nieuwegein, Netherlands. [Kersten, Marie Jose] Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands. [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800183 ER PT J AU Weinacht, KG Charbonnier, LM Plant, A Torgerson, T Rosenzweig, S Fleisher, T Notarangelo, LD AF Weinacht, Katja G. Charbonnier, Louis M. Plant, Ashley Torgerson, Troy Rosenzweig, Serge Fleisher, Thomas Notarangelo, Luigi Daniele TI Successful Therapy of a Patient with a Novel STAT1 Gain of Function Mutation and Life-Threatening Cytopenias with Janus Kinase Inhibitor Ruxolitinib SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Weinacht, Katja G.] Childrens Hosp Boston, Dana Farber Canc Inst, Hematol Oncol, Boston, MA USA. [Charbonnier, Louis M.] Boston Childrens Hosp, Dept Pediat Immunol, Boston, MA USA. [Plant, Ashley] Boston Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA USA. [Torgerson, Troy] Univ Washington, Seattle, WA 98195 USA. [Torgerson, Troy] Seattle Childrens Res Inst, Seattle, WA USA. [Rosenzweig, Serge] NIAID, NIH, Bethesda, MD 20892 USA. [Fleisher, Thomas] NIAID, NCI, Lab Med, NIH, Bethesda, MD 20892 USA. [Notarangelo, Luigi Daniele] Boston Childrens Hosp, Div Immunol, Boston, MA USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7XY UT WOS:000368020105001 ER PT J AU Whangbo, J Koreth, J Kim, HT Dusenbury, K Alho, AC Reynolds, CG Chammas, MJ Jones, KT Nikiforow, S Cutler, CS Ho, VT Armand, P Alyea, EP Soiffer, RJ Antin, JH Ritz, J AF Whangbo, Jennifer Koreth, John Kim, Haesook T. Dusenbury, Katharine Alho, Ana Cristina Reynolds, Carol G. Chammas, Marie J. Jones, Kyle T. Nikiforow, Sarah Cutler, Corey S. Ho, Vincent T. Armand, Philippe Alyea, Edwin P. Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome TI Long-Term Homeostatic Effects of Daily Low-Dose IL-2 on CD4+FoxP3+Regulatory T Cells in Patients with Active Chronic Graft-Versus-Host Disease SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Whangbo, Jennifer; Dusenbury, Katharine; Alho, Ana Cristina; Reynolds, Carol G.; Chammas, Marie J.; Jones, Kyle T.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Whangbo, Jennifer] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Koreth, John; Jones, Kyle T.; Ho, Vincent T.; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Nikiforow, Sarah; Cutler, Corey S.; Armand, Philippe; Alyea, Edwin P.; Antin, Joseph H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Nikiforow, Sarah; Cutler, Corey S.; Armand, Philippe; Alyea, Edwin P.; Antin, Joseph H.] Harvard Univ, Sch Med, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 4 WC Hematology SC Hematology GA DA7XY UT WOS:000368020104015 ER PT J AU Wildes, TM Fiala, MA Rosko, AE Tuchman, S Guerard, E O'Donnell, EK Campagnaro, EL Stockerl-Goldstein, K Vij, R AF Wildes, Tanya M. Fiala, Mark A. Rosko, Ashley E. Tuchman, Sascha Guerard, Emily O'Donnell, Elizabeth K. Campagnaro, Erica L. Stockerl-Goldstein, Keith Vij, Ravi TI Falls in Older Adults with Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Wildes, Tanya M.; Fiala, Mark A.; Stockerl-Goldstein, Keith; Vij, Ravi] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Rosko, Ashley E.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Tuchman, Sascha] Duke Univ, Durham, NC USA. [Guerard, Emily] Univ N Carolina, Chapel Hill, NC USA. [O'Donnell, Elizabeth K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Campagnaro, Erica L.] Univ Michigan, Ann Arbor, MI 48109 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021802110 ER PT J AU Will, CM Scholle, M St Pierre, R Schiltz, G Bradner, JE Mrksich, M Licht, JD AF Will, Christine M. Scholle, Michael St Pierre, Roodolph Schiltz, Gary Bradner, James E. Mrksich, Milan Licht, Jonathan D. TI High Throughput Screening Identifies Potential Inhibitors of WHSC1/MMSET, a Histone Methyltransferase Oncoprotein in Multiple Myeloma and Acute Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Will, Christine M.; Licht, Jonathan D.] Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. [Scholle, Michael; Mrksich, Milan] Northwestern Univ, Dept Biomed Engn & Chem, Chicago, IL 60611 USA. [St Pierre, Roodolph; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Schiltz, Gary] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chicago, IL 60611 USA. RI Mrksich, Milan/G-2469-2011 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020104133 ER PT J AU Xu, Y Deng, SH An, G Li, ZJ Qin, XQ Sui, WW Feng, XY Zou, DH Qiu, LG AF Xu, Yan Deng, Shuhui An, Gang Li, Zengjun Qin, Xiaoqi Sui, Weiwei Feng, Xiaoyan Zou, Dehui Qiu, Lugui TI Voriconazole Increase the Risk of PN in Multiple Myeloma Patients Treated with Bortezomib-Based Chemotherapy SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Xu, Yan; Deng, Shuhui] Chinese Acad Med Sci, Inst Hematol, Lymphoma & Myeloma Dept, Tianjin, Peoples R China. [Xu, Yan; Deng, Shuhui; Li, Zengjun; Qin, Xiaoqi; Sui, Weiwei; Feng, Xiaoyan; Zou, Dehui] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [Xu, Yan; Deng, Shuhui; Li, Zengjun; Qin, Xiaoqi; Sui, Weiwei; Feng, Xiaoyan; Zou, Dehui] Peking Union Med Coll, Tianjin, Peoples R China. [An, Gang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [An, Gang; Feng, Xiaoyan] Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Li, Zengjun; Qin, Xiaoqi; Sui, Weiwei; Feng, Xiaoyan; Qiu, Lugui] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. [Zou, Dehui] Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China. [Qiu, Lugui] Blood Dis Hosp, Tianjin, Peoples R China. 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021805047 ER PT J AU Yang, G Liu, X Chen, J Xu, L Tsakmaklis, N Chen, JJ Patterson, CJ Castillo, JJ Cohen, P Tan, L Buhrlage, S Gray, N Treon, SP AF Yang, Guang Liu, Xia Chen, Jie Xu, Lian Tsakmaklis, Nicholas Chen, Jiaji Patterson, Christopher J. Castillo, Jorge J. Cohen, Philip Tan, Li Buhrlage, Sara Gray, Nathanael Treon, Steven P. TI Targeting IRAK1 /IRAK4 Signaling in Waldenstrom's Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Yang, Guang; Liu, Xia; Chen, Jie; Xu, Lian; Tsakmaklis, Nicholas; Chen, Jiaji; Patterson, Christopher J.; Castillo, Jorge J.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr WM, Boston, MA 02115 USA. [Cohen, Philip] Univ Dundee, Coll Life Sci, Prot Phosphorylat & Ubiquitylat Unit 2MRC, Dundee, Scotland. [Tan, Li; Buhrlage, Sara; Gray, Nathanael] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800261 ER PT J AU Yee, AJ Laubach, JP Nooka, AK O'Donnell, EK Weller, EA Couture, NR Wallace, EE Burke, JN Harrington, CC Puccio-Pick, M Laadem, A Sherman, ML Raje, NS AF Yee, Andrew J. Laubach, Jacob P. Nooka, Ajay K. O'Donnell, Elizabeth K. Weller, Edie A. Couture, Nicole R. Wallace, Ellen E. Burke, Jill N. Harrington, Cynthia C. Puccio-Pick, Marie Laadem, Abderrahmane Sherman, Matthew L. Raje, Noopur S. TI Phase 1 Dose-Escalation Study of Sotatercept (ACE-011) in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Yee, Andrew J.; O'Donnell, Elizabeth K.; Couture, Nicole R.; Wallace, Ellen E.; Burke, Jill N.; Harrington, Cynthia C.; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Laubach, Jacob P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nooka, Ajay K.] Emory Univ, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA. [Weller, Edie A.] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Puccio-Pick, Marie; Laadem, Abderrahmane] Celgene Corp, Summit, NJ USA. [Sherman, Matthew L.] Acceleron Pharma, Cambridge, MA 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 2 WC Hematology SC Hematology GA DA7YP UT WOS:000368021801183 ER PT J AU Yee, AJ Bensinger, W Voorhees, PM Berdeja, JG Richardson, PG Supko, J Tamang, D Jones, SS Wheeler, C Markelewicz, RJ Raje, NS AF Yee, Andrew J. Bensinger, William Voorhees, Peter M. Berdeja, Jesus G. Richardson, Paul G. Supko, Jeffrey Tamang, David Jones, Simon S. Wheeler, Catherine Markelewicz, Robert J., Jr. Raje, Noopur S. TI Ricolinostat (ACY-1215), the First Selective HDAC6 Inhibitor, in Combonation with Lenalidomide and Dexamethasone in Patients with Relapsed and Relapsed -and Refractory Multiple Myeloma: Phase lb Results (ACE-MM-101 Study) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Yee, Andrew J.; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bensinger, William] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Voorhees, Peter M.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Supko, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tamang, David; Jones, Simon S.; Wheeler, Catherine; Markelewicz, Robert J., Jr.] Acetylon Pharmaceut Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 4 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103250 ER PT J AU Yeh, AC Dey, BR Spitzer, TR Akter, M Biswas, A Khan, MA Ara, T Ferdous, J Aforse, S Islam, M AF Yeh, Albert C. Dey, Bimalangshu R. Spitzer, Thomas R. Akter, Mafruha Biswas, Akhil Khan, Mohiuddin Ahmed Ara, Tasneem Ferdous, Jannatul Aforse, Salma Islam, Manirul TI Hematopoeitic Stem Cell Transplantation in the Developing World: A Case Study of Dhaka Medical College, Bangladesh SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Yeh, Albert C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Dey, Bimalangshu R.] Massachusetts Gen Hosp, Med Oncol, Boston, MA 02114 USA. [Spitzer, Thomas R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Akter, Mafruha; Biswas, Akhil; Khan, Mohiuddin Ahmed; Ara, Tasneem; Ferdous, Jannatul; Aforse, Salma; Islam, Manirul] Dhaka Med Coll Hosp, Dhaka, Bangladesh. 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021805279 ER PT J AU Yellapragada, SV Sarosiek, S Prabhala, ND Kemalsamur, M Houranieh, A Girnius, S Tumula, P Kambhampati, S Bhoopalam, N Prabhala, RH Roodman, D Lichtenstein, A Munshi, NC AF Yellapragada, Sarvari V. Sarosiek, Shayna Prabhala, Neelima D. Kemalsamur, Mehmet Houranieh, Antoun Girnius, Saulius Tumula, Praveen Kambhampati, Suman Bhoopalam, Nirmala Prabhala, Rao H. Roodman, David Lichtenstein, Alan Munshi, Nikhil C. TI Evaluating the Efficacy and Toxicity of Two Lenalidomide Dose Regimens for the Treatment of Older Relapsed Multiple Myeloma Patients with Co-Morbidities: A Multi-Site Study at the Veteran's Administration Hospitals SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Yellapragada, Sarvari V.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Yellapragada, Sarvari V.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Sarosiek, Shayna] Boston Univ, Med Ctr, Boston, MA USA. [Sarosiek, Shayna; Prabhala, Neelima D.; Houranieh, Antoun; Tumula, Praveen; Prabhala, Rao H.; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Kemalsamur, Mehmet; Prabhala, Rao H.; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Girnius, Saulius] Univ Cincinnati, Cinncinati, OH USA. [Kambhampati, Suman] Kansas City VA Med Ctr, Kansas City, MO USA. [Bhoopalam, Nirmala] Hines VA Med Ctr, Hines, IL USA. [Roodman, David] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Roodman, David] Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA USA. [Lichtenstein, Alan] VA Greater Los Angeles Healthcare Syst, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021805023 ER PT J AU Yu, LJ Kim, HT Kasar, S Benien, P Du, W Hoang, K Improgo, R Fernandes, SM Klitgaard, JL Lee, C Getz, G Setlur, SR Brown, JR AF Yu, Lijian Kim, Haesook T. Kasar, Siddha Benien, Parul Du, Wei Hoang, Kevin Improgo, Reina Fernandes, Stacey M. Klitgaard, Josephine L. Lee, Charles Getz, Gady Setlur, Sunita R. Brown, Jennifer R. TI Comprehensive Genetic Characterization of 17p Deleted CLL Identifies Predictors of Overall Survival SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Yu, Lijian; Improgo, Reina; Klitgaard, Josephine L.; Brown, Jennifer R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Yu, Lijian; Kasar, Siddha; Hoang, Kevin; Improgo, Reina; Fernandes, Stacey M.; Klitgaard, Josephine L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Benien, Parul; Du, Wei; Lee, Charles; Setlur, Sunita R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Getz, Gady] Broad Inst, Cambridge, MA USA. [Brown, Jennifer R.] Dana Farber Canc Inst, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020103102 ER PT J AU Zeidan, AM Long, JB Hall, J Wang, R Huntington, SF Abel, G Prebet, T Podoltsev, NA Gross, CP Gore, SD Ma, XM Davidoff, AJ AF Zeidan, Amer M. Long, Jessica B. Hall, Jane Wang, Rong Huntington, Scott F. Abel, Gregory Prebet, Thomas Podoltsev, Nikolai A. Gross, Cary P. Gore, Steven D. Ma, Xiaomei Davidoff, Amy J. TI Comparative Effectiveness of Azacitidine Versus Decitabine Among Older Adults Diagnosed with Higher-Risk Myelodysplastic Syndromes (HR-MDS) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Zeidan, Amer M.; Huntington, Scott F.; Podoltsev, Nikolai A.; Gross, Cary P.] Yale Univ, Sch Med, New Haven, CT USA. [Long, Jessica B.; Hall, Jane; Wang, Rong; Ma, Xiaomei; Davidoff, Amy J.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Abel, Gregory] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prebet, Thomas] Yale Univ, Sch Med, Dept Internal Med, Sect Hematol, New Haven, CT 06510 USA. [Gore, Steven D.] Yale Canc Ctr, New Haven, CT 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7XY UT WOS:000368020104167 ER PT J AU Zinzani, PL Ribrag, V Moskowitz, CH Michot, JM Kuruvilla, J Balakumaran, A Snyder, E Marinello, P Shipp, MA Armand, P AF Zinzani, Pier Luigi Ribrag, Vincent Moskowitz, Craig H. Michot, Jean-Marie Kuruvilla, John Balakumaran, Arun Snyder, Ellen Marinello, Patricia Shipp, Margaret A. Armand, Philippe TI Phase 1b Study of PD-1 Blockade with Pembrolizumab in Patients with Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL) SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Zinzani, Pier Luigi] Univ Bologna, Inst Hematol L & A Seragnoli, Bologna, Italy. [Ribrag, Vincent] Gustave Roussy Canc Campus, DITEP Med, Villejuif, France. [Moskowitz, Craig H.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Michot, Jean-Marie] Gustave Roussy Comprehens Canc Ctr, Villejuif, France. [Kuruvilla, John] Univ Toronto, Princess Margaret Canc Ctr, Div Med Oncol & Hematol, Toronto, ON, Canada. [Balakumaran, Arun; Snyder, Ellen; Marinello, Patricia] Merck & Co Inc, Kenilworth, NJ USA. [Shipp, Margaret A.; Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Zinzani, Pier Luigi/J-9182-2016 OI Zinzani, Pier Luigi/0000-0002-2112-2651 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800243 ER PT J AU Zou, T Perry, AM Brunner, AM Philip, CC Neuberg, DS Fathi, AT AF Zou, Tao Perry, Ashley M. Brunner, Andrew M. Philip, Chepsy C. Neuberg, Donna S. Fathi, Amir T. TI Comparison of Age at Diagnosis, Cytogenetic Risk, and Overall Survival Between Acute Myeloid Leukemia Patients of White and South Asian Race/Ethnicity in the United States SO BLOOD LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2015 CL Orlando, FL SP Amer Soc Hematol C1 [Zou, Tao; Perry, Ashley M.; Brunner, Andrew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brunner, Andrew M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Philip, Chepsy C.] Christian Med Coll & Hosp, Dept Clin Haematol Haemato Oncol & Bone Marrow St, Ludhiana, Punjab, India. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 EI 1528-0020 J9 BLOOD JI Blood PD DEC 3 PY 2015 VL 126 IS 23 PG 3 WC Hematology SC Hematology GA DA7YP UT WOS:000368021800010 ER PT J AU Fields, AP Rodriguez, EH Jovanovic, M Stern-Ginossar, N Haas, BJ Mertins, P Raychowdhury, R Hacohen, N Carr, SA Ingolia, NT Regev, A Weissman, JS AF Fields, Alexander P. Rodriguez, Edwin H. Jovanovic, Marko Stern-Ginossar, Noam Haas, Brian J. Mertins, Philipp Raychowdhury, Raktima Hacohen, Nir Carr, Steven A. Ingolia, Nicholas T. Regev, Aviv Weissman, Jonathan S. TI A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation SO MOLECULAR CELL LA English DT Article ID OPEN READING FRAMES; NUCLEOTIDE RESOLUTION; NONCODING RNAS; MESSENGER-RNA; CELLS; INITIATION; EXPRESSION; PEPTIDES; REPRESSION; REGIONS AB A fundamental goal of genomics is to identify the complete set of expressed proteins. Automated annotation strategies rely on assumptions about protein-coding sequences (CDSs), e.g., they are conserved, do not overlap, and exceed a minimum length. However, an increasing number of newly discovered proteins violate these rules. Here we present an experimental and analytical framework, based on ribosome profiling and linear regression, for systematic identification and quantification of translation. Application of this approach to lipopolysaccharide- stimulated mouse dendritic cells and HCMV-infected human fibroblasts identifies thousands of novel CDSs, including micropeptides and variants of known proteins, that bear the hallmarks of canonical translation and exhibit translation levels and dynamics comparable to that of annotated CDSs. Remarkably, many translation events are identified in both mouse and human cells even when the peptide sequence is not conserved. Our work thus reveals an unexpected complexity to mammalian translation suited to provide both conserved regulatory or protein-based functions. C1 [Fields, Alexander P.; Rodriguez, Edwin H.; Weissman, Jonathan S.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Howard Hughes Med Inst, San Francisco, CA 94158 USA. [Fields, Alexander P.; Rodriguez, Edwin H.; Weissman, Jonathan S.] Calif Inst Quantitat Biomed Res, San Francisco, CA 94158 USA. [Jovanovic, Marko; Haas, Brian J.; Mertins, Philipp; Raychowdhury, Raktima; Hacohen, Nir; Carr, Steven A.; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Stern-Ginossar, Noam] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ingolia, Nicholas T.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02140 USA. RP Weissman, JS (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Howard Hughes Med Inst, San Francisco, CA 94158 USA. EM jonathan.weissman@ucsf.edu FU Helen Hay Whitney Foundation; Howard Hughes Medical Institute (HHMI) Gilliam Fellowship for Advanced Studies; Swiss National Science Foundation; Marie Sklodowska-Curie International Outgoing Fellowship; National Human Genome Research Institute Centers of Excellence in Genomics Science [P50 HG006193]; Klarman Cell Observatory; Center for RNA Systems Biology; HHMI FX We thank J. Dunn, M. Kampmann, G.-W. Li, M. Thomson, G. Brar, C. Jan, and L. Gilbert for helpful discussion and technical advice. We also thank Y. Chen, E. Chow, J. Lund, and the UCSF Center for Advanced Technology for help with sequencing and C. Reiger and M. DeVera for administrative support. This research was supported by the Helen Hay Whitney Foundation postdoctoral fellowship (A.P.F.), the Howard Hughes Medical Institute (HHMI) Gilliam Fellowship for Advanced Studies (E.H.R.), the advanced postdoctoral fellowship of the Swiss National Science Foundation and the Marie Sklodowska-Curie International Outgoing Fellowship (M. J.), National Human Genome Research Institute Centers of Excellence in Genomics Science P50 HG006193 (A.R., N.H., S.A.C.), the Klarman Cell Observatory (A.R.), the Center for RNA Systems Biology (J.S.W.), and HHMI (A.R. and J.S.W.). NR 42 TC 15 Z9 15 U1 4 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD DEC 3 PY 2015 VL 60 IS 5 BP 816 EP 827 DI 10.1016/j.molcel.2015.11.013 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DB1SX UT WOS:000368290300011 PM 26638175 ER PT J AU Chung, YG Matoba, S Liu, YT Eum, JH Lu, FL Jiang, W Lee, JE Sepilian, V Cha, KY Lee, DR Zhang, Y AF Chung, Young Gie Matoba, Shogo Liu, Yuting Eum, Jin Hee Lu, Falong Jiang, Wei Lee, Jeoung Eun Sepilian, Vicken Cha, Kwang Yul Lee, Dong Ryul Zhang, Yi TI Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells SO CELL STEM CELL LA English DT Article ID EMBRYONIC-DEVELOPMENT; IMPLANTATION; PREGNANCY; DISEASE; RATES AB The extremely low efficiency of human embryonic stem cell (hESC) derivation using somatic cell nuclear transfer (SCNT) limits its potential application. Blastocyst formation from human SCNT embryos occurs at a low rate and with only some oocyte donors. We previously showed in mice that reduction of histone H3 lysine 9 trimethylation (H3K9me3) through ectopic expression of the H3K9me3 demethylase Kdm4d greatly improves SCNT embryo development. Here we show that overexpression of a related H3K9me3 demethylase KDM4A improves human SCNT, and that, as in mice, H3K9me3 in the human somatic cell genome is an SCNT reprogramming barrier. Overexpression of KDM4A significantly improves the blastocyst formation rate in human SCNT embryos by facilitating transcriptional reprogramming, allowing efficient derivation of SCNT-derived ESCs using adult Age-related Macular Degeneration (AMD) patient somatic nuclei donors. This conserved mechanistic insight has potential applications for improving SCNT in a variety of contexts, including regenerative medicine. C1 [Chung, Young Gie; Sepilian, Vicken; Lee, Dong Ryul] CHA Hlth Syst, Res Inst Stem Cell Res, Los Angeles, CA 90036 USA. [Chung, Young Gie; Eum, Jin Hee; Lee, Jeoung Eun; Cha, Kwang Yul; Lee, Dong Ryul] CHA Univ, CHA Stem Cell Inst, Seoul 135081, South Korea. [Matoba, Shogo; Liu, Yuting; Lu, Falong; Jiang, Wei; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Matoba, Shogo; Liu, Yuting; Lu, Falong; Jiang, Wei; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Matoba, Shogo; Liu, Yuting; Lu, Falong; Jiang, Wei; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Lee, DR (reprint author), CHA Hlth Syst, Res Inst Stem Cell Res, Los Angeles, CA 90036 USA. EM drleedr@cha.ac.kr; yzhang@genetics.med.harvard.edu RI Jiang, Wei/J-7993-2012; Lu, Falong/Q-3013-2016 OI Jiang, Wei/0000-0002-6463-7356; FU HHMI; Bio & Medical Technology Development Program of NRF and MSIP of Republic of Korea [2012M3A9C6049723, 2015M3A9C6028961]; Cha Medical Foundation in Republic of Korea; Japan Society for the Promotion of Science (JSPS); Juvenile Diabetes Research Foundation [3-2012-293] FX We thank Dr. Luis Tuesta for critical reading of the manuscript; Drs. Sungwook Hong and Yumie Lee for oocyte preparations and donor recruitments, respectively; and Dr. Young Ho Choi for technical help in SCNT. This project is supported by HHMI (to Y.Z.) and the Bio & Medical Technology Development Program (2012M3A9C6049723 and 2015M3A9C6028961) of NRF and MSIP of Republic of Korea (to D.R.L). This project is also partially supported by Cha Medical Foundation in Republic of Korea (to D.R.L). S.M. is supported by a postdoctoral fellowship from the Japan Society for the Promotion of Science (JSPS). W.J. is supported by a Juvenile Diabetes Research Foundation postdoctoral fellowship (3-2012-293). Y.Z. is an Investigator of the Howard Hughes Medical Institute. NR 24 TC 9 Z9 9 U1 4 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD DEC 3 PY 2015 VL 17 IS 6 BP 758 EP 766 DI 10.1016/j.stem.2015.10.001 PG 9 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CY1AS UT WOS:000366139100016 PM 26526725 ER PT J AU Parmar, C Grossmann, P Rietveld, D Rietbergen, MM Lambin, P Aerts, HJWL AF Parmar, Chintan Grossmann, Patrick Rietveld, Derek Rietbergen, Michelle M. Lambin, Philippe Aerts, Hugo J. W. L. TI Radiomic Machine-Learning Classifiers for Prognostic Biomarkers of Head and Neck Cancer SO FRONTIERS IN ONCOLOGY LA English DT Article DE quantitative imaging; radiology; radiomics; cancer; machine learning; computational science ID CELL LUNG-CANCER; TEXTURAL FEATURES; HETEROGENEITY; TUMOR; GLIOBLASTOMA; VARIABILITY; CT; PREDICTION; PARAMETERS; SURVIVAL AB Introduction: "Radiomics" extracts and mines a large number of medical imaging features in a non-invasive and cost-effective way. The underlying assumption of radiomics is that these imaging features quantify phenotypic characteristics of an entire tumor. In order to enhance applicability of radiomics in clinical oncology, highly accurate and reliable machine-learning approaches are required. In this radiomic study, 13 feature selection methods and 11 machine learning classification methods were evaluated in terms of their performance and stability for predicting overall survival in head and neck cancer patients. Methods: Two independent head and neck cancer cohorts were investigated. Training cohort HN1 consisted of 101 head and neck cancer patients. Cohort HN2 (n = 95) was used for validation. A total of 440 radiomic features were extracted from the segmented tumor regions in CT images. Feature selection and classification methods were compared using an unbiased evaluation framework. Results: We observed that the three feature selection methods minimum redundancy maximum relevance (AUG = 0.69, Stability = 0.66), mutual information feature selection (AUG = 0.66, Stability = 0.69), and conditional infomax feature extraction (AUG = 0.68, Stability = 0.7) had high prognostic performance and stability. The three classifiers BY (AUG = 0.67, RSD = 11.28), RF (AUG = 0.61, RSD = 7.36), and NN (AUG = 0.62, RSD = 10.52) also showed high prognostic performance and stability. Analysis investigating performance variability indicated that the choice of classification method is the major factor driving the performance variation (29.02% of total variance). Conclusion: Our study identified prognostic and reliable machine-learning methods for the prediction of overall survival of head and neck cancer patients. Identification of optimal machine-learning methods for radiomics-based prognostic analyses could broaden the scope of radiomics in precision oncology and cancer care. C1 [Parmar, Chintan; Grossmann, Patrick; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Parmar, Chintan; Grossmann, Patrick; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol,Med Sch, Boston, MA 02115 USA. [Parmar, Chintan; Lambin, Philippe] Maastricht Univ, Res Inst GROW, Radiat Oncol MAASTRO, NL-6200 MD Maastricht, Netherlands. [Grossmann, Patrick; Aerts, Hugo J. W. L.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Rietveld, Derek] Vrije Univ Amsterdam, Med Ctr, Dept Radiat Oncol, Amsterdam, Netherlands. [Rietbergen, Michelle M.] Vrije Univ Amsterdam, Med Ctr, Dept Otolaryngol Head & Neck Surg, Amsterdam, Netherlands. RP Parmar, C (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. EM chintan_parmar@dfci.harvard.edu; hugo_aerts@dfci.harvard.edu RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 FU NCI NIH HHS [U01 CA190234, U24 CA194354] NR 43 TC 9 Z9 10 U1 3 U2 22 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2234-943X J9 FRONT ONCOL JI Front. Oncol. PD DEC 3 PY 2015 VL 5 AR 272 DI 10.3389/fonc.2015.00272 PG 10 WC Oncology SC Oncology GA CY3UT UT WOS:000366336100001 PM 26697407 ER PT J AU Kwoh, CK Vina, ER Cloonan, YK Hannon, MJ Boudreau, RM Ibrahim, SA AF Kwoh, C. Kent Vina, Ernest R. Cloonan, Yona K. Hannon, Michael J. Boudreau, Robert M. Ibrahim, Said A. TI Determinants of patient preferences for total knee replacement: African-Americans and whites SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE Osteoarthritis; Knee replacement surgery; Race; Health disparity; Treatment preference ID TOTAL JOINT ARTHROPLASTY; RACIAL-DIFFERENCES; ETHNIC-DIFFERENCES; SOCIAL SUPPORT; UNITED-STATES; OSTEOARTHRITIS; HIP; ARTHRITIS; WILLINGNESS; SURGERY AB Introduction: Patient preferences contribute to marked racial disparities in the utilization of total knee replacement (TKR). The objectives of this study were to identify the determinants of knee osteoarthritis (OA) patients' preferences regarding TKR by race and to identify the variables that may mediate racial differences in willingness to undergo TKR. Methods: Five hundred fourteen White (WH) and 285 African-American (AA) patients with chronic knee pain and radiographic evidence of OA participated in the study. Participants were recruited from the community, an academic medical center, and a Veterans Affairs hospital. Structured interviews were conducted to collect socio-demographics, disease severity, socio-cultural determinants, and treatment preferences. Logistic regression was performed, stratified by race, to identify determinants of preferences. Clinical and socio-cultural factors were entered simultaneously into the models. Stepwise selection identified factors for inclusion in the final models (p < 0.20). Results: Compared to WHs, AAs were less willing to undergo TKR (80 % vs. 62 %, respectively). Better expectations regarding TKR surgery outcomes determined willingness to undergo surgery in both AAs (odds ratio (OR) 2.08, 95 % confidence interval (CI) 0.91-4.79 for 4th vs. 1st quartile) and WHs (OR 5.11, 95 % CI 2.31-11.30 for 4th vs. 1st quartile). Among AAs, better understanding of the procedure (OR 1.80, 95 % CI 0.97-3.35), perceiving a short hospital course (OR 0.81, 95 % CI 0.58-1.13), and believing in less post-surgical pain (OR 0.73, 95 % CI 0.39-1.35) and walking difficulties (OR 0.66, 95 % CI 0.37-1.16) also determined willingness. Among WHs, having surgical discussion with a physician (OR 1.96, 95 % CI 1.05-3.68), not ever receiving surgical referral (OR 0.56, 95 % CI 0.32-0.99), and higher trust in the healthcare system (OR 1.58, 95 % CI 0.75-3.31 for 4th vs. 1st quartile) additionally determined willingness. Among the variables considered, only knowledge-related matters pertaining to TKR attenuated the racial difference in knee OA patients' treatment preference. Conclusions: Expectations of surgical outcomes influence preference for TKR in all patients, but clinical and socio-cultural factors exist that shape marked racial differences in preferences for TKR. Interventions to reduce or eliminate racial disparities in the utilization of TKR should consider and target these factors. C1 [Kwoh, C. Kent; Vina, Ernest R.] Univ Arizona, Sch Med, Tucson, AZ 85724 USA. [Kwoh, C. Kent; Vina, Ernest R.] Univ Arizona, Arthrit Ctr, Tucson, AZ 85724 USA. [Cloonan, Yona K.; Boudreau, Robert M.] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Kwoh, CK (reprint author), Univ Arizona, Sch Med, 1501 N Campbell Ave,POB 245093, Tucson, AZ 85724 USA. EM CKwoh@arthritis.arizona.edu OI Boudreau, Robert/0000-0003-0162-5187; Cloonan, Yona/0000-0003-3893-3693; Vina, Ernest/0000-0001-8135-1731 FU NIH/National Institute of Arthritis and Musculoskeletal Skin Diseases [P60-AR-054731]; K24 Mid-Career Development Award from the National Institute of Arthritis and Musculoskeletal and Skin Disorders [K24AR055259] FX This study was supported by the NIH/National Institute of Arthritis and Musculoskeletal Skin Diseases (Grant P60-AR-054731). Dr. Ibrahim is supported in part by a K24 Mid-Career Development Award from the National Institute of Arthritis and Musculoskeletal and Skin Disorders (K24AR055259). NR 44 TC 3 Z9 3 U1 3 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PD DEC 3 PY 2015 VL 17 AR 348 DI 10.1186/s13075-015-0864-2 PG 11 WC Rheumatology SC Rheumatology GA CX3YJ UT WOS:000365635100001 PM 26635132 ER PT J AU Stransky, N Ghandi, M Kryukov, GV Garraway, LA Lehar, J Liu, M Sonkin, D Kauffmann, A Venkatesan, K Edelman, EJ Riester, M Barretina, J Caponigro, G Schlegel, R Sellers, WR Stegmeier, F Morrissey, M Amzallag, A Pruteanu-Malinici, I Haber, DA Ramaswamy, S Benes, CH Menden, MP Iorio, F Stratton, MR McDermott, U Garnett, MJ Saez-Rodriguez, J AF Stransky, Nicolas Ghandi, Mahmoud Kryukov, Gregory V. Garraway, Levi A. Lehar, Joseph Liu, Manway Sonkin, Dmitriy Kauffmann, Audrey Venkatesan, Kavitha Edelman, Elena J. Riester, Markus Barretina, Jordi Caponigro, Giordano Schlegel, Robert Sellers, William R. Stegmeier, Frank Morrissey, Michael Amzallag, Arnaud Pruteanu-Malinici, Iulian Haber, Daniel A. Ramaswamy, Sridhar Benes, Cyril H. Menden, Michael P. Iorio, Francesco Stratton, Michael R. McDermott, Ultan Garnett, Mathew J. Saez-Rodriguez, Julio CA Drug Sensitivity Canc Cancer Cell Line Broad Inst Novartis Inst Biomed Res Genomics Drug Sensitivity Massachusetts Gen Hosp European Mol Biol Lab European Bioinformatics Inst Wellcome Trust Sanger Inst TI Pharmacogenomic agreement between two cancer cell line data sets SO NATURE LA English DT Article ID DRUG-SENSITIVITY AB Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases. C1 [Stransky, Nicolas; Ghandi, Mahmoud; Kryukov, Gregory V.; Garraway, Levi A.; Broad Inst] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Garraway, Levi A.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol,Dept Med,Med Sch, Boston, MA 02115 USA. [Amzallag, Arnaud; Pruteanu-Malinici, Iulian; Haber, Daniel A.; Ramaswamy, Sridhar; Benes, Cyril H.; Massachusetts Gen Hosp] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Lehar, Joseph; Liu, Manway; Sonkin, Dmitriy; Kauffmann, Audrey; Venkatesan, Kavitha; Edelman, Elena J.; Riester, Markus; Barretina, Jordi; Caponigro, Giordano; Schlegel, Robert; Sellers, William R.; Stegmeier, Frank; Morrissey, Michael; Novartis Inst Biomed Res] Novartis Inst Biorvlecl Res, Cambridge, MA 02139 USA. [Menden, Michael P.; Iorio, Francesco; Saez-Rodriguez, Julio] European Mol Biol Lab, European Bioinformat Inst, Hinxton CB10 1SD, England. [Iorio, Francesco; Stratton, Michael R.; McDermott, Ultan; Garnett, Mathew J.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. RP Garraway, LA (reprint author), Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA. EM Levi_Garraway@dfci.harvard.edu; CBENES@mgh.harvard.edu OI Sonkin, Dmitriy/0000-0002-1649-0652; McDermott, Ultan/0000-0001-9032-4700; Ghandi, Mahmoud/0000-0003-1897-2265; Saez-Rodriguez, Julio/0000-0002-8552-8976 FU Novartis Institutes for BioMedical Research; Wellcome Trust [086357, 102696]; National Institutes of Health [1U54HG006097-01]; Novartis; Dr. Miriam and Sheldon Adelson Medical Research Foundation; Slim Foundation; EMBL-EBI; Wellcome Trust Sanger Institute Post-Doctoral (ESPOD) programme; Cancer Research UK Clinician Scientist Fellowship [A16629] FX We thank T. Golub, E. Lander, S. Schreiber, P. Clemons and J. Engelman for helpful discussions. This work was supported by research grants from the Novartis Institutes for BioMedical Research (CCLE; L.A.G., M.G., and G.V.K.) and by grants from the Wellcome Trust (086357 and 102696; D.A.H., M.R.S., U.M., M.J.G., A. A., C.H.B.) and the National Institutes of Health (1U54HG006097-01, A. A. and C.H.B.). L.A.G. was supported in part by grants from Novartis and the Dr. Miriam and Sheldon Adelson Medical Research Foundation. G.V.K. was supported in part by the Slim Foundation. F.I. was supported in part by the EMBL-EBI and Wellcome Trust Sanger Institute Post-Doctoral (ESPOD) programme, and U.M. was funded by a Cancer Research UK Clinician Scientist Fellowship (A16629). NR 9 TC 2 Z9 2 U1 4 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 3 PY 2015 VL 528 IS 7580 BP 84 EP + DI 10.1038/nature15736 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX3NO UT WOS:000365606000052 ER PT J AU Phillips, A Shroufi, A Vojnov, L Cohn, J Roberts, T Ellman, T Bonner, K Rousseau, C Garnett, G Cambiano, V Nakagawa, F Ford, D Bansi-Matharu, L Miners, A Lundgren, JD Eaton, JW Parkes-Ratanshi, R Katz, Z Maman, D Ford, N Vitoria, M Doherty, M Dowdy, D Nichols, B Murtagh, M Wareham, M Palamountain, KM Musanhu, CC Stevens, W Katzenstein, D Ciaranello, A Barnabas, R Braithwaite, RS Bendavid, E Nathoo, KJ van de Vijver, D Wilson, DP Holmes, C Bershteyn, A Walker, S Raizes, E Jani, I Nelson, LJ Peeling, R Terris-Prestholt, F Murungu, J Mutasa-Apollo, T Hallett, TB Revill, P AF Phillips, Andrew Shroufi, Amir Vojnov, Lara Cohn, Jennifer Roberts, Teri Ellman, Tom Bonner, Kimberly Rousseau, Christine Garnett, Geoff Cambiano, Valentina Nakagawa, Fumiyo Ford, Deborah Bansi-Matharu, Loveleen Miners, Alec Lundgren, Jens D. Eaton, Jeffrey W. Parkes-Ratanshi, Rosalind Katz, Zachary Maman, David Ford, Nathan Vitoria, Marco Doherty, Meg Dowdy, David Nichols, Brooke Murtagh, Maurine Wareham, Meghan Palamountain, Kara M. Musanhu, Christine Chakanyuka Stevens, Wendy Katzenstein, David Ciaranello, Andrea Barnabas, Ruanne Braithwaite, R. Scott Bendavid, Eran Nathoo, Kusum J. van de Vijver, David Wilson, David P. Holmes, Charles Bershteyn, Anna Walker, Simon Raizes, Elliot Jani, Ilesh Nelson, Lisa J. Peeling, Rosanna Terris-Prestholt, Fern Murungu, Joseph Mutasa-Apollo, Tsitsi Hallett, Timothy B. Revill, Paul CA Working Grp Modelling TI Sustainable HIV treatment in Africa through viral-load-informed differentiated care SO NATURE LA English DT Article ID DRIED BLOOD SPOTS; RESOURCE-LIMITED SETTINGS; CD4 CELL COUNT; STRATALL ANRS 12110/ESTHER; NON-INFERIORITY TRIAL; ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; DRUG-RESISTANCE; SOUTH-AFRICA; ASSAY AB There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future. C1 [Phillips, Andrew; Cambiano, Valentina; Nakagawa, Fumiyo; Bansi-Matharu, Loveleen] UCL, Dept Infect & Populat Hlth, London NW3 2PF, England. [Shroufi, Amir; Ellman, Tom; Maman, David] Medecinssans Frontieres MSF SA, SAMU, ZA-7700 Cape Town, South Africa. [Vojnov, Lara; Katz, Zachary; Wareham, Meghan] Clinton Hlth Access Initiat, Boston, MA 02127 USA. [Cohn, Jennifer; Roberts, Teri] Med Sans Frontieres, Access Campaign, CH-1202 Geneva, Switzerland. [Bonner, Kimberly] Med Sans Frontieres, CH-1211 Geneva 21, Switzerland. [Rousseau, Christine; Garnett, Geoff] Bill & Melinda Gates Fdn, Seattle, WA 98199 USA. [Ford, Deborah] UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit, London WC2B 6NH, England. [Miners, Alec] London Sch Hyg & Trop Med, Hlth Serv Res & Policy, London WC1H 9SY, England. [Lundgren, Jens D.] Univ Copenhagen, Rigshosp, Dept Infect Dis, CHIP, DK-92100 Copenhagen, Denmark. [Eaton, Jeffrey W.; Hallett, Timothy B.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London W2 1PG, England. [Parkes-Ratanshi, Rosalind] Makerere Univ, Coll Hlth Sci, IDI, Kampala, Uganda. [Ford, Nathan; Vitoria, Marco; Doherty, Meg] WHO, HIV AIDS & Global Hepatitis Programme, CH-1211 Geneva, Switzerland. [Dowdy, David] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Nichols, Brooke; van de Vijver, David] Erasmus MC, Dept Virosci, NL-3000 CA Rotterdam, Netherlands. [Murtagh, Maurine] Univ London London Sch Hyg & Trop Med, Int Diagnost Ctr, London WC1E 7HT, England. [Palamountain, Kara M.] Northwestern Univ, Kellogg Sch Management, Evanston, IL 60208 USA. [Musanhu, Christine Chakanyuka] WHO Country Off, Harare, Zimbabwe. [Stevens, Wendy] Univ Witwatersrand, Dept Mol Med & Haematol, ZA-2050 Johannesburg, South Africa. [Katzenstein, David] Stanford Univ, Med Ctr, Div Infect Dis, Stanford, CA 94305 USA. [Ciaranello, Andrea] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Barnabas, Ruanne] Univ Washington, Med Global Hlth & Epidemiol, Seattle, WA 98104 USA. [Braithwaite, R. Scott] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. [Bendavid, Eran] Stanford Univ, Dept Med, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Nathoo, Kusum J.] Univ Zimbabwe, Coll Hlth Sci, Dept Paediat & Child Hlth, Harare, Zimbabwe. [Wilson, David P.] Univ New S Wales, Sydney, NSW 2052, Australia. [Holmes, Charles] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Bershteyn, Anna] Inst Dis Modeling, Bellevue, WA 98005 USA. [Walker, Simon; Revill, Paul] Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. [Raizes, Elliot] CDC, Care & Treatment Branch, Ctr Global Hlth, Div Global HIV AIDS GAP, Atlanta, GA 30333 USA. [Jani, Ilesh] Minist Hlth, INS, Maputo, Mozambique. [Nelson, Lisa J.] US Dept State, Off US Global AIDS Coordinator & Hlth Diplomacy S, Washington, DC 20520 USA. [Peeling, Rosanna] London Sch Hyg & Trop Med, Dept Clin Res, London WC1E 7HT, England. [Terris-Prestholt, Fern] London Sch Hyg & Trop Med, Dept Global Hlth & Dev, London WC1H 9SH, England. [Murungu, Joseph; Mutasa-Apollo, Tsitsi] Minist Hlth & Child Care, Harare, Zimbabwe. RP Phillips, A (reprint author), UCL, Dept Infect & Populat Hlth, Rowland Hill St, London NW3 2PF, England. EM andrew.phillips@ucl.ac.uk RI Phillips, Andrew/B-4427-2008; Garnett, Geoffrey/A-9312-2008; OI Phillips, Andrew/0000-0003-2384-4807; Nakagawa, Fumiyo/0000-0002-6646-8744; Lundgren, Jens/0000-0001-8901-7850; Eaton, Jeffrey/0000-0001-7728-728X FU HIV Modelling Consortium; Bill and Melinda Gates Foundation; World Health Organization; HIV Diagnostics Modelling Consortium; Danish National Research Foundation [DNRF:126] FX Funding for the study was received from the HIV Modelling Consortium, the Bill and Melinda Gates Foundation, the World Health Organization and the HIV Diagnostics Modelling Consortium. We are grateful for the use of cluster computing facilities at UCL, Legion@UCL, without which this work would not have been possible. J. L. is supported by the Danish National Research Foundation (DNRF:126). NR 63 TC 16 Z9 16 U1 7 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 3 PY 2015 VL 528 IS 7580 BP S68 EP S76 DI 10.1038/nature16046 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX3NO UT WOS:000365606000013 ER PT J AU Shukla, C Koch, LG Britton, SL Cai, M Hruby, VJ Bednarek, M Novak, CM AF Shukla, C. Koch, L. G. Britton, S. L. Cai, M. Hruby, V. J. Bednarek, M. Novak, C. M. TI CONTRIBUTION OF REGIONAL BRAIN MELANOCORTIN RECEPTOR SUBTYPES TO ELEVATED ACTIVITY ENERGY EXPENDITURE IN LEAN, ACTIVE RATS SO NEUROSCIENCE LA English DT Article DE non-exercise activity thermogenesis (NEAT); obesity; spontaneous physical activity; HCR/LCR ID MELANOCYTE-STIMULATING-HORMONE; EXERCISE ACTIVITY THERMOGENESIS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CORTICOTROPIN-RELEASING HORMONE; SPONTANEOUS PHYSICAL-ACTIVITY; SELECTIVE PEPTIDE AGONISTS; EVALUATION IN-VITRO; BLOOD-PRESSURE; FOOD-INTAKE; METABOLIC SYNDROME AB Physical activity and non-exercise activity thermogenesis (NEAT) are crucial factors accounting for individual differences in body weight, interacting with genetic predisposition. In the brain, a number of neuroendocrine intermediates regulate food intake and energy expenditure (EE); this includes the brain melanocortin (MC) system, consisting of MC peptides as well as their receptors (MCR). MC3R and MC4R have emerged as critical modulators of EE and food intake. To determine how variance in MC signaling may underlie individual differences in physical activity levels, we examined behavioral response to MC receptor agonists and antagonists in rats that show high and low levels of physical activity and NEAT, that is, high-and low-capacity runners (HCR, LCR), developed by artificial selection for differential intrinsic aerobic running capacity. Focusing on the hypothalamus, we identified brain region-specific elevations in expression of MCR 3, 4, and also MC5R, in the highly active, lean HCR relative to the less active and obesity-prone LCR. Further, the differences in activity and associated EE as a result of MCR activation or suppression using specific agonists and antagonists were similarly region-specific and directly corresponded to the differential MCR expression patterns. The agonists and antagonists investigated here did not significantly impact food intake at the doses used, suggesting that the differential pattern of receptor expression may by more meaningful to physical activity than to other aspects of energy balance regulation. Thus, MCR-mediated physical activity may be a key neural mechanism in distinguishing the lean phenotype and a target for enhancing physical activity and NEAT. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Shukla, C.; Novak, C. M.] Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA. [Shukla, C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Koch, L. G.; Britton, S. L.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Koch, L. G.; Britton, S. L.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Cai, M.; Hruby, V. J.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ USA. [Bednarek, M.] MedImmune Ltd, Cambridge, England. RP Shukla, C (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02067 USA. EM charu_shukla@hms.harvard.edu FU AHA [11PRE7320029]; NIH [R01NS055859, R15DK097644-01A1, R01 GM108040]; Office of Research Infrastructure Programs/OD grant from the National Institutes of Health (NIH) [R24OD010950]; Department of Anesthesiology at the University of Michigan, Ann Arbor, Michigan FX C.S. was funded by AHA 11PRE7320029, C.M.N. by NIH R01NS055859 and R15DK097644-01A1, and V.J.H. and M.C. by NIH R01 GM108040. We thank Lydia Heemstra for her help with the Western blots on MC4R rats. The LCR-HCR rat model system was supported by the Office of Research Infrastructure Programs/OD grant R24OD010950 (L.G.K., S.B.) from the National Institutes of Health (NIH). We acknowledge the expert care of the rat colony provided by Molly Kalahar and Lori Heckenkamp. Contact L.G.K. (lgkoch@med.umich.edu) or S.L.B. (brittons@umich.edu) for information on the LCR and HCR rats: these rat models are maintained as an international resource with support from the Department of Anesthesiology at the University of Michigan, Ann Arbor, Michigan. NR 97 TC 2 Z9 2 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD DEC 3 PY 2015 VL 310 BP 252 EP 267 DI 10.1016/j.neuroscience.2015.09.035 PG 16 WC Neurosciences SC Neurosciences & Neurology GA CV3HM UT WOS:000364149800021 PM 26404873 ER PT J AU Zhang, J Wang, CY Chen, X Takada, M Fan, C Zheng, XN Wen, HT Liu, Y Wang, CG Pestell, RG Aird, KM Kaelin, WG Liu, XS Zhang, Q AF Zhang, Jing Wang, Chengyang Chen, Xi Takada, Mamoru Fan, Cheng Zheng, Xingnan Wen, Haitao Liu, Yong Wang, Chenguang Pestell, Richard G. Aird, Katherine M. Kaelin, William G., Jr. Liu, Xiaole Shirley Zhang, Qing TI EglN2 associates with the NRF1-PGC1 alpha complex and controls mitochondrial function in breast cancer SO EMBO JOURNAL LA English DT Article DE EglN2; hypoxia; mitochondria; NRF1; tumorigenesis ID HYPOXIA-INDUCIBLE-FACTOR; PROLYL HYDROXYLASE; INTRACELLULAR-LOCALIZATION; OXIDATIVE-PHOSPHORYLATION; DEOXYNUCLEOTIDE POOLS; OXYGEN-CONSUMPTION; ENERGY-METABOLISM; MAMMALIAN-CELLS; GENE-EXPRESSION; TUMOR HYPOXIA AB The EglN2/PHD1 prolyl hydroxylase is an important oxygen sensor contributing to breast tumorigenesis. Emerging studies suggest that there is functional cross talk between oxygen sensing and mitochondrial function, both of which play an essential role for sustained tumor growth. However, the potential link between EglN2 and mitochondrial function remains largely undefined. Here, we show that EglN2 depletion decreases mitochondrial respiration in breast cancer under normoxia and hypoxia, which correlates with decreased mitochondrial DNA in a HIF1/2 alpha-independent manner. Integrative analyses of gene expression profile and genomewide binding of EglN2 under hypoxic conditions reveal nuclear respiratory factor 1 (NRF1) motif enrichment in EglN2-activated genes, suggesting NRF1 as an EglN2 binding partner. Mechanistically, by forming an activator complex with PGC1 alpha and NRF1 on chromatin, EglN2 promotes the transcription of ferridoxin reductase (FDXR) and maintains mitochondrial function. In addition, FDXR, as one of effectors for EglN2, contributes to breast tumorigenesis in vitro and in vivo. Our findings suggest that EglN2 regulates mitochondrial function in ER alpha-positive breast cancer. C1 [Zhang, Jing; Takada, Mamoru; Fan, Cheng; Zheng, Xingnan; Wen, Haitao; Liu, Yong; Zhang, Qing] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Wang, Chengyang] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Chen, Xi] Baylor Coll Med, Dept Mol & Cellular Biol, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Wen, Haitao] Univ N Carolina, Dept Surg, Chapel Hill, NC USA. [Wang, Chenguang] Chinese Acad Med Sci, Peking Union Med Coll, Inst Radiat Med, Program Radiat Protect & Drug Discovery, Tianjin, Peoples R China. [Pestell, Richard G.] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA. [Pestell, Richard G.] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Aird, Katherine M.] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA. [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Liu, Xiaole Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, Xiaole Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Zhang, Qing] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. RP Zhang, Q (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. EM qing_zhang@med.unc.edu FU NIH [K99/R00 (CA160351)]; University of North Carolina at Chapel Hill; Kimmel Scholar Award; V Foundation Scholar Award; Susan G. Komen Career Catalyst Award; [2R01CA68490] FX The authors thank members of Zhang and Kaelin laboratory for helpful discussions; W. Kimryn Rathmell, Kimberly Briggs, Li Qian, Gang Greg Wang, Jiandong Liu, and Kevin Byrd for critical readings and suggestions. The authors thank Ella Liberzon for providing pSG-TETr-EglN2 fusion plasmid. The authors also want to thank UNC Lineberger comprehensive cancer center functional genomic core facility for technical help. This work has been partially supported by K99/R00 (CA160351) award from NIH (QZ), 2R01CA68490 (WGK), University Cancer Research Fund (QZ) from University of North Carolina at Chapel Hill, Kimmel Scholar Award (QZ), The V Foundation Scholar Award (QZ) and Susan G. Komen Career Catalyst Award (QZ). [Correction added on 2 December 2015 after first online publication: The last sentence has been added to the Acknowledgements section.] NR 71 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD DEC 2 PY 2015 VL 34 IS 23 BP 2953 EP 2970 DI 10.15252/embj.201591437 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DA6LZ UT WOS:000367917600007 PM 26492917 ER PT J AU Sadri-Vakili, G AF Sadri-Vakili, Ghazaleh TI Cocaine triggers epigenetic alterations in the corticostriatal circuit SO BRAIN RESEARCH LA English DT Review DE Epigenetics; Cocaine; DNA methylation; Histone modifications; Micro RNA; Transgenerational inheritance ID DNA METHYLATION; GENE-EXPRESSION; HISTONE METHYLATION; DRUG-ADDICTION; INDUCED PLASTICITY; NUCLEUS-ACCUMBENS; BEHAVIORAL-RESPONSES; CHROMATIN REGULATION; SYNAPTIC PLASTICITY; NEURONAL PLASTICITY AB Acute and repeated exposure to cocaine induces long-lasting alterations in neural networks that underlie compulsive drug seeking and taking. Cocaine exposure triggers complex adaptations in the brain that are mediated by dynamic patterns of gene expression that are translated into enduring changes. Recently, epigenetic modifications have been unveiled as critical mechanisms underlying addiction that contribute to drug-induced plasticity by regulating gene expression. These alterations are also now linked to the heritability of cocaine-induced phenotypes. This review focuses on how changes in the epigenome, such as altered DNA methylation, histone modifications, and microRNAs, regulate transcription of specific genes that contribute to cocaine addiction. This article is part of a Special Issue entitled SI:Addiction circuits. (C) 2014 Elsevier B.V. All rights reserved. C1 [Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Sadri-Vakili, G (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM gsadrivakili@mgh.harvard.edu FU NIH [DA033641] FX G.S-V. is supported by NIH, DA033641. NR 111 TC 3 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD DEC 2 PY 2015 VL 1628 SI SI BP 50 EP 59 DI 10.1016/j.brainres.2014.09.069 PN A PG 10 WC Neurosciences SC Neurosciences & Neurology GA CZ9IV UT WOS:000367412200006 PM 25301690 ER PT J AU Hanlon, CA Dowdle, LT Austelle, CW DeVries, W Mithoefer, O Badran, BW George, MS AF Hanlon, Colleen A. Dowdle, Logan T. Austelle, Christopher W. DeVries, William Mithoefer, Oliver Badran, Bashar W. George, Mark S. TI What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals SO BRAIN RESEARCH LA English DT Article DE Brain stimulation; Functional MRI; Orbitofrontal cortex; BA 10; Caudate ID TRANSCRANIAL MAGNETIC STIMULATION; MEDIAL PREFRONTAL CORTEX; HUMAN MOTOR CORTEX; HF-RTMS SESSION; SYNAPTIC PLASTICITY; COCAINE DEPENDENCE; ALCOHOL DEPENDENCE; CIGARETTE-SMOKING; BASAL GANGLIA; ADDICTION AB Vulnerability to drug related cues is one of the leading causes for continued use and relapse among substance dependent individuals. Using drugs in the face of cues may be associated with dysfunction in at least two frontal-striatal neural circuits: (1) elevated activity in medial and ventral areas that govern limbic arousal (including the medial prefrontal cortex (MPFC) and ventral striatum) or (2) depressed activity in dorsal and lateral areas that govern cognitive control (including the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum): Transcranial magnetic stimulation (TMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. To date however, nearly all repetitive TMS studies in addiction have focused on amplifying activity in frontal-striatal circuits that govern cognitive control. This manuscript reviews recent work using TMS as a tool to decrease craving for multiple substances and provides a theoretical model for how clinical researchers might approach target and frequency selection for TMS of addiction. To buttress this model, preliminary data from a single-blind, sham-controlled, crossover study of 11 cocaine-dependent individuals is also presented. These results suggest that attenuating MPFC activity through theta burst stimulation decreases activity in the striatum and anterior insula. It is also more likely to attenuate craving than sham TMS. Hence, while many TMS studies are focused on applying LTP-like stimulation to the DLPFC, the MPFC might be a new, efficacious, and treatable target for craving in cocaine dependent individuals. This article is part of a Special Issue entitled SI:Addiction circuits. (C) 2015 Published by Elsevier B.V. C1 [Hanlon, Colleen A.; Dowdle, Logan T.; Austelle, Christopher W.; DeVries, William; Mithoefer, Oliver; Badran, Bashar W.; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Hanlon, Colleen A.; Dowdle, Logan T.; Badran, Bashar W.; George, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC USA. [Hanlon, Colleen A.; George, Mark S.] Med Univ S Carolina, Ctr Biomed Imaging, Charleston, SC USA. [George, Mark S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Hanlon, CA (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. EM hanlon@musc.edu OI Dowdle, Logan/0000-0002-1879-705X FU NIH [K01DA027756, R01DA036617, P50 DA015369, P50 AA010761] FX This effort was funded directly by NIH Grants K01DA027756 (Hanlon), R01DA036617 (Hanlon), P50 DA015369 (Kalivas), P50 AA010761 (Becker). Additional assistance was given by the South Carolina Translational Research Institute UL1 TR000062 and R25 DA033680. The authors would also like to acknowledge the Neuroscience Institute at the Medical University of South Carolina, the Neurobiology of Addiction Research Center, the Center for Biomedical Imaging, Truman R. Brown, Jayce Doose, James Purl, Melanie Canterberry, and Kathleen Brady, all of whom provided intellectual support and resources for this endeavor. NR 65 TC 8 Z9 8 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD DEC 2 PY 2015 VL 1628 SI SI BP 199 EP 209 DI 10.1016/j.brainres.2015.02.053 PN A PG 11 WC Neurosciences SC Neurosciences & Neurology GA CZ9IV UT WOS:000367412200018 PM 25770818 ER PT J AU Achar, YJ Balogh, D Neculai, D Juhasz, S Morocz, M Gali, H Dhe-Paganon, S Venclovas, C Haracska, L AF Achar, Yathish Jagadheesh Balogh, David Neculai, Dante Juhasz, Szilvia Morocz, Monika Gali, Himabindu Dhe-Paganon, Sirano Venclovas, Ceslovas Haracska, Lajos TI Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-DAMAGE TOLERANCE; BLOOMS SYNDROME HELICASE; CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; CRYSTAL-STRUCTURE; UBIQUITIN LIGASE; PROTEIN; REVERSAL; RAD5 AB Defects in the ability to respond properly to an unrepaired DNA lesion blocking replication promote genomic instability and cancer. Human HLTF, implicated in error-free replication of damaged DNA and tumour suppression, exhibits a HIRAN domain, a RING domain, and a SWI/SNF domain facilitating DNA-binding, PCNA-polyubiquitin-ligase, and dsDNA-translocase activities, respectively. Here, we investigate the mechanism of HLTF action with emphasis on its HIRAN domain. We found that in cells HLTF promotes the filling-in of gaps left opposite damaged DNA during replication, and this postreplication repair function depends on its HIRAN domain. Our biochemical assays show that HIRAN domain mutant HLTF proteins retain their ubiquitin ligase, ATPase and dsDNA translocase activities but are impaired in binding to a model replication fork. These data and our structural study indicate that the HIRAN domain recruits HLTF to a stalled replication fork, and it also provides the direction for the movement of the dsDNA translocase motor domain for fork reversal. In more general terms, we suggest functional similarities between the HIRAN, the OB, the HARP2, and other domains found in certain motor proteins, which may explain why only a subset of DNA translocases can carry out fork reversal. C1 [Achar, Yathish Jagadheesh; Balogh, David; Juhasz, Szilvia; Gali, Himabindu; Dhe-Paganon, Sirano; Haracska, Lajos] Hungarian Acad Sci, Inst Genet, Biol Res Ctr, H-6726 Szeged, Hungary. [Neculai, Dante] Zhejiang Univ, Hangzhou 310058, Zhejiang, Peoples R China. [Dhe-Paganon, Sirano] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Venclovas, Ceslovas] Vilnius State Univ, Inst Biotechnol, LT-02241 Vilnius, Lithuania. RP Haracska, L (reprint author), Hungarian Acad Sci, Inst Genet, Biol Res Ctr, Temesvari Krt 62, H-6726 Szeged, Hungary. EM haracska@brc.hu RI Neculai, Dante/A-9923-2011 FU European Union; European Social Fund [TAMOP 4.2.4.A/2-11-1-2012-0001]; Hungarian Science Foundation [OTKA 101225, GOP-1.1.1-11.2012-0384]; State of Hungary FX European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TAMOP 4.2.4.A/2-11-1-2012-0001 'National Excellence Program'; Hungarian Science Foundation [OTKA 101225 and GOP-1.1.1-11.2012-0384]. Funding for open access charge: Hungarian Science Foundation [OTKA 101225]. NR 47 TC 3 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 2 PY 2015 VL 43 IS 21 BP 10277 EP 10291 DI 10.1093/nar/gkv896 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CY4WZ UT WOS:000366410900027 PM 26350214 ER PT J AU Richardson, PG Krishnan, A Giralt, S Soiffer, RJ AF Richardson, Paul G. Krishnan, Amrita Giralt, Sergio Soiffer, Robert J. TI Defibrotide for the treatment of severe hepatic veno-occlusive disease/sinusoidal obstruction syndrome: evidence for clinical benefit SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Article DE antithrombotic activity; defibrotide; endothelial dysfunction; hematopoietic stem cell transplant; hyperbilirubinemia; multi-organ failure; pro-fibrinolysis; prophylaxis; sinusoidal obstruction syndrome; treatment; veno-occlusive disease ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; INTRAHEPATIC PORTOSYSTEMIC SHUNT; TISSUE-PLASMINOGEN-ACTIVATOR; SUBGROUP SURVIVAL ANALYSIS; RENAL-DISEASE PATIENTS; HIGH-RISK POPULATION; ENDOTHELIAL-CELLS; OPEN-LABEL; SIGNIFICANT TOXICITY AB Introduction: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), characterized by hepatic sinusoidal endothelial damage and liver dysfunction, is an unpredictable and potentially life-threatening complication of hematopoietic stem cell transplantation that occurs in an estimated 14% of these patients (range 0 - 62.3%). VOD/SOS typically occurs following high-dose radiotherapy and/or chemotherapy as conditioning. Although mild/moderate VOD/SOS may not progress in some patients and may resolve at an early stage (i.e., within 2 or 3weeks), in others it develops into severe VOD/SOS, commonly identified by the presence of multi-organ failure (defined by pulmonary and/or renal dysfunction), which, in turn, is associated with mortality rates >80%.Areas covered: This review of severe hepatic VOD/SOS discusses the disease characteristics, diagnostic criteria, prevalence, pathogenesis and current treatment guidelines for VOD/SOS, as well as prophylactic measures. The clinical trial evidence for associated therapies is reviewed, along with evaluations of these therapies by VOD/SOS expert consensus groups. Defibrotide, the only medication approved for the treatment of severe VOD/SOS in the European Union, is discussed in detail with regard to chemistry, pharmacodynamics/pharmacokinetics, proposed mechanisms of action and evidence from clinical trials of efficacy and safety.Expert opinion: Clinical data show that defibrotide reduces the mortality associated with VOD/SOS. Given the lack of therapeutic options and the favorable benefit/risk profile of defibrotide, this agent may therefore help fill an important and unmet therapeutic need. C1 [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Krishnan, Amrita] City Hope Natl Med Ctr, Multiple Myeloma Program, Med Educ & Training Hematol & Hematopoiet Cell Tr, Duarte, CA 91010 USA. [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, Adult Bone Marrow Transplant Serv, New York, NY 10065 USA. [Soiffer, Robert J.] Harvard Univ, Div Hematol Malignancies, Stem Cell Transplantat, Dana Farber Canc Inst,Med Sch,Dept Med Oncol, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 73 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD DEC 2 PY 2015 VL 3 IS 12 BP 1491 EP 1501 DI 10.1517/21678707.2015.1114455 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CY4GT UT WOS:000366367300002 ER PT J AU Smith, EH Banks, GP Mikell, CB Cash, SS Patel, SR Eskandar, EN Sheth, SA AF Smith, Elliot H. Banks, Garrett P. Mikell, Charles B. Cash, Syndey S. Patel, Shaun R. Eskandar, Emad N. Sheth, Sameer A. TI Frequency-Dependent Representation of Reinforcement-Related Information in the Human Medial and Lateral Prefrontal Cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE electrocorticography; feedback-related negativity; frontal midline theta; information representation; prefrontal cortex; reinforcement ID ANTERIOR CINGULATE CORTEX; ERROR-RELATED-NEGATIVITY; FRONTAL MIDLINE THETA; PREDICTION ERROR; ELECTROPHYSIOLOGICAL RESPONSES; BEHAVIORAL ADAPTATION; INTEGRATIVE THEORY; COGNITIVE CONTROL; BRAIN POTENTIALS; FEEDBACK AB The feedback-related negativity (FRN) is a commonly observed potential in scalp electroencephalography (EEG) studies related to the valence of feedback about a subject's performance. This potential classically manifests as a negative deflection in medial frontocentral EEG contacts following negative feedback. Recent work has shown prominence of theta power in the spectral composition of the FRN, placing it within the larger class of "frontal midline theta" cognitive control signals. Although the dorsal anterior cingulate cortex (dACC) is thought to be the cortical generator of the FRN, conclusive data regarding its origin and propagation are lacking. Here we examine intracranial electrophysiology from the human medial and lateral prefrontal cortex (PFC) to better understand the anatomical localization and communication patterns of the FRN. We show that the FRN is evident in both low-and high-frequency local field potentials (LFPs) recorded on electrocorticography. The FRN is larger in medial compared with lateral PFC, and coupling between theta band phase and high-frequency LFP power is also greater in medial PFC. Using Granger causality and conditional mutual information analyses, we provide evidence that feedback-related information propagates from medial to lateral PFC, and that this information transfer oscillates with theta-range periodicity. These results provide evidence for the dACC as the cortical source of the FRN, provide insight into the local computation of frontal midline theta, and have implications for reinforcement learning models of cognitive control. C1 [Smith, Elliot H.; Banks, Garrett P.; Mikell, Charles B.; Sheth, Sameer A.] Columbia Univ, Med Ctr, Dept Neurol Surg, New York, NY 10032 USA. [Cash, Syndey S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Patel, Shaun R.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Sheth, SA (reprint author), 710 West 168th St,Room 551, New York, NY 10032 USA. EM ss4451@cumc.columbia.edu FU NIH [K12 NS080223]; Dana Foundation FX This work supported by NIH Grants K12 NS080223 and the Dana Foundation. We thank Jennifer Russo for help collecting data; and Lucia Melloni, Saskia Haegens, Guillermo Horga, Nima Mesgarani, and Charles Schroeder for helpful developmental advice. NR 75 TC 2 Z9 2 U1 1 U2 10 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 DEC 2 PY 2015 VL 35 IS 48 BP 15827 EP 15836 DI 10.1523/JNEUROSCI.1864-15.2015 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CX9WD UT WOS:000366055500006 PM 26631465 ER PT J AU Vuong, HE Hardi, CN Barnes, S Brecha, NC AF Vuong, Helen E. Hardi, Claudia N. Barnes, Steven Brecha, Nicholas C. TI Parallel Inhibition of Dopamine Amacrine Cells and Intrinsically Photosensitive Retinal Ganglion Cells in a Non-Image-Forming Visual Circuit of the Mouse Retina SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amacrine cells; dopamine; interneuron; melanopsin ipRGCs; microcircuit; somatostatin ID SUBTYPE 2A EXPRESSION; ROD BIPOLAR CELLS; CONE PHOTORECEPTORS; MAMMALIAN RETINA; RABBIT RETINA; RAT RETINA; RECEPTOR ACTIVATION; CALCIUM-CHANNELS; MELANOPSIN CELLS; CIRCADIAN CLOCK AB An inner retinal microcircuit composed of dopamine (DA)-containing amacrine cells and melanopsin-containing, intrinsically photosensitive retinal ganglion cells (M1 ipRGCs) process information about the duration and intensity of light exposures, mediating light adaptation, circadian entrainment, pupillary reflexes, and other aspects of non-image-forming vision. The neural interaction is reciprocal: M1 ipRGCs excite DA amacrine cells, and these, in turn, feed inhibition back onto M1 ipRGCs. We found that the neuropeptide somatostatin [somatotropin release inhibiting factor (SRIF)] also inhibits the intrinsic light response of M1 ipRGCs and postulated that, to tune the bidirectional interaction of M1 ipRGCs and DA amacrine cells, SRIF amacrine cells would provide inhibitory modulation to both cell types. SRIF amacrine cells, DA amacrine cells, and M1 ipRGCs form numerous contacts. DA amacrine cells and M1 ipRGCs express the SRIF receptor subtypes sst(2A) and sst(4) respectively. SRIF modulation of the microcircuit was investigated with targeted patch-clamp recordings of DA amacrine cells in TH-RFP mice and M1 ipRGCs in OPN4-EGFP mice. SRIF increases K+ currents, decreases Ca2+ currents, and inhibits spike activity in both cell types, actions reproduced by the selective sst(2A) agonist L-054,264 (N-[(1R)-2-[[[(1S*,3R*)-3-(aminomethyl)cyclohexyl]methyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]spiro[1H-indene-1,4'-piperidine]-1'-carboxamide) in DA amacrine cells and the selective sst(4) agonist L-803,087 (N-2-[4-(5,7-difluoro-2-phenyl-1H-indol-3-yl)-1-oxobutyl]-l-arginine methyl ester trifluoroacetate) in M1 ipRGCs. These parallel actions of SRIF may serve to counteract the disinhibition of M1 ipRGCs caused by SRIF inhibition of DA amacrine cells. This allows the actions of SRIF on DA amacrine cells to proceed with adjusting retinal DA levels without destabilizing light responses by M1 ipRGCs, which project to non-image-forming targets in the brain. C1 [Vuong, Helen E.; Hardi, Claudia N.; Barnes, Steven; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Vuong, Helen E.; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol Cellular & Integrat Physiol, Los Angeles, CA 90095 USA. [Vuong, Helen E.; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, CURE: Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Barnes, Steven] Dalhousie Univ, Dept Physiol & Biophys, Halifax, NS B3H 4R2, Canada. [Barnes, Steven] Dalhousie Univ, Dept Ophthalmol & Visual Sci, Halifax, NS B3H 4R2, Canada. [Barnes, Steven; Brecha, Nicholas C.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Brecha, NC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM nbrecha@ucla.edu FU National Institutes of Health [R01 EY04067, T32 EY007026, P30 DK41301]; Veterans Administration Merit Review; Plum Foundation; Canadian Institutes of Health Research-Nova Scotia Health Research Foundation Regional Partnership Program [MOP-10968]; Natural Sciences and Engineering Research Council of Canada Discovery Award [194640]; Whitcome Summer Undergraduate Research Fellowship FX This work was supported by National Institutes of Health Grants R01 EY04067 (N.C.B.), T32 EY007026 (H.E.V.), and P30 DK41301 (Imaging and Stem Cell Biology Core; CURE: Digestive Diseases Research Center), a Veterans Administration Merit Review (N.C.B.), the Plum Foundation (S.B. and N.C.B.), Canadian Institutes of Health Research-Nova Scotia Health Research Foundation Regional Partnership Program MOP-10968 (S.B.), a Natural Sciences and Engineering Research Council of Canada Discovery Award 194640 (S.B.), and a Whitcome Summer Undergraduate Research Fellowship (C.N.H.). N.C.B. is a Veterans Administration Career Research Scientist. We thank Dr. Douglas McMahon for providing the TH-RFP mouse line, Dr. David Berson for providing the OPN4-EGFP mouse line, and Drs. Kristopher G. Sheets, Arlene A. Hirano, and Luis Perez de Sevilla Muller for assistance with data interpretation and comments on this manuscript. NR 68 TC 3 Z9 3 U1 3 U2 15 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 DEC 2 PY 2015 VL 35 IS 48 BP 15955 EP 15970 DI 10.1523/JNEUROSCI.3382-15.2015 PG 16 WC Neurosciences SC Neurosciences & Neurology GA CX9WD UT WOS:000366055500017 PM 26631476 ER PT J AU Suzuki, R Kikuchi, S Harada, T Mimura, N Minami, J Ohguchi, H Yoshida, Y Sagawa, M Gorgun, G Cirstea, D Cottini, F Jakubikova, J Tai, YT Chauhan, D Richardson, PG Munshi, N Ando, K Utsugi, T Hideshima, T Anderson, KC AF Suzuki, Rikio Kikuchi, Shohei Harada, Takeshi Mimura, Naoya Minami, Jiro Ohguchi, Hiroto Yoshida, Yasuhiro Sagawa, Morihiko Gorgun, Gullu Cirstea, Diana Cottini, Francesca Jakubikova, Jana Tai, Yu-Tzu Chauhan, Dharminder Richardson, Paul G. Munshi, Nikhil Ando, Kiyoshi Utsugi, Teruhiro Hideshima, Teru Anderson, Kenneth C. TI Combination of a Selective HSP90 alpha/beta Inhibitor and a RAS-RAF-MEK-ERK Signaling Pathway Inhibitor Triggers Synergistic Cytotoxicity in Multiple Myeloma Cells SO PLOS ONE LA English DT Article ID PROTEIN 90 INHIBITOR; PHASE-I; ANTITUMOR ACTIVITIES; DRUG-RESISTANCE; BRAF INHIBITION; HSP90 INHIBITOR; CANCER; MELANOMA; THERAPY; KINASE AB Heat shock protein (HSP) 90 inhibitors have shown significant anti-tumor activities in preclinical settings in both solid and hematological tumors. We previously reported that the novel, orally available HSP90 alpha/beta inhibitor TAS-116 shows significant anti-MM activities. In this study, we further examined the combination effect of TAS-116 with a RAS-RAF-MEK-ERK signaling pathway inhibitor in RAS-or BRAF-mutated MM cell lines. TAS-116 monotherapy significantly inhibited growth of RAS-mutated MM cell lines and was associated with decreased expression of downstream target proteins of the RAS-RAF-MEK-ERK signaling pathway. Moreover, TAS-116 showed synergistic growth inhibitory effects with the farnesyltransferase inhibitor tipifarnib, the BRAF inhibitor dabrafenib, and the MEK inhibitor selumetinib. Importantly, treatment with these inhibitors paradoxically enhanced p-C-Raf, p-MEK, and p-ERK activity, which was abrogated by TAS-116. TAS-116 also enhanced dabrafenib-induced MM cytotoxicity associated with mitochondrial damage-induced apoptosis, even in the BRAF-mutated U266 MM cell line. This enhanced apoptosis in RAS-mutated MM triggered by combination treatment was observed even in the presence of bone marrow stromal cells. Taken together, our results provide the rationale for novel combination treatment with HSP90 alpha/beta inhibitor and RAS-RAF-MEK-ERK signaling pathway inhibitors to improve outcomes in patients with in RAS-or BRAF-mutated MM. C1 [Suzuki, Rikio; Kikuchi, Shohei; Harada, Takeshi; Mimura, Naoya; Minami, Jiro; Ohguchi, Hiroto; Yoshida, Yasuhiro; Sagawa, Morihiko; Gorgun, Gullu; Cirstea, Diana; Cottini, Francesca; Jakubikova, Jana; Tai, Yu-Tzu; Chauhan, Dharminder; Richardson, Paul G.; 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. [Suzuki, Rikio; Ando, Kiyoshi] Tokai Univ, Sch Med, Dept Hematol Oncol, Isehara, Kanagawa 25911, Japan. [Utsugi, Teruhiro] Taiho Pharmaceut Co Ltd, Tsukuba Res Ctr, Tsukuba, Ibaraki, Japan. [Munshi, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, VA Boston Healthcare Syst,Jerome Lipper Multiple, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU National Institutes of Health [P50-100707, PO1-CA078378, PO1-155258, RO1-CA050947, RO1-178264, IO1-BX001584]; SENSHIN Medical Research Foundation FX This study was supported by the National Institutes of Health Grants (http://grants.nih.gov/grants/oer.htm) P50-100707, PO1-CA078378, and PO1-155258 (K.C.A., N.M.); RO1-CA050947 (K.C.A.) and RO1-178264 (T.H., K.C.A.); IO1-BX001584 (N.M.); and SENSHIN Medical Research Foundation (http://www.mt-pharma.co.jp/zaidan/) (R.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 3 Z9 3 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 2 PY 2015 VL 10 IS 12 AR e0143847 DI 10.1371/journal.pone.0143847 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX8BI UT WOS:000365926300111 PM 26630652 ER PT J AU Harrington, KJ Puzanov, I Hecht, JR Hodi, FS Szabo, Z Murugappan, S Kaufman, HL AF Harrington, Kevin J. Puzanov, Igor Hecht, J. Randolph Hodi, F. Stephen Szabo, Zsolt Murugappan, Swami Kaufman, Howard L. TI Clinical development of talimogene laherparepvec (T-VEC): a modified herpes simplex virus type-1-derived oncolytic immunotherapy SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE GM-CSF; Immune checkpoint inhibitors; Immunotherapy; Intralesional therapy; Melanoma; Oncolytic virus; Talimogene laherparepvec ID COLONY-STIMULATING FACTOR; METASTATIC MELANOMA; STAGE-III; TUMOR-IMMUNOTHERAPY; UNTREATED MELANOMA; GM-CSF; THERAPY; CANCER; IPILIMUMAB; PEMBROLIZUMAB AB Tumor immunotherapy is emerging as a promising new treatment option for patients with cancer. T-VEC is an intralesional oncolytic virus therapy based on a modified herpes simplex virus type-1. T-VEC selectively targets tumor cells, causing regression in injected lesions and inducing immunologic responses that mediate regression at uninjected/distant sites. In a randomized phase III trial, T-VEC met its primary endpoint of improving the durable response rate vs granulocyte-macrophage colony-stimulating factor in patients with unresectable melanoma. Responses were observed in injected and uninjected regional and visceral lesions. Exploratory analyses suggested survival differences in favor of T-VEC in patients with untreated or stage IIIB/IIIC/IVM1a disease. T-VEC was generally well tolerated, the most common adverse events being flu-like symptoms. Here, we overview recent advances in cancer immunotherapy, focusing on the clinical development of T-VEC, from first-in-human studies and studies in other cancer types, to ongoing combination trials with checkpoint inhibitors. C1 [Puzanov, Igor] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA. [Hecht, J. Randolph] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Ctr, Boston, MA 02115 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Ctr Immuno Oncol, Boston, MA 02115 USA. [Szabo, Zsolt] Amgen Europe GmbH, Dept Oncol, Zug, Switzerland. [Murugappan, Swami] Amgen Inc, Dept Oncol, Thousand Oaks, CA 91320 USA. [Kaufman, Howard L.] Rutgers Canc Inst New Jersey, Div Surg Oncol, New Brunswick, NJ USA. RP Harrington, KJ (reprint author), Royal Marsden Hosp, Inst Canc Res, NIHR Biomed Res Ctr, London SW3 6JJ, England. EM Kevin.Harrington@icr.ac.uk FU Amgen; RM/ICR NIHR Biomedical Research Centre FX KJH has acted as a consultant/in an advisory role for Amgen, Genelux Corp., Lytix, Oncolytics Biotech, Oncos Therapeutics, Viralytics. IP has acted as a consultant/in an advisory role for Amgen and has also received research support from Amgen. JRH has received honorarium and participated in advisory boards for Amgen and has received research funding (to institution) from Amgen. KJH acknowledges support from the RM/ICR NIHR Biomedical Research Centre. NR 64 TC 8 Z9 8 U1 8 U2 21 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD DEC 2 PY 2015 VL 15 IS 12 BP 1389 EP 1403 DI 10.1586/14737140.2015.1115725 PG 15 WC Oncology SC Oncology GA CX5DI UT WOS:000365721500001 PM 26558498 ER PT J AU Brown, JR Tesar, B Yu, LJ Werner, L Takebe, N Mikler, E Reynolds, HM Thompson, C Fisher, DC Neuberg, D Freedman, AS AF Brown, Jennifer R. Tesar, Bethany Yu, Lijian Werner, Lillian Takebe, Naoko Mikler, Evgeny Reynolds, Hazel M. Thompson, Christina Fisher, David C. Neuberg, Donna Freedman, A. S. TI Obatoclax in combination with fludarabine and rituximab is well-tolerated and shows promising clinical activity in relapsed chronic lymphocytic leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE Chronic lymphocytic leukemia; phase I-III trials; obatoclax; BCL-2; fludarabine; rituximab ID PAN-BCL-2 FAMILY ANTAGONIST; MIMETIC GX15-070 OBATOCLAX; PROGRESSION-FREE SURVIVAL; MESYLATE GX15-070; OPEN-LABEL; PHASE-I; CELLS; CYCLOPHOSPHAMIDE; INHIBITOR; APOPTOSIS AB Obatoclax is a small molecule mimetic of the BH3 domain of BCL-2 family proteins. This phase 1 study combining obatoclax with FR was undertaken in chronic lymphocytic leukemia (CLL) patients relapsed after at least one prior therapy. Obatoclax was given as a 3-h infusion on days 1 and 3 and escalated through three dose levels, with standard dose FR days 1-5. Thirteen patients were enrolled, with a median of two prior therapies. One dose-limiting toxicity (DLT) of a 2-week treatment delay for persistent grade 2-3 neutropenia was observed at the highest obatoclax dose (20 mg/m(2)), but no maximum tolerated dose (MTD) was reached. The overall response rate (ORR) was 85%, with 15% complete responses (CRs) by NCI-96 criteria and 54% by IWCLL 2008 criteria. Median time to progression was 20 months. It is concluded that obatoclax can be safely administered to relapsed CLL patients in combination with FR and shows promising clinical activity. C1 [Brown, Jennifer R.; Tesar, Bethany; Yu, Lijian; Mikler, Evgeny; Reynolds, Hazel M.; Thompson, Christina; Fisher, David C.; Freedman, A. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Brown, Jennifer R.; Tesar, Bethany; Yu, Lijian; Fisher, David C.; Freedman, A. S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Takebe, Naoko] NCI, Invest Drug Branch, NIH, Bethesda, MD 20892 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jbrown2@partners.org FU NIH [K23 CA115682-01]; Scholar in Clinical Research of the Leukemia and Lymphoma Society FX We are indebted to the nurses and clinical research staff of the Dana-Farber Cancer Institute for their excellent care of these patients and to the patients for their participation in this study. JRB was supported by NIH grant K23 CA115682-01 and is a Scholar of the American Society of Hematology as well as a Scholar in Clinical Research of the Leukemia and Lymphoma Society. NR 39 TC 3 Z9 3 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC 2 PY 2015 VL 56 IS 12 BP 3336 EP 3342 DI 10.3109/10428194.2015.1048441 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA CX2IX UT WOS:000365521500017 PM 25971907 ER PT J AU Tandon, B Swerdlow, SH Hasserjian, RP Surti, U Gibson, SE AF Tandon, Bevan Swerdlow, Steven H. Hasserjian, Robert P. Surti, Urvashi Gibson, Sarah E. TI Chronic lymphocytic leukemia/small lymphocytic lymphoma: another neoplasm related to the B-cell follicle? SO LEUKEMIA & LYMPHOMA LA English DT Article DE B-cell follicle; chronic lymphocytic leukemia; small lymphocytic lymphoma (CLL/SLL); follicular dendritic cells ID BONE-MARROW INVOLVEMENT; GERMINAL-CENTERS; DENDRITIC CELLS; PHENOTYPE; SECTIONS; EXPRESS; REVEALS; GENES AB Although there has been increased attention paid to the critical nature of nodal involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the B-cell compartment it is most closely related to and its relationship to the follicle remain uncertain. A clinicopathologic investigation of 60 extramedullary biopsies of LEF1+ CLL/SLL, including 29 cases with perifollicular/follicular (PF/F) growth, was therefore performed. A subset of PF/F cases demonstrated inner mantle zone preservation or intra-mantle zone growth. All PF/F and 16/31 other cases contained CD21+ follicular dendritic cells. No cytogenetic, IGHV mutational or gene usage differences were seen between PF/F and diffuse cases. PF/F cases were more often kappa positive (p < 0.03) and had fewer involved nodal sites (p = 0.0004). These findings suggest that at least a subset of bona fide CLL/SLL is related to the follicle, most likely the outer mantle zone, and that at least a subset of the diffuse cases may represent "later" disease. C1 [Tandon, Bevan; Swerdlow, Steven H.; Surti, Urvashi; Gibson, Sarah E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gibson, SE (reprint author), UPMC Presbyterian Hosp, 200 Lothrop St,Room G-314, Pittsburgh, PA 15213 USA. EM gibsonse@upmc.edu NR 32 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC 2 PY 2015 VL 56 IS 12 BP 3378 EP 3386 DI 10.3109/10428194.2015.1037759 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CX2IX UT WOS:000365521500023 PM 25860247 ER PT J AU Wu, JN Pinello, L Yissachar, E Wischhusen, JW Yuan, GC Roberts, CWM AF Wu, Jennifer N. Pinello, Luca Yissachar, Elinor Wischhusen, Jonathan W. Yuan, Guo-Cheng Roberts, Charles W. M. TI Functionally distinct patterns of nucleosome remodeling at enhancers in glucocorticoid-treated acute lymphoblastic leukemia SO EPIGENETICS & CHROMATIN LA English DT Article DE Chromatin remodeling; Nucleosome; Glucocorticoid receptor; Transcription enhancer; Transcription regulation; ChIP-seq ID HUMAN GENOME; CHROMATIN ACCESSIBILITY; REGULATORY ELEMENTS; GENE-EXPRESSION; RECEPTOR; DYNAMICS; RESISTANCE; VISUALIZATION; DETERMINANTS; ORGANIZATION AB Background: Precise nucleosome positioning is an increasingly recognized feature of promoters and enhancers, reflecting complex contributions of DNA sequence, nucleosome positioning, histone modification and transcription factor binding to enhancer activity and regulation of gene expression. Changes in nucleosome position and occupancy, histone variants and modifications, and chromatin remodeling are also critical elements of dynamic transcriptional regulation, but poorly understood at enhancers. We investigated glucocorticoid receptor-associated (GR) nucleosome dynamics at enhancers in acute lymphoblastic leukemia. Results: For the first time, we demonstrate functionally distinct modes of nucleosome remodeling upon chromatin binding by GR, which we term central, non-central, phased, and minimal. Central and non-central remodeling reflect nucleosome eviction by GR and cofactors, respectively. Phased remodeling involves nucleosome repositioning and is associated with rapidly activated enhancers and induction of gene expression. Minimal remodeling sites initially have low levels of enhancer-associated histone modification, but the majority of these regions gain H3K4me2 or H3K27Ac to become de novo enhancers. Minimal remodeling regions are associated with gene ontologies specific to decreased B cell number and mTOR inhibition and may make unique contributions to glucocorticoid-induced leukemia cell death. Conclusions: Our findings form a novel framework for understanding the dynamic interplay between transcription factor binding, nucleosome remodeling, enhancer function, and gene expression in the leukemia response to glucocorticoids. C1 [Wu, Jennifer N.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, TH Chan Sch Publ Heath, Boston, MA 02115 USA. [Yissachar, Elinor] SBH Sci Inc, Natick, MA USA. [Wischhusen, Jonathan W.] Morsani Coll Med, Tampa, FL USA. [Roberts, Charles W. M.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. RP Roberts, CWM (reprint author), St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,MS 281, Memphis, TN 38105 USA. EM charles_roberts@dfci.harvard.edu FU NIH [R01CA172152, R01CA113794, 5T32 CA136432-02, R01HG005085]; U01NCI Mouse Models of Cancer Consortium Award; Alex's Lemonade Stand Foundation; Hyundai Hope on Wheels; Cure AT/RT Now Fund; Avalanna Fund; Garrett B. Smith Foundation; Miles for Mary Fund; Ellison Medical Foundation; St. Baldrick's Foundation; Boston Children's Hospital Office of Faculty Development; William Lawrence and Blanche Hughes Foundation FX We are grateful to M. Brown, J. Perry, M. Silverman, and K. Walsh for critical reading of the manuscript and insightful suggestions, and all members of the Roberts, Yuan, Cantor and Orkin labs for helpful discussions. The authors wish to thank R. Rubio and F. Abderazzaq at The Center for Cancer Computational Biology for their experimental support and expertise. They are greatly indebted to the community of open-source programmers and computational biologists, without whom this work would not have been possible. The work in CWMR's laboratory is partly supported by NIH grants R01CA172152 (to CWMR) and R01CA113794 (to CWMR) and a U01NCI Mouse Models of Cancer Consortium Award (to CWMR). Alex's Lemonade Stand Foundation, Hyundai Hope on Wheels, the Cure AT/RT Now Fund, the Avalanna Fund, the Garrett B. Smith Foundation, the Miles for Mary Fund, and the Ellison Medical Foundation provided additional support. The work of JNW, EY, and JWW has been supported by St. Baldrick's Foundation, Alex's Lemonade Stand Foundation, Boston Children's Hospital Office of Faculty Development, NIH grant 5T32 CA136432-02, and William Lawrence and Blanche Hughes Foundation. This work of GY and LP was supported by the NIH grant R01HG005085. NR 57 TC 2 Z9 2 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PD DEC 2 PY 2015 VL 8 AR 53 DI 10.1186/s13072-015-0046-0 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA CX2YZ UT WOS:000365564000001 PM 26633995 ER PT J AU Newhouse, JP Price, M Mcwilliams, JM Hsu, J Mcguire, TG AF Newhouse, Joseph P. Price, Mary Mcwilliams, J. Michael Hsu, John Mcguire, Thomas G. TI HOW MUCH FAVORABLE SELECTION IS LEFT IN MEDICARE ADVANTAGE? SO AMERICAN JOURNAL OF HEALTH ECONOMICS LA English DT Article DE selection; Medicare; Medicare Advantage ID HEALTH-INSURANCE EXCHANGES; SERVICE-LEVEL SELECTION; RISK-ADJUSTMENT; ADVERSE SELECTION; PRIVATE INFORMATION; CARE; MARKETS; PLANS; PROVIDERS; PAYMENT AB The health economics literature contains two models of selection, one with endogenous plan characteristics to attract good risks and one with fixed plan characteristics; neither model contains a regulator. Medicare Advantage, a principal example of selection in the literature, is, however, subject to anti-selection regulations. Because selection causes economic inefficiency and because the historically favorable selection into Medicare Advantage plans increased government cost, the effectiveness of the anti-selection regulations is an important policy question, especially since the Medicare Advantage program has grown to comprise 30 percent of Medicare beneficiaries. Moreover, similar anti-selection regulations are being used in health insurance exchanges for those under 65. Contrary to earlier work, we show that the strengthened anti-selection regulations that Medicare introduced starting in 2004 markedly reduced government overpayment attributable to favorable selection in Medicare Advantage. At least some of the remaining selection is plausibly related to fixed plan characteristics of Traditional Medicare versus Medicare Advantage rather than changed selection strategies by Medicare Advantage plans. C1 [Newhouse, Joseph P.; Price, Mary; Mcwilliams, J. Michael; Hsu, John; Mcguire, Thomas G.] Harvard Med Sch, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Newhouse, Joseph P.] Harvard John F Kennedy Sch Govt, Cambridge, MA USA. [Newhouse, Joseph P.; Mcguire, Thomas G.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Price, Mary; Hsu, John] Kaiser Permanente, Div Res, Rockville, MD USA. [Price, Mary; Hsu, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Newhouse, JP (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM joseph_newhouse@harvard.edu FU National Institute of Aging [P01 AG032952] FX The authors are grateful to the National Institute of Aging, Grant # P01 AG032952, for support. Newhouse wishes to disclose that he is a director of Aetna, which sells Medicare Advantage plans as well as Medigap plans. Hsu has consulted for Kaiser Permanente, which sells Medicare Advantage plans, and has consulted for Boston Consulting Group, which has advised Medicare Advantage plans. NR 47 TC 8 Z9 8 U1 1 U2 3 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 2332-3493 EI 2332-3507 J9 AM J HEALTH ECON JI AM. J. HEALTH ECON. PD WIN PY 2015 VL 1 IS 1 BP 1 EP 26 DI 10.1162/ajhe_a_00001 PG 26 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA DS1OR UT WOS:000380366300003 PM 26389127 ER PT J AU Borra, RJH Cho, HS Bowen, SL Attenberger, U Arabasz, G Catana, C Josephson, L Rosen, BR Guimaraes, AR Hooker, JM AF Borra, Ronald J. H. Cho, Hoon-Sung Bowen, Spencer L. Attenberger, Ulrike Arabasz, Grae Catana, Ciprian Josephson, Lee Rosen, Bruce R. Guimaraes, Alexander R. Hooker, Jacob M. TI Effects of ferumoxytol on quantitative PET measurements in simultaneous PET/MR whole-body imaging: a pilot study in a baboon model SO EJNMMI PHYSICS LA English DT Article DE PET; MRI; PET/MR; Multimodal imaging; Ferumoxytol; Attenuation correction ID CHRONIC KIDNEY-DISEASE; ATTENUATION CORRECTION; IRON-OXIDE; MRI; THERAPY; CONCANAVALIN; ANEMIA; ADULTS AB Background: Simultaneous PET/MR imaging depends on MR-derived attenuation maps (mu-maps) for accurate attenuation correction of PET data. Currently, these maps are derived from gradient-echo-based MR sequences, which are sensitive to susceptibility changes. Iron oxide magnetic nanoparticles have been used in the measurement of blood volume, tumor microvasculature, tumor-associated macrophages, and characterizing lymph nodes. Our aim in this study was to assess whether the susceptibility effects associated with iron oxide nanoparticles can potentially affect measured F-18-FDG PET standardized uptake values (SUV) through effects on MR-derived attenuation maps. Methods: The study protocol was approved by the Institutional Animal Care and Use Committee. Using a Siemens Biograph mMR PET/MR scanner, we evaluated the effects of increasing concentrations of ferumoxytol and ferumoxytol aggregates on MR-derived mu-maps using an agarose phantom. In addition, we performed a baboon experiment evaluating the effects of a single i.v. ferumoxytol dose (10 mg/kg) on the liver, spleen, and pancreas F-18-FDG SUV at baseline (ferumoxytol-naive), within the first hour and at 1, 3, 5, and 11 weeks. Results: Phantom experiments showed mu-map artifacts starting at ferumoxytol aggregate concentrations of 10 to 20 mg/kg. The in vivo baboon data demonstrated a 53% decrease of observed F-18-FDG SUV compared to baseline within the first hour in the liver, persisting at least 11 weeks. Conclusions: A single ferumoxytol dose can affect measured SUV for at least 3 months, which should be taken into account when administrating ferumoxytol in patients needing sequential PET/MR scans. Advances in knowledge 1. Ferumoxytol aggregates, but not ferumoxytol alone, produce significant artifacts in MR-derived attenuation correction maps at approximate clinical dose levels of 10 mg/kg. 2. When performing simultaneous whole-body F-18-FDG PET/MR, a single dose of ferumoxytol can result in observed SUV decreases up to 53%, depending on the amount of ferumoxytol aggregates in the studied tissue. Implications for patient care Administration of a single, clinically relevant, dose of ferumoxytol can potentially result in changes in observed SUV for a prolonged period of time in the setting of simultaneous PET/MR. These potential changes should be considered in particular when administering ferumoxytol to patients with expected future PET/MR studies, as ferumoxytol-induced SUV changes might interfere with therapy assessment. C1 [Borra, Ronald J. H.; Bowen, Spencer L.; Arabasz, Grae; Catana, Ciprian; Rosen, Bruce R.; Guimaraes, Alexander R.; Hooker, Jacob M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. [Borra, Ronald J. H.] Univ Turku, Dept Diagnost Radiol, Med Imaging Ctr Southwest Finland, Turku, Finland. [Borra, Ronald J. H.] Turku Univ Hosp, Turku, Finland. [Cho, Hoon-Sung; Josephson, Lee] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Charlestown, MA 02129 USA. [Cho, Hoon-Sung] Chonnam Natl Univ, Sch Mat Sci & Engn, Gwangju, South Korea. [Attenberger, Ulrike] Heidelberg Univ, Univ Med Ctr Mannheim, Inst Clin Radiol & Nucl Med, Mannheim, Germany. [Rosen, Bruce R.] Kyung Hee Univ, East West Med Res Inst, Collaborating Ctr Tradit Med, Dept Meridian & Acupuncture, Seoul, South Korea. [Rosen, Bruce R.] Kyung Hee Univ, Sch Korean Med, Seoul, South Korea. [Guimaraes, Alexander R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA USA. RP Hooker, JM (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu FU NCRR NIH HHS [S10 RR019933, S10 RR023452, S10 RR022976]; NIBIB NIH HHS [P41 EB015896, R01 EB017699] NR 26 TC 1 Z9 1 U1 2 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2197-7364 J9 EJNMMI PHYS JI EJNMMI Phys. PD DEC PY 2015 VL 2 IS 1 AR 6 DI 10.1186/s40658-015-0109-0 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DQ4XQ UT WOS:000379208500006 PM 26501808 ER PT J AU Hope, TA Verdin, EF Bergsland, EK Ohliger, MA Corvera, CU Nakakura, EK AF Hope, Thomas A. Verdin, Emily F. Bergsland, Emily K. Ohliger, Michael A. Corvera, Carlos U. Nakakura, Eric K. TI Correcting for respiratory motion in liver PET/MRI: preliminary evaluation of the utility of bellows and navigated hepatobiliary phase imaging SO EJNMMI PHYSICS LA English DT Article ID WHOLE-BODY PET/MRI; ATTENUATION CORRECTION; PET QUANTIFICATION; MRI; RESOLUTION; CONTRAST; ONCOLOGY; LESIONS; IMPACT; TUMOR AB Background: The purpose of this study was to evaluate the utility of bellows-based respiratory compensation and navigated hepatobiliary phase imaging to correct for respiratory motion in the setting of dedicated liver PET/MRI. Methods: Institutional review board approval and informed consent were obtained. Six patients with metastatic neuroendocrine tumor were imaged using Ga-68 DOTA-TOC PET/MRI. Whole body imaging and a dedicated 15-min liver PET acquisition was performed, in addition to navigated and breath-held hepatobiliary phase (HBP) MRI. Liver PET data was reconstructed three ways: the entire data set (liver PET), gated using respiratory bellows (RC-liver PET), and a non-gated data set reconstructed using the same amount of data used in the RC-liver PET (shortened liver PET). Liver lesions were evaluated using SUVmax, SUVpeak, SUVmean, and Vol(isocontour). Additionally, the displacement of each lesion between the RC-liver PET images and the navigated and breath-held HBP images was calculated. Results: Respiratory compensation resulted in a 43 % increase in SUVs compared to ungated data (liver vs RC-liver PET SUVmax 26.0 vs 37.3, p < 0.001) and a 25 % increase compared to a non-gated reconstruction using the same amount of data (RC-liver vs shortened liver PET SUVmax 26.0 vs 32.6, p < 0.001). Lesion displacement was minimized using navigated HBP MRI (1.3 +/- 1.0 mm) compared to breath-held HBP MRI (23.3 +/- 1.0 mm). Conclusions: Respiratory bellows can provide accurate respiratory compensation when imaging liver lesions using PET/MRI, and results in increased SUVs due to a combination of increased image noise and reduced respiratory blurring. Additionally, navigated HBP MRI accurately aligns with respiratory compensated PET data. C1 [Hope, Thomas A.; Verdin, Emily F.; Ohliger, Michael A.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Hope, Thomas A.] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA USA. [Bergsland, Emily K.] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA USA. [Ohliger, Michael A.] San Francisco Gen Hosp, Dept Radiol, San Francisco, CA 94110 USA. [Corvera, Carlos U.; Nakakura, Eric K.] Univ Calif San Francisco, Dept Surg, Div Surg Oncol, San Francisco, CA USA. RP Hope, TA (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. EM thomas.hope@ucsf.edu FU NIDDK NIH HHS [P30 DK026743] NR 27 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2197-7364 J9 EJNMMI PHYS JI EJNMMI Phys. PD DEC PY 2015 VL 2 IS 1 AR 21 DI 10.1186/s40658-015-0125-0 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DQ4XQ UT WOS:000379208500021 PM 26501822 ER PT J AU Kenny, A Basu, G Ballard, M Griffiths, T Kentoffio, K Niyonzima, JB Sechler, GA Selinsky, S Panjabi, RR Siedner, MJ Kraemer, JD AF Kenny, Avi Basu, Gaurab Ballard, Madeleine Griffiths, Thomas Kentoffio, Katherine Niyonzima, Jean Bosco Sechler, G. Andrew Selinsky, Stephen Panjabi, Rajesh R. Siedner, Mark J. Kraemer, John D. TI Remoteness and maternal and child health service utilization in rural Liberia: A population-based survey SO JOURNAL OF GLOBAL HEALTH LA English DT Article ID ANTIRETROVIRAL THERAPY; DISTANCE; CARE; MORTALITY; BARRIERS; POOR; TANZANIA; DELIVERY; IMPACT; UGANDA AB Background This study seeks to understand distance from health facilities as a barrier to maternal and child health service uptake within a rural Liberian population. Better understanding the relationship between distance from health facilities and rural health care utilization is important for post-Ebola health systems reconstruction and for general rural health system planning in sub-Saharan Africa. Methods Cluster-sample survey data collected in 2012 in a very rural southeastern Liberian population were analyzed to determine associations between quartiles of GPS-measured distance from the nearest health facility and the odds of maternal (ANC, facility-based delivery, and PNC) and child (deworming and care seeking for ARI, diarrhea, and fever) service use. We estimated associations by fitting simple and multiple logistic regression models, with standard errors adjusted for clustered data. Findings Living in the farthest quartile was associated with lower odds of attending 1-or-more ANC checkup (AOR = 0.04, P < 0.001), 4-or-more ANC checkups (AOR = 0.13, P < 0.001), delivering in a facility (AOR = 0.41, P = 0.006), and postnatal care from a health care worker (AOR = 0.44, P = 0.009). Children living in all other quartiles had lower odds of seeking facility-based fever care (AOR for fourth quartile = 0.06, P < 0.001) than those in the nearest quartile. Children in the fourth quartile were less likely to receive deworming treatment (AOR = 0.16, P < 0.001) and less likely (but with only marginal statistical significance) to seek ARI care from a formal HCW (AOR = 0.05, P = 0.05). Parents in distant quartiles more often sought ARI and diarrhea care from informal providers. Conclusions Within a rural Liberian population, distance is associated with reduced health care uptake. As Liberia rebuilds its health system after Ebola, overcoming geographic disparities, including through further dissemination of providers and greater use of community health workers should be prioritized. C1 [Kenny, Avi; Griffiths, Thomas; Niyonzima, Jean Bosco; Selinsky, Stephen] Last Mile Hlth, Zwedru, Liberia. [Basu, Gaurab; Ballard, Madeleine; Sechler, G. Andrew; Panjabi, Rajesh R.] Last Mile Hlth, Boston, MA USA. [Basu, Gaurab; Kentoffio, Katherine; Sechler, G. Andrew] Harvard Univ, Sch Med, Boston, MA USA. [Basu, Gaurab] Cambridge Hlth Alliance, Cambridge, MA USA. [Sechler, G. Andrew; Panjabi, Rajesh R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Siedner, Mark J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kraemer, John D.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Kraemer, JD (reprint author), Georgetown Univ, Dept Hlth Syst Adm, 3700 Reservoir Rd NW,231 St Marys Hall, Washington, DC 20007 USA. EM jdk32@georgetown.edu RI Ballard, Madeleine/M-8510-2016 OI Ballard, Madeleine/0000-0003-0107-4047 FU NIMH NIH HHS [K23 MH099916] NR 48 TC 5 Z9 5 U1 2 U2 22 PU UNIV EDINBURGH, GLOBAL HEALTH SOC PI EDINBURGH PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG, ENGLAND SN 2047-2978 EI 2047-2986 J9 J GLOB HEALTH JI J. Glob. Health PD DEC PY 2015 VL 5 IS 2 BP 48 EP 59 AR 020401 DI 10.7189/jogh.05.020401 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DI9WJ UT WOS:000373853100006 PM 26207180 ER PT J AU Boyce, R Reyes, R Ntaro, M Mulogo, E Matte, M Boum, Y Siedner, MJ AF Boyce, Ross Reyes, Raquel Ntaro, Moses Mulogo, Edgar Matte, Michael Boum, Yap, II Siedner, Mark J. TI Association between HRP-2/pLDH rapid diagnostic test band positivity and malaria-related anemia at a peripheral health facility in Western Uganda SO JOURNAL OF GLOBAL HEALTH LA English DT Article ID SEVERE FALCIPARUM-MALARIA; CEREBRAL MALARIA; CHILDREN; TRANSMISSION; MANAGEMENT; MORBIDITY; MORTALITY; TRAVELERS; IMMUNITY; AFRICA AB The detection of severe malaria in resource-constrained settings is often difficult because of requirements for laboratory infrastructure and/or clinical expertise. The aim of this study, therefore, was to explore the utility of a multiple antigen (HRP-2/pLDH) rapid diagnostic test (RTD) as a low-cost, surrogate marker of patients at high risk for complications of severe malaria. We reviewed programmatic data at a peripheral health center in Western Uganda. Available demographic and clinical data on all individuals presenting to the center who underwent an RDT for suspected malaria infection were reviewed. We fit logistic regression models to identify correlates of two outcomes of interest: 1) severe malaria-related anemia, defined here as hemoglobin <= 7g/dL and 2) receipt of parenteral quinine. 1509 patients underwent malaria testing with an SD FK60 RDT during the observation period. A total of 637 (42%) RDTs were positive for at least one species of malaria, of which 326 (51%) exhibited a single HRP-2 band and 307 (48%) exhibited both HRP-2 and pLDH bands, while 4 exhibited only a single pLDH band. There was a trend towards more severe anemia in patients with a HRP-2/pLDH positive RDT compared to a HRP-2 only RDT (beta = -0.99 g/dl, 95% CI - 1.99 to 0.02, P = 0.055). A HRP-2/pLDH positive RDT was associated with an increased risk of severe malaria-related anemia compared to a negative RDT (adjusted odds ratio (AOR) 18.8, 95% CI 4.32 to 82.0, P < 0.001) and to a HRP-2 only RDT (AOR 2.46, 95% CI 0.75 to 8.04, P = 0.14). There was no significant association between RDT result and the administration of parenteral quinine. These results offer preliminary evidence that specific patterns of antigen positivity on RDTs could be utilized to identify patients at an increased risk for complications of severe malaria. C1 [Boyce, Ross; Reyes, Raquel] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. [Ntaro, Moses; Mulogo, Edgar; Matte, Michael] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda. [Boum, Yap, II] Epictr Mbarara Res Ctr, Mbarara, Uganda. [Siedner, Mark J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. RP Boyce, R (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM roboyce@gmail.com OI Boyce, Ross/0000-0002-9489-6324 NR 43 TC 0 Z9 0 U1 0 U2 0 PU UNIV EDINBURGH, GLOBAL HEALTH SOC PI EDINBURGH PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG, ENGLAND SN 2047-2978 EI 2047-2986 J9 J GLOB HEALTH JI J. Glob. Health PD DEC PY 2015 VL 5 IS 2 BP 60 EP 66 DI 10.7189/jogh.05.020402 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DI9WJ UT WOS:000373853100007 ER PT J AU Shanbhogue, VV Yu, E Finkelstein, J Bouxsein, M AF Shanbhogue, V. V. Yu, E. Finkelstein, J. Bouxsein, M. TI ASSOCIATION BETWEEN INSULIN RESISTANCE AND BONE STRUCTURE IN NON-DIABETIC POSTMENOPAUSAL WOMEN SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT IOF Regionals 3rd Middle East and Africa Osteoporosis Meeting CY DEC 05-07, 2015 CL Abu Dhabi, U ARAB EMIRATES SP IOF Reg C1 [Shanbhogue, V. V.] Odense Univ Hosp, Endocrinol, DK-5000 Odense, Denmark. [Yu, E.; Finkelstein, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bouxsein, M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD DEC PY 2015 VL 26 SU 2 MA OC02 BP S427 EP S428 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DI8RI UT WOS:000373768300014 ER PT J AU Duntas, LH Stathatos, N AF Duntas, Leonidas H. Stathatos, Nikos TI Toxic chemicals and thyroid function: hard facts and lateral thinking SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Review DE Thyroid; Thyroid receptor; TSH; Organochlorines; Pesticides; Lateral thinking ID ENDOCRINE-DISRUPTING CHEMICALS; POLYBROMINATED DIPHENYL ETHERS; LONG-TERM EXPOSURE; POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE PESTICIDES; OCCUPATIONAL-EXPOSURE; SCIENTIFIC STATEMENT; AGRICULTURAL HEALTH; PREGNANT-WOMEN; BISPHENOL-A AB Increasing quantities of evidence-based data incriminate a large number of environmental pollutants for toxic effects on the thyroid. Among the many chemical contaminants, halogenated organochlorines and pesticides variably affect the hypothalamic-pituitary-thyroid axis and disrupt thyroid function. PCBs and their metabolites and PBDEs bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Meanwhile, at the molecular level, PCB congeners may activate phosphorylation of Akt, p-Akt, and forkhead box O3a (FoxO3a) protein resulting in inhibition of the natrium/iodide symporter. Given therefore the growing concern developing around these multiple toxic chemicals today invading numerous environments and their long-term deleterious effects not only on the thyroid but also on general health, we strongly advocate their strict regulation and, moreover, their gradual reduction. A good degree of "lateral thinking", we feel, will lead to a use of chemicals that will enhance life while concurrently carefully protecting the environment. C1 [Duntas, Leonidas H.] Univ Athens, Evgenid Hosp, Unit Endocrinol Metab & Diabet, Thyroid Sect, 20 Papadiamantopoulou Str, Athens 10520, Greece. [Stathatos, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Thyroid Unit, Boston, MA 02115 USA. RP Duntas, LH (reprint author), Univ Athens, Evgenid Hosp, Unit Endocrinol Metab & Diabet, Thyroid Sect, 20 Papadiamantopoulou Str, Athens 10520, Greece. EM ledunt@otenet.gr NR 58 TC 3 Z9 3 U1 6 U2 135 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 EI 1573-2606 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD DEC PY 2015 VL 16 IS 4 BP 311 EP 318 DI 10.1007/s11154-016-9331-x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DH9NW UT WOS:000373123900006 PM 26801661 ER PT J AU Schwartz, KR Prentiss, KA AF Schwartz, Kevin R. Prentiss, Kimball A. TI Simulation in Pre-departure Training for Residents Planning Clinical Work in a Low-Income Country SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Global Health; Simulation; Malaria; Malnutrition; Pre-departure ID GLOBAL CHILD HEALTH; EMERGENCY-MEDICINE; PEDIATRIC RESIDENTS; CURRICULUM; PROGRAMS; MODEL; CARE AB Introduction: Increasingly, pediatric and emergency medicine (EM) residents are pursuing clinical rotations in low-income countries. Optimal pre-departure preparation for such rotations has not yet been established. High-fidelity simulation represents a potentially effective modality for such preparation. This study was designed to assess whether a pre-departure high-fidelity medical simulation curriculum is effective in helping to prepare residents for clinical rotations in a low-income country. Methods: 43 pediatric and EM residents planning clinical rotations in Liberia, West Africa, participated in a simulation-based curriculum focused on severe pediatric malaria and malnutrition and were then assessed by survey at three time points: pre-simulation, post-simulation, and after returning from work abroad. Results: Prior to simulation, 1/43 (2%) participants reported they were comfortable with the diagnosis and management of severe malnutrition; this increased to 30/42 (71%) after simulation and 24/31 (77%) after working abroad. Prior to simulation, 1/43 (2%) of residents reported comfort with the diagnosis and management of severe malaria; this increased to 26/42 (62%) after simulation and 28/31 (90%) after working abroad; 36/42 (86%) of residents agreed that a simulation-based global health curriculum is more useful than a didactic curriculum alone, and 41/42 (98%) felt a simulator-based curriculum should be offered to all residents planning a clinical trip to a low-income country. Conclusion: High-fidelity simulation is effective in increasing residents' self-rated comfort in management of pediatric malaria and malnutrition and a majority of participating residents feel it should be included as a component of pre-departure training for all residents rotating clinically to low-income countries. C1 [Schwartz, Kevin R.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schwartz, Kevin R.] Dept Emergency Med, Boston, MA USA. [Prentiss, Kimball A.] Tufts Univ, Sch Med, Baystate Med Ctr, Dept Emergency Med, Springfield, MA 01199 USA. RP Schwartz, KR (reprint author), Massachusetts Gen Hosp, Dept Pediat, Dept Emergency Med, 175 Cambridge St, Boston, MA 02114 USA. EM krschwartz@mgh.harvard.edu NR 21 TC 0 Z9 0 U1 0 U2 0 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD DEC PY 2015 VL 16 IS 7 BP 1166 EP 1172 DI 10.5811/westjem.2015.9.28164 PG 7 WC Emergency Medicine SC Emergency Medicine GA DH9OX UT WOS:000373126600034 PM 26759672 ER PT J AU Corse, T Thomas, K Broderick, J Kabiri, NS Margulies, J Masri, T McCullen, J McMahon, M AF Corse, Teija Thomas, Kevin Broderick, John Kabiri, Nina Shaafi Margulies, Joshua Masri, Taha McCullen, Justin McMahon, Maureen TI Using Ebola as a Lens to Examine Medical Waste Sterilization SO WORLD MEDICAL & HEALTH POLICY LA English DT Editorial Material DE Ebola; medical waste; Category A; sterilization; autoclaves AB The Ebola outbreak in the Fall of 2014 exposed issues surrounding the medical waste disposal of Category A substances. Current regulations by the Centers for Disease Control and Prevention and the Department of Transportation on the disposal of Category A medical waste state that the waste must be sterilized before disposal. Approved methods of sterilization are autoclaving and incineration. For hospitals that do not have on-site autoclaves large enough to sterilize the immense amount of waste, they must contract with companies to transport the waste to an off-site sterilization center. Hospitals are required to follow the UN system of triple-packaging medical waste for transportation. Hospitals in the United States that treated Ebola patients during the outbreak faced the issue of having to transport an immense amount of waste to off-site facilities. A focus on medical waste sterilization has led to the development of new technologies that can allow hospitals to sterilize their increased amount of medical waste on-site. These new technologies have the potential to better prepare hospitals for Category A infection outbreaks, and help limit the risk of both in-hospital exposure and out-of-hospital exposures that can occur during waste transportation. C1 [Corse, Teija] Boston Univ, Sch Med, Dept Healthcare Emergency Management, Boston, MA 02118 USA. [Thomas, Kevin] Boston Univ, Sch Med, Dept Healthcare Emergency Management, Healthcare Emergency Management Program,Sci, Boston, MA 02118 USA. [Broderick, John] Boston Univ, Sch Med, Dept Healthcare Emergency Management, Healthcare Emergency Management Program, Boston, MA 02118 USA. [Kabiri, Nina Shaafi] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Margulies, Joshua] Mt Auburn Hosp, Cambridge, MA USA. [Masri, Taha] Boston Univ, Sch Med, Boston, MA 02118 USA. [McCullen, Justin] Dana Farber Canc Inst, Boston, MA 02115 USA. [McMahon, Maureen] Boston Med Ctr, Boston, MA USA. EM tcorse@bu.edu NR 25 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1948-4682 J9 World Med Health Pol JI World Med. Health Policy PD DEC PY 2015 VL 7 IS 4 BP 402 EP 411 DI 10.1002/wmh3.164 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DH8UC UT WOS:000373071300007 ER PT J AU Hodnett, BL Schmitt, NC Thirumala, PD Duvvuri, U AF Hodnett, Benjamin L. Schmitt, Nicole C. Thirumala, Parthasarathy D. Duvvuri, Umamaheswar TI Intraoperative identification of the human communicating nerve during thyroidectomy SO JOURNAL OF SURGICAL CASE REPORTS LA English DT Article ID SUPERIOR LARYNGEAL NERVE AB The human communicating nerve (HCN) is a connection between the superior and recurrent laryngeal nerves that has been described in cadaveric studies. We report a case of an extralaryngeal variant of the HCN that was identified and stimulated intraoperatively during thyroidectomy. This appears to be the first case of intraoperative identification of this anatomic variant, of which the functional significance remains unclear. C1 [Hodnett, Benjamin L.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Schmitt, Nicole C.] Johns Hopkins Univ, Dept Otorhinolaryngol Head & Neck Surg, NIDCD, NIH, Bethesda, MD USA. [Thirumala, Parthasarathy D.] UPMC Presbyterian Hosp, Dept Neurol Surg & Neurol, Ctr Clin Neurophysiol, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Sch Med, Dept Otolaryngol, VA Pittsburgh Hlth Syst,Eye & Ear Inst, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Sch Med, Dept Otolaryngol, VA Pittsburgh Hlth Syst,Eye & Ear Inst, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu NR 6 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2042-8812 J9 J SURG CASE REP JI J. Surg. Case Rep. PD DEC PY 2015 IS 12 AR UNSP rjv154 DI 10.1093/jscr/rjv154 PG 4 WC Surgery SC Surgery GA DH2EO UT WOS:000372597200006 ER PT J AU Fehling, M Jarrah, ZM Tiernan, ME Albezreh, S VanRooyen, MJ Alhokair, A Nelson, BD AF Fehling, M. Jarrah, Z. M. Tiernan, M. E. Albezreh, S. VanRooyen, M. J. Alhokair, A. Nelson, B. D. TI Youth in crisis in the Middle East and North Africa: a systematic literature review and focused landscape analysis SO EASTERN MEDITERRANEAN HEALTH JOURNAL LA English DT Review ID INTIMATE-PARTNER VIOLENCE; MENTAL-HEALTH; PALESTINIAN YOUTH; PARTICIPATORY RESEARCH; POSTTRAUMATIC STRESS; PSYCHOLOGICAL IMPACT; PROTRACTED CONFLICT; POLITICAL VIOLENCE; REFUGEE CAMP; GAZA-STRIP AB Recent political and demographic factors have exposed the vulnerability of the youth in the Middle East and North Africa (MENA) region. This study aimed to elucidate the current needs, activities, stakeholders and solutions related to at-risk youth and young adults in the MENA region. A systematic literature review was conducted of the peer-reviewed and grey literature. This was complemented by an in-region landscape analysis involving key-informant interviews and focus group discussions. After extensive screening of 1160 unique articles, 275 articles were considered relevant to this study. Of these 275, 145 (52.7%) were related to health (64.8% of these related to mental health), 101 (36.7%) to livelihood, 87 (31.6%) to violence prevention and 68 (24.7%) to education. Important themes and challenges identified in the literature and discussions included the MENA region's growing youth bulge; youth unemployment; critical gender gaps; and the impact of conflict on livelihoods, education and health, especially mental health. C1 [Fehling, M.; Jarrah, Z. M.; Tiernan, M. E.; Albezreh, S.; VanRooyen, M. J.; Alhokair, A.] Harvard Humanitarian Initiat, Cambridge, MA USA. [VanRooyen, M. J.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Nelson, B. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Global Hlth, Boston, MA USA. [Nelson, B. D.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Nelson, B. D.] Massachusetts Gen Hosp, Dept Paediat, Boston, MA 02114 USA. RP Nelson, BD (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. EM brett.d.nelson@gmail.com NR 68 TC 0 Z9 0 U1 5 U2 7 PU WHO EASTERN MEDITERRANEAN REGIONAL OFFICE PI NASR CITY, CAIRO PA P. O. BOX 7608, NASR CITY, CAIRO, EGYPT SN 1020-3397 EI 1687-1634 J9 E MEDITERR HEALTH J JI East Mediterr. Health J. PD DEC PY 2015 VL 21 IS 12 BP 916 EP 930 PG 15 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DG4FM UT WOS:000372026900009 ER PT J AU Henderson, T Nelson, C Chemali, Z AF Henderson, Tanya Nelson, Camille Chemali, Zeina TI Increasing Women's Political Participation in Lebanon: Reflections on Hurdles, Opportunities and Hope SO JOURNAL OF POLITICS AND LAW LA English DT Article DE political participation; women; gender studies; Lebanon AB Lebanon stands out in the Middle East for its relative political openness, religious freedom, and the academic and professional achievements of Lebanese women. Yet, paradoxically, it has one of the lowest rates of women's political participation in the region. This paper is the result of an initiative undertaken by the Lebanese government in July 2012 to increase women's political participation. Through this initiative, sex-segregated workshops on women's political empowerment were held for male and female representatives of Lebanon's political parties. The goal was to start a productive conversation that would ultimately lead to progress from the 2012 status quo of women constituting only three percent of the National Parliament of Lebanon. In this paper, we will describe the process and content explored during the women's political empowerment workshops. Opportunities to affect change of the current level of women's participation will be highlighted and conclusions will be drawn to aid similar initiatives. C1 [Nelson, Camille; Chemali, Zeina] Suffolk Univ, Sch Law, Boston, MA 02108 USA. [Chemali, Zeina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Chemali, Z (reprint author), Suffolk Univ, Sch Law, Boston, MA 02108 USA. EM zelchemali@mgh.harvard.edu NR 22 TC 0 Z9 0 U1 2 U2 4 PU CANADIAN CENTER SCIENCE & EDUCATION PI TORONTO PA 1120 FINCH AVE W, STE 701-309, TORONTO, ON M3J 3H7, CANADA SN 1913-9047 EI 1913-9055 J9 J POLIT LAW JI J. Polit. Law PD DEC PY 2015 VL 8 IS 4 BP 233 EP 241 DI 10.5539/jpl.v8n4p233 PG 9 WC Political Science SC Government & Law GA DF7BJ UT WOS:000371512200008 ER PT J AU Hobeika, L Hunt, KJ Neely, BA Arthur, JM AF Hobeika, Liliane Hunt, Kelly J. Neely, Benjamin A. Arthur, John M. TI Comparison of the Rate of Renal Function Decline in NonProteinuric Patients With and Without Diabetes SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Diabetes; Renal function decline; Chronic kidney disease; Proteinuria; Hypertension ID GLOMERULAR-FILTRATION-RATE; RISK-FACTORS; KIDNEY-DISEASE; INSUFFICIENCY; MICROALBUMINURIA; ALBUMINURIA; NEPHROPATHY; PREVALENCE; MELLITUS; STAGE AB Background: Patients with diabetes and chronic kidney disease (CKD) without proteinuria are often believed to have a cause of CKD other than diabetes. It was hypothesized that if this is true, the rate of renal function decline should be similar among nonproteinuric patients with and without diabetes. Methods: Patients seen in the nephrology, endocrinology and general internal medicine clinics at the Medical University of South Carolina (MUSC) between 2008 and 2012 with hypertension and diabetes were identified by ICD9 diagnosis codes. Patients with less than 2 measures of serum creatinine, without urine studies over the study period and with proteinuria were excluded. Four hundred seventy-two patients met the inclusion and exclusion criteria and had an initial estimated glomerular filtration rate (eGFR) between 35 and 80 mL/min per 1.73 m(2). The annual rate of decline in eGFR was estimated for each patient from the lowest eGFR in each year by fitting a regression model with random intercept and slope. Results: In unadjusted analyses, the rate of eGFR decline was greater in patients with diabetes than without diabetes (-0.71 versus -0.30 mL.min(-1).yr(-1), P = 0.03). After adjusting for age, race, sex, baseline eGFR and use of renin-angiotensin-aldosterone system blockade, the rate of decline was still greater among patients with diabetes than among those without diabetes (-0.68 versus -0.36 mL.min(-1).yr(-1), P = 0.03). Conclusions: Patients with diabetes had more rapid decline in kidney function compared with individuals without diabetes, despite the absence of proteinuria. These results suggest that even in the absence of proteinuria, diabetes may be associated with CKD. C1 [Hobeika, Liliane] Univ Louisville, Dept Internal Med, Div Nephrol, Louisville, KY 40202 USA. [Hunt, Kelly J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Hunt, Kelly J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Neely, Benjamin A.] Univ S Carolina, Dept Internal Med, Div Nephrol, Charleston, SC USA. [Arthur, John M.] Univ Arkansas Med Sci, Dept Internal Med, Div Nephrol, Little Rock, AR 72205 USA. [Arthur, John M.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Hobeika, L (reprint author), Univ Louisville, Div Nephrol & Hypertens, 615 South Preston St, Louisville, KY 40202 USA. EM liliane.hobeika@louisville.edu OI Neely, Benjamin/0000-0001-6120-7695 FU NIH [R01DK101034]; South Carolina Clinical & Translational Research (SCTR) Institute through NIH [UL1 TR000062] FX Supported by NIH grant R01DK101034 and by the South Carolina Clinical & Translational Research (SCTR) Institute through NIH Grant Number UL1 TR000062. NR 24 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 2015 VL 350 IS 6 BP 447 EP 452 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DF4MQ UT WOS:000371323100005 PM 26624901 ER PT J AU Bradner, J AF Bradner, James TI Targeting enhancers in CNS tumors SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Brain Cancer Research CY MAY 27-30, 2015 CL Washington, DC SP Amer Assoc Canc Res C1 [Bradner, James] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2015 VL 75 SU 23 MA IA11 PG 1 WC Oncology SC Oncology GA DF3RK UT WOS:000371263800067 ER PT J AU Brastianos, PK Carter, SL Santagata, S Cahill, D Taylor-Weiner, A Jones, RT Van Allen, E Horowitz, P Ligon, KL Curry, WT Dunn, IF Van Hummelen, P Meyerson, M Garraway, L Tabernero, J Seoane, J Gabriel, S Lander, ES Beroukhim, R Batchelor, TT Baselga, J Louis, DN Hahn, WC Getz, G AF Brastianos, Priscilla K. Carter, Scott L. Santagata, Sandro Cahill, Daniel Taylor-Weiner, Amaro Jones, Robert T. Van Allen, Eliezer Horowitz, Peleg Ligon, Keith L. Curry, William T. Dunn, Ian F. Van Hummelen, Paul Meyerson, Matthew Garraway, Levi Tabernero, Josep Seoane, Joan Gabriel, Stacey Lander, Eric S. Beroukhim, Rameen Batchelor, Tracy T. Baselga, Jose Louis, David N. Hahn, William C. Getz, Gad TI Genomic characterization of brain metastases reveals branched evolution and metastasis-specific mutations SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Brain Cancer Research CY MAY 27-30, 2015 CL Washington, DC SP Amer Assoc Canc Res C1 [Brastianos, Priscilla K.; Cahill, Daniel; Curry, William T.; Batchelor, Tracy T.; Louis, David N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carter, Scott L.; Taylor-Weiner, Amaro; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Getz, Gad] Broad Inst, Cambridge, MA USA. [Santagata, Sandro; Horowitz, Peleg; Ligon, Keith L.; Dunn, Ian F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jones, Robert T.; Van Allen, Eliezer; Van Hummelen, Paul; Meyerson, Matthew; Garraway, Levi; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tabernero, Josep; Seoane, Joan] Vall dHebron Univ Hosp, Barcelona, Spain. [Tabernero, Josep; Seoane, Joan] Inst Oncol, Barcelona, Spain. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2015 VL 75 SU 23 MA PR04 PG 2 WC Oncology SC Oncology GA DF3RK UT WOS:000371263800080 ER PT J AU Kaelin, WG AF Kaelin, William G., Jr. TI Molecular pathogenesis of IDH mutant cancers and evolving treatment strategies SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Brain Cancer Research CY MAY 27-30, 2015 CL Washington, DC SP Amer Assoc Canc Res C1 [Kaelin, William G., Jr.] Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2015 VL 75 SU 23 MA IA02 PG 1 WC Oncology SC Oncology GA DF3RK UT WOS:000371263800062 ER PT J AU Kupp, R Lo Cascio, C Rauf, F Meijer, D Stiles, CD Sanai, N LaBaer, J Mehta, SV AF Kupp, Robert Lo Cascio, Costanza Rauf, Femina Meijer, Dimphna Stiles, Charles D. Sanai, Nader LaBaer, Joshua Mehta, Shwetal V. TI Targeting Olig2 co-regulators for malignant glioma therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Brain Cancer Research CY MAY 27-30, 2015 CL Washington, DC SP Amer Assoc Canc Res C1 [Kupp, Robert; Lo Cascio, Costanza; Sanai, Nader; Mehta, Shwetal V.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Rauf, Femina; LaBaer, Joshua] Arizona State Univ, Tempe, AZ USA. [Meijer, Dimphna; Stiles, Charles D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2015 VL 75 SU 23 MA B20 PG 1 WC Oncology SC Oncology GA DF3RK UT WOS:000371263800044 ER PT J AU Michor, F AF Michor, Franziska TI Evolution of glioblastoma subtypes SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Brain Cancer Research CY MAY 27-30, 2015 CL Washington, DC SP Amer Assoc Canc Res C1 [Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2015 VL 75 SU 23 MA IA05 PG 1 WC Oncology SC Oncology GA DF3RK UT WOS:000371263800064 ER PT J AU Djulbegovic, B Hamm, RM Mayrhofer, T Hozo, I Van den Ende, J AF Djulbegovic, Benjamin Hamm, Robert M. Mayrhofer, Thomas Hozo, Iztok Van den Ende, Jef TI Rationality, practice variation and person-centred health policy: a threshold hypothesis SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE epistemology; health policy; person-centred medicine ID NEGATIVE PULMONARY TUBERCULOSIS; THERAPEUTIC DECISION-MAKING; PHYSICIANS; TREAT; MODEL; HARM; CARE AB Variation in practice of medicine is one of the major health policy issues of today. Ultimately, it is related to physicians' decision making. Similar patients with similar likelihood of having disease are often managed by different doctors differently: some doctors may elect to observe the patient, others decide to act based on diagnostic testing and yet others may elect to treat without testing. We explain these differences in practice by differences in disease probability thresholds at which physicians decide to act: contextual social and clinical factors and emotions such as regret affect the threshold by influencing the way doctors integrate objective data related to treatment and testing. However, depending on a theoretical construct each of the physician's behaviour can be considered rational. In fact, we showed that the current regulatory policies lead to predictably low thresholds for most decisions in contemporary practice. As a result, we may expect continuing motivation for overuse of treatment and diagnostic tests. We argue that rationality should take into account both formal principles of rationality and human intuitions about good decisions along the lines of Rawls' 'reflective equilibrium/considered judgment'. In turn, this can help define a threshold model that is empirically testable. C1 [Djulbegovic, Benjamin] Univ S Florida, Morsani Coll Med, Dept Internal Med, Div Evidence Based Med,USF Hlth Comparat Effectiv, 12901 Bruce B Downs Blvd,MDC02, Tampa, FL USA. [Djulbegovic, Benjamin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Djulbegovic, Benjamin] Tampa Gen Hosp, Tampa, FL 33606 USA. [Hamm, Robert M.] Univ Oklahoma, Hlth Sci Ctr, Dept Family & Prevent Med, Oklahoma City, OK USA. [Mayrhofer, Thomas] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA USA. [Mayrhofer, Thomas] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mayrhofer, Thomas] Univ Appl Sci Stralsund, Sch Business Studies, Stralsund, Germany. [Hozo, Iztok] Indiana Univ Northwest, Dept Math, Gary, IN USA. [Van den Ende, Jef] Inst Trop Med, B-2000 Antwerp, Belgium. RP Djulbegovic, B (reprint author), Univ S Florida, Morsani Coll Med, Dept Internal Med, Div Evidence Based Med,USF Hlth Comparat Effectiv, 12901 Bruce B Downs Blvd,MDC02, Tampa, FL USA. EM bdjulbeg@health.usf.edu RI Djulbegovic, Benjamin/I-3661-2012; Hozo, Iztok/R-3498-2016 OI Djulbegovic, Benjamin/0000-0003-0671-1447; Hozo, Iztok/0000-0003-2349-5707 FU DoD grant [W81 XWH 09-2-0175] FX Supported in part by DoD grant (no. W81 XWH 09-2-0175; Djulbegovic). NR 24 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-1294 EI 1365-2753 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD DEC PY 2015 VL 21 IS 6 BP 1121 EP 1124 DI 10.1111/jep.12486 PG 4 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA DF5TD UT WOS:000371414500025 PM 26639018 ER PT J AU Iyer, SP Pancake, LS Dandino, ES Wells, KB AF Iyer, Sharat P. Pancake, Laura S. Dandino, Elizabeth S. Wells, Kenneth B. TI Consumer-Involved Participatory Research to Address General Medical Health and Wellness in a Community Mental Health Setting SO PSYCHIATRIC SERVICES LA English DT Article ID SCHIZOPHRENIA; MORTALITY; ENGAGEMENT; SERVICES; COHORT AB Barriers to sustainably implementing general medical interventions in community mental health (CMH) settings include role uncertainty, consumer engagement, workforce limitations, and sustainable reimbursement. To address these barriers, this project used a community-partnered participatory research framework to create a stakeholder-based general medical and wellness intervention in a large CMH organization, with consumers involved in all decision-making processes. Consumers faced practical barriers to participating in organizational decision making, but their narratives were critical in establishing priorities and ensuring sustainability. Addressing baseline knowledge and readiness of stakeholders and functional challenges to consumer involvement can aid stakeholder-based approaches to implementing general medical interventions in CMH settings. C1 [Iyer, Sharat P.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, Bronx, NY USA. [Iyer, Sharat P.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Pancake, Laura S.; Dandino, Elizabeth S.] Pacific Clin, Pasadena, CA USA. [Wells, Kenneth B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Wells, Kenneth B.] RAND Corp, Santa Monica, CA USA. RP Iyer, SP (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, Bronx, NY USA. EM sharat.iyer@mssm.edu FU Robert Wood Johnson Foundation; U.S. Department of Veterans Affairs FX This material is the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, New York, and the West Los Angeles VA Medical Center, Los Angeles. Funding for Dr. Iyer was provided by the Robert Wood Johnson Foundation Clinical Scholars program and the U.S. Department of Veterans Affairs. The authors thank the members of the Pacific Clinics Physical Health Stakeholder Committee for their efforts in this work: Erika Aguirre-Miyamoto, Angela Crenshaw, Dolly Ehlen, Sandra Escobar, Viola Gaffaney, Joana Garcia, Rosa Hernandez, Samantha James-Perez, Lisa Lansing, Lou Mallory, David Martel, Lana Martin, Yolanda Mendez, Nina Paddock, Irene Pines, Elizabeth Torres, and Wendy Wang. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 10 TC 0 Z9 0 U1 3 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2015 VL 66 IS 12 BP 1268 EP 1270 DI 10.1176/appi.ps.201500157 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE7WK UT WOS:000370847300011 PM 26174950 ER PT J AU Marx, BP Wolf, EJ Cornette, MM Schnurr, PP Rosen, MI Friedman, MJ Keane, TM Speroff, T AF Marx, Brian P. Wolf, Erika J. Cornette, Michelle M. Schnurr, Paula P. Rosen, Marc I. Friedman, Matthew J. Keane, Terence M. Speroff, Theodore TI Using the WHODAS 2.0 to Assess Functioning Among Veterans Seeking Compensation for Posttraumatic Stress Disorder SO PSYCHIATRIC SERVICES LA English DT Article ID PTSD; DISABILITY; DIAGNOSIS; SCALE AB Objective: One of the major changes in DSM-5 was removal of the Global Assessment of Functioning (GAF). To determine whether the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a suitable replacement for the GAF, this study compared how well the WHODAS 2.0 and the GAF measured functional impairment and other phenomena related to posttraumatic stress disorder (PTSD) among veterans applying for financial compensation (service connection) for PTSD. Methods: Clinicians evaluating veteran claimants administered the Clinician Administered PTSD Scale (CAPS) and the WHODAS 2.0 to 177 veterans during their evaluations. Veterans also completed the Inventory of Psychosocial Functioning (IPF), a self-report measure of functional impairment, and received a GAF rating from the examiner. Actual benefit determinations and ratings were obtained. Results: Confirmatory factor analyses demonstrated that the WHODAS 2.0 and the IPF were stronger indicators of a latent variable reflecting functioning compared with the GAF. In receiver operating characteristic curve analyses, the WHODAS 2.0, IPF, and GAF all displayed similar ability to identify veterans with PTSD-related impairment assessed by the CAPS. Compared with the GAF, the WHODAS 2.0 and IPF were less strongly related to PTSD symptom severity and disability ratings by the U.S. Department of Veterans Affairs, but these variables are typically influenced by GAF scores. Conclusions: The WHODAS 2.0 and IPF are acceptable replacements for the GAF and can be used to assess functional impairment among veterans seeking compensation for PTSD. C1 [Marx, Brian P.; Wolf, Erika J.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Marx, Brian P.; Wolf, Erika J.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Cornette, Michelle M.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Schnurr, Paula P.; Friedman, Matthew J.] White River Junct VA Med Ctr, Natl Ctr PTSD, Execut Div, White River Jct, VT USA. [Schnurr, Paula P.; Friedman, Matthew J.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Rosen, Marc I.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Rosen, Marc I.] VA Connecticut Healthcare Syst, Dept Psychiat, West Haven, CT USA. [Speroff, Theodore] Vet Affairs Tennessee Valley Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ctr Hlth Serv Res, Nashville, TN USA. [Speroff, Theodore] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. EM brian.marx@va.gov OI Wolf, Erika/0000-0003-2666-2435 FU U.S. Department of Veterans Affairs (VA) Health Services Research and Development Service's Quality Enhancement Research Initiative Program [SDR 06-331]; VA Clinical Sciences Research and Development program; National Institute of Mental Health [1R01MH095737-01A1]; U.S. Department of Defense [W81XWH-10-2-0181, W81XWH-12-2-0117-PTSD-IIRA-INT]; Defense Advanced Research Projects Agency [N66001-11-C-4006]; VA (Cooperative Studies Program) [591] FX This project was supported by the U.S. Department of Veterans Affairs (VA) Health Services Research and Development Service's Quality Enhancement Research Initiative Program (SDR 06-331). This work was also supported by a Career Development Award to Dr. Wolf from the VA Clinical Sciences Research and Development program. Dr. Marx was supported by the National Institute of Mental Health (1R01MH095737-01A1), the U.S. Department of Defense (W81XWH-10-2-0181 and W81XWH-12-2-0117-PTSD-IIRA-INT), the Defense Advanced Research Projects Agency (N66001-11-C-4006), and the VA (Cooperative Studies Program no. 591). The contents of this article do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 19 TC 1 Z9 1 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2015 VL 66 IS 12 BP 1312 EP 1317 DI 10.1176/appi.ps.201400400 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE7WK UT WOS:000370847300018 PM 26278226 ER PT J AU Nelson, CB Zivin, K Walters, H Ganoczy, D Wadsworth, SM Valenstein, M AF Nelson, C. Beau Zivin, Kara Walters, Heather Ganoczy, Dara Wadsworth, Shelley MacDermid Valenstein, Marcia TI Factors Associated With Civilian Employment, Work Satisfaction, and Performance Among National Guard Members SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH-SERVICES; GENERALIZED ANXIETY DISORDER; TREATMENT-SEEKING; US MILITARY; IRAQ; VETERANS; SOLDIERS; AFGHANISTAN; DEPRESSION; BARRIERS AB Objective: Employment is a vital part of the postdeployment return to civilian life. This study investigated factors associated with employment-related outcomes (employment status, self-reported work performance, and self-reported work satisfaction) among National Guard members returning from Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn deployments. Methods: The sample consisted of 1,151 National Guard service members who had returned from overseas deployments approximately six months earlier. Bivariate and multivariable analyses were performed to examine associations between predictors and employment-related outcome variables. Results: Higher-risk alcohol use was associated with reduced odds of being employed as well as with lower ratings of work satisfaction, whereas psychiatric symptom load was associated with lower self-reported work performance and work satisfaction ratings. Perceived social resources were associated with higher self-reported work performance and work satisfaction, whereas better physical functioning was associated with better self-reported work performance. Conclusions: Policy makers and clinicians may need to consider and assess alcohol use among unemployed National Guard members. They may also need to consider psychiatric symptom load and physical functioning among employed service members who perceive poor work performance and have low work satisfaction. Further research is needed on causal links between these predictors and employment outcomes. C1 [Nelson, C. Beau] Vet Affairs Ann Arbor Healthcare Syst, Div Mental Hlth Serv, Ann Arbor, MI USA. [Nelson, C. Beau] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Zivin, Kara; Valenstein, Marcia] US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI USA. [Walters, Heather; Ganoczy, Dara; Wadsworth, Shelley MacDermid] Purdue Univ, Ctr Families, W Lafayette, IN 47907 USA. [Walters, Heather; Ganoczy, Dara; Wadsworth, Shelley MacDermid] Purdue Univ, Mil Family Res Inst, W Lafayette, IN 47907 USA. RP Nelson, CB (reprint author), Vet Affairs Ann Arbor Healthcare Syst, Div Mental Hlth Serv, Ann Arbor, MI USA. EM claytonn@med.umich.edu FU Department of Veterans Affairs Health Services Research and Development Service [RRP 09-420, SDP 10-047] FX This study was funded by grants RRP 09-420 and SDP 10-047 from the Department of Veterans Affairs Health Services Research and Development Service. NR 42 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2015 VL 66 IS 12 BP 1318 EP 1325 DI 10.1176/appi.ps.201400334 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE7WK UT WOS:000370847300019 PM 26278223 ER PT J AU Ha, Y Collins, ME Martino, D AF Yoonsook Ha Collins, Mary Elizabeth Martino, David TI Child care burden and the risk of child maltreatment among low-income working families SO CHILDREN AND YOUTH SERVICES REVIEW LA English DT Article DE Child care burden; Child maltreatment; Child abuse; Child neglect; Child care issues; Child care subsidies ID COMMUNITY-LEVEL FACTORS; OF-THE-LITERATURE; SUBSTANCE-ABUSE; PHYSICAL ABUSE; SOCIAL-ISOLATION; YOUNG-CHILDREN; NEIGHBORHOODS; NEGLECT; STRESS; RATES AB Studies suggest that a substantial proportion of low-income working mothers experience work disruptions and parental stress related to child care, which may lead to increases in the risk of physical and psychological abuse and neglect of children. However, little research has examined the relationship between child care burden and the risk of child maltreatment among low-income working families. Using the Fragile Families and Child Wellbeing Study 3-year data, this study explores how child care burden is associated with the risk of child maltreatment (physical aggression, psychological aggression, and neglectful behavior) among low-income working mothers. We find that instability in child care arrangements is likely to increase mothers' physical and psychological aggression, while not having someone reliable for emergency child care is likely to increase mothers' neglectful behaviors. Findings also show that the risk of child maltreatment related to child care burden measures is more significant for single mothers than married mothers. Potential policy implications are discussed. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Yoonsook Ha; Collins, Mary Elizabeth] Boston Univ, Boston, MA 02215 USA. [Martino, David] US Dept Vet Affairs, Washington, DC USA. RP Ha, Y (reprint author), Boston Univ, Boston, MA 02215 USA. OI Martino, David/0000-0002-4068-5329 NR 55 TC 1 Z9 1 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0190-7409 EI 1873-7765 J9 CHILD YOUTH SERV REV JI Child. Youth Serv. Rev. PD DEC PY 2015 VL 59 BP 19 EP 27 DI 10.1016/j.childyouth.2015.10.008 PG 9 WC Family Studies; Social Work SC Family Studies; Social Work GA DE2MZ UT WOS:000370462700003 ER PT J AU Nowak, N Hohendorff, J Solecka, I Szopa, M Skupien, J Kiec-Wilk, B Mlynarski, W Malecki, MT AF Nowak, Natalia Hohendorff, Jerzy Solecka, Iwona Szopa, Magdalena Skupien, Jan Kiec-Wilk, Beata Mlynarski, Wojciech Malecki, Maciej T. TI Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic forms of diabetes mellitus SO ENDOCRINE LA English DT Article DE GCK-MODY; HNF1A-MODY; T1DM; T2DM; Ghrelin ID INSULIN-SECRETION; PLASMA GHRELIN; TRANSCRIPTION FACTORS; ACYLATED GHRELIN; HEALTHY HUMANS; GLUCOSE; TYPE-1; EXPRESSION; MUTATIONS; DIAGNOSIS AB Ghrelin is a hormone that regulates appetite. It is likely to be involved in the pathophysiology of varying forms of diabetes. In animal studies, the ghrelin expression was regulated by the hepatocyte nuclear factor 1 alpha (HNF1A). Mutations of the HNF1A gene cause maturity onset diabetes of the young (MODY). We aimed to assess the circulating ghrelin levels in HNF1A-MODY and in other types of diabetes and to evaluate its association with HNF1A mutation status. Our cohort included 46 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes (T2DM) subjects, 42 type 1 diabetes (T1DM) patients, and 31 glucokinase (GCK) gene mutation carriers with diabetes as well as 51 healthy controls. Plasma ghrelin concentration was measured using the immunoenzymatic assay with polyclonal antibody against the C-terminal fragment of its acylated and desacylated forms. Ghrelin concentrations were 0.75 +/- 0.32, 0.70 +/- 0.21, 0.50 +/- 0.20, and 0.40 +/- 0.16 ng/ml in patients with HNF1A-MODY, GCK-MODY, T1DM, and T2DM, respectively. The ghrelin levels were higher in HNF1A-MODY and GCK-MODY than in T1DM and T2DM (p < 0.001 for all comparisons) but lower than in nondiabetic controls (1.02 +/- 0.29 ng/ml, p < 0.001 for both comparisons). In the multivariate linear model, the differences between both MODY groups and common diabetes types remained significant. Analysis by a HNF1A mutation type indicated that ghrelin concentration is similar in patients with different types of sequence differences. Plasma ghrelin level is higher in HNF1A-MODY and GCK-MODY than in the common polygenic forms of diabetes. C1 [Nowak, Natalia; Hohendorff, Jerzy; Szopa, Magdalena; Skupien, Jan; Kiec-Wilk, Beata; Malecki, Maciej T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31501 Krakow, Poland. [Nowak, Natalia] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Hohendorff, Jerzy; Solecka, Iwona; Szopa, Magdalena; Skupien, Jan; Kiec-Wilk, Beata; Malecki, Maciej T.] Univ Hosp, Krakow, Poland. [Mlynarski, Wojciech] Med Univ Lodz, Dept Pediat Oncol Hematol & Diabetol, Lodz, Poland. RP Malecki, MT (reprint author), Jagiellonian Univ, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31501 Krakow, Poland.; Malecki, MT (reprint author), Univ Hosp, Krakow, Poland. EM malecki_malecki@yahoo.com FU Jagiellonian University Medical College [K/ZDS/002808]; EU Framework 7 CEED3 grant [HEALTH-F2-2008-223211] FX The study was supported by the grant from the Jagiellonian University Medical College (K/ZDS/002808) and by the EU Framework 7 CEED3 grant (HEALTH-F2-2008-223211). The results of the study were presented as an Oral Presentation during EASD 2013 Scientific Sessions. The authors would like to express their gratitude to Stephanie Croall, MPH (Joslin Diabetes Center) for her editorial help in the preparation of the manuscript. NR 32 TC 2 Z9 2 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD DEC PY 2015 VL 50 IS 3 BP 643 EP 649 DI 10.1007/s12020-015-0627-5 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD7CX UT WOS:000370082400015 PM 25987348 ER PT J AU Wang, YY Wang, XH Ferrone, CR Schwab, JH Ferrone, S AF Wang, Yangyang Wang, Xinhui Ferrone, Cristina R. Schwab, Joseph H. Ferrone, Soldano TI Intracellular antigens as targets for antibody based immunotherapy of malignant diseases SO MOLECULAR ONCOLOGY LA English DT Review DE Intracellular tumor antigen; PRL-3; Hsp70; Grp78; Grp94; Monoclonal antibodies ID HEAT-SHOCK PROTEINS; GROWTH-FACTOR RECEPTOR; ENDOPLASMIC-RETICULUM CHAPERONE; FACTOR-I RECEPTOR; BREAST-CANCER; CELL-SURFACE; MONOCLONAL-ANTIBODIES; COLORECTAL-CANCER; REGENERATING LIVER-3; HEAT-SHOCK-PROTEIN-70 HSP70 AB This review discusses the potential use of intracellular tumor antigens as targets of antibody-based immunotherapy for the treatment of solid tumors. In addition, it describes the characteristics of the intracellular tumor antigens targeted with antibodies which have been described in the literature and have been identified in the authors' laboratory. Finally, the mechanism underlying the trafficking of the intracellular tumor antigens to the plasma membrane of tumor cells are reviewed. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Wang, Yangyang; Wang, Xinhui; Ferrone, Cristina R.; Ferrone, Soldano] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. [Schwab, Joseph H.; Ferrone, Soldano] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ferrone, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM sferrone@mgh.harvard.edu FU National Cancer Institute [R21 CA164756, 1R21CA173120, 1R03CA175957, R21 CA181851]; Massachusetts General Hospital ECOR Deliberative Interim Supports FX This study was supported by the National Cancer Institute (grants R21 CA164756, 1R21CA173120 and 1R03CA175957 to S.F.; grant R21 CA181851 to X.W.) and by the Massachusetts General Hospital ECOR Deliberative Interim Supports to S.F. and to X.W. NR 123 TC 1 Z9 1 U1 6 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD DEC PY 2015 VL 9 IS 10 BP 1982 EP 1993 DI 10.1016/j.molonc.2015.10.019 PG 12 WC Oncology SC Oncology GA DE2NI UT WOS:000370463600007 PM 26597109 ER PT J AU Frank, RM Taylor, D Verma, NN Romeo, AA Mologne, TS Provencher, MT AF Frank, Rachel M. Taylor, Dean Verma, Nikhil N. Romeo, Anthony A. Mologne, Timothy S. Provencher, Matthew T. TI The Rotator Interval of the Shoulder Implications in the Treatment of Shoulder Instability SO ORTHOPAEDIC JOURNAL OF SPORTS MEDICINE LA English DT Review DE rotator interval; shoulder instability; rotator interval plication; coracohumeral ligament ID MULTIPLE SUTURE TECHNIQUE; MULTIDIRECTIONAL INSTABILITY; ARTHROSCOPIC TREATMENT; CORACOHUMERAL LIGAMENT; GLENOHUMERAL JOINT; MR ARTHROGRAPHY; CUFF INTERVAL; LONG HEAD; ALTERNATIVE TECHNIQUE; CAPSULE CLOSURE AB Biomechanical studies have shown that repair or plication of rotator interval (RI) ligamentous and capsular structures decreases glenohumeral joint laxity in various directions. Clinical outcomes studies have reported successful outcomes after repair or plication of these structures in patients undergoing shoulder stabilization procedures. Recent studies describing arthroscopic techniques to address these structures have intensified the debate over the potential benefit of these procedures as well as highlighted the differences between open and arthroscopic RI procedures. The purposes of this study were to review the structures of the RI and their contribution to shoulder instability, to discuss the biomechanical and clinical effects of repair or plication of rotator interval structures, and to describe the various surgical techniques used for these procedures and outcomes. C1 [Frank, Rachel M.; Taylor, Dean; Verma, Nikhil N.; Romeo, Anthony A.; Mologne, Timothy S.; Provencher, Matthew T.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Provencher, MT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 175 Cambridge St,4th Floor, Boston, MA 02114 USA. EM mtprovencher@partners.org NR 77 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2325-9671 J9 ORTHOP J SPORTS MED JI Orthop. J. Sports Med. PD DEC PY 2015 VL 3 IS 12 AR 2325967115621494 DI 10.1177/2325967115621494 PG 10 WC Sport Sciences SC Sport Sciences GA DE2AE UT WOS:000370427600004 PM 26779554 ER PT J AU Gregory, KE LaPlante, RD Shan, G Kumar, DV Gregas, M AF Gregory, Katherine E. LaPlante, Rose D. Shan, Gururaj Kumar, Deepak Vijaya Gregas, Matt TI Mode of Birth Influences Preterm Infant Intestinal Colonization With Bacteroides Over the Early Neonatal Period SO ADVANCES IN NEONATAL CARE LA English DT Article DE Bacteroides; bacterial colonization; cesarean; microbiome; mode of birth; neonate; newborn intensive care; preterm infant ID GUT MICROBIOTA; BACTERIA; WEIGHT AB Background: Intestinal colonization during infancy is important to short-and long-term health outcomes. Bacteroides, an early member of the intestinal microbiome, is necessary for breaking down complex molecules within the intestine and function to assist the body's immune system in fighting against potentially harmful pathogens. Little is known about the colonization pattern of Bacteroides in preterm infants during the early neonatal period. Purpose: This study measured Bacteroides colonization during the early neonatal period in a population of preterm infants, based on clinical factors including mode of birth, antibiotics, and nutrition. Methods: Bacterial DNA was isolated from 144 fecal samples from 29 preterm infants and analyzed using quantitative real-time polymerase chain reaction. Analyses included liner mixed models to determine which clinical factors affect Bacteroides colonization of the infant gut. Results: We found that infants born via vaginal canal had a higher rate of increase in Bacteroides than infants born via cesarean section (P<.001). We did not find significant associations between antibiotic administration and differences in nutritional exposures with Bacteroides colonization. Implications for Practice: These findings highlight the significant influence of mode of birth on Bacteroides colonization. While mode of birth is not always modifiable, these study findings may help develop interventions for preterm infants born via cesarean section aimed at overcoming delayed Bacteroides colonization. Implications for Research: Greater study of the intestinal microbiome and the clinical factors relevant to the preterm infant is needed so that interventions may be developed and tested, resulting in optimal microbial and immune health. C1 [Gregory, Katherine E.; LaPlante, Rose D.] Brigham & Womens Hosp, Dept Pediat Newborn Med, 75 Francis St, Boston, MA 02115 USA. [Gregory, Katherine E.; LaPlante, Rose D.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Shan, Gururaj] Rowan Univ, Cooper Med Sch, Camden, NJ USA. [Kumar, Deepak Vijaya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gregas, Matt] Boston Coll, Chestnut Hill, MA 02167 USA. RP Gregory, KE (reprint author), Brigham & Womens Hosp, Dept Pediat Newborn Med, 75 Francis St, Boston, MA 02115 USA. EM kgregory1@partners.org FU NINR NIH HHS [K23 NR011320] NR 21 TC 2 Z9 2 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1536-0903 EI 1536-0911 J9 ADV NEONAT CARE JI Adv. Neonatal Care PD DEC PY 2015 VL 15 IS 6 BP 386 EP 393 DI 10.1097/ANC.0000000000000237 PG 8 WC Nursing SC Nursing GA DD4KK UT WOS:000369891300008 PM 26551793 ER PT J AU Park, M Shlipak, MG Vittinghoff, E Katz, R Siscovick, D Sarnak, M Lima, JA Hsu, CY Peralta, CA AF Park, Meyeon Shlipak, Michael G. Vittinghoff, Eric Katz, Ronit Siscovick, David Sarnak, Mark Lima, Joao A. Hsu, Chi-yuan Peralta, Carmen A. TI Associations of kidney injury markers with subclinical cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis SO CLINICAL NEPHROLOGY LA English DT Letter ID GELATINASE-ASSOCIATED LIPOCALIN; GLOMERULAR-FILTRATION-RATE; LEFT-VENTRICULAR MASS; ARTERIAL COMPLIANCE; MOLECULE-1 KIM-1; FUNCTION DECLINE; NORMAL VALUES; RISK; ABNORMALITIES; ELASTICITY C1 [Park, Meyeon; Shlipak, Michael G.; Vittinghoff, Eric; Hsu, Chi-yuan; Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Seattle, WA 98195 USA. [Siscovick, David] New York Acad Med, New York, NY USA. [Sarnak, Mark] Tufts Med Ctr, Boston, MA USA. [Lima, Joao A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Park, M (reprint author), 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA. EM meyeon.park@ucsf.edu FU NCATS NIH HHS [UL1-TR-000040, UL1-TR-001079]; NHLBI NIH HHS [N01-HC-95162, N01-HC-95159, N01-HC-95160, N01-HC-95164, N01-HC-95166, N01-HC-95168, N01-HC-95161, N01-HC-95163, N01-HC-95165, N01-HC-95167, N01-HC-95169]; NIA NIH HHS [R01 AG027002]; NIDDK NIH HHS [K23 DK099238, 1K23DK082793, K24 DK92291] NR 23 TC 0 Z9 0 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD DEC PY 2015 VL 84 IS 6 BP 358 EP 364 DI 10.5414/CN108668 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DC5GQ UT WOS:000369249900007 PM 26558369 ER PT J AU Nino, PKB Durik, M Danser, AHJ de Vries, R Musterd-Bhaggoe, UM Meima, ME Kavousi, M Ghanbari, M Hoeijmakers, JH O'Donnell, CJ Franceschini, N Janssen, GMJ De Mey, JGR Liu, YW Shanahan, CM Franco, OH Dehghan, A Roks, AJM AF Nino, Paula K. Bautista Durik, Matej Danser, A. H. Jan de Vries, Rene Musterd-Bhaggoe, Usha M. Meima, Marcel E. Kavousi, Maryam Ghanbari, Mohsen Hoeijmakers, Jan H. O'Donnell, Christopher J. Franceschini, Nora Janssen, Ger M. J. De Mey, Jo G. R. Liu, Yiwen Shanahan, Catherine M. Franco, Oscar H. Dehghan, Abbas Roks, Anton J. M. TI Phosphodiesterase 1 regulation is a key mechanism in vascular aging SO CLINICAL SCIENCE LA English DT Review DE aging; blood pressure; genetic association; phosphodiesterases; vascular disease ID CONGESTIVE-HEART-FAILURE; CARDIOVASCULAR-DISEASE RISK; MUSCLE-CELL-PROLIFERATION; NITRIC-OXIDE; BLOOD-PRESSURE; ENDOTHELIAL DYSFUNCTION; OXIDATIVE-STRESS; ASSOCIATION; HUMANS; ATHEROSCLEROSIS AB Reduced nitric oxide (NO)/cGMP signalling is observed in age-related vascular disease. We hypothesize that this disturbed signalling involves effects of genomic instability, a primary causal factor in aging, on vascular smooth muscle cells (VSMCs) and that the underlying mechanism plays a role in human age-related vascular disease. To test our hypothesis, we combined experiments in mice with genomic instability resulting from the defective nucleotide excision repair gene ERCC1 (Ercc1(d/-) mice), human VSMC cultures and population genome-wide association studies (GWAS). Aortic rings of Ercc1(d/-) mice showed 43% reduced responses to the soluble guanylate cyclase (sGC) stimulator sodium nitroprusside (SNP). Inhibition of phosphodiesterase (PDE) 1 and 5 normalized SNP-relaxing effects in Ercc1(d/-) to wild-type (WT) levels. PDE1C levels were increased in lung and aorta. cGMP hydrolysis by PDE in lungs was higher in Ercc1(d/-) mice. No differences in activity or levels of cGMP-dependent protein kinase 1 or sGC were observed in Ercc1(d/-) mice compared with WT. Senescent human VSMC showed elevated PDE1A and PDE1C and PDE5 mRNA levels (11.6-, 9- and 2.3-fold respectively), which associated with markers of cellular senescence. Conversely, PDE1 inhibition lowered expression of these markers. Human genetic studies revealed significant associations of PDE1A single nucleotide polymorphisms with diastolic blood pressure (DBP; beta = 0.28, P = 2.47x10(-5)) and carotid intima-media thickness (cIMT; beta = -0.0061, P = 2.89 x 10(-5)). In summary, these results show that genomic instability and cellular senescence in VSMCs increase PDE1 expression. This might play a role in aging-related loss of vasodilator function, VSMC senescence, increased blood pressure and vascular hypertrophy. C1 [Nino, Paula K. Bautista; Durik, Matej; Danser, A. H. Jan; de Vries, Rene; Musterd-Bhaggoe, Usha M.; Roks, Anton J. M.] Erasmus MC, Dept Internal Med, Div Vasc Dis & Pharmacol, NL-3015 CN Rotterdam, Netherlands. [Nino, Paula K. Bautista; Kavousi, Maryam; Ghanbari, Mohsen; Franco, Oscar H.; Dehghan, Abbas] Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands. [Durik, Matej] Acad Sci Czech Republic, Inst Mol Genet, CR-14220 Prague, Czech Republic. [Meima, Marcel E.] Erasmus MC, Div Endocrinol, Dept Internal Med, NL-3015 CN Rotterdam, Netherlands. [Hoeijmakers, Jan H.] Erasmus MC, Dept Genet, NL-3015 CN Rotterdam, Netherlands. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02114 USA. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Janssen, Ger M. J.; De Mey, Jo G. R.] Maastricht Univ, Dept Pharmacol, NL-6211 LK Maastricht, Netherlands. [De Mey, Jo G. R.] Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, DK-5230 Odense, Denmark. [Liu, Yiwen; Shanahan, Catherine M.] Kings Coll London, James Black Ctr, Div Cardiovasc, London SE5 9NU, England. RP Roks, AJM (reprint author), Erasmus MC, Dept Internal Med, Div Vasc Dis & Pharmacol, NL-3015 CN Rotterdam, Netherlands. EM a.roks@erasmusmc.nl OI Dehghan, Abbas/0000-0001-6403-016X FU Academy of Sciences of the Czech Republic [RVO 68378050]; BIOCEV - Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University [CZ.1.05/1.1.00/02.0109] FX This work was supported by the Academy of Sciences of the Czech Republic [grant number RVO 68378050 (to M.D.)]; the BIOCEV - Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University [grant number CZ.1.05/1.1.00/02.0109]. NR 47 TC 5 Z9 5 U1 3 U2 11 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0143-5221 EI 1470-8736 J9 CLIN SCI JI Clin. Sci. PD DEC 1 PY 2015 VL 129 IS 12 BP 1061 EP 1075 DI 10.1042/CS20140753 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DD1WS UT WOS:000369714400007 ER PT J AU Cetrulo, CL Drijkoningen, T Sachs, DH AF Cetrulo, Curtis L., Jr. Drijkoningen, Tessa Sachs, David H. TI Tolerance induction via mixed chimerism in vascularized composite allotransplantation: is it time for clinical application? SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE bone marrow transplantation; mixed chimerism; tolerance; vascularized composite allograft ID BONE-MARROW-TRANSPLANTATION; TOTAL-LYMPHOID IRRADIATION; LARGE ANIMAL-MODEL; NONHUMAN-PRIMATES; HEMATOPOIETIC CHIMERISM; TISSUE ALLOGRAFTS; IMMUNE TOLERANCE; SWINE MODEL; T-CELLS; SKIN AB Purpose of review The present review summarizes current data on the induction of immunologic tolerance through mixed hematopoietic chimerism relevant to applying this approach to vascularized composite allotransplantation. Recent findings Clinical allograft tolerance has been achieved recently for kidney transplants, using nonmyeloablative conditioning regimens and bone marrow transplantation from living donors. The mixed chimerism attained in these studies was either transient or durable, and both permitted tolerance of the renal allografts to be achieved across MHC-matched and MHC-mismatched barriers. In order to extend these protocols to deceased donor transplants across full MHC-mismatched combinations, as will be required for vascularized composite allografts (VCA), a delayed tolerance protocol has recently been developed, in which the donor bone marrow is given 4 months posttransplant. Recent primate studies of kidney transplants using this protocol have been successful and have demonstrated that strategies to abrogate memory T cells may be helpful. Summary Induction of tolerance in renal allograft transplantation has been achieved clinically, via mixed chimerism protocols. Modifications of these protocols for transplants, which require use of deceased donors across full MHC mismatches, have shown promise in preclinical models. It is therefore appropriate to consider evaluation of these protocols in clinical trials for kidney transplants, and if successful, for VCA. C1 [Cetrulo, Curtis L., Jr.; Drijkoningen, Tessa; Sachs, David H.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Vascularized Composite Allotransplantat Lab, Boston, MA 02114 USA. [Cetrulo, Curtis L., Jr.; Drijkoningen, Tessa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02129 USA. [Cetrulo, Curtis L., Jr.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Transplantat Biol Res Ctr Labs, Boston, MA 02114 USA. RP Cetrulo, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci,Transplantat Biol Res Ctr La, MGH East Bldg 149,13th St, Boston, MA 02114 USA. EM ccetrulo@mgh.harvard.edu NR 38 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD DEC PY 2015 VL 20 IS 6 BP 602 EP 607 DI 10.1097/MOT.0000000000000248 PG 6 WC Transplantation SC Transplantation GA DD1TT UT WOS:000369705400003 PM 26536420 ER PT J AU Ramirez, M Groff, S Kowalewski, C AF Ramirez, Mary Groff, Sarah Kowalewski, Catherine TI Eruptive Keratoacanthomas After Photodynamic Therapy SO DERMATOLOGIC SURGERY LA English DT Letter C1 [Ramirez, Mary] Texas Tech Univ, Hlth Sci Ctr, Sch Med, Lubbock, TX 79409 USA. [Groff, Sarah; Kowalewski, Catherine] Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol, San Antonio, TX 78229 USA. [Kowalewski, Catherine] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Ramirez, M (reprint author), Texas Tech Univ, Hlth Sci Ctr, Sch Med, Lubbock, TX 79409 USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD DEC PY 2015 VL 41 IS 12 BP 1426 EP 1429 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA DD5DY UT WOS:000369944000015 PM 26580847 ER PT J AU Armand, P AF Armand, Philippe TI Checkpoint blockade in lymphoma SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID B-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; ANTI-PD-L1 ANTIBODY; HODGKIN LYMPHOMAS; ADVANCED MELANOMA; PD-1 EXPRESSION; T-CELLS; CANCER; SAFETY; TOLERANCE AB Immune checkpoint blockade therapy (CBT) was born of the combination of several elements: the understanding of some of the important immune regulation pathways in humans; the recognition that tumors can engage those pathways to evade immune responses; and the clinical development of monoclonal antibodies targeting checkpoint receptors to restore effective anti-tumor immunity. This form of therapy, focused to date mostly on the cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed-death 1 (PD-1) pathways, has already revolutionized the treatment of several solid tumors. Hematologic malignancies (HMs) offer a promising testing ground for this strategy, and several trials have already demonstrated evidence of therapeutic activity with checkpoint blockade, especially in lymphoma. This review will discuss the current clinical results of CBT in lymphoma in the context of their scientific underpinning, and build from this summary a projection of how the field may evolve in the near future. C1 [Armand, Philippe] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02215 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM parmand@partners.org FU Bristol-Myers Squibb; Merck FX The author has received research funding from Bristol-Myers Squibb and Merck, and has consulted for Merck and Infinity Pharmaceuticals. NR 38 TC 3 Z9 3 U1 2 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2015 BP 69 EP 73 PG 5 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA DD0JU UT WOS:000369607000011 ER PT J AU Nikiforow, S Berliner, N AF Nikiforow, Sarah Berliner, Nancy TI The unique aspects of presentation and diagnosis of hemophagocytic lymphohistiocytosis in adults SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID PROGNOSTIC-FACTORS; PERFORIN GENE; EARLY DEATH; LYMPHOMA; MUTATIONS; CHILDREN; STXBP2; INFECTION; FERRITIN; OUTCOMES AB Hemophagocytic lymphohistiocytosis (HLH) was initially described as an inflammatory condition affecting young children but is increasingly diagnosed in adults. Presenting features such as fever, cytopenias, phagocytosis, elevated ferritin, and increased levels of soluble IL-2 receptor are common in both age groups, but the prevalence of several clinical and biochemical criteria differ between pediatric and adult patients. Specifically, an elevated ferritin level does not have the same specificity for HLH in adults, and many other inflammatory conditions need to be considered in the differential. In contrast to the high incidence of infectious triggers seen in pediatric HLH, HLH in adults is often precipitated by a hematologic malignancy. Malignancy-associated HLH has unique manifestations and a uniformly very poor prognosis. Given these differences, diagnostic scoring systems unique to adult HLH have been proposed, and additional prognostic clinical and immunologic parameters are being explored. Although a genetic predisposition is increasingly found to underlie cases of adult-onset HLH, the mutations are less likely to be bi-allelic and differ slightly from those seen in pediatric cases of familial HLH. The facilitating genetic and environmental factors governing presentation of HLH in adults remain elusive. Understanding the clinical aspects and pathophysiology specific to adults with HLH is necessary to tailor therapies derived in pediatric disease to this under-recognized population. C1 [Nikiforow, Sarah] Dana Farber Canc Ctr, Boston, MA USA. [Berliner, Nancy] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Berliner, N (reprint author), Brigham & Womens Hosp, Div Hematol, 75 Francis St, Boston, MA 02115 USA. EM nberliner@partners.org NR 50 TC 4 Z9 4 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2015 BP 183 EP 189 PG 7 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA DD0JU UT WOS:000369607000027 ER PT J AU Arber, DA Hasserjian, RP AF Arber, Daniel A. Hasserjian, Robert P. TI Reclassifying myelodysplastic syndromes: what's where in the new WHO and why SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; ACUTE ERYTHROID LEUKEMIA; REFRACTORY CYTOPENIA; MONOSOMAL KARYOTYPE; CLINICAL-SIGNIFICANCE; CLONAL HEMATOPOIESIS; FLOW-CYTOMETRY; WORKING GROUP; MUTATIONS AB A revision to the 4th edition of the WHO Classification of myelodysplastic syndromes (MDSs), originally published in 2008, is expected in mid-2016. Based on recommendations of a Clinical Advisory Committee, the revision will aim to incorporate new discoveries in MDS that impact existing disease categories. Although the basic diagnostic principles of the WHO classification remain unchanged, several changes to the classification are proposed. All revisions are considered preliminary until the actual publication of the monograph and online document. Proposals for change include abandoning the routine use of "refractory anemia/cytopenia" in the various disease names, including the prognostic significance of gene mutations in MDS, revising the diagnostic criteria for MDS entities with ring sideroblasts based on the detection of SF3B1 mutations, modifying the cytogenetic criteria for MDS with isolated del(5q), reclassifying most cases of the erythroid/myeloid type of acute erythroleukemia, and recognizing the familial link in some cases of MDS. This review will provide details of the major proposed changes as well as rationale for the revisions. C1 [Arber, Daniel A.] Stanford Univ, Dept Pathol, 300 Pasteur Dr,H1507C, Stanford, CA 94305 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hasserjian, Robert P.] Harvard Univ, Sch Med, Boston, MA USA. RP Arber, DA (reprint author), Stanford Univ, Dept Pathol, 300 Pasteur Dr,H1507C, Stanford, CA 94305 USA. EM darber@stanford.edu NR 40 TC 4 Z9 5 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2015 BP 294 EP 298 PG 5 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA DD0JU UT WOS:000369607000044 ER PT J AU DeAngelo, DJ AF DeAngelo, Daniel J. TI The use of novel monoclonal antibodies in the treatment of acute lymphoblastic leukemia SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; PHASE-II; INOTUZUMAB OZOGAMICIN; ADULT PATIENTS; HYPER-CVAD; THERAPY; BLINATUMOMAB; ANTI-CD19; TRIAL; CHEMOIMMUNOTHERAPY AB Regardless of age, patients with relapsed or refractory acute lymphoblastic leukemia (ALL) have extremely poor outcomes. The success of reinduction chemotherapy remains dismal, because complete remission rates are low and seldom durable. Clearly, new and novel strategies are needed to improve the outcome of patients with relapsed or refractory ALL. Patients with early relapse, especially those still receiving chemotherapy, tend to have a much poorer outcome and are often chemotherapy resistant. Although high-dose approaches may overcome chemotherapy resistance, long-term disease-free and overall survival remains limited. Several approaches have been used to target antigens, including cluster of differentiation (CD) 19, CD20, CD22, and CD52, on the surface of the malignant lymphoblast with striking efficacy. This review will focus on the clinical application of the major classes of antibodies, including naked antibodies, drug-antibody conjugates, immunotoxins, and T cell-engaging bispecific antibodies. Hopefully, these novel monoclonal antibodies will result in a significant improvement in the outcome of patients with relapsed or refractory ALL. C1 [DeAngelo, Daniel J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM daniel_deangelo@dfci.harvard.edu NR 44 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 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2015 BP 400 EP 405 PG 6 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA DD0JU UT WOS:000369607000057 ER PT J AU LeBlanc, TW El-Jawahri, A AF LeBlanc, Thomas W. El-Jawahri, Areef TI When and why should patients with hematologic malignancies see a palliative care specialist? SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; SYMPTOM BURDEN; ONCOLOGY CARE; OUTCOMES; COMMUNICATION; PERCEPTIONS; SURVIVAL; HOSPICE AB Palliative care is a multidisciplinary approach to symptom management, psychosocial support, and assistance in treatment decision-making for patients with serious illness and their families. It emphasizes well-being at any point along the disease trajectory, regardless of prognosis. The term "palliative care" is often incorrectly used as a synonym for end-of-life care, or "hospice care". However, palliative care does not require a terminal diagnosis or proximity to death, a misconception that we will address in this article. Multiple randomized clinical trials demonstrate the many benefits of early integration of palliative care for patients with cancer, including reductions in symptom burden, improvements in quality-of-life, mood, and overall survival, as well as improved caregiver outcomes. Thus, early concurrent palliative care integrated with cancer-directed care has emerged as a standard-of-care practice for patients with cancer. However, patients with hematologic malignancies rarely utilize palliative care services, despite their many unmet palliative care needs, and are much less likely to use palliative care compared to patients with solid tumors. In this article, we will define "palliative care" and address some common misconceptions regarding its role as part of high-quality care for patients with cancer. We will then review the evidence supporting the integration of palliative care into comprehensive cancer care, discuss perceived barriers to palliative care in hematologic malignancies, and suggest opportunities and triggers for earlier and more frequent palliative care referral in this population. C1 [LeBlanc, Thomas W.] Duke Univ, Sch Med, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC 27710 USA. [El-Jawahri, Areef] Harvard Univ, Sch Med, Dept Med, Ctr Canc,Massachusetts Gen Hosp,Div Hematol Malig, Boston, MA USA. RP LeBlanc, TW (reprint author), Duke Univ, Sch Med, Dept Med, Div Hematol Malignancies & Cellular Therapy,DUMC, Box 2715, Durham, NC 27710 USA. EM thomas.leblanc@duke.edu NR 44 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2015 BP 471 EP 478 PG 8 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA DD0JU UT WOS:000369607000068 ER PT J AU Dickerson, B AF Dickerson, Brad TI Tau pet imaging in neurodegenerative dementias SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 [Dickerson, Brad] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Brad] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD DEC PY 2015 VL 27 SU 1 MA S10.03 BP S20 EP S20 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA DD1UD UT WOS:000369706400041 ER PT J AU Monlezun, DJ Camargo, CA Mullen, JT Quraishi, SA AF Monlezun, Dominique J. Camargo, Carlos A., Jr. Mullen, John T. Quraishi, Sadeq A. TI Vitamin D Status and the Risk of Anemia in Community-Dwelling Adults Results from the National Health and Nutrition Examination Survey 2001-2006 SO MEDICINE LA English DT Article ID D DEFICIENCY; HEMOGLOBIN CONCENTRATION; 25-HYDROXYVITAMIN D; IRON-DEFICIENCY; RENAL ANEMIA; PREVALENCE; ASSOCIATION; METABOLISM; RESISTANCE; REGRESSION AB Low vitamin D status has been implicated in several chronic medical conditions and unfavorable health outcomes. Our goal was to investigate whether serum 25-hydroxyvitamin D (25OHD) levels are a potentially modifiable risk factor for anemia in a nationally representative cohort of community-dwelling individuals in the United States. We performed a cross-sectional study of 5456 individuals (>= 17 years) from the National Health and Nutrition Examination Survey from 2001 to 2006. Locally weighted scatterplot smoothing (LOWESS) was used to graphically depict the relationship between serum 25OHD levels and the cumulative frequency of anemia. Multi-variable logistic regression models were then used to assess the independent association of 25OHD levels with anemia, while controlling for age, sex, race, body mass index, chronic kidney disease, as well as serum levels of C-reactive protein, ferritin, iron, vitamin B12, and folic acid. The mean (standard error) 25OHD and hemoglobin levels in the analytic group were 23.5 (0.4) ng/mL and 14.4 (0.1) g/dL, respectively. Prevalence of anemia was 3.9%. Locally weighted scatterplot smoothing analysis demonstrated a near-linear relationship between vitamin D status and cumulative frequency of anemia up to 25OHD levels of approximately 20 ng/mL. With increasing 25OHD levels, the curve flattened out progressively. Multivariable regression analysis demonstrated an inverse association of 25OHD levels with the risk of anemia (adjusted odds ratio 0.97; 95% confidence interval 0.95-0.99 per 1 ng/mL change in 25OHD). Compared to individuals with >= 20 ng/mL, individuals with 25OHD levels <20 ng/mL were more likely to be anemic (adjusted odds ratio 1.64; 95% confidence interval 1.08-2.49). In a nationally representative sample of community-dwelling individuals in the United States, low 25OHD levels were associated with increased risk of anemia. Randomized controlled trials are needed to determine whether optimizing vitamin D status can reduce the burden of anemia in the general population. C1 [Monlezun, Dominique J.] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Monlezun, Dominique J.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Camargo, Carlos A., Jr.; Mullen, John T.; Quraishi, Sadeq A.] Harvard Univ, Sch Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRJ 402, Boston, MA 02114 USA. RP Quraishi, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRJ 402, Boston, MA 02114 USA. EM squraishi@mgh.harvard.edu FU US National Institutes of Health [T32 GM007592, L30 TR001257] FX SAQ received support from the US National Institutes of Health T32 GM007592 and L30 TR001257. NR 49 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD DEC PY 2015 VL 94 IS 50 AR e1799 DI 10.1097/MD.0000000000001799 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DD3XE UT WOS:000369855900004 PM 26683908 ER PT J AU Joffe, H Crawford, S Freeman, MP Athappilly, G David, W Kim, S Galvan, T Camuso, J Cathryn, F Cohen, LS Hall, J AF Joffe, Hadine Crawford, Sybil Freeman, Marlene P. Athappilly, Geena David, Wolfe Kim, Semmie Galvan, Thania Camuso, Julia Cathryn, Freid Cohen, Lee S. Hall, Janet TI Influence of Reproductive Hormones and Nighttime Hot Flashes on Mood in Depressed Perimenopausal Women reporting Stressful Life Events SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 26th Annual Meeting of the North-American-Menopause-Society CY SEP 30-OCT 03, 2015 CL Las Vegas, NV SP N Amer Menopause Soc C1 [Joffe, Hadine; Freeman, Marlene P.; Cohen, Lee S.] Massachusetts Gen Hosp, Psychiat Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Joffe, Hadine; Athappilly, Geena; David, Wolfe; Kim, Semmie; Galvan, Thania; Camuso, Julia; Cathryn, Freid] Brigham & Womens Hosp, Psychiat Womens Hormones & Aging Res Program, Boston, MA 02115 USA. [Crawford, Sybil] Univ Massachusetts, Sch Med, Worcester, MA USA. [Hall, Janet] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. OI Hall, Janet/0000-0003-4644-3061 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2015 VL 22 IS 12 MA S-1 BP 1367 EP 1368 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD4JO UT WOS:000369888500048 ER PT J AU Carpenter, J Woods, NF Otte, J Guthrie, K Hohensee, C Newton, KM Joffe, H Cohen, L Sternfeld, B Lau, RJ Reed, SD LaCroix, AZ AF Carpenter, Janet Woods, Nancy F. Otte, Julie Guthrie, Katherine Hohensee, Chancellor Newton, Katherine M. Joffe, Hadine Cohen, Lee Sternfeld, Barbara Lau, R. Jane Reed, Susan D. LaCroix, Andrea Z. TI MsFLASH Participants' Priorities for Alleviating Menopausal Symptoms SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 26th Annual Meeting of the North-American-Menopause-Society CY SEP 30-OCT 03, 2015 CL Las Vegas, NV SP N Amer Menopause Soc C1 [Carpenter, Janet; Otte, Julie] Indiana Univ, Sch Nursing, Sci Nursing Care, Indianapolis, IN 46204 USA. [Woods, Nancy F.] Univ Washington, Biobehav Nursing, Seattle, WA 98195 USA. [Guthrie, Katherine; Hohensee, Chancellor] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Newton, Katherine M.] Grp Hlth Res Inst, Seattle, WA USA. [Joffe, Hadine] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Cohen, Lee] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Cohen, Lee] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. [Sternfeld, Barbara] Kaiser Permanente Med Program Northern Calif, Div Res, Oakland, CA USA. [Lau, R. Jane] Indiana Univ, Sch Med, Dept Obstet & Gynecol, Indianapolis, IN 46202 USA. [Reed, Susan D.] Univ Washington, Sch Med, Dept Obstet Gynecol, Seattle, WA USA. [Reed, Susan D.] Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA USA. [LaCroix, Andrea Z.] Univ Calif San Diego, Dept Prevent Med, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2015 VL 22 IS 12 MA P-15 BP 1379 EP 1379 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD4JO UT WOS:000369888500086 ER PT J AU Goldstein, SR Mischoulon, D AF Goldstein, Steven R. Mischoulon, David TI Does Relizen, a non-hormonal treatment for the relief of menopausal hot flashes, work through a serotonergic mechanism of action? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 26th Annual Meeting of the North-American-Menopause-Society CY SEP 30-OCT 03, 2015 CL Las Vegas, NV SP N Amer Menopause Soc C1 [Goldstein, Steven R.] NYU, Sch Med, New York, NY USA. [Mischoulon, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mischoulon, David] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2015 VL 22 IS 12 MA P-30 BP 1383 EP 1383 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD4JO UT WOS:000369888500101 ER PT J AU Kaplan, TB Berkowitz, AL Samuels, MA AF Kaplan, Tamara B. Berkowitz, Aaron L. Samuels, Martin A. TI Cardiovascular Dysfunction in Multiple Sclerosis SO NEUROLOGIST LA English DT Review DE multiple sclerosis; cardiovascular; autonomic dysfunction; blood pressure; heart rate; takotsubo cardiomyopathy; fingolimod; mitoxantrone ID NEUROGENIC PULMONARY-EDEMA; TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; ORTHOSTATIC TACHYCARDIA SYNDROME; PAROXYSMAL ATRIAL-FIBRILLATION; HEART-RATE-VARIABILITY; BRAIN-STEM LESIONS; P-WAVE DISPERSION; AUTONOMIC DYSFUNCTION; MITOXANTRONE NOVANTRONE; CARDIAC REPOLARIZATION AB Background: Multiple sclerosis (MS) can affect cardiovascular function in a variety of ways leading to abnormalities in blood pressure response, heart rate, heart rhythm, left ventricular systolic function, and may cause pulmonary edema or cardiomyopathy. Cardiovascular dysfunction in MS is incompletely understood and likely underrecognized. Review Summary: The clinical presentation and pathophysiology of cardiovascular dysfunction in MS are reviewed, as are the cardiovascular toxicities of MS therapies, fingolimod and mitoxantrone. Cardiovascular dysfunction in MS can be caused by brainstem lesions affecting autonomic pathways in the medulla, overall plaque burden, and clinical severity of the disease. Conclusions: Cardiovascular abnormalities may be clinical or subclinical, and can lead to sudden death in some cases. Neurologists should be aware of the clinical presentation and pathophysiology of cardiovascular dysfunction in MS so as to ameliorate cardiovascular symptoms, prevent cardiovascular complications, and choose therapeutic agents that do not worsen underlying cardiovascular disease. C1 [Kaplan, Tamara B.; Berkowitz, Aaron L.; Samuels, Martin A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Kaplan, Tamara B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Samuels, Martin A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Miriam Sydney Joseph Prof Neurol, Boston, MA 02115 USA. RP Kaplan, TB (reprint author), Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. EM tbkaplan@partners.org NR 73 TC 2 Z9 2 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD DEC PY 2015 VL 20 IS 6 BP 108 EP 114 DI 10.1097/NRL.0000000000000064 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DD5HB UT WOS:000369952600005 PM 26671744 ER PT J AU Li, Q Chen, L Halpern, EF Samir, AE AF Li, Qian Chen, Lei Halpern, Elkan F. Samir, Anthony E. TI Detection and Measurement of Stones With Ultrasound Strain Elastography A Phantom Study SO ULTRASOUND QUARTERLY LA English DT Article DE ultrasonography; strain elastography; stone; horizontal dimension; vertical dimension ID TIME TISSUE ELASTOGRAPHY; SOLID BREAST MASSES; DIAGNOSIS; BENIGN; SONOGRAPHY; MANAGEMENT; FIBROSIS AB The sonoelastographic appearances of stones in a phantom were evaluated in this study. Ten stones were embedded into a tissue-mimicking meat phantom. The stone axial (vertical) and transverse (horizontal) dimensions measured by an electronic digital caliper, gray-scale ultrasound, and strain elastography (SE) were compared in 5 groups with stones embedded at different depths. In this study, physically measured axial and transverse stone dimensions were 1.17 to 6.86 and 1.30 to 11.15 mm, respectively. Strain elastography showed a characteristic 3-layer pattern associated with stones, comprising a superficial transition region, a hard region, and a deep transition region. As SE data were available in group 5, only data of groups 1 to 4 were analyzed. Compared with physical measurements, measurement mean errors of SE horizontal and SE vertical dimensions ranged from -0.20 to 0.42 mm and from -1.28 to -0.05 mm, respectively, in the 4 groups. Paired t testing demonstrated a significant horizontal dimension measurement error difference between B mode and SE method in group 4 (0.44 vs -0.20 mm, P < 0.05; F = 1.18, P > 0.05), but not in the other groups. Strain elastography horizontal dimension measurement error was not statistically correlated with stone size in the 4 groups. Strain elastography vertical dimension measurement error significantly correlated with stone size only in group 4 (P < 0.05). Preliminary results indicate that stone horizontal and vertical dimensions can be measured using SE in a soft tissue phantom, including when shadowing precludes measurement of vertical dimension on conventional 2-dimensional ultrasound. These results provide substantial motivation to further investigate SE as a modality to image stones in clinical practice. C1 [Li, Qian; Chen, Lei] Peking Univ, Hlth Sci Ctr, Hosp 1, Dept Ultrasound, Beijing 100871, Peoples R China. [Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Samir, Anthony E.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, 55 Fruit St, Boston, MA 02114 USA. RP Samir, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM asamir@mgh.harvard.edu NR 26 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD DEC PY 2015 VL 31 IS 4 BP 272 EP 278 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD5JG UT WOS:000369958900006 PM 26656990 ER PT J AU Graetz, I Huang, J Brand, R Shortell, SM Rundall, TG Bellows, J Hsu, J Jaffe, M Reed, ME AF Graetz, Ilana Huang, Jie Brand, Richard Shortell, Stephen M. Rundall, Thomas G. Bellows, Jim Hsu, John Jaffe, Marc Reed, Mary E. TI The Impact of Electronic Health Records and Teamwork on Diabetes Care Quality SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CENTERED MEDICAL HOME; OF-CARE; DISEASE MANAGEMENT; CHRONIC ILLNESS; OUTCOMES; ORGANIZATIONS; ASSOCIATION; ATTRIBUTES; TEAMS AB Objectives: Evidence of the impact electronic health records (EHRs) have on clinical outcomes remains mixed. The impact of EHRs likely depends on the organizational context in which they are used. This study focuses on one aspect of the organizational context: cohesion of primary care teams. We examined whether team cohesion among primary care team members changed the association between EHR use and changes in clinical outcomes for patients with diabetes. Study Design: Retrospective longitudinal study. Methods: We combined provider-reported primary care team cohesion with lab values for patients with diabetes collected during the staggered EHR implementation (2005-2009). We used multivariate regression models with patient-level fixed effects to assess whether team cohesion levels changed the association between outpatient EHR use and clinical outcomes for patients with diabetes. Subjects were comprised of 80,611 patients with diabetes, in whom we measured changes in glycated hemoglobin (A1C) and low-density lipoprotein cholesterol (LDL-C). Results: For A1C, EHR use was associated with an average decrease of 0.11% for patients with higher-cohesion primary care teams compared with a decrease of 0.08% for patients with lower-cohesion teams (difference = 0.02% in A1C; 95% CI, 0.01%-0.03%). For LDL-C, EHR use was associated with a decrease of 2.15 mg/dL for patients with higher-cohesion primary care teams compared with a decrease of 1.42 mg/dL for patients with lower-cohesion teams (difference = 0.73 mg/dL; 95% CI, 0.41-1.11 mg/dL). Conclusions: Patients cared for by higher cohesion primary care teams experienced modest but statistically significantly greater EHR-related health outcome improvements, compared with patients cared for by providers practicing in lower cohesion teams. C1 [Graetz, Ilana] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, 66 N Pauline St,Ste 633, Memphis, TN 38163 USA. [Graetz, Ilana; Reed, Mary E.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Brand, Richard] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shortell, Stephen M.; Rundall, Thomas G.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Bellows, Jim] Kaiser Permanente, Care Management Inst, Oakland, CA USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jaffe, Marc] Kaiser South San Francisco Med Ctr, Endocrinol & Internal Med, San Francisco, CA USA. RP Graetz, I (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, 66 N Pauline St,Ste 633, Memphis, TN 38163 USA. EM igraetz@uthsc.edu RI Graetz, Ilana/N-1189-2016 OI Graetz, Ilana/0000-0003-3664-5815 FU Agency for Healthcare Research and Quality [1R36HS021082-01, R01HS015280]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK085070] FX This research was supported by grants from the Agency for Healthcare Research and Quality (1R36HS021082-01 and R01HS015280) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK085070). The content, findings, and conclusions of this paper are the sole responsibility of the authors; the sponsors were not involved in any way in the determination of the content of this paper. NR 36 TC 1 Z9 1 U1 4 U2 7 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2015 VL 21 IS 12 BP 878 EP 884 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DC7GQ UT WOS:000369388100012 PM 26671699 ER PT J AU Levy, DE Munshi, VN Ashburner, JM Zai, AH Grant, RW Atlas, SJ AF Levy, Douglas E. Munshi, Vidit N. Ashburner, Jeffrey M. Zai, Adrian H. Grant, Richard W. Atlas, Steven J. TI Health IT-Assisted Population-Based Preventive Cancer Screening: A Cost Analysis SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; TAILORED INTERVENTIONS; MANAGEMENT-SYSTEM; PATIENT; ADHERENCE; REMINDERS AB Objectives: Novel health information technology (IT)-based strategies harnessing patient registry data seek to improve care at a population level. We analyzed costs from a randomized trial of 2 health IT strategies to improve cancer screening compared with usual care from the perspective of a primary care network. Study Design: Monte Carlo simulations were used to compare costs across management strategies. Methods: We assessed the cost of the software, materials, and personnel for baseline usual care (BUC) compared with augmented usual care (AUC [ie, automated patient outreach]) and augmented usual care with physician input (AUCPI [ie, outreach mediated by physicians' knowledge of their patient panels]) over 1 year. Results: AUC and AUCPI each reduced the time physicians spent on cancer screening by 6.5 minutes per half-day clinical session compared with BUC without changing cancer screening rates. Assuming the value of this time accrues to the network, total costs of cancer screening efforts over the study year were $3.83 million for AUC, $3.88 million for AUCPI, and $4.10 million for BUC. AUC was cost-saving relative to BUC in 87.1% of simulations. AUCPI was cost-saving relative to BUC in 82.5% of simulations. Ongoing per patient costs were lower for both AUC ($35.63) and AUCPI ($35.58) relative to BUC ($39.51). Conclusions: Over the course of the study year, the value of reduced physician time devoted to preventive cancer screening outweighed the costs of the interventions. Primary care networks considering similar interventions will need to capture adequate physician time savings to offset the costs of expanding IT infrastructure. C1 [Levy, Douglas E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Ashburner, Jeffrey M.; Atlas, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Internal Med,Med Serv, Boston, MA USA. [Zai, Adrian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA USA. [Munshi, Vidit N.] Harvard Univ, Boston, MA 02115 USA. [Grant, Richard W.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Levy, DE (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM dlevy3@mgh.harvard.edu FU Agency for Healthcare Research and Quality (AHRQ) [R03-HS020308, R18-HS018161]; Controlled Risk Insurance Company/Risk Management Foundation; Massachusetts General Hospital Primary Care Operations Improvement Program; Massachusetts General Physicians Organization FX This study was supported by grants from the Agency for Healthcare Research and Quality (AHRQ R03-HS020308 [DEL], R18-HS018161 [SJA]), and the Controlled Risk Insurance Company/Risk Management Foundation, and by institutional funding through the Massachusetts General Hospital Primary Care Operations Improvement Program and the Massachusetts General Physicians Organization. No funding source had a 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. Dr Levy had full access to all of the data in the study and takes responsibility for the integrity and the accuracy of the data/analysis. NR 23 TC 0 Z9 0 U1 3 U2 3 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2015 VL 21 IS 12 BP 885 EP 891 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DC7GQ UT WOS:000369388100013 PM 26671700 ER PT J AU Reid, MW Cohen, S Wang, H Kaung, A Patel, A Tashjian, V Williams, DL Martinez, B Spiegel, BMR AF Reid, Mark W. Cohen, Samuel Wang, Hank Kaung, Aung Patel, Anish Tashjian, Vartan Williams, Demetrius L., Jr. Martinez, Bibiana Spiegel, Brennan M. R. TI Preventing Patient Absenteeism: Validation of a Predictive Overbooking Model SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID NON-ATTENDANCE; SCREENING COLONOSCOPY; OUTPATIENT ENDOSCOPY; GENERAL-PRACTICE; PRIMARY-CARE; NO-SHOWS; APPOINTMENTS; ACCESS; NONATTENDANCE; TRIAL AB Objectives: To develop a model that identifies patients at high risk for missing scheduled appointments ("no-shows" and cancellations) and to project the impact of predictive overbooking in a gastrointestinal endoscopy clinic-an exemplar resource-intensive environment with a high no-show rate. Study Design: We retrospectively developed an algorithm that uses electronic health record (EHR) data to identify patients who do not show up to their appointments. Next, we prospectively validated the algorithm at a Veterans Administration healthcare network clinic. Methods: We constructed a multivariable logistic regression model that assigned a no-show risk score optimized by receiver operating characteristic curve analysis. Based on these scores, we created a calendar of projected open slots to offer to patients and compared the daily performance of predictive overbooking with fixed overbooking and typical "1 patient, 1 slot" scheduling. Results: Data from 1392 patients identified several predictors of no-show, including previous absenteeism, comorbid disease burden, and current diagnoses of mood and substance use disorders. The model correctly classified most patients during the development (area under the curve [AUC] = 0.80) and validation phases (AUC = 0.75). Prospective testing in 1197 patients found that predictive overbooking averaged 0.51 unused appointments per day versus 6.18 for typical booking (difference = -5.67; 95% CI, -6.48 to -4.87; P < .0001). Predictive overbooking could have increased service utilization from 62% to 97% of capacity, with only rare clinic overflows. Conclusions: Information from EHRs can accurately predict whether patients will no-show. This method can be used to overbook appointments, thereby maximizing service utilization while staying within clinic capacity. C1 [Reid, Mark W.; Cohen, Samuel; Kaung, Aung; Patel, Anish; Williams, Demetrius L., Jr.; Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Reid, Mark W.; Williams, Demetrius L., Jr.; Martinez, Bibiana; Spiegel, Brennan M. R.] Cedars Sinai Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Wang, Hank] Kaiser Permanente No Calif, Oakland, CA USA. [Tashjian, Vartan; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), West Los Angeles VA Med Ctr, Div Gastroenterol, Med & Publ Hlth, 11301 Wilshire Blvd,Bldg 115,Rm 215, Los Angeles, CA 90073 USA. EM brennan.spiegel@cshs.org FU VA Health Services Research and Development Merit Award [IIR 12-055] FX This study was funded by a VA Health Services Research and Development Merit Award (IIR 12-055). NR 40 TC 1 Z9 1 U1 3 U2 9 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2015 VL 21 IS 12 BP 902 EP 910 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DC7GQ UT WOS:000369388100015 PM 26671702 ER PT J AU Haverhals, LM Sayre, G Helfrich, CD Battaglia, C Aron, D Stevenson, LD Kirsh, S Ho, PM Lowery, J AF Haverhals, Leah M. Sayre, George Helfrich, Christian D. Battaglia, Catherine Aron, David Stevenson, Lauren D. Kirsh, Susan Ho, P. Michael Lowery, Julie TI E-Consult Implementation: Lessons Learned Using Consolidated Framework for Implementation Research SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CONSENSUAL QUALITATIVE RESEARCH; WEIGHT MANAGEMENT PROGRAM; HEALTH-CARE; VETERANS; ACCESS; VA AB Objectives: In 2011, the Veterans Health Administration (VHA) implemented electronic consults (e-consults) as an alternative to in-person specialty visits to improve access and reduce travel for veterans. We conducted an evaluation to understand variation in the use of the new e-consult mechanism and the causes of variable implementation, guided by the Consolidated Framework for Implementation Research (CFIR). Study Design: Qualitative case studies of 3 high-and 5 low-implementation e-consult pilot sites. Participants included e-consult site leaders, primary care providers, specialists, and support staff identified using a modified snowball sample. Methods: We used a 3-step approach, with a structured survey of e-consult site leaders to identify key constructs, based on the CFIR. We then conducted open-ended interviews, focused on key constructs, with all participants. Finally, we produced structured, site-level ratings of CFIR constructs and compared them between high-and low-implementation sites. Results: Site leaders identified 14 initial constructs. We conducted 37 interviews, from which 4 CFIR constructs distinguished high-implementation e-consult sites: compatibility, networks and communications, training, and access to knowledge and information. For example, illustrating compatibility, a specialist at a high-implementation site reported that the site changed the order of consult options so that all specialties listed e-consults first to maintain consistency. High-implementation sites also exhibited greater agreement on constructs. Conclusions: By using the CFIR to analyze results, we facilitate future synthesis with other findings, and we better identify common patterns of implementation determinants common across settings. C1 [Haverhals, Leah M.; Battaglia, Catherine; Ho, P. Michael] VA Eastern Colorado Hlth Care Syst, Denver, CO 80220 USA. [Sayre, George; Helfrich, Christian D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Aron, David; Stevenson, Lauren D.; Kirsh, Susan] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Kirsh, Susan] Off Specialty Care & Specialty Care Transformat, Washington, DC USA. [Lowery, Julie] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. RP Haverhals, LM (reprint author), VA Eastern Colorado Hlth Care Syst, Res A151, 1055 Clermont St, Denver, CO 80220 USA. EM leah.haverhals@va.gov FU US Department of Veterans Affairs; Office of Specialty Care Transformation; Office of Health Services Research FX This work was supported by the US Department of Veterans Affairs, Office of Specialty Care Transformation and Office of Health Services Research, and undertaken by the Specialty Care Transformation Initiative Evaluation Center. 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. NR 26 TC 0 Z9 0 U1 3 U2 4 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2015 VL 21 IS 12 BP E640 EP + PG 21 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DC7GQ UT WOS:000369388100003 PM 26760426 ER PT J AU Kirsh, S Carey, E Aron, DC Cardenas, O Graham, G Jain, R Au, DH Tseng, CL Franklin, H Ho, PM AF Kirsh, Susan Carey, Evan Aron, David C. Cardenas, Omar Graham, Glenn Jain, Rajiv Au, David H. Tseng, Chin-Lin Franklin, Heather Ho, P. Michael TI Impact of a National Specialty E-Consultation Implementation Project on Access SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID ELECTRONIC HEALTH RECORD; CENTERED MEDICAL HOME; PRIMARY-CARE; REFERRALS; COMMUNICATION; SYSTEM; TRANSFORMATION; PHYSICIANS; LESSONS; SERVICE AB Objective:s To assess the early impact of implementation of the electronic consults (e-consults) initiative by the Veterans Health Administration (VHA), designed to improve specialty care access. Study Design: Observational cohort study exploiting a natural experiment begun in May 2011 at 12 VHA medical centers and expanded to 122 medical centers by December 2013. Methods: The following were assessed: 1) growth of e-consults by VHA regional networks, medical centers, and specialty; 2) location of patient's primary care provider (medical center vs community-based outpatient clinic [CBOC]); 3) potential patient miles needed to travel for a specialty care face-to-face consult in place of the observed e-consults using estimated geodesic distance; 4) use of specialty care subsequent to the e-consult. Results: Of 11,270,638 consults completed in 13 clinics of interest, 217,014 were e-consults (adjusted rate, 1.93 e-consults per 100 consults). The e-consult rate was highest in endocrinology (5.0 per 100), hematology (3.0 per 100), and gastroenterology (3.0 per 100). The percentage of e-consult patients with CBOC-based primary care grew from 28.5% to 44.4% in the first year of implementation and to 45.6% at year 3. Of those e-consult patients from community clinics, the average potential miles needed to travel was 72.1 miles per patient (SD = 72.6; median = 54.6; interquartile range = 17.1-108), translating to a potential savings of 6,875,631 total miles and travel reimbursement costs of $2,853,387. Conclusions: E-consult volume increased significantly since inception within many medical and surgical specialties. For patients receiving primary care at one of more than 800 CBOCs, e-consults may decrease travel burden and direct travel costs for patients. C1 [Kirsh, Susan; Cardenas, Omar; Graham, Glenn] Vet Hlth Adm, Off Specialty Care Serv, Washington, DC USA. [Jain, Rajiv] Vet Hlth Adm, Patient Care Serv, Washington, DC USA. [Kirsh, Susan; Aron, David C.] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Kirsh, Susan; Aron, David C.] Case Western Reserve Univ, Sch Med, 10701 East Blvd, Cleveland, OH 44106 USA. [Carey, Evan; Ho, P. Michael] Eastern Colorado VA Med Ctr, Denver, CO USA. [Au, David H.] US Dept Vet Affairs, Puget Sound Hlth Serv, Res & Dev Ctr Innovat, Seattle, WA USA. [Au, David H.] Univ Washington, Dept Med, Seattle, WA USA. [Tseng, Chin-Lin; Franklin, Heather] New Jersey Vet Hlth Care Syst, East Orange Campus, E Orange, NJ USA. RP Kirsh, S (reprint author), Case Western Reserve Univ, Sch Med, 10701 East Blvd, Cleveland, OH 44106 USA. EM susan.kirsh@va.gov FU US Department of Veterans Affairs; Office of Research and Development Quality Enhancement Research Initiative; Office of Specialty Care Transformation FX This material is based upon work supported by the US Department of Veterans Affairs, the Office of Specialty Care Transformation and the Office of Research and Development Quality Enhancement Research Initiative. NR 30 TC 4 Z9 4 U1 2 U2 2 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2015 VL 21 IS 12 BP E648 EP + PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DC7GQ UT WOS:000369388100004 PM 26760427 ER PT J AU Reed, M Graetz, I Gordon, N Fung, V AF Reed, Mary Graetz, Ilana Gordon, Nancy Fung, Vicki TI Patient-Initiated E-mails to Providers: Associations With Out-of-Pocket Visit Costs, and Impact on Care-Seeking and Health SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID EMERGENCY-DEPARTMENT; KAISER PERMANENTE; CHRONICALLY ILL; COMMUNICATION; BENEFITS; QUALITY; ACCESS; RECORD; COORDINATION; SATISFACTION AB Objectives: To understand when patients use secure e-mail messaging with healthcare providers across several types of questions or concerns, associations between out-of-pocket costs for in-person visits and use of secure messaging, and to examine patient-reported impacts on care-seeking behavior and overall health. Study Design: Cross-sectional survey of patients in an integrated healthcare delivery system, with access to a patient portal to send secure e-mail messages to providers at no out-of-pocket cost. Methods: The study included patients with a chronic condition (N = 1041). We described patient-reported preferences for contacting providers and patient-reported impact of e-mail use on phone calls, in-person visits, and overall health. We used multivariate analyses to examine patient characteristics associated with using e-mail as a first contact method, and effects on care-seeking and health. Results: Overall, 56% of patients sent their provider an e-mail within 1 year, and 46% reported e-mail as their first method of contact for 1 or more types of medical concerns. After adjustment, higher out-of-pocket costs for in-person visits were significantly associated with choosing e-mail as a first method of contact (P < .05). Among patients who had e-mailed their provider, 42% reported that it reduced their phone contacts, 36% reduced in-person office visits and 32% reported e-mailing improved their overall health. Conclusions: Patients reported using e-mail broadly to initiate conversations with their providers, and patients with higher out-of-pocket costs for in-person visits were more likely to choose e-mail as a first contact method. Use of secure e-mails reduced patients' use of other types of healthcare and resulted in improved overall health. C1 [Reed, Mary; Graetz, Ilana; Gordon, Nancy] Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. [Graetz, Ilana] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Fung, Vicki] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Reed, M (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Mary.e.reed@kp.org RI Graetz, Ilana/N-1189-2016 OI Graetz, Ilana/0000-0003-3664-5815 FU Kaiser Permanente Community Benefit Fund FX Kaiser Permanente Community Benefit Fund. NR 36 TC 1 Z9 1 U1 3 U2 4 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2015 VL 21 IS 12 BP E632 EP E639 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DC7GQ UT WOS:000369388100002 PM 26760425 ER PT J AU Daniel, CL Emmons, KM Fasciano, K Nevidjon, B Fuemmeler, BF Demark-Wahnefried, W AF Daniel, Casey L. Emmons, Karen M. Fasciano, Karen Nevidjon, Brenda Fuemmeler, Bernard F. Demark-Wahnefried, Wendy TI Needs and Lifestyle Challenges of Adolescents and Young Adults With Cancer: Summary of an Institute of Medicine and Livestrong Foundation Workshop SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article DE adolescent; young adult; cancer; survivor; physical activity; substance abuse ID PHYSICAL-ACTIVITY INTERVENTION; CHILDHOOD-CANCER; HEALTH BEHAVIORS; EXERCISE INTERVENTIONS; CARDIOVASCULAR RISK; CHRONIC DISEASES; SURVIVORS; SMOKING; PREDICTORS; DIAGNOSIS AB Background: Among adolescents and young adults (AYAs) in the United States, cancer is the leading cause of disease-related death. AYA survivors face numerous short-and long-term health and psychosocial issues, as well as increased risk for behavioral and lifestyle challenges, including poor diet, low physical activity (PA), and substance abuse. Many of these behaviors are modifiable, but gaps in care serve as barriers for AYA survivors. Objectives: The purpose of this article is to (a) raise awareness of AYAs' increased risk for poor diet, low PA, and substance abuse; (b) examine previous interventions addressing these issues; and (c) provide recommendations for future directions. Methods: This article summarizes a workshop coordinated by the Institute of Medicine and the Livestrong Foundation to address AYA survivors' needs and ways to enhance their quality of care. Findings: Oncology nurses can promote the inclusion of lifestyle behaviors in survivorship care plans of AYA patients and serve as a valuable resource in improving AYA care on a larger scale. In addition, oncology nurse researchers may offer greater understanding of AYA patients' and survivors' needs and best practices by conducting much-needed research with this understudied population. C1 [Daniel, Casey L.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 665 Huntington Ave, Boston, MA 02115 USA. [Emmons, Karen M.] Kaiser Fdn Res Inst, Oakland, CA USA. [Fasciano, Karen] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Nevidjon, Brenda] Oncol Nursing Soc, Pittsburgh, PA USA. [Fuemmeler, Bernard F.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Demark-Wahnefried, Wendy] Univ Alabama, Dept Nutr Sci, Tuscaloosa, AL 35487 USA. RP Daniel, CL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM casey_daniel@dfci.harvard.edu FU Livestrong Foundation; Centers for Disease Control and Prevention; National Cancer Institute; Association of American Cancer Institutes; American Association for Cancer Research; American Cancer Society; American Society of Clinical Oncology; American Society for Radiation Oncology; C-Change; Cancer Support Community; CEO Roundtable on Cancer; GlaxoSmithKline Oncology; National Comprehensive Cancer Network; Novartis Oncology; Oncology Nursing Society; Sanofi Oncology FX The authors gratefully acknowledge the Livestrong Foundation for generously co-sponsoring the Institute of Medicine (IOM) workshop and Critical Mass: The Young Adult Cancer Alliance for supporting the workshop. The activities of the IOM's National Cancer Policy Forum are supported by its sponsoring members, which currently include the Centers for Disease Control and Prevention, the National Cancer Institute, the Association of American Cancer Institutes, the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, the American Society for Radiation Oncology, C-Change, the Cancer Support Community, the CEO Roundtable on Cancer, GlaxoSmithKline Oncology, the Livestrong Foundation, the National Comprehensive Cancer Network, Novartis Oncology, the Oncology Nursing Society, and Sanofi Oncology. The authors thank the planning committee members, speakers, and participants for their contributions to the workshop. NR 65 TC 1 Z9 1 U1 1 U2 7 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD DEC PY 2015 VL 19 IS 6 BP 675 EP 681 DI 10.1188/15.CJON.19-06AP PG 7 WC Oncology; Nursing SC Oncology; Nursing GA DC5EJ UT WOS:000369243900011 PM 26583632 ER PT J AU Rubin, KM AF Rubin, Krista M. TI Understanding Immune Checkpoint Inhibitors for Effective Patient Care SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article DE immunotherapy; melanoma; programmed cell death-1 pathway; PD-1; adverse events ID ADVANCED MELANOMA; METASTATIC MELANOMA; PHASE-III; MALIGNANT-MELANOMA; UNTREATED MELANOMA; IMPROVED SURVIVAL; MEK INHIBITION; OPEN-LABEL; IPILIMUMAB; BRAF AB Background: Immune checkpoint inhibitors represent a paradigm change in the treatment of melanoma and other advanced cancers. These agents manipulate key immune-regulating pathways to restore immune responses against tumors. The success of this approach is demonstrated by ipilimumab (Yervoy (R)) for the treatment of advanced melanoma, with improvement in three-year survival rates of about 20%. Newer checkpoint inhibitors targeting the programmed death-1 (PD-1) pathway have been approved and may have higher response rates and improved tolerability. Objectives: This article aims to educate nurses and increase their comfort level with these new therapies. Methods: The mechanism of action of immune checkpoint inhibitors is reviewed, and insight is provided on how nurses can use this knowledge to more effectively care for patients receiving these therapies. Findings: The use of immuno-oncology agents is increasing. Oncology nurses must understand the basic immune mechanism of action responsible for the novel toxicity profile characterized by immune-related adverse events (irAEs) and clinical response patterns. Managing irAEs with immune checkpoint inhibitors is not necessarily more difficult than with conventional agents, but a difference does exist. Nurses and other healthcare providers must consider the underlying cause of toxicity with immune checkpoint inhibitors when making management decisions. C1 [Rubin, Krista M.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Ctr Melanoma, Boston, MA USA. [Rubin, Krista M.] Massachusetts Gen Hosp, Dept Dermatol, Ctr Canc, Boston, MA 02114 USA. RP Rubin, KM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Ctr Melanoma, Boston, MA USA. EM kmrubin@mgh.harvard.edu FU Bristol-Myers Squibb; Amgen, Inc.; Merck Oncology FX Krista M. Rubin, RN, MS, FNP-BC, is a nurse practitioner in the Center for Melanoma in the Division of Hematology-Oncology and Department of Dermatology at the Massachusetts General Hospital Cancer Center in Boston. The author takes full responsibility for the content of the article. Writing and editorial support were provided by Britt Anderson, PhD, and Karin McGlynn at StemScientific, an Ashfield Company, and were funded by Bristol-Myers Squibb. Rubin received support from Amgen, Inc., Bristol-Myers Squibb, and Merck Oncology. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers or editorial staff. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Clinical Journal of Oncology Nursing or the Oncology Nursing Society. Rubin can be reached at kmrubin@mgh.harvard.edu, with copy to editor at CJONEditor@ons.org. (Submitted December 2014. Revision submitted February 2015. Accepted for publication February 13, 2015.) NR 55 TC 0 Z9 0 U1 0 U2 7 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD DEC PY 2015 VL 19 IS 6 BP 709 EP 717 DI 10.1188/15.CJON.709-717 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA DC5EJ UT WOS:000369243900014 PM 26583635 ER PT J AU Chase, AB Markel, K Tawa, MC AF Chase, Allister Benjamin Markel, Kristen Tawa, Marianne C. TI Optimizing Care and Compliance for the Treatment of Mycosis Fungoides Cutaneous T-Cell Lymphoma With Mechlorethamine Gel SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article DE mechlorethamine hydrochloride; cutaneous T-cell lymphoma; mycosis fungoides ID UNITED-STATES; INTERNATIONAL-SOCIETY; TOPICAL CHEMOTHERAPY; PROGNOSTIC-FACTORS; NITROGEN-MUSTARD; SEZARY-SYNDROME; ORGANIZATION; PATTERNS; PROPOSAL; THERAPY AB Background: Mycosis fungoides is the most common form of cutaneous T-cell lymphoma (MF-CTCL). Quality nursing care is necessary for effective diagnosis and treatment of patients with MF-CTCL. Early-stage MF-CTCL (stages Ia and Ib) is most often managed in both dermatology and multi-disciplinary settings. These stages can be effectively controlled by skin-directed therapies such as mechlorethamine gel (Valchlor (R)). Topical mechlorethamine has been used since the 1940s as an alkylating agent; however, compounded formulas have disadvantages that limit patient compliance. In contrast, newly approved mechlorethamine gel has demonstrated an efficacious and well-tolerated profile that has longer stability and is quicker to dry than its compounded counterpart. Objectives: This article aims to provide recommendations for optimal nursing care of patients who have been diagnosed with stage Ia or Ib MF-CTCL. Methods: Four real-world patient cases are examined, along with practical considerations for the use of mechlorethamine gel to treat patients with MF-CTCL. Findings: Nurses can promote patient adherence through specific interventions and strategies, such as education about mechlorethamine gel, its mechanism of action, and safety and efficacy, as well as connecting patients with patient assistance programs or other supportive services. C1 [Chase, Allister Benjamin] Univ Calif Los Angeles, Med Ctr, Santa Monica, CA USA. [Markel, Kristen] Stanford Univ, Sch Med, Multidisciplinary Cutaneous Lymphoma Program, Stanford, CA 94305 USA. [Tawa, Marianne C.] Dana Farber Canc Inst, Dermatol & Cutaneous Oncol, Boston, MA 02115 USA. RP Chase, AB (reprint author), Univ Calif Los Angeles, Med Ctr, Santa Monica, CA USA. EM achase@mednet.ucla.edu NR 29 TC 0 Z9 0 U1 1 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD DEC PY 2015 VL 19 IS 6 BP E131 EP E139 DI 10.1188/15.CJON.E131-E139 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA DC5EJ UT WOS:000369243900004 ER PT J AU Shields, RK Nguyen, MH Clancy, CJ AF Shields, Ryan K. Nguyen, M. Hong Clancy, Cornelius J. TI Clinical perspectives on echinocandin resistance among Candida species SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE Candida; echinocandin; FKS mutation; resistance; susceptibility testing ID EPIDEMIOLOGIC CUTOFF VALUES; INVASIVE CANDIDIASIS; FKS MUTATIONS; ANTIFUNGAL SUSCEPTIBILITY; MULTIDRUG-RESISTANCE; CASPOFUNGIN MICS; AMPHOTERICIN-B; GLABRATA; BREAKPOINTS; MICAFUNGIN AB Purpose of reviewWe review and offer our clinical perspectives on the emergence of echinocandin-resistant Candida.Recent findingsCandida FKS gene mutations attenuate echinocandin activity, but overall mutation rates among clinical isolates remain low (Candida glabrata, approximate to 4%; other species, <1%). Rates are higher with prior echinocandin exposure, exceeding 50% among C. glabrata or Candida albicans isolates causing breakthrough invasive candidiasis. The median duration of prior echinocandin exposure among FKS mutant isolates is approximate to 100 days. The clinical usefulness of echinocandin susceptibility testing is limited by the low overall prevalence of resistance, and uncertainties surrounding testing methods and interpretation of minimum inhibitory concentrations (MICs). In single-center studies, caspofungin resistance (defined using institution-specific MIC breakpoints) was 32-53% sensitive and 75-95% specific for predicting treatment outcomes of C. glabrata invasive candidiasis; corresponding values for the presence of an FKS mutation were 35-41% and 90-98%. Results were similar using anidulafungin and micafungin MICs. Clinical data are scarce for non-C. glabrata species.SummaryEchinocandins remain preferred agents against invasive Candida infections. Susceptibility testing and FKS genotypic testing do not have roles in routine clinical practice, but may be useful in newly-diagnosed patients who are echinocandin-experienced or those who have not responded to echinocandin treatment. C1 [Shields, Ryan K.; Nguyen, M. Hong; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Med, 3550 Terrace St,S867 Scaife Hall, Pittsburgh, PA 15261 USA. EM cjc76@pitt.edu FU National Institutes of Health [K08AI114883, R21AI107290]; Astellas; Merck; Pfizer; U.S. Department of Veterans Affairs through VA Merit Award [1IO1BX001955] FX R.K.S. is supported by the National Institutes of Health through grant number K08AI114883, and through research grants from Astellas and Merck. M.H.N. is supported by the National Institutes of Health through grant number R21AI107290, and through research grants from Astellas, Merck and Pfizer. C.J.C. is supported by the U.S. Department of Veterans Affairs through VA Merit Award 1IO1BX001955, and through research grants from Astellas, Merck and Pfizer. NR 57 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0951-7375 EI 1473-6527 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 2015 VL 28 IS 6 BP 514 EP 522 DI 10.1097/QCO.0000000000000215 PG 9 WC Infectious Diseases SC Infectious Diseases GA DC7TC UT WOS:000369422300003 PM 26524326 ER PT J AU Robinson, EB Neale, BM Hyman, SE AF Robinson, Elise B. Neale, Benjamin M. Hyman, Steven E. TI Genetic research in autism spectrum disorders SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE autism; exome sequencing; genetics; GWAS ID DE-NOVO MUTATIONS; GENOME-WIDE ASSOCIATION; PSYCHIATRIC-DISORDERS; SCHIZOPHRENIA; RISK; 16P11.2; RARE; EPIDEMIOLOGY; POPULATION; RECURRENCE AB Purpose of reviewThe recent explosion of genetic findings in autism spectrum disorder (ASD) research has improved knowledge of the disorder's underlying biology and etiologic architecture. This review introduces concepts and results from recent genetic studies and discusses the manner in which those findings can influence the trajectory of ASD research.Recent findingsLarge consortium studies have associated ASDs with many types of genetic risk factors, including common polygenic risk, de novo single nucleotide variants, copy number variants, and rare inherited variants. In aggregate, these results confirm the heterogeneity and complexity of ASDs. The rare variant findings in particular point to genes and pathways that begin to bridge the gap between behavior and biology.SummaryGenetic studies have the potential to identify the biological underpinnings of ASDs and other neuropsychiatric disorders. The data they generate are already being used to examine disease pathways and pathogenesis. The results also speak to ASD heterogeneity and, in the future, may be used to stratify research studies and treatment trials. C1 [Robinson, Elise B.; Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Robinson, Elise B.; Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA USA. [Robinson, Elise B.; Neale, Benjamin M.; Hyman, Steven E.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Robinson, Elise B.; Neale, Benjamin M.; Hyman, Steven E.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Hyman, Steven E.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Robinson, EB (reprint author), Broad Inst, Stanley Ctr Psychiat Res, 75 Ames St, Cambridge, MA 02142 USA. EM erob@broadinstitute.org OI Robinson, Elise/0000-0003-2314-2792 FU National Institute of Mental Health [1K01MH099286-02, 5U01MH094432-04] FX E.B.R. was funded by National Institute of Mental Health Grant 1K01MH099286-02. S.E.H is supported by a gift from the Stanley Foundation. B.M.N. was supported by National Institute of Mental Health Grant 5U01MH094432-04. NR 42 TC 6 Z9 6 U1 8 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8703 EI 1531-698X J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD DEC PY 2015 VL 27 IS 6 BP 685 EP 691 DI 10.1097/MOP.0000000000000278 PG 7 WC Pediatrics SC Pediatrics GA DC5NR UT WOS:000369268200005 PM 26371945 ER PT J AU Ozieh, MN Taber, DJ Egede, LE AF Ozieh, Mukoso N. Taber, David J. Egede, Leonard E. TI Does African American Race Impact Statin Efficacy in Renal Transplant Outcomes? SO MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; ALLOGRAFT REJECTION; CARDIOVASCULAR-DISEASE; KIDNEY-TRANSPLANT; CARDIAC OUTCOMES; RECIPIENTS; FLUVASTATIN; TRIAL; MULTICENTER; DISPARITIES AB There is a lack of studies assessing if race impacts the efficacy of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) inhibitor (statin) therapy on renal transplantation (RTx) outcomes. We examined the association between statin therapy and RTx outcomes, while concurrently quantifying the effect modification African American (AA) race has on statin efficacy.This was a retrospective longitudinal cohort study of solitary adult RTx (n=1176) between June 2005 and May 2013. The Cox proportional hazard model was used to examine the impact of statin therapy on graft loss, death, and acute rejection and determine if significant interactions exist between statin therapy and race. Models were adjusted for demographics, socioeconomic status, cardiovascular history, medication use, and transplant characteristics.AAs (n=624) and non-African Americans (n=552) were equally likely to receive statin therapy (P=0.922). Mean LDL and TGs in AA were 94mg/dL and 133mg/dL compared to 90mg/dL and 163mg/dL in non-AA, respectively. After adjusting for confounders, high statin users had 52% lower risk of developing graft loss (HR 0.48, 95% CI 0.29-0.80) and a nonstatistically significant reduction in death (HR 0.50, 95% CI 0.23-1.06) compared to low statin users. Acute rejection was not significantly influenced by statin use (HR 0.77 95% CI 0.46-1.27). There was a significant interaction between race and statin therapy for death (P=0.007), but not for graft loss (P=0.121) or rejection (P=0.605). After stratifying by race, high statin use reduced the risk of death in AAs (HR 0.43, 95% CI 0.20-0.94), but not in non-AAs (HR 1.09, 95% CI 0.49-2.44).High statin use reduces the risk of graft loss in RTx, with a mortality benefit in AAs compared to non-AA, despite similar LDL levels. These results suggest a compelling reason to optimize statin therapy in renal transplant recipients (RTR), especially in AAs. C1 [Ozieh, Mukoso N.] Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. [Ozieh, Mukoso N.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Taber, David J.] Med Univ S Carolina, Div Transplant Surg, Charleston, SC 29425 USA. [Taber, David J.] Ralph H Johnson VAMC, Dept Pharm, Charleston, SC USA. [Egede, Leonard E.] Ralph H Johnson VAMC, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699, K23DK099440, T35 DK007431] FX this study was supported by grants K24DK093699 (PI: Leonard Egede), K23DK099440 (PI: David Taber), and T35 DK007431(PI: Leonard Egede) from The National Institute of Diabetes and Digestive and Kidney Disease. NR 23 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD DEC PY 2015 VL 94 IS 49 AR e2283 DI 10.1097/MD.0000000000002283 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DC9KX UT WOS:000369541600057 PM 26656377 ER PT J AU Vedantham, S Karellas, A Vijayaraghavan, GR Kopans, DB AF Vedantham, Srinivasan Karellas, Andrew Vijayaraghavan, Gopal R. Kopans, Daniel B. TI Digital Breast Tomosynthesis: State of the Art SO RADIOLOGY LA English DT Review ID COMPUTER-AIDED DETECTION; FLAT-PANEL DETECTOR; RECONSTRUCTED PROJECTION IMAGES; SCREEN-FILM MAMMOGRAPHY; X-RAY TOMOSYNTHESIS; AMORPHOUS SELENIUM; DIAGNOSTIC MAMMOGRAPHY; OBSERVER-PERFORMANCE; CLINICAL-EXPERIENCE; MASS CHARACTERIZATION AB This topical review on digital breast tomosynthesis (DBT) is provided with the intent of describing the state of the art in terms of technology, results from recent clinical studies, advanced applications, and ongoing efforts to develop multimodality imaging systems that include DBT. Particular emphasis is placed on clinical studies. The observations of increase in cancer detection rates, particularly for invasive cancers, and the reduction in false-positive rates with DBT in prospective trials indicate its benefit for breast cancer screening. Retrospective multireader multicase studies show either noninferiority or superiority of DBT compared with mammography. Methods to curtail radiation dose are of importance. (C) RSNA, 2015 C1 [Vedantham, Srinivasan; Karellas, Andrew; Vijayaraghavan, Gopal R.] Univ Massachusetts, Dept Radiol, Sch Med, 55 Lake Ave North, Worcester, MA 01655 USA. [Kopans, Daniel B.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Karellas, A (reprint author), Univ Massachusetts, Dept Radiol, Sch Med, 55 Lake Ave North, Worcester, MA 01655 USA. EM andrew.karellas@umassmed.edu RI Vedantham, Srinivasan/H-1987-2012 OI Vedantham, Srinivasan/0000-0003-4123-8392 FU National Institutes of Health [R01 CA139449, R21 CA176470] FX This research was supported by the National Institutes of Health (grants R01 CA139449 and R21 CA176470). NR 163 TC 10 Z9 10 U1 2 U2 15 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2015 VL 277 IS 3 BP 663 EP 684 DI 10.1148/radiol.2015141303 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DC9EY UT WOS:000369525100007 PM 26599926 ER PT J AU Shinagare, AB O'Neill, AC Cheng, SC Somarouthu, B Tirumani, SH Nishino, M Van den Abbeele, AD Ramaiya, NH AF Shinagare, Atul B. O'Neill, Ailbhe C. Cheng, SuChun Somarouthu, Bhanusupriya Tirumani, Sree H. Nishino, Mizuki Van den Abbeele, Annick D. Ramaiya, Nikhil H. TI Advanced High-Grade Serous Ovarian Cancer: Frequency and Timing of Thoracic Metastases and the Implications for Chest Imaging Follow-up SO RADIOLOGY LA English DT Article ID GYNECOLOGIC MALIGNANCIES; CARCINOMA; CT AB Purpose: To study the frequency, timing, and associations of thoracic metastases in advanced (stage III and IV) high-grade serous ovarian cancer (HGSC) to help optimize the use of cross-sectional chest imaging. Materials and Methods: This institutional review board-approved retrospective study with waived informed consent included 186 consecutive patients with pathologically proven advanced HGSC after primary cytoreduction (mean age 6 standard deviation, 60 years 6 +/- 9.7) who underwent imaging at our tertiary cancer institution from January 2012 to December 2012 with at least 1 year of follow-up, unless there was thoracic metastasis or death. Electronic medical records and all available imaging studies were reviewed to record patient and tumor characteristics, frequency and timing of abdominal and thoracic metastases, and visibility of the first thoracoabdominal metastasis on abdominal images. Patient and tumor characteristics associated with thoracic metastases were studied by using univariate and multivariate Cox proportional analysis. Results: After median follow-up of 57 months (interquartile range [IQR], 38-93), 175 patients (94%) developed metastatic disease; each had abdominal disease, and 76 (41%) had thoracic metastases. The first thoracoabdominal metastasis was visible on abdominal images in all 175 patients. The thoracic metastasis-free interval was longer than the abdominal disease-free interval (median, 85 months [IQR, 28-131] vs 14 months [IQR, 7-27], respectively; P<.0001). Presence of disease on abdominal images (hazard ratio, 2.56; 95% confidence interval: 1.35, 4.76) was the only factor independently associated with thoracic metastases. Conclusion: Thoracic metastases in advanced HGSC rarely occur before abdominal disease, and first thoracoabdominal metastases are invariably visible on abdominal images. Therefore, cross-sectional chest imaging may be deferred until development of abdominal disease, with minimal risk of missing thoracic metastases. (C) RSNA, 2015 C1 [Shinagare, Atul B.; O'Neill, Ailbhe C.; Somarouthu, Bhanusupriya; Tirumani, Sree H.; Nishino, Mizuki; Van den Abbeele, Annick D.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Cheng, SuChun] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM ashinagare@partners.org NR 16 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2015 VL 277 IS 3 BP 733 EP 740 DI 10.1148/radiol.2015142467 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DC9EY UT WOS:000369525100013 PM 26053310 ER PT J AU Singh, N Winston, DJ Limaye, AP Pelletier, S Safdar, N Morris, MI Meneses, K Busuttil, RW Wagener, MM Wheat, LJ AF Singh, Nina Winston, Drew J. Limaye, Ajit P. Pelletier, Shawn Safdar, Nasia Morris, Michele I. Meneses, Katherine Busuttil, Ronald W. Wagener, Marilyn M. Wheat, L. Joseph TI Performance Characteristics of Galactomannan and beta-d-Glucan in High-Risk Liver Transplant Recipients SO TRANSPLANTATION LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; ENZYME-IMMUNOASSAY; EARLY-DIAGNOSIS; DOUBLE-BLIND; ASPERGILLOSIS; ASSAY; ANTIGENEMIA; DISEASES; PLASMA; (1->3)-BETA-D-GLUCAN AB Background. The utility of Aspergillus galactomannan (GM) and beta-D-glucan (BG) in liver transplant recipients remains uncertain. Methods. As part of a randomized, double-blind trial of antifungal prophylaxis in liver transplant recipients at risk for invasive fungal infections (IFIs), GM and BG were assessed in 199 patients at baseline (enrollment) and weekly thereafter for the duration of study drug. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of these for the diagnosis of IFIs. Results. Overall, 46.4% of the patients at baseline had positive GM(index >= 0.5) and 89.6% had BG of 80 pg/mL or greater with BG level of 500 pg/mL or greater in 31.8%. Patients with invasive aspergillosis (IA) (3/3) had positive GM at baseline as did 45.5% of those without IA (P = 0.098); the area under the ROC curve for the diagnosis of IA was 0.77 (fair test, ie, good sensitivity but poor specificity). Using BG cutoff of 80 pg/mL or higher, 100%(12/12) of the patients with IFI had positive baseline BG and as did 88.9% (160/180) of those without IFI (P = 0.618); the area under the ROC curve for predicting IFIs was 0.56 (poor test). In multivariate analyses, GM positivity was associated with study site (P = 0.041), and BG positivity with renal replacement therapy (P = 0.05) and study site (P = 0.01). The GM and BG levels declined over time; positivity at subsequent time points was lower in comparison with baseline (P < 0.001). Conclusions. The GM and BG tests had significant center variability and limited accuracy for the diagnosis of IFIs in high-risk liver transplant recipients. C1 [Singh, Nina] VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA USA. [Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. [Winston, Drew J.; Meneses, Katherine; Busuttil, Ronald W.] Univ Calif Los Angeles, Med Ctr, Dept Surg, Los Angeles, CA 90024 USA. [Limaye, Ajit P.] Univ Washington, Div Infect Dis, Seattle, WA USA. [Pelletier, Shawn] Univ Michigan, Div Infect Dis, Ann Arbor, MI 48109 USA. [Safdar, Nasia] Univ Wisconsin, Div Infect Dis, Madison, WI USA. [Morris, Michele I.] Univ Miami, Div Infect Dis, Miami, FL USA. [Wagener, Marilyn M.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Wheat, L. Joseph] Mira Vista Diagnost, Indianapolis, IN USA. RP Singh, N (reprint author), Vet Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu FU Pfizer Inc. [GA8851MQ] FX The study was supported by an Investigator-Initiated Research Grant from Pfizer Inc. (GA8851MQ). The sponsor had no role in the design and conduct of the study, data collection, analysis and interpretation or preparation of the manuscript. The study was registered at ClinicalTrials.gov NCT00841971. NR 39 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD DEC PY 2015 VL 99 IS 12 BP 2543 EP 2550 DI 10.1097/TP.0000000000000763 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC7AA UT WOS:000369369500021 PM 26050015 ER PT J AU Butala, NM King, MD Reitsma, W Formica, RN Abt, PL Reese, PP Parikh, CR AF Butala, Neel M. King, Marissa D. Reitsma, William Formica, Richard N. Abt, Peter L. Reese, Peter P. Parikh, Chirag R. TI Association Between Organ Procurement Organization Social Network Centrality and Kidney Discard and Transplant Outcomes SO TRANSPLANTATION LA English DT Article ID PATIENT-SHARING NETWORKS; CENTER-LEVEL PATTERNS; UNITED-STATES; RENAL-TRANSPLANTATION; SCIENTIFIC REGISTRY; ADMINISTRATIVE DATA; RESCUE ALLOCATION; PHYSICIANS; RECIPIENTS; DONORNET AB Background. Given growth in kidney transplant waitlists and discard rates, donor kidney acceptance is an important problem. We used network analysis to examine whether organ procurement organization (OPO) network centrality affects discard and outcomes. Methods. We identified 106,160 deceased donor kidneys recovered for transplant from 2000 to 2010 in Scientific Registry of Transplant Recipients. We constructed the transplant network by year with each OPO representing a node and each kidney-sharing relationship between OPOs representing a directed tie between nodes. Primary exposures were the number of different OPOs to which an OPO has given a kidney or from which an OPO has received a kidney in year preceding procurement year. Primary outcomes were discard, cold-ischemia time, delayed graft function, and 1-year graft loss. We used multivariable regression, restricting analysis to the 50% of OPOs with highest discard and stratifying remaining OPOs by kidney volume. Models controlled for kidney donor risk index, waitlist time, and kidney pumping. Results. An increase in one additional OPO to which a kidney was given by a procuring OPO in a year was associated with 1.4% lower likelihood of discard for a given kidney (odds ratio, 0.986; 95% confidence interval, 0.974-0.998) among OPOs procuring high kidney volume, but 2% higher likelihood of discard (odds ratio, 1.021; 95% confidence interval, 1.006-1.037) among OPOs procuring low kidney volume, with mixed associations with recipient outcomes. Conclusions. Our study highlights the value of network analysis in revealing how broader kidney sharing is associated with levels of organ acceptance. We conclude interventions to promote broader inter-OPO sharing could be developed to reduce discard for a subset of OPOs. C1 [Butala, Neel M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [King, Marissa D.] Yale Univ, Sch Management, New Haven, CT 06510 USA. [Reitsma, William] NJ Sharing Network, New Providence, NJ USA. [Formica, Richard N.; Parikh, Chirag R.] Yale Univ, Nephrol Sect, Dept Med, Sch Med, New Haven, CT 06510 USA. [Abt, Peter L.] Univ Penn, Dept Surg, Div Transplant Surg, Philadelphia, PA 19104 USA. [Reese, Peter P.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Reese, Peter P.] Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA. [Parikh, Chirag R.] Yale Univ, Program Appl Translat Res, Dept Med, Sch Med, New Haven, CT 06510 USA. [Parikh, Chirag R.] Vet Affairs Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT USA. RP Parikh, CR (reprint author), Yale Univ, Program Appl Translat Res, 60 Temple St,Suite 6C, New Haven, CT 06510 USA. EM chirag.parikh@yale.edu FU NIH [K24-DK090203] FX Dr. Parikh was supported by the K24-DK090203 grant from NIH. NR 25 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD DEC PY 2015 VL 99 IS 12 BP 2617 EP 2624 DI 10.1097/TP.0000000000000773 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC7AA UT WOS:000369369500030 PM 26102610 ER PT J AU Aldridge, MD Kelley, AS AF Aldridge, Melissa D. Kelley, Amy S. TI The Myth Regarding the High Cost of End-of-Life Care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID LONG-TERM TRENDS; LAST YEAR; HEALTH-CARE; MEDICAL EXPENDITURES; REGIONAL-VARIATIONS; COORDINATED CARE; UNITED-STATES; PAYMENTS; QUALITY; SAVINGS AB Health care reform debate in the United States is largely focused on the highly concentrated health care costs among a small proportion of the population and policy proposals to identify and target this "high-cost" group. To better understand this population, we conducted an analysis for the Institute of Medicine Committee on Approaching Death using existing national data sets, peer-reviewed literature, and published reports. We estimated that in 2011, among those with the highest costs, only 11% were in their last year of life, and approximately 13% of the $1.6 trillion spenton personal health care costs in the United States was devoted to care of individuals in their last year of life. Public health interventions to reduce health care costs should target those with long-term chronic conditions and functional limitations. C1 [Aldridge, Melissa D.; Kelley, Amy S.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, One Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. [Aldridge, Melissa D.; Kelley, Amy S.] James J Peters VA Med Ctr, Bronx, NY USA. RP Aldridge, MD (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, One Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM melissa.aldridge@mssm.edu FU NIA NIH HHS [K23 AG040774] NR 31 TC 4 Z9 4 U1 2 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2015 VL 105 IS 12 BP 2411 EP 2415 DI 10.2105/AJPH.2015.302889 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC4BB UT WOS:000369163600019 PM 26469646 ER PT J AU Trivedi, RB Post, EP Sun, HL Pomerantz, A Saxon, AJ Piette, JD Maynard, C Arnow, B Curtis, I Fihn, SD Nelson, K AF Trivedi, Ranak B. Post, Edward P. Sun, Haili Pomerantz, Andrew Saxon, Andrew J. Piette, John D. Maynard, Charles Arnow, Bruce Curtis, Idamay Fihn, Stephan D. Nelson, Karin TI Prevalence, Comorbidity, and Prognosis of Mental Health Among US Veterans SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CENTERED MEDICAL HOME; POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE; COLLABORATIVE CARE; BEHAVIORAL HEALTH; DEPRESSION; MORTALITY; ILLNESS; PATIENT; MANAGEMENT AB Objectives. We evaluated the association of mental illnesses with clinical outcomes among US veterans and evaluated the effects of Primary Care-Mental Health Integration (PCMHI). Methods. A total of 4 461 208 veterans were seen in the Veterans Health Administration's patient-centered medical homes called Patient Aligned Care Teams (PACT) in 2010 and 2011, of whom 1 147 022 had at least 1 diagnosis of depression, posttraumatic stress disorder (PTSD), substance use disorder (SUD), anxiety disorder, or serious mental illness (SMI; i.e., schizophrenia or bipolar disorder). We estimated 1-year risk of emergency department (ED) visits, hospitalizations, and mortality by mental illness category and by PCMHI involvement. Results. A quarter of all PACT patients reported 1 or more mental illnesses. Depression, SMI, and SUD were associated with increased risk of hospitalization or death. PTSD was associated with lower odds of ED visits and mortality. Having 1 or more contact with PCMHI was associated with better outcomes. Conclusions. Mental illnesses are associated with poor outcomes, but integrating mental health treatment in primary care may be associated with lower risk of those outcomes. C1 [Arnow, Bruce] Stanford Univ, Dept Psychiat & Behav Sci, 795 Willow Rd MPD-152 Bldg 324, Menlo Pk, CA 94025 USA. [Trivedi, Ranak B.] Vet Affairs VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Sun, Haili; Saxon, Andrew J.; Maynard, Charles; Curtis, Idamay; Nelson, Karin] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Post, Edward P.; Piette, John D.] VA Ann Arbor Hlth Care Syst, Ctr Clin Management Res, Ann Arbor, MI USA. [Pomerantz, Andrew] VA Mental Hlth Serv, Washington, DC USA. [Fihn, Stephan D.] Off Analyt & Business Informat, Seattle, WA USA. RP Trivedi, RB (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, 795 Willow Rd MPD-152 Bldg 324, Menlo Pk, CA 94025 USA. EM ranak.trivedi@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU National PACT Evaluation Center; VA Office of Analytics and Business Intelligence; VA HSR&D Career Development Award [CDA-09-206]; Michigan Diabetes Translational Research Center [P30DK092926]; National Institute of Diabetes and Digestive and Kidney Diseases [R18DK088294] FX This project was supported by the National PACT Evaluation Center and the VA Office of Analytics and Business Intelligence. R. B. Trivedi is supported by a VA HSR&D Career Development Award (CDA-09-206). J. D. Piette is a VA Senior Research Career Scientist. Other financial support came from the Michigan Diabetes Translational Research Center (grant P30DK092926) and National Institute of Diabetes and Digestive and Kidney Diseases (grant R18DK088294). NR 32 TC 8 Z9 8 U1 4 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2015 VL 105 IS 12 BP 2564 EP 2569 DI 10.2105/AJPH.2015.302836 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC4BB UT WOS:000369163600040 PM 26474009 ER PT J AU Fanzio, PM Cheng, MH Samcam, I Lin, YT Gorantla, V Lee, BT Singhal, D AF Fanzio, Paolo Maria Cheng, Ming-Huei Samcam, Ivan Lin, Yu-Te Gorantla, Vijay Lee, Bernard T. Singhal, Dhruv TI High-Volume Hydrodissection Assessment of Deep Inferior Epigastric Perforator Flap Perfusion Using Laser Doppler SO ANNALS OF PLASTIC SURGERY LA English DT Article DE hydrodissection; intramuscular perforator; perforator flap; laser Doppler imaging ID ABDOMINAL-WALL; ARTERY; DISSECTION; HARVEST; TIME; TRAM AB High-volume hydrodissection of intramuscular perforators of deep inferior epigastric perforator (DIEP) flaps in Sprague-Dawley rats has previously demonstrated a significant reduction in dissection time while simultaneously increasing the safety of dissection. However, increasing volumes of fluid injected into the closed rectus compartment may have adverse consequences on perfusion to the overlying flap. A prospective experimental animal study was performed to define a safe upper limit of volume injection for high-volume hydrodissection. Eight Sprague-Dawley rats underwent bilateral "DIEP" flap dissections with varying volumes of fluid (1, 3, 6, and 9 mL) injected into the study side. The primary outcome measurement was overlying tissue perfusion, measured using laser Doppler imaging, at 6 separate time points during the flap harvest. Although no significant difference in perfusion was noted between study and control sides despite increasing volumes of injection, a trend toward significant altered perfusion was noted immediately after injection in the 9-mL study group. Six milliliters is defined as the safe upper limit volume of injection into the closed rectus compartment without significantly altering overlying flap perfusion in our Sprague-Dawley rats. Using volumetric analysis, these data translate to 425 mL as the safe upper limit for high-volume hydrodissection for a single average sized human rectus sheath during DIEP flap harvesting. The mechanical and potentially pharmacologic implications of these data in humans remain to be seen. C1 [Fanzio, Paolo Maria; Cheng, Ming-Huei; Lin, Yu-Te; Singhal, Dhruv] Chang Gung Univ, Chang Gung Mem Hosp, Div Reconstruct Microsurg, Coll Med,Dept Plast & Reconstruct Surg, Taoyuan, Taiwan. [Samcam, Ivan] Univ Florida, Univ Florida Hlth Syst, Div Plast & Reconstruct Surg, Dept Surg,Med Sch, Gainesville, FL 32610 USA. [Gorantla, Vijay] Univ Pittsburgh, UPMC Med Ctr, Dept Plast Surg, Pittsburgh, PA USA. [Lee, Bernard T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Plast & Reconstruct Surg, Dept Surg,Med Sch, Boston, MA 02215 USA. RP Singhal, D (reprint author), Univ Florida, Div Plast Surg, 1600 Archer Rd,POB 100138, Gainesville, FL 32610 USA. EM dhruv.singhal@surgery.ufl.edu RI Lee, Bernard/K-1106-2016 OI Lee, Bernard/0000-0002-5533-3166 NR 25 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-7043 EI 1536-3708 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD DEC PY 2015 VL 75 IS 6 BP 652 EP 656 DI 10.1097/SAP.0000000000000183 PG 5 WC Surgery SC Surgery GA DC2TT UT WOS:000369070300017 PM 25003454 ER PT J AU Ravandi, F Pigneux, A DeAngelo, DJ Raffoux, E Delaunay, J Thomas, X Kadia, T Kantarjian, H Scheuenpflug, J Zhao, C Guo, W Smith, BD AF Ravandi, F. Pigneux, A. DeAngelo, D. J. Raffoux, E. Delaunay, J. Thomas, X. Kadia, T. Kantarjian, H. Scheuenpflug, J. Zhao, C. Guo, W. Smith, B. D. TI Clinical, pharmacokinetic and pharmacodynamic data for the MEK1/2 inhibitor pimasertib in patients with advanced hematologic malignancies SO BLOOD CANCER JOURNAL LA English DT Letter ID ACUTE MYELOID-LEUKEMIA; MUTATIONS C1 [Ravandi, F.; Kadia, T.; Kantarjian, H.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Div Canc Med, Houston, TX 77030 USA. [Pigneux, A.] Hop Haut Leveque, Ctr Francois Magendie, Serv Malad Sang, Pessac, France. [DeAngelo, D. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Raffoux, E.] Hop St Louis, Dept Adult Hematol, Paris, France. [Delaunay, J.] Hop Hotel Dieu, Dept Hematol, Nantes, France. [Thomas, X.] Hop Edouard Herriot, Dept Hematol, Lyon, France. [Scheuenpflug, J.] Merck KGaA, Clin Biomarkers, Darmstadt, Germany. [Zhao, C.; Guo, W.] EMD Serono, Early Dev, Clin Oncol, Billerica, MA USA. [Smith, B. D.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Global Biostat Hematol Canc & BMT, Baltimore, MD USA. RP Ravandi, F (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Div Canc Med, Houston, TX 77030 USA. EM fravandi@mdanderson.org NR 12 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD DEC PY 2015 VL 5 AR e375 DI 10.1038/bcj.2015.103 PG 4 WC Oncology SC Oncology GA DC0PY UT WOS:000368921300006 PM 26657199 ER PT J AU Grishchuk, Y Pena, KA Coblentz, J King, VE Humphrey, DM Wang, SL Kiselyov, KI Slaugenhaupt, SA AF Grishchuk, Yulia Pena, Karina A. Coblentz, Jessica King, Victoria E. Humphrey, Daniel M. Wang, Shirley L. Kiselyov, Kirill I. Slaugenhaupt, Susan A. TI Impaired myelination and reduced brain ferric iron in the mouse model of mucolipidosis IV SO DISEASE MODELS & MECHANISMS LA English DT Article DE Lysosome; Myelination; Oligodendrocytes; Transient receptor potential channel mucolipin-1 ID CENTRAL-NERVOUS-SYSTEM; CULTURED FIBROBLASTS; MEMBRANE-PROTEIN; FERROUS-IRON; BELGRADE RAT; H-FERRITIN; NG2 CELLS; OLIGODENDROCYTE; CHANNEL; TRPML1 AB Mucolipidosis type IV (MLIV) is a lysosomal storage disease caused by mutations in the MCOLN1 gene, which encodes the lysosomal transient receptor potential ion channel mucolipin-1 (TRPML1). MLIV causes impaired motor and cognitive development, progressive loss of vision and gastric achlorhydria. How loss of TRPML1 leads to severe psychomotor retardation is currently unknown, and there is no therapy for MLIV. White matter abnormalities and a hypoplastic corpus callosum are the major hallmarks of MLIV brain pathology. Here, we report that loss of TRPML1 in mice results in developmental aberrations of brain myelination as a result of deficient maturation and loss of oligodendrocytes. Defective myelination is evident in Mcoln1(-/-) mice at postnatal day 10, an active stage of postnatal myelination in the mouse brain. Expression of mature oligodendrocyte markers is reduced in Mcoln1(-/-) mice at postnatal day 10 and remains lower throughout the course of the disease. We observed reduced Perls' staining in Mcoln1(-/-) brain, indicating lower levels of ferric iron. Total iron content in unperfused brain is not significantly different between Mcoln1(-/-) and wild-type littermate mice, suggesting that the observed maturation delay or loss of oligodendrocytes might be caused by impaired iron handling, rather than by global iron deficiency. Overall, these data emphasize a developmental rather than a degenerative disease course in MLIV, and suggest that there should be a stronger focus on oligodendrocyte maturation and survival to better understand MLIV pathogenesis and aid treatment development. C1 [Grishchuk, Yulia; King, Victoria E.; Humphrey, Daniel M.; Wang, Shirley L.; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. [Grishchuk, Yulia; King, Victoria E.; Humphrey, Daniel M.; Wang, Shirley L.; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Grishchuk, Yulia; King, Victoria E.; Humphrey, Daniel M.; Wang, Shirley L.; Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pena, Karina A.; Coblentz, Jessica; Kiselyov, Kirill I.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. RP Grishchuk, Y (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM ygrishchuk@mgh.harvard.edu FU ML4 Foundation; National Institutes of Health [HD058577, ES01678] FX This work was supported by grants from ML4 Foundation to S.A.S. and Y.G. and National Institutes of Health grants HD058577 and ES01678 to K.I.K. NR 73 TC 4 Z9 4 U1 5 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD DEC PY 2015 VL 8 IS 12 BP 1591 EP 1601 DI 10.1242/dmm.021154 PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DC0KG UT WOS:000368905300010 PM 26398942 ER PT J AU Hung, GCL Hahn, J Alamiri, B Buka, SL Goldstein, JM Laird, N Nelson, CA Smoller, W Gilman, SE AF Hung, Galen Chin-Lun Hahn, Jill Alamiri, Bibi Buka, Stephen L. Goldstein, Jill M. Laird, Nan Nelson, Charles A. Smoller, Jordan W. Gilman, Stephen E. TI Socioeconomic disadvantage and neural development from infancy through early childhood SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Neural development; soft signs; neurological abnormality; socioeconomic status ID NEUROLOGICAL SOFT SIGNS; COLLABORATIVE PERINATAL PROJECT; 1ST-EPISODE SCHIZOPHRENIA; BIPOLAR DISORDER; SEX-DIFFERENCES; BIRTH COHORT; CHILDREN; STRESS; NEURODEVELOPMENT; OUTCOMES AB Background: Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children's neural functioning, a core domain of neurodevelopment. Methods: We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function. Results: Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children. Conclusions: Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children's neural functioning, the timing of such mechanisms and their potential reversibility. C1 [Hung, Galen Chin-Lun] Taipei City Hosp, Taipei City Psychiat Ctr, Dept Gen Psychiat, Taipei, Taiwan. [Hung, Galen Chin-Lun] Natl Yang Ming Univ, Sch Med, Dept Publ Hlth, Taipei 112, Taiwan. [Hahn, Jill; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Alamiri, Bibi] Lahey Hosp & Med Ctr, Sect Child & Adolescent Psychiat, Burlington, MA USA. [Alamiri, Bibi; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Buka, Stephen L.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. [Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Laird, Nan] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Nelson, Charles A.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Smoller, Jordan W.; Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Gilman, Stephen E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD USA. RP Gilman, SE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Room 7B13M, Rockville, MD 20852 USA. EM stephen.gilman@nih.gov OI Gilman, Stephen/0000-0002-8331-6419 FU National Institutes of Health [RO1MH087544, P50MH082679]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported in part by grants from the National Institutes of Health [RO1MH087544 to S.E.G. and P50MH082679 to J.M.G.] and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 79 TC 5 Z9 5 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2015 VL 44 IS 6 BP 1889 EP 1899 DI 10.1093/ije/dyv303 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC0NW UT WOS:000368915400019 ER PT J AU Ananthakrishnan, AN Khalili, H Song, MY Higuchi, LM Richter, JM Chan, AT AF Ananthakrishnan, Ashwin N. Khalili, Hamed Song, Mingyang Higuchi, Leslie M. Richter, James M. Chan, Andrew T. TI Zinc intake and risk of Crohn's disease and ulcerative colitis: a prospective cohort study SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Zinc; Crohn's disease; diet; risk; epidemiology ID INFLAMMATORY-BOWEL-DISEASE; EUROPEAN PROSPECTIVE COHORT; LONG-TERM INTAKE; NF-KAPPA-B; OXIDATIVE STRESS; SMOKING; CELLS; WOMEN; RATS; DIET AB Background: Diet plays a role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Dietary zinc may influence risk of disease through effects on autophagy, innate and adaptive immune response and maintenance of the intestinal barrier. Methods: We analysed data from 170 776 women from the Nurses Health Study I and Nurses Health Study II, who were followed for 26 years. Zinc intake was assessed using semi-quantitative food frequency questionnaires administered every 4 years. Incident CD and UC were ascertained by medical record review. Cox proportional hazards models adjusting for potential confounders determined the independent association between zinc intake and incident disease. Results: Over 3 317 550 person-years (p-y) of follow-up, we identified 269 incident cases of CD and 338 incident cases of UC. Zinc intake ranged from 9 mg/day in the lowest quintile to 27 mg/day in the highest quintile. Compared with women with the lowest quintile of intake, the multivariate hazard ratios (HR) for CD were 0.92 [95% confidence interval (CI), 0.65 - 1.29) for women in the second quintile of intake, 0.60 (95% CI, 0.40 - 0.89) for the third quintile, 0.57 (95% CI, 0.38 - 0.86) for fourth quintile and 0.74 (95% CI, 0.50 - 1.10) for the highest quintile (P-trend = 0.003). The association was stronger for dietary zinc (HR 0.63, 95% CI, 0.43 - 0.93, comparing extreme quintiles) than for zinc intake from supplements. Neither dietary nor supplemental zinc modified risk of UC. Conclusions: In two large prospective cohorts of women, intake of zinc was inversely associated with risk of CD but not UC. C1 [Ananthakrishnan, Ashwin N.; Khalili, Hamed; Richter, James M.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Khalili, Hamed; Higuchi, Leslie M.; Richter, James M.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Song, Mingyang] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Song, Mingyang] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Higuchi, Leslie M.] Childrens Hosp Boston, Div Gastroenterol & Nutr, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU American Gastroenterological Association; Crohn's and Colitis Foundation of America; National Institutes of Health [K24 DK098311, P01 CA87969, P30 DK043351, K08 DK064256, K23 DK091742, K23 DK099681, UM1 CA176276] FX This work was supported by a Research Scholars Award of the American Gastroenterological Association (A.N.A., H.K), a Senior Investigator Award from the Crohn's and Colitis Foundation of America (A.T.C), and the National Institutes of Health (K24 DK098311, P01 CA87969, P30 DK043351, K08 DK064256, K23 DK091742, K23 DK099681, and UM1 CA176276). NR 42 TC 3 Z9 3 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2015 VL 44 IS 6 BP 1995 EP 2005 DI 10.1093/ije/dyv301 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC0NW UT WOS:000368915400030 PM 26546032 ER PT J AU Murphy, JM Gilman, S Colman, I AF Murphy, Jane M. Gilman, Stephen Colman, Ian TI Psychiatric epidemiology: dimensions and categories SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID NATIONAL-COMORBIDITY-SURVEY; DSM-III; PREVALENCE; DISORDERS C1 [Murphy, Jane M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Murphy, Jane M.; Gilman, Stephen] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Murphy, Jane M.] Dalhousie Fac Med, Dept Psychiat, Halifax, NS, Canada. [Colman, Ian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Murphy, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. EM murphy.jane@mgh.harvard.edu OI Gilman, Stephen/0000-0002-8331-6419 FU Canadian Institutes of Health Research [126099] NR 21 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2015 VL 44 IS 6 BP 2020 EP 2022 DI 10.1093/ije/dyv297 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC0NW UT WOS:000368915400032 PM 26559547 ER PT J AU Nepomuceno, R Sun, DD AF Nepomuceno, Rachel Sun, Dandan TI Pharmacological inhibition of cation-chloride cotransporters for neurological diseases SO NEURAL REGENERATION RESEARCH LA English DT Editorial Material ID TEMPORAL-LOBE EPILEPSY; BUMETANIDE; MODEL; SEIZURES; TRIAL; BRAIN C1 [Nepomuceno, Rachel; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sun, Dandan] Ctr Geriatr Res Educ & Clin, Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Sun, DD (reprint author), Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. EM sund@upmc.edu NR 13 TC 1 Z9 1 U1 2 U2 2 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1673-5374 EI 1876-7958 J9 NEURAL REGEN RES JI Neural Regen. Res. PD DEC PY 2015 VL 10 IS 12 BP 1924 EP 1925 DI 10.4103/1673-5374.172313 PG 2 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA DC0RU UT WOS:000368926200010 PM 26889170 ER PT J AU Huang, FW Bielski, CM Rinne, ML Hahn, WC Sellers, WR Stegmeier, F Garraway, LA Kryukov, GV AF Huang, F. W. Bielski, C. M. Rinne, M. L. Hahn, W. C. Sellers, W. R. Stegmeier, F. Garraway, L. A. Kryukov, G. V. TI TERT promoter mutations and monoallelic activation of TERT in cancer SO ONCOGENESIS LA English DT Article ID SOMATIC MUTATIONS; EXPRESSION AB Here we report that promoter mutations in telomerase (TERT), the most common noncoding mutations in cancer, give rise to monoallelic expression of TERT. Through deep RNA sequencing, we find that TERT activation in human cancer cell lines can occur in either mono-or biallelic manner. Without exception, hotspot TERT promoter mutations lead to the re-expression of only one allele, accounting for approximately half of the observed cases of monoallelic TERT expression. Furthermore, we show that monoallelic TERT expression is highly prevalent in certain tumor types and widespread across a broad spectrum of cancers. Taken together, these observations provide insights into the mechanisms of TERT activation and the ramifications of noncoding mutations in cancer. C1 [Huang, F. W.; Rinne, M. L.; Hahn, W. C.; Garraway, L. A.; Kryukov, G. V.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huang, F. W.; Hahn, W. C.; Garraway, L. A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Huang, F. W.; Bielski, C. M.; Rinne, M. L.; Hahn, W. C.; Garraway, L. A.; Kryukov, G. V.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Rinne, M. L.; Stegmeier, F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Sellers, W. R.] Novartis Inst Biomed Res, Oncol Dis Area, Cambridge, MA USA. [Kryukov, G. V.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. RP Huang, FW (reprint author), Broad Inst MIT & Harvard, Canc Program, 415 Main St, Cambridge, MA 02142 USA. EM fwhuang@broadinstitute.org; kryukov@broadinstitute.org FU Novartis Institutes for Biomedical Research; Prostate Cancer Foundation Young Investigator Award; ASCO Young Investigator Award; Department of Defense FX We thank Drs JL Stern and TR Cech for helpful discussions. This work was supported by a research grant from Novartis Institutes for Biomedical Research. FWH is supported by the Prostate Cancer Foundation Young Investigator Award, ASCO Young Investigator Award and the Department of Defense. The BAM files for the CCLE whole genome sequencing data corresponding to the TERT locus can be accessed at ftp://tertguest:broad@ftp.broadinstitute.org. NR 19 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2157-9024 J9 ONCOGENESIS JI Oncogenesis PD DEC PY 2015 VL 4 AR e176 DI 10.1038/oncsis.2015.39 PG 4 WC Oncology SC Oncology GA DC0NJ UT WOS:000368914000001 PM 26657580 ER PT J AU Bader, MK Figueroa, SA Leary, M Guanci, MM Mathiesen, C Delfin, G AF Bader, Mary Kay Figueroa, Stephen A. Leary, Marion Guanci, Mary McKenna Mathiesen, Claranne Delfin, Gail TI Clinical Q & A: Translating Therapeutic Temperature Management from Theory to Practice SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Letter ID SICKLE-CELL-DISEASE C1 [Figueroa, Stephen A.] Univ Texas SW Med Ctr Dallas, Div Neurocrit Care, Dallas, TX 75390 USA. [Bader, Mary Kay] Mission Hosp, Mission Viejo, CA USA. [Leary, Marion] Univ Penn, Sch Nursing, Ctr Resuscitat Sci, Dept Emergency Med, Philadelphia, PA 19104 USA. [Guanci, Mary McKenna] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mathiesen, Claranne] Lehigh Valley Hlth Network, Allentown, PA USA. [Delfin, Gail] Univ Penn, Ctr Resuscitat Sci, Philadelphia, PA 19104 USA. RP Figueroa, SA (reprint author), Univ Texas SW Med Ctr Dallas, Div Neurocrit Care, Dallas, TX 75390 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD DEC 1 PY 2015 VL 5 IS 4 BP 235 EP 235 DI 10.1089/ther.2015.29006.mkb PG 1 WC Critical Care Medicine SC General & Internal Medicine GA DC6XI UT WOS:000369362500011 ER PT J AU Guanci, MM AF Guanci, Mary McKenna TI A patient arrested intraoperatively requiring 10 minutes of CPR and resuscitation. The patient had an ROSC. In trying to make a decision to induce hypothermia post-cardiac arrest, should we try to reverse anesthesia and attempt to wake the patient up prior to inducing hypothermia? How long would you give the patient to emerge from anesthesia? SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Letter C1 [Guanci, Mary McKenna] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Guanci, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD DEC 1 PY 2015 VL 5 IS 4 BP 237 EP 237 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA DC6XI UT WOS:000369362500013 ER PT J AU Luo, C Omelchenko, I Manson, R Robbins, C Oesterle, EC Cao, GZ Shen, IY Hume, CR AF Luo, Chuan Omelchenko, Irina Manson, Robert Robbins, Carol Oesterle, Elizabeth C. Cao, Guo Zhong Shen, I. Y. Hume, Clifford R. TI Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator SO TRENDS IN HEARING LA English DT Article DE Cochlear implant; hearing aid; PZT; cochlea; piezoelectric; perilymph; hybrid; electroacoustic ID BRAIN-STEM RESPONSE; COCHLEAR IMPLANT ELECTRODE; ROUND-WINDOW STIMULATION; INDUCED HEARING-LOSS; GUINEA-PIG; ELECTROACOUSTIC STIMULATION; RESIDUAL HEARING; INNER-EAR; EVOKED-RESPONSES; MOUSE AB Combined electric and acoustic stimulation has proven to be an effective strategy to improve hearing in some cochlear implant users. We describe an acoustic microactuator to directly deliver stimuli to the perilymph in the scala tympani. The 800 mm by 800 mm actuator has a silicon diaphragm driven by a piezoelectric thin film (e.g., lead-zirconium-titanium oxide or PZT). This device could also be used as a component of a bimodal acoustic-electric electrode array. In the current study, we established a guinea pig model to test the actuator for its ability to deliver auditory signals to the cochlea in vivo. The actuator was placed through the round window of the cochlea. Auditory brainstem response (ABR) thresholds, peak latencies, and amplitude growth were calculated for an ear canal speaker versus the intracochlear actuator for tone burst stimuli at 4, 8, 16, and 24 kHz. An ABR was obtained after removal of the probe to assess loss of hearing related to the procedure. In some animals, the temporal bone was harvested for histologic analysis of cochlear damage. We show that the device is capable of stimulating ABRs in vivo with latencies and growth functions comparable to stimulation in the ear canal. Further experiments will be necessary to evaluate the efficiency and safety of this modality in long-term auditory stimulation and its ability to be integrated with conventional cochlear implant arrays. C1 [Luo, Chuan; Manson, Robert; Shen, I. Y.] Univ Washington, Dept Mech Engn, Box 352600, Seattle, WA 98195 USA. [Luo, Chuan] Tsinghua Univ, Dept Precis Instruments, Beijing 100084, Peoples R China. [Omelchenko, Irina; Robbins, Carol; Oesterle, Elizabeth C.; Hume, Clifford R.] Univ Washington, Dept Otolaryngol Head & Neck Surg, Virginia Merrill Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. [Cao, Guo Zhong] Univ Washington, Dept Mat Sci, Seattle, WA 98195 USA. [Hume, Clifford R.] VA Puget Sound, Seattle, WA USA. RP Shen, IY (reprint author), Univ Washington, Dept Mech Engn, Box 352600, Seattle, WA 98195 USA. EM ishen@u.washington; hume@uw.edu RI Cao, Guozhong/E-4799-2011 FU Division of Chemical, Bioengineering, Environmental, and Transport Systems-NSF [CBET-1159623]; National Institute on Deafness and Other Communication Disorders-NIDCD [DC-03944]; NIDCD [DC-006437, P30 DC-04661]; NICHD [P30 HD-02774] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is supported by Division of Chemical, Bioengineering, Environmental, and Transport Systems-NSF CBET-1159623 (to I.-Y. S., G. Z., and C. R. H.)-and by National Institute on Deafness and Other Communication Disorders-NIDCD DC-03944 (to E. C. O.), NIDCD DC-006437 (to C. R. H.), NIDCD P30 DC-04661, and NICHD P30 HD-02774. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies. NR 51 TC 0 Z9 0 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2331-2165 J9 TRENDS HEAR JI Trends Hear. PD DEC 1 PY 2015 VL 19 DI 10.1177/2331216515616942 PG 14 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA DB6AQ UT WOS:000368595900003 ER PT J AU Shorter, D Hsieh, J Kosten, TR AF Shorter, Daryl Hsieh, John Kosten, Thomas R. TI Pharmacologic Management of Comorbid Post-Traumatic Stress Disorder and Addictions SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE DISORDERS; DRUG-RELATED BEHAVIORS; D-CYCLOSERINE; CANNABIS DEPENDENCE; ALCOHOL DEPENDENCE; COMBAT VETERANS; MILITARY VETERANS; ANXIETY DISORDERS; TREATMENT OPTIONS AB Background and Objectives: Post-traumatic Stress Disorder (PTSD) and substance use disorders (SUD) frequently co-occur, and their combination can increase poor health outcomes as well as mortality. Methods: Using PUBMED and the list of references from key publications, this review article covered the epidemiology, neurobiology and pharmacotherapy of PTSD with comorbid alcohol, opiate, and cannabis use disorders. These SUD represent two with and one without FDA approved pharmacotherapies. Results: SUD is two to three times more likely among individuals with lifetime PTSD, and suicide, which is made more likely by both of these disorders, appears to be additively increased by having this comorbidity of SUD and PTSD. The shared neurobiological features of these two illnesses include amygdalar hyperactivity with hippocampal, medial prefrontal and anterior cingulate cortex dysfunction. Medications for comorbid PTSD and SUD include the PTSD treatment sertraline, often used in combination with anticonvulsants, antipsychotics, and adrenergic blockers. When PTSD is comorbid with alcohol use disorder (AUD), naltrexone, acamprosate or disulfiram may be combined with PTSD treatments. Disulfiram alone may treat both PTSD and AUD. For PTSD combined with opiate use disorder methadone or buprenorphine are most commonly used with sertraline. Marijuana use has been considered by some to be a treatment for PTSD, but no FDA treatment for this addiction is approved. Pregabalin and D-cycloserine are two innovations in pharmacotherapy for PTSD and SUD. Conclusions and Scientific Significance: Comorbid PTSD and SUD amplifies their lethality and treatment complexity. Although they share important neurobiology, these patients uncommonly respond to a single pharmacotherapy such as sertraline or disulfiram and more typically require medication combinations and consideration of the specific type of SUD. C1 [Shorter, Daryl; Kosten, Thomas R.] Michael E DeBakey Med Ctr, Mental Hlth Care Line, Houston, TX USA. [Shorter, Daryl; Hsieh, John; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Shorter, D (reprint author), 2002 Holcombe Blvd,Bldg 121,135, Houston, TX 77030 USA. EM shorter@bcm.edu FU VA grant [VA CS RD CDA-14-001]; NIH [K05-DA0454, P50-DA18197] FX Dr. Shorter is supported by VA grant: VA CS R&D CDA-14-001 and Dr. Kosten is supported by NIH grants K05-DA0454, P50-DA18197. NR 69 TC 6 Z9 6 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD DEC PY 2015 VL 24 IS 8 BP 705 EP 712 DI 10.1111/ajad.12306 PG 8 WC Substance Abuse SC Substance Abuse GA DB4TK UT WOS:000368506100003 PM 26587796 ER PT J AU Marino, K Parlee, A Orlando, R Lerner, L Strymish, J Gupta, K AF Marino, Kaylee Parlee, Anne Orlando, Ralph Lerner, Lori Strymish, Judith Gupta, Kalpana TI Comparative Effectiveness of Single versus Combination Antibiotic Prophylaxis for Infections after Transrectal Prostate Biopsy SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIMICROBIAL PROPHYLAXIS; COMPLICATIONS; RISK; CANCER; MEN AB An increase in fluoroquinolone resistance and transrectal ultrasound-guided prostate (TRUS) biopsy infections has prompted the need for alternative effective antibiotic prophylaxis. We aimed to compare ciprofloxacin and other single-agent therapies to combination therapy for efficacy and adverse effects. Men who underwent a TRUS biopsy within the VA Boston health care system with documented receipt of prophylactic antibiotics periprocedure were eligible for inclusion. Postprocedure infections within 30 days were ascertained by chart review from electronic records, including any inpatient, outpatient, or urgent-care visits. Among 455 evaluable men over a 3-year period, there were 25 infections (5.49%), with sepsis occurring in 2.4%, urinary tract infections (UTI) in 1.54%, and bacteremia in 0.44% of patients. Escherichia coli was the most common urine (89%) and blood (92%) pathogen, with fluoroquinolone resistance rates of 88% and 91%, respectively. Ciprofloxacin alone was associated with significantly more infections than ciprofloxacin plus an additional agent (P = 0.014). Intramuscular gentamicin alone was also significantly associated with a higher infection rate obtained with all other regimens (P = 0.004). Any single-agent regimen, including ciprofloxacin, ceftriaxone, or gentamicin, was associated with significantly higher infection rates than any combination regimen (odds ratio [OR], 4; 95% confidence interval [CI], 1.47, 10.85; P = 0.004). Diabetes, immunosuppressive condition or medication, hospitalization within the previous year, and UTI within the previous 6 months were not associated with infection risk. Clostridium difficile infections were similar. These findings suggest that ciprofloxacin, ceftriaxone, and gentamicin alone are inferior to a combination regimen. Institutions with high failure rates of prophylaxis for TRUS biopsies should consider combination regimens derived from their local data. C1 [Marino, Kaylee; Parlee, Anne] VA Boston Healthcare Syst, Dept Pharm, Boston, MA USA. [Orlando, Ralph; Lerner, Lori] VA Boston Healthcare Syst, Dept Surg, Div Urol, Boston, MA USA. [Strymish, Judith; Gupta, Kalpana] VA Boston Healthcare Syst, Dept Med, Div Infect Dis, Boston, MA 02132 USA. [Strymish, Judith] Harvard Univ, Sch Med, Boston, MA USA. [Lerner, Lori; Gupta, Kalpana] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Gupta, K (reprint author), VA Boston Healthcare Syst, Dept Med, Div Infect Dis, Boston, MA 02132 USA. EM kalpana.gupta@va.gov NR 9 TC 3 Z9 3 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2015 VL 59 IS 12 BP 7273 EP 7275 DI 10.1128/AAC.01457-15 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DB2KO UT WOS:000368337300014 PM 26369958 ER PT J AU Shields, RK Nguyen, MH Press, EG Cumbie, R Driscoll, E Pasculle, AW Clancy, CJ AF Shields, Ryan K. Nguyen, M. Hong Press, Ellen G. Cumbie, Richard Driscoll, Eileen Pasculle, A. William Clancy, Cornelius J. TI Rate of FKS Mutations among Consecutive Candida Isolates Causing Bloodstream Infection SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ECHINOCANDIN RESISTANCE; INVASIVE CANDIDIASIS; MULTIDRUG-RESISTANCE; CASPOFUNGIN MICS; GLABRATA; SUSCEPTIBILITY; ANIDULAFUNGIN; MANAGEMENT; OUTCOMES; FLUCONAZOLE AB Precise FKS mutation rates among Candida species are undefined because studies have not systematically screened consecutive, disease-causing isolates. The Sensititre YeastOne (SYO) assay measures echinocandin MICs against Candida with less variability than reference broth microdilution methods. However, clinical breakpoint MICs may overstate caspofungin nonsusceptibility compared to other agents. Our objectives were to determine Candida FKS mutation rates by studying consecutive bloodstream isolates and to determine if discrepant susceptibility results were associated with FKS mutations. FKS hot spots were sequenced in echinocandin-intermediate and -resistant isolates and those from patients with breakthrough candidemia or >= 3 days of prior echinocandin exposure. Overall, 453 isolates from 384 patients underwent susceptibility testing; 16% were echinocandin intermediate or resistant. Intermediate susceptibility rates were higher for Candida glabrata than for other species (P<0.0001) and higher for caspofungin than for other agents (P<0.0001). Resistance rates were similar between agents. FKS mutations were detected in 5% of sequenced isolates and 2% of isolates overall. Corresponding rates among C. glabrata isolates were 8% and 4%, respectively. Among Candida albicans isolates, rates were 5% and <1%, respectively. Mutations occurred exclusively with prior echinocandin exposure and were not detected in other species. Isolates with discrepant susceptibility results did not harbor FKS mutations. Mutation rates among isolates resistant to >= 2, 1, and 0 agents were 75%, 13%, and 0%, respectively. In conclusion, FKS mutations were uncommon among non-C. glabrata species, even with prior echinocandin exposure. Discrepancies in echinocandin susceptibility by SYO testing were not driven by mutations and likely reflect imprecise caspofungin clinical breakpoints. C1 [Shields, Ryan K.; Nguyen, M. Hong; Press, Ellen G.; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Shields, Ryan K.; Nguyen, M. Hong; Clancy, Cornelius J.] Univ Pittsburgh, Med Ctr, XDR Pathogen Lab, Pittsburgh, PA USA. [Cumbie, Richard; Driscoll, Eileen; Pasculle, A. William] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Nguyen, MH (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. EM mhn5@pitt.edu FU Astellas; Merck; National Institutes of Health [K08AI114883, KL2TR000146] FX This work was supported by investigator-initiated grants from Astellas and Merck and by the National Institutes of Health through grant numbers K08AI114883 and KL2TR000146 awarded to R.K.S. NR 30 TC 3 Z9 4 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2015 VL 59 IS 12 BP 7465 EP 7470 DI 10.1128/AAC.01973-15 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DB2KO UT WOS:000368337300037 PM 26392494 ER PT J AU Linsenmeyer, K Strymish, J Gupta, K AF Linsenmeyer, Katherine Strymish, Judith Gupta, Kalpana TI Two Simple Rules for Improving the Accuracy of Empiric Treatment of Multidrug-Resistant Urinary Tract Infections SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SPECTRUM-BETA-LACTAMASE; BACTEREMIA; ENTEROBACTERIACEAE; OUTCOMES; IMPACT AB The emergence of multidrug-resistant (MDR) uropathogens is making the treatment of urinary tract infections (UTIs) more challenging. We sought to evaluate the accuracy of empiric therapy for MDR UTIs and the utility of prior culture data in improving the accuracy of the therapy chosen. The electronic health records from three U.S. Department of Veterans Affairs facilities were retrospectively reviewed for the treatments used for MDR UTIs over 4 years. An MDR UTI was defined as an infection caused by a uropathogen resistant to three or more classes of drugs and identified by a clinician to require therapy. Previous data on culture results, antimicrobial use, and outcomes were captured from records from inpatient and outpatient settings. Among 126 patient episodes of MDR UTIs, the choices of empiric therapy against the index pathogen were accurate in 66 (52%) episodes. For the 95 patient episodes for which prior microbiologic data were available, when empiric therapy was concordant with the prior microbiologic data, the rate of accuracy of the treatment against the uropathogen improved from 32% to 76% (odds ratio, 6.9; 95% confidence interval, 2.7 to 17.1; P < 0.001). Genitourinary tract (GU)-directed agents (nitrofurantoin or sulfa agents) were equally as likely as broad-spectrum agents to be accurate (P = 0.3). Choosing an agent concordant with previous microbiologic data significantly increased the chance of accuracy of therapy for MDR UTIs, even if the previous uropathogen was a different species. Also, GU-directed or broad-spectrum therapy choices were equally likely to be accurate. The accuracy of empiric therapy could be improved by the use of these simple rules. C1 [Linsenmeyer, Katherine; Strymish, Judith; Gupta, Kalpana] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Linsenmeyer, Katherine; Gupta, Kalpana] Boston Univ, Sch Med, Boston, MA 02118 USA. [Strymish, Judith] Harvard Univ, Sch Med, Boston, MA USA. [Gupta, Kalpana] VA Natl Ctr Occupat Hlth & Infect Control, Gainesville, FL USA. RP Linsenmeyer, K (reprint author), VA Boston Healthcare Syst, Boston, MA 02132 USA. EM Katherine.Linsenmeyer@bmc.org NR 13 TC 3 Z9 3 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2015 VL 59 IS 12 BP 7593 EP 7596 DI 10.1128/AAC.01638 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DB2KO UT WOS:000368337300052 PM 26416859 ER PT J AU Gebremariam, T Wiederhold, NP Fothergill, AW Garvey, EP Hoekstra, WJ Schotzinger, RJ Patterson, TF Filler, SG Ibrahim, AS AF Gebremariam, Teclegiorgis Wiederhold, Nathan P. Fothergill, Annette W. Garvey, Edward P. Hoekstra, William J. Schotzinger, Robert J. Patterson, Thomas F. Filler, Scott G. Ibrahim, Ashraf S. TI VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; TRANSPLANT RECIPIENTS; IMPROVES SURVIVAL; MOLD INFECTIONS; ZYGOMYCOSIS; MUCORMYCOSIS; EPIDEMIOLOGY; ORYZAE; EFFICACY; CYP51 AB We studied the efficacy of the investigational drug VT-1161 against mucormycosis. VT-1161 had more potent in vitro activity against Rhizopus arrhizus var. arrhizus than against R. arrhizus var. delemar. VT-1161 treatment demonstrated dose-dependent plasma drug levels with prolonged survival time and lowered tissue fungal burden in immunosuppressed mice infected with R. arrhizus var. arrhizus and was as effective as high-dose liposomal amphotericin B treatment. These results support further development of VT-1161 against mucormycosis. C1 [Gebremariam, Teclegiorgis; Filler, Scott G.; Ibrahim, Ashraf S.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Infect Dis, Torrance, CA 90509 USA. [Gebremariam, Teclegiorgis; Filler, Scott G.; Ibrahim, Ashraf S.] St Johns Cardiovasc Res Ctr, Torrance, CA 90509 USA. [Wiederhold, Nathan P.; Fothergill, Annette W.; Patterson, Thomas F.] Univ Texas Hlth Sci San Antonio, San Antonio, TX USA. [Garvey, Edward P.; Hoekstra, William J.; Schotzinger, Robert J.] Viamet Pharmaceut Inc, Durham, NC USA. [Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Filler, Scott G.; Ibrahim, Ashraf S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Ibrahim, AS (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Infect Dis, Torrance, CA 90509 USA. EM ibrahim@labiomed.org OI Wiederhold, Nathan/0000-0002-2225-5122 FU Public Health Service (NIH) [HHSN272201000038I, R01 AI063503] FX This work was supported by Public Health Service contract HHSN272201000038I (NIH task order A13) and grant R01 AI063503. NR 24 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2015 VL 59 IS 12 BP 7815 EP 7817 DI 10.1128/AAC.01437-15 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DB2KO UT WOS:000368337300083 PM 26369977 ER PT J AU Black, JC Whetstine, JR AF Black, Joshua C. Whetstine, Johnathan R. TI RNF2 E3 or Not to E3: Dual Roles of RNF2 Overexpression in Melanoma SO CANCER DISCOVERY LA English DT Editorial Material ID PROTEINS AB RNF2/RING1B is amplified and overexpressed in numerous tumors and contributes to tumorigenicity; however, the biologic importance is poorly understood. Surprisingly, the role of RNF2 in tumorigenesis and invasion can be separated into catalytically independent and catalytically dependent processes. (C) 2015 AACR. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA USA. RP Whetstine, JR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,Room 7-213,13th St, Charlestown, MA 02129 USA. EM jwhetstine@hms.harvard.edu FU NIGMS NIH HHS [R01 GM097360, R01GM097360] NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD DEC PY 2015 VL 5 IS 12 BP 1241 EP 1243 DI 10.1158/2159-8290.CD-15-1285 PG 3 WC Oncology SC Oncology GA DB5TW UT WOS:000368577500019 PM 26637658 ER PT J AU Perera, RM Bardeesy, N AF Perera, Rushika M. Bardeesy, Nabeel TI Pancreatic Cancer Metabolism: Breaking It Down to Build It Back Up SO CANCER DISCOVERY LA English DT Review ID RAS-TRANSFORMED CELLS; BODY-MASS INDEX; DUCTAL ADENOCARCINOMA; TUMOR-GROWTH; LYSOSOMAL BIOGENESIS; ONCOGENIC KRAS; MITOCHONDRIAL METABOLISM; TRANSCRIPTIONAL CONTROL; LACTATE-DEHYDROGENASE; INSULIN-RESISTANCE AB How do cancer cells escape tightly controlled regulatory circuits that link their proliferation to extracellular nutrient cues? An emerging theme in cancer biology is the hijacking of normal stress response mechanisms to enable growth even when nutrients are limiting. Pancreatic ductal adenocarcinoma (PDA) is the quintessential aggressive malignancy that thrives in nutrient-poor, hypoxic environments. PDAs overcome these limitations through appropriation of unorthodox strategies for fuel source acquisition and utilization. In addition, the interplay between evolving PDA and whole-body metabolism contributes to disease pathogenesis. Deciphering how these pathways function and integrate with one another can reveal novel angles of therapeutic attack. Significance: Alterations in tumor cell and systemic metabolism are central to the biology of pancreatic cancer. Further investigation of these processes will provide important insights into how these tumors develop and grow, and suggest new approaches for its detection, prevention, and treatment. (C) 2015 AACR. C1 [Perera, Rushika M.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Perera, Rushika M.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Perera, Rushika M.; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Bardeesy, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 185 Cambridge St,Room 4216, Boston, MA 02114 USA. EM rushika.perera@ucsf.edu; Bardeesy.Nabeel@mgh.harvard.edu RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 FU NIH [P50CA1270003, P01 CA117969-07, R01 CA133557-05]; Linda J. Verville Cancer Research Foundation; Hirshberg Foundation for Pancreatic Cancer seed grant FX This work was supported by grants from the NIH (P50CA1270003, P01 CA117969-07, and R01 CA133557-05) and the Linda J. Verville Cancer Research Foundation to N. Bardeesy and a Hirshberg Foundation for Pancreatic Cancer seed grant to R.M. Perera. NR 140 TC 9 Z9 9 U1 4 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD DEC PY 2015 VL 5 IS 12 BP 1247 EP 1261 DI 10.1158/2159-8290.CD-15-0671 PG 15 WC Oncology SC Oncology GA DB5TW UT WOS:000368577500021 PM 26534901 ER PT J AU Kwak, EL Ahronian, LG Siravegna, G Mussolin, B Godfrey, JT Clark, JW Blaszkowsky, LS Ryan, DP Lennerz, JK Iafrate, AJ Bardelli, A Hong, TS Corcoran, RB AF Kwak, Eunice L. Ahronian, Leanne G. Siravegna, Giulia Mussolin, Benedetta Godfrey, Jason T. Clark, Jeffrey W. Blaszkowsky, Lawrence S. Ryan, David P. Lennerz, Jochen K. Iafrate, A. John Bardelli, Alberto Hong, Theodore S. Corcoran, Ryan B. TI Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer SO CANCER DISCOVERY LA English DT Article ID CIRCULATING TUMOR DNA; CELL LUNG-CANCER; ACQUIRED-RESISTANCE; KINASE INHIBITOR; GASTRIC-CANCER; ADENOCARCINOMA; AMPLIFICATION; EGFR; SENSITIVITY; CRIZOTINIB AB MET inhibition is effective in some patients with MET-amplified esophagogastric cancer (EGC), but understanding acquired and de novo resistance mechanisms will be critical to improving therapy. We identified KRAS mutation as a novel cause of acquired resistance in a patient after a 2-year response to a MET inhibitor. We also observed that 40% to 50% of patients with MET-amplified EGC harbor coamplification of HER2 and/or EGFR concurrently in the same tumor cells, which can drive de novo resistance. One patient with concurrent MET and HER2 amplification was refractory to HER2 blockade, but responded to combined MET/HER2 inhibition. We also found striking heterogeneity in MET amplification between distinct metastatic lesions and primary tumors in individual patients with EGC. In these patients, MET inhibition led to mixed responses and disease progression through outgrowth of non-MET-amplified clones, which could be monitored in circulating tumor DNA. Thus, receptor coamplification and molecular heterogeneity may be key drivers of clinical resistance in MET-amplified EGC. SIGNIFICANCE: Coamplification of driver oncogenes occurs frequently in EGC and can drive therapeutic resistance, supporting a role for comprehensive molecular analysis prior to targeted therapy. EGCs can also exhibit extensive heterogeneity in gene amplification between distinct tumor lesions within the same patient, suggesting that molecular profiling of a single-lesion biopsy may be insufficient to guide targeted therapy selection. (C) 2015 AACR. C1 [Kwak, Eunice L.; Ahronian, Leanne G.; Godfrey, Jason T.; Clark, Jeffrey W.; Blaszkowsky, Lawrence S.; Ryan, David P.; Hong, Theodore S.; Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Boston, MA 02129 USA. [Kwak, Eunice L.; Ahronian, Leanne G.; Godfrey, Jason T.; Clark, Jeffrey W.; Blaszkowsky, Lawrence S.; Ryan, David P.; Corcoran, Ryan B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Siravegna, Giulia; Mussolin, Benedetta; Bardelli, Alberto] Univ Turin, Dept Oncol, Turin, Italy. [Siravegna, Giulia; Mussolin, Benedetta; Bardelli, Alberto] IRCCS, Candiolo Canc Inst FPO, Turin, Italy. [Lennerz, Jochen K.; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lennerz, Jochen K.; Iafrate, A. John] Harvard Univ, Sch Med, Boston, MA USA. [Hong, Theodore S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Corcoran, RB (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Boston, MA 02129 USA. EM ekwak@partners.org; rbcorcoran@partners.org FU NIH Gastrointestinal Cancer SPORE [P50 CA127003]; Damon Runyon Clinical Investigator Award; NIH/NCI [1K08CA166510]; NIH/NCI Cancer Clinical Investigator Team Leadership Award [P30CA006516] FX This study is supported by grants from the NIH Gastrointestinal Cancer SPORE P50 CA127003, a Damon Runyon Clinical Investigator Award, NIH/NCI 1K08CA166510 (all to R.B. Corcoran), and an NIH/NCI Cancer Clinical Investigator Team Leadership Award supplement to P30CA006516 (to T.S. Hong). NR 25 TC 14 Z9 14 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD DEC PY 2015 VL 5 IS 12 BP 1271 EP 1281 DI 10.1158/2159-8290.CD-15-0748 PG 11 WC Oncology SC Oncology GA DB5TW UT WOS:000368577500023 PM 26432108 ER PT J AU Chong, DQ Mehta, RS Song, MY Kedrin, D Meyerhardt, JA Ng, K Wu, K Fuchs, CS Giovannucci, EL Ogino, S Chan, AT AF Chong, Dawn Q. Mehta, Raaj S. Song, Mingyang Kedrin, Dmitriy Meyerhardt, Jeffrey A. Ng, Kimmie Wu, Kana Fuchs, Charles S. Giovannucci, Edward L. Ogino, Shuji Chan, Andrew T. TI Prediagnostic Plasma Adiponectin and Survival among Patients with Colorectal Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; MOLECULAR-WEIGHT ADIPONECTIN; NATIONAL DEATH INDEX; COLON-CANCER; CIRCULATING ADIPONECTIN; INSULIN SENSITIVITY; RISK; OBESITY; METAANALYSIS; INFLAMMATION AB Circulating adiponectin is inversely related to the risk of colorectal cancer. However, its influence on colorectal cancer survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with colorectal cancer. We identified 621 incident colorectal cancer cases who provided blood specimens prior to diagnosis within the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to colorectal cancer. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21-2.97; P-trend = 0.01) for colorectal cancer-specific mortality and 1.66 (95% CI, 1.15-2.39; P-trend = 0.009) for overall mortality. The apparent increased risk in colorectal cancer-specific mortality was more pronounced in patients with metastatic disease (HR, 3.02: 95% CI, 1.50-6.08). Among patients with colorectal cancer, prediagnostic plasma adiponectin is associated with an increased risk of colorectal cancer-specific and overall mortality and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings. (C) 2015 AACR. C1 [Chong, Dawn Q.; Mehta, Raaj S.; Song, Mingyang; Kedrin, Dmitriy; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chong, Dawn Q.; Mehta, Raaj S.; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A.; Ng, Kimmie; Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chong, Dawn Q.; Mehta, Raaj S.; Song, Mingyang; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Chong, Dawn Q.] Natl Canc Ctr Singapore, Div Med Oncol, Singapore, Singapore. [Wu, Kana; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Song, Mingyang; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Meyerhardt, Jeffrey A.; Ng, Kimmie; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Dept Med, Clin & Translat Epidemiol Unit, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org FU U.S. NIH [P01 CA 087969, R01 CA49449, UM1 CA167552, P01 CA55075, P50 CA127003, R01 CA151993, R35 CA197735, K24 DK 098311, R01 CA137178]; Singhealth Health Manpower Development Plan (HMDP) fellowship award from Singapore FX This work was supported by U.S. NIH grants [P01 CA 087969 and R01 CA49449 (to S.E. Hankinson), UM1 CA167552 and P01 CA55075 (to W.C. Willett), P50 CA127003 (to C.S. Fuchs), R01 CA151993 and R35 CA197735 (to S. Ogino), K24 DK 098311 and R01 CA137178 (to A.T. Chan)]. D.Q. Chong is a recipient of the Singhealth Health Manpower Development Plan (HMDP) fellowship award from Singapore. R.S. Mehta is a Howard Hughes Medical Institute Medical Research Fellow and an AGA-Eli and Edythe Broad Student Research Fellow. NR 49 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD DEC PY 2015 VL 8 IS 12 BP 1138 EP 1145 DI 10.1158/1940-6207.CAPR-15-0175 PG 8 WC Oncology SC Oncology GA DB5BS UT WOS:000368528700002 PM 26382604 ER PT J AU Petrick, JL Sahasrabuddhe, VV Chan, AT Alavanja, MC Beane-Freeman, LE Buring, JE Chen, J Chong, DQ Freedman, ND Fuchs, CS Gaziano, JM Giovannucci, E Graubard, BI Hollenbeck, AR Hou, LF Jacobs, EJ King, LY Koshiol, J Lee, IM Linet, MS Palmer, JR Purdue, MP Rosenberg, L Schairer, C Sesso, HD Sigurdson, AJ Wactawski-Wende, J Zeleniuch-Jacquotte, A Campbell, PT McGlynn, KA AF Petrick, Jessica L. Sahasrabuddhe, Vikrant V. Chan, Andrew T. Alavanja, Michael C. Beane-Freeman, Laura E. Buring, Julie E. Chen, Jie Chong, Dawn Q. Freedman, Neal D. Fuchs, Charles S. Michael Gaziano, John Giovannucci, Edward Graubard, Barry I. Hollenbeck, Albert R. Hou, Lifang Jacobs, Eric J. King, Lindsay Y. Koshiol, Jill Lee, I-Min Linet, Martha S. Palmer, Julie R. Purdue, Mark P. Rosenberg, Lynn Schairer, Catherine Sesso, Howard D. Sigurdson, Alice J. Wactawski-Wende, Jean Zeleniuch-Jacquotte, Anne Campbell, Peter T. McGlynn, Katherine A. TI NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project SO CANCER PREVENTION RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLORECTAL-CANCER; UNITED-STATES; CELL-GROWTH; ASPIRIN; CYCLOOXYGENASE-2; INHIBITORS; PREVENTION; APOPTOSIS; SURVIVAL AB Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the associationbetween aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5-and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin usewas associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P-interaction = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. (C) 2015 AACR. C1 [Petrick, Jessica L.; Sahasrabuddhe, Vikrant V.; Alavanja, Michael C.; Beane-Freeman, Laura E.; Chen, Jie; Freedman, Neal D.; Graubard, Barry I.; Koshiol, Jill; Linet, Martha S.; Purdue, Mark P.; Schairer, Catherine; Sigurdson, Alice J.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sahasrabuddhe, Vikrant V.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Sahasrabuddhe, Vikrant V.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Sahasrabuddhe, Vikrant V.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Chan, Andrew T.; Chong, Dawn Q.; King, Lindsay Y.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Chong, Dawn Q.; Fuchs, Charles S.; King, Lindsay Y.] Harvard Univ, Sch Med, Boston, MA USA. [Buring, Julie E.; Giovannucci, Edward; Lee, I-Min; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chong, Dawn Q.] Natl Canc Ctr Singapore, Div Med Oncol, Singapore, Singapore. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Michael Gaziano, John] VA Boston Healthcare Syst, Brockton, MA USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Hou, Lifang] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Jacobs, Eric J.; Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Palmer, Julie R.; Rosenberg, Lynn] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. RP Petrick, JL (reprint author), NCI, 9609 Med Ctr Dr,7E-232, Bethesda, MD 20892 USA. EM jessica.petrick@nih.gov RI Purdue, Mark/C-9228-2016; Beane Freeman, Laura/C-4468-2015; OI Purdue, Mark/0000-0003-1177-3108; Beane Freeman, Laura/0000-0003-1294-4124; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NIH Intramural Research Program, National Cancer Institute; National Cancer Institute [CA047988, HL043851, HL080467, HL099355, DK098311, CA186107, CA87969, CA167552] FX The study was supported by NIH Intramural Research Program, National Cancer Institute (J.L. Petrick, V.V. Sahasrabuddhe, M.C. Alavanja, L. Beane-Freeman, J. Chen, N.D. Freedman, B.I. Graubard, J. Koshiol, M.S. Linet, C. Schairer, A.J. Sigurdson, K.A. McGlynn). National Cancer Institute Grants CA047988 (I. Lee, J.E. Buring), HL043851 (I. Lee, J.E. Buring), HL080467 (I. Lee, J.E. Buring), HL099355 (I. Lee, J. E. Buring), DK098311 (A.T. Chan), CA186107 (A.T. Chan), CA87969 (A.T. Chan), and CA167552 (A.T. Chan). NR 46 TC 1 Z9 1 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD DEC PY 2015 VL 8 IS 12 BP 1156 EP 1162 DI 10.1158/1940-6207.CAPR-15-0126 PG 7 WC Oncology SC Oncology GA DB5BS UT WOS:000368528700004 PM 26391917 ER PT J AU Niesor, EJ Benghozi, R Amouyel, P Ferdinand, KC Schwartz, GG AF Niesor, Eric J. Benghozi, Renee Amouyel, Philippe Ferdinand, Keith C. Schwartz, Gregory G. TI Adenylyl Cyclase 9 Polymorphisms Reveal Potential Link to HDL Function and Cardiovascular Events in Multiple Pathologies: Potential Implications in Sickle Cell Disease SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Review DE Adenylyl cyclase 9; beta 2-adrenergic receptor; High-density lipoprotein; Apolipoprotein A1; Sickle cell disease; Malaria ID REVERSE CHOLESTEROL TRANSPORT; HIGH-DENSITY-LIPOPROTEINS; PROTEIN-COUPLED RECEPTOR; BETA-ADRENERGIC-RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; GENE POLYMORPHISMS; NITRIC-OXIDE; LIPID RAFTS; ERYTHROCYTE-MEMBRANES; SIGNAL-TRANSDUCTION AB Adenylyl cyclase 9 (ADCY9) mediates beta 2-adrenoceptor (beta 2-AR) signalling. Both proteins are associated with caveolae, specialized cholesterol-rich membrane substructures. Apolipoprotein A1 (ApoA1), the major protein component of high-density lipoprotein (HDL), removes cholesterol from cell membrane and caveolae and may thereby influence beta 2-AR signalling, shown in vitro to be modulated by cholesterol. Patients with Sickle Cell Disease (SCD) typically have low HDL and ApoA1 levels. In patients, mainly of African origin, with SCD, beta 2-AR activation may trigger adhesion of red blood cells to endothelial cells, leading to vascular occlusive events. Moreover, ADCY9 polymorphism is associated with risk of stroke in SCD. In recent clinical trials, ADCY9 polymorphism was found to be a discriminant factor associated with the risk of cardiovascular (CV) events in Caucasian patients treated with the HDL-raising compound dalcetrapib. We hypothesize that these seemingly disparate observations share a common mechanism related to interaction of HDL/ApoA1 and ADCY9 on beta 2-AR signalling. This review also raises the importance of characterizing polymorphisms that determine the response to HDL-raising and -mimicking agents in the non-Caucasian population at high risk of CV diseases and suffering from SCD. This may facilitate personalized CV treatments. C1 [Niesor, Eric J.; Benghozi, Renee] F Hoffmann La Roche Ltd, Basel, Switzerland. [Niesor, Eric J.] Pre Ss1 Consulting, CH-1260 Nyon, Switzerland. [Benghozi, Renee] Cerenis Therapeut Holding, Labege, France. [Amouyel, Philippe] Univ Hosp Lille, Lille, France. [Ferdinand, Keith C.] Tulane Univ, Sch Med, New Orleans, LA USA. [Schwartz, Gregory G.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Niesor, EJ (reprint author), F Hoffmann La Roche Ltd, Basel, Switzerland. EM eric.niesor@bluewin.ch FU Roche FX R.B. was an F. Hoffmann-La Roche Ltd. employee and currently CMO of Cerenis Therapeutics; G.G.S. received research funding from Roche through his institution. NR 84 TC 0 Z9 0 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 EI 1573-7241 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD DEC PY 2015 VL 29 IS 6 BP 563 EP 572 DI 10.1007/s10557-015-6626-1 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA DB4AC UT WOS:000368454100008 PM 26619842 ER PT J AU Hochedlinger, K Jaenisch, R AF Hochedlinger, Konrad Jaenisch, Rudolf TI Induced Pluripotency and Epigenetic Reprogramming SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; HUMAN SOMATIC-CELLS; GENE-EXPRESSION SIGNATURES; X-CHROMOSOME INACTIVATION; SMALL-MOLECULE COMPOUNDS; ZINC-FINGER NUCLEASES; DEFINED FACTORS; IPS CELLS; MOUSE EMBRYOS; SELF-RENEWAL AB Induced pluripotency defines the process by which somatic cells are converted into induced pluripotent stem cells (iPSCs) upon overexpression of a small set of transcription factors. In this article, we put transcription factor-induced pluripotency into a historical context, review current methods to generate iPSCs, and discuss mechanistic insights that have been gained into the process of reprogramming. In addition, we focus on potential therapeutic applications of induced pluripotency and emerging technologies to efficiently engineer the genomes of human pluripotent cells for scientific and therapeutic purposes. C1 [Hochedlinger, Konrad] Harvard Univ, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Hochedlinger, Konrad] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jaenisch, Rudolf] MIT, Whitehead Inst, Cambridge, MA 02142 USA. [Jaenisch, Rudolf] MIT, Dept Biol, Cambridge, MA 02142 USA. RP Hochedlinger, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu NR 168 TC 7 Z9 8 U1 4 U2 20 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD DEC PY 2015 VL 7 IS 12 AR a019448 DI 10.1101/cshperspect.a019448 PG 25 WC Cell Biology SC Cell Biology GA DB5EN UT WOS:000368537300006 ER PT J AU Zhu, LR Xu, PW Cao, XH Yang, YJ Hinton, AO Xia, Y Saito, KJ Yan, XF Zou, F Ding, HF Wang, CM Yan, CL Saha, P Khan, SA Zhao, J Fukuda, M Tong, QC Clegg, DJ Chan, L Xu, Y AF Zhu, Liangru Xu, Pingwen Cao, Xuehong Yang, Yongjie Hinton, Antentor Othrell, Jr. Xia, Yan Saito, Kenji Yan, Xiaofeng Zou, Fang Ding, Hongfang Wang, Chunmei Yan, Chunling Saha, Pradip Khan, Sohaib A. Zhao, Jean Fukuda, Makoto Tong, Qingchun Clegg, Deborah J. Chan, Lawrence Xu, Yong TI The ER alpha-PI3K Cascade in Proopiomelanocortin Progenitor Neurons Regulates Feeding and Glucose Balance in Female Mice SO ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; SELECTIVE INSULIN-RESISTANCE; POMC-EXPRESSING PROGENITORS; FOOD-INTAKE; OVARIECTOMIZED RATS; ENERGY HOMEOSTASIS; BODY-WEIGHT; HYPOTHALAMIC NEURONS; ADIPOSE-TISSUE; METABOLIC SYNDROME AB Estrogens act upon estrogen receptor (ER)alpha to inhibit feeding and improve glucose homeostasis in female animals. However, the intracellular signals that mediate these estrogenic actions remain unknown. Here, we report that anorexigenic effects of estrogens are blunted in female mice that lack ER alpha specifically in proopiomelanocortin (POMC) progenitor neurons. These mutant mice also develop insulin resistance and are insensitive to the glucose-regulatory effects of estrogens. Moreover, we showed that propyl pyrazole triol (an ER alpha agonist) stimulates the phosphatidyl inositol 3-kinase (PI3K) pathway specifically in POMC progenitor neurons, and that blockade of PI3K attenuates propyl pyrazole triol-induced activation of POMC neurons. Finally, we show that effects of estrogens to inhibit food intake and to improve insulin sensitivity are significantly attenuated in female mice with PI3K genetically inhibited in POMC progenitor neurons. Together, our results indicate that an ER alpha-PI3K cascade in POMC progenitor neurons mediates estrogenic actions to suppress food intake and improve insulin sensitivity. C1 [Zhu, Liangru; Xu, Pingwen; Cao, Xuehong; Yang, Yongjie; Hinton, Antentor Othrell, Jr.; Xia, Yan; Saito, Kenji; Yan, Xiaofeng; Zou, Fang; Ding, Hongfang; Wang, Chunmei; Yan, Chunling; Fukuda, Makoto; Xu, Yong] Baylor Coll Med, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA. [Saha, Pradip; Chan, Lawrence] Baylor Coll Med, Dept Med, Diabet Res Ctr, Houston, TX 77030 USA. [Chan, Lawrence; Xu, Yong] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Tong, Qingchun] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA. [Zhu, Liangru] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Gastroenterol, Wuhan 430022, Peoples R China. [Yan, Chunling] Qingdao Univ, Coll Med, Qingdao 266020, Peoples R China. [Khan, Sohaib A.] Univ Cincinnati, Coll Med, Dept Canc Biol, Vontz Ctr Mol Studies, Cincinnati, OH 45267 USA. [Zhao, Jean] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Clegg, Deborah J.] Cedars Sinai Med Ctr, Dept Biomed Res, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA. RP Xu, Y (reprint author), Baylor Coll Med, 1100 Bates St,Room 8070, Houston, TX 77030 USA. EM yongx@bcm.edu RI Fukuda, Makoto/I-7915-2014 OI Fukuda, Makoto/0000-0003-0112-9925 FU National Institutes of Health [R01DK093587, R01DK101379, R00DK085330, P30 DK079638-03, P30 DK079638, P01 DK088761, T32CA059268, R01DK092605, HL051586/DK105527]; US Department of Agriculture Agriculture Research Service Award [6250-51000-055]; American Diabetes Association; American Heart Association postdoctoral fellowship; American Heart Association National Scientist Development grant; National Natural Science Foundation of China Award [81200623]; USDA ARS FX This work was supported by National Institutes of Health Grants R01DK093587, R01DK101379, R00DK085330, and P30 DK079638-03 (to Y.Xu); P01 DK088761 (to D.J.C.); T32CA059268 (to S.A.K.); R01DK092605 (to Q.T.); and HL051586/DK105527 (to L.C.); the US Department of Agriculture Agriculture Research Service Award 6250-51000-055 (to Y.Xu); the American Diabetes Association (Y.Xu); an American Heart Association postdoctoral fellowship (P.X.), an American Heart Association National Scientist Development grant (Q.T.); and the National Natural Science Foundation of China Award 81200623 (to L.Z.). The hyperinsulinemic-euglycemic clamp study was performed in the Mouse Metabolism Core at the Diabetes Research Center, Baylor College of Medicine, which is supported by the National Institutes of Health Grant P30 DK079638. Measurements of body composition and energy expenditure were performed in the Mouse Metabolic Research Unit at the USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, which is supported by funds from the USDA ARS. NR 60 TC 5 Z9 5 U1 2 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2015 VL 156 IS 12 BP 4474 EP 4491 DI 10.1210/en.2015-1660 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB3KT UT WOS:000368410900010 PM 26375425 ER PT J AU Yoon, WJ Kim, YT Daglilar, ES Mino-Kenudson, M Brugge, WR AF Yoon, Won Jae Kim, Yong-Tae Daglilar, Ebubekir S. Mino-Kenudson, Mari Brugge, William R. TI Evaluation of bipolar radiofrequency ablation for occluded self-expandable metal stents in the bile duct: in vivo and in vitro study SO ENDOSCOPY LA English DT Article ID MALIGNANT BILIARY OBSTRUCTION; MANAGEMENT; THERAPY AB Background and aims: Endobiliary radiofrequency ablation (RFA) has been used to treat occluded self-expandable metal stents (SEMSs). The aim of this study was to determine the characteristics of bipolar RFA in occluded SEMSs using both in vivo and in vitro models. Methods: For the in vivo study, uncovered SEMSs were deployed in the bile ducts of three pigs; another pig was used as the control. RFA was performed at 10W for 90 seconds. The bile duct was examined for histological changes. For the in vitro simulation of tissue ingrowth in SEMSs, RFA at 10W for 30 seconds was performed on SEMS-occlusion polyacrylamide-gel phantoms. Results: The ablation depth was markedly reduced in the stented porcine bile duct. RFA of uncovered SEMS-occlusion gel phantoms resulted in early termination of RFA when the coagulated area contacted the SEMS. This phenomenon was not observed in RFA of the covered SEMS-occlusion gel phantoms. Conclusions: The presence of SEMSs attenuated the effect of bipolar endobiliary RFA. Tumorous tissue outside the SEMS is unlikely to be affected. C1 [Kim, Yong-Tae] Seoul Natl Univ, Coll Med, Dept Internal Med, 101 Daehak Ro, Seoul 110744, South Korea. [Yoon, Won Jae] Inje Univ, Coll Med, Seoul Paik Hosp, Dept Internal Med, Seoul, South Korea. [Yoon, Won Jae; Daglilar, Ebubekir S.; Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kim, YT (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, 101 Daehak Ro, Seoul 110744, South Korea. EM yongtkim@snu.ac.kr NR 14 TC 2 Z9 2 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PD DEC PY 2015 VL 47 IS 12 BP 1167 EP 1170 DI 10.1055/s-0034-1392252 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DB3ME UT WOS:000368414900013 PM 26111360 ER PT J AU Mishuris, RG Stewart, M Fix, GM Marcello, T McInnes, DK Hogan, TP Boardman, JB Simon, SR AF Mishuris, Rebecca G. Stewart, Max Fix, Gemmae M. Marcello, Thomas McInnes, D. Keith Hogan, Timothy P. Boardman, Judith B. Simon, Steven R. TI Barriers to patient portal access among veterans receiving home-based primary care: a qualitative study SO HEALTH EXPECTATIONS LA English DT Article DE access to care; health information technology; vulnerable populations ID PERSONAL HEALTH RECORD; DIGITAL DIVIDE; INTERNET; USERS; COMMUNICATION; SATISFACTION; PREFERENCES; INFORMATION; ADOPTION; SYSTEM AB Background Electronic, or web-based, patient portals can improve patient satisfaction, engagement and health outcomes and are becoming more prevalent with the advent of meaningful use incentives. However, adoption rates are low, particularly among vulnerable patient populations, such as those patients who are home-bound with multiple comorbidities. Little is known about how these patients view patient portals or their barriers to using them. Objective To identify barriers to and facilitators of using My HealtheVet (MHV), the United States Department of Veterans Affairs (VA) patient portal, among Veterans using home-based primary care services. Design Qualitative study using in-depth semi-structured interviews. We conducted a content analysis informed by grounded theory. Participants Fourteen Veterans receiving home-based primary care, surrogates of two of these Veterans, and three home-based primary care (HBPC) staff members. Key Results We identified five themes related to the use of MHV: limited knowledge; satisfaction with current HBPC care; limited computer and Internet access; desire to learn more about MHV and its potential use; and value of surrogates acting as intermediaries between Veterans and MHV. Conclusions Despite their limited knowledge of MHV and computer access, home-bound Veterans are interested in accessing MHV and using it as an additional point of care. Surrogates are also potential users of MHV on behalf of these Veterans and may have different barriers to and benefits from use. C1 [Mishuris, Rebecca G.; Stewart, Max; Marcello, Thomas; Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. [Mishuris, Rebecca G.; Marcello, Thomas; Simon, Steven R.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Med, Boston, MA 02120 USA. [Mishuris, Rebecca G.; Simon, Steven R.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Fix, Gemmae M.; Marcello, Thomas; McInnes, D. Keith; Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, VA Hlth Serv, Res & Dev Serv, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Fix, Gemmae M.; McInnes, D. Keith] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [McInnes, D. Keith] Edith Nourse Rogers Mem Vet Hosp, HIV Hepatitis Qual Enhancement Res Initiat QUERI, Bedford, MA USA. [McInnes, D. Keith; Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, eHlth Qual Enhancement Res Initiat QUERI, Bedford, MA USA. [Hogan, Timothy P.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Hlth Informat & Implementat Sci, Worcester, MA USA. [Boardman, Judith B.] VA Boston Healthcare Syst, Home Based Primary Care Program, Boston, MA USA. [Boardman, Judith B.] Salem State Univ, Salem, MA USA. RP Mishuris, RG (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St,BC-3-2, Boston, MA 02120 USA. EM rmishuris@partners.org OI Fix, Gemmae/0000-0001-6055-4177; /0000-0002-4804-3128 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative [RRP 11-241]; Institutional National Research Service Award [T32 HP10251]; VA Career Development Award [CDA 09-016] FX The project reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative (RRP 11-241). Dr. Mishuris is supported by an Institutional National Research Service Award to the Harvard Medical School Fellowship in General Medicine and Primary Care (T32 HP10251). Dr. McInnes is supported by a VA Career Development Award (CDA 09-016). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Authors report no conflict of interests. NR 29 TC 4 Z9 4 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-6513 EI 1369-7625 J9 HEALTH EXPECT JI Health Expect. PD DEC PY 2015 VL 18 IS 6 BP 2296 EP 2305 DI 10.1111/hex.12199 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DB1EH UT WOS:000368250300040 PM 24816246 ER PT J AU Sepucha, K Feibelmann, S Chang, YC Hewitt, S Ziogas, A AF Sepucha, Karen Feibelmann, Sandra Chang, Yuchiao Hewitt, Sarah Ziogas, Argyrios TI Measuring the quality of surgical decisions for Latina breast cancer patients SO HEALTH EXPECTATIONS LA English DT Article DE decision quality; shared decision making ID ACCULTURATION; WOMEN; MASTECTOMY; HISPANICS; OUTCOMES; SURGERY AB Background A high-quality decision for breast cancer surgery requires that patients are well informed, meaningfully involved in decision making, and receive treatments that match their goals. There is little in the existing literature that examines a comprehensive measure of decision quality for Latina breast cancer patients. Objective To examine the quality of surgical decisions among Latina breast cancer survivors and explore factors associated with decision quality and decision regret. Design Cross-sectional mailed survey. Main outcome measures English and certified Spanish translations of Breast Cancer Surgery Decision Quality Instrument (BCS-DQI), Short Acculturation Scale for Hispanics (SASH) and decision regret. Participants and setting Ninety-seven breast cancer survivors of Hispanic or Spanish descent identified through the cancer registry from Orange or San Diego Counties in California. Results The 97 respondents were on average 55.7 years old, 39.1% had high school diploma or more education, and 62.9% had low acculturation (SASH scores < 2.99). The average knowledge score was 48.2%, the average decision process score was 67.5%, and many (77.3%) received treatments that matched their goals. In multivariable models, there were no significant associations with education, age, acculturation and any aspect of decision quality or decision regret in this sample. Respondents who had higher decision process scores, indicating more involvement in decision making, had significantly lower decision regret. Conclusions The BCS-DQI may require some adaptation for Latina populations to improve acceptability. The different aspects of decision quality, including knowledge, decision process and concordance, did not vary by level of acculturation. C1 [Sepucha, Karen; Feibelmann, Sandra; Hewitt, Sarah] Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Dept Gen Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Gen Med, Boston, MA 02114 USA. [Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. RP Sepucha, K (reprint author), Massachusetts Gen Hosp, Hlth Decis Sci Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ksepucha@partners.org FU Informed Medical Decisions Foundation, Boston, MA, USA FX Informed Medical Decisions Foundation, Boston, MA, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-6513 EI 1369-7625 J9 HEALTH EXPECT JI Health Expect. PD DEC PY 2015 VL 18 IS 6 BP 2389 EP 2400 DI 10.1111/hex.12207 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DB1EH UT WOS:000368250300047 PM 24813584 ER PT J AU Butow, P Brown, R Aldridge, J Juraskova, I Zoller, P Boyle, F Wilson, M Bernhard, J AF Butow, P. Brown, R. Aldridge, J. Juraskova, I. Zoller, P. Boyle, F. Wilson, M. Bernhard, J. TI Can consultation skills training change doctors' behaviour to increase involvement of patients in making decisions about standard treatment and clinical trials: a randomized controlled trial SO HEALTH EXPECTATIONS LA English DT Article DE clinical trials; consultation skills training; decision making; oncology; physician behaviour; randomized controlled trial ID SEEKING INFORMED-CONSENT; CANCER-PATIENTS; BREAST-CANCER; COMMUNICATION; EFFICACY; ONCOLOGISTS; INFORMATION; CARE AB Background Informed consent is required for both standard cancer treatments and experimental cancer treatments in a clinical trial. Effective and sensitive physician-patient communication about informed consent is difficult to achieve. Our aim was to train doctors in clear, collaborative and ethical communication about informed consent and evaluate the impact of training on doctor behaviour, stress and satisfaction. Participants and Methods Participants were 21 oncologists from 10 Australian/New Zealand (ANZ) centres and 41 oncologists from 10 Swiss/German/Austrian (SGA) centres. Oncologists were randomized to participate in a 1-day workshop or not. Patients were recruited before and after the training. Doctors were asked to submit 1-2 audiotaped consultations before and after training. Doctors completed outcome measures before and after completing the post-training cohort recruitment. Results Ninety-five consultation interactions were audiotaped. Doctors strongly endorsed the training. ANZ intervention doctors demonstrated a significant increase in collaborative communication (P = 0.03). There was no effect of training on other doctor behaviours. Trained doctors did not demonstrate reduced stress and burnout. Patient outcomes are presented elsewhere. Conclusions Training can improve some aspects of the process of obtaining informed consent. Methods to increase the impact of training are required and may include longer training and more intensive follow-up. C1 [Butow, P.; Juraskova, I.] Univ Sydney, Ctr Med Psychol & Evidence Based Decis Making CeM, Sydney, NSW 2060, Australia. [Brown, R.; Wilson, M.] Virginia Commonwealth Univ, Dept Social & Behav Hlth, Richmond, VA USA. [Aldridge, J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Int Breast Canc Study Grp IBCSG Stat Ctr, Boston, MA 02115 USA. [Zoller, P.] Univ Hosp Bern, Inselspital, CH-3010 Bern, Switzerland. [Bernhard, J.] Univ Hosp Bern, IBCSG Coordinating Ctr, Qual Life Off, Inselspital, CH-3010 Bern, Switzerland. [Bernhard, J.] Univ Hosp Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. [Boyle, F.] Univ Sydney, Northern Clin Sch, Pam McLean Ctr, Sydney, NSW 2060, Australia. RP Butow, P (reprint author), Univ Sydney, Sch Psychol, Sydney, NSW 2060, Australia. EM phyllis.butow@sydney.edu.au FU National Breast Cancer Foundation of Australia; Oncosuisse/Swiss Cancer League [OCS - 01165-09-2001/KLS - 01648-02-2005]; Deutsche Krebshilfe [106668]; IBCSG; US National Cancer Institute [CA-75362] FX This trial was a collaborative effort between the Centre for Medical Psychology and Evidence-based Decision-making, School of Psychology, University of Sydney, and the International Breast Cancer Study Group (IBCSG). We acknowledge the considerable logistic efforts of these groups. We would like to thank the physicians who participated in the trial, the patients who took the time to complete the questionnaires, the data managers and local coordinators who took care of this study in the centres, and Cornelia Zuberbuhler, Monika Dzidowska, Gwynneth Wong, Gina Bark, Karen Ribi and Anna-Lena Lopez for central trial coordination. This study was funded by National Breast Cancer Foundation of Australia and Oncosuisse/Swiss Cancer League (OCS - 01165-09-2001/KLS - 01648-02-2005), Deutsche Krebshilfe (106668) and IBCSG. The IBCSG Statistical Center (J.A.) is partially funded through a grant from the US National Cancer Institute (CA-75362). NR 35 TC 3 Z9 3 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-6513 EI 1369-7625 J9 HEALTH EXPECT JI Health Expect. PD DEC PY 2015 VL 18 IS 6 BP 2570 EP 2583 DI 10.1111/hex.12229 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DB1EH UT WOS:000368250300062 PM 24975503 ER PT J AU Hanoch, Y Miron-Shatz, T Rolison, JJ Omer, Z Ozanne, E AF Hanoch, Yaniv Miron-Shatz, Talya Rolison, Jonathan J. Omer, Zehra Ozanne, Elisa TI Shared decision making in patients at risk of cancer: the role of domain and numeracy SO HEALTH EXPECTATIONS LA English DT Article DE cancer; objective numeracy and subjective numeracy; shared decision making ID HEALTH-CARE; PATIENTS PREFERENCES; BREAST-CANCER; PATIENTS WANT; STATISTICAL NUMERACY; INFORMATION; PARTICIPATION; INVOLVEMENT; SCALE; DESIRE AB Background Shared decision making has become an integral part of medical consultation. Research has, however, reported wide differences in individuals' desires to be involved in the decision-making process, and these differences in preferences are likely to be the result of a number of factors including age, education and numeracy. Objective To investigate whether patients at genetic risk for cancer had preferences for shared decision making that differed depending on medical domain (general health vs. cancer) and whether decision preferences are linked to numeracy abilities. Methods Four hundred and seventy-six women who consented to participate in response to an email sent by a local branch of the U.S.-based Cancer Genetics Network (CGN) to its members. Participants completed the Control Preference Scale, as well as an objective and subjective numeracy scales. Results Decision domain (cancer vs. general health) was not associated with women's preferences for involvement in decision making. Objective and subjective numeracy predicted a preference for decision involvement in general, and only objective numeracy was predictive with regard to cancer. Conclusion Participants were equally likely to state they wanted to play an active, collaborative or passive role in both medical domains (general and cancer). High-numeracy participants were more likely to express a desire for an active role in general and in case they were diagnosed with cancer. C1 [Hanoch, Yaniv] Univ Plymouth, Sch Psychol, Cognit Inst, Plymouth PL4 8AA, Devon, England. [Miron-Shatz, Talya] Ono Acad Coll, Ctr Med Decis Making, Kiryat Ono, Israel. [Rolison, Jonathan J.] Queens Univ Belfast, Sch Psychol, Belfast BT7 1NN, Antrim, North Ireland. [Omer, Zehra] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Ozanne, Elisa] Geisel Sch Med Dartmouth, Dartmouth Inst, Lebanon, NH USA. RP Hanoch, Y (reprint author), Univ Plymouth, Sch Psychol, Cognit Inst, PSQ B204, Plymouth PL4 8AA, Devon, England. EM yaniv.hanoch@plymouth.ac.uk FU Cancer Genetics Network [RFA CA-97-004, RFA CA-97-019, N01-PC-55049-40]; University of Plymouth award FX This research was supported by the Cancer Genetics Network, RFA CA-97-004, RFA CA-97-019 and RFP No. N01-PC-55049-40 (EO), and a University of Plymouth award (YH). NR 42 TC 2 Z9 2 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-6513 EI 1369-7625 J9 HEALTH EXPECT JI Health Expect. PD DEC PY 2015 VL 18 IS 6 BP 2799 EP 2810 DI 10.1111/hex.12257 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DB1EH UT WOS:000368250300081 PM 25186806 ER PT J AU Hagg, S Ganna, A Van der Laan, SW Esko, T Pers, TH Locke, AE Berndt, SI Justice, AE Kahali, B Siemelink, MA Pasterkamp, G Strachan, DP Speliotes, EK North, KE Loos, RJF Hirschhorn, JN Pawitan, Y Ingelsson, E AF Hagg, Sara Ganna, Andrea Van der Laan, Sander W. Esko, Tonu Pers, Tune H. Locke, Adam E. Berndt, Sonja I. Justice, Anne E. Kahali, Bratati Siemelink, Marten A. Pasterkamp, Gerard Strachan, David P. Speliotes, Elizabeth K. North, Kari E. Loos, Ruth J. F. Hirschhorn, Joel N. Pawitan, Yudi Ingelsson, Erik CA GIANT Consortium TI Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity SO HUMAN MOLECULAR GENETICS LA English DT Article ID ACTIN-INTERACTING PROTEIN; BODY-MASS INDEX; MITOCHONDRIAL TRNA(ILE); MISSING HERITABILITY; DATABASE; VARIANTS; TISSUE; CELLS; KRAP; MICE AB To date, genome-wide association studies (GWASs) have identified > 100 loci with single variants associated with body mass index (BMI). This approach may miss loci with high allelic heterogeneity; therefore, the aim of the present study was to use gene-based meta-analysis to identify regions with high allelic heterogeneity to discover additional obesity susceptibility loci. We included GWAS data from 123 865 individuals of European descent from 46 cohorts in Stage 1 and Metabochip data from additional 103 046 individuals from 43 cohorts in Stage 2, all within the Genetic Investigation of AN thropometric Traits (GIANT) consortium. Each cohort was tested for association between similar to 2.4million (Stage 1) or similar to 200 000 (Stage 2) imputed or genotyped single variants and BMI, and summary statistics were subsequently meta-analyzed in 17 941 genes. We used the 'VErsatile Gene-based Association Study' (VEGAS) approach to assign variants to genes and to calculate gene-based P-values based on simulations. The VEGAS method was applied to each cohort separately before a gene-based meta-analysis was performed. In Stage 1, two known (FTO and TMEM18) and six novel (PEX2, MTFR2, SSFA2, IARS2, CEP295 and TXNDC12) loci were associated with BMI (P < 2.8x10(-6) for 17 941 gene tests). We confirmed all loci, and six of them were gene-wide significant in Stage 2 alone. We provide biological support for the loci by pathway, expression and methylation analyses. Our results indicate that gene-based meta-analysis of GWAS provides a useful strategy to find loci of interest that were not identified in standard single-marker analyses due to high allelic heterogeneity. C1 [Hagg, Sara; Pawitan, Yudi] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Hagg, Sara; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, SE-75141 Uppsala, Sweden. [Ganna, Andrea] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Ganna, Andrea] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ganna, Andrea] Harvard Univ, Sch Med, Boston, MA USA. [Van der Laan, Sander W.; Siemelink, Marten A.; Pasterkamp, Gerard] Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, NL-3584 CX Utrecht, Netherlands. [Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol & Genet, Boston, MA 02115 USA. [Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA. [Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia. [Pers, Tune H.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Pers, Tune H.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Locke, Adam E.] Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA. [Kahali, Bratati; Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Kahali, Bratati; Speliotes, Elizabeth K.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Justice, Anne E.; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Pasterkamp, Gerard] UMC Utrecht, Lab Clin Chem & Hematol, Div Labs & Pharm, Utrecht, Netherlands. [Strachan, David P.] Univ London, London SW17 0RE, England. [Loos, Ruth J. F.] Univ Cambridge, Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge CB2 0QQ, England. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Loos, Ruth J. F.] Univ Oxford, Genet Obes & Related Metab Traits Program, Oxford, England. [Loos, Ruth J. F.] Univ Oxford, Mindich Child Hlth & Dev Inst, Oxford, England. [Ingelsson, Erik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Ingelsson, Erik] Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA. RP Ingelsson, E (reprint author), Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, SE-75141 Uppsala, Sweden. EM erik.ingelsson@medsci.uu.se OI Locke, Adam/0000-0001-6227-198X; Ganna, Andrea/0000-0002-8147-240X FU Foundation for Geriatric Diseases, Karolinska Institutet FX The study was supported by the Foundation for Geriatric Diseases, Karolinska Institutet. NR 43 TC 6 Z9 6 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2015 VL 24 IS 23 BP 6849 EP 6860 DI 10.1093/hmg/ddv379 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DB2WP UT WOS:000368371600023 PM 26376864 ER PT J AU Shelton, RC Pencina, MJ Barrentine, LW Ruiz, JA Fava, M Zajecka, JM Papakostas, GI AF Shelton, Richard C. Pencina, Michael J. Barrentine, Lori W. Ruiz, Juan A. Fava, Maurizio Zajecka, John M. Papakostas, George I. TI Association of Obesity and Inflammatory Marker Levels on Treatment Outcome: Results From a Double-Blind, Randomized Study of Adjunctive L-Methylfolate Calcium in Patients With MDD Who Are Inadequate Responders to SSRIs SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Antidepressants; Depression; Weight ID MAJOR DEPRESSIVE DISORDER; C-REACTIVE PROTEIN; MIDDLE-AGED WOMEN; BODY-MASS INDEX; ADIPOSE-TISSUE; CARDIOVASCULAR-DISEASE; MOOD DISORDERS; VISCERAL FAT; METAANALYSIS; CYTOKINES AB Objective: Adjunctive treatment with L-methylfolate calcium significantly improved treatment outcomes in patients with major depressive disorder (MDD) and an inadequate response to antidepressants. This post hoc exploratory analysis evaluated baseline concentrations of cytokines (interleukin [IL]-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, and IL-17; tumor necrosis factor alpha [TNF-alpha]; and interferon gamma [IFN-gamma]), high-sensitivity C-reactive protein (hsCRP), insulin, adiponectin and leptin and body mass index (BMI [kg/m(2)]) on l-methylfolate calcium treatment response. Method: Adults with DSM-IV MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) were eligible. Patients were randomized 3: 3: 2 according to the sequential parallel comparison design to placebo versus placebo, placebo versus l-methylfolate calcium (15 mg/ d), or L-methylfolate calcium versus L-methylfolate calcium (15 mg/ d) during two 30-day phases. The primary outcome was change on the 17-item Hamilton Depression Rating Scale (HDRS-17). Treatment effect with 95% CIs was estimated from baseline concentrations of individual biomarkers and combinations. Cytokines were measured by immunoassay; adiponectin, insulin, and leptin by radioimmunoassay; and hsCRP by a standard turbidimetric assay. The effects of baseline biomarker levels (above and below the median) on outcome were analyzed. The first participant was enrolled July 14, 2009, and the last participant completed April 28, 2011. Results: Mean change on HDRS-17 from baseline was significantly improved with L-methylfolate calcium versus placebo (pooled treatment effect, -2.74; 95% CI, -4.99 to -0.48; P =.017) overall and for those with baseline BMI = 30 (pooled treatment effect, -4.66; 95% CI, -7.22 to -1.98; P =.001) but not BMI < 30. Pooled mean changes in depression across treatment for baseline levels of individual markers above median were significant (L-methylfolate calcium vs placebo) for TNF-alpha, IL-8, hsCRP, and leptin (pooled treatment effects, -4.33 to -3.94 [P =.02]) and for combinations of BMI = 30 with elevated levels of TNF-alpha, IL-6, IL-8, hsCRP, and leptin (pooled treatment effects, -6.31 to -3.98 [P =.05]). Conclusions: In this exploratory analysis, inflammatory and obesityrelated factors were associated with greater symptom improvement with L-methylfolate calcium. Combinations of BMI = 30 with elevated IL-6, IL-8, hsCRP, TNF-a, and leptin predicted improved response to L-methylfolate calcium in MDD patients with an inadequate antidepressant response. Further studies are necessary to confirm these findings. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Shelton, Richard C.] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. [Pencina, Michael J.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Barrentine, Lori W.; Ruiz, Juan A.] Nestle Hlth Sci Pamlab Inc, Covington, LA USA. [Fava, Maurizio; Papakostas, George I.] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA. [Zajecka, John M.] Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, Chicago, IL USA. RP Shelton, RC (reprint author), Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, 1713 6th Ave S, Birmingham, AL 35294 USA. EM rshelton@uab.edu FU Nestle Health Science-Pamlab, Inc, Covington, Louisiana FX This work was supported by grants from Nestle Health Science-Pamlab, Inc, Covington, Louisiana. NR 51 TC 5 Z9 5 U1 3 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2015 VL 76 IS 12 BP 1635 EP + DI 10.4088/JCP.14m09587 PG 24 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DB2RE UT WOS:000368355900012 PM 26613389 ER PT J AU Baer, L Trivedi, MH Huz, I Rush, AJ Wisniewski, SR Fava, M AF Baer, Lee Trivedi, Madhukar H. Huz, Ilana Rush, A. John Wisniewski, Stephen R. Fava, Maurizio TI Prevalence and Impact of Obsessive-Compulsive Symptoms in Depression: A STAR*D Report SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Comorbidity; Depression; Obessive-Compulsive and Related Disorders ID QUALITY-OF-LIFE; HELP-SEEKING; CLINICAL-FEATURES; MAJOR DEPRESSION; RATING-SCALE; DISORDER; COMORBIDITY; SEVERITY; THOUGHTS; ILLNESS AB Objective: Obsessive-compulsive symptoms (OCS) may be underrecognized in patients suffering from major depressive disorder. These patients may not receive optimal psychopharmacologic or psychological treatment if their OCS are not attended to. We performed a secondary analysis of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial database, the largest effectiveness study of "real-world" depression ever conducted, to determine the frequency of OCS and their effects on depression outcome. Method: 3,984 adult subjects without a previous selective serotonin reuptake inhibitor trial for their current major depressive episode, per DSM-IV diagnostic criteria, had data for rating scales of interest at entry into Level 1 of the STAR*D trial, a 12-week open trial of citalopram at a dose of 20-60 mg/d to assess rates of depression remission. Our primary interest was the OCD subscale of the Psychiatric Diagnostic Screening Questionnaire. Results: At study entry, 53% of the STAR*D sample (which excluded patients with primary obsessive-compulsive disorder) endorsed >= 1 OCS, and 14% endorsed >= 4 OCS. Subjects endorsing >= 4 OCS had significantly lower corrected odds of depression remission on both the 17-item Hamilton Depression Rating Scale (HDRS-17) (OR = 0.61) and the Quick Inventory of Depressive Symptomatology (odds ratio [OR] = 0.51). Number of OCS endorsed was positively correlated with HDRS-17 score (r = 0.26, P <.0001). Consistent with findings from the Dunedin, New Zealand Community Study, the most common obsessions were doubts of having inadvertently caused harm and violent obsessions. Conclusions: OCS are common in depressed outpatients and are often not attended to. They impact clinical recovery from depression and should be screened for since sufferers are often reluctant to disclose these symptoms. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Baer, Lee; Huz, Ilana; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore. [Wisniewski, Stephen R.] Univ Pittsburgh, Hlth Policy Inst, Pittsburgh, PA USA. RP Baer, L (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM lbaer@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860 FU Chirag Foundation FX Chirag Foundation. NR 29 TC 0 Z9 0 U1 0 U2 3 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 DEC PY 2015 VL 76 IS 12 BP 1668 EP 1674 DI 10.4088/JCP.14m09670 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DB2RE UT WOS:000368355900017 PM 26717526 ER PT J AU Youngstrom, EA Hameed, A Mitchell, MA Van Meter, AR Freeman, AJ Algorta, GP White, AM Clayton, PJ Gelenberg, AJ Meyer, RE AF Youngstrom, Eric A. Hameed, Ahmad Mitchell, Michael A. Van Meter, Anna R. Freeman, Andrew J. Algorta, Guillermo Perez White, Amanda M. Clayton, Paula J. Gelenberg, Alan J. Meyer, Roger E. TI Direct Comparison of the Psychometric Properties of Multiple Interview and Patient-Rated Assessments of Suicidal Ideation and Behavior in an Adult Psychiatric Inpatient Sample SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; SEVERITY RATING-SCALE; TOWER-OF-BABEL; REVISED NOMENCLATURE; SMOKING-CESSATION; DSM-IV; RISK; RELIABILITY; AGREEMENT; ANTIDEPRESSANTS AB Objective: Compare the accuracy, agreement, internal consistency, and interrater reliability of 3 interviews to assess suicidal ideation and behavior in accordance with US Food and Drug Administration guidance about reporting categories. Method: Adults admitted to a psychiatric inpatient unit (N = 199) completed 3 assessments of past month and lifetime suicidal ideation and behavior-the Columbia Suicide Severity Rating Scale (C-SSRS), the Suicide Tracking Scale (STS), and the Sheehan Suicidality Tracking Scale (S-STS)-in randomized, counterbalanced order. "Missing gold standard" latent class analyses defined categories for ideation and behavior. Analyses also evaluated the S-STS mapping to C-SSRS categories. Three trained judges re-rated 89 randomly selected interview videotapes. Cohen., the primary outcome measure, quantified agreement above chance. Data were collected between November 2011 and June 2013. Results: All 3 assessments showed excellent accuracy for suicidal ideation (kappa = 0.72 to 1.00) and attempts (kappa = 0.82 to 0.95) calibrated against latent classes. Interrater agreement ranged from kappa = 0.52 to 1.00. Interrater agreement about more granular C-SSRS categories varied more widely (kappa = 0.48 to 1.00), and the C-SSRS and S-STS assigned significantly different numbers of cases to many categories. Cronbach a was < 0.55 for the C-SSRS ideation and between 0.78 and 0.92 for the other scales. Conclusions: All 3 assessments showed good accuracy for broad categories of suicidal ideation and behavior. More granular, specific categories usually were rated reliably, but the C-SSRS and S-STS differed significantly in regard to which patients were assigned to these subcategories. Using any of these interviews would improve reliability over unstructured assessment in evaluating suicidal ideation and behavior. Clinical predictive validity of these interviews, and particularly the more granular categories, remains to be shown. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Youngstrom, Eric A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Hameed, Ahmad; White, Amanda M.; Gelenberg, Alan J.; Meyer, Roger E.] Penn State Univ, Coll Med, Dept Psychiat, Hershey, PA USA. [Hameed, Ahmad; White, Amanda M.; Gelenberg, Alan J.; Meyer, Roger E.] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. [Mitchell, Michael A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Van Meter, Anna R.] Yeshiva Univ, Ferkauf Grad Sch, Bronx, NY USA. [Freeman, Andrew J.] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. [Algorta, Guillermo Perez] Univ Lancaster, Div Hlth Res, Lancaster, England. [Clayton, Paula J.] Univ Minnesota, Minneapolis, MN USA. [Clayton, Paula J.] Univ New Mexico, Albuquerque, NM 87131 USA. RP Youngstrom, EA (reprint author), Univ N Carolina, Dept Psychol, CB 3270,Davie Hall, Chapel Hill, NC 27599 USA. EM eay@unc.edu OI White, Amanda/0000-0002-5747-9257 FU Pfizer; Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Addiction Treatment FX This research was supported in part by an investigator initiated grant from Pfizer (PI: Dr Gelenberg) and partially supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Addiction Treatment (Mr Mitchell) and with resources and facilities at the VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. NR 46 TC 0 Z9 0 U1 16 U2 18 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 DEC PY 2015 VL 76 IS 12 BP 1676 EP 1682 DI 10.4088/JCP.14m09353 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DB2RE UT WOS:000368355900019 PM 26613136 ER PT J AU Pan, SJ Tapley, A Adamson, J Little, T Urbanowski, M Cohen, K Pym, A Almeida, D Dorasamy, A Layre, E Young, DC Singh, R Patel, VB Wallengren, K Ndung'u, T Wilson, D Moody, DB Bishai, W AF Pan, Shih-Jung Tapley, Asa Adamson, John Little, Tessa Urbanowski, Michael Cohen, Keira Pym, Alexander Almeida, Deepak Dorasamy, Afton Layre, Emilie Young, David C. Singh, Ravesh Patel, Vinod B. Wallengren, Kristina Ndung'u, Thumbi Wilson, Douglas Moody, D. Branch Bishai, William TI Biomarkers for Tuberculosis Based on Secreted, Species-Specific, Bacterial Small Molecules SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE biomarker; diagnostic; mycobactin; small molecule; tuberculosinyladenosine; tuberculosis ID MYCOBACTERIUM-TUBERCULOSIS; LIPOARABINOMANNAN; CHALLENGES; VIRULENCE; GROWTH; IRON AB Improved biomarkers are needed for tuberculosis. To develop tests based on products secreted by tubercle bacilli that are strictly associated with viability, we evaluated 3 bacterialderived, species-specific, small molecules as biomarkers: 2 mycobactin siderophores and tuberculosinyladenosine. Using liquid chromatography-tandem mass spectrometry, we demonstrated the presence of 1 or both mycobactins and/or tuberculosinyladenosine in serum and whole lung tissues from infected mice and sputum, cerebrospinal fluid (CSF), or lymph nodes from infected patients but not uninfected controls. Detection of the target molecules distinguished host infection status in 100% of mice with both serum and lung as the target sample. In human subjects, we evaluated detection of the bacterial small molecules (BSMs) in multiple body compartments in 3 patient cohorts corresponding to different forms of tuberculosis. We detected at least 1 of the 3 molecules in 90%, 71%, and 40% of tuberculosis patients' sputum, CSF, and lymph node samples, respectively. In paucibacillary forms of human tuberculosis, which are difficult to diagnose even with culture, detection of 1 or more BSM was rapid and compared favorably to polymerase chain reaction-based detection. Secreted BSMs, detectable in serum, warrant further investigation as a means for diagnosis and therapeutic monitoring in patients with tuberculosis. C1 [Pan, Shih-Jung; Adamson, John; Pym, Alexander; Dorasamy, Afton; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV K RITH, Durban, South Africa. [Pan, Shih-Jung; Bishai, William] Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD USA. [Tapley, Asa] Univ Calif, San Francisco Sch Med, Oakland, CA USA. [Tapley, Asa; Bishai, William] Howard Hughes Med Inst, Chevy Chase, MD USA. [Little, Tessa] Univ KwaZulu Natal, Sch Lab Med & Med Sci, Durban, South Africa. [Cohen, Keira] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pulm & Crit Care Med,Dept Med, Boston, MA USA. [Layre, Emilie; Young, David C.; Moody, D. Branch] Harvard Univ, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA USA. [Singh, Ravesh; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Patel, Vinod B.] Univ KwaZulu Natal, Dept Neurol, Durban, South Africa. [Wallengren, Kristina] TB & HIV Investigat Network KwaZulu Natal THINK, Durban, South Africa. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. [Ndung'u, Thumbi] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Ndung'u, Thumbi] Harvard Univ, Cambridge, MA 02138 USA. [Wilson, Douglas] Univ KwaZulu Natal, Edendale Hosp, Dept Med, Pietermaritzburg, South Africa. RP Bishai, W (reprint author), Johns Hopkins Sch Med, CRB2 Rm 108,1550 Orleans St, Baltimore, MD 21287 USA. EM wbishai@jhmi.edu OI Ndung'u, Thumbi/0000-0003-2962-3992; Pym, Alexander/0000-0002-6260-8180 FU US National Institutes of Health [AI097138]; Howard Hughes Medical Institute; South African Research Chairs Initiative; Victor Daitz Foundation FX This work was supported by the US National Institutes of Health award AI097138 (W. B.), the Howard Hughes Medical Institute (W. B. and T. N.), the South African Research Chairs Initiative (T. N.), and the Victor Daitz Foundation (T. N.). NR 15 TC 5 Z9 5 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2015 VL 212 IS 11 BP 1827 EP 1834 DI 10.1093/infdis/jiv312 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DB7BN UT WOS:000368669500018 PM 26014799 ER PT J AU Crowley, JT Drouin, EE Pianta, A Strle, K Wang, Q Costello, CE Steere, AC AF Crowley, Jameson T. Drouin, Elise E. Pianta, Annalisa Strle, Klemen Wang, Qi Costello, Catherine E. Steere, Allen C. TI A Highly Expressed Human Protein, Apolipoprotein B-100, Serves as an Autoantigen in a Subgroup of Patients With Lyme Disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE apolipoprotein B; autoantibodies; Borrelia burgdorferi; erythema migrans; autoimmunity; Lyme arthritis; Lyme disease ID CELL GROWTH-FACTOR; BORRELIA-BURGDORFERI; LIPOPROTEIN OXIDATION; RHEUMATOID-ARTHRITIS; ANTIBIOTIC-TREATMENT; T-CELLS; ATHEROSCLEROSIS; TISSUE; MICE; CHOLESTEROL AB To discover novel autoantigens associated with Lyme arthritis (LA), we identified T-cell epitopes presented in vivo by human leukocyte antigen (HLA)-DR molecules in patients' inflamed synovial tissue or joint fluid and tested each epitope for autoreactivity. Using this approach, we identified the highly expressed human protein, apolipoprotein B-100 (apoB-100), as a target of T-and B-cell responses in a subgroup of LA patients. Additionally, the joint fluid of these patients had markedly elevated levels of apoB-100 protein, which may contribute to its autoantigenicity. In patients with antibiotic-refractory LA, the magnitude of apoB-100 antibody responses correlated with increased numbers of plasma cells in synovial tissue, greater numbers and activation of endothelial cells, and more synovial fibroblast proliferation. Thus, a subset of LA patients have high levels of apoB-100 in their joints and autoreactive T-and B-cell responses to the protein, which likely contributes to pathogenic autoimmunity in patients with antibiotic-refractory LA. C1 [Crowley, Jameson T.; Drouin, Elise E.; Pianta, Annalisa; Strle, Klemen; Steere, Allen C.] Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Massachusetts Gen, Cambridge, MA 02138 USA. [Wang, Qi; Costello, Catherine E.] Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Boston, MA 02215 USA. RP Crowley, JT (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, CNY 149-8301,149 13th St, Charlestown, MA 02129 USA. EM jcrowley6@mgh.harvard.edu FU NIH [R01 AI-110175, K01-AR062098, P41 GM104603, S10 OD010724]; Mathers Foundation; English, Bonter, Mitchel Foundation; Littauer Foundation; Eshe Fund; Lillian B. Davey Foundation; Proteomics Center Contract [HHSN268201000031C] FX This work was supported by funding from the NIH (R01 AI-110175 to A. C. S., K01-AR062098 to K. S., and P41 GM104603 and S10 OD010724 to C. E. C.), Mathers Foundation; English, Bonter, Mitchel Foundation; Littauer Foundation; Eshe Fund; and the Lillian B. Davey Foundation (to A. C. S.), and Proteomics Center Contract (HHSN268201000031C to C. E. C.). NR 49 TC 5 Z9 5 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2015 VL 212 IS 11 BP 1841 EP 1850 DI 10.1093/infdis/jiv310 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DB7BN UT WOS:000368669500020 PM 26014802 ER PT J AU Dhyani, M Gee, MS Misdraji, J Israel, EJ Shah, U Samir, AE AF Dhyani, Manish Gee, Michael S. Misdraji, Joseph Israel, Esther Jacobowitz Shah, Uzma Samir, Anthony E. TI Feasibility study for assessing liver fibrosis in paediatric and adolescent patients using real-time shear wave elastography SO JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY LA English DT Article DE liver biopsy; liver fibrosis; liver stiffness; shear wave elastography; ultrasound ID UNIDIMENSIONAL TRANSIENT ELASTOGRAPHY; FORCE IMPULSE ELASTOGRAPHY; NONALCOHOLIC STEATOHEPATITIS; NONINVASIVE ASSESSMENT; MEDICAL-MANAGEMENT; VIRAL-HEPATITIS; ARFI TECHNOLOGY; SINGLE-CENTER; CHILDREN; DISEASE AB Introduction: The objective of this study was to evaluate the feasibility of shear wave elastography (SWE), as a non-invasive means of assessing liver fibrosis stage in paediatric and adolescent patients. Materials and Methods: Consecutive paediatric and adolescent subjects scheduled for liver biopsy (LB) evaluation of known or suspected diffuse liver disease were included after informed guardian consent and subject assent in this IRB-approved single institution study. Elastograms were acquired prior to liver biopsy, from the liver under a breath-hold after normal inspiration when possible. Biopsy specimens underwent blinded pathologist review using the METAVIR scoring system. Results: Twenty-four patients (M : F = 13:11) with a mean age of 17 years (range: 1-21 years) underwent liver biopsy. The distribution of fibrosis on pathological examination was: F0 = 10, F1 = 9, F2 = 1, F3 = 3, and F4 = 1. Subjects with stages F0 and F1 fibrosis had a mean SWE value of 6.93 kPa (95% CI: 6.33-7.44 kPa) and 8.33 kPa (95% CI: 6.83-10.80 kPa) respectively. The SWE value for the one subject with stage F2 fibrosis was 6.36 kPa, whereas for F3 and F4 were 8.86 (95% CI: 5.70-11.40) and 17.85 kPa respectively. The correlation between SWE values and fibrosis grade was strong (r = 0.58, P = 0.003), and the area under the ROC curve differentiatiang >= F2 fibrosis was 0.62 (95% CI: 0.26-0.98). Conclusion: Estimation of liver stiffness using real-time SWE is feasible using the SC6-1 ultrasound probe in paediatric and adolescent patients and strongly correlates with the stage of fibrosis. C1 [Dhyani, Manish; Gee, Michael S.; Samir, Anthony E.] Harvard Univ, Sch Med, MGH, Dept Radiol, Boston, MA 02115 USA. [Misdraji, Joseph] Harvard Univ, Sch Med, MGH, Dept Pathol, Boston, MA 02115 USA. [Israel, Esther Jacobowitz; Shah, Uzma] Harvard Univ, Sch Med, MGH, Dept Pediat, Boston, MA 02115 USA. RP Dhyani, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM dhyani.manish@mgh.harvard.edu OI Dhyani, Manish/0000-0002-2651-1859 NR 36 TC 1 Z9 1 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1754-9477 EI 1754-9485 J9 J MED IMAG RADIAT ON JI J. Med. Imag. Radiat. Oncol. PD DEC PY 2015 VL 59 IS 6 BP 687 EP 694 DI 10.1111/1754-9485.12388 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB4WK UT WOS:000368514100006 PM 26503488 ER PT J AU Siglinsky, E Krueger, D Ward, RE Caserotti, P Strotmeyer, ES Harris, TB Binkley, N Buehring, B AF Siglinsky, E. Krueger, D. Ward, R. E. Caserotti, P. Strotmeyer, E. S. Harris, T. B. Binkley, N. Buehring, B. TI Effect of age and sex on jumping mechanography and other measures of muscle mass and function SO JOURNAL OF MUSCULOSKELETAL & NEURONAL INTERACTIONS LA English DT Article DE Aging; Skeletal Muscle; Sarcopenia; Jumping Mechanography; Muscle Function Tests ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE BATTERY; X-RAY ABSORPTIOMETRY; OLDER-ADULTS; BODY-COMPOSITION; SUBSEQUENT DISABILITY; WALKING SPEED; GAIT SPEED; SARCOPENIA; POWER AB Objectives: Sarcopenia increases falls and fracture risk. Sarcopenia clinical trials require robust quantitative tools to evaluate muscle function; jumping mechanography (JM) is likely one such tool. However, US data comparing JM with traditional tests across the lifespan is limited. This study evaluated the effect of age and sex on JM compared with traditional function tests and lean mass. Methods: US adults (213 women/119 men; mean age 65.4 years, range 27-96) performed functional tests including JM, Short Physical Performance Battery (SPPB) and grip strength (GS). Appendicular lean mass (ALM) was measured using DXA. Results: Men had higher relative jump power [mean (SD) 28.5 (10.52) vs. 21.9 (7.11) W/kg], GS [35.5 (9.84) vs. 22.7 (6.98) kg] and ALM/ht(2) [8.25 (1.35) vs. 6.99 (1.38) kg/m(2)] (all p< 0.0001); no difference was observed for SPPB components. JM parameters were more strongly correlated with age than traditional tests (R-2= 0.38-0.61 vs. R-2= 0.01-0.28) and weakly with GS and chair rise time (R-2= 0.30-0.36). Conclusion: JM parameters are correlated with GS and chair rise time and demonstrate stronger correlations with age. JM shows promise as a valuable tool to evaluate and monitor interventions for sarcopenia as it could potentially detect change in muscle function more precisely than existing tools. C1 [Siglinsky, E.; Krueger, D.; Binkley, N.; Buehring, B.] Univ Wisconsin, Osteoporosis Clin Res Program, Madison, WI 53705 USA. [Ward, R. E.] Spaulding Rehabil Hosp, Cambridge, MA USA. [Ward, R. E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Caserotti, P.] Univ Southern Denmark, Odense, Denmark. [Strotmeyer, E. S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA USA. [Harris, T. B.] NIA, Bethesda, MA USA. [Buehring, B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Buehring, B (reprint author), Univ Wisconsin, Osteoporosis Clin Res Program, 2870 Univ Ave,Suite 100, Madison, WI 53705 USA. EM bbuehring@medicine.wisc.edu RI Buehring, Bjoern/L-5581-2013; OI Buehring, Bjoern/0000-0003-3841-624X; Strotmeyer, Elsa/0000-0002-4093-6036 FU National Institute on Aging [P01-AG020166]; General Clinical Research Centers Program; National Center for Advancing Translational Sciences (NCATS), National Institutes of Health [UL1TR000427]; Merck Co., Inc. FX The MIDUS research is supported by a grant from the National Institute on Aging (P01-AG020166). The research was further supported by the General Clinical Research Centers Program and UL1TR000427 (UW) from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health". Jump Validation and Vitamin D studies at the University of Wisconsin sponsored by an investigator initiated research grant from Merck & Co., Inc. NR 43 TC 3 Z9 3 U1 2 U2 7 PU JMNI PI NAFPLION PA 7 SPILIADOU SQ, NAFPLION, 21 100, GREECE SN 1108-7161 J9 J MUSCULOSKEL NEURON JI J. Musculoskelet. Neuronal Interact. PD DEC PY 2015 VL 15 IS 4 BP 301 EP 308 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DB1CF UT WOS:000368244900001 PM 26636275 ER PT J AU Sorond, FA Cruz-Almeida, Y Clark, DJ Viswanathan, A Scherzer, CR De Jager, P Csiszar, A Laurienti, PJ Hausdorff, JM Chen, WG Ferrucci, L Rosano, C Studenski, SA Black, SE Lipsitz, LA AF Sorond, Farzaneh A. Cruz-Almeida, Yenisel Clark, David J. Viswanathan, Anand Scherzer, Clemens R. De Jager, Philip Csiszar, Anna Laurienti, Paul J. Hausdorff, Jeffery M. Chen, Wen G. Ferrucci, Luiggi Rosano, Caterina Studenski, Stephanie A. Black, Sandra E. Lipsitz, Lewis A. TI Aging, the Central Nervous System, and Mobility in Older Adults: Neural Mechanisms of Mobility Impairment SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE CNS; Aging; Mobility; Imaging ID SMALL VESSEL DISEASE; VASCULAR COGNITIVE IMPAIRMENT; WHITE-MATTER LESIONS; CEREBROVASCULAR HEMODYNAMICS; ISCHEMIC-STROKE; GAIT SPEED; CADASIL; ASSOCIATION; PLASTICITY; WALKING AB Background. Mobility is crucial for successful aging and is impaired in many older adults. We know very little about the subtle, subclinical age-related changes in the central nervous system (CNS) that mediate mobility impairment. Methods. A conference series focused on aging, the CNS, and mobility was launched. The second conference addressed major age-associated mechanisms of CNS-mediated mobility impairment. Speakers and conference attendees recommended key areas for future research, identified barriers to progress, and proposed strategies to overcome them. Results. Priorities identified for future research include (a) studying interactions among different mechanisms; (b) examining effects of interventions targeting these mechanisms; (c) evaluating the effect of genetic polymorphisms on risks and course of age-related mobility impairment; and (d) examining the effect of age on CNS repair processes, neuroplasticity, and neuronal compensatory mechanisms. Key strategies to promote research include (a) establish standard measures of mobility across species; (b) evaluate the effect of aging in the absence of disease on CNS and mobility; and (c) use advanced computational methods to better evaluate the interactions between CNS and other systems involved in mobility. Conclusions. CNS is a major player in the process, leading to mobility decline with aging. Future research in this area has the potential to prolong independence in older persons. Better interactions among disciplines and shared research paradigms are needed to make progress. Research priorities include the development of innovative approaches to integrate research on aging, cognition, and movement with attention to neurovascular function, neuroplasticity, and neurophysiological reserve. C1 [Sorond, Farzaneh A.] Brigham & Womens Hosp, Stroke Div, Dept Neurol, Boston, MA 02115 USA. [Cruz-Almeida, Yenisel] Univ Florida, Coll Med, Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL USA. [Clark, David J.] Univ Florida, Dept Aging & Geriatr Res, North Florida South Georgia Vet Hlth Syst, Brain Rehabil Res Ctr, Gainesville, FL USA. [Viswanathan, Anand] Harvard Univ, Sch Med, Dept Neurol, Stroke Div,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Scherzer, Clemens R.; De Jager, Philip] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Csiszar, Anna] Univ Oklahoma, Hlth Sci Center, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, Norman, OK 73019 USA. [Laurienti, Paul J.] Wake Forest Sch Med, Dept Radiol, Winston Salem, NC USA. [Hausdorff, Jeffery M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Med, IL-69978 Tel Aviv, Israel. [Chen, Wen G.] NIA, Sensory & Motor Disorders Aging, Bethesda, MD 20892 USA. [Ferrucci, Luiggi] NIA, Longitudinal Studies Sect, Bethesda, MD 20892 USA. [Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Studenski, Stephanie A.] Pittsburgh Healthcare Syst, Div Geriatr Med, Dept Med, Pittsburgh, PA USA. [Black, Sandra E.] Univ Toronto, Sunnybrook Res Inst, Dept Neurol, Toronto, ON M5S 1A1, Canada. [Lipsitz, Lewis A.] Harvard Univ, Sch Med, Hebrew Senior Life, Inst Aging Res,Res, Boston, MA USA. RP Sorond, FA (reprint author), Brigham & Womens Hosp, Stroke Div, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM fsorond@partners.org OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU National Institute on Aging [U13-AG-041613-01, T32-AG-000181]; University of Pittsburgh Claude D. Pepper Older Americans Independence Center (National Institute on Aging) [P30-AG-024827]; [RO1-NS-085002] FX This work was supported by a cooperative conference grant (National Institute on Aging, U13-AG-041613-01), the University of Pittsburgh Claude D. Pepper Older Americans Independence Center (National Institute on Aging, P30-AG-024827), a postdoctoral training grant (National Institute on Aging, T32-AG-000181), and RO1-NS-085002. NR 45 TC 6 Z9 6 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2015 VL 70 IS 12 BP 1526 EP 1532 DI 10.1093/gerona/glv130 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DB2UB UT WOS:000368364100009 PM 26386013 ER PT J AU Marcum, ZA Perera, S Newman, AB Thorpe, JM Switzer, GE Gray, SL Simonsick, EM Shorr, RI Bauer, DC Castle, NG Studenski, SA Hanlon, JT AF Marcum, Zachary A. Perera, Subashan Newman, Anne B. Thorpe, Joshua M. Switzer, Galen E. Gray, Shelly L. Simonsick, Eleanor M. Shorr, Ronald I. Bauer, Douglas C. Castle, Nicholas G. Studenski, Stephanie A. Hanlon, Joseph T. CA Hlth ABC Study TI Antihypertensive Use and Recurrent Falls in Community-Dwelling Older Adults: Findings From the Health ABC Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Falls; Medication; Epidemiology; Drug related ID BODY-COMPOSITION; DRUG-USE; HYPERTENSION; MEDICATIONS; RISK; PREDICTORS; FRACTURES; PEOPLE; ELDERS; AGE AB Background. Despite wide-spread use of antihypertensives in older adults, the literature is unclear about their association with incident recurrent falls over time. Methods. Health, Aging and Body Composition study participants (n = 2,948) who were well functioning at baseline (1997) were followed to Year 7 (2004). The main outcome was recurrent falls (>= 2) in the ensuing 12 months. Antihypertensive use was examined as: (a) any versus none, (b) long-versus short-term (<= 2 vs <2 years), and by (c) summated standardized daily dose (SDD; 1 = maximum recommended daily dose for one antihypertensive), and (d) subclass. Results. Controlling for potential demographic, health status/behavior and access to care confounders, we found no increase in risk of recurrent falls in antihypertensive users compared to nonusers (adjusted odds ratio [AOR] = 1.13; 95% CI = 0.88-1.46), or those taking higher SDDs or for longer durations. Only those using a loop diuretic were found to have a modest increased risk of recurrent falls (AOR = 1.50; 95% CI = 1.11-2.03). Conclusions. Antihypertensive use overall was not statistically significantly associated with recurrent falls after adjusting for important confounders. Loop diuretic use may be associated with recurrent falls and needs further study. C1 [Marcum, Zachary A.; Perera, Subashan; Newman, Anne B.; Hanlon, Joseph T.; Hlth ABC Study] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA 15260 USA. [Perera, Subashan; Hanlon, Joseph T.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. [Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Thorpe, Joshua M.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA 15260 USA. [Thorpe, Joshua M.; Switzer, Galen E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Med Gen Internal, Pittsburgh, PA 15260 USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Shorr, Ronald I.] North Florida South Georgia Vet Hlth Syst GRECC, Gainesville, FL USA. [Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Castle, Nicholas G.] Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA 15260 USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. RP Marcum, ZA (reprint author), Univ Washington, Sch Pharm, Dept Pharm, 1959 NE Pacific St,Box 357630, Seattle, WA 98195 USA. EM zmarcum@uw.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU National Institute on Aging (NIA) [R01AG027017, P30AG024827, T32AG021885, K07AG033174]; Intramural Research program of the National Institutes of Health [N01AG62101, N01AG62103, N01AG62106, R01AG028050]; National Institute of Nursing Research grant [R01NR012459] FX This work was supported by National Institute on Aging (NIA) grants (R01AG027017, P30AG024827, T32AG021885, and K07AG033174). This work was also supported in part by the Intramural Research program of the National Institutes of Health (N01AG62101, N01AG62103, N01AG62106, and R01AG028050) and a National Institute of Nursing Research grant (R01NR012459). NR 33 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 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2015 VL 70 IS 12 BP 1562 EP 1568 DI 10.1093/gerona/glv095 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DB2UB UT WOS:000368364100014 PM 26265732 ER PT J AU Berghaus, KV Yun, SH Scarcelli, G AF Berghaus, Kim V. Yun, Seok H. Scarcelli, Giuliano TI High Speed Sub-GHz Spectrometer for Brillouin Scattering Analysis SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Bioengineering; Issue 106; Spectrometers; Scattering; Brillouin; Biomaterials; Confocal Microscopes; Mechanical Imaging ID OPTICAL MICROSCOPY; SPECTROSCOPY; LENS; EYE AB The goal of this protocol is to build a parallel high-extinction and high-resolution optical Brillouin spectrometer. Brillouin spectroscopy is a non-contact measurement method that can be used to obtain direct readouts of viscoelastic material properties. It has been a useful tool in material characterization, structural monitoring and environmental sensing. In the past, Brillouin spectroscopy has usually employed scanning Fabry-Perot etalons to perform spectral analysis. This process requires high illumination power and long acquisition times, making the technique unsuitable for biomedical applications. A recently introduced novel spectrometer overcomes this challenge by employing two VIPAs in a cross-axis configuration. This innovation enables sub-Gigahertz (GHz) resolution spectral analysis with sub-second acquisition time and illumination power within the safety limits of biological tissue. The multiple new applications facilitated by this improvement are currently being explored in biological research and clinical application. C1 [Berghaus, Kim V.; Scarcelli, Giuliano] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Yun, Seok H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02138 USA. [Yun, Seok H.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Scarcelli, G (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. EM scarc@umd.edu FU National Institutes of Health [P41-EB015903, R21EY023043, K25EB015885]; National Science of Foundation [CBET-0853773]; Human Frontier Science Program (Young Investigator Grant) FX This work was supported in part by the National Institutes of Health (P41-EB015903, R21EY023043, K25EB015885), National Science of Foundation (CBET-0853773) and Human Frontier Science Program (Young Investigator Grant). NR 14 TC 0 Z9 0 U1 0 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD DEC PY 2015 IS 106 AR e53468 DI 10.3791/53468 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB5SR UT WOS:000368574400063 PM 26779654 ER PT J AU Korpal, M Feala, J Puyang, XL Zou, J Ramos, AH Wu, J Baumeister, T Yu, LH Warmuth, M Zhu, P AF Korpal, Manav Feala, Jacob Puyang, Xiaoling Zou, Jian Ramos, Alex H. Wu, Jeremy Baumeister, Timm Yu, Lihua Warmuth, Markus Zhu, Ping TI Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 106; resistance; Next-generation Sequencing; Molecular Mechanisms; in vitro; Xenograft; Clones; Cancer ID SOMATIC POINT MUTATIONS; MICROSATELLITE INSTABILITY; SEQUENCING DATA; CELL-LINES; CANCER-THERAPY; GENOME; PROTEIN; IDENTIFICATION; HETEROGENEITY; INHIBITORS AB Although targeted therapies are initially effective, resistance inevitably emerges. Several methods, such as genetic analysis of resistant clinical specimens, have been applied to uncover these resistance mechanisms to facilitate follow-up care. Although these approaches have led to clinically relevant discoveries, difficulties in attaining the relevant patient material or in deconvoluting the genomic data collected from these specimens have severely hampered the path towards a cure. To this end, we here describe a tool for expeditious discovery that may guide improvement in first-line therapies and alternative clinical management strategies. By coupling preclinical in vitro or in vivo drug selection with next-generation sequencing, it is possible to identify genomic structural variations and/or gene expression alterations that may serve as functional drivers of resistance. This approach facilitates the spontaneous emergence of alterations, enhancing the probability that these mechanisms may be observed in the patients. In this protocol we provide guidelines to maximize the potential for uncovering single nucleotide variants that drive resistance using adherent lines. C1 [Korpal, Manav; Feala, Jacob; Puyang, Xiaoling; Zou, Jian; Wu, Jeremy; Baumeister, Timm; Yu, Lihua; Warmuth, Markus; Zhu, Ping] H3 Biomed, Cambridge, MA 02139 USA. [Ramos, Alex H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zhu, P (reprint author), H3 Biomed, Cambridge, MA 02139 USA. EM ping_zhu@h3biomedicine.com FU H3 Biomedicine FX Publication fees for this article are paid by H3 Biomedicine. NR 40 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD DEC PY 2015 IS 106 AR e52879 DI 10.3791/52879 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB5SR UT WOS:000368574400005 PM 26710000 ER PT J AU Humalda, JK Goldsmith, DJA Thadhani, R de Borst, MH AF Humalda, Jelmer K. Goldsmith, David J. A. Thadhani, Ravi de Borst, Martin H. TI Vitamin D analogues to target residual proteinuria: potential impact on cardiorenal outcomes SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE cardiovascular disease; chronic kidney disease; proteinuria; vitamin D ID CHRONIC KIDNEY-DISEASE; RENIN-ANGIOTENSIN SYSTEM; RANDOMIZED CONTROLLED-TRIAL; DIETARY-SODIUM RESTRICTION; CHRONIC RENAL-DISEASE; D-BINDING PROTEIN; CARDIOVASCULAR EVENTS; DIABETIC-NEPHROPATHY; URINARY SODIUM; 1,25-DIHYDROXYVITAMIN D-3 AB Residual proteinuria, the amount of proteinuria that remains during optimally dosed renin-angiotensin-aldosterone system (RAAS) blockade, is an independent risk factor for progressive renal function loss and cardiovascular complications in chronic kidney disease (CKD) patients. Dual RAAS blockade may reduce residual proteinuria but without translating into improved cardiorenal outcomes at least in diabetic nephropathy; rather, dual RAAS blockade may increase the risk of adverse events. These findings have challenged the concept of residual proteinuria as an absolute treatment target. Therefore, new strategies must be explored to address whether by further reduction of residual proteinuria using interventions not primarily targeting the RAAS benefit in terms of cardiorenal risk reduction would accrue. Both clinical and experimental intervention studies have demonstrated that vitamin D can reduce residual proteinuria through both RAAS-dependent and RAAS-independent pathways. Future research should prospectively explore vitamin D treatment as an adjunct to RAAS blockade in an interventional trial exploring clinically relevant cardiorenal end points. C1 [Humalda, Jelmer K.; de Borst, Martin H.] Univ Groningen, Univ Med Ctr Groningen, Dept Med, Div Nephrol, Groningen, Netherlands. [Goldsmith, David J. A.] Guys & St Thomas NHS Fdn Hosp, Renal Unit, London, England. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP de Borst, MH (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Med, Div Nephrol, Groningen, Netherlands. EM m.h.de.borst@umcg.nl FU Dutch Kidney Foundation (NIGRAM consortium) [CP10.11]; Dutch Kidney Foundation [KJPB.08.07]; Netherlands Organization for Scientific Research FX This work is supported by a consortium grant from the Dutch Kidney Foundation (NIGRAM consortium, grant no CP10.11). M.H.D.B. is supported by grants from the Dutch Kidney Foundation (grant no KJPB.08.07) and the Netherlands Organization for Scientific Research (Veni grant). The funding sources had no role in the preparation, review, or approval of the manuscript. NR 50 TC 3 Z9 3 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 2015 VL 30 IS 12 BP 1988 EP 1994 DI 10.1093/ndt/gfu404 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA DB3ZY UT WOS:000368453700010 PM 25609737 ER PT J AU Fishbane, SN Singh, AK Cournoyer, SH Jindal, KK Fanti, P Guss, CD Lin, VH Pratt, RD Gupta, A AF Fishbane, Steven N. Singh, Ajay K. Cournoyer, Serge H. Jindal, Kailash K. Fanti, Paolo Guss, Carrie D. Lin, Vivian H. Pratt, Raymond D. Gupta, Ajay TI Ferric pyrophosphate citrate (Triferic (TM)) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE anemia; erythropoiesis-stimulating agent; ferric pyrophosphate citrate; hemodialysis; iron ID THERAPY; ANEMIA; CKD AB Background. Administration of ferric pyrophosphate citrate (FPC, Triferic (TM)) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Methods. Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 mu M FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin. Results. In both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2-0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (-0.9 pg versus -0.4 pg, P < 0.001) and serum ferritin (-133.1 mu g/L versus -69.7 mu g/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups. Conclusions. FPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients. C1 [Fishbane, Steven N.] Hofstra North Shore LIJ Sch Med, Great Neck, NY USA. [Singh, Ajay K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Cournoyer, Serge H.] Univ Sherbrooke, Hop Charles LeMoyne, Quebec City, PQ, Canada. [Jindal, Kailash K.] Univ Alberta, Dept Med, Div Nephrol, Edmonton, AB, Canada. [Fanti, Paolo] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Div Nephrol, San Antonio, TX 78229 USA. [Guss, Carrie D.; Lin, Vivian H.; Pratt, Raymond D.; Gupta, Ajay] Rockwell Med Inc, Wixom, MI USA. [Gupta, Ajay] Univ Calif Irvine, Irvine, CA USA. RP Gupta, A (reprint author), Rockwell Med Inc, Wixom, MI USA. EM ajayg1@uci.edu FU Rockwell Medical, Inc. FX This study was funded by Rockwell Medical, Inc. (ClinicalTrials.gov identifiers NCT01320202 and NCT01322347). NR 13 TC 11 Z9 12 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 2015 VL 30 IS 12 BP 2019 EP 2026 DI 10.1093/ndt/gfv277 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA DB3ZY UT WOS:000368453700014 PM 26175145 ER PT J AU Filbin, MG Segal, RA AF Filbin, Mariella G. Segal, Rosalind A. TI How neuronal activity regulates glioma cell proliferation SO NEURO-ONCOLOGY LA English DT Editorial Material ID ORIGIN C1 [Filbin, Mariella G.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Filbin, Mariella G.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM rosalind_segal@dfci.harvard.edu FU NCI NIH HHS [P01 CA142536, CA142536, K12CA090354] NR 7 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD DEC PY 2015 VL 17 IS 12 BP 1543 EP 1544 DI 10.1093/neuonc/nov188 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DB3ZO UT WOS:000368452700001 PM 26359210 ER PT J AU Blanke, CD Rankin, C Corless, C Eary, JF Mulder, K Okuno, SH George, S Heinrich, M AF Blanke, Charles D. Rankin, Cathy Corless, Christopher Eary, Janet F. Mulder, Karen Okuno, Scott H. George, Suzanne Heinrich, Michael TI S0502: A SWOG Phase III Randomized Study of Imatinib, With or Without Bevacizumab, in Patients With Untreated Metastatic or Unresectable Gastrointestinal Stromal Tumors SO ONCOLOGIST LA English DT Article AB Background. Imatinib mesylate, a potent inhibitor of the KIT and PDGFR tyrosine kinases, is highly effective in the treatment of advanced gastrointestinal stromal tumors (GISTs). However, most imatinib-treated tumors eventually become resistant, accounting for a median progression-free survival of 19-23 months. Expression of vascular endothelial growth factor (VEGF) correlates with poor prognosis in GIST; bevacizumab, a monoclonal antibody against VEGF, is effective in a variety of solid tumors. We postulated combination therapy with imatinib plus bevacizumab would benefit patients with advanced GIST, particularly those reliant on VEGFA-dependent angiogenesis. Methods. Patients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial, S0502. At registration, patients were randomly assigned to either imatinib 400mg (standard) or 800 mg (patients with exon 9 KIT mutations), or imatinib plus bevacizumab, 7.5 mg/kg i.v. every 3 weeks. Patients were treated to progression, symptomatic deterioration, unacceptable toxicity, treatment delay greater than 4 weeks, or patient choice to withdraw from the study. The primary objective was to determine whether the addition of bevacizumab to imatinib would improve progression-free survival (PFS) in first-line treatment of incurable GIST. Results. S0502 opened on April 15, 2008. As of fall 2009, only 12 patients from at least 178 eligible SWOG centers plus those participating through Cancer Trials Support Unit had been entered in the study. Despite an aggressive promotion scheme involving the other cooperative groups and a major GIST patient advocacy group, accrual remained slow. The trial was closed on October 1, 2009, having accrued only 2% of the 572 patients planned. No scientific conclusions were forthcoming because of the small number of patients entered in the study. Two patients of the 6 in the combination arm reported grade 3 toxicities, 1 with proteinuria and 1 with fatigue, upper gastrointestinal hemorrhage, and anemia. Conclusion. No conclusions may be drawn from this trial and, thus, the combination of imatinib plus bevacizumab cannot be recommended for use. C1 [Blanke, Charles D.] Oregon Hlth & Sci Univ, SWOG, Portland, OR 97239 USA. [Blanke, Charles D.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Rankin, Cathy] SWOG Stat Ctr, Seattle, WA USA. [Corless, Christopher; Heinrich, Michael] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Eary, Janet F.] Univ Washington, Seattle, WA 98195 USA. [Mulder, Karen] Univ Alberta, Edmonton, AB, Canada. [Okuno, Scott H.] Mayo Clin, Rochester, MN USA. [George, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Blanke, CD (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, 3181 SW Sam Jackson Pk Rd,L-586, Portland, OR 97239 USA. EM blankec@ohsu.edu FU NCI NIH HHS [U10 CA180819, U10 CA180888] NR 1 TC 2 Z9 2 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD DEC PY 2015 VL 20 IS 12 BP 1353 EP 1354 DI 10.1634/theoncologist.2015-0295 PG 2 WC Oncology SC Oncology GA DB3MS UT WOS:000368416400002 PM 26576593 ER PT J AU Setia, N Clark, JW Duda, DG Hong, TS Kwak, EL Mullen, JT Lauwers, GY AF Setia, Namrata Clark, Jeffrey W. Duda, Dan G. Hong, Theodore S. Kwak, Eunice L. Mullen, John T. Lauwers, Gregory Y. TI Familial Gastric Cancers SO ONCOLOGIST LA English DT Article ID PEUTZ-JEGHERS-SYNDROME; NONPOLYPOSIS COLORECTAL-CANCER; LI-FRAUMENI-SYNDROME; FUNDIC GLAND POLYPS; OF-THE-LITERATURE; GENOTYPE-PHENOTYPE CORRELATIONS; UPPER GASTROINTESTINAL CANCER; CDH1 GERMLINE MUTATIONS; LARGE GENOMIC DELETIONS; MUIR-TORRE-SYNDROME AB Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%-3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. C1 [Setia, Namrata; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Clark, Jeffrey W.; Kwak, Eunice L.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Duda, Dan G.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Mullen, John T.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM glauwers@partners.org FU Merrimack; HealthCare Pharma; Novartis FX Dan G. Duda: Hexal (C/A), Merrimack, HealthCare Pharma (RF);; Theodore S. Hong: Eisai (C/A), Novartis (RF). The other authors indicated no financial relationships. NR 139 TC 3 Z9 3 U1 2 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD DEC PY 2015 VL 20 IS 12 BP 1365 EP 1377 DI 10.1634/theoncologist.2015-0205 PG 13 WC Oncology SC Oncology GA DB3MS UT WOS:000368416400004 PM 26424758 ER PT J AU Morgans, A Schapira, L AF Morgans, Alicia Schapira, Lidia TI Confronting Oncologists' Emotions Reply SO ONCOLOGIST LA English DT Letter ID EMPATHY C1 [Morgans, Alicia] Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Morgans, A (reprint author), Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD DEC PY 2015 VL 20 IS 12 BP 1461 EP 1461 DI 10.1634/theoncologist.2015-0350 PG 1 WC Oncology SC Oncology GA DB3MS UT WOS:000368416400018 PM 26671174 ER PT J AU Deng, WJ Babu, IR Su, D Yin, SY Begley, TJ Dedon, PC AF Deng, Wenjun Babu, I. Ramesh Su, Dan Yin, Shanye Begley, Thomas J. Dedon, Peter C. TI Trm9-Catalyzed tRNA Modifications Regulate Global Protein Expression by Codon-Biased Translation SO PLOS GENETICS LA English DT Article ID DOSAGE COMPENSATION; GENE-EXPRESSION; WOBBLE POSITION; METHYLTRANSFERASE; EVOLUTION; USAGE; EFFICIENCY; MAMMALS; SYSTEM; YEAST AB Post-transcriptional modifications of transfer RNAs (tRNAs) have long been recognized to play crucial roles in regulating the rate and fidelity of translation. However, the extent to which they determine global protein production remains poorly understood. Here we use quantitative proteomics to show a direct link between wobble uridine 5-methoxycarbonylmethyl (mcm5) and 5-methoxy-carbonyl-methyl-2-thio (mcm(5)s(2)) modifications catalyzed by tRNA methyltransferase 9 (Trm9) in tRNA(Arg(UCU)) and tRNA(Glu(UUC)) and selective translation of proteins from genes enriched with their cognate codons. Controlling for bias in protein expression and alternations in mRNA expression, we find that loss of Trm9 selectively impairs expression of proteins from genes enriched with AGA and GAA codons under both normal and stress conditions. Moreover, we show that AGA and GAA codons occur with high frequency in clusters along the transcripts, which may play a role in modulating translation. Consistent with these results, proteins subject to enhanced ribosome pausing in yeast lacking mcm(5)U and mcm(5)s(2)U are more likely to be down-regulated and contain a larger number of AGA/GAA clusters. Together, these results suggest that Trm9-catalyzed tRNA modifications play a significant role in regulating protein expression within the cell. C1 [Deng, Wenjun; Babu, I. Ramesh; Su, Dan; Dedon, Peter C.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Yin, Shanye] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Begley, Thomas J.] SUNY Albany, Coll Nanoscale Sci & Engn, Albany, NY 12222 USA. [Begley, Thomas J.] SUNY Albany, RNA Inst, Albany, NY 12222 USA. [Begley, Thomas J.] SUNY Albany, Canc Res Ctr, Albany, NY 12222 USA. [Dedon, Peter C.] Singapore MIT Alliance Res & Technol, Singapore, Singapore. RP Deng, WJ (reprint author), Massachusetts Gen Hosp, Clin Prote Res Ctr, Dept Neurol, WACC 7-739, Boston, MA 02114 USA. EM pcdedon@mit.edu FU US National Science Foundation [CHE-1308839]; US National Institute of Environmental Health Science [ES002109, ES017010]; Singapore-MIT Alliance for Research and Technology, National Research Foundation of Singapore FX This work was supported by the US National Science Foundation (www.nsf.gov), CHE-1308839, PCD and by the US National Institute of Environmental Health Science (http://www.niehs.nih.gov), grants: ES002109 to PCD and ES017010 to TJB. This work was also supported by Singapore-MIT Alliance for Research and Technology, National Research Foundation of Singapore (http://www.nrf.gov.sg) to PCD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 5 Z9 7 U1 1 U2 3 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 DEC PY 2015 VL 11 IS 12 AR e1005706 DI 10.1371/journal.pgen.1005706 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA DB4YB UT WOS:000368518400037 PM 26670883 ER PT J AU Kim, SY Kotelchuck, M Wilson, HG Diop, H Shapiro-Mendoza, CK England, LJ AF Kim, Shin Y. Kotelchuck, Milton Wilson, Hoyt G. Diop, Hafsatou Shapiro-Mendoza, Carrie K. England, Lucinda J. TI Prevalence of Adverse Pregnancy Outcomes, by Maternal Diabetes Status at First and Second Deliveries, Massachusetts, 1998-2007 SO PREVENTING CHRONIC DISEASE LA English DT Article ID LIFE-STYLE INTERVENTION; MELLITUS; BIRTHS; HYPERGLYCEMIA; PREVENTION; RECURRENCE; METFORMIN; GLUCOSE; OBESITY; TRENDS AB Introduction Understanding patterns of diabetes prevalence and diabetes-related complications across pregnancies could inform chronic disease prevention efforts. We examined adverse birth outcomes by diabetes status among women with sequential, live singleton deliveries. Methods We used data from the 1998-2007 Massachusetts Pregnancy to Early Life Longitudinal Data System, a population-based cohort of deliveries. We restricted the sample to sets of parity 1 and 2 deliveries. We created 8 diabetes categories using gestational diabetes mellitus (GDM) and chronic diabetes mellitus (CDM) status for the 2 deliveries. Adverse outcomes included large for gestational age (LGA), macrosomia, preterm birth, and cesarean delivery. We computed prevalence estimates for each outcome by diabetes status. Results We identified 133,633 women with both parity 1 and 2 deliveries. Compared with women who had no diabetes in either pregnancy, women with GDM or CDM during any pregnancy had increased risk for adverse birth outcomes; the prevalence of adverse outcomes was higher in parity 1 deliveries among women with no diabetes in parity 1 and GDM in parity 2 (for LGA [8.5% vs 15.1%], macrosomia [9.7% vs. 14.9%], cesarean delivery [24.7% vs 31.3%], and preterm birth [7.7% vs 12.9%]); and higher in parity 2 deliveries among those with GDM in parity 1 and no diabetes in parity 2 (for LGA [12.3% vs 18.2%], macrosomia [12.3% vs 17.2%], and cesarean delivery [27.0% vs 37.9%]). Conclusions Women with GDM during one of 2 sequential pregnancies had elevated risk for adverse outcomes in the unaffected pregnancy, whether the diabetes-affected pregnancy preceded or followed it. C1 [Kim, Shin Y.; England, Lucinda J.] Ctr Dis Control & Prevent, 4770 Buford Highway NE,MS F74, Atlanta, GA 30341 USA. [Kotelchuck, Milton] MassGen Hosp Children, Boston, MA USA. [Kotelchuck, Milton] Harvard Univ, Sch Med, Boston, MA USA. [Wilson, Hoyt G.] DB Consulting Grp Inc, Silver Spring, MD USA. [Diop, Hafsatou] Bur Family Hlth & Nutr, Dept Publ Hlth, Boston, MA USA. RP Kim, SY (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway NE,MS F74, Atlanta, GA 30341 USA. EM skim1@cdc.gov NR 31 TC 0 Z9 0 U1 0 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD DEC PY 2015 VL 12 AR 150362 DI 10.5888/pcd12.150362 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DB7AC UT WOS:000368665800008 ER PT J AU Garcia-Romero, MT Geller, AC Kawachi, I AF Garcia-Romero, Maria T. Geller, Alan C. Kawachi, Ichiro TI Using behavioral economics to promote healthy behavior toward sun exposure in adolescents and young adults SO PREVENTIVE MEDICINE LA English DT Review DE Behavioral economics; Skin cancer; Skin neoplasms; Ultraviolet rays; Adolescents ID SKIN-CANCER PREVENTION; APPEARANCE-BASED INTERVENTIONS; PURPOSE-BUILT SHADE; SUNSCREEN USE; ULTRAVIOLET-RADIATION; PROTECTION BEHAVIORS; RANDOMIZED-TRIAL; SUNSMART; BELIEFS; SCHOOLS AB Skin cancer represents an important public health problem, and it is associated with ultraviolet radiation exposure, particularly at early ages. Unhealthy sun exposure and intentional tanning continue to be the trend among young people. Multiple interventions to raise awareness of the risks of sun exposure have been implemented, without necessarily translating into decreased unhealthy behaviors or skin cancer incidence rates. Behavioral economics adds a set of concepts and tools to potentially boost the efficacy of existing approaches to decrease unhealthy sun exposure. This paper reviews public health interventions that have been based in behavioral economics concepts and their results, and provides examples of new and creative ways physicians and health professionals can actively apply insights from behavioral economics to counsel teenagers and young adults about skin cancer prevention. (C) 2015 Elsevier Inc. All rights reserved. C1 [Garcia-Romero, Maria T.] Natl Inst Pediat, Dept Dermatol, Mexico City 04530, DF, Mexico. [Geller, Alan C.; Kawachi, Ichiro] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Geller, Alan C.] Massachusetts Gen Hosp, Melanoma Epidemiol, Boston, MA 02114 USA. RP Garcia-Romero, MT (reprint author), Natl Inst Pediat, Dept Dermatol, Insurgentes Sur 3700c, Mexico City 04530, DF, Mexico. EM mtgr@mail.harvard.edu NR 36 TC 0 Z9 0 U1 9 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD DEC PY 2015 VL 81 BP 184 EP 188 DI 10.1016/j.ypmed.2015.08.025 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DB3OP UT WOS:000368421300028 PM 26361753 ER PT J AU Tan, ASL Lee, CJ Bigman, CA AF Tan, Andy S. L. Lee, Chul-joo Bigman, Cabral A. TI Public support for selected e-cigarette regulations and associations with overall information exposure and contradictory information exposure about e-cigarettes: Findings from a national survey of US adults SO PREVENTIVE MEDICINE LA English DT Article DE Electronic cigarette; Tobacco control policy; United States; Public opinion ID TOBACCO HARM REDUCTION; ELECTRONIC CIGARETTES; CLASSIFICATION; MESSAGES; SMOKERS; HEALTH; IMPACT AB Objective. We assessed public support for six e-cigarette regulations and examined whether self-reported exposure to e-cigarette information and contradictory e-cigarette information were associated with support. Method. We conducted an online survey among a nationally representative sample of 527 U.S. adults in July 2014. Weighted, fully adjusted multinomial logistic regression models predicted support for banning e-cigarettes in smoke-free areas, prohibiting e-cigarette sales to youth, requiring addiction warnings, banning flavors, requiring labeling nicotine and harmful ingredients, and banning youth-targeted marketing. Results. Between 34% and 72% supported these six policies (disagreed 6-24%; no opinion 18-38%). We found higher support for policies to protect youth (prohibit sales to youth and youth-targeted marketing) and to require labeling e-cigarette constituents (nicotine and harmful ingredients). Banning the use of flavors in e-cigarettes was the least supported. Overall information exposure predicted lower relative risk of support for three policies (prohibit sales to youth, nicotine and harmful ingredient labeling, addiction warnings). In comparison, contradictory information exposure predicted lower relative risk of support for two policies (prohibit sales to youth, nicotine and harmful ingredient labeling). Conclusions. Exposure to overall and conflicting information about e-cigarettes in the public sphere is associated with reduced support for certain proposed e-cigarette policies. These findings are important for policymakers and tobacco control advocates involved in promulgation of e-cigarette policies. The results provide insights on which policies may meet some public resistance and therefore require efforts to first gain public support. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tan, Andy S. L.] Dana Farber Canc Inst, Div Populat Sci, Ctr Community Based Res, Boston, MA 02115 USA. [Tan, Andy S. L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Lee, Chul-joo] Seoul Natl Univ, Dept Commun, Seoul, South Korea. [Bigman, Cabral A.] Univ Illinois, Dept Commun, Urbana, IL USA. RP Tan, ASL (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW 662, Boston, MA 02115 USA. EM andy_tan@dfci.harvard.edu OI Tan, Andy/0000-0001-6459-6171 FU SNU Invitation Program for Distinguished Scholar; ICT R&D program of MSIP/IITP [2013-005-002-013]; National Research Foundation of Korea [2015S1A58017994] FX Preparation of this article was supported by the SNU Invitation Program for Distinguished Scholar, the ICT R&D program of MSIP/IITP [2013-005-002-013, How to create an ICT-based eco-system for content industry], and grant no. 2015S1A58017994 from the National Research Foundation of Korea to Chul-joo Lee. Andy Tan conducted this work while an assistant professor at the Dana-Farber Cancer Institute and Harvard TH Chan School of Public Health. Cabral Bigman conducted this work while an assistant professor at the University of Illinois at Urbana-Champaign. The study was initiated and analyzed by the investigators. The funding source had no involvement in the design, conduct, writing, or submission of this manuscript. NR 41 TC 2 Z9 2 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD DEC PY 2015 VL 81 BP 268 EP 274 DI 10.1016/j.ypmed.2015.09.009 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DB3OP UT WOS:000368421300041 PM 26400638 ER PT J AU Thomas, DM Kyle, TK Stanford, FC AF Thomas, Diana M. Kyle, Theodore K. Stanford, Fatima Cody TI The gap between expectations and reality of exercise-induced weight loss is associated with discouragement SO PREVENTIVE MEDICINE LA English DT Article DE Exercise; Weight loss; Obesity; Weight status; Overweight ID PHYSICAL-ACTIVITY; BODY-COMPOSITION; ENERGY-BALANCE; LIFE-STYLE; INTERVENTION; OBESITY; ADULTS; EFFICACY AB Background. Exercise interventions result in modest weight loss, yet exercise is frequently prescribed for weight loss. Purpose. To identify individuals who become discouraged when exercise fails to achieve weight loss. Methods. Representative samples of U.S. adults were recruited using Google Consumer Surveys in August-October 2014. Respondents were asked about beliefs and potential discouragement regarding the role of exercise and weight loss. An analysis of variance was performed to predict individuals that become discouraged if exercise does not lead to weight loss. Results. The belief that exercise is a very effective way to lose weight was common (71% of respondents). Stronger belief that exercise is an effective way to lose weight (p < 0.001) in individuals with higher weight status (p = 0.04) positively predicted discouragement with exercise. Higher weight status combined with the belief that exercise reduces weight was a significant positive predictor of discouragement (p = 0.01). Conclusions. Individuals with higher weight status that believe that exercise is an effective way to lose weight are more likely to become discouraged when exercise does not lead to weight loss. Prescribing exercise for weight loss might contribute to discouragement. Future studies should evaluate ways to encourage exercise without promoting the belief that exercise will yield weight loss. (C) 2015 Elsevier Inc. All rights reserved. C1 [Thomas, Diana M.] Montclair State Univ, Ctr Quantitat Obes Res, Montclair, NJ 07043 USA. [Kyle, Theodore K.] ConscienHealth, Pittsburgh, PA USA. [Kyle, Theodore K.] Obes Act Coalit, Tampa, FL USA. [Stanford, Fatima Cody] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Weight Ctr, Boston, MA USA. RP Thomas, DM (reprint author), Montclair State Univ, Ctr Quantitat Obes Res, Montclair, NJ 07043 USA. EM thomasdia@mail.montclair.edu OI Stanford, Fatima/0000-0003-4616-533X FU ConscienHealth FX We would like to acknowledge ConscienHealth for funding this study. NR 17 TC 3 Z9 3 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD DEC PY 2015 VL 81 BP 357 EP 360 DI 10.1016/j.ypmed.2015.10.001 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DB3OP UT WOS:000368421300055 PM 26500086 ER PT J AU Borstelmann, NA Rosenberg, SM Ruddy, KJ Tamimi, RM Gelber, S Schapira, L Come, S Borges, V Morgan, E Partridge, AH AF Borstelmann, Nancy A. Rosenberg, Shoshana M. Ruddy, Kathryn J. Tamimi, Rulla M. Gelber, Shari Schapira, Lidia Come, Steven Borges, Virginia Morgan, Evan Partridge, Ann H. TI Partner support and anxiety in young women with breast cancer SO PSYCHO-ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; SOCIAL SUPPORT; PSYCHOLOGICAL DISTRESS; LONG-TERM; SURVIVORS; ADJUSTMENT; STRESS; INTERVENTION; CHEMOTHERAPY; DIAGNOSIS AB Objective: Using a large prospective cohort of women age 40 or younger diagnosed with breast cancer, we examined the relationship between perceived partner support and anxiety. Methods: Six hundred seventy-five young women with breast cancer Stages I-III, median age 36, completed a self-report baseline questionnaire. Perceived partner support was assessed using items extracted from the marital subscale of the Cancer Rehabilitation Evaluation System; generalized social support was assessed with the Medical Outcomes Study-Social Support Survey. Anxiety was measured using the anxiety subscale of the Hospital Anxiety and Depression Scale. Multivariable logistic regression analyses evaluated the association between partner support, other sociodemographic factors, and anxiety. Results: Mean age at diagnosis was 35.4 years. Fourteen percent of the women were not partnered, and among those who were partnered or in a significant relationship, 20% were categorized as unsupported. In univariate and multivariable analysis adjusting for sociodemographic factors, women in an unsupported-partnered relationship had higher odds of anxiety symptoms compared with women in a supported-partnered relationship. Young age and being financially insecure were also both independently associated with anxiety. Conclusions: Our findings suggest that partner support may play a key role in a young woman's adjustment to a serious stressor such as breast cancer. In addition, younger age increases vulnerability to anxiety as does struggling with finances. Because supportive efforts of a partner have potential to protect against the impact of stress, interventions to enhance partner support and reduce anxiety might be beneficial to address challenges experienced as a couple in this setting. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Rosenberg, Shoshana M.; Tamimi, Rulla M.; Schapira, Lidia; Come, Steven; Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Borstelmann, Nancy A.; Rosenberg, Shoshana M.; Gelber, Shari; Morgan, Evan; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Borstelmann, Nancy A.] Simmons Coll, Sch Social Work, Boston, MA 02115 USA. [Ruddy, Kathryn J.] Mayo Clin, Rochester, MN USA. [Tamimi, Rulla M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Come, Steven] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Borges, Virginia] Univ Colorado, Denver, CO 80202 USA. RP Partridge, AH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ann_partridge@dfci.harvard.edu NR 39 TC 1 Z9 1 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD DEC PY 2015 VL 24 IS 12 BP 1679 EP 1685 DI 10.1002/pon.3780 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DB3TP UT WOS:000368435000012 PM 25765893 ER PT J AU Newby, TA Graff, JN Ganzini, LK McDonagh, MS AF Newby, Timothy A. Graff, Julie N. Ganzini, Linda K. McDonagh, Marian S. TI Interventions that may reduce depressive symptoms among prostate cancer patients: a systematic review and meta-analysis SO PSYCHO-ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; ANDROGEN DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY; MEN; DIAGNOSIS; IMPACT; EFFICACY; PROGRAM; STYLE AB Objective: Prostate cancer patients are at increased risk of depression yet there is no standard intervention to address this. The purpose of this meta-analysis is to examine the efficacy of interventions in reducing depressive symptoms in men with prostate cancer. Methods: Searches for studies were conducted in four databases and by hand. Randomized controlled trials of any intervention relative to control for depression in prostate cancer patients at any stage of their cancer treatment were included. Results: We identified 11 studies that randomized men with prostate cancer to either an intervention meant to improve some aspect of quality of life or control and reported depressive symptoms scores before and after the intervention or control condition. Two of these were not used in our meta-analysis either for concerns about quality or for lack of depression scores. The interventions identified in the remaining nine articles were exercise (four), information (three), psychotherapy or peer support (three), massage therapy (one), and medication (one). Several publications included more than one type of intervention. A meta-analysis of all studies showed that an intervention of some types significantly improved depressive symptom scores relative to the control condition (improvement in depression score by -0.86 unit (95% CI: -1.42, -0.31)). Isolating the peer support/psychotherapy studies also showed significant improvement (improvement in depression score by -1.09 unit (95% CI: -2.05, -0.13)). Conclusion: Treatments to improve depressive symptoms in men with prostate cancer may be effective, with the best evidence supporting the use of peer support/psychotherapy. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Newby, Timothy A.; Graff, Julie N.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Graff, Julie N.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Div Hosp & Specialty Med, Portland, OR 97201 USA. [Ganzini, Linda K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci, Portland, OR USA. [Ganzini, Linda K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Ganzini, Linda K.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [McDonagh, Marian S.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Graff, JN (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,MC P3CHEMO, Portland, OR 97239 USA. EM graffj@ohsu.edu NR 31 TC 3 Z9 3 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD DEC PY 2015 VL 24 IS 12 BP 1686 EP 1693 DI 10.1002/pon.3781 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DB3TP UT WOS:000368435000013 PM 25753507 ER PT J AU Fujisawa, D Temel, JS Traeger, L Greer, JA Lennes, IT Mimura, M Pirl, WF AF Fujisawa, Daisuke Temel, Jennifer S. Traeger, Lara Greer, Joseph A. Lennes, Inga T. Mimura, Masaru Pirl, William F. TI Psychological factors at early stage of treatment as predictors of receiving chemotherapy at the end of life SO PSYCHO-ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; CARE NEAR-DEATH; CANCER-PATIENTS; PROSPECTIVE COHORT; BREAST-CANCER; ASSOCIATIONS; PREFERENCES; DEPRESSION; AGGRESSIVENESS; ANXIETY AB Introduction: Administration of chemotherapy in the last 14 days of life is a widely recognized indicator of poor end-of-life (EOL) care. The current study aimed to investigate predictors of this outcome, focusing on patients' self-reported psychological symptoms. Methods and Materials: This is a secondary analysis of a randomized controlled trial that examined the efficacy of early palliative care integrated with standard oncology practice in patients with metastatic non-small cell lung cancer (NSCLC). We analyzed associations between receipt of chemotherapy within 14 days of death and demographic, clinical, and quality-of-life variables in the 125 patients who received chemotherapy in the course of their illness and died during the 50-month follow-up. Results: Twenty-five patients (20%) received chemotherapy within the last 14 days of their life. Among demographic and clinical variables, only route of chemotherapy was significantly associated with receipt of chemotherapy within 14 days of death (oral 34.1% vs. intravenous (IV) 12.3%, p< 0.05). In the subsample of participants who received IV chemotherapy as their last regimen, greater anxiety and depression and lower quality of life in emotional, social, and existential domains were associated with greater likelihood of receiving chemotherapy at the EOL. These associations were not observed in patients who received oral chemotherapy as their last regimen. Conclusion: Anxiety, depression, and worse psychological quality of life at early stage of treatment may be associated with the receipt of IV chemotherapy at the EOL. Further research is needed to examine how these factors might influence decision-making about the discontinuation of chemotherapy at the EOL. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Fujisawa, Daisuke; Temel, Jennifer S.; Traeger, Lara; Greer, Joseph A.; Lennes, Inga T.; Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Fujisawa, Daisuke; Mimura, Masaru] Keio Univ, Dept Neuropsychiat, Sch Med, Tokyo, Japan. RP Fujisawa, D (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.; Fujisawa, D (reprint author), Keio Univ, Dept Neuropsychiat, Sch Med, Tokyo, Japan.; Fujisawa, D (reprint author), Keio Univ, Dept Neuropsychiat, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo, Japan. EM dai_fujisawa@yahoo.co.jp NR 39 TC 0 Z9 0 U1 4 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD DEC PY 2015 VL 24 IS 12 BP 1731 EP 1737 DI 10.1002/pon.3840 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DB3TP UT WOS:000368435000019 PM 25959002 ER PT J AU Epstein, AS Shuk, E O'Reilly, EM Gary, KA Volandes, AE AF Epstein, A. S. Shuk, E. O'Reilly, E. M. Gary, K. A. Volandes, A. E. TI 'We have to discuss it': cancer patients' advance care planning impressions following educational information about cardiopulmonary resuscitation SO PSYCHO-ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OF-LIFE DISCUSSIONS; ONCOLOGY PATIENTS; POOR-PROGNOSIS; HEALTH-CARE; VIDEO; COMMUNICATION; PHYSICIANS; END; PREFERENCES AB Objective: Most cancer patients desire information about care options at the end of life, including cardiopulmonary resuscitation (CPR). Communicating such care options can be challenging and is part of advance care planning (ACP). Our prior studies with video educational media produced data on patients' categoric preferences (yes/no/unsure) for CPR; however, the thematic underpinnings of these educated preferences in patients treated for advanced cancer aren't well known. Methods: Qualitative thematic content analysis of participants' responses in a randomized trial of an educational video (V) or narrative (N) about CPR in patients with advanced gastrointestinal cancers. Responses were independently coded and categorized for thematic content by two reviewers. Results: Of 54 study participants, 26 total (41% of V arm, 56% of N arm) articulated questions, comments, or both. Reviewer analyses demonstrated thematic consensus and resulted in seven distinct themes listed in decreasing order of prevalence: (a) ACP should be started early; (b) educational information about CPR affirmed participants' existing beliefs/knowledge/values about advanced illness; (c) participants were apprehensive about ACP but wanted to discuss it; (d) gaps in knowledge about ACP emerged; (e) CPR information was helpful/acceptable; (f) physicians should be involved in ACP; and (g) medical questions about critical illness arose. Conclusions: Findings identified that while sometimes difficult to discuss, advance care planning is desired, deemed helpful, and ideally begun early by clinicians, and that video education is an appropriate and affirming initiator of discussions. These themes are incorporated into our ongoing research on cancer patient-specific values and education about care options. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Epstein, A. S.; O'Reilly, E. M.; Gary, K. A.] Mem Sloan Kettering Canc Ctr, Dept Med, Gastrointestinal Med Oncol Serv, 1275 York Ave, New York, NY 10021 USA. [Shuk, E.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 1275 York Ave, New York, NY 10021 USA. [Volandes, A. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Epstein, AS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Gastrointestinal Med Oncol Serv, 1275 York Ave, New York, NY 10021 USA.; Epstein, AS (reprint author), Dept Med, Gastrointestinal Med Oncol Serv, 300 E 66th St,Room 1013, New York, NY 10065 USA. EM epsteina@mskcc.org FU American Society of Clinical Oncology FX This work was supported by the American Society of Clinical Oncology 2010 Young Investigator Award to Andrew S. Epstein, MD NR 40 TC 2 Z9 2 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD DEC PY 2015 VL 24 IS 12 BP 1767 EP 1773 DI 10.1002/pon.3786 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DB3TP UT WOS:000368435000024 PM 25708116 ER PT J AU Smith, KB Iezzoni, LI Kilbridge, KL Pajolek, H Colson, KE Park, ER AF Smith, Kelly B. Iezzoni, Lisa I. Kilbridge, Kerry L. Pajolek, Hannah Colson, Katherine Ellicott Park, Elyse R. TI Body image perceptions among women with pre-existing physical disability who developed breast cancer: a qualitative exploration SO PSYCHO-ONCOLOGY LA English DT Letter ID DIAGNOSIS; CARE C1 [Smith, Kelly B.] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. [Iezzoni, Lisa I.; Pajolek, Hannah; Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Kilbridge, Kerry L.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Pajolek, Hannah; Park, Elyse R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Colson, Katherine Ellicott] Univ Calif Berkeley, Dept Epidemiol, Berkeley, CA 94720 USA. RP Smith, KB (reprint author), Gordon & Leslie Diamond Hlth Care Ctr, 2775 Laurel St,6th Floor, Vancouver, BC V5Z 1M9, Canada. EM Kelly.Smith@vch.ca FU Michael Smith Foundation for Health Research; National Cancer Institute [NCI R21 CA122130] FX Kelly B. Smith is supported by a Post-Doctoral Fellowship Trainee Award from the Michael Smith Foundation for Health Research. This research was funded by the National Cancer Institute, grant no. NCI R21 CA122130. NR 11 TC 0 Z9 0 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD DEC PY 2015 VL 24 IS 12 BP 1826 EP 1829 DI 10.1002/pon.3791 PG 4 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DB3TP UT WOS:000368435000032 PM 25976233 ER PT J AU Li, Y Yin, J Li, T Huang, S Yan, H Leavenworth, J Wang, X AF Li Yang Yin Jie Li Ting Huang Shan Yan Han Leavenworth JianMei Wang Xi TI NK cell-based cancer immunotherapy: from basic biology to clinical application SO SCIENCE CHINA-LIFE SCIENCES LA English DT Review DE NK cell; cancer; cytokine infusion; adoptive transfer; immunotherapy ID NATURAL-KILLER-CELLS; ACUTE MYELOID-LEUKEMIA; HUMAN CYTOMEGALOVIRUS-INFECTION; APOPTOSIS-INDUCING LIGAND; COLONY-STIMULATING FACTOR; LOW-DOSE INTERLEUKIN-2; RELAPSE RISK EVIDENCE; PHASE-I TRIAL; RECOMBINANT INTERLEUKIN-2; BREAST-CANCER AB Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy. C1 [Li Yang; Yin Jie; Li Ting; Huang Shan; Yan Han; Wang Xi] Tianjin Med Univ, Dept Cell Biol,Tianjin Key Lab Med Epigenet, Collaborat Innovat Ctr Tianjin Med Epigenet 2011, Lab Epigenet Dev & Tumorigenesis,Tianjin Res Ctr, Tianjin 300070, Peoples R China. [Leavenworth JianMei] Harvard Univ, Sch Med, Dept Canc Immunol & Virol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leavenworth JianMei] Harvard Univ, Div Immunol, Dept Microbiol & Immunobiol, Sch Med, Boston, MA 02115 USA. RP Li, Y (reprint author), Tianjin Med Univ, Dept Cell Biol,Tianjin Key Lab Med Epigenet, Collaborat Innovat Ctr Tianjin Med Epigenet 2011, Lab Epigenet Dev & Tumorigenesis,Tianjin Res Ctr, Tianjin 300070, Peoples R China. EM Jianmei_Leavenworth@dfci.harvard.edu; wangxi@tmu.edu.cn FU Ministry of Science and Technology of China [2014CB910104]; National Natural Science Foundation of China [81171899, 81372230]; Claudia Adams Barr Program for Innovative Cancer Research FX We are grateful to Dr. Jonathan D. Leavenworth from Southern Illinois University School of Medicine for language editing. We thank Drs. Jeffrey S. Miller from University of Minnesota, Xudong Wu from Tianjin Medical University and members of the laboratory of X.W. for discussions and comments. This work was supported by grants from the Ministry of Science and Technology of China (2014CB910104) and the National Natural Science Foundation of China (81171899, 81372230), and the Claudia Adams Barr Program for Innovative Cancer Research. NR 131 TC 7 Z9 7 U1 4 U2 14 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7305 EI 1869-1889 J9 SCI CHINA LIFE SCI JI Sci. China-Life Sci. PD DEC PY 2015 VL 58 IS 12 BP 1233 EP 1245 DI 10.1007/s11427-015-4970-9 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DB5BX UT WOS:000368529300007 PM 26588912 ER PT J AU Jahn, B Rochau, U Kurzthaler, C Hubalek, M Miksad, R Sroczynski, G Paulden, M Kluibenschadl, M Krahn, M Siebert, U AF Jahn, B. Rochau, U. Kurzthaler, C. Hubalek, M. Miksad, R. Sroczynski, G. Paulden, M. Kluibenschaedl, M. Krahn, M. Siebert, U. TI Cost effectiveness of personalized treatment in women with early breast cancer: the application of OncotypeDX and Adjuvant! Online to guide adjuvant chemotherapy in Austria SO SPRINGERPLUS LA English DT Article DE 21-Gene assay; Genetic testing; Adjuvant! Online; Cost effectiveness; Decision-analytic model; Discrete event simulation ID MODEL PARAMETER-ESTIMATION; DISCRETE-EVENT SIMULATION; RT-PCR ASSAY; GENE-EXPRESSION; ECONOMIC-EVALUATION; RECURRENCE; DECISIONS; IMPACT; UNCERTAINTY; VALIDATION AB A Breast Cancer Outcomes model was developed at the ONCOTYROL research center to evaluate personalized test-treatment strategies in Austria. The goal was to evaluate the cost-effectiveness of a new 21-gene assay (ODX) when used in conjunction with the Adjuvant! Online (AO) decision aid to support personalized decisions about use of adjuvant chemotherapy in early-stage breast cancer patients in Austria. We applied a validated discrete-event-simulation model to a hypothetical cohort of 50 years old women over a lifetime horizon. The test-treatment strategies of interest were defined using three-letter acronyms. The first (second, third) letter indicates whether patients with a low (intermediate, high) risk according to AO were tested using ODX (Y yes, N no). The main outcomes were life-years gained, quality-adjusted life-years (QALYs), costs and cost effectiveness. Robustness of the results was tested in sensitivity analyses. Results were compared to a Canadian analysis conducted by the Toronto Health Economics and Technology Assessment Collaborative (THETA). Five of eight strategies were dominated (i.e., more costly and less effective: NNY, NYN, YNN, YNY, YYN). The base-case analysis shows that YYY (ODX provided to all patients) is the most effective strategy and is cost effective with an incremental cost-effectiveness ratio of 15,700 EUR per QALY gained. These results are sensitive to changes in the probabilities of distant recurrence, age and costs of chemotherapy. The results of the base-case analysis were comparable to the THETA results. Based on our analyses, using ODX in addition to AO is effective and cost effective in all women in Austria. The development of future genetic tests may require alternative or additional test-treatment strategies to be evaluated. C1 [Jahn, B.; Rochau, U.; Kurzthaler, C.; Sroczynski, G.; Kluibenschaedl, M.; Siebert, U.] UMIT Univ Hlth Sci Med Informat & Technol, Hlth Serv Res & Hlth Technol Assessment, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth,Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol IT, Austria. [Jahn, B.; Rochau, U.; Kurzthaler, C.; Sroczynski, G.; Kluibenschaedl, M.; Siebert, U.] ONCOTYROI Ctr Personalized Canc Med, Div Publ Hlth Decis Modelling Hlth Technol Assess, Innsbruck, Austria. [Hubalek, M.] Med Univ Innsbruck, Dept Obstet & Gynaecol, A-6020 Innsbruck, Austria. [Miksad, R.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Paulden, M.; Krahn, M.] Univ Toronto, Toronto Hlth Econ & Technol Assessment THETA Coll, Toronto, ON, Canada. [Paulden, M.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. [Siebert, U.] Harvard Univ, TH Chan Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02115 USA. [Siebert, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Siebert, U (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Hlth Serv Res & Hlth Technol Assessment, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth,Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol IT, Austria. EM uwe.siebert@umit.at RI Paulden, Michael/E-2061-2016; OI Krahn, Murray/0000-0001-5836-397X FU COMET Center ONCOTYROL - Austrian Federal Ministries BMVIT/BMWFJ (via FFG); Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT) FX Financial support for this study was provided in part by the COMET Center ONCOTYROL, which is funded by the Austrian Federal Ministries BMVIT/BMWFJ (via FFG) and the Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT). The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. The following authors were/are employed by the sponsor: B. Jahn, U. Rochau, C. Kurzthaler, M. Kluibenschadl, G. Sroczynski, U. Siebert. NR 50 TC 0 Z9 0 U1 4 U2 8 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PD DEC 1 PY 2015 VL 4 AR 752 DI 10.1186/s40064-015-1440-6 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB7RC UT WOS:000368712400010 PM 26693110 ER PT J AU Tucker, RP Crowley, KJ Davidson, CL Gutierrez, PM AF Tucker, Raymond P. Crowley, Kevin J. Davidson, Collin L. Gutierrez, Peter M. TI Risk Factors, Warning Signs, and Drivers of Suicide: What Are They, How Do They Differ, and Why Does It Matter? SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID PERCEIVED BURDENSOMENESS; BEHAVIOR; MODEL; INTERNET; CARE AB Research investigating suicide attempts and deaths by suicide has yielded many specific risk factors and warning signs for future suicidal behaviors. Yet, even though these variables are each valuable for suicide prevention efforts, they may be limited in their applicability to clinical practice. The differences among risk factors, warning signs, and "drivers," which are person-specific variables that lead individuals to desire death by suicide, are highlighted. The scarce evidence on drivers is described and specific recommendations for conducting future drivers-focused research and targeting them in clinical practice are suggested. C1 [Tucker, Raymond P.] Oklahoma State Univ, Dept Psychol, 116 North Murray Hall, Stillwater, OK 74078 USA. [Crowley, Kevin J.] Capital Inst Cognit Therapy, Washington, DC USA. [Davidson, Collin L.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Gutierrez, Peter M.] Denver VA Med Ctr, VA VISN MIRECC 19, Denver, CO USA. [Gutierrez, Peter M.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. RP Tucker, RP (reprint author), Oklahoma State Univ, Dept Psychol, 116 North Murray Hall, Stillwater, OK 74078 USA. EM raymopt@okstate.edu NR 43 TC 4 Z9 4 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD DEC PY 2015 VL 45 IS 6 BP 679 EP 689 DI 10.1111/sltb.12161 PG 11 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DB3VS UT WOS:000368441700003 PM 25858332 ER PT J AU Kanzaria, HK McCabe, AM Meisel, ZM LeBlanc, A Schaffer, JT Bellolio, MF Vaughan, W Merck, LH Applegate, KE Hollander, JE Grudzen, CR Mills, AM Carpenter, CR Hess, EP AF Kanzaria, Hemal K. McCabe, Aileen M. Meisel, Zachary M. LeBlanc, Annie Schaffer, Jason T. Bellolio, M. Fernanda Vaughan, William Merck, Lisa H. Applegate, Kimberly E. Hollander, Judd E. Grudzen, Corita R. Mills, Angela M. Carpenter, Christopher R. Hess, Erik P. TI Advancing Patient-centered Outcomes in Emergency Diagnostic Imaging: A Research Agenda SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Academic-Emergency-Medicine (AEM) Consensus Conference CY MAY 12, 2015 CL San Diego, CA SP Acad Emergency Med ID SHARED DECISION-MAKING; HEALTH-CARE DECISIONS; COMPUTED-TOMOGRAPHY; DEPARTMENT UTILIZATION; KNOWLEDGE TRANSLATION; PHYSICIAN PERCEPTIONS; RISK COMMUNICATION; REPORTED OUTCOMES; RANDOMIZED-TRIAL; INVOLVE PATIENTS AB Diagnostic imaging is integral to the evaluation of many emergency department (ED) patients. However, relatively little effort has been devoted to patient-centered outcomes research (PCOR) in emergency diagnostic imaging. This article provides background on this topic and the conclusions of the 2015 Academic Emergency Medicine consensus conference PCOR work group regarding "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The goal was to determine a prioritized research agenda to establish which outcomes related to emergency diagnostic imaging are most important to patients, caregivers, and other key stakeholders and which methods will most optimally engage patients in the decision to undergo imaging. Case vignettes are used to emphasize these concepts as they relate to a patient's decision to seek care at an ED and the care received there. The authors discuss applicable research methods and approaches such as shared decision-making that could facilitate better integration of patient-centered outcomes and patient-reported outcomes into decisions regarding emergency diagnostic imaging. Finally, based on a modified Delphi process involving members of the PCOR work group, prioritized research questions are proposed to advance the science of patient-centered outcomes in ED diagnostic imaging. (C) 2015 by the Society for Academic Emergency Medicine C1 [Kanzaria, Hemal K.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Kanzaria, Hemal K.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [McCabe, Aileen M.] Univ Penn, Dept Emergency Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schaffer, Jason T.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Bellolio, M. Fernanda; Hess, Erik P.] Mayo Clin, Dept Emergency Med, Rochester, MN 55905 USA. [Merck, Lisa H.] Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Hollander, Judd E.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Emergency Med, Philadelphia, PA 19107 USA. [Grudzen, Corita R.] NYU, Dept Emergency Med, New York, NY USA. [Kanzaria, Hemal K.] Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. [Kanzaria, Hemal K.] US Dept Vet Affairs, Los Angeles, CA USA. [Kanzaria, Hemal K.] RAND Hlth, Santa Monica, CA USA. [McCabe, Aileen M.] Royal Coll Surgeons Ireland, Emergency Care Res Unit, Div Populat Hlth Sci, Dublin 2, Ireland. [Meisel, Zachary M.] Univ Penn, Perelman Sch Med, Ctr Emergency Care Policy & Res, Philadelphia, PA 19104 USA. [Meisel, Zachary M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [LeBlanc, Annie] Mayo Clin, Dept Hlth Sci Res, Knowledge & Evaluat Res Unit, Div Hlth Care Policy & Res, Rochester, MN USA. [Bellolio, M. Fernanda; Hess, Erik P.] Mayo Clin, Robert D & Patricia E Kern Ctr Sci Hlth Care Deli, Rochester, MN USA. [Merck, Lisa H.] Brown Univ, Warren Alpert Med Sch, Dept Diagnost Imaging, Providence, RI 02912 USA. [Applegate, Kimberly E.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA USA. [Hollander, Judd E.] Natl Acad Ctr Telehlth, Philadelphia, PA USA. [Grudzen, Corita R.] NYU, Dept Populat Hlth, New York, NY USA. [Carpenter, Christopher R.] Washington Univ, Sch Med, Div Emergency Med, St Louis, MO USA. [Carpenter, Christopher R.] Washington Univ, Emergency Care Res Core, St Louis, MO USA. [Hess, Erik P.] Mayo Clin, Dept Hlth Sci Res, Div Healthcare Policy Res, Knowledge & Evaluat Res Unit, Rochester, MN USA. RP Hess, EP (reprint author), Mayo Clin, Dept Emergency Med, Rochester, MN 55905 USA. EM hess.erik@mayo.edu RI Carpenter, Christopher/E-3720-2013; OI Carpenter, Christopher/0000-0002-2603-7157; Grudzen, Corita/0000-0003-3039-8497 FU Agency for Healthcare Research and Quality (AHRQ) [1R13HS023498-01]; National Institute of Biomedical Imaging and Bioengineering [1 R13 EB 019813-01] FX Funding for this conference was made possible (in part) by grant number 1R13HS023498-01 from the Agency for Healthcare Research and Quality (AHRQ) and grant number 1 R13 EB 019813-01 from the National Institute of Biomedical Imaging and Bioengineering. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. NR 72 TC 10 Z9 10 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2015 VL 22 IS 12 SI SI BP 1435 EP 1446 DI 10.1111/acem.12832 PG 12 WC Emergency Medicine SC Emergency Medicine GA DA5FP UT WOS:000367828900010 PM 26574729 ER PT J AU Probst, MA Dayan, PS Raja, AS Slovis, BH Yadav, K Lam, SH Shapiro, JS Farris, C Babcock, CI Griffey, RT Robey, TE Fortin, EM Johnson, JO Chong, ST Davenport, M Grigat, DW Lang, EL AF Probst, Marc A. Dayan, Peter S. Raja, Ali S. Slovis, Benjamin H. Yadav, Kabir Lam, Samuel H. Shapiro, Jason S. Farris, Coreen Babcock, Charlene I. Griffey, Richard T. Robey, Thomas E. Fortin, Emily M. Johnson, Jamlik O. Chong, Suzanne T. Davenport, Moira Grigat, Daniel W. Lang, Eddy L. TI Knowledge Translation and Barriers to Imaging Optimization in the Emergency Department: A Research Agenda SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Academic-Emergency-Medicine (AEM) Consensus Conference CY MAY 12, 2015 CL San Diego, CA SP Acad Emergency Med ID CLINICAL DECISION-SUPPORT; HEALTH INFORMATION EXCHANGE; MINOR HEAD-INJURY; THEORETICAL DOMAINS FRAMEWORK; COMPUTED-TOMOGRAPHY USE; TRAUMATIC BRAIN-INJURY; PHYSICIAN ORDER ENTRY; C-SPINE RULE; PRACTICE GUIDELINES; PRIMARY-CARE AB Researchers have attempted to optimize imaging utilization by describing which clinical variables are more predictive of acute disease and, conversely, what combination of variables can obviate the need for imaging. These results are then used to develop evidence-based clinical pathways, clinical decision instruments, and clinical practice guidelines. Despite the validation of these results in subsequent studies, with some demonstrating improved outcomes, their actual use is often limited. This article outlines a research agenda to promote the dissemination and implementation (also known as knowledge translation) of evidence-based interventions for emergency department (ED) imaging, i.e., clinical pathways, clinical decision instruments, and clinical practice guidelines. We convened a multidisciplinary group of stakeholders and held online and telephone discussions over a 6-month period culminating in an in-person meeting at the 2015 Academic Emergency Medicine consensus conference. We identified the following four overarching research questions: 1) what determinants (barriers and facilitators) influence emergency physicians' use of evidence-based interventions when ordering imaging in the ED; 2) what implementation strategies at the institutional level can improve the use of evidence-based interventions for ED imaging; 3) what interventions at the health care policy level can facilitate the adoption of evidence-based interventions for ED imaging; and 4) how can health information technology, including electronic health records, clinical decision support, and health information exchanges, be used to increase awareness, use, and adherence to evidence-based interventions for ED imaging? Advancing research that addresses these questions will provide valuable information as to how we can use evidence-based interventions to optimize imaging utilization and ultimately improve patient care. (C) 2015 by the Society for Academic Emergency Medicine C1 [Probst, Marc A.; Slovis, Benjamin H.; Shapiro, Jason S.] Icahn Sch Med Mt Sinai, Dept Emergency Med, New York, NY 10029 USA. [Raja, Ali S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Yadav, Kabir] Univ Calif Los Angeles, Los Angeles Sch Med, Dept Emergency Med, Los Angeles, CA USA. [Lam, Samuel H.] Advocate Christ Med Ctr, Dept Emergency Med, Oak Lawn, IL USA. [Babcock, Charlene I.] St John Hosp & Med Ctr, Dept Emergency Med, Detroit, MI USA. [Griffey, Richard T.] Washington Univ, Sch Med, Dept Emergency Med, St Louis, MO USA. [Robey, Thomas E.] Yale Univ, Waterbury Hosp, Dept Emergency Med, New Haven, CT USA. [Davenport, Moira] Allegheny Gen Hosp, Dept Emergency Med, Pittsburgh, PA 15212 USA. [Lang, Eddy L.] Univ Calgary, Dept Emergency Med, Calgary, AB, Canada. [Dayan, Peter S.] Columbia Univ Coll Phys & Surg, Dept Pediat, Div Emergency Med, New York, NY 10032 USA. [Farris, Coreen] RAND Corp, Santa Monica, CA USA. [Farris, Coreen; Fortin, Emily M.] Cent Michigan Univ, Coll Med, Mt Pleasant, MI 48859 USA. [Johnson, Jamlik O.] Emory Healthcare, Dept Radiol, Atlanta, GA USA. [Chong, Suzanne T.] Univ Michigan Hlth Syst, Dept Radiol, Ann Arbor, MI USA. [Grigat, Daniel W.] Emergency Strateg Clin Network, Alberta Hlth Serv, Calgary, AB, Canada. RP Probst, MA (reprint author), Icahn Sch Med Mt Sinai, Dept Emergency Med, New York, NY 10029 USA. EM mprobst@gmail.com FU Agency for Healthcare Research and Quality (AHRQ) [1R13HS023498-01]; National Institute of Biomedical Imaging and Bioengineering [1 R13 EB 019813-01] FX Funding for this conference was made possible (in part) by grant number 1R13HS023498-01 from the Agency for Healthcare Research and Quality (AHRQ) and grant number 1 R13 EB 019813-01 from the National Institute of Biomedical Imaging and Bioengineering. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. NR 96 TC 6 Z9 6 U1 9 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2015 VL 22 IS 12 SI SI BP 1455 EP 1464 DI 10.1111/acem.12830 PG 10 WC Emergency Medicine SC Emergency Medicine GA DA5FP UT WOS:000367828900012 PM 26568148 ER PT J AU Moore, CL Broder, J Gunn, ML Bhargavan-Chatfield, M Cody, D Cullison, K Daniels, B Gans, B Hall, MK Gaines, BA Goldman, S Heil, J Liu, R Marin, JR Melnick, ER Novelline, RA Pare, J Repplinger, MD Taylor, RA Sodickson, AD AF Moore, Christopher L. Broder, Joshua Gunn, Martin L. Bhargavan-Chatfield, Mythreyi Cody, Dianna Cullison, Kevin Daniels, Brock Gans, Bradley Hall, M. Kennedy Gaines, Barbara A. Goldman, Sarah Heil, John Liu, Rachel Marin, Jennifer R. Melnick, Edward R. Novelline, Robert A. Pare, Joseph Repplinger, Michael D. Taylor, Richard A. Sodickson, Aaron D. TI Comparative Effectiveness Research: Alternatives to "Traditional" Computed Tomography Use in the Acute Care Setting SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Academic-Emergency-Medicine (AEM) Consensus Conference CY MAY 12, 2015 CL San Diego, CA SP Acad Emergency Med ID ACUTE ABDOMINAL-PAIN; EMERGENCY-DEPARTMENT; TRAUMA PATIENTS; RADIATION-EXPOSURE; BODY CT; SUSPECTED APPENDICITIS; BLUNT TRAUMA; CANCER-RISK; HEAD-INJURY; METAANALYSIS AB Computed tomography (CT) scanning is an essential diagnostic tool and has revolutionized care of patients in the acute care setting. However, there is widespread agreement that overutilization of CT, where benefits do not exceed possible costs or harms, is occurring. The goal was to seek consensus in identifying and prioritizing research questions and themes that involve the comparative effectiveness of "traditional" CT use versus alternative diagnostic strategies in the acute care setting. A modified Delphi technique was used that included input from emergency physicians, emergency radiologists, medical physicists, and an industry expert to achieve this. (C) 2015 by the Society for Academic Emergency Medicine C1 [Moore, Christopher L.; Liu, Rachel; Melnick, Edward R.; Pare, Joseph; Taylor, Richard A.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06520 USA. [Cullison, Kevin] Washington Univ, Dept Emergency Med, St Louis, MO USA. [Daniels, Brock] Univ Calif Davis, Dept Emergency Med, Davis, CA 95616 USA. [Hall, M. Kennedy] Univ Washington, Dept Emergency Med, Seattle, WA 98195 USA. [Goldman, Sarah] Jacobi Med Ctr, Dept Emergency Med, New York, NY USA. [Marin, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. [Marin, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Emergency Med, Pittsburgh, PA USA. [Repplinger, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Emergency Med, Madison, WI USA. [Repplinger, Michael D.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Broder, Joshua] Duke Univ, Dept Surg, Sect Emergency Med, Durham, NC USA. [Gans, Bradley] Ohio State Univ, Dept Radiol, Cleveland, OH USA. [Gunn, Martin L.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Novelline, Robert A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sodickson, Aaron D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Bhargavan-Chatfield, Mythreyi] Amer Coll Radiol, Reston, VA USA. [Cody, Dianna] Univ Texas Houston, Dept Imaging Phys, Houston, TX USA. [Gaines, Barbara A.] Univ Pittsburgh, Sch Med, Div Pediat Gen & Thorac Surg, Pittsburgh, PA USA. [Heil, John] Medint Holdings LLC, Dba Imalogix, King Of Prussia, PA USA. [Marin, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. RP Moore, CL (reprint author), Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06520 USA. EM Chris.moore@yale.edu OI Repplinger, Michael/0000-0002-6518-3907 FU Agency for Healthcare Research and Quality (AHRQ) [R18HS023778, 1R13HS023498-01]; Agency for Healthcare Research and Quality [R13HS023498-01]; Siemens Healthcare; Philips Healthcare; National Institute of Biomedical Imaging and Bioengineering [1 R13 EB 019813-01] FX Dr. Moore is supported by a grant from the Agency for Healthcare Research and Quality (AHRQ) entitled "Minimizing unnecessary irradiation from renal colic CT scans in the United States" (R18HS023778). Dr. Moore, an associate editor for this journal, had no role in the peer-review process or publication decision for this paper. John Heil is CEO of Imalogix Inc. Dr. Marin was supported by the Agency for Healthcare Research and Quality (R13HS023498-01), receives support as teaching faculty for 3rd Rock Ultrasound, LLC, and has served as a consultant for Venaxis, Inc. Dr. Sodickson is partially funded by a research grant from Siemens Healthcare. Dr. Gunn receives research support from Philips Healthcare and is the Medical Advisor for Transformative Med.; Funding for this conference was made possible (in part) by grant number 1R13HS023498-01 from the Agency for Healthcare Research and Quality (AHRQ) and grant number 1 R13 EB 019813-01 from the National Institute of Biomedical Imaging and Bioengineering. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. NR 63 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2015 VL 22 IS 12 SI SI BP 1465 EP 1473 DI 10.1111/acem.12831 PG 9 WC Emergency Medicine SC Emergency Medicine GA DA5FP UT WOS:000367828900013 PM 26576033 ER PT J AU Maughan, BC Baren, JM Shea, JA Merchant, RM AF Maughan, Brandon C. Baren, Jill M. Shea, Judy A. Merchant, Raina M. TI Choosing Wisely in Emergency Medicine: A National Survey of Emergency Medicine Academic Chairs and Division Chiefs SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Academic-Emergency-Medicine (AEM) Consensus Conference CY MAY 12, 2015 CL San Diego, CA SP Acad Emergency Med ID CARE; IMPROVE; LIST AB Objectives: The Choosing Wisely campaign was launched in 2011 to promote stewardship of medical resources by encouraging patients and physicians to speak with each other regarding the appropriateness of common tests and procedures. Medical societies including the American College of Emergency Physicians (ACEP) have developed lists of potentially low-value practices for their members to address with patients. No research has described the awareness or attitudes of emergency physicians (EPs) regarding the Choosing Wisely campaign. The study objective was to assess these beliefs among leaders of academic departments of emergency medicine (EM). Methods: This was a Web-based survey of emergency department (ED) chairs and division chiefs at institutions with allopathic EM residency programs. The survey examined awareness of Choosing Wisely, anticipated effects of the program, and discussions of Choosing Wisely with patients and professional colleagues. Participants also identified factors they associated with the use of potentially low-value services in the ED. Questions and answer scales were refined using iterative pilot testing with EPs and health services researchers. Results: Seventy-eight percent (105/134) of invited participants responded to the survey. Eighty percent of respondents were aware of Choosing Wisely. A majority of participants anticipate the program will decrease costs of care (72% of respondents) and use of ED diagnostic imaging (69%) but will have no effect on EP salaries (94%) or medical-legal risks (65%). Only 45% of chairs have ever addressed Choosing Wisely with patients, in contrast to 88 and 82% who have discussed it with faculty and residents, respectively. Consultant-requested tests were identified by 97% of residents as a potential contributor to low-value services in the ED. Conclusions: A substantial majority of academic EM leaders in our study were aware of Choosing Wisely, but only slightly more than half could recall any ACEP recommendations for the program. Respondents familiar with Choosing Wisely anticipated generally positive effects, but chairs reported only infrequently discussing Choosing Wisely with patients. Future research should identify potentially low-value tests requested by consultants and objectively measure the utility and cost of these tests among ED patient populations. (C) 2015 by the Society for Academic Emergency Medicine C1 [Maughan, Brandon C.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Maughan, Brandon C.; Baren, Jill M.; Merchant, Raina M.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Shea, Judy A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Maughan, Brandon C.; Shea, Judy A.; Merchant, Raina M.] Univ Penn, Perelman Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Maughan, BC (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM bmaughan@gmail.com FU University of Pennsylvania FX This study was specifically funded by an Eisenberg Scholar Research Grant from the University of Pennsylvania. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The authors have no potential conflicts of interest to disclose, in accordance with ICMJE guidelines. NR 10 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2015 VL 22 IS 12 SI SI BP 1506 EP 1510 DI 10.1111/acem.12821 PG 5 WC Emergency Medicine SC Emergency Medicine GA DA5FP UT WOS:000367828900018 PM 26568385 ER PT J AU Kohsaka, S Miyata, H Ueda, I Masoudi, FA Peterson, ED Maekawa, Y Kawamura, A Fukuda, K Roe, MT Rumsfeld, JS AF Kohsaka, Shun Miyata, Hiroaki Ueda, Ikuko Masoudi, Frederick A. Peterson, Eric D. Maekawa, Yuichiro Kawamura, Akio Fukuda, Keiichi Roe, Matthew T. Rumsfeld, John S. CA JCD-KiCS NCDR TI An international comparison of patients undergoing percutaneous coronary intervention: A collaborative study of the National Cardiovascular Data Registry (NCDR) and Japan Cardiovascular Database-Keio interhospital Cardiovascular Studies (JCD-KiCS) SO AMERICAN HEART JOURNAL LA English DT Article ID IN-HOSPITAL OUTCOMES; MYOCARDIAL-INFARCTION; RISK; IMPACT; MODEL AB Background Details on Japanese patients undergoing percutaneous coronary intervention (PCI) and how they compare to US patients remain unclear. Furthermore, the application of US risk models has not been evaluated internationally. Methods The JCD-KiCS, a multicenter registry of consecutive PCI patients, was launched in 2008, with variables defined in accordance with the US NCDR. Patient and procedural characteristics from patients enrolled from 2008 to 2010 in the JCD-KiCS database (n = 9,941) and those in the NCDR (n = 732,345) were compared. The primary outcomes of this analysis were the hospital-level all-cause mortality and bleeding complications. The NCDR risk models for these 2 outcomes were evaluated in the Japanese data set; from the expected mortality and bleeding rates, the observed/expected ratios were calculated. Results The Japanese patients were older, with a higher proportion of men, diabetes, and smoking than the US patients. The Japanese patients also had a higher rate of complex lesions (26.1 vs 12.7% for bifurcation and 6.2% vs 3.2% for chronic total occlusions, all P < .001), longerprocedure time (29.7 +/- 21.5 vs 14.4 +/- 11.5 minutes, P < .001), and higher mortality (1.6% vs 0.9%, P < .001) and bleeding rates (2.9% vs 1.8%, P < .001) compared with US patients. The observed/expected ratios for mortality and bleeding were 0.921 and 0.467, respectively, in Japanese patients, and 1.002 and 0.981, respectively, for US patients. Conclusions The characteristics of patients undergoing PCI in clinical practice in Japan and the US differ substantially. The NCDR risk models applied well in Japanese patients for prediction of mortality, but not for bleeding, which tended to underestimate the risk. C1 [Kohsaka, Shun; Ueda, Ikuko; Maekawa, Yuichiro; Kawamura, Akio; Fukuda, Keiichi] Keio Univ, Tokyo, Japan. [Miyata, Hiroaki] Univ Tokyo, Tokyo, Japan. [Masoudi, Frederick A.; Rumsfeld, John S.] Univ Colorado, Aurora, CO USA. [Masoudi, Frederick A.; Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Peterson, Eric D.; Roe, Matthew T.] Duke Univ, Durham, NC USA. RP Kohsaka, S (reprint author), Keio Univ, Sch Med, Div Cardiol, 35 Shinanomachi, Tokyo, Japan. EM kohsaka@cpnet.med.keio.ac.jp OI Kohsaka, Shun/0000-0003-3779-2972 FU Japan Society for the Promotion of Science [25460630, 25460777]; National Cardiovascular Data Registry FX The present study was funded by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (25460630 and 25460777) and the National Cardiovascular Data Registry. The authors disclose no relationship with the industry. Dr Masoudi is a Senior Medical Officer, and Dr. Rumsfeld is the Chief Science Officer for the NCDR. NR 20 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD DEC PY 2015 VL 170 IS 6 BP 1077 EP 1085 DI 10.1016/j.ahj.2015.09.017 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB1GH UT WOS:000368255700003 PM 26678628 ER PT J AU Celano, CM Millstein, RA Bedoya, CA Healy, BC Roest, AM Huffman, JC AF Celano, Christopher M. Millstein, Rachel A. Bedoya, C. Andres Healy, Brian C. Roest, Annelieke M. Huffman, Jeff C. TI Association between anxiety and mortality in patients with coronary artery disease: A meta-analysis SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HEART-DISEASE; CARDIAC EVENTS; CARDIOVASCULAR EVENTS; PROGNOSTIC ASSOCIATION; RISK-FACTOR; FOLLOW-UP; CLINICAL-TRIALS; DEPRESSION; SYMPTOMS AB Background Depression and anxiety are common in patients with coronary artery disease (CAD). Although depression clearly has been associated with mortality in this population, the relationship between anxiety and mortality is less clear. Accordingly, we performed a series ofmeta-analyses to (1) examine the relationship between anxiety and mortality in patientswith established CAD and (2) determine if this relationship differs in patients with stable CAD compared to those who have just had an acute coronary syndrome (ACS). Methods and results Systematic literature searches identified 44 articles (totalN= 30,527) evaluating the prospective relationship between anxiety and mortality in individuals with established CAD. A series of 8 adjusted and unadjusted meta-analyses were performed to examine this relationship across all patients, with sensitivity analyses completed in post-ACS and stable CAD cohorts. In unadjusted analyses, anxiety was associated with a moderate increase in mortality risk (odds ratio 1.21 per SD increase in anxiety). However, when adjusting for covariates, nearly all associations became nonsignificant. In sensitivity analyses, anxiety was associated with an increased risk of poor outcomes in the stable CAD-but not post-ACS-cohort. Conclusions These analyses confirm that anxiety is associated with increased risk of mortality in patients with CAD; however, this relationship is not as strong as that of depression and may be explained partly by other clinical factors. If anxiety screening is performed, it should be performed during a period of clinical stability and should target anxiety disorders rather than anxiety symptoms alone. C1 [Celano, Christopher M.; Millstein, Rachel A.; Bedoya, C. Andres; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Celano, Christopher M.; Millstein, Rachel A.; Bedoya, C. Andres; Healy, Brian C.] Harvard Univ, Sch Med, Boston, MA USA. [Healy, Brian C.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Roest, Annelieke M.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands. RP Celano, CM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 11, Boston, MA 02114 USA. EM ccelano@partners.org FU NHLBI NIH HHS [R01 HL113272, K23 HL123607] NR 68 TC 5 Z9 8 U1 2 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD DEC PY 2015 VL 170 IS 6 BP 1105 EP 1115 DI 10.1016/j.ahj.2015.09.013 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB1GH UT WOS:000368255700007 PM 26678632 ER PT J AU Sacks, NC Ash, AS Ghosh, K Rosen, AK Wong, JB Rosen, AB AF Sacks, Naomi C. Ash, Arlene S. Ghosh, Kaushik Rosen, Amy K. Wong, John B. Rosen, Allison B. TI Trends in acute myocardial infarction hospitalizations: Are we seeing the whole picture? SO AMERICAN HEART JOURNAL LA English DT Article ID UNIVERSAL DEFINITION; HEART-FAILURE; UNITED-STATES; OUTCOMES; BENEFICIARIES; DIAGNOSIS; MORTALITY; DISEASE; UPDATE; STROKE AB Background Payers and policy makers rely on studies of trends in acute myocardial infarction (AMI) hospitalizations and spending that count only hospitalizations where the AMI is the principal discharge diagnosis. Hospitalizations with AMI coded as a secondary diagnosis are ignored. The effects of excluding these hospitalizations on estimates of trends are unknown. Methods Observational study of all AMI hospitalizations in Fee-for-Service Medicare beneficiaries 65 years and older, from 2002 through 2011. Results We studied 3,663,137 hospitalizations with any AMI discharge diagnosis over 288,873,509 beneficiary-years. Of these, 66% had AMI coded as principal (versus secondary). From 2002 to 2011, AMI hospitalization rates declined 24.5% (from 1,485 per 100,000 beneficiary-years in 2002 to 1,122 in 2011). Meanwhile, the proportion of these hospitalizations with a secondary AMI diagnosis increased from 28% to 40%; by 2011 these secondary AMI hospitalizations accounted for 43% of all expenditures for hospitalizations with AMI, or $2.8 billion. Major changes in comorbidities, principal diagnoses and mean costs for hospitalizations with a non-principal AMI diagnosis occurred in the 2006-2008 timeframe. Conclusions Current estimates of the burden of AMI ignore an increasingly large proportion of overall AMI hospitalizations and spending. Changes in the characteristics of hospitalizations that coincided with major payment and policy changes suggest that non-clinical factors affect AMI coding. Failing to consider all AMIs could inflate estimates of population health improvements, overestimate the value of AMI prevention and treatment and underestimate current and future AMI burden and expenditures. C1 [Sacks, Naomi C.; Ash, Arlene S.; Rosen, Amy K.; Rosen, Allison B.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01605 USA. [Ghosh, Kaushik; Rosen, Allison B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Rosen, Amy K.] VA Boston Healthcare Syst, CHOIR, Boston, MA USA. [Wong, John B.] Tufts Med Ctr, Dept Med, Div Clin Decis Making, Boston, MA USA. RP Sacks, NC (reprint author), Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, 368 Plantat St,AS9-1083, Worcester, MA 01605 USA. EM naomi.sacks@umassmed.edu FU NCATS NIH HHS [UL1 TR000161, UL1 TR001453] NR 27 TC 2 Z9 2 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD DEC PY 2015 VL 170 IS 6 BP 1211 EP 1219 DI 10.1016/j.ahj.2015.09.009 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB1GH UT WOS:000368255700018 PM 26678643 ER PT J AU Koutroumpakis, E Wu, BCU Bakker, OJ Dudekula, A Singh, VK Besselink, MG Yadav, D van Santvoort, HC Whitcomb, DC Gooszen, HG Banks, PA Papachristou, GI AF Koutroumpakis, Efstratios Wu, Bechien U. Bakker, Olaf J. Dudekula, Anwar Singh, Vikesh K. Besselink, Marc G. Yadav, Dhiraj van Santvoort, Hjalmar C. Whitcomb, David C. Gooszen, Hein G. Banks, Peter A. Papachristou, Georgios I. TI Admission Hematocrit and Rise in Blood Urea Nitrogen at 24 h Outperform other Laboratory Markers in Predicting Persistent Organ Failure and Pancreatic Necrosis in Acute Pancreatitis: A Post Hoc Analysis of Three Large Prospective Databases SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID DETERMINANT-BASED CLASSIFICATION; NECROTIZING PANCREATITIS; SERUM CREATININE; HEMOCONCENTRATION; MORTALITY; SEVERITY; MANAGEMENT; ACCURACY; ATLANTA AB OBJECTIVES: Predicting severe acute pancreatitis (AP) remains a challenge. The present study compares admission blood urea nitrogen (BUN), hematocrit, and creatinine, as well as changes in their levels over 24 h, aiming to determine the most accurate laboratory test for predicting persistent organ failure and pancreatic necrosis. METHODS: Clinical data of 1,612 AP patients, enrolled prospectively in three independent cohorts (University of Pittsburgh, Brigham and Women's Hospital, Dutch Pancreatitis Study Group), were abstracted. The predictive accuracy of the studied laboratories was measured using area under the receiver-operating characteristic curve (AUC) analysis. A pooled analysis was conducted to determine their impact on the risk for persistent organ failure and pancreatic necrosis. Finally, a classification tree was developed on the basis of the most accurate laboratory parameters. RESULTS: Admission hematocrit >= 44% and rise in BUN at 24 h were the most accurate in predicting persistent organ failure (AUC: 0.67 and 0.71, respectively) and pancreatic necrosis (0.66 and 0.67, respectively), outperforming the other laboratory parameters and the acute physiology and chronic health evaluation-II score. In a pooled analysis, admission hematocrit >= 44% and rise in BUN at 24 h were associated with an odds ratio of 3.54 and 5.84 for persistent organ failure, and 3.11 and 4.07, respectively, for pancreatic necrosis. In addition, the classification tree illustrated that when both admission hematocrit was >= 44% and BUN levels increased at 24 h, the rates of persistent organ failure and pancreatic necrosis reached 53.6% and 60.3%, respectively. CONCLUSIONS: Admission hematocrit >= 44% and rise in BUN at 24 h may be the optimal predictive tools in clinical practice among existing laboratory parameters and scoring systems. C1 [Koutroumpakis, Efstratios; Yadav, Dhiraj; Whitcomb, David C.; Papachristou, Georgios I.] Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Wu, Bechien U.; Singh, Vikesh K.; Banks, Peter A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Pancreat Dis,Div Gastroenterol, Boston, MA 02115 USA. [Bakker, Olaf J.; Besselink, Marc G.; van Santvoort, Hjalmar C.; Gooszen, Hein G.] Univ Med Ctr Utrecht, Dept Surg, Utrecht, Netherlands. [Dudekula, Anwar] Univ Pittsburgh, Med Ctr, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Dept Med, Div Gastroenterol, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, 200 Lothrop St,3rd Floor, Pittsburgh, PA 15213 USA. EM papachri@pitt.edu FU Veterans Affairs Merit Review Award [PRO00000496] FX The study was financially supported by a Veterans Affairs Merit Review Award (PRO00000496; PI: G.I.P.). The study design as well as the analysis and interpretation of the data were independent of the funding. NR 31 TC 7 Z9 7 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2015 VL 110 IS 12 BP 1707 EP 1716 DI 10.1038/ajg.2015.370 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB1NJ UT WOS:000368274700020 PM 26553208 ER PT J AU Laine, L Kaltenbach, T Barkun, A McQuaid, KR Subramanian, V Soetikno, R AF Laine, Loren Kaltenbach, Tonya Barkun, Alan McQuaid, Kenneth R. Subramanian, Venkataraman Soetikno, Roy TI ACG Guidelines on Management of PTEN-Hamartoma Tumor Syndrome: Does the Evidence Support so Much so Young? Response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID SURVEILLANCE C1 [Laine, Loren] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Laine, Loren] VA Connecticut Healthcare Syst, West Haven, CT USA. [Kaltenbach, Tonya; Soetikno, Roy] Vet Affair Palo Alto Healthcare Syst, Palo Alto, CA USA. [Kaltenbach, Tonya; Soetikno, Roy] Stanford Univ, Sch Med Affiliate, Palo Alto, CA 94304 USA. [Barkun, Alan] McGill Univ, Montreal, PQ, Canada. [McQuaid, Kenneth R.] UCSF, San Francisco, CA USA. [McQuaid, Kenneth R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Subramanian, Venkataraman] Univ Leeds, Leeds, W Yorkshire, England. RP Laine, L (reprint author), Yale Univ, Sch Med, Sect Digest Dis, POB 208019, New Haven, CT 06520 USA. EM loren.laine@yale.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2015 VL 110 IS 12 BP 1734 EP 1735 DI 10.1038/ajg.2015.345 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB1NJ UT WOS:000368274700027 PM 26673505 ER PT J AU Imler, TD Morea, J Kahi, C Sherer, EA Cardwell, J Johnson, CS Xu, HP Ahnen, D Antaki, F Ashley, C Baffy, G Cho, I Dominitz, J Hou, J Korsten, M Nagar, A Promrat, K Robertson, D Saini, S Shergill, A Smalley, W Imperiale, TF AF Imler, Timothy D. Morea, Justin Kahi, Charles Sherer, Eric A. Cardwell, Jon Johnson, Cynthia S. Xu, Huiping Ahnen, Dennis Antaki, Fadi Ashley, Christopher Baffy, Gyorgy Cho, Ilseung Dominitz, Jason Hou, Jason Korsten, Mark Nagar, Anil Promrat, Kittichai Robertson, Douglas Saini, Sameer Shergill, Amandeep Smalley, Walter Imperiale, Thomas F. TI Multi-Center Colonoscopy Quality Measurement Utilizing Natural Language Processing (vol 110, pg 543, 2015) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Correction C1 [Imler, Timothy D.; Kahi, Charles; Imperiale, Thomas F.] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Imler, Timothy D.; Morea, Justin; Kahi, Charles; Imperiale, Thomas F.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Imler, Timothy D.; Morea, Justin] Regenstrief Inst LLC, Dept Biomed Informat, Indianapolis, IN USA. [Kahi, Charles; Sherer, Eric A.; Cardwell, Jon; Imperiale, Thomas F.] Richard L Roudebush VA Med Ctr, Ctr Innovat Hlth Serv Res & Dev, Indianapolis, IN USA. [Sherer, Eric A.] Louisiana Tech Univ, Dept Chem Engn, Ruston, LA 71270 USA. [Johnson, Cynthia S.; Xu, Huiping] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. [Ahnen, Dennis] Univ Colorado, Div Gastroenterol, Denver, CO 80202 USA. [Antaki, Fadi] Wayne State Univ, Div Gastroenterol, Detroit, MI USA. [Ashley, Christopher] Albany Med Coll, Div Gastroenterol, Albany, NY 12208 USA. [Baffy, Gyorgy] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Cho, Ilseung] NYU, Sch Med, Div Gastroenterol, New York, NY USA. [Dominitz, Jason] Univ Washington, Sch Med, Div Gastroenterol, Seattle, WA USA. [Hou, Jason] Baylor Coll Med, Div Gastroenterol & Hepatol, Houston, TX 77030 USA. [Korsten, Mark] Icahn Sch Med Mt Sinai, Div Gastroenterol, Bronx, NY USA. [Nagar, Anil] Yale Univ, Sch Med, Div Digest Dis, New Haven, CT USA. [Promrat, Kittichai] Brown Med Sch, Div Gastroenterol, Providence, RI USA. [Robertson, Douglas] Dartmouth Inst, Div Gastroenterol, Lebanon, NH USA. [Saini, Sameer] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Shergill, Amandeep] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. [Smalley, Walter] Vanderbilt Univ, Div Gastroenterol, Nashville, TN 37235 USA. [Imperiale, Thomas F.] Regenstrief Inst Hlth Care, Hlth Serv Res, Indianapolis, IN USA. RP Imler, TD (reprint author), Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2015 VL 110 IS 12 BP 1743 EP 1743 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB1NJ UT WOS:000368274700035 PM 26673514 ER PT J AU Auladell, M Boronat, S Barber, I Thiele, EA AF Auladell, Maria Boronat, Susana Barber, Ignasi Thiele, Elizabeth A. TI Thyroid Nodules on Chest CT of Patients with Tuberous Sclerosis Complex SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE endocrine; incidentaloma; computed tomography; TSC ID CONSENSUS CONFERENCE; COMPUTED-TOMOGRAPHY; DIAGNOSTIC-CRITERIA; RADIATION-EXPOSURE; MAMMALIAN TARGET; TSC2; SONOGRAPHY; DISEASE; ULTRASONOGRAPHY; INCIDENTALOMAS AB A few cases of thyroid disease have been reported in tuberous sclerosis complex (TSC); however, studies on prevalence and characterization of lesions have not been done. Patients with TSC are routinely screened using chest CT for assessment of lung disease. Incidental thyroid findings on chest CT have been reported in large studies of the general population. The purpose of this study is to evaluate the frequency and type of thyroid anomalies in a cohort of TSC patients. We performed a retrospective review of 93 patients with a definite diagnosis of TSC, who had a chest CT. Images of the thyroid gland and final radiological report were reviewed. Reports of additional thyroid studies performed in some patients were also reviewed. Thyroid abnormalities were present in 19 of 93 (20.4%) patients. They consisted mainly of hypodense lesions categorized as nodules. Multiple nodules were found in 10 patients (52.6%). There was one papillary carcinoma. Thyroid gland lesions may be part of the clinical spectrum of TSC. They are usually asymptomatic. As some cases of thyroid carcinoma have been described in TSC, ultrasound exams are recommended, given that CT is not the gold standard technique for thyroid evaluation. (C) 2015 Wiley Periodicals, Inc. C1 [Auladell, Maria; Boronat, Susana; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Boronat, Susana] Univ Autonoma Barcelona, Vall dHebron Hosp, Dept Pediat Neurol, E-08193 Barcelona, Spain. [Barber, Ignasi] Univ Autonoma Barcelona, Vall dHebron Hosp, Dept Pediat Radiol, E-08193 Barcelona, Spain. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Herscot Center for Tuberous Sclerosis Complex; BAE FX Grant sponsor: Herscot Center for Tuberous Sclerosis Complex; Grant sponsor: BAE. NR 44 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC PY 2015 VL 167 IS 12 BP 2992 EP 2997 DI 10.1002/ajmg.a.37339 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA DA3AP UT WOS:000367668600014 PM 26332136 ER PT J AU Ravi, P Sood, A Schmid, M Abdollah, F Sammon, JD Sun, M Klett, DE Varda, B Peabody, JO Menon, M Kibel, AS Nguyen, PL Trinh, QD AF Ravi, Praful Sood, Akshay Schmid, Marianne Abdollah, Firas Sammon, Jesse D. Sun, Maxine Klett, Dane E. Varda, Briony Peabody, James O. Menon, Mani Kibel, Adam S. Nguyen, Paul L. Quoc-Dien Trinh TI Racial/Ethnic Disparities in Perioperative Outcomes of Major Procedures Results From the National Surgical Quality Improvement Program SO ANNALS OF SURGERY LA English DT Article DE ACS-NSQIP; cancer surgery; major noncancer surgery; perioperative outcomes; race; ethnicity ID LENGTH-OF-STAY; RADICAL PROSTATECTOMY; RACIAL DISPARITIES; CANCER-SURGERY; COLORECTAL-CANCER; AMERICAN-COLLEGE; INPATIENT SAMPLE; HOSPITAL VOLUME; BREAST-CANCER; CARE AB Objective:To determine the association between race/ethnicity and perioperative outcomes in individuals undergoing major oncologic and nononcologic surgical procedures in the United States.Background:Prior work has shown that there are significant racial/ethnic disparities in perioperative outcomes after several types of major cardiac, general, vascular, orthopedic, and cancer surgical procedures. However, recent evidence suggests attenuation of these racial/ethnic differences, particularly at academic institutions.Methods:We utilized the American College of Surgeons National Surgical Quality Improvement Program database to identify 142,344 patients undergoing one of the 16 major cancer and noncancer surgical procedures between 2005 and 2011.Results:Eighty-five percent of the cohort was white, with black and Hispanic individuals comprising 8% and 4%, respectively. In multivariable analyses, black patients had greater odds of experiencing prolonged length of stay after 10 of the 16 procedures studied (all P<0.05), though there was no disparity in odds of 30-day mortality after any surgery. Hispanics were more likely to experience prolonged length of stay after 5 surgical procedures (all P<0.04), and were at greater odds of dying within 30 days after colectomy, heart valve repair/replacement, or abdominal aortic aneurysm repair (all P<0.03). Fewer disparities were observed for Hispanics, than for black patients, and also for cancer, than for noncancer surgical procedures.Conclusions:Important racial/ethnic disparities in perioperative outcomes were observed among patients undergoing major cancer and noncancer surgical procedures at American College of Surgeons National Surgical Quality Improvement Program institutions. There were fewer disparities among individuals undergoing cancer surgery, though black patients, in particular, were more likely to experience prolonged length of stay. C1 [Ravi, Praful] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, London, England. [Sood, Akshay; Abdollah, Firas; Sammon, Jesse D.; Klett, Dane E.; Peabody, James O.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA. [Sood, Akshay; Schmid, Marianne; Varda, Briony; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Div Urol Surg, Boston, MA 02115 USA. [Sood, Akshay; Schmid, Marianne; Varda, Briony; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Trinh, QD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 45 Francis St,ASB 2-3, Boston, MA 02115 USA. EM qtrinh@partners.org; qtrinh@partners.org FU Prof Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital FX Supported by the Prof Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital (for Quoc-Dien Trinh). NR 47 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2015 VL 262 IS 6 BP 955 EP 964 DI 10.1097/SLA.0000000000001078 PG 10 WC Surgery SC Surgery GA DA6JP UT WOS:000367910100011 PM 26501490 ER PT J AU Marchegiani, G Mino-Kenudson, M Ferrone, CR Morales-Oyarvide, V Warshaw, AL Lillemoe, KD Fernandez-del Castillo, C AF Marchegiani, Giovanni Mino-Kenudson, Mari Ferrone, Cristina R. Morales-Oyarvide, Vicente Warshaw, Andrew L. Lillemoe, Keith D. Fernandez-del Castillo, Carlos TI Patterns of Recurrence After Resection of IPMN Who, When, and How? SO ANNALS OF SURGERY LA English DT Article DE follow-up; intraductal papillary mucinous neoplasm; IPMN; PDAC; recurrence ID PAPILLARY-MUCINOUS NEOPLASM; INTERNATIONAL-CONSENSUS-GUIDELINES; CYSTIC NEOPLASMS; SURGICAL RESECTION; PANCREAS; DUCT; EXPERIENCE; MANAGEMENT; PANCREATECTOMY; SURVIVAL AB Objective:To describe the patterns of recurrence after resection of intraductal papillary mucinous neoplasms (IPMN) of the pancreas.Background:IPMNs represent an increasing indication for pancreatic resection, but little is known about the actual incidence and the patterns of recurrence after surgical excision.Methods:Retrospective review of 412 resected IPMNs from 1990 to 2013 who have had near-complete follow-up.Results:Median age of the cohort was 68 years, 56% had branch duct (BD)-IPMN and 21% had invasive cancers. Nineteen patients (5%) had distinct pancreatic ductal adenocarcinoma (PDAC) and were excluded from the recurrence analysis. After a median of 58 months, 65 of 381 patients (17%) experienced recurrence of the IPMN, and 5- and 10-year disease-free survival (DFS) was 82% and 78%, respectively. Only 2 patients (0.5%) developed metachronous PDAC. In 33 patients (9%), a residual BD-IPMN was left in the pancreatic remnant, but none of these significantly grew or required reoperation. Invasive component and resection margin positive for IPMN were predictors of recurrence (P <0.05). Invasive IPMN recurred in 45% of cases, whereas noninvasive in only 9% and later (P <0.001), but patterns depended on IPMN subtypes. Only 9 patients required reoperation for recurrence, with good long-term outcome particularly for oncocytic IPMNs.Conclusions:Recurrence of noninvasive BD-IPMN is infrequent and surveillance may be avoided in selected cases. In invasive IPMN recurrence depends on N status, pancreatic margin, and invasive type. C1 [Marchegiani, Giovanni; Ferrone, Cristina R.; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Morales-Oyarvide, Vicente] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Wang Ambulatory Care Ctr 460,15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org NR 41 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2015 VL 262 IS 6 BP 1108 EP 1114 DI 10.1097/SLA.0000000000001008 PG 7 WC Surgery SC Surgery GA DA6JP UT WOS:000367910100031 PM 25793719 ER PT J AU Bloom, JP Ott, HC AF Bloom, Jordan P. Ott, Harald C. TI Regenerative Medicine Applications in Organ Transplantation SO ANNALS OF SURGERY LA English DT Book Review C1 [Bloom, Jordan P.; Ott, Harald C.] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. RP Bloom, JP (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2015 VL 262 IS 6 BP 1166 EP 1166 DI 10.1097/SLA.0000000000001066 PG 1 WC Surgery SC Surgery GA DA6JU UT WOS:000367910800001 ER PT J AU Bloom, JP Ott, HC AF Bloom, Jordan P. Ott, Harald C. TI Regenerative Medicine Applications in Organ Transplantation SO ANNALS OF SURGERY LA English DT Letter C1 [Bloom, Jordan P.; Ott, Harald C.] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. RP Bloom, JP (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2015 VL 262 IS 6 BP 1166 EP 1166 DI 10.1097/SLA.0000000000001066 PG 1 WC Surgery SC Surgery GA DA6JR UT WOS:000367910400001 ER PT J AU Barbeau, EB Meilleur, AAS Zeffiro, TA Mottron, L AF Barbeau, Elise B. Meilleur, Andree-Anne S. Zeffiro, Thomas A. Mottron, Laurent TI Comparing Motor Skills in Autism Spectrum Individuals With and Without Speech Delay SO AUTISM RESEARCH LA English DT Article DE autism spectrum; Asperger syndrome; motor skills; motor control; coordination; speech onset delay ID HIGH-FUNCTIONING AUTISM; REACTION TIME TASK; ASPERGER-SYNDROME; PRESCHOOL-CHILDREN; KINEMATIC ANALYSIS; YOUNG-CHILDREN; DISORDER; COORDINATION; INTELLIGENCE; METAANALYSIS AB Movement atypicalities in speed, coordination, posture, and gait have been observed across the autism spectrum (AS) and atypicalities in coordination are more commonly observed in AS individuals without delayed speech (DSM-IV Asperger) than in those with atypical or delayed speech onset. However, few studies have provided quantitative data to support these mostly clinical observations. Here, we compared perceptual and motor performance between 30 typically developing and AS individuals (21 with speech delay and 18 without speech delay) to examine the associations between limb movement control and atypical speech development. Groups were matched for age, intelligence, and sex. The experimental design included: an inspection time task, which measures visual processing speed; the Purdue Pegboard, which measures finger dexterity, bimanual performance, and hand-eye coordination; the Annett Peg Moving Task, which measures unimanual goal-directed arm movement; and a simple reaction time task. We used analysis of covariance to investigate group differences in task performance and linear regression models to explore potential associations between intelligence, language skills, simple reaction time, and visually guided movement performance. AS participants without speech delay performed slower than typical participants in the Purdue Pegboard subtests. AS participants without speech delay showed poorer bimanual coordination than those with speech delay. Visual processing speed was slightly faster in both AS groups than in the typical group. Altogether, these results suggest that AS individuals with and without speech delay differ in visually guided and visually triggered behavior and show that early language skills are associated with slower movement in simple and complex motor tasks. (C) 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research C1 [Barbeau, Elise B.; Meilleur, Andree-Anne S.; Mottron, Laurent] Univ Montreal, Hop Riviere Prairies, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ H1E 1A4, Canada. [Barbeau, Elise B.; Mottron, Laurent] Univ Montreal, Dept Psychiat, Ctr Rech Fernand Seguin, Montreal, PQ H3C 3J7, Canada. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. RP Mottron, L (reprint author), Hop Riviere Prairies, 7070 Blvd Perras, Montreal, PQ H1E 1A4, Canada. EM laurent.mottron@gmail.com FU Canadian Institutes of Health Research (CIHR) [MOP-84243] FX This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR, No. MOP-84243) awarded to L. Mottron, and scholarships from the CIHR awarded to E.B. Barbeau and A.-A.S. Meilleur. The authors also want to thank the participants for their invaluable contribution to this project. The authors report no potential conflicts of interest. NR 66 TC 1 Z9 1 U1 7 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-3792 EI 1939-3806 J9 AUTISM RES JI Autism Res. PD DEC PY 2015 VL 8 IS 6 BP 682 EP 693 DI 10.1002/aur.1483 PG 12 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA DB0HU UT WOS:000368190000004 PM 25820662 ER PT J AU Silva, ZS Bussadori, SK Fernandes, KPS Huang, YY Hamblin, MR AF Silva, Zenildo Santos, Jr. Bussadori, Sandra Kalil Santos Fernandes, Kristianne Porta Huang, Ying-Ying Hamblin, Michael R. TI Animal models for photodynamic therapy (PDT) SO BIOSCIENCE REPORTS LA English DT Review DE autochthonous; cancer; genetically-engineered mouse model; infection; orthotopic tumour; photodynamic therapy; subcutaneous tumour; xenograft ID SQUAMOUS-CELL CARCINOMA; IN-VIVO; 5-AMINOLEVULINIC ACID; WOUND INFECTIONS; MURINE MODEL; METHYLENE-BLUE; BREAST-CANCER; NUDE-MICE; ALUMINUM PHTHALOCYANINE; STAPHYLOCOCCUS-AUREUS AB Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for various disease indications, many studies around the world are using animal models to investigate the further utility of PDT. The present review will cover the main groups of animal models that have been described in the literature. Cancer comprises the single biggest group of models including syngeneic mouse/rat tumours that can either be subcutaneous or orthotopic and allow the study of anti-tumour immune response; human tumours that need to be implanted in immunosuppressed hosts; carcinogen-induced tumours; and mice that have been genetically engineered to develop cancer (often by pathways similar to those in patients). Infections are the second biggest class of animal models and the anatomical sites include wounds, burns, oral cavity, ears, eyes, nose etc. Responsible pathogens can include Gram-positive and Gram-negative bacteria, fungi, viruses and parasites. A smaller and diverse group of miscellaneous animal models have been reported that allow PDT to be tested in ophthalmology, atherosclerosis, atrial fibrillation, dermatology and wound healing. Successful studies using animal models of PDT are blazing the trail for tomorrow's clinical approvals. C1 [Silva, Zenildo Santos, Jr.; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Silva, Zenildo Santos, Jr.; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Silva, Zenildo Santos, Jr.; Bussadori, Sandra Kalil; Santos Fernandes, Kristianne Porta] Nove Julho Univ, Postgrad Program Biophoton Appl Hlth Sci, BR-02117010 Sao Paulo, SP, Brazil. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Fernandes, Kristianne/I-4417-2016 FU CAPES-Ministry of Education, Brazil [99999.002158/2014-00]; National Institute of Health [R01AI050875] FX This work was supported by the CAPES-Ministry of Education, Brazil [grant number 99999.002158/2014-00 (to Z.S.S.)]; and the National Institute of Health [grant number R01AI050875 (to M.R.H.)]. NR 112 TC 3 Z9 3 U1 14 U2 29 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0144-8463 EI 1573-4935 J9 BIOSCIENCE REP JI Biosci. Rep. PD DEC 1 PY 2015 VL 35 AR e00265 DI 10.1042/BSR20150188 PN 6 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DB1VJ UT WOS:000368296800001 ER PT J AU Kiyota, N Schlumberger, M Muro, K Ando, Y Takahashi, S Kawai, Y Wirth, L Robinson, B Sherman, S Suzuki, T Fujino, K Gupta, A Hayato, S Tahara, M AF Kiyota, Naomi Schlumberger, Martin Muro, Kei Ando, Yuichi Takahashi, Shunji Kawai, Yasukazu Wirth, Lori Robinson, Bruce Sherman, Steven Suzuki, Takuya Fujino, Katsuki Gupta, Anubha Hayato, Seiichi Tahara, Makoto TI Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer SO CANCER SCIENCE LA English DT Article DE Japanese patients; lenvatinib; progression-free survival; thyroid cancer; treatment efficacy ID RENAL-CELL CARCINOMA; ANTITUMOR ACTIVITIES; DOUBLE-BLIND; SORAFENIB; INHIBITOR; E7080; ANGIOGENESIS; EFFICACY; THERAPY; SAFETY AB Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib in Japanese patients who participated in SELECT. Outcomes for Japanese patients (lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT population (lenvatinib, n = 261; placebo, n = 131). The primary endpoint was PFS; secondary endpoints included overall survival, overall response rate, and safety. Lenvatinib PFS benefit was shown in Japanese patients (median PFS: lenvatinib, 16.5 months; placebo, 3.7 months), although significance was not reached, presumably due to sample size (hazard ratio, 0.39; 95% confidence interval, 0.10-1.57; P = 0.067). Overall response rates were 63.3% and 0% for lenvatinib and placebo, respectively. No significant difference was found in overall survival. The lenvatinib safety profile was similar between the Japanese and overall SELECT population, except for higher incidences of hypertension (any grade: Japanese, 87%; overall, 68%; grade >= 3: Japanese, 80%; overall, 42%), palmar-plantar erythrodysesthesia syndrome (any grade: Japanese, 70%; overall, 32%; grade >= 3: Japanese, 3%; overall, 3%), and proteinuria (any grade: Japanese, 63%; overall, 31%; grade >= 3: Japanese, 20%; overall, 10%). Japanese patients had more dose reductions (Japanese, 90%; overall, 67.8%), but fewer discontinuations due to adverse events (Japanese, 3.3%; overall, 14.2%). There was no difference in lenvatinib exposure between the Japanese and overall SELECT populations after adjusting for body weight. In Japanese patients with radioiodine-refractory differentiated thyroid cancer, lenvatinib showed similar clinical outcomes to the overall SELECT population. Some differences in adverse event frequencies and dose modifications were observed. C1 [Kiyota, Naomi] Kobe Univ Hosp, Dept Haematol & Med Oncol, Kobe, Hyogo, Japan. [Schlumberger, Martin] Gustave Roussy & Univ Paris Sud, Dept Nucl Med & Endocrine Oncol, Villejuif, France. [Muro, Kei] Aichi Canc Ctr Hosp, Dept Clin Oncol, Nagoya, Aichi 464, Japan. [Ando, Yuichi] Nagoya Univ Hosp, Dept Clin Oncol & Chemotherapy, Nagoya, Aichi, Japan. [Takahashi, Shunji] Canc Inst Hosp JFCR, Dept Med Oncol, Tokyo, Japan. [Kawai, Yasukazu] Fukui Prefectural Hosp, Dept Hematol & Oncol, Fukui, Japan. [Wirth, Lori] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Robinson, Bruce] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2006, Australia. [Sherman, Steven] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. [Suzuki, Takuya] Eisai & Co Ltd, Oncol Clin Dev, Tokyo, Japan. [Fujino, Katsuki] Eisai & Co Ltd, Japan Biostat, Tokyo, Japan. [Gupta, Anubha] Eisai Ltd, Clin Pharmacol, Hatfield, Herts, England. [Hayato, Seiichi] Eisai & Co Ltd, Clin Pharmacol, Tokyo, Japan. [Tahara, Makoto] Natl Canc Ctr Hosp East, Dept Head & Neck Med Oncol, Kashiwa, Chiba, Japan. RP Kiyota, N (reprint author), Kobe Univ Hosp, Dept Haematol & Med Oncol, Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo, Japan. EM nkiyota@med.kobe-u.ac.jp RI Kiyota, Naomi/K-3226-2016; OI Sherman, Steven/0000-0002-3079-5153 FU Eisai Inc. FX Eisai Inc. NR 24 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1347-9032 EI 1349-7006 J9 CANCER SCI JI Cancer Sci. PD DEC PY 2015 VL 106 IS 12 BP 1714 EP 1721 DI 10.1111/cas.12826 PG 8 WC Oncology SC Oncology GA DB1DY UT WOS:000368249400008 PM 26426092 ER PT J AU Murakami, Y Ikeda, Y Nakatake, S Miller, JW Vavvas, DG Sonoda, KH Ishibashi, T AF Murakami, Y. Ikeda, Y. Nakatake, S. Miller, J. W. Vavvas, D. G. Sonoda, K. H. Ishibashi, T. TI Necrotic cone photoreceptor cell death in retinitis pigmentosa SO CELL DEATH & DISEASE LA English DT Editorial Material ID RECEPTOR INTERACTING PROTEIN; MOUSE MODEL; DEGENERATION; MECHANISMS; PATHWAY C1 [Murakami, Y.; Ikeda, Y.; Nakatake, S.; Sonoda, K. H.; Ishibashi, T.] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 8128582, Japan. [Miller, J. W.; Vavvas, D. G.] Harvard Univ, Sch Med, Dept Ophthalmol, Retina Serv,Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Murakami, Y (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 8128582, Japan. EM ymuraka3@med.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016 FU NEI NIH HHS [R01 EY025362, R21EY023079-01A1] NR 13 TC 0 Z9 0 U1 0 U2 2 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 DEC PY 2015 VL 6 AR e2038 DI 10.1038/cddis.2015.385 PG 2 WC Cell Biology SC Cell Biology GA DB0BA UT WOS:000368172400037 PM 26720347 ER PT J AU Tanner, NT Silvestri, GA AF Tanner, Nichole T. Silvestri, Gerard A. TI POINT: Is N2 Disease a Contraindication for Surgical Resection for Superior Sulcus Tumors? Yes SO CHEST LA English DT Editorial Material ID CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; SOUTHWEST-ONCOLOGY-GROUP; INDUCTION CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; ENDOBRONCHIAL ULTRASOUND; REPEAT MEDIASTINOSCOPY; NEEDLE ASPIRATION; PHASE-III; THERAPY C1 [Tanner, Nichole T.] Ralph H Johnson Vet Affairs Hosp, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Tanner, Nichole T.; Silvestri, Gerard A.] Med Univ S Carolina, Div Pulm & Crit Care Allergy & Sleep Med, Charleston, SC 29425 USA. RP Tanner, NT (reprint author), Med Univ S Carolina, Div Pulm & Crit Care Allergy & Sleep Med, 96 Jonathan Lucas St,Ste 812-CSB, Charleston, SC 29425 USA. EM tripici@musc.edu NR 23 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2015 VL 148 IS 6 BP 1373 EP 1375 DI 10.1378/chest.15-1194 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DB1NC UT WOS:000368273900019 PM 26110373 ER PT J AU Tanner, NT Silvestri, GA AF Tanner, Nichole T. Silvestri, Gerard A. TI Rebuttal From Drs Tanner and Silvestri SO CHEST LA English DT Editorial Material ID CELL LUNG-CANCER; TRIMODALITY THERAPY C1 [Tanner, Nichole T.] Ralph H Johnson Vet Affairs Hosp, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Tanner, Nichole T.; Silvestri, Gerard A.] Med Univ S Carolina, Div Pulm & Crit Care Allergy & Sleep Med, Charleston, SC 29425 USA. RP Tanner, NT (reprint author), Med Univ S Carolina, Div Pulm & Crit Care Allergy & Sleep Med, 96 Jonathan Lucas St,Ste 812-CSB, Charleston, SC 29425 USA. EM tripici@musc.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2015 VL 148 IS 6 BP 1379 EP 1380 DI 10.1378/chest.15-1195 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DB1NC UT WOS:000368273900021 PM 26110565 ER PT J AU Cooper, LA Page, ST Amory, JK Anawalt, BD Matsumoto, AM AF Cooper, Lori A. Page, Stephanie T. Amory, John K. Anawalt, Bradley D. Matsumoto, Alvin M. TI The association of obesity with sex hormone-binding globulin is stronger than the association with ageing - implications for the interpretation of total testosterone measurements SO CLINICAL ENDOCRINOLOGY LA English DT Article ID DECREASED ANDROGEN LEVELS; TANDEM MASS-SPECTROMETRY; OLDER MEN; METABOLIC SYNDROME; REFERENCE RANGES; HYPOGONADISM; DEFICIENCY; SERUM; POPULATION; PREVALENCE AB Objective Total testosterone concentrations are influenced by sex hormone-binding globulin (SHBG) concentrations, which are decreased by obesity and increased with ageing. Therefore, we sought to understand and compare the associations of ageing and obesity with SHBG. Design We performed a retrospective, cross-sectional analysis of the associations of obesity and age on SHBG and testosterone measurements in men being evaluated for hypogonadism. Patients, Measurements and Analysis A total of 3671 men who underwent laboratory testing for testosterone deficiency from the Veterans Administration Puget Sound Health Care System from 1997 through 2007 was included. Univariate and multivariate linear regression modelling of the associations between age and body mass index (BMI) and SHBG was performed. Results Obesity was associated with a significantly lower SHBG [beta = -1.26 (95% CI -1.14, -1.38) nmol/l] per unit increase in BMI. In contrast, ageing was associated with a significantly increased SHBG [beta = 0.46 (95% CI 0.39, 0.53) nmol/l per year] (P < 0.001 for both effects). The association of obesity with lower SHBG was two to three times larger than the association of ageing with increased SHBG in both univariate and multivariate modelling. On average, obese men (BMI > 30 kg/m(2)) had significantly lower SHBG and total testosterone concentrations than nonobese men [(mean +/- SD) SHBG: 36 +/- 22 vs 50 +/- 27 nmol/l and total testosterone: 10.5 +/- 5.4 nmol/l vs 14.1 +/- 7.4 nmol/l; (P < 0.001 for both comparisons)], but calculated free testosterone concentrations did not differ between obese and nonobese men. Conclusions We found that the association between obesity and lowered SHBG is greater than the association of ageing with increased SHBG. These competing effects may impact total testosterone measurements for the diagnosis of low testosterone, particularly in obese men. C1 [Cooper, Lori A.; Page, Stephanie T.; Amory, John K.; Anawalt, Bradley D.; Matsumoto, Alvin M.] Univ Washington, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. [Cooper, Lori A.; Matsumoto, Alvin M.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. [Cooper, Lori A.; Page, Stephanie T.; Amory, John K.; Anawalt, Bradley D.; Matsumoto, Alvin M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Anawalt, BD (reprint author), Univ Washington, Dept Med, Box 356420,1959 NE Pacific St, Seattle, WA 98195 USA. EM banawalt@medicine.washington.edu FU National Institutes of Health (NIH) [T32HL0007028]; VA Fellowship in Advanced Geriatrics; National Institute of Aging (NIH) [AG037603A]; Department of Veterans Affairs Puget Sound Health Care System, Geriatric Research Education and Clinical Center FX L.A.C was supported by a training grant from the National Institutes of Health (NIH), T32HL0007028 and a VA Fellowship in Advanced Geriatrics; S.T.P. was supported by the National Institute of Aging (NIH), Grant AG037603A; A.M.M. was supported by the Department of Veterans Affairs Puget Sound Health Care System, Geriatric Research Education and Clinical Center. NR 32 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2015 VL 83 IS 6 BP 828 EP 833 DI 10.1111/cen.12768 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB1TX UT WOS:000368293000012 PM 25777143 ER PT J AU Kleiss, IJ Hohman, MH Susarla, SM Marres, HAM Hadlock, TA AF Kleiss, I. J. Hohman, M. H. Susarla, S. M. Marres, H. A. M. Hadlock, T. A. TI Health-related quality of life in 794 patients with a peripheral facial palsy using the FaCE Scale: a retrospective cohort study SO CLINICAL OTOLARYNGOLOGY LA English DT Article ID GRADING SYSTEM; ACOUSTIC NEUROMA; DISABILITY INDEX; HOUSE-BRACKMANN; NERVE PARALYSIS; VALIDATION; SYNKINESIS; DISFIGUREMENT; RELIABILITY; INSTRUMENT AB Objectives: To describe the health-related quality of life of patients visiting a tertiary referral centre for facial palsy, and to analyse factors associated with health-related quality of life, using the FaCE Scale instrument. Design: Retrospective cohort study. Setting: The Facial Nerve Center at the Massachusetts Eye and Ear Infirmary, a tertiary referral centre. Participants: Patients with a peripheral facial palsy visiting the centre for an initial consultation between August 2007 and June 2012. Main outcome measures: The total FaCE score and the FaCE social function subdomain. Multiple regression models were developed to identify factors associated with the total FaCE score and FaCE social function score. Results: A total of 794 patients with a mean age of 47.0 +/- 16.0 years were analysed in this study, of which 59.9% were female. The mean House-Brackmann, Sunnybrook, total FaCE and FaCE social function scores were 3.6 +/- 1.5, 48.2 +/- 21.2, 47.3 +/- 19.3 and 55.5 +/- 19.2, respectively. Increasing age (r = -0.229, P < 0.001) was associated with a lower total FaCE score. Female gender (r = -4.422, P = 0.033) and increased duration of palsy (r = -0.018, P = 0.041) were associated with lower FaCE social function scores. Conclusions: While counselling patients on what to expect during the recovery process after facial paralysis is an important part of any clinical visit, FaCE score correlations suggest that female patients with chronic facial palsy and increased age constitute a patient category that may require additional time and attention to prevent or mitigate psychosocial dysfunction. C1 [Kleiss, I. J.; Hohman, M. H.; Hadlock, T. A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Kleiss, I. J.; Hohman, M. H.; Hadlock, T. A.] Harvard Univ, Sch Med, Boston, MA USA. [Kleiss, I. J.; Marres, H. A. M.] Radboud Univ Nijmegen Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, NL-6500 HB Nijmegen, Netherlands. [Susarla, S. M.] Johns Hopkins Univ, Dept Plast & Reconstruct Surg, Johns Hopkins Hosp, Baltimore, MD USA. RP Kleiss, IJ (reprint author), Radboud Univ Nijmegen Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM ingrid.kleiss@radboudumc.nl OI Susarla, Srinivas/0000-0003-0155-8260 NR 30 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1749-4478 EI 1749-4486 J9 CLIN OTOLARYNGOL JI Clin. Otolaryngol. PD DEC PY 2015 VL 40 IS 6 BP 651 EP 656 DI 10.1111/coa.12434 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA DA7PI UT WOS:000367995900018 PM 25858429 ER PT J AU Dejanovic, B Djemie, T Grunewald, N Suls, A Kress, V Hetsch, F Craiu, D Zemel, M Gormley, P Lal, D Myers, CT Mefford, HC Palotie, A Helbig, I Meier, JC De Jonghe, P Weckhuysen, S Schwarz, G AF Dejanovic, Borislav Djemie, Tania Gruenewald, Nora Suls, Arvid Kress, Vanessa Hetsch, Florian Craiu, Dana Zemel, Matthew Gormley, Padhraig Lal, Dennis Myers, Candace T. Mefford, Heather C. Palotie, Aarno Helbig, Ingo Meier, Jochen C. De Jonghe, Peter Weckhuysen, Sarah Schwarz, Guenter CA EuroEPINOMICS Dravet Working Grp TI Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in a patient with epileptic encephalopathy SO EMBO MOLECULAR MEDICINE LA English DT Article DE Dravet syndrome; epileptic encephalopathy; GABA(A) receptors; gephyrin; molybdenum cofactor ID MOLYBDENUM COFACTOR DEFICIENCY; DE-NOVO MUTATIONS; ACID TYPE-A; ESCHERICHIA-COLI MOEA; GLYCINE RECEPTOR; GABA(A) RECEPTOR; INHIBITORY SYNAPSES; PROTEIN GEPHYRIN; MOLECULAR-BASIS; BINDING AB Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition plays an important role in neurological disorders. Gephyrin is a central player at inhibitory postsynapses, directly binds and organizes GABA(A) and glycine receptors (GABA(A)Rs and GlyRs), and is thereby indispensable for normal inhibitory neurotransmission. Additionally, gephyrin catalyzes the synthesis of the molybdenum cofactor (MoCo) in peripheral tissue. We identified a de novo missense mutation (G375D) in the gephyrin gene (GPHN) in a patient with epileptic encephalopathy resembling Dravet syndrome. Although stably expressed and correctly folded, gephyrin-G375D was non-synaptically localized in neurons and acted dominant-negatively on the clustering of wild- type gephyrin leading to a marked decrease in GABA(A)R surface expression and GABAergic signaling. We identified a decreased binding affinity between gephyrin-G375D and the receptors, suggesting that Gly375 is essential for gephyrin-receptor complex formation. Surprisingly, gephyrin-G375D was also unable to synthesize MoCo and activate MoCo-dependent enzymes. Thus, we describe a missense mutation that affects both functions of gephyrin and suggest that the identified defect at GABAergic synapses is the mechanism underlying the patient's severe phenotype. C1 [Dejanovic, Borislav; Gruenewald, Nora; Kress, Vanessa; Schwarz, Guenter] Univ Cologne, Dept Chem, Inst Biochem, D-50931 Cologne, Germany. [Djemie, Tania; Suls, Arvid; De Jonghe, Peter; Weckhuysen, Sarah] VIB, Dept Mol Genet, Neurogenet Grp, Antwerp, Belgium. [Djemie, Tania; Suls, Arvid; De Jonghe, Peter; Weckhuysen, Sarah] Univ Antwerp, Neurogenet Lab, Inst Born Bunge, B-2020 Antwerp, Belgium. [Suls, Arvid] Univ Antwerp, Ctr Med Genet, GENOMED, B-2020 Antwerp, Belgium. [Hetsch, Florian] Tech Univ Carolo Wilhelmina Braunschweig, Inst Zool, Div Cell Physiol, Braunschweig, Germany. [Craiu, Dana] Al Obregia Hosp, Pediat Neurol Clin, Bucharest, Romania. [Craiu, Dana] Carol Davila Univ Med & Pharm, Dept Neurol Pediat Neurol Psychiat Child & Adoles, Bucharest, Romania. [Zemel, Matthew] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. [Gormley, Padhraig; Palotie, Aarno] Wellcome Trust Sanger Inst, Hinxton, England. [Gormley, Padhraig; Schwarz, Guenter] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany. [Gormley, Padhraig; Schwarz, Guenter] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany. [Gormley, Padhraig; Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet, Boston, MA 02114 USA. [Gormley, Padhraig; Palotie, Aarno] Harvard Univ, Sch Med, Boston, MA USA. [Lal, Dennis] Univ Cologne, Cologne Ctr Genom, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany. [Lal, Dennis] Univ Med Fac Giessen & Marburg, Dept Neuropediat, Giessen, Germany. [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Palotie, Aarno] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Helbig, Ingo] Univ Kiel, Univ Med Ctr Schleswig Holstein, Dept Neuropediat, Kiel, Germany. [Helbig, Ingo] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [De Jonghe, Peter] Univ Antwerp Hosp, Div Neurol, Antwerp, Belgium. [Weckhuysen, Sarah] Univ Paris 06, Sorbonne Univ, CNRS,UMR S 1127,U1127, INSERM,ICM,Inst Cerveau & Moelle Epiniere,UMR 722, Paris, France. [Weckhuysen, Sarah] Grp Hosp Pitie Salpetriere, AP HP, Ctr Reference Epilepsies Rares, Epilepsy unit, F-75013 Paris, France. RP Dejanovic, B (reprint author), Univ Cologne, Dept Chem, Inst Biochem, D-50931 Cologne, Germany. EM b.dejanovic@uni-koeln.de; sarahweck@hotmail.com; gschwarz@uni-koeln.de OI Gormley, Padhraig/0000-0002-8908-6968 FU German Science Foundation [DFG SFB635]; program "Investissements d'avenir" [ANR-10-IAIHU-06]; Wellcome Trust [089062, 098051]; European Commission [Synsys-242167, gEUVADIS-261123]; Academy of Finland [251704, 263401]; Sigrid Juselius Foundation; US NIH [HL113315]; Eurocores program EuroEPINOMICS of the European Science Foundation (ESF); Fund for Scientific Research Flanders (FWO); University of Antwerp; French program "Investissements d'avenir" [ANR-10-IAIHU-06]; Bundesministerium fur Bildung und Forschung BMBF (Era-Net NEURON II CIPRESS); Deutsche Forschungsgemeinschaft DFG Priority Programme SPP 1784 [ME2075/7-1] FX We thank the patients and their families for their cooperation to this study. We thank Joana Stegemann, Monika Laurien and Veronika Georgieva for technical assistance, Belaidi Abdel Ali and Sita Arjune for help with the MoCo assay, Ines Neundorf for peptide synthesis, and Marcus Semtner and Aline Winkelmann for their experimental support of the neuronal culture electrophysiology. T.D. is a PhD fellow of the Institute of Science and Technology (IWT). A.S. is a postdoctoral fellow of the Research Foundation-Flanders (FWO). This work was supported by the German Science Foundation (DFG SFB635 to G.S.), the program "Investissements d'avenir" ANR-10-IAIHU-06, Wellcome Trust grants 089062 and 098051 (A.P.), European Commission Framework Programme 7 (FP7) projects Synsys-242167 and gEUVADIS-261123 (A.P.), Academy of Finland grants 251704 and 263401 (A.P.), the Sigrid Juselius Foundation (A.P.), the US NIH grant HL113315 (A.P.), the Eurocores program EuroEPINOMICS of the European Science Foundation (ESF), the Fund for Scientific Research Flanders (FWO) (P.D.J.), and the University of Antwerp (P.D.J.), the French program "Investissements d'avenir" (ANR-10-IAIHU-06) (S.W.), the Bundesministerium fur Bildung und Forschung BMBF (Era-Net NEURON II CIPRESS to J.C.M.), and the Deutsche Forschungsgemeinschaft DFG Priority Programme SPP 1784 (ME2075/7-1 to J.C.M.). NR 57 TC 2 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD DEC PY 2015 VL 7 IS 12 BP 1580 EP 1594 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DA9NF UT WOS:000368135400006 PM 26613940 ER PT J AU Sadow, PM Dias-Santagata, D Zheng, ZL Lin, DT Le, LP Nucera, C AF Sadow, Peter M. Dias-Santagata, Dora Zheng, Zongli Lin, Derrick T. Long Phi Le Nucera, Carmelo TI Identification of insertions in PTEN and TP53 in anaplastic thyroid carcinoma with angiogenic brain metastasis SO ENDOCRINE-RELATED CANCER LA English DT Letter ID ORTHOTOPIC MOUSE MODEL; CANCER; ASSOCIATION C1 [Sadow, Peter M.; Dias-Santagata, Dora; Zheng, Zongli; Long Phi Le] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,WRN219, Boston, MA 02114 USA. [Sadow, Peter M.; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Sadow, Peter M.; Lin, Derrick T.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Nucera, Carmelo] Harvard Univ, Lab Human Thyroid Canc Preclin & Translat Res, Beth Israel Deaconess Med Ctr,Dept Pathol, Div Canc Biol & Angiogenesis,Med Sch,CRI,CVBR, Boston, MA 02215 USA. RP Nucera, C (reprint author), Harvard Univ, Lab Human Thyroid Canc Preclin & Translat Res, Beth Israel Deaconess Med Ctr,Dept Pathol, Div Canc Biol & Angiogenesis,Med Sch,CRI,CVBR, 99 Brookline Ave,RN270G, Boston, MA 02215 USA. EM psadow@mgh.harvard.edu; cnucera@bidmc.harvard.edu RI Zheng, Zongli/B-2917-2011 OI Zheng, Zongli/0000-0003-4849-4903 FU NCI NIH HHS [1R21CA165039-01A1, R21 CA165039, R01 CA181183, 1R01CA181183-01A1] NR 18 TC 1 Z9 1 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD DEC PY 2015 VL 22 IS 6 BP L23 EP L28 DI 10.1530/ERC-15-0198 PG 6 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA DB0XB UT WOS:000368230300002 PM 26472209 ER PT J AU Stamou, MI Cox, KH Crowley, WF AF Stamou, M. I. Cox, K. H. Crowley, William F., Jr. TI Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the "-Omics" Era SO ENDOCRINE REVIEWS LA English DT Review ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; OF-FUNCTION MUTATIONS; STEROID SULFATASE DEFICIENCY; ADRENAL HYPOPLASIA CONGENITA; ISOLATED GNRH DEFICIENCY; CAUSE KALLMANN-SYNDROME; X-LINKED ICHTHYOSIS; DISTAL SHORT ARM; NEUROKININ-B AB The neuroendocrine regulation of reproduction is an intricate process requiring the exquisite coordination of an assortment of cellular networks, all converging on the GnRH neurons. These neurons have a complex life history, migrating mainly from the olfactory placode into the hypothalamus, where GnRH is secreted and acts as the master regulator of the hypothalamic-pituitary-gonadal axis. Much of what we know about the biology of the GnRH neurons has been aided by discoveries made using the human disease model of isolated GnRH deficiency (IGD), a family of rare Mendelian disorders that share a common failure of secretion and/or action of GnRH causing hypogonadotropic hypogonadism. Over the last 30 years, research groups around the world have been investigating the genetic basis of IGD using different strategies based on complex cases that harbor structural abnormalities or single pleiotropic genes, endogamous pedigrees, candidate gene approaches as well as pathway gene analyses. Although such traditional approaches, based on well-validated tools, have been critical to establish the field, newstrategies, such as next-generation sequencing, are now providing speed and robustness, but also revealing a surprising number of variants in known IGD genes in both patients and healthy controls. Thus, before the field moves forward with new genetic tools and continues discovery efforts, we must reassess what we know about IGD genetics and prepare to hold our work to a different standard. The purpose of this review is to: 1) look back at the strategies used to discover the "known" genes implicated in the rare forms of IGD; 2) examine the strengths and weaknesses of the methodologies used to validate genetic variation; 3) substantiate the role of known genes in the pathophysiology of the disease; and 4) project forward as we embark upon a widening use of these new and powerful technologies for gene discovery. (Endocrine Reviews 36: 603-621, 2015) C1 [Stamou, M. I.; Cox, K. H.; Crowley, William F., Jr.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Harvard Natl Ctr Translat Res Reprod & Infertil, Boston, MA 02114 USA. RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Bartlett Hall Extens 511, Boston, MA 02114 USA. EM wcrowley@partners.org RI Cox, Kimberly/P-1931-2016 OI Cox, Kimberly/0000-0002-7097-9563 FU National Institutes of Health (NIH) [U54 HD028138]; Daland Fellowship/American Philosophical Society; NIH [T32 DK007028] FX This work was supported by National Institutes of Health (NIH) grant U54 HD028138. M.I.S. was supported by the Daland Fellowship/American Philosophical Society. K.H.C. was supported by NIH T32 DK007028. NR 154 TC 6 Z9 6 U1 1 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD DEC PY 2015 VL 36 IS 6 BP 603 EP 621 DI 10.1210/er.2015-1045 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB1OL UT WOS:000368277700003 PM 26394276 ER PT J AU Touroutoglou, A Andreano, JM Barrett, LF Dickerson, BC AF Touroutoglou, Alexandra Andreano, Joseph M. Barrett, Lisa Feldman Dickerson, Bradford C. TI Brain Network Connectivity-Behavioral Relationships Exhibit Trait-Like Properties: Evidence From Hippocampal Connectivity and Memory SO HIPPOCAMPUS LA English DT Article DE resting-state fMRI; hippocampus; individual differences; reliability; memory ID INTRINSIC FUNCTIONAL CONNECTIVITY; RESTING-STATE CONNECTIVITY; TEST-RETEST RELIABILITY; INDIVIDUAL-DIFFERENCES; DEFAULT MODE; AMYGDALA; PERFORMANCE; STRESS; CORTEX; MRI AB Despite a growing number of studies showing relationships between behavior and resting-state functional MRI measures of large-scale brain network connectivity, no study to our knowledge has sought to investigate whether intrinsic connectivity-behavioral relationships are stable over time. In this study, we investigated the stability of such brain-behavior relationships at two timepoints, approximately 1 week apart. We focused on the relationship between the strength of hippocampal connectivity to posterior cingulate cortex and episodic memory performance. Our results showed that this relationship is stable across samples of a different age and reliable over two points in time. These findings provide the first evidence that the relationship between large-scale intrinsic network connectivity and episodic memory performance is a stable characteristic that varies between individuals. (C) 2015 Wiley Periodicals, Inc. C1 [Touroutoglou, Alexandra] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Touroutoglou, Alexandra; Andreano, Joseph M.; Barrett, Lisa Feldman; Dickerson, Bradford C.] Harvard Univ, Sch Med, Charlestown, MA USA. [Touroutoglou, Alexandra; Andreano, Joseph M.; Barrett, Lisa Feldman; Dickerson, Bradford C.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Touroutoglou, Alexandra; Andreano, Joseph M.; Barrett, Lisa Feldman; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neuroimaging, Charlestown, MA USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, Charlestown, MA USA. RP Dickerson, BC (reprint author), MGH Frontotemporal Disorders Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU National Institutes of Health Director's Pioneer Award [DP1OD003312]; National Institute on Aging [R01 AG030311-06A1] FX Grant sponsor: National Institutes of Health Director's Pioneer Award; Grant number: DP1OD003312; Grant sponsor: National Institute on Aging; Grant number: R01 AG030311-06A1. NR 46 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD DEC PY 2015 VL 25 IS 12 BP 1591 EP 1598 DI 10.1002/hipo.22480 PG 8 WC Neurosciences SC Neurosciences & Neurology GA DB1PT UT WOS:000368281700010 PM 26105075 ER PT J AU Robinson, JL Barron, DS Kirby, LAJ Bottenhorn, KL Hill, AC Murphy, JE Katz, JS Salibi, N Eickhoff, SB Fox, PT AF Robinson, Jennifer L. Barron, Daniel S. Kirby, Lauren A. J. Bottenhorn, Katherine L. Hill, Ashley C. Murphy, Jerry E. Katz, Jeffrey S. Salibi, Nouha Eickhoff, Simon B. Fox, Peter T. TI Neurofunctional Topography of the Human Hippocampus SO HUMAN BRAIN MAPPING LA English DT Article DE meta-analysis; fMRI; 7T; high field; DTI ID ACTIVATION-BASED PARCELLATION; INFERIOR PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; METAANALYTIC CONNECTIVITY; WORKING-MEMORY; GENDER-DIFFERENCES; EPISODIC MEMORY; SPATIAL MEMORY; HUMAN THALAMUS; BRAIN IMAGES AB Much of what was assumed about the functional topography of the hippocampus was derived from a single case study over half a century ago. Given advances in the imaging sciences, a new era of discovery is underway, with potential to transform the understanding of healthy processing as well as the ability to treat disorders. Coactivation-based parcellation, a meta-analytic approach, and ultra-high field, high-resolution functional and structural neuroimaging to characterize the neurofunctional topography of the hippocampus was employed. Data revealed strong support for an evolutionarily preserved topography along the long-axis. Specifically, the left hippocampus was segmented into three distinct clusters: an emotional processing cluster supported by structural and functional connectivity to the amygdala and parahippocampal gyrus, a cognitive operations cluster, with functional connectivity to the anterior cingulate and inferior frontal gyrus, and a posterior perceptual cluster with distinct structural connectivity patterns to the occipital lobe coupled with functional connectivity to the precuneus and angular gyrus. The right hippocampal segmentation was more ambiguous, with plausible 2- and 5-cluster solutions. Segmentations shared connectivity with brain regions known to support the correlated processes. This represented the first neurofunctional topographic model of the hippocampus using a robust, bias-free, multimodal approach. (C) 2015 Wiley Periodicals, Inc. C1 [Robinson, Jennifer L.; Kirby, Lauren A. J.; Bottenhorn, Katherine L.; Hill, Ashley C.; Murphy, Jerry E.; Katz, Jeffrey S.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [Robinson, Jennifer L.; Kirby, Lauren A. J.; Bottenhorn, Katherine L.; Hill, Ashley C.; Murphy, Jerry E.; Katz, Jeffrey S.; Salibi, Nouha] Auburn Univ, Dept Elect & Comp Engn, Magnet Resonance Imaging Res Ctr, Auburn, AL 36849 USA. [Robinson, Jennifer L.] Auburn Univ, Dept Kinesiol, Auburn, AL 36849 USA. [Barron, Daniel S.] Yale Univ, Sch Med, New Haven, CT USA. [Salibi, Nouha] MR Res & Dev, Siemens Healthcare, Malvern, PA USA. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Eickhoff, Simon B.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Fox, Peter T.] Shenzhen Univ, Sch Med, Neuroimaging Lab, Shenzhen 518060, Guangong, Peoples R China. RP Robinson, JL (reprint author), Auburn Univ, Dept Psychol, 226 Thach Hall, Auburn, AL 36849 USA. EM jrobinson@auburn.edu OI Murphy, Jerry/0000-0002-2841-9087 FU National Institute of Mental Health [R01 074457] FX National Institute of Mental Health; Contract grant number: R01 074457 (Fox PI) NR 71 TC 8 Z9 8 U1 9 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2015 VL 36 IS 12 BP 5018 EP 5037 DI 10.1002/hbm.22987 PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DB1QF UT WOS:000368283100021 PM 26350954 ER PT J AU Korkmaz, H Yao, WC Korkmaz, M Bleier, BS AF Korkmaz, Hakan Yao, William C. Korkmaz, Mukadder Bleier, Benjamin S. TI Safety and efficacy of concentrated topical epinephrine use in endoscopic endonasal surgery SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE endoscopic sinus surgery; concentrated epinephrine; intraoperative bleeding; postoperative epistaxis; vasoconstriction ID TOTAL INTRAVENOUS ANESTHESIA; OF-THE-LITERATURE; SINUS SURGERY; SURGICAL CONDITIONS; CATECHOLAMINE CARDIOMYOPATHY; INHALATIONAL ANESTHESIA; BLOOD-LOSS; COMPLICATIONS; HYPOTENSION; VASOCONSTRICTION AB Background: Effective topical decongestion is critical for the safe performance of endoscopic endonasal surgery (EES). Despite the vasoconstriction offered by topical concentrated (1: 1000) epinephrine (CE), its use has not gained widespread acceptance because of concerns over systemic absorption and its effect on blood pressure and postoperative rebound epistaxis. The purpose of this study was to examine the physiological changes in blood pressure and rate of epistaxis with use of topical CE in a variety of endoscopic nasal procedures. Methods: EES procedures using inhalational anesthesia and topical CE performed on 1140 consecutive patients (14 patients under 18 years) between 2011 and 2014 were evaluated retrospectively. Demographic data, intraoperative hemodynamic parameters, and postoperative epistaxis rates were recorded. Results: The mean patient age was 45.8 years (range, 5-97 years). No intraoperative cardiovascular complications related to CE use were found. Four patients (0.35%) developed postoperative epistaxis requiring intervention. The mean estimated blood loss among patients undergoing bilateral sinus surgery, skull-base surgery, and orbital decompression was (mean +/- SD) 61.7 +/- 51.6 mL, 60.1 +/- 115 mL, and 67.9 +/- 42.2 mL, respectively. The maximum mean systolic blood pressure among these groups was 108.3 +/- 28.3 mmHg, 111.9 +/- 27.6 mmHg, and 95.1 +/- 31.7 mmHg, respectively. Conclusion: The use of topical CE is safe when performing endoscopic endonasal procedures. CE was not associated with any intraoperative complications. The profound intraoperative vasoconstriction does not confer a higher rate of postoperative rebound epistaxis. (C) 2015 ARS-AAOA, LLC. C1 [Korkmaz, Hakan; Korkmaz, Mukadder] Ordu Univ, Fac Med, Otorhinolaryngol Dept, TR-52200 Ordu, Turkey. [Yao, William C.; Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. RP Korkmaz, H (reprint author), Ordu Univ, Egitim & Arastirma Hastanesi, Bucak Mah,Nefsi Bucak Cad, TR-52200 Ordu, Turkey. EM hakankorkmaz@hotmail.com NR 38 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD DEC PY 2015 VL 5 IS 12 BP 1118 EP 1123 DI 10.1002/alr.21590 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA DA7TQ UT WOS:000368007400006 PM 26152362 ER PT J AU Kim, H Hung, WW Paik, MC Ross, JS Zhao, ZL Kim, GS Boockvar, K AF Kim, Hongsoo Hung, William W. Paik, Myunghee Cho Ross, Joseph S. Zhao, Zhonglin Kim, Gi-Soo Boockvar, Kenneth TI Predictors and outcomes of unplanned readmission to a different hospital SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE readmissions; hospital care; patient outcomes; health policy ID ADVERSE EVENTS; PREVALENCE; REHOSPITALIZATIONS; RECORDS; MODELS AB Objectives: To examine patient, hospital and market factors and outcomes associated with readmission to a different hospital compared with the same hospital. Design: A population-based, secondary analysis using multilevel causal modeling. Setting: Acute care hospitals in California in the USA. Participants: In total, 509 775 patients aged 50 or older who were discharged alive from acute care hospitals (index hospitalizations), and 59 566 who had a rehospitalization within 30 days following their index discharge. Intervention: No intervention. Main Outcome Measures(s): Thirty-day unplanned readmissions to a different hospital compared with the same hospital and also the costs and health outcomes of the readmissions. Results: Twenty-one percent of patients with a rehospitalization had a different-hospital readmission. Compared with the same-hospital readmission group, the different-hospital readmission group was more likely to be younger, male and have a lower income. The index hospitals of the different-hospital readmission group were more likely to be smaller, for-profit hospitals, which were also more likely to be located in counties with higher competition. The different-hospital readmission group had higher odds for in-hospital death (8.1 vs. 6.7%; P < 0.0001) and greater readmission hospital costs ($15 671.8 vs. $14 286.4; P < 0.001) than the same-hospital readmission group. Conclusions: Patient, hospital and market characteristics predicted different-hospital readmissions compared with same-hospital readmissions. Mortality and cost outcomes were worse among patients with different-hospital readmissions. Strategies for better care coordination targeting people at risk for different-hospital readmissions are necessary. C1 [Kim, Hongsoo] Seoul Natl Univ, Grad Sch Publ Hlth, Seoul, South Korea. [Kim, Hongsoo] Seoul Natl Univ, Inst Hlth & Environm, Seoul, South Korea. [Hung, William W.; Boockvar, Kenneth] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Hung, William W.; Boockvar, Kenneth] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Paik, Myunghee Cho; Kim, Gi-Soo] Seoul Natl Univ, Coll Nat Sci, Dept Stat, Seoul 151742, South Korea. [Ross, Joseph S.] Yale Univ, Sch Med, Gen Internal Med, New Haven, CT USA. [Boockvar, Kenneth] Jewish Home Lifecare, Res Inst Aging, New York, NY USA. RP Kim, H (reprint author), Seoul Natl Univ, Grad Sch Publ Hlth, 1 Gwanak Ro, Seoul, South Korea. EM hk65@snu.ac.kr OI Boockvar, Kenneth/0000-0003-1165-5558 FU University Research Challenge Fund of New York University, NY; National Research Foundation of Korea (NRF) grant - Korean government (MSIP) [2013R1A2A2A01067262]; National Institute on Aging [K08AG032886]; United States Department of Veterans Affairs Health Services Research and Development Service [REA 08-260]; Greenwall Foundation, New York, NY FX This work was supported by the University Research Challenge Fund of New York University, NY (H.K.); a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2013R1A2A2A01067262 to M.C.P. and J.K.) and the National Institute on Aging (K08AG032886 to J.S.R.); and the United States Department of Veterans Affairs Health Services Research and Development Service (REA 08-260 to K.B.) and the Greenwall Foundation, New York, NY (K.B.). The contents do not represent the views of any funding agency addressed above. NR 26 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 EI 1464-3677 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD DEC 1 PY 2015 VL 27 IS 6 BP 513 EP 519 DI 10.1093/intqhc/mzv082 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DB1EI UT WOS:000368250400013 PM 26472739 ER PT J AU Zhou, J Jin, JO Du, J Yu, Q AF Zhou, Jing Jin, Jun-O Du, Juan Yu, Qing TI Innate Immune Signaling Induces IL-7 Production, Early Inflammatory Responses, and Sjogren's-Like Dacryoadenitis in C57BL/6 Mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE lacrimal gland; Sjogren's syndrome; poly I:C; interleukin-7; innate immune response ID TOLL-LIKE RECEPTOR-3; SALIVARY EPITHELIAL-CELLS; TRIF-DEPENDENT PATHWAYS; INDEPENDENT PATHWAYS; ANTIBODY-PRODUCTION; DENDRITIC CELLS; CHRONIC COLITIS; ACTIVATION; INDUCTION; DISEASE AB PURPOSE. Innate immune signaling elicited by polyinosinic-polycytidylic acid (poly I:C) induces IL-7 production and early inflammatory responses in the salivary gland and accelerates the development of Sjogren's syndrome (SS)-like sialadenitis. Whether poly I:C can induce similar responses in the lacrimal gland (LAC) has not been characterized. In this study, we examined the early responses and pathologic changes of the LAC tissue in response to poly I:C treatment. METHODS. Poly I:C or recombinant human IL-7 was injected intraperitoneally into C57BL/6 mice, and the LAC was harvested at different time points. Expression of chemokines and cytokines in the LAC was measured by RT-PCR, immunofluorescence staining, and immunohistochemistry. Leukocytic infiltration and caspase-3 activation were analyzed by hematoxylin and eosin staining and immunohistochemistry. Serum antinuclear antibody levels were also determined. Tear secretion was measured by phenol red cotton threads. RESULTS. Administration of poly I:C induced IL-7 gene expression and protein production in the LAC. Poly I:C also induced the expression of CXCR3 ligands, monocyte chemoattractant protein-1, IL-23p19, and TNF-alpha in the LAC in an IL-7-dependent fashion. Similarly to poly I:C, administration of exogenous IL-7 also up-regulated these proinflammatory mediators. Furthermore, repeated administration of poly I:C to C57BL/6 mice over an 8-day period caused leukocytic infiltration and caspase-3 activation in the LAC, antinuclear antibody production, and impaired tear secretion. CONCLUSIONS. Poly I:C induces IL-7 production, early inflammatory responses, and characteristic pathologies of SS-like dacryoadenitis in non-autoimmune-prone C57BL/6 mice. These findings provide new evidence that viral infection-elicited innate immune signaling may be one of the early triggers of SS-like dacryoadenitis. C1 [Zhou, Jing; Jin, Jun-O; Du, Juan; Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. [Zhou, Jing; Yu, Qing] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Yu, Q (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. EM qyu@forsyth.org RI Zhou, jing/B-4718-2016 FU National Institutes of Health [P30DE020751, R01 DE023838] FX Supported by grants from the National Institutes of Health (P30DE020751, R01 DE023838). NR 40 TC 4 Z9 4 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2015 VL 56 IS 13 BP 7831 EP 7838 DI 10.1167/iovs.15-17368 PG 8 WC Ophthalmology SC Ophthalmology GA DB1BU UT WOS:000368243800026 PM 26658504 ER PT J AU Mansh, M Katz, KA Linos, E Chren, MM Arron, S AF Mansh, Matthew Katz, Kenneth A. Linos, Eleni Chren, Mary-Margaret Arron, Sarah TI Association of Skin Cancer and Indoor Tanning in Sexual Minority Men and Women SO JAMA DERMATOLOGY LA English DT Article ID UNITED-STATES; CUTANEOUS MELANOMA; RISK BEHAVIORS; PREVALENCE; METAANALYSIS; POPULATION; RADIATION; HISTORY; DEPRESSION; EXPOSURE AB IMPORTANCE Skin cancer, the most common cancer in the United States, is highly associated with outdoor and indoor tanning behaviors. Although indoor tanning has been suggested to be more common among sexual minority (self-reported as homosexual, gay, or bisexual) men compared with heterosexual men, whether rates of skin cancer vary by sexual orientation is unknown. OBJECTIVE To investigate whether skin cancer prevalence and indoor tanning behaviors vary by sexual orientation in the general population. DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional study using data from the 2001, 2003, 2005, and 2009 California Health Interview Surveys (CHISs) and the 2013 National Health Interview Survey (NHIS) of population-based samples of the California and US noninstitutionalized civilian population. Participants included 192 575 men and women 18 years or older who identified as heterosexual or a sexual minority. MAIN OUTCOMES AND MEASURES Self-reported lifetime history of skin cancer and 12-month history of indoor tanning. RESULTS The study included 78 487 heterosexual men, 3083 sexual minority men, 107 976 heterosexual women, and 3029 sexual minority women. Sexual minority men were more likely than heterosexual men to report having skin cancer (2001-2005 CHISs: adjusted odds ratio [aOR], 1.56; 95% CI, 1.18-2.06, P < .001; 2013 NHIS: aOR, 2.13; 95% CI, 1.14-3.96, P = .02) and having tanned indoors (2009 CHIS: aOR, 5.80; 95% CI, 2.90-11.60, P < .001; 2013 NHIS: aOR, 3.16; 95% CI, 1.77-5.64, P < .001). Sexual minority women were less likely than heterosexual women to report having had nonmelanoma skin cancer (2001-2005 CHIS: aOR, 0.56; 95% CI, 0.37-0.86, P = .008) and having tanned indoors (2009 CHIS: aOR, 0.43; 95% CI, 0.20-0.92, P = .03; 2013 NHIS: aOR, 0.46; 95% CI, 0.26-0.81, P = .007). CONCLUSIONS AND RELEVANCE Sexual minority men indoor tan more frequently and report higher rates of skin cancer than heterosexual men. Primary and secondary prevention efforts targeted at sexual minority men might reduce risk factors for, and consequences of, skin cancer. C1 [Mansh, Matthew; Linos, Eleni; Chren, Mary-Margaret; Arron, Sarah] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94115 USA. [Mansh, Matthew] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Katz, Kenneth A.] Kaiser Permanente, Dept Dermatol, Pleasanton, CA USA. [Chren, Mary-Margaret; Arron, Sarah] San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA USA. RP Arron, S (reprint author), Univ Calif San Francisco, Dept Dermatol, 1701 Divisadero St,Third Floor,Box 316, San Francisco, CA 94115 USA. EM sarah.arron@ucsf.edu OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700 FU Stanford Medical Scholars Research Grant; National Center for Advancing Translational Sciences, National Institutes of Health [KL2TR000143]; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [K24 AR052667] FX This study was supported by a Stanford Medical Scholars Research Grant (Mr Mansh); grant KL2TR000143 from the National Center for Advancing Translational Sciences, National Institutes of Health to the University of California, San Francisco, Clinical and Translational Science Institute (Drs Linos and Arron); and grant K24 AR052667 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (Dr Chren). NR 48 TC 5 Z9 5 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD DEC PY 2015 VL 151 IS 12 BP 1308 EP 1316 DI 10.1001/jamadermatol.2015.3126 PG 9 WC Dermatology SC Dermatology GA DA7OX UT WOS:000367994700006 ER PT J AU Datta, SK Warshaw, EM Edison, KE Kapur, K Thottapurathu, L Moritz, TE Reda, DJ Whited, JD AF Datta, Santanu K. Warshaw, Erin M. Edison, Karen E. Kapur, Kush Thottapurathu, Lizy Moritz, Thomas E. Reda, Domenic J. Whited, John D. TI Cost and Utility Analysis of a Store-and-Forward Teledermatology Referral System A Randomized Clinical Trial SO JAMA DERMATOLOGY LA English DT Article ID HEALTH-STATE UTILITIES; QUALITY-OF-LIFE; CONSULT SYSTEM AB IMPORTANCE The costs and utility of teledermatology are important features of implementation. Such an analysis requires a description of the perspective of the entity that will bear the cost. OBJECTIVE To assess the costs and utility of a store-and-forward teledermatology referral process compared with a conventional referral process from the perspectives of the Department of Veterans Affairs (VA) and society. DESIGN, SETTING, AND PARTICIPANTS Three hundred ninety-one randomized participants were referred from remote sites of primary care to the dermatology services of 2 VA medical facilities for ambulatory skin conditions from December 2008 through June 2010, and follow-up was completed in March 2011. The time trade-off utility measures and costs were collected during a 9-month period among participants in a 2-site parallel group randomized clinical trial. The perspectives of the VA and society were evaluated. The multiple imputation procedure or weighted means were used for missing data elements. Data were analyzed from January to July 2014. INTERVENTIONS Referrals were managed using store-and-forward teledermatology or a conventional text-based referral process. MAIN OUTCOMES AND MEASURES Total costs from the perspectives of the VA and society incurred during the 9-month follow-up were used to derive per-participant costs. Utility, using the time trade-off method, was the measure of effectiveness. RESULTS From the VA perspective, the total cost for conventional referrals was $66 145 (minimum, $58 697; maximum, $71 635), or $338 (SD, $291) per participant (196 participants); the total cost for teledermatology referrals was $59 917 (mimimum, $51 794; maximum, $70 398), or $308 (SD, $298) per participant (195 participants). The $30 difference in per-participant cost was not statistically significant (95% CI, -$79 to $20). From the societal perspective, the total cost for conventional referrals was $106 194 (minimum, $98 746; maximum, $111 684), or $542 (SD, $403) per participant (196 participants); the total cost for teledermatology referrals was $89 523 (minimum, $81 400; maximum, $100 400) or $460 (SD, $428) per participant. This $82 difference in per-participant cost was statistically significant (95% CI, -$12 to -$152). From baseline to the 9-month follow-up, the time trade-off utility value improved by 0.02 in the conventional referral group and 0.03 in the teledermatology group. This difference was not statistically significant (P = .50). CONCLUSIONS AND RELEVANCE Compared with conventional referrals, store-and-forward teledermatology referrals were performed at a comparable cost (VA perspective) or at a lower cost (societal perspective) with no evidence of a difference in utility as measured by the time trade-off method. C1 [Datta, Santanu K.; Whited, John D.] Durham Vet Affairs Med Ctr, Res & Dev, Durham, NC 27705 USA. [Datta, Santanu K.; Whited, John D.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Warshaw, Erin M.] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Warshaw, Erin M.] Minneapolis Vet Affairs Hlth Care Syst, Dermatol Serv, Minneapolis, MN USA. [Edison, Karen E.] Univ Missouri, Dept Dermatol, Columbia, MO 65211 USA. [Kapur, Kush] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Thottapurathu, Lizy; Moritz, Thomas E.; Reda, Domenic J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. RP Whited, JD (reprint author), Durham Vet Affairs Med Ctr, Res & Dev, Mail Stop 151,508 Fulton St, Durham, NC 27705 USA. EM john.whited@va.gov FU Department of Veterans Affairs Office of Research and Development, Health Services Research and Development [IIR 05-278] FX This study was supported by Service Award IIR 05-278 from the Department of Veterans Affairs Office of Research and Development, Health Services Research and Development. NR 16 TC 7 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD DEC PY 2015 VL 151 IS 12 BP 1323 EP 1329 DI 10.1001/jamadermatol.2015.2362 PG 7 WC Dermatology SC Dermatology GA DA7OX UT WOS:000367994700009 PM 26375589 ER PT J AU Goddard, AL Vleugels, RA LeBoeuf, NR O'Farrell, DA Cormack, RA Hansen, JL Kupper, TS Devlin, PM AF Goddard, Allison L. Vleugels, Ruth Ann LeBoeuf, Nicole R. O'Farrell, Desmond A. Cormack, Robert A. Hansen, Jorgen L. Kupper, Thomas S. Devlin, Phillip M. TI Palliative Therapy for Recalcitrant Cutaneous T-Cell Lymphoma of the Hands and Feet With Low-Dose, High Dose-Rate Brachytherapy SO JAMA DERMATOLOGY LA English DT Article ID MYCOSIS-FUNGOIDES; RADIATION-THERAPY AB IMPORTANCE Cutaneous T-cell lymphoma (CTCL) of the hands and feet can be challenging to treat and cause significant disability for patients. Although CTCL is a highly radiosensitive tumor, the complex topography of acral surfaces presents challenges to achieving homogeneous superficial dosing of traditional electron beam therapy. In addition, traditional dosing may result in substantial acute cutaneous toxic effects. Recent reports demonstrate that low-dose palliative radiotherapy may be as effective as traditional regimens in CTCL. High dose-rate (HDR) brachytherapy allows for control of the depth of radiation penetration over complex curved surfaces. This study investigated the role of low-dose HDR brachytherapy for acral CTCL lesions. OBSERVATIONS Six patients with a total of 8 acral CTCL lesions received low-dose HDR brachytherapy during a 3-year period. Rapid improvement and clinical clearance were observed in all treated lesions with minimal to no acute cutaneous toxic effects. During a mean follow-up period of 15.8 months, 1 lesion recurred locally; the remaining 7 lesions had sustained clinical remission. No long-term sequelae were observed. CONCLUSIONS AND RELEVANCE This case series demonstrates that low-dose HDR brachytherapy provides excellent palliation for local control of acral CTCL lesions, offering homogeneous, controlled dosing for complex topographic sites with minimal to no cutaneous toxic effects. C1 [Goddard, Allison L.; Vleugels, Ruth Ann; LeBoeuf, Nicole R.; Kupper, Thomas S.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Goddard, Allison L.; Vleugels, Ruth Ann; LeBoeuf, Nicole R.; Kupper, Thomas S.; Devlin, Phillip M.] Harvard Univ, Sch Med, Boston, MA USA. [Goddard, Allison L.; LeBoeuf, Nicole R.; Kupper, Thomas S.; Devlin, Phillip M.] Dana Farber Canc Inst, Ctr Cutaneous Oncol, Boston, MA 02115 USA. [O'Farrell, Desmond A.; Cormack, Robert A.; Hansen, Jorgen L.; Devlin, Phillip M.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Goddard, AL (reprint author), Brigham & Womens Hosp, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA. EM agoddard@partners.org NR 13 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD DEC PY 2015 VL 151 IS 12 BP 1354 EP 1357 DI 10.1001/jamadermatol.2015.3028 PG 4 WC Dermatology SC Dermatology GA DA7OX UT WOS:000367994700016 ER PT J AU Chang, DC Parina, RP Wilson, SE AF Chang, David C. Parina, Ralitza P. Wilson, Samuel E. TI Survival After Endovascular vs Open Aortic Aneurysm Repairs SO JAMA SURGERY LA English DT Article ID MEDICARE BENEFICIARIES; RANDOMIZED-TRIAL; MORTALITY; OUTCOMES; EVAR AB IMPORTANCE To our knowledge, long-term outcomes of open and endovascular (EVAR) repairs of abdominal aortic aneurysms (AAAs) have not been studied on a population level outside a controlled trial setting. OBJECTIVE To determine long-term outcomes of EVAR vs open repair on a population level. DESIGN, SETTING, AND PARTICIPANTS Analysis of the longitudinally linked California Office of Statewide Health Planning and Development inpatient database from 2001 to 2009. Median follow-up was 3.3 years. EXPOSURES Endovascular vs open repairs. MAIN OUTCOMES AND MEASURES Mortality and complications at 30 days, as well as long-term mortality and complications up to 9 years. RESULTS In this observational study, a total of 23 670 patients were studied, with 52% receiving EVAR. Endovascular repair was associated with improved 30-day outcomes (all-cause mortality, readmission, surgical site infection, pneumonia, and sepsis), as well as significantly improved survival until 3 years postoperatively. After 3 years, mortality was higher for patients who underwent an EVAR repair. No significant difference in long-term mortality was observed for the entire cohort on adjusted analysis (hazard ratio, 0.99; 95% CI, 0.94-1.04; P = .64). Endovascular repair was found to be associated with a significantly higher rate of reinterventions and AAA late ruptures. CONCLUSIONS AND RELEVANCE The survival advantage for EVAR repair in a state wide population is maintained for 3 years. After 3 years, EVAR repair was associated with higher mortality; however, these mortality differences did not reach statistical significance over the entire study period. Reintervention and late AAA rupture rates are higher after EVAR repair. C1 [Chang, David C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Parina, Ralitza P.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Wilson, Samuel E.] Univ Calif Irvine, Dept Surg, Orange, CA 92868 USA. RP Wilson, SE (reprint author), Univ Calif Irvine, Dept Surg, Med Ctr, 101 City Dr,Bldg 53,Room 208,Rte 81, Orange, CA 92868 USA. EM wilsonse@uci.edu NR 11 TC 4 Z9 5 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD DEC PY 2015 VL 150 IS 12 BP 1160 EP 1166 DI 10.1001/jamasurg.2015.2644 PG 7 WC Surgery SC Surgery GA DA7NJ UT WOS:000367990700012 PM 26331571 ER PT J AU Jemal, A Lin, CC DeSantis, C Sineshaw, H Freedman, RA AF Jemal, Ahmedin Lin, Chun Chieh DeSantis, Carol Sineshaw, Helmneh Freedman, Rachel A. TI Temporal Trends in and Factors Associated With Contralateral Prophylactic Mastectomy Among US Men With Breast Cancer SO JAMA SURGERY LA English DT Letter C1 [Jemal, Ahmedin; Lin, Chun Chieh; DeSantis, Carol; Sineshaw, Helmneh] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30303 USA. [Freedman, Rachel A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jemal, A (reprint author), Amer Canc Soc, Surveillance & Hlth Serv Res, 250 Williams St NW, Atlanta, GA 30303 USA. EM ahmedin.jemal@cancer.org NR 6 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD DEC PY 2015 VL 150 IS 12 BP 1192 EP 1194 DI 10.1001/jamasurg.2015.2657 PG 3 WC Surgery SC Surgery GA DA7NJ UT WOS:000367990700020 PM 26333114 ER PT J AU Graham, LA Hollis, RH Richman, JS Hawn, MT AF Graham, Laura A. Hollis, Robert H. Richman, Joshua S. Hawn, Mary T. TI Frequency of Surgery Cancellations Associated With Myocardial Infarction or Death 6 Months After Coronary Stent Placement SO JAMA SURGERY LA English DT Letter ID NONCARDIAC SURGERY; RISK C1 [Graham, Laura A.; Hollis, Robert H.; Richman, Joshua S.; Hawn, Mary T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Graham, Laura A.; Hollis, Robert H.; Richman, Joshua S.; Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL USA. [Hawn, Mary T.] Stanford Univ, Dept Surg, Stanford, CA 94305 USA. RP Hawn, MT (reprint author), Stanford Univ, 300 Pasteur Dr,M121 Alway Bldg, Palo Alto, CA 94306 USA. EM mhawn@stanford.edu NR 6 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD DEC PY 2015 VL 150 IS 12 BP 1199 EP 1201 DI 10.1001/jamasurg.2015.3078 PG 4 WC Surgery SC Surgery GA DA7NJ UT WOS:000367990700024 PM 26443936 ER PT J AU Kachooei, AR Rivlin, M Shojaie, B van Dijk, CN Mudgal, C AF Kachooei, Amir Reza Rivlin, Michael Shojaie, Babak van Dijk, C. Niek Mudgal, Chaitanya TI Intraoperative Technique for Evaluation of the Interosseous Ligament of the Forearm SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Interosseous ligament; interosseous membrane; lateral pull ID RADIAL HEAD FRACTURES; MEMBRANE; DISRUPTION; CADAVER AB Purpose To introduce a technique for the diagnosis of interosseous ligament (IOL) disruption based on lateral displacement of the radius after radial head resection and to determine the cutoff value of the lateral displacement for the diagnosis of disruption, the best elbow position for testing, and the diagnostic performance of the technique in different positions. Methods We used 10 fresh-frozen cadavers. After resection of the radial head, a Steinman pin was placed into the radius medullary canal and used to mark the pin location on the capitellum. We applied 1 kg force to pull the proximal radius laterally and measured the displacement in full supination, neutral, and full pronation of the forearm with the elbow in extension and then in 90 degrees flexion. All measurements were performed once with the IOL intact and again with it cut. To assess diagnostic efficacy, receiver operating characteristics curves were constructed. To determine the quality of the technique, we measured the area under the receiver operating characteristics curve for each position. We also determined the cutoff value to obtain the highest sensitivity and specificity. Results The area under the curve of the test in extension-supination and flexion-supination showed that these positions were excellent for the diagnosis of IOL disruption. The cutoff value of 5.5 mm lateral displacement in extension-supination had 100% sensitivity and 90% specificity. In flexion-supination, the cutoff value of 9 mm had 100% sensitivity and 90% specificity for the diagnosis of IOL disruption. Conclusions This maneuver was reliable and accurate in cadavers with complete IOL disruption. It is likely that in an intraoperative setting, these results will be reproducible. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved. C1 [Kachooei, Amir Reza] Mashhad Univ Med Sci, Orthoped Res Ctr, Mashhad, Iran. [Shojaie, Babak; Mudgal, Chaitanya] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Rivlin, Michael] Thomas Jefferson Univ, Rothman Inst, Dept Hand & Orthoped Surg, Philadelphia, PA 19107 USA. [van Dijk, C. Niek] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. RP Mudgal, C (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100 55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 16 TC 2 Z9 2 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2015 VL 40 IS 12 BP 2372 EP 2376 DI 10.1016/j.jhsa.2015.08.030 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DB1LV UT WOS:000368270600007 PM 26547797 ER PT J AU Moradi, A Mellema, JJ Oflazoglu, K Isakov, A Ring, D Vranceanu, AM AF Moradi, Ali Mellema, Jos J. Oflazoglu, Kamilcan Isakov, Aleksandr Ring, David Vranceanu, Ana-Maria TI The Relationship Between Catastrophic Thinking and Hand Diagram Areas SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Hand diagram; psychosocial; catastrophic thinking; symptoms; pain and numbness ID CARPAL-TUNNEL-SYNDROME; LOW-BACK-PAIN; SYMPTOM DIAGRAM; DISABILITY; DEPRESSION; DIAGNOSIS; SHOULDER; PATIENT; DETERMINANTS; INSTRUMENTS AB Purpose To evaluate the relationship between the total area marked on pain and numbness diagrams and psychosocial factors (depression, pain catastrophic thinking, and health anxiety). Methods A total of 155 patients marked painful and numb areas on separate hand diagrams. Patients also completed demographic, condition-related, and psychosocial (Pain Catastrophizing Scale, Patient-Reported Outcomes Measurement Information System Depression Computer Adaptive Test, and Short Health Anxiety Inventory) questionnaires. Bivariate and multivariable analyses were used to determine factors associated with total area marked on the pain and numbness diagrams. Results The total area marked on the pain diagram correlated with catastrophic thinking, symptoms of depression, and health anxiety. In multivariable analysis, catastrophic thinking was the sole predictor of marked pain area, accounting for 10% of variance in the hand pain diagram. The total area marked on the numbness diagram correlated with the interval between onset and visit, diagnosis, catastrophic thinking, and symptoms of depression. In multivariable analysis, the interval between onset and visit, a diagnosis of carpal tunnel syndrome, and catastrophic thinking were independently associated with total area marked on the hand numbness diagram. Conclusions Catastrophic thinking was independently associated with larger pain and numbness areas on a hand diagram. This suggests that larger symptom markings on hand diagrams may indicate less effective coping strategies. Hand diagrams might be used as a basis for discussion of coping strategies and illness behavior in patients with upper extremity conditions. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved. C1 [Moradi, Ali; Mellema, Jos J.; Oflazoglu, Kamilcan; Isakov, Aleksandr; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg,Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Vranceanu, Ana-Maria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Behav Med, Boston, MA 02114 USA. [Moradi, Ali] Mashhad Univ Med Sci, Orthoped Res Ctr, Mashhad, Iran. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Dept Orthoped Surg,Hand & Upper Extrem, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 33 TC 2 Z9 2 U1 2 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2015 VL 40 IS 12 BP 2440 EP 2446 DI 10.1016/j.jhsa.2015.07.031 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DB1LV UT WOS:000368270600018 PM 26409578 ER PT J AU Sensor, JD Suydam, R George, JC Liberman, MC Lovano, D Rhaganti, MA Usip, S Vinyard, CJ Thewissen, JGM AF Sensor, Jennifer D. Suydam, Robert George, John C. Liberman, M. C. Lovano, Denise Rhaganti, Mary Ann Usip, Sharon Vinyard, Christopher J. Thewissen, J. G. M. TI The Spiral Ganglion and Rosenthal's Canal in Beluga Whales SO JOURNAL OF MORPHOLOGY LA English DT Article DE Cetacea; Odontoceti; Delphinapterus leucas; hearing; cochlea; inner ear ID INDUCED HEARING-LOSS; DELPHINAPTERUS-LEUCAS; TURSIOPS-TRUNCATUS; ACOUSTIC OVERSTIMULATION; MORPHOMETRIC-ANALYSIS; DEGENERATION PATTERN; COCHLEAR STRUCTURE; CELL DEGENERATION; TIME SEQUENCE; GUINEA-PIGS AB With the increase of human activity and corresponding increase in anthropogenic sounds in marine waters of the Arctic, it is necessary to understand its effect on the hearing of marine wildlife. We have conducted a baseline study on the spiral ganglion and Rosenthal's canal of the cochlea in beluga whales (Delphinapterus leucas) as an initial assessment of auditory anatomy and health. We present morphometric data on the length of the cochlea, number of whorls, neuron densities along its length, Rosenthal's canal length, and cross-sectional area, and show some histological results. In belugas, Rosenthal's canal is not a cylinder of equal cross-sectional area, but its cross-section is greatest near the apex of the basal whorl. We found systematic variation in the numbers of neurons along the length of the spiral ganglion, indicating that neurons are not dispersed evenly in Rosenthal's canal. These results provide data on functionally important structural parameters of the beluga ear. We observed no signs of acoustic trauma in our sample of beluga whales. (C) 2015 Wiley Periodicals, Inc. C1 [Sensor, Jennifer D.; Lovano, Denise; Usip, Sharon; Vinyard, Christopher J.; Thewissen, J. G. M.] Northeast Ohio Med Univ, Dept Anat & Neurobiol, Rootstown, OH 44240 USA. [Suydam, Robert; George, John C.] North Slope Borough, Dept Wildlife Management, Barrow, AK 99723 USA. [Liberman, M. C.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Liberman, M. C.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Rhaganti, Mary Ann] Kent State Univ, Dept Anthropol, Kent, OH 44240 USA. RP Sensor, JD (reprint author), Northeast Ohio Med Univ, Dept Anat & Neurobiol, Rootstown, OH 44240 USA. EM jsensor@neomed.edu OI Thewissen, J. G. M./0000-0002-0973-4137 FU North-Slope Borough; North Slope Borough School District; Kent State University School of Biomedical Science; NEOMED; NSB-Shell Baseline Studies Program FX Contract grant sponsors: North-Slope Borough, North Slope Borough School District, Kent State University School of Biomedical Science, NEOMED, and the NSB-Shell Baseline Studies Program. NR 52 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0362-2525 EI 1097-4687 J9 J MORPHOL JI J. Morphol. PD DEC PY 2015 VL 276 IS 12 BP 1455 EP 1466 DI 10.1002/jmor.20434 PG 12 WC Anatomy & Morphology SC Anatomy & Morphology GA DB1IT UT WOS:000368262600006 PM 26769322 ER PT J AU Rostami, R Badran, BW Kazemi, R Habibnezhad, M George, MS AF Rostami, Reza Badran, Bashar W. Kazemi, Reza Habibnezhad, Mohammad George, Mark S. TI Long-lasting analgesic effect of transcranial direct current stimulation in treatment of chronic endometriosis pain SO JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH LA English DT Article DE endometriosis; motor cortex; pain; transcranial direct current stimulation ID CORTEX; TDCS AB Approximately 10-20% of women of reproductive age suffer from endometriosis, with 70-90% of these women reporting chronic pain symptoms that persist during their menstrual cycle. We are presenting a case in which a novel form of noninvasive brain stimulation called transcranial direct current stimulation was used as an intervention in a 32-year-old woman with persistent, chronic pain symptoms caused by endometriosis for 20 years. Ten daily, 20-min sessions of 2-mA anodal transcranial direct current stimulation were applied over the left primary motor cortex. Acutely, visual analog scale pain symptoms were reduced by 60%. There were also significant decreases in modules of the Endometriosis Health Profile. At the 4-month follow-up, the patient still expressed an overall decrease in pain symptoms of 30%. C1 [Rostami, Reza; Badran, Bashar W.; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Rostami, Reza] Univ Tehran, Fac Psychol & Educ, Tehran, Iran. [Rostami, Reza; Kazemi, Reza; Habibnezhad, Mohammad] Shahid Beheshti Univ, Atieh Clin Neurosci Ctr, Tehran, Iran. [Habibnezhad, Mohammad] Shahid Beheshti Univ, Inst Cognit & Brain Sci, Tehran, Iran. [Kazemi, Reza] Lorestan Univ, Fac Literature & Human Sci, Dept Psychol, Khorramabad, Iran. RP Rostami, R (reprint author), Univ Tehran, Fac Educ & Psychol, Jalal Al Ahmad St, Tehran, Iran. EM rrostami@ut.ac.ir NR 12 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1341-8076 EI 1447-0756 J9 J OBSTET GYNAECOL RE JI J. Obstet. Gynaecol. Res. PD DEC PY 2015 VL 41 IS 12 BP 1998 EP 2001 DI 10.1111/jog.12817 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DA7YG UT WOS:000368020900021 PM 26419900 ER PT J AU Kotton, CN AF Kotton, Camille Nelson TI Cytomegalovirus Immunodiagnostics: Getting Closer to Personalized Cytomegalovirus Prevention? SO LIVER TRANSPLANTATION LA English DT Editorial Material ID TRANSPLANT RECIPIENTS; IMMUNE-RESPONSE; ELISPOT ASSAY C1 [Kotton, Camille Nelson] Harvard Univ, Massachusetts Gen Hosp, Transplant & Immunocompromised Host Infect Dis, Div Infect Dis,Sch Med, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplant & Immunocompromised Host Infect Dis, Div Infect Dis,Sch Med, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD DEC PY 2015 VL 21 IS 12 BP 1462 EP 1464 DI 10.1002/lt.24355 PG 3 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA DA9OK UT WOS:000368138700002 PM 26443070 ER PT J AU Yip, SSF Rottmann, J Berbeco, RI AF Yip, Stephen S. F. Rottmann, Joerg Berbeco, Ross I. TI Beam's-eye-view imaging during non-coplanar lung SBRT SO MEDICAL PHYSICS LA English DT Article DE stereotactic body radiation therapy; non-coplanar radiotherapy; markerless tracking; beam's-eye-view imaging; EPID imaging ID BODY RADIATION-THERAPY; STEREOTACTIC RADIOTHERAPY; GUIDED RADIOTHERAPY; TUMORS; VERIFICATION; CANCER; FEASIBILITY; CARCINOMA; TRACKING; MOTION AB Purpose: Beam's-eye-view (BEV) imaging with an electronic portal imaging device (EPID) can be performed during lung stereotactic body radiation therapy (SBRT) to monitor the tumor location in real-time. Image quality for each patient and treatment field depends on several factors including the patient anatomy and the gantry and couch angles. The authors investigated the angular dependence of automatic tumor localization during non-coplanar lung SBRT delivery. Methods: All images were acquired at a frame rate of 12 Hz with an amorphous silicon EPID. A previously validated markerless lung tumor localization algorithm was employed with manual localization as the reference. From ten SBRT patients, 12 987 image frames of 123 image sequences acquired at 48 different gantry-couch rotations were analyzed. delta was defined by the position difference of the automatic and manual localization. Results: Regardless of the couch angle, the best tracking performance was found in image sequences with a gantry angle within 20 degrees of 250 degrees (delta = 1.40 mm). Image sequences acquired with gantry angles of 150 degrees, 210 degrees, and 350 degrees also led to good tracking performances with delta = 1.77-2.00 mm. Overall, the couch angle was not correlated with the tracking results. Among all the gantry-couch combinations, image sequences acquired at (theta = 30 degrees, phi = 330 degrees.), (theta = 210 degrees, phi= 10 degrees), and (theta = 250 degrees, phi = 30 degrees) led to the best tracking results with delta = 1.19-1.82 mm. The worst performing combinations were (theta = 90 degrees and 230 degrees, phi= 10 degrees.) and (theta= 270 degrees, phi = 30 degrees) with delta > 3.5 mm. However, 35% (17/48) of the gantry-couch rotations demonstrated substantial variability in tracking performances between patients. For example, the field angle (theta= 70 degrees, phi= 10 degrees) was acquired for five patients. While the tracking errors were = 1.98 mm for three patients, poor performance was found for the other two patients with delta = 2.18 mm, leading to average tracking error of 2.70 mm. Only one image sequence was acquired for all other gantry-couch rotations (delta = 1.18-10.29 mm). Conclusions: Non-coplanar beams with gantry-couch rotation of (theta = 30 degrees, phi= 330 degrees), (theta = 210 degrees, phi = 10 degrees), and (theta = 250 degrees, phi = 30 degrees) have the highest accuracy for BEV lung tumor localization. Additionally, gantry angles of 150 degrees, 210 degrees, 250 degrees, and 350 degrees also offer good tracking performance. The beam geometries (theta = 90 degrees and 230 degrees, phi = 10 degrees) and (theta= 270 degrees, phi= 30 degrees) are associated with substantial automatic localization errors. Overall, lung tumor visibility and tracking performance were patient dependent for a substantial number of the gantry-couch angle combinations studied. (C) 2015 American Association of Physicists in Medicine. C1 [Yip, Stephen S. F.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yip, SSF (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM syip@lroc.harvard.edu FU National Cancer Institute [R01CA188446-01]; Varian Medical Systems, Inc. FX The project described was supported, in part, by a grant from Varian Medical Systems, Inc., and Award No. R01CA188446-01 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 24 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2015 VL 42 IS 12 BP 6776 EP 6783 DI 10.1118/1.4934824 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB1BX UT WOS:000368244100002 PM 26632035 ER PT J AU Gholipour, A Afacan, O Aganj, I Scherrer, B Prabhu, SP Sahin, M Warfield, SK AF Gholipour, Ali Afacan, Onur Aganj, Iman Scherrer, Benoit Prabhu, Sanjay P. Sahin, Mustafa Warfield, Simon K. TI Super-resolution reconstruction in frequency, image, and wavelet domains to reduce through-plane partial voluming in MRI SO MEDICAL PHYSICS LA English DT Article DE super-resolution; image reconstruction; image fusion; nonuniform reconstruction; density compensation; slice profile; partial voluming; tuberous sclerosis complex ID FETAL-BRAIN MRI; DENSITY COMPENSATION; QUALITY EVALUATION; ACQUISITIONS; RESOLUTION; REGISTRATION; MOTION; DTI AB Purpose: To compare and evaluate the use of super-resolution reconstruction (SRR), in frequency, image, and wavelet domains, to reduce through-plane partial voluming effects in magnetic resonance imaging. Methods: The reconstruction of an isotropic high-resolution image from multiple thick-slice scans has been investigated through techniques in frequency, image, and wavelet domains. Experiments were carried out with thick-slice T2-weighted fast spin echo sequence on the Academic College of Radiology MRI phantom, where the reconstructed images were compared to a reference high-resolution scan using peak signal-to-noise ratio (PSNR), structural similarity image metric (SSIM), mutual information (MI), and the mean absolute error (MAE) of image intensity profiles. The application of super-resolution reconstruction was then examined in retrospective processing of clinical neuroimages of ten pediatric patients with tuberous sclerosis complex (TSC) to reduce through-plane partial voluming for improved 3D delineation and visualization of thin radial bands of white matter abnormalities. Results: Quantitative evaluation results show improvements in all evaluation metrics through super-resolution reconstruction in the frequency, image, and wavelet domains, with the highest values obtained from SRR in the image domain. The metric values for image-domain SRR versus the original axial, coronal, and sagittal images were PSNR = 32.26 vs 32.22, 32.16, 30.65; SSIM = 0.931 vs 0.922, 0.924, 0.918; MI = 0.871 vs 0.842, 0.844, 0.831; and MAE= 5.38 vs 7.34, 7.06, 6.19. All similarity metrics showed high correlations with expert ranking of image resolution with MI showing the highest correlation at 0.943. Qualitative assessment of the neuroimages of ten TSC patients through in-plane and out-of-plane visualization of structures showed the extent of partial voluming effect in a real clinical scenario and its reduction using SRR. Blinded expert evaluation of image resolution in resampled out-of-plane views consistently showed the superiority of SRR compared to original axial and coronal image acquisitions. Conclusions: Thick-slice 2D T2-weighted MRI scans are part of many routine clinical protocols due to their high signal-to-noise ratio, but are often severely affected by through-plane partial voluming effects. This study shows that while radiologic assessment is performed in 2D on thick-slice scans, super-resolution MRI reconstruction techniques can be used to fuse those scans to generate a high-resolution image with reduced partial voluming for improved postacquisition processing. Qualitative and quantitative evaluation showed the efficacy of all SRR techniques with the best results obtained from SRR in the image domain. The limitations of SRR techniques are uncertainties in modeling the slice profile, density compensation, quantization in resampling, and uncompensated motion between scans. (C) 2015 American Association of Physicists in Medicine. C1 [Gholipour, Ali; Afacan, Onur; Scherrer, Benoit; Prabhu, Sanjay P.; Warfield, Simon K.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Gholipour, Ali; Afacan, Onur; Aganj, Iman; Scherrer, Benoit; Prabhu, Sanjay P.; Sahin, Mustafa; Warfield, Simon K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Aganj, Iman] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Sahin, Mustafa] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Gholipour, A (reprint author), Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. EM ali.gholipour@childrens.harvard.edu OI Warfield, Simon/0000-0002-7659-3880 FU National Institutes of Health (NIH) [U01NS082320, R01EB018988, R01NS079788, R01EB013248, R41MH086984, R03DE22109]; Harvard Catalyst- Harvard Clinical and Translational Science Center for Research Resources Award [UL1TR001102] FX The authors declare no conflict of interest. This work was supported in part by National Institutes of Health (NIH) Grant Nos. U01NS082320, R01EB018988, R01NS079788, R01EB013248, R41MH086984, R03DE22109, and the Harvard Catalyst- Harvard Clinical and Translational Science Center for Research Resources Award No. UL1TR001102. NR 36 TC 1 Z9 2 U1 4 U2 17 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2015 VL 42 IS 12 BP 6919 EP 6932 DI 10.1118/1.4935149 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB1BX UT WOS:000368244100015 PM 26632048 ER PT J AU Wang, W Viswanathan, AN Damato, AL Chen, Y Tse, Z Pan, L Tokuda, J Seethamraju, RT Dumoulin, CL Schmidt, EJ Cormack, RA AF Wang, Wei Viswanathan, Akila N. Damato, Antonio L. Chen, Yue Tse, Zion Pan, Li Tokuda, Junichi Seethamraju, Ravi T. Dumoulin, Charles L. Schmidt, Ehud J. Cormack, Robert A. TI Evaluation of an active magnetic resonance tracking system for interstitial brachytherapy SO MEDICAL PHYSICS LA English DT Article DE active tracking; interstitial brachytherapy interventional MRI; treatment planning ID CERVIX CANCER BRACHYTHERAPY; RATE PROSTATE BRACHYTHERAPY; GEC-ESTRO; APPLICATOR RECONSTRUCTION; CATHETER RECONSTRUCTION; GUIDED BRACHYTHERAPY; RECOMMENDATIONS; UNCERTAINTIES; GUIDELINES; THERAPY AB Purpose: In gynecologic cancers, magnetic resonance (MR) imaging is the modality of choice for visualizing tumors and their surroundings because of superior soft-tissue contrast. Real-time MR guidance of catheter placement in interstitial brachytherapy facilitates target coverage, and would be further improved by providing intraprocedural estimates of dosimetric coverage. A major obstacle to intraprocedural dosimetry is the time needed for catheter trajectory reconstruction. Herein the authors evaluate an active MR tracking (MRTR) system which provides rapid catheter tip localization and trajectory reconstruction. The authors assess the reliability and spatial accuracy of the MRTR system in comparison to standard catheter digitization using magnetic resonance imaging (MRI) and CT. Methods: The MRTR system includes a stylet with microcoils mounted on its shaft, which can be inserted into brachytherapy catheters and tracked by a dedicated MRTR sequence. Catheter tip localization errors of the MRTR system and their dependence on catheter locations and orientation inside the MR scanner were quantified with a water phantom. The distances between the tracked tip positions of the MRTR stylet and the predefined ground-truth tip positions were calculated for measurements performed at seven locations and with nine orientations. To evaluate catheter trajectory reconstruction, fifteen brachytherapy catheters were placed into a gel phantom with an embedded catheter fixation framework, with parallel or crossed paths. The MRTR stylet was then inserted sequentially into each catheter. During the removal of the MRTR stylet from within each catheter, a MRTR measurement was performed at 40 Hz to acquire the instantaneous stylet tip position, resulting in a series of three-dimensional (3D) positions along the catheter's trajectory. A 3D polynomial curve was fit to the tracked positions for each catheter, and equally spaced dwell points were then generated along the curve. High-resolution 3D MRI of the phantom was performed followed by catheter digitization based on the catheter's imaging artifacts. The catheter trajectory error was characterized in terms of the mean distance between corresponding dwell points in MRTR-generated catheter trajectory and MRI-based catheter digitization. The MRTR-based catheter trajectory reconstruction process was also performed on three gynecologic cancer patients, and then compared with catheter digitization based on MRI and CT. Results: The catheter tip localization error increased as the MRTR stylet moved further off-center and as the stylet's orientation deviated from the main magnetic field direction. Fifteen catheters' trajectories were reconstructed by MRTR. Compared with MRI-based digitization, the mean 3D error of MRTR-generated trajectories was 1.5 +/- 0.5 mm with an in-plane error of 0.7 +/- 0.2 mm and a tip error of 1.7 +/- 0.5 mm. MRTR resolved ambiguity in catheter assignment due to crossed catheter paths, which is a common problem in image-based catheter digitization. In the patient studies, the MRTR-generated catheter trajectory was consistent with digitization based on both MRI and CT. Conclusions: The MRTR system provides accurate catheter tip localization and trajectory reconstruction in the MR environment. Relative to the image-based methods, it improves the speed, safety, and reliability of the catheter trajectory reconstruction in interstitial brachytherapy. MRTR may enable in-procedural dosimetric evaluation of implant target coverage. (C) 2015 American Association of Physicists in Medicine. C1 [Wang, Wei; Tokuda, Junichi; Schmidt, Ehud J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Wang, Wei; Viswanathan, Akila N.; Damato, Antonio L.; Cormack, Robert A.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Yue; Tse, Zion] Univ Georgia, Dept Engn, Athens, GA 30602 USA. [Pan, Li] Siemens Healthcare USA, Baltimore, MD 21287 USA. [Seethamraju, Ravi T.] Siemens Healthcare USA, Boston, MA 02115 USA. [Dumoulin, Charles L.] Cincinnati Childrens Hosp Med Ctr, Radiol, Cincinnati, OH 45229 USA. RP Wang, W (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM wwang21@partners.org FU American Heart Association [10SDG261039, NIH/NIBIB-P41EB015898]; University of Georgia-Georgia Regent University seed grant; BWH Department of Radiation Oncology post-doctoral fellowship; Department of Radiation Oncology/Kaye Family Grant; [NIH/NCI-R21CA167800] FX This work was supported by No. NIH/NCI-R21CA167800, American Heart Association No. 10SDG261039, No. NIH/NIBIB-P41EB015898, University of Georgia-Georgia Regent University seed grant, BWH Department of Radiation Oncology post-doctoral fellowship, and Department of Radiation Oncology/Kaye Family Grant. NR 26 TC 4 Z9 4 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2015 VL 42 IS 12 BP 7114 EP 7121 DI 10.1118/1.4935535 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB1BX UT WOS:000368244100032 ER PT J AU Nadol, JB Handzel, O Amr, S AF Nadol, Joseph B., Jr. Handzel, Ophir Amr, Sami TI Histopathology of the Human Inner Ear in a Patient With Sensorineural Hearing Loss Caused by a Variant in DFNA5 SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Cochlear implant; DFNA5; Histopathology; Human; Inner ear; Mutation; Sensorineural hearing loss ID COCHLEAR IMPLANTATION; CHINESE FAMILY; MUTATION; GENE; IMPAIRMENT AB Hypothesis: Describe the histopathology of the inner ear in a patient with hearing loss caused by a pathogenic variant of the DFNA5 gene. Background: Variants in DFNA5 have been described as causing an autosomal dominant nonsyndromic sensorineural hearing loss. To date, there has been no description of the histopathology of the inner ear in humans with hearing loss because of pathogenic variants in DFNA5. Methods: Temporal bone histopathology by light microscopy, next-generation sequencing (NGS) of DNA obtained from blood, and Sanger sequencing of DNA obtained from formalin fixed temporal bone sections. Results: Both the temporal bone donor and her daughter were shown to have the same pathogenic variant in the DFNA5 gene. The principal histopathologic correlates of the hearing loss were loss of the inner and outer hair cells and severe degeneration of the stria vascularis and spiral ligament throughout the cochlea. In addition, there was severe degeneration of spiral ganglion cells, particularly in the basal turn, and degeneration of vestibular neuroepithelium and neurons. The donor had undergone unilateral cochlear implantation during life. Histopathology demonstrated that the cochlear implant was inserted into the scala vestibuli with considerable new bone formation around the track of the implanted electrode. Conclusions: This is the first report of the histopathology of the inner ear in a patient with hearing loss caused by a pathogenic variant in the DFNA5 gene. C1 [Nadol, Joseph B., Jr.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. [Handzel, Ophir] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Otolaryngol Head & Neck & Maxillofacial Surg, IL-69978 Tel Aviv, Israel. [Amr, Sami] Partners HealthCare Personalized Med, Mol Med Lab, Cambridge, England. [Amr, Sami] Massachusetts Gen Hosp, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.harvard.edu RI Handzel, Ophir/D-8236-2017; OI Handzel, Ophir/0000-0002-6905-3034; Amr, Sami/0000-0003-0927-6057 FU National Institute of Deafness and Other Communication Disorders [R01-DC000152] FX This study was supported by Grant R01-DC000152 from the National Institute of Deafness and Other Communication Disorders. NR 25 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2015 VL 36 IS 10 BP 1616 EP 1621 DI 10.1097/MAO.0000000000000888 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DA7XZ UT WOS:000368020200007 PM 26496673 ER PT J AU Quesnel, AM Nadol, JB Nielsen, GP Curtin, HD Lesperance, MM AF Quesnel, Alicia M. Nadol, Joseph B. Nielsen, G. Petur Curtin, Hugh D. Lesperance, Marci M. TI Temporal Bone Histopathology in NOG-Symphalangism Spectrum Disorder SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Conductive hearing loss; NOG; Stapedectomy; Symphalangism ID CONDUCTIVE HEARING-LOSS; STAPES ANKYLOSIS; FIXATION AB Objective: To describe the human temporal bone histopathology in NOG-related symphalangism spectrum disorder, a spectrum of congenital stape fixation syndromes caused by mutations in the NOG gene. To discuss implications for clinical management. Patient: A patient with a mutation in the NOG gene. Intervention(s): Removal of temporal bones, postmortem temporal bone computed tomography, histologic processing, and review of temporal bones. Main Outcome Measure(s): Temporal bone histopathology and correlation with clinical, genetic, audiologic, and radiologic evaluations. Results: Both temporal bones demonstrated fixation of the stapes footplate to the otic capsule because of a circumferential bridge of calcified cartilage. In the right ear (unoperated), there was no additional abnormality of the ossicles or ossicular joints. In the left ear, fenestrations of the stapes footplate and the lateral semicircular canal were seen, consistent with a history of stapedectomy and fenestration procedure. Severe loss of spiral ganglion neurons throughout the left cochlea accounted for the profound sensorineural hearing loss; there was a normal number of spiral ganglion neurons in the right ear. In both ears, the cochleae demonstrated grossly preserved organs of Corti. Conclusion: The temporal bone pathologic correlate for conductive hearing loss in this patient with a NOG mutation was circumferentially calcified cartilage bridging the stapedovestibular joint space. The temporal bone histopathology findings suggest that conductive hearing loss related to NOG mutation should be improved after stapedectomy; however, care must be taken in extrapolating to all patients with NOG mutations because there may be variability in the pathology, especially given the variability of NOG spectrum disorders. C1 [Quesnel, Alicia M.; Nadol, Joseph B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Nielsen, G. Petur] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Lesperance, Marci M.] Univ Michigan Hlth Syst, Div Pediat Otolaryngol, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI USA. RP Quesnel, AM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM alicia_quesnel@meei.harvard.edu FU National Institutes of Health [U24 DC011943-03] FX This work was supported by a grant from the National Institutes of Health U24 DC011943-03. NR 17 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2015 VL 36 IS 10 BP 1651 EP 1656 DI 10.1097/MAO.0000000000000861 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DA7XZ UT WOS:000368020200013 PM 26474326 ER PT J AU Santos, F Salviz, M Domond, H Nadol, JB AF Santos, Felipe Salviz, Mehti Domond, Haris Nadol, Joseph B. TI Otopathology of Vasculitis in Granulomatosis With Polyangitis SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Facial nerve paralysis; Granulomatosis with polyangitis; Sensorineural hearing loss; Temporal bone; Vasculitis; Wegener's granulomatosis ID WEGENERS-GRANULOMATOSIS; SYSTEMIC VASCULITIS; HEARING-LOSS AB Objective: To describe the temporal bone histopathology of vasculitis in granulomatosis with polyangitis. Background: Granulomatosis with polyangitis is an autoimmune disease that presents as granulomatosis and vasculitis. Otologic findings, including otitis media, hearing loss, vertigo, and facial paralysis are common in this condition. Material and Methods: The temporal bones of four subjects with manifestations of vasculitis attributed to granulomatosis with polyangitis were studied under light microscopy. Results: The four subjects had manifestations of vasculitis including hemorrhage within the cochlea and vestibule, and inflammation and occlusion of vessels in the lateral cochlear wall and the vasa nervorum of the facial nerve. Conclusions: We infer that sensorineural hearing loss, vestibulopathy, and facial nerve paresis in granulomatosis with polyangitis can be the results of vasculitis. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Santos, F (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM felipe_santos@meei.harvard.edu OI Santos, Felipe/0000-0002-3523-665X FU NIH [1U24DC011943-01] FX This work is supported in part by NIH grant 1U24DC011943-01. NR 12 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2015 VL 36 IS 10 BP 1657 EP 1662 DI 10.1097/MAO.0000000000000868 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DA7XZ UT WOS:000368020200014 PM 26496669 ER PT J AU Roland, LT Kallogjeri, D Sinks, BC Rauch, SD Shepard, NT White, JA Goebel, JA AF Roland, Lauren T. Kallogjeri, Dorina Sinks, Belinda C. Rauch, Steven D. Shepard, Neil T. White, Judith A. Goebel, Joel A. TI Utility of an Abbreviated Dizziness Questionnaire to Differentiate Between Causes of Vertigo and Guide Appropriate Referral: A Multicenter Prospective Blinded Study SO OTOLOGY & NEUROTOLOGY LA English DT Article DE History; Questionnaire; Vertigo AB Objective: Test performance of a focused dizziness questionnaire's ability to discriminate between peripheral and nonperipheral causes of vertigo. Study Design: Prospective multicenter. Setting: Four academic centers with experienced balance specialists. Patients: New dizzy patients. Interventions: A 32-question survey was given to participants. Balance specialists were blinded and a diagnosis was established for all participating patients within 6 months. Main Outcomes: Multinomial logistic regression was used to evaluate questionnaire performance in predicting final diagnosis and differentiating between peripheral and nonperipheral vertigo. Univariate and multivariable stepwise logistic regression were used to identify questions as significant predictors of the ultimate diagnosis. C-index was used to evaluate performance and discriminative power of the multivariable models. Results: In total, 437 patients participated in the study. Eight participants without confirmed diagnoses were excluded and 429 were included in the analysis. Multinomial regression revealed that the model had good overall predictive accuracy of 78.5% for the final diagnosis and 75.5% for differentiating between peripheral and nonperipheral vertigo. Univariate logistic regression identified significant predictors of three main categories of vertigo: peripheral, central, and other. Predictors were entered into forward stepwise multivariable logistic regression. The discriminative power of the final models for peripheral, central, and other causes was considered good as measured by c-indices of 0.75, 0.7, and 0.78, respectively. Conclusion: This multicenter study demonstrates a focused dizziness questionnaire can accurately predict diagnosis for patients with chronic/relapsing dizziness referred to outpatient clinics. Additionally, this survey has significant capability to differentiate peripheral from nonperipheral causes of vertigo and may, in the future, serve as a screening tool for specialty referral. Clinical utility of this questionnaire to guide specialty referral is discussed. C1 [Roland, Lauren T.; Kallogjeri, Dorina; Sinks, Belinda C.; Goebel, Joel A.] Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. [Rauch, Steven D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Shepard, Neil T.] Mayo Clin, Div Audiol, Rochester, MN USA. [White, Judith A.] Cleveland Clin, Head & Neck Inst, Sect Vestibular & Balance Disorders, Cleveland, OH USA. RP Roland, LT (reprint author), 660 S Euclid Ave,POB 8115, St Louis, MO 63110 USA. EM rolandl@ent.wustl.edu FU P30 Research Center for Auditory and Vestibular Studies; National Institutes of Health (NIDCD) [P30DC04665] FX The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors gratefully acknowledge Dorina Kallogjeri, M.D., M.P.H., for statistical support and the support of the P30 Research Center for Auditory and Vestibular Studies and the National Institutes of Health (NIDCD Grant no. P30DC04665). NR 6 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2015 VL 36 IS 10 BP 1687 EP 1694 DI 10.1097/MAO.0000000000000884 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DA7XZ UT WOS:000368020200019 PM 26485598 ER PT J AU Remenschneider, AK Owoc, M Kozin, ED McKenna, MJ Lee, DJ Jung, DH AF Remenschneider, Aaron K. Owoc, Maryanna Kozin, Elliott D. McKenna, Michael J. Lee, Daniel J. Jung, David H. TI Health Utility Improves After Surgery for Superior Canal Dehiscence Syndrome SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Health utility; QALY; Quality of life; Superior canal dehiscence ID QUALITY-OF-LIFE; DIZZINESS HANDICAP; COCHLEAR IMPLANT; SF-36; OUTCOMES; VALUES; SF-6D; MANAGEMENT; INVENTORY; AUTOPHONY AB Objective: Health utility value (HUV) is an outcome measure used to calculate quality adjusted life years (QALYs) and to determine cost-effectiveness of medical treatments. Herein, we measure HUV in patients with superior canal dehiscence syndrome (SCDS) before and after surgical repair. Health utility values of patients with SCDS are compared to normative data of the general United States population. Study Design: Retrospective review of prospectively collected data. Patients: Adult patients with SCDS. Setting: Tertiary referral center. Interventions: SCD repair via middle fossa craniotomy or transmastoid approaches. Main Outcome Measure: Primary outcome: change in HUV, as measured by the Short-Form 6-Dimension questionnaire. Secondary outcomes: autophony index (AI), dizziness handicap inventory (DHI), and hearing handicap inventory (HHI). Results: Fifty-one patients with SCDS were enrolled, 23 underwent surgical repair. Mean HUV in patients with SCDS is significantly lower than the general U.S. population: 0.68 (SD=0.13) versus 0.80 (0.29), p<0.01, respectively. Patients electing to undergo surgical repair had similar values relative to nonoperated patients: 0.65 (0.13) versus 0.71 (0.14), p=0.20, respectively. At mean follow-up of 12 months (range 3-39), postoperative HUV improved to 0.79 (0.12), p<0.01. AI decreased (improved) after repair: 32.7 (28.0) to 4.8 (8.3), p<0.001. DHI and HHI did not change significantly after surgery, p>0.14. Nonoperated patients had no significant change in HUV during a mean follow-up period of 21 months (range 9-39), p=0.33. Conclusions: SCDS patients have significantly lower HUV compared with the general U.S. population. HUV demonstrated improvement after surgery. Nonoperated patients have ongoing impaired quality of life. C1 [Remenschneider, Aaron K.; Owoc, Maryanna; Kozin, Elliott D.; McKenna, Michael J.; Lee, Daniel J.; Jung, David H.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Remenschneider, Aaron K.; Owoc, Maryanna; Kozin, Elliott D.; McKenna, Michael J.; Lee, Daniel J.; Jung, David H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Remenschneider, AK (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Aaron_Remenschneider@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 NR 34 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2015 VL 36 IS 10 BP 1695 EP 1701 DI 10.1097/MAO.0000000000000886 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DA7XZ UT WOS:000368020200020 PM 26485590 ER PT J AU Stojanovic, MP Engel, AJ AF Stojanovic, Milan P. Engel, Andrew J. TI An Expedited Diagnostic Algorithm for Lumbosacral Pain: "The Best Likelihood Scenario Approach" SO PAIN MEDICINE LA English DT Review DE Spine; Facet Joints; Medial Branch; Zygoapophyseal Joint; Block; Chronic Pain ID LUMBAR MEDIAL BRANCH; LOW-BACK-PAIN; ZYGAPOPHYSIAL JOINT BLOCKS; CHRONIC SPINAL PAIN; FALSE-POSITIVE RATE; FACET JOINT; RADIOFREQUENCY NEUROTOMY; INTRAVASCULAR INJECTION; COST-EFFECTIVENESS; GANGLION BLOCK AB Introduction. The logic behind diagnostic blocks is very straightforward. What has not been determined is the way diagnostic blocks can be best used. Study Design. Philosophical essay. Discussion. The interventional pain management physician would serve as the diagnostic expert by efficiently determining the source of the patient's pain. Conclusion. "The Best Likelihood Scenario" might improve diagnostic accuracy while decreasing societal costs. C1 [Stojanovic, Milan P.] VA Boston Healthcare Syst, Anesthesiol Crit Care & Pain Med Serv, Boston, MA 02130 USA. [Engel, Andrew J.] Affordable Pain Management, Chicago, IL USA. RP Stojanovic, MP (reprint author), VA Boston Healthcare Syst, Anesthesiol Crit Care & Pain Med Serv, Pain Med, 150 South Huntington Ave, Boston, MA 02130 USA. EM mpstojanovic@gmail.com NR 41 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD DEC PY 2015 VL 16 IS 12 BP 2271 EP 2276 DI 10.1111/pme.12839 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DB1VL UT WOS:000368297000009 PM 26179137 ER PT J AU Finkelman, MD Kulich, RJ Zacharoff, KL Smits, N Magnuson, BE Dong, JH Butler, SF AF Finkelman, Matthew D. Kulich, Ronald J. Zacharoff, Kevin L. Smits, Niels Magnuson, Britta E. Dong, Jinghui Butler, Stephen F. TI Shortening the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R): A Proof-of-Principle Study for Customized Computer-Based Testing SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Substance Abuse; Opioids; SOAPP-R; Respondent Burden; Risk Stratification ID INFORMATION-SYSTEM PROMIS; OUTCOMES MEASUREMENT; PHYSICAL FUNCTION; SHORT-FORMS; STOCHASTIC CURTAILMENT; UNIVERSAL PRECAUTIONS; QUESTIONNAIRE LENGTH; ADAPTIVE VERSION; NONCANCER PAIN; MISUSE MEASURE AB Background. The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a 24-item self-report instrument that was developed to aid providers in predicting aberrant medication-related behaviors among chronic pain patients. Although the SOAPP-R has garnered widespread use, certain patients may be dissuaded from taking it because of its length. Administrative barriers associated with lengthy questionnaires further limit its utility. Objective. To investigate the extent to which two techniques for computer-based administration (curtailment and stochastic curtailment) reduce the average test length of the SOAPP-R without unduly affecting sensitivity and specificity. Design. Retrospective study. Setting. Pain management centers. Subjects. Four hundred and twenty-eight chronic non-cancer pain patients. Methods. Subjects had taken the full-length SOAPP-R and been classified by the Aberrant Drug Behavior Index (ADBI) as having engaged or not engaged in aberrant medication-related behavior. Curtailment and stochastic curtailment were applied to the data in post-hoc simulation. Sensitivity and specificity with respect to the ADBI, as well as average test length, were computed for the full-length test, curtailment, and stochastic curtailment. Results. The full-length SOAPP-R exhibited a sensitivity of 0.745 and a specificity of 0.671 for predicting the ADBI. Curtailment reduced the average test length by 26% while exhibiting the same sensitivity and specificity as the full-length test. Stochastic curtailment reduced the average test length by as much as 65% while always exhibiting sensitivity and specificity for the ADBI within 0.035 of those of the full-length test. Conclusions. Curtailment and stochastic curtailment have potential to improve the SOAPP-R's efficiency in computer-based administrations. C1 [Finkelman, Matthew D.] Tufts Univ, Sch Dent Med, Dept Publ Hlth & Community Serv, Boston, MA 02111 USA. [Kulich, Ronald J.] Tufts Univ, Sch Dent Med, Craniofacial Pain & Headache Div, Dept Diagnost Sci, Boston, MA 02111 USA. [Kulich, Ronald J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Zacharoff, Kevin L.] Med Affairs Inc, Newton, MA USA. [Smits, Niels] Vrije Univ Amsterdam, Dept Methods, Fac Psychol & Educ, Amsterdam, Netherlands. [Magnuson, Britta E.] Tufts Univ, Sch Dent Med, Dept Oral & Maxillofacial Pathol, Oral Med & Craniofacial Pain, Boston, MA 02111 USA. [Dong, Jinghui] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Butler, Stephen F.] Inflexxion Inc, Hlth Analyt Dept, Newton, MA USA. RP Finkelman, MD (reprint author), 1 Kneeland St, Boston, MA 02111 USA. EM matthew.finkelman@tufts.edu FU National Institute on Drug Abuse of the National Institutes of Health [R03DA036683]; NIDA grant [R44DA015617] FX Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R03DA036683. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Data used in this study were collected as part of a NIDA grant (Grant no: R44DA015617, P.I. Butler). Data for this study were provided by Inflexxion, Inc. NR 60 TC 3 Z9 3 U1 5 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD DEC PY 2015 VL 16 IS 12 BP 2344 EP 2356 DI 10.1111/pme.12864 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA DB1VL UT WOS:000368297000017 PM 26176496 ER PT J AU Heesters, BA Lindqvist, M Vagefi, PA Scully, EP Schildberg, FA Altfeld, M Walker, BD Kaufmann, DE Carroll, MC AF Heesters, Balthasar A. Lindqvist, Madelene Vagefi, Parsia A. Scully, Eileen P. Schildberg, Frank A. Altfeld, Marcus Walker, Bruce D. Kaufmann, Daniel E. Carroll, Michael C. TI Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; COMPLEMENT-MEDIATED ENHANCEMENT; T-CELLS; LYMPHOID-TISSUE; CLASSICAL PATHWAY; IMMUNE-COMPLEXES; GERMINAL-CENTERS; B-CELLS; REPLICATION AB Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4+ T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans. C1 [Heesters, Balthasar A.; Carroll, Michael C.] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Heesters, Balthasar A.; Schildberg, Frank A.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Lindqvist, Madelene; Scully, Eileen P.; Altfeld, Marcus; Walker, Bruce D.; Kaufmann, Daniel E.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Lindqvist, Madelene; Scully, Eileen P.; Altfeld, Marcus; Walker, Bruce D.; Kaufmann, Daniel E.] Harvard Univ, Cambridge, MA 02138 USA. [Lindqvist, Madelene; Walker, Bruce D.; Kaufmann, Daniel E.] Scripps Res Inst, Ctr & Ctr HIV AIDS Vaccine Immunol & Immunogen Di, La Jolla, CA 92037 USA. [Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Scully, Eileen P.] Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Scully, Eileen P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Altfeld, Marcus] Leibniz Inst Expt Virol, Dept Viral Immunol, Hamburg, Germany. [Kaufmann, Daniel E.] Ctr Rech CHUM, Montreal, PQ, Canada. [Kaufmann, Daniel E.] Univ Montreal, Dept Med, Montreal, PQ, Canada. [Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Heesters, BA (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM balthasar_heesters@hms.harvard.edu FU Ragon Institute FX This study was supported by an Innovation Award from the Ragon Institute awarded to MCC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 11 Z9 11 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2015 VL 11 IS 12 AR e1005285 DI 10.1371/journal.ppat.1005285 PG 18 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DB2IZ UT WOS:000368332800016 PM 26623655 ER PT J AU Freund, NT Roitburd-Berman, A Sui, JH Marasco, WA Gershoni, JM AF Freund, Natalia T. Roitburd-Berman, Anna Sui, Jianhua Marasco, Wayne A. Gershoni, Jonathan M. TI Reconstitution of the receptor-binding motif of the SARS coronavirus SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE bioactive peptide; conformational library; phage-display; virus spike ID ACUTE RESPIRATORY SYNDROME; B-CELL EPITOPES; ANGIOTENSIN-CONVERTING ENZYME-2; HUMAN MONOCLONAL-ANTIBODIES; AFFINITY-SELECTED PEPTIDES; SPIKE PROTEIN; COMPUTATIONAL PREDICTION; NEUTRALIZING EPITOPE; STRUCTURAL BASIS; AMINO-ACIDS AB The severe acute respiratory syndrome (SARS) coronavirus (CoV) identified in 2003 has infected similar to 8000 people worldwide, killing nearly 10% of them. The infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2). The SARS CoV receptor-binding domain (amino acids N318-T509 of S protein) harbors an extended excursion along its periphery that contacts ACE2 and is designated the receptor-binding motif (RBM, amino acids S432-T486). In addition, the RBM is a major antigenic determinant, able to elicit production of neutralizing antibodies. Hence, the role of the RBM is a bi-functional bioactive surface that can be demonstrated by antibodies such as the neutralizing human anti-SARS monoclonal antibody (mAb) 80R which targets the RBM and competes with the ACE2 receptor for binding. Here, we employ phage-display peptide-libraries to reconstitute a functional RBM. This is achieved by generating a vast collection of candidate RBM peptides that present a diversity of conformations. Screening such 'Conformer Libraries' with corresponding ligands has produced short RBM constructs (ca. 40 amino acids) that can bind both the ACE2 receptor and the neutralizing mAb 80R. C1 [Freund, Natalia T.; Roitburd-Berman, Anna; Gershoni, Jonathan M.] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. [Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gershoni, JM (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. EM gershoni@tauex.tau.ac.il OI SUI, JIANHUA/0000-0002-1272-9662 FU US-Israel Binational Science Foundation [2005290] FX This work has been supported by a grant from the US-Israel Binational Science Foundation [2005290 to J.M.G. and W.A.M]. NR 43 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 EI 1741-0134 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD DEC PY 2015 VL 28 IS 12 BP 567 EP 575 DI 10.1093/protein/gzv052 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA DB3NX UT WOS:000368419500004 PM 26487711 ER PT J AU Raab, PA Mackintosh, MA Gros, DF Morland, LA AF Raab, Phillip A. Mackintosh, Margaret-Anne Gros, Daniel F. Morland, Leslie A. TI Examination of the Content Specificity of Posttraumatic Cognitions in Combat Veterans With Posttraumatic Stress Disorder SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID ADMINISTERED PTSD SCALE; PSYCHOMETRIC PROPERTIES; PROCESSING THERAPY; INVENTORY PTCI; DEPRESSION; SYMPTOMS; ANXIETY; METAANALYSIS; INDIVIDUALS; VALIDATION AB Objective: Cognitive theories have proposed the idea of content specificity, which holds that emotional disorders are associated with unique sets of negative cognitions. The existent research exploring the content specificity related to posttraumatic stress disorder (PTSD) and depression is sparse, and research is especially needed in veteran samples. The purpose of this study was to examine the associations of PTSD symptom clusters and comorbid depressive symptoms with posttraumatic cognitions. Method: This study was cross-sectional in design, and the sample consisted of data from 150 male combat veterans with PTSD drawn from the baseline assessments of a large clinical trial. Analyses involved a series of separate and simultaneous linear regressions to examine the unique associations of comorbid depressive symptoms and PTSD symptom clusters with posttraumatic cognitions, as well as post hoc analyses to examine the mediational role of comorbid depressive symptoms. Results: Findings demonstrated that posttraumatic negative cognitions about the self and self-blame were most strongly associated with comorbid depressive symptoms and the depression-related PTSD numbing cluster. Comorbid depressive symptoms also partially mediated nearly all the relationships between posttraumatic cognitions and PTSD symptom clusters. Conclusions: The findings of this study suggest that posttraumatic cognitions about the self and self-blame are not specific to PTSD but rather are more strongly related to symptoms of depression and negative affect. The results also suggest a potential pathway from posttraumatic cognitions to PTSD through the partially mediating influence of comorbid depression, and highlight the need to assess and treat comorbid depression in veterans with PTSD. C1 [Raab, Phillip A.; Mackintosh, Margaret-Anne; Morland, Leslie A.] Dept Vet Affairs Pacific Isl Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Pacific Isl Div, Honolulu, HI USA. [Gros, Daniel F.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Morland, Leslie A.] Univ Hawaii Manoa, Dept Psychiat, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Raab, PA (reprint author), Natl Ctr Posttraumat Stress Disorder, Pacific Isl Div, 3375 Koapaka St,Suite I-560, Honolulu, HI 96819 USA. EM drewraab@gmail.com FU Department of Defense and the Office of Research and Development, Medical Research Service [PT074516]; Department of Veterans Affairs FX This work is partially supported by Grant PT074516 from the Department of Defense and the Office of Research and Development, Medical Research Service, Department of Veterans Affairs. This study's funding organizations had no role in the study's design, in its collection, analysis, and interpretation of data, in writing this report, or the decision to submit this article for publication. All views and opinions expressed herein are those of the authors and do not necessarily reflect those of our respective institutions or the Department of Veterans Affairs. We declare no conflicts of interest. NR 41 TC 0 Z9 0 U1 3 U2 7 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 2015 VL 78 IS 4 BP 328 EP 340 DI 10.1080/00332747.2015.1082337 PG 13 WC Psychiatry SC Psychiatry GA DB3BD UT WOS:000368383600004 PM 26745686 ER PT J AU Pal, SK Choueiri, TK Karam, JA Heng, DYC AF Pal, Sumanta K. Choueiri, Toni K. Karam, Jose A. Heng, Daniel Y. C. TI Metastatic renal cell carcinoma: Contending with a sea change in therapy SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Editorial Material C1 [Pal, Sumanta K.] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA 91010 USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Karam, Jose A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Heng, Daniel Y. C.] Univ Calgary, Dept Med Oncol, Tom Baker Canc Ctr, Calgary, AB, Canada. RP Pal, SK (reprint author), City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA 91010 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD DEC PY 2015 VL 33 IS 12 BP 507 EP 508 DI 10.1016/j.urolonc.2015.10.005 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA DB1UG UT WOS:000368293900014 PM 26584741 ER PT J AU de Velasco, G Hamieh, L Mickey, S Choueiri, TK AF de Velasco, Guillermo Hamieh, Lana Mickey, Suzanne Choueiri, Toni K. TI Optimizing systemic therapy for metastatic renal cell carcinoma beyond the first-line setting SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Sequence; Systemic therapy; Renal cell carcinoma ID PHASE-III TRIAL; DOUBLE-BLIND; INTERFERON-ALPHA; TARGETED THERAPY; RANDOMIZED-TRIAL; C-MET; CANCER; SUNITINIB; PAZOPANIB; SAFETY AB The introduction of molecularly targeted therapies (TTs) has transformed the management of metastatic renal cell carcinoma (mRCC). Within a relatively short period of time, systemic treatment of mRCC has evolved from a disease treated only by cytokines to a disease where TT is the cornerstone of patient management. Since the approval of sorafenib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), in December 2005, 7 drugs have been introduced that have provided a high level of clinical efficacy in patients with mRCC, with a median survival of similar to 30 months in an unselected patient population that generally fits trials eligibility. Despite such success, advancements in therapies have reached a plateau: different combinations of targeted agents have not demonstrated additional benefit mainly owing to toxicity concerns, and some novel agents have failed to show benefit over approved drugs in clinics. In this review, we aim to focus on optimizing selection of agents in mRCC after progression on first-line TT. We also review how new drugs may transform existing guidelines and break through the current plateau reached with approved agents. (C) 2015 Elsevier Inc. All rights reserved. C1 [de Velasco, Guillermo; Hamieh, Lana; Mickey, Suzanne; Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu FU NCI NIH HHS [P50 CA101942] NR 57 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 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD DEC PY 2015 VL 33 IS 12 BP 538 EP 545 DI 10.1016/j.urolonc.2015.08.007 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA DB1UG UT WOS:000368293900018 PM 26482392 ER PT J AU Cole, AP Dalela, D Hanske, J Mullane, SA Choueiri, TK Meyer, CP Nguyen, PL Menon, M Kibel, AS Preston, MA Bellmunt, J Trinh, QD AF Cole, Alexander P. Dalela, Deepansh Hanske, Julian Mullane, Stephanie A. Choueiri, Toni K. Meyer, Christian P. Nguyen, Paul L. Menon, Mani Kibel, Adam S. Preston, Mark A. Bellmunt, Joaquim Trinh, Quoc-Dien TI Temporal trends in receipt of adequate lymphadenectomy in bladder cancer 1988 to 2010 SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Bladder cancer; Epidemiology; Lymphadenectomy; Lymph node dissection; Quality improvement; Health services research; Radical cystectomy; Urothelial carcinoma of urinary bladder ID LYMPH-NODE DISSECTION; ASSISTED RADICAL CYSTECTOMY; EXTENDED LYMPHADENECTOMY; SURGICAL CARE; SURVIVAL; IMPACT; TIME; MORTALITY; QUALITY; COUNT AB Introduction and objective: The importance of pelvic lymphadenectomy (LND) for diagnostic and therapeutic purposes at the time of radical cystectomy (RC) for bladder cancer is well documented. Although some debate remains on the optimal number of lymph nodes removed, 10 nodes has been proposed as constituting an adequate LND. We used data from the Surveillance, Epidemiology, and End Results database to examine predictors and temporal trends in the receipt of an adequate LND at the time of RC for bladder cancer. Material and methods: Within the Surveillance, Epidemiology, and End Results database, we extracted data on all patients with nonmetastatic bladder cancer receiving RC in the years 1988 to 2010. First, we assess the proportion of individuals undergoing RC who received an adequate LND (>10 nodes removed) over time. Second, we calculate odds ratios (ORs) of receiving an adequate LND using logistic regression modeling to compare study periods. Covariates included sex, race, age, region, tumor stage, urban vs. rural location, and insurance status. Results: Among the 5,696 individuals receiving RC during the years 1988 to 2010, 2,576 (45.2%) received an adequate LND. Over the study period, the proportion of individuals receiving an adequate LND increased from 26.4% to 61.3%. The odds of receiving an adequate LND increased over the study period; a patient undergoing RC in 2008 to 2010 was over 4-fold more likely to receive an adequate LND relative to a patient treated in 1988 to 1991 (OR = 4.63, 95% CI: 3.32-6.45). In addition to time of surgery, tumor stage had a positive association with receipt of adequate LND (OR = 1.49 for stage IV [T4 N1 or N0] vs. stage I [T1 or Tis], 95% CI: 1.22-1.82). Age, sex, marital status, and race were not significant predictors of adequate LND. Conclusion: Adequacy of pelvic LND remains an important measure of surgical quality in bladder cancer. Our data show that over the years 1988 to 2010, the likelihood of receiving an adequate LND has increased substantially; however, a substantial minority of patients still does not receive LND. Further study into factors leading to adequate LND is needed to increase the use of this important technique. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cole, Alexander P.; Hanske, Julian; Meyer, Christian P.; Kibel, Adam S.; Preston, Mark A.; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA. [Cole, Alexander P.; Hanske, Julian; Meyer, Christian P.; Kibel, Adam S.; Preston, Mark A.; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Dalela, Deepansh; Menon, Mani] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA. [Mullane, Stephanie A.; Choueiri, Toni K.; Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Trinh, QD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA. EM trinh.qd@gmail.com NR 45 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 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD DEC PY 2015 VL 33 IS 12 AR 504.e9 DI 10.1016/j.urolonc.2015.07.015 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA DB1UG UT WOS:000368293900006 PM 26320810 ER PT J AU Pucheril, D Sammon, JD Sood, A Abdollah, F Choueiri, TK Meyer, C Hanske, J Kim, SP Nguyen, PL Kibel, AS Weissman, JS Menon, M Trinh, QD AF Pucheril, Daniel Sammon, Jesse D. Sood, Akshay Abdollah, Firas Choueiri, Toni K. Meyer, Christian Hanske, Julian Kim, Simon P. Nguyen, Paul L. Kibel, Adam S. Weissman, Joel S. Menon, Mani Quoc-Dien Trinh TI Contemporary nationwide patterns of self-reported prostate-specific antigen screening in US veterans SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Veterans; Prostate-specific antigen; Screening ID HEALTH-CARE-SYSTEM; COLORECTAL-CANCER; UNITED-STATES; SERVICES; MEDICARE; TRANSFORMATION; INSURANCE; MORTALITY; BARRIERS; OUTCOMES AB Introduction and objectives: The quality of medical care to US veterans, as provided by the Veterans Health Administration, has recently been subjected to heightened scrutiny. We sought to report prostate-specific antigen screening (PSAS) in a contemporary cohort of veteran men (VM) vs. nonveteran men (NVM). We hypothesize that VM are less likely to receive age-appropriate PSAS compared with NVM. Materials and methods: We identified VM and NVM aged 55 to 69 years without history of prostate cancer who underwent PSA testing in the year preceding that of the 2012 Behavioral Risk Factor and Surveillance System survey. The prevalence of PSAS among VM and NVM was determined in aggregate and on a state-by-state basis. Complex samples logistic regression models calculated the odds of PSAS based on veteran status, adjusted for patient/demographic characteristics. Results: In all, 56,962 responses were collected, yielding a weighted estimate of 23.7 million men, of which 30.5% were VM. Overall, 45.2% (CI: 43.9%-46.5%) of VM reported PSAS compared with only 37.5% (CI: 36.5%-38.5%) of NVM. VM were more likely to have health insurance (92.0%; CI: 91.3%-92.8% vs. 86.2%; CI: 85.4%-87.0%) and a regular health care provider (89.0%; CI: 88.2%-89.8% vs. 85.9%; CI: 85.1%-86.6%) compared with NVM. Unadjusted prevalence of PSAS varied widely across the United States for VM and NVM. In multivariable analyses, VM had higher odds for PSAS (odds ratio = 1.10, CI: 1.02%-1.18%). Conclusions: Contrary to our initial hypothesis, our findings suggest a continued pattern of greater preventive health services use by veterans. VM were more likely to undergo PSAS than NVM. This is, in part, attributable to better access to primary care and health insurance. Nonetheless, heterogeneity in screening practices remained largely dependent on geography. (C) 2015 Elsevier Inc. All rights reserved. C1 [Pucheril, Daniel; Sammon, Jesse D.; Sood, Akshay; Abdollah, Firas; Menon, Mani; Quoc-Dien Trinh] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyer, Christian; Hanske, Julian; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Div Urol Oncol, Boston, MA 02115 USA. [Meyer, Christian; Hanske, Julian; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Kim, Simon P.] Yale Univ, Dept Urol & Canc Outcomes, Publ Policy & Effectiveness Res Ctr, New Haven, CT USA. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Weissman, Joel S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Trinh, QD (reprint author), Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. EM trinh.qd@gmail.com NR 33 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD DEC PY 2015 VL 33 IS 12 AR 503.e7 DI 10.1016/j.urolonc.2015.07.019 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA DB1UG UT WOS:000368293900003 PM 26319352 ER PT J AU Lall, C Houshyar, R Landman, J Verma, S Goyenechea, M Bhargava, P Pulford, C Okhunov, Z Siaghani, PJ Menias, C AF Lall, Chandana Houshyar, Roozbeh Landman, Jaime Verma, Sadhna Goyenechea, Martin Bhargava, Puneet Pulford, Christopher Okhunov, Zhamshid Siaghani, Parwiz J. Menias, Christine TI Renal Collision and Composite Tumors: Imaging and Pathophysiology SO UROLOGY LA English DT Article ID OF-THE-LITERATURE; CELL CARCINOMA; METASTASIS; CANCER; ANGIOMYOLIPOMA; KIDNEY AB OBJECTIVE To illustrate the imaging appearances of a spectrum of renal collision and composite tumors. Occurrence of collision and composite tumors in the genitourinary tract is rare compared to the usual occurrence of synchronous tumors. METHODS Case studies were chosen that represent the different tumors. Analysis was made on both the imaging and the pathology if excision was performed. RESULTS Presence of 2 different cell types can lead to confusing imaging findings, and biopsy or excision is typically needed for final diagnosis. Some composite tumors have a characteristic appearance on imaging based on their pathologic features. CONCLUSION Familiarity with imaging findings may help radiologists include these tumors in their differential diagnosis. Published by Elsevier Inc. C1 [Okhunov, Zhamshid] Univ Calif Irvine, Dept Urol, Orange, CA 92868 USA. Univ Cincinnati, Med Ctr, Dept Radiol, Cincinnati, OH 45267 USA. Univ Washington, Dept Radiol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Mayo Clin, Dept Radiol, Scottsdale, AZ USA. RP Okhunov, Z (reprint author), Univ Calif Irvine, Dept Urol, 333 City Blvd West,Suite 2100, Orange, CA 92868 USA. EM Zokhunov@uci.edu NR 22 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 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD DEC PY 2015 VL 86 IS 6 BP 1159 EP 1164 DI 10.1016/j.urology.2015.07.032 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DB2LD UT WOS:000368339100028 PM 26431891 ER PT J AU Allard, CB Coret, A Dason, S Tajzler, C Shayegan, B Matsumoto, ED Kapoor, A AF Allard, Christopher B. Coret, Alexander Dason, Shawn Tajzler, Camilla Shayegan, Bobby Matsumoto, Edward D. Kapoor, Anil TI Contrast-enhanced Ultrasonography for Surveillance of Radiofrequency-ablated Renal Tumors: A Prospective, Radiologist-blinded Pilot Study SO UROLOGY LA English DT Article ID FOCAL LIVER-LESIONS; CELL CARCINOMA; ONCOLOGIC OUTCOMES; FOLLOW-UP; ULTRASOUND; SONOGRAPHY; NEOPLASMS; KIDNEY; CT AB OBJECTIVE To prospectively evaluate the performance of contrast-enhanced ultrasonography (CEUS) for surveillance after radiofrequency ablation (RFA) of small renal masses by comparing CEUS to the contrast-enhanced computed tomography (CECT), the current gold standard. PATIENTS AND METHODS Patients underwent surveillance after RFA of small renal masses (<= 4 cm) consisting of CECT scans at 3 and 6 months and every 6 months thereafter. Participants additionally underwent >= 1 CEUS within 90 days before CECT. Percutaneous biopsy was performed for lesions suspicious for recurrence on CECT. Independent, blinded radiologists interpreted CEUS and CECT scans. Intermodality agreement was evaluated with the kappa coefficient. RESULTS In total, 37 pairs of CEUS and CECT scans were performed. Median tumor size was 2.5 cm (range, 1.4-4.0 cm). Median follow-up from RFA to CEUS was 25 months. Renal tumor recurrences were diagnosed by CECT in 3 patients and confirmed histopathologically by percutaneous biopsy; 34 CECT scans were negative for recurrence. The diagnostic rate of CEUS was 94.6%; 2 CEUS scans were nondiagnostic because of patient body habitus. Among diagnostic CEUS scans, tumor enhancement was present in 3 and absent in 32. We observed perfect concordance between CEUS and CECT (= 1.0; P < .0001). CONCLUSION This is the first prospective study incorporating radiologist blinding to evaluate CEUS for RFA surveillance. Our findings suggest CEUS may ultimately be incorporated into RFA surveillance protocols. The operator dependency of CEUS is a possible barrier to its widespread adoption. These findings justify larger studies with longer follow-up. (C) 2015 Elsevier Inc. C1 Massachusetts Gen Hosp, Div Urol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. St Josephs Healthcare, Dept Radiol, Hamilton, ON, Canada. McMaster Univ, Dept Urol, Hamilton, ON, Canada. RP Kapoor, A (reprint author), 50 Charlton Ave E,Room G344, Hamilton, ON L8N 4A6, Canada. EM AKapoor@mcmaster.ca FU Canadian Urologic Oncology Group FX The Canadian Urologic Oncology Group funded this study. NR 26 TC 2 Z9 2 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD DEC PY 2015 VL 86 IS 6 BP 1174 EP 1178 DI 10.1016/j.urology.2015.04.062 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA DB2LD UT WOS:000368339100030 PM 26123518 ER PT J AU Bratslavsky, G Cheng, JS AF Bratslavsky, Gennady Cheng, Jed-Sian TI Robotic-assisted Radical Nephrectomy With Retrohepatic Vena Caval Tumor Thrombectomy (Level III) Combined With Extended Retroperitoneal Lymph Node Dissection SO UROLOGY LA English DT Article ID RENAL-CELL CARCINOMA; THROMBUS; LYMPHADENECTOMY; RESECTION; CANCER AB OBJECTIVE To describe a case of robotic-assisted radical nephrectomy (RARN) with level III retrohepatic vena caval tumor thrombectomy (11 cm) and extended retroperitoneal lymph node dissection (RPLND) for renal cell carcinoma (RCC). MATERIALS AND METHODS A 52-year-old woman with a large right renal mass, 11-cm (level III) inferior vena cava (IVC) thrombus, with a negative metastatic workup presented to our clinic and was consented to undergo RARN. Intraoperative ultrasound confirmed the presence of tumor thrombus. After the division of the renal artery, control of the vena cava above and below the tumor thrombus as well as contralateral renal vein was obtained. A cavotomy was performed, the thrombus was removed, and the cavotomy was repaired. Additionally, an extended RPLND was performed with robotic assistance. RESULTS Total operative time was 6 hours and 6 minutes. Estimated blood loss was 1200 cc. The final pathology demonstrated an 8.5-cm, Fuhrman grade 3, clear cell RCC with sarcomatoid features and negative surgical margins. All 44 lymph nodes removed (hilar, paracaval, precaval, retrocaval, interaortocaval, and preaortic) were negative. Final staging was pT3b, N0, M0. The patient was discharged to home 36 hours postoperatively and experienced no perioperative or postoperative complications. CONCLUSION RARN with retrohepatic (level III) vena caval tumor thrombectomy and extended RPLND is technically feasible and has potential benefits. Robotic assistance may allow for improved intracorporal repair of the IVC and shortened recovery time, while maintaining oncologic principles. (C) 2015 Elsevier Inc. C1 [Bratslavsky, Gennady] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Bratslavsky, G (reprint author), SUNY Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA. EM bratslag@upstate.edu NR 17 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD DEC PY 2015 VL 86 IS 6 BP 1235 EP 1240 DI 10.1016/j.urology.2015.05.042 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DB2LD UT WOS:000368339100046 PM 26254172 ER PT J AU Wu, YL Sequist, LV Geater, SL Orlov, S Lee, KH Tsai, CM Kato, T Kiura, K Barrios, CH Schuler, M Hirsh, V Yamamoto, N O'Byrne, K Mok, T Massey, D Marten, A Yang, JCH AF Wu, Y. -L. Sequist, L. V. Geater, S. L. Orlov, S. Lee, K. H. Tsai, C. -M. Kato, T. Kiura, K. Barrios, C. H. Schuler, M. Hirsh, V. Yamamoto, N. O'Byrne, K. Mok, T. Massey, D. Maerten, A. Yang, J. C. -H. TI Afatinib (A) versus chemotherapy (CT) for EGFR mutation-positive NSCLC patients (pts) aged >= 65 years: Subgroup analyses of LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Wu, Y. -L.] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Wu, Y. -L.] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. [Sequist, L. V.] Massachusetts Gen Hosp, Dept Thorac Oncol, Boston, MA 02114 USA. [Sequist, L. V.] Harvard Univ, Sch Med, Boston, MA USA. [Geater, S. L.] Prince Songkla Univ, Fac Med, Hat Yai, Thailand. [Orlov, S.] Pavlov State Med Univ, Dept Thorac Oncol, St Petersburg, Russia. [Lee, K. H.] Chungbuk Natl Univ Hosp, Dept Internal Med, Cheongju, South Korea. [Tsai, C. -M.] Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan. [Kato, T.] Kanagawa Cardiovasc & Resp Ctr, Dept Resp Med, Yokohama, Kanagawa, Japan. [Kiura, K.] Okayama Univ Hosp, Univ Hosp Med & Dent, Okayama, Japan. [Barrios, C. H.] PUCRS Sch Med, Dept Oncol, Porto Alegre, RS, Brazil. [Schuler, M.] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Essen, Germany. [Hirsh, V.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Yamamoto, N.] Wakayama Med Univ, Dept Internal Med 3, Wakayama, Japan. [O'Byrne, K.] Princess Alexandra Hosp, Translat Res Inst, Brisbane, Qld 4102, Australia. [O'Byrne, K.] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Mok, T.] Chinese Univ Hong Kong, State Key Lab South China, Hong Kong Canc Inst, Hong Kong, Hong Kong, Peoples R China. [Massey, D.] Boehringer Ingelheim Ltd UK, Biomet Clin, Bracknell, Berks, England. [Maerten, A.] Boehringer Ingelheim Pharma GmbH & Co KG, TA Oncol, Ingelheim, Rheine, Germany. [Yang, J. C. -H.] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. [Yang, J. C. -H.] Natl Taiwan Univ, Taipei 10764, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 446P BP 136 EP 137 PG 2 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700445 ER PT J AU Wu, YL Sequist, LV Schuler, M Yamamoto, N Zhou, C Hu, CP O'Byrne, K Hirsh, V Mok, T Zazulina, V Yang, JCH AF Wu, Y. -L. Sequist, L. V. Schuler, M. Yamamoto, N. Zhou, C. Hu, C. -P. O'Byrne, K. Hirsh, V. Mok, T. Zazulina, V. Yang, J. C. -H. TI Overall survival (OS) with afatinib (A) vs chemotherapy (CT) in patients (pts) with NSCLC harboring EGFR mutations (mut): Subgroup analyses by race in LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Wu, Y. -L.] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Wu, Y. -L.] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. [Sequist, L. V.] Massachusetts Gen Hosp, Dept Thorac Oncol, Boston, MA 02114 USA. [Sequist, L. V.] Harvard Univ, Sch Med, Boston, MA USA. [Schuler, M.] Univ Hosp Essen, Univ Duisburg Essen, West German Canc Ctr, Essen, Germany. [Yamamoto, N.] Wakayama Med Univ, Dept Internal Med 3, Wakayama, Japan. [Zhou, C.] Tongji Univ, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China. [Hu, C. -P.] Cent S Univ, Xiangya Hosp, Changsha, Hunan, Peoples R China. [O'Byrne, K.] Princess Alexandra Hosp, Translat Res Inst, Brisbane, Qld 4102, Australia. [O'Byrne, K.] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Hirsh, V.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Mok, T.] Chinese Univ Hong Kong, State Key Lab South China, Hong Kong Canc Inst, Hong Kong, Hong Kong, Peoples R China. [Zazulina, V.] Boehringer Ingelheim Ltd UK, Med, Bracknell, Berks, England. [Yang, J. C. -H.] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. [Yang, J. C. -H.] Natl Taiwan Univ, Taipei 10764, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 445P BP 136 EP 136 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700444 ER PT J AU Janne, PA Son, J Voccia, I Uttenreuther-Fischer, M Park, K AF Janne, P. A. Son, J. Voccia, I. Uttenreuther-Fischer, M. Park, K. TI Phase II study of BI1482694 in patients (pts) with T790M-positive non-small cell lung cancer (NSCLC) after treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Janne, P. A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Son, J.] Hanmi Pharmaceut Co Ltd, R&D, Seoul, South Korea. [Voccia, I.] Boehringer Ingelheim Canada Ltd, Clin Operat, Burlington, ON, Canada. [Uttenreuther-Fischer, M.] Boehringer Ingelheim Pharma GmbH & Co KG, TA Oncol, Biberach, Germany. [Park, K.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 476TiP BP 145 EP 145 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700475 ER PT J AU Lin, M Gao, Y Hornicek, F Xu, F Lu, TJ Amiji, M Duan, ZF AF Lin, Min Gao, Yan Hornicek, Francis Xu, Feng Lu, Tian Jian Amiji, Mansoor Duan, Zhenfeng TI Near-infrared light activated delivery platform for cancer therapy SO ADVANCES IN COLLOID AND INTERFACE SCIENCE LA English DT Article DE Upconversion nanoparticle; Payload encapsulation strategies; Photoactivation; Controlled delivery; Cancer therapy ID UP-CONVERSION NANOPARTICLES; CORE-SHELL NANOPARTICLES; LANTHANIDE-DOPED NANOCRYSTALS; VIVO PHOTODYNAMIC THERAPY; ANTICANCER DRUG-DELIVERY; IRON-OXIDE NANOPARTICLES; IN-VIVO; UPCONVERTING NANOPARTICLES; MESOPOROUS-SILICA; FLUORESCENT NANOPARTICLES AB Cancer treatment using conventional drug delivery platforms may lead to fatal damage to normal cells. Among various intelligent delivery platforms, photoresponsive delivery platforms are becoming popular, as light can be easily focused and tuned in terms of power intensity, wavelength, and irradiation time, allowing remote and precise control over therapeutic payload release both spatially and temporally. This unprecedented controlled delivery manner is important to improve therapeutic efficacy while minimizing side effects. However, most of the existing photoactive delivery platforms require UV/visible excitation to initiate their function, which suffers from phototoxicity and low level of tissue penetration limiting their practical applications in biomedicine. With the advanced optical property of converting near infrared (NIR) excitation to localized UV/visible emission, upconversion nanoparticles (UCNPs) have emerged as a promising photoactive delivery platform that provides practical applications for remote spatially and temporally controlled release of therapeutic payload molecules using low phototoxic and high tissue penetration NIR light as the excitation source. This article reviews the state-of-the-art design, synthesis and therapeutic molecular payload encapsulation strategies of UCNP-based photoactive delivery platforms for cancer therapy. Challenges and promises for engineering of advanced delivery platforms are also highlighted. (C) 2015 Elsevier B.V. All rights reserved. C1 [Lin, Min; Gao, Yan; Hornicek, Francis; Duan, Zhenfeng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Lin, Min; Xu, Feng; Lu, Tian Jian] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. [Lin, Min; Xu, Feng; Lu, Tian Jian] Xi An Jiao Tong Univ, Bioinspired Engn & Biomech Ctr BEBC, Xian 710049, Peoples R China. [Amiji, Mansoor] Northeastern Univ, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Lin, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. EM minlin@mail.xjtu.edu.cn; ZDUAN@mgh.harvard.edu RI Xu, Feng/C-7430-2011; Lu, Tian Jian/E-6063-2016; Xu, Feng/H-4468-2011 OI Xu, Feng/0000-0003-4351-0222 FU Gategno and Wechsler funds [020572]; Sarcoma Foundation of America [222433]; National Cancer Institute (NCI)/National Institutes of Health (NIH) UO1 [CA 151452]; Fundamental Research Funds for the Central Universities [2012jdhz46]; China Scholarship Council FX This study is supported in part, by grants from the Gategno and Wechsler funds (020572). Dr. Duan is supported, in part, through a grant from the Sarcoma Foundation of America (222433), a grant from the National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452, and by the Fundamental Research Funds for the Central Universities (2012jdhz46). Dr. Lin is supported by a scholarship from the China Scholarship Council. NR 195 TC 5 Z9 5 U1 24 U2 82 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-8686 EI 1873-3727 J9 ADV COLLOID INTERFAC JI Adv. Colloid Interface Sci. PD DEC PY 2015 VL 226 BP 123 EP 137 DI 10.1016/j.cis.2015.10.003 PN B PG 15 WC Chemistry, Physical SC Chemistry GA DA5RS UT WOS:000367860800001 PM 26520243 ER PT J AU Gavillet, M Martinod, K Renella, R Harris, C Shapiro, NI Wagner, DD Williams, DA AF Gavillet, Mathilde Martinod, Kimberly Renella, Raffaele Harris, Chad Shapiro, Nate I. Wagner, Denisa D. Williams, David A. TI Flow cytometric assay for direct quantification of neutrophil extracellular traps in blood samples SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID CHROMATIN DECONDENSATION; THROMBOSIS; CONTRIBUTE; SEPSIS; RAC2; PAD4; MICE AB Neutrophil extracellular traps (NETs) contribute to innate immunity as well as numerous diseases processes such as deep vein thrombosis, myocardial ischemia, and autoimmune disease. To date, most knowledge on NETs formation has been gathered via the qualitative microscopic examination of individual neutrophils in vitro, or aggregate structures in vivo. Here we describe a novel flow cytometry (FLOW)-based assay to identify and quantify NETs using antibodies against key NETs constituents, specifically DNA, modified histones, and granular enzymes. This method is applicable to both murine and human samples for the assessment of induced NETs in vitro, or detection of NETosis in vivo in blood samples. This FLOW-based method was validated by comparison with the well-established microscopy assay using two genetic mouse models previously demonstrated to show defective NETosis. It was then used on healthy human neutrophils for detection of ex vivo induced NETs and on blood samples from patients with sepsis for direct assessment of in vivo NET-forming neutrophils. This new methodology allows rapid and robust assessment of several thousand cells per sample and is independent of potential observer-bias, the two main limitations of the microscopic quantification. Using this new technology facilitates the direct detection of in vivo circulating NETs in blood samples and purification of NETting neutrophils by fluorescence-activated cell sorting (FACS) for further analysis. (C) 2015 Wiley Periodicals, Inc. C1 [Gavillet, Mathilde; Renella, Raffaele; Harris, Chad; Wagner, Denisa D.; Williams, David A.] Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA USA. [Martinod, Kimberly] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Martinod, Kimberly; Renella, Raffaele; Wagner, Denisa D.; Williams, David A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Renella, Raffaele; Williams, David A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Shapiro, Nate I.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Williams, DA (reprint author), 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA. EM DAWilliams@childrens.harvard.edu RI Shapiro, Nathan/F-1718-2016; OI Martinod, Kimberly/0000-0002-1026-6107 FU National Institutes of Health [5R01DK062757, NHLBI R01 HL102101, NHLBI T32 HL066987]; Department of Medicine, Boston Children's Hospital; Swiss National Science Foundation [PBLAP3-140046] FX Contract grant sponsor: the National Institutes of Health; Contract grant numbers: 5R01DK062757 [D.A.W.]; NHLBI R01 HL102101 [D.D.W]; NHLBI T32 HL066987 (KM).; Contract grant sponsor: the Department of Medicine, Boston Children's Hospital (D.A.W. and D.D.W.) and the Swiss National Science Foundation; Contract grant number: PBLAP3-140046 [M.G.]. NR 16 TC 12 Z9 12 U1 4 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2015 VL 90 IS 12 BP 1155 EP 1158 DI 10.1002/ajh.24185 PG 4 WC Hematology SC Hematology GA DA2ZS UT WOS:000367666300022 PM 26347989 ER PT J AU Freedman, A AF Freedman, Arnold TI Follicular lymphoma: 2015 update on diagnosis and management SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; HIGH-DOSE THERAPY; LOW-TUMOR-BURDEN; TERM-FOLLOW-UP; INTERNATIONAL PROGNOSTIC INDEX; FONDAZIONE ITALIANA LINFOMI; BENDAMUSTINE PLUS RITUXIMAB; PROGRESSION-FREE SURVIVAL; ANTI-CD20 MONOCLONAL-ANTIBODY AB Disease overview: Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma (FL) is characterized by diffuse lymphoadenopathy, bone marrow involvement, splenomegaly, and less commonly other extranodal sites of involvement. In general, cytopenias can occur but constitutional symptoms of fever, night sweats, and weight loss are uncommon. Diagnosis: Diagnosis is based on histology of preferably a biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10, and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes. Risk stratification: The Follicular Lymphoma International Prognostic Index prognostic model for FL uses five independent predictors of inferior survival: age >60 years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of involved nodal areas >4. The presence of 0, 1, 2, and >= 3 adverse factors defines low, intermediate, and high-risk disease. With the use of more modern therapies, outcomes have improved. Risk-adapted therapy: Observation continues to be adequate for asymptomatic patients with low bulk disease and no cytopenias, with no survival advantage for early treatment with either chemotherapy or rituximab alone. For patients needing therapy, most patients are treated with chemotherapy plus rituximab, which has improved response rates, duration of response and overall survival. Randomized studies have shown additional benefit for maintenance rituximab both following chemotherapy-rituximab and single agent rituximab. Experimental therapies as well as stem cell transplantation (SCT) are considered for recurrent disease. (C) 2015 Wiley Periodicals, Inc. C1 [Freedman, Arnold] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Freedman, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM afreedman@partners.org NR 116 TC 4 Z9 4 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2015 VL 90 IS 12 BP 1172 EP 1178 DI 10.1002/ajh.24200 PG 7 WC Hematology SC Hematology GA DA2ZS UT WOS:000367666300025 PM 26769125 ER PT J AU Shih, AR Murali, MR AF Shih, Angela R. Murali, Mandakolathur R. TI Laboratory tests for disorders of complement and complement regulatory proteins SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID HEMOLYTIC-UREMIC-SYNDROME; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; HEREDITARY ANGIONEUROTIC-EDEMA; C1 INHIBITOR CONCENTRATE; PIG-A GENE; FACTOR-H ABNORMALITIES; PRIMARY IMMUNODEFICIENCIES; NORMAL C1-INHIBITOR; APOPTOTIC CELLS; ACID THERAPY AB The complement pathway is a cascade of proteases that is involved in immune surveillance and innate immunity, as well as adaptive immunity. Dysfunction of the complement cascade may be mediated by aberrations in the pathways of activation, complement regulatory proteins, or complement deficiencies, and has been linked to a number of hematologic disorders, including paroxysmal noctural hemoglobinuria (PNH), hereditary angioedema (HAE), and atypical hemolytic-uremic syndrome (aHUS). Here, current laboratory tests for disorders of the complement pathway are reviewed, and their utility and limitations in hematologic disorders and systemic diseases are discussed. Current therapeutic advances targeting the complement pathway in treatment of complement-mediated hematologic disorders are also reviewed. (C) 2015 Wiley Periodicals, Inc. C1 [Shih, Angela R.; Murali, Mandakolathur R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Murali, MR (reprint author), Massachusetts Gen Hosp, Clin Immunol Lab, Bullfinch 422,55 Fruit St, Boston, MA 02114 USA. EM mmurali@mgh.harvard.edu NR 71 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2015 VL 90 IS 12 BP 1180 EP 1186 DI 10.1002/ajh.24209 PG 7 WC Hematology SC Hematology GA DA2ZS UT WOS:000367666300027 PM 26437749 ER PT J AU Roussakis, E Li, ZX Nowell, NH Nichols, AJ Evans, CL AF Roussakis, Emmanuel Li, Zongxi Nowell, Nicholas H. Nichols, Alexander J. Evans, Conor L. TI Bright, "Clickable" Porphyrins for the Visualization of Oxygenation under Ambient Light SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE biotechnology; dendrimers; luminescence; porphyrins; sensors ID PI-EXTENDED PORPHYRINS; PHOSPHORESCENCE; LUMINESCENCE; SENSORS AB A new group of "clickable" and brightly emissive metalloporphyrins has been developed for the visualization of oxygenation under ambient light with the naked eye. These alkynyl-terminated compounds permit the rapid and facile synthesis of oxygen-sensing dendrimers through azide-alkyne click chemistry. With absorption maxima overlapping with the wavelengths of common commercial laser sources, they are readily applicable to biomedical imaging of tissue oxygenation. An efficient synthetic methodology, featuring the stable trimethylacetyl (pivaloyl) protecting group, is described for their preparation. A paint-on liquid bandage containing a new, click-synthesized porphyrin dendrimer has been used to map oxygenation across an ex vivo porcine skin burn model. C1 [Roussakis, Emmanuel; Li, Zongxi; Nowell, Nicholas H.; Nichols, Alexander J.; Evans, Conor L.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Charlestown, MA 02129 USA. [Nichols, Alexander J.; Evans, Conor L.] Harvard Univ, Program Biophys, Boston, MA 02115 USA. [Nichols, Alexander J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Evans, CL (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, CNY 149-3210,13th St, Charlestown, MA 02129 USA. EM evans.conor@mgh.harvard.edu FU Air Force Office for Scientific Research [FA9550-13-1-0068]; National Institutes of Health through the NIH Director's New Innovator Award Program [1 DP2 OD007096-1]; NSF Graduate Research Fellowship; NDSEG Fellowship FX This work was funded by the Air Force Office for Scientific Research (FA9550-13-1-0068) and the National Institutes of Health through the NIH Director's New Innovator Award Program, Grant No. 1 DP2 OD007096-1. Information on the New Innovator Award Program can be found at http://nihroadmap.nih.gov/newinnovator/. A. J. N. would like to acknowledge the support of an NSF Graduate Research Fellowship and NDSEG Fellowship. We thank Dr. Gabriela Apiou-Sbirlea and Dr. Reginald Birngruber for their contributions to the development of the oxygen-sensing bandage. We acknowledge Ryan Caulfield and John L. Beagle from the Knight Surgical Facility at Massachusetts General Hospital for obtaining the excised porcine skin. Finally, we thank Dr. Lauren A. Austin, Sam Osseiran, Stefano Belfiore, Taylor M. Cannon, and Emily J. Keeley for their help in editing this manuscript. NR 29 TC 5 Z9 5 U1 8 U2 33 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD DEC 1 PY 2015 VL 54 IS 49 BP 14728 EP 14731 DI 10.1002/anie.201506847 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA DA3UB UT WOS:000367723400019 PM 26510549 ER PT J AU Feng, WW Wang, J Chhatbar, PY Doughty, C Landsittel, D Lioutas, VA Kautz, SA Schlaug, G AF Feng, Wuwei Wang, Jasmine Chhatbar, Pratik Y. Doughty, Christopher Landsittel, Douglas Lioutas, Vasileios-Arsenios Kautz, Steven A. Schlaug, Gottfried TI Corticospinal Tract Lesion Load: An Imaging Biomarker for Stroke Motor Outcomes SO ANNALS OF NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; PROGNOSTIC VALUE; RECOVERY; STIMULATION; RELIABILITY; IMPAIRMENT; POSTSTROKE; INTEGRITY; DEPENDS; SIZE AB Objective: The aim of this work was to investigate whether an imaging measure of corticospinal tract (CST) injury in the acute phase can predict motor outcome at 3 months in comparison to clinical assessment of initial motor impairment. Methods: A two-site prospective cohort study followed up a group of first-ever ischemic stroke patients using the Upper-Extremity Fugl-Meyer (UE-FM) Scale to measure motor impairment in the acute phase and at 3 months. A weighted CST lesion load (wCST-LL)was calculated by overlaying the patient's lesion map on magnetic resonance imaging with a probabilistic CST constructed from healthy control subjects. Regression models were fit to assess the predictive value of wCST-LL and compared with initial motor impairment. Results: Seventy-six patients (37 from cohort 1 and 39 from cohort 2) completed the study. wCST-LL as well as assessment of motor impairment (UE-FM) in the acute phase correlated with motor impairment (UE-FM) at 3 months in both cohort 1 (R-2 = 0.69 vs. R-2 = 0.67; p = 0.43) and cohort 2 (R-2 = 0.69 vs. R-2 = 0.62; p = 0.25). In the severely impaired subgroup (defined as UE-FM <= 10 at baseline), wCST-LL correlated with outcomes significantly better than clinical assessment (R-2 = 0.47 vs. R-2 = 0.11; p = 0.03). In the nonseverely impaired subgroup, stroke patients recovered approximately 70% of their maximal recovery potential. All stroke patients in both cohorts had poor motor outcomes at 3 months (defined as UE-FM <= 25) when wCST-LL was >= 7.0 cc (positive predictive value was 100%). Interpretation: wCST-LL, an imaging biomarker determined in the acute phase, can predict poststroke motor outcomes at 3 months, especially in patients with severe impairment at baseline. C1 [Feng, Wuwei; Chhatbar, Pratik Y.] Med Univ S Carolina, Dept Neurol, MUSC Stroke Ctr, Charleston, SC 29425 USA. [Wang, Jasmine; Doughty, Christopher; Lioutas, Vasileios-Arsenios; Schlaug, Gottfried] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Neuroimaging & Stroke Recovery Lab, Boston, MA 02215 USA. [Landsittel, Douglas] Univ Pittsburgh, Dept Med, Sect Biomarkers & Predict Modeling, Pittsburgh, PA USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Feng, Wuwei; Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. RP Schlaug, G (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Neuroimaging & Stroke Recovery Lab, 330 Brookline Ave, Boston, MA 02215 USA. EM gschlaug@bidmc.harvard.edu FU American Heart Association Scientist Development Grant [14SDG1829003]; National Institutes of Health (NIH) [UL1 RR029882, UL1 TR000062, P20GM109040, 1R01 DC008796, R01 DC009823-01]; Rehabilitation Research & Development Service of Department of Veterans Affairs; Mary Crown and William Ellis Fund; Richard and Rosalyn Slifka Family Fund; Tom and Suzanne McManmon Family Fund; Doris Duke Charitable Foundation; South Carolina Clinical & Translational Research Institute/Medical University of South Carolina FX The authors acknowledge grant support from American Heart Association Scientist Development Grant 14SDG1829003 (W.F.) and the South Carolina Clinical & Translational Research Institute/Medical University of South Carolina, through National Institutes of Health (NIH) grant numbers UL1 RR029882 and UL1 TR000062 (W.F.), NIH P20GM109040 (W.F., P.Y.C., and S.K.), Rehabilitation Research & Development Service of the Department of Veterans Affairs (S.K.), NIH 1R01 DC008796 (G.S.), R01 DC009823-01 (G.S.), the Mary Crown and William Ellis Fund (G.S.), the Richard and Rosalyn Slifka Family Fund (G.S.), and the Tom and Suzanne McManmon Family Fund (G.S.) and the Doris Duke Charitable Foundation (C.D.). NR 33 TC 18 Z9 18 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2015 VL 78 IS 6 BP 860 EP 870 DI 10.1002/ana.24510 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA3DY UT WOS:000367678100004 PM 26289123 ER PT J AU El Khattabi, I Sharma, A AF El Khattabi, Ilham Sharma, Arun TI Proper activation of MafA is required for optimal differentiation and maturation of pancreatic beta-cells SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE MafA; insulin transcription factor; beta-cell maturation; beta-cell differentiation; beta-cells; stem cell differentiation ID INSULIN-PRODUCING CELLS; EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR; IN-VIVO; GENE-TRANSCRIPTION; SEGMENTATION GENE; OXIDATIVE STRESS; LENS DEVELOPMENT; P38 MAPK; C-MAF AB A key therapeutic approach for the treatment of Type 1 diabetes (T1D) is transplantation of functional islet beta-cells. Despite recent advances in generating stem cell-derived glucose-responsive insulin(+) cells, their further maturation to fully functional adult beta-cells still remains a daunting task. Conquering this hurdle will require a better understanding of the mechanisms driving maturation of embryonic insulin(+) cells into adult beta-cells, and the implementation of that knowledge to improve current differentiation protocols. Here, we will review our current understanding of beta-cell maturation, and discuss the contribution of key beta-cell transcription factor MafA, to this process. The fundamental importance of MafA in regulating adult beta-cell maturation and function indicates that enhancing MafA expression may improve the generation of definitive beta-cells for transplantation. Additionally, we suggest that the temporal control of MafA induction at a specific stage of beta-cell differentiation will be the next critical challenge for achieving optimum maturation of beta-cells. (C) 2015 Elsevier Ltd. All rights reserved. C1 [El Khattabi, Ilham] Joslin Diabet Ctr, Boston, MA 02215 USA. [Sharma, Arun] MedImmune, Cardiovasc & Metab Dis, Gaithersburg, MD 20878 USA. RP Sharma, A (reprint author), MedImmune, Cardiovasc & Metab Dis, Gaithersburg, MD 20878 USA. EM elkhattabilham@gmail.com; sharmaar@medimmune.com FU NIH/NIDDK [RO1DK06127]; Juvenile Diabetes Research Foundation [1-2008-53]; American Diabetes Association [7-08-RA-146, 1-12-BS-187]; Herbert Graetz Fund; Shirley and William Fleisher Family Foundation; Alexander and Margaret Stewart Trust FX Studies from Sharma laboratory discussed in this review were conducted at the Joslin Diabetes Center, Harvard Medical School, and were supported by NIH/NIDDK (RO1DK06127), Juvenile Diabetes Research Foundation (1-2008-53), American Diabetes Association (7-08-RA-146; 1-12-BS-187), Herbert Graetz Fund, Shirley and William Fleisher Family Foundation, and the Alexander and Margaret Stewart Trust to AS. We thank former members of Sharma laboratory for their contributions to those studies. We thank Drs. Joseph Grimsby and John Le Lay (MedImmune, Gaithersburg, MD) for constructive criticisms of this review. NR 79 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X EI 1532-1908 J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD DEC PY 2015 VL 29 IS 6 BP 821 EP 831 DI 10.1016/j.beem.2015.09.006 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DA4IG UT WOS:000367763000002 PM 26696512 ER PT J AU Stanojevic, V Habener, JF AF Stanojevic, Violeta Habener, Joel F. TI Evolving function and potential of pancreatic alpha cells SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE alpha cells; diabetes; proglucagon; transdifferentiation; beta cells; GLP-1 ID GLUCAGON-LIKE PEPTIDE-1; PROHORMONE CONVERTASE 1/3; BETA-LIKE CELLS; ENDOCRINE PANCREAS; DIABETES-MELLITUS; GLUCOSE-TOLERANCE; NOD MICE; RECEPTOR; INSULIN; GLP-1 AB The alpha cells that co-occupy the islets in association with beta cells have been long recognized as the source of glucagon, a hyperglycemia-producing and diabetogenic hormone. Although the mechanisms that control the functions of alpha cells, glucagon secretion, and the role of glucagon in diabetes have remained somewhat enigmatic over the fifty years since their discovery, seminal findings during the past few years have moved alpha cells into the spotlight of scientific discovery. These findings obtained largely from studies in mice are: Alpha cells have the capacity to trans-differentiate into insulin-producing beta cells. Alpha cells contain a GLP-1 generating system that produces GLP-1 locally for paracrine actions within the islets that likely promotes beta cell growth and survival and maintains beta cell mass. Impairment of glucagon signaling both prevents the occurrence of diabetes in conditions of the near absence of insulin and expands alpha cell mass. Alpha cells appear to serve as helper cells or guardians of beta cells to ensure their health and well-being. Of potential relevance to the possibility of promoting the transformation of alpha to beta cells is the observation that impairment of glucagon signaling leads to a marked increase in alpha cell mass in the islets. Such alpha cell hyperplasia provides an increased supply of alpha cells for their transdifferentiation into new beta cells. In this review we discuss these recent discoveries from the perspective of their potential relevance to the treatment of diabetes. (C) 2015 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Thier Bldg 306,50 Blossom St, Boston, MA 02114 USA. EM jhabener@mgh.harvard.edu FU NIDDK NIH HHS [P30 DK057521] NR 78 TC 4 Z9 4 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X EI 1532-1908 J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD DEC PY 2015 VL 29 IS 6 BP 859 EP 871 DI 10.1016/j.beem.2015.10.002 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DA4IG UT WOS:000367763000005 PM 26696515 ER PT J AU Groer, MW Gregory, KE Louis-Jacques, A Thibeau, S Walker, WA AF Groer, Maureen W. Gregory, Katherine E. Louis-Jacques, Adetola Thibeau, Shelley Walker, W. Allan TI The Very Low Birth Weight Infant Microbiome and Childhood Health SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS LA English DT Review DE preterm infant; microbome; childhood diseases ID INTESTINAL MICROBIOTA; NECROTIZING ENTEROCOLITIS; SPECTRUM DISORDERS; PREMATURE-INFANTS; CESAREAN-SECTION; PRETERM INFANTS; BREAST-MILK; GUT; INFECTION; CHILDREN AB This review describes current understandings about the nature of the very low birth weight infant (VLBW) gut microbiome. VLBW infants often experience disruptive pregnancies and births, and prenatal factors can influence the maturity of the gut and immune system, and disturb microbial balance and succession. Many VLBWs experience rapid vaginal or Caesarean births. After birth these infants often have delays in enteral feeding, and many receive little or no mother's own milk. Furthermore the stressors of neonatal life in the hospital environment, common use of antibiotics, invasive procedures and maternal separation can contribute to dysbiosis. These infants experience gastrointestinal dysfunction, sepsis, transfusions, necrotizing enterocolitis, oxygen toxicity, and other pathophysiological consditions that affect the normal microbiota. The skin is susceptible to dysbiosis, due to its fragility and contact with NICU organisms. Dysbiosis in early life may resolve but little is known about the timing of the development of the signature gut microbiome in VLBWs. Dysbiosis has been associated with a number of physical and behavioral problems, including autism spectrum disorders, allergy and asthma, gastrointestinal disease, obesity, depression, and anxiety. Dysbiosis may be prevented or ameliorated in part by prenatal care, breast milk feeding, skin to skin contact, use of antibiotics only when necessary, and vigilance during infancy and early childhood. (C) 2015 Wiley Periodicals, Inc. C1 [Groer, Maureen W.; Louis-Jacques, Adetola] Univ S Florida, Coll Nursing, Morsani Coll Med, Tampa, FL USA. [Gregory, Katherine E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pediat Newborn Med, Boston, MA 02115 USA. [Gregory, Katherine E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Nursing, Boston, MA 02115 USA. [Thibeau, Shelley] Ochsner Hlth Syst, New Orleans, LA USA. [Walker, W. Allan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mucosal Immunol & Biol Res Ctr, Boston, MA 02115 USA. RP Groer, MW (reprint author), Univ S Florida, Coll Nursing, Morsani Coll Med, Tampa, FL USA. EM mgroer@health.usf.edu FU NIDDK NIH HHS [P30 DK040561]; NINR NIH HHS [R01 NR015446] NR 42 TC 3 Z9 4 U1 9 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-975X EI 1542-9768 J9 BIRTH DEFECTS RES C JI Birth Defects Res. Part C-Embryo Today-Rev. PD DEC PY 2015 VL 105 IS 4 BP 252 EP 264 DI 10.1002/bdrc.21115 PG 13 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA DA3ZM UT WOS:000367739900004 PM 26663857 ER PT J AU Cassaday, RD Stevenson, PA Gooley, TA Chauncey, TR Pagel, JM Rajendran, J Till, BG Philip, M Orozco, JJ Bensinger, WI Holmberg, LA Shustov, AR Green, DJ Smith, SD Libby, EN Maloney, DG Press, OW Gopal, AK AF Cassaday, Ryan D. Stevenson, Philip A. Gooley, Theodore A. Chauncey, Thomas R. Pagel, John M. Rajendran, Joseph Till, Brian G. Philip, Mary Orozco, Johnnie J. Bensinger, William I. Holmberg, Leona A. Shustov, Andrei R. Green, Damian J. Smith, Stephen D. Libby, Edward N. Maloney, David G. Press, Oliver W. Gopal, Ajay K. TI High-dose CD20-targeted radioimmunotherapy-based autologous transplantation improves outcomes for persistent mantle cell lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE non-Hodgkin lymphoma; stem cell transplantation; antibody therapy; radiotherapy ID Y-90 IBRITUMOMAB TIUXETAN; PROSPECTIVE RANDOMIZED-TRIAL; PROGRESSION-FREE SURVIVAL; NON-HODGKINS-LYMPHOMA; YTTRIUM-90-IBRITUMOMAB TIUXETAN; PHASE-II; MYELOABLATIVE RADIOCHEMOTHERAPY; ALLOGENEIC TRANSPLANTATION; PLUS RITUXIMAB; BEAM AB Autologous stem cell transplant (ASCT) can improve outcomes for mantle cell lymphoma (MCL) patients, yet relapses are frequent. We hypothesized that high-dose anti-CD20 radioimmunotherapy (RIT)-based conditioning could improve results in this setting. We thus assessed 162 consecutive patients with MCL at our centre undergoing ASCT following high-dose RIT-based (n = 61) or standard (n = 101) conditioning. RIT patients were less likely to be in first remission (48% vs. 72%; P = 0.002), be in complete remission (CR) (26% vs. 61%; P < 0.001) and have chemosensitive disease (84% vs. 96%; P = 0.006). Rh-based conditioning was associated with a reduced risk of treatment failure [hazard ratio (HR) 0.40; P = 0.001] and mortality (HR 0.49; P = 0.01) after adjusting for these imbalances. This difference increased as disease status worsened (from CR to partial remission to stable/progressive disease), with respective HRs of 1.14, 0.53 and 0.04 for mortality, and 0.66, 0.36 and 0.14 for treatment failure. RIT-based conditioning appears to improve outcome following ASCT for MCL patients unable to achieve CR after controlling for imbalances in important risk factors. These data support the further study of PIT and radiation-based strategies in a risk-adapted approach to ASCT for persistent MCL. C1 [Cassaday, Ryan D.; Gooley, Theodore A.; Chauncey, Thomas R.; Rajendran, Joseph; Till, Brian G.; Philip, Mary; Orozco, Johnnie J.; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Smith, Stephen D.; Libby, Edward N.; Maloney, David G.; Press, Oliver W.; Gopal, Ajay K.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. [Cassaday, Ryan D.; Philip, Mary; Orozco, Johnnie J.; Shustov, Andrei R.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. [Stevenson, Philip A.; Gooley, Theodore A.] Univ Washington, Fred Hutchinson Canc Res Ctr, Clin Stat Div, Seattle, WA 98195 USA. [Chauncey, Thomas R.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Chauncey, Thomas R.; Pagel, John M.; Till, Brian G.; Bensinger, William I.; Holmberg, Leona A.; Green, Damian J.; Smith, Stephen D.; Libby, Edward N.; Maloney, David G.; Press, Oliver W.; Gopal, Ajay K.] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA 98195 USA. [Rajendran, Joseph] Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. RP Gopal, AK (reprint author), 825 Eastlake Ave E,Mailstop G3-200, Seattle, WA 98109 USA. EM agopal@uw.edu FU National Institutes of Health [K12 CA076930, P01 CA044991, K24 CA184039]; Lymphoma Research Foundation Mantle Cell Lymphoma Research Initiative; Hutchinson Center/University of Washington Cancer Consortium Cancer Center Support Grant [P30 CA015704] FX This work was supported by grants from the National Institutes of Health [K12 CA076930 (R.D.C.), P01 CA044991 (O.W.P.), and K24 CA184039 (A.K.G.)] and the Lymphoma Research Foundation Mantle Cell Lymphoma Research Initiative. Support was also provided by Hutchinson Center/University of Washington Cancer Consortium Cancer Center Support Grant (P30 CA015704) and philanthropic gifts from Frank and Betty Vandermeer, Don and Debbie Hunkins, the Mary Aileen Wright Memorial Fund and the David and Patricia Giuliani Family Foundation, A.K.G. is a Scholar in Clinical Research for the Leukemia and Lymphoma Society. NR 37 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2015 VL 171 IS 5 BP 788 EP 797 DI 10.1111/bjh.13773 PG 10 WC Hematology SC Hematology GA DA4AB UT WOS:000367741400012 PM 26455717 ER PT J AU Das, DS Ray, A Song, Y Richardson, P Trikha, M Chauhan, D Anderson, KC AF Das, Deepika S. Ray, Arghya Song, Yan Richardson, Paul Trikha, Mohit Chauhan, Dharminder Anderson, Kenneth C. TI Synergistic anti-myeloma activity of the proteasome inhibitor marizomib and the IMiD (R) immunomodulatory drug pomalidomide SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE marizomib; pomalidomidc; multiple mycloma; cancer and drug therapy ID REFRACTORY MULTIPLE-MYELOMA; SINGLE-AGENT CARFILZOMIB; DOSE DEXAMETHASONE; CELL-GROWTH; OPEN-LABEL; BORTEZOMIB; THERAPY; LENALIDOMIDE; PHASE-2; CYTOTOXICITY AB The proteasome inhibitor bortezomib is an effective therapy for the treatment of relapsed and refractory multiple myeloma (RRMM); however, prolonged treatment can be associated with toxicity, peripheral neuropathy and drug resistance. Our earlier studies showed that the novel proteasome inhibitor marizomib is distinct from bortezomib in its chemical structure, mechanisms of action and effects on proteasomal activities, and that it can overcome bortezomib resistance. Pomalidomide, like lenalidomide, has potent immunomodulatory activity and has been approved by the US Food and Drug Administration for the treatment of RRMM. Here, we demonstrate that combining low concentrations of marizomib with pomalidomide induces synergistic anti-MM activity. Marizomib plus pomalidomide-induced apoptosis is associated with: (i) activation of caspase-8, caspase-9, caspase-3 and PARP cleavage, (ii) downregulation of cereblon (CRBN), IRF4, MYC and MCL1, and (iii) suppression of chymotrypsin-like, caspase-like, and trypsin-like proteasome activities. CRBN-siRNA attenuates marizomib plus pomalidomidc-induced MM cells death. Furthermore, marizomib plus pomalidomide inhibits the migration of MM cells and tumour-associated angiogenesis, as well as overcomes cytoprotective effects of bone marrow microenvironrnent. In human MM xenograft model studies, the combination of marizomib and pomalidomide is well tolerated, inhibits tumour growth and prolongs survival. These preclinical studies provide the rationale for on-going clinical trials of combined marizomib and pomalidomide to improve outcome in patients with RRMM. C1 [Das, Deepika S.; Ray, Arghya; Song, Yan; Richardson, Paul; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Das, Deepika S.; Ray, Arghya; Song, Yan; 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. [Trikha, Mohit] Triphase Accelerator, San Diego, CA USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 557, Boston, MA 02115 USA. EM dharminder_chauhan@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU National Institutes of Health Specialized Programs of Research Excellence (SPORE) grant [P50100707, PO1-CA078378, RO1 CA050947] FX This investigation was supported by National Institutes of Health Specialized Programs of Research Excellence (SPORE) grant P50100707, PO1-CA078378, and RO1 CA050947. K.C.A. is an American Cancer Society Clinical Research Professor. NR 56 TC 3 Z9 3 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2015 VL 171 IS 5 BP 798 EP 812 DI 10.1111/bjh.13780 PG 15 WC Hematology SC Hematology GA DA4AB UT WOS:000367741400013 PM 26456076 ER PT J AU Bendapudi, PK Li, A Hamdan, A Uhl, L Kaufman, R Stowell, C Dzik, W Makar, RS AF Bendapudi, Pavan K. Li, Ang Hamdan, Ayad Uhl, Lynne Kaufman, Richard Stowell, Christopher Dzik, Walter Makar, Robert S. TI Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE thrombotic microangiopathy; plasma exchange; ADAMTS13; autoimmune thrombotic thrombocytopenic purpura ID VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; HEMOLYTIC-UREMIC SYNDROME; THROMBOCYTOPENIC PURPURA; PLASMA-EXCHANGE AB The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TIP). Patients with severe ADAMTS13 deficiency (activity <= 10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TIP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93.0% vs. 47.5%, P < 0.0001). Almost all patients with severe deficiency received therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13 activity >10% varied significantly across the institutions in our consortium (13.2-63.8%, P < 0-0001). Nevertheless, 90-d mortality was not different in patients with ADAMTS13 activity >10% between the three hospitals (P = 0-98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA. without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE. C1 [Bendapudi, Pavan K.] Massachusetts Gen Hosp, Div Hematol, Boston, MA 02139 USA. [Bendapudi, Pavan K.; Li, Ang; Hamdan, Ayad; Uhl, Lynne; Kaufman, Richard; Stowell, Christopher; Dzik, Walter; Makar, Robert S.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Ang] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hamdan, Ayad] Brigham & Womens Hosp, Div Hematol & Oncol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Uhl, Lynne] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Kaufman, Richard] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Stowell, Christopher; Dzik, Walter; Makar, Robert S.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02139 USA. RP Bendapudi, PK (reprint author), Massachusetts Gen Hosp, Div Hematol, Yawkey 7,55 Fruit St, Boston, MA 02139 USA. EM pkbendapudi@partners.org FU Luick Family Fund of the Massachusetts General Hospital FX This work was generously supported by the Luick Family Fund of the Massachusetts General Hospital. NR 20 TC 4 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2015 VL 171 IS 5 BP 836 EP 844 DI 10.1111/bjh.13658 PG 9 WC Hematology SC Hematology GA DA4AB UT WOS:000367741400017 PM 26314936 ER PT J AU Inkelas, M Brown, AF Vassar, SD Sankare, IC Martinez, AB Kubicek, K Kuo, T Mahajan, A Gould, M Mittman, BS AF Inkelas, Moira Brown, Arleen F. Vassar, Stefanie D. Sankare, Ibrahima C. Martinez, Arturo B. Kubicek, Katrina Kuo, Tony Mahajan, Anish Gould, Michael Mittman, Brian S. TI Enhancing Dissemination, Implementation, and Improvement Science in CTSAs through Regional Partnerships SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE dissemination; implementation; improvement science; translational research; institutional collaboration ID CLINICAL-RESEARCH ENTERPRISE; HEALTH-CARE; INTEGRATION AB Background and ImportanceChallenges in healthcare policy and practice have stimulated interest in dissemination and implementation science. The Institute of Medicine Committee on the Clinical Translational Science Award (CTSA) program recommended expanding the CTSA program's investment and activity in this domain. Guidance is needed to facilitate successful growth of DII science infrastructure, activity and impacts. ObjectivesSeveral CTSAs in Southern California collaborated to identify and respond to local challenges and opportunities to expand dissemination, implementation and improvement research by strengthening capacity and relationships between DII researchers and community, health system, and population health partners. Main outcomesPlanning and outreach by the Southern California CTSAs increased awareness and interest in DII research and generated recommendations for growth. Recommendations include: increasing strong partnerships with healthcare and population health systems to guide policy research agendas and collaborative DII science; promoting multi-sector partnerships that involve researchers and delivery systems throughout DII processes; bringing together multiple disciplines; and addressing national and international barriers as well as opportunities in DII science. ImplicationsCTSAs through regional collaboration can increase their contributions to improved community health via skill-building, partnership development and enhanced outreach to local healthcare and public health agencies and delivery systems. C1 [Inkelas, Moira] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Clin & Translat Sci Inst, Los Angeles, CA 90095 USA. [Brown, Arleen F.; Vassar, Stefanie D.; Sankare, Ibrahima C.; Martinez, Arturo B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Clin & Translat Sci Inst,Hlth Serv Res, Los Angeles, CA 90095 USA. [Kuo, Tony] Los Angeles Cty Dept Publ Hlth, Div Chron Dis & Injury Prevent, Los Angeles, CA USA. [Kuo, Tony] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Kuo, Tony] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90095 USA. [Mahajan, Anish] Los Angeles Cty Dept Hlth Serv, Syst Planning Improvement & Data Analyt, Los Angeles, CA USA. [Gould, Michael; Mittman, Brian S.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Kubicek, Katrina] Univ So Calif, Southern Calif Clin & Translat Sci Inst, Los Angeles, CA USA. [Kubicek, Katrina] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Mittman, Brian S.] VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support CIPRS, Los Angeles, CA USA. RP Inkelas, M (reprint author), Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Clin & Translat Sci Inst, Los Angeles, CA 90095 USA. EM minkelas@ucla.edu OI Kuo, Tony/0000-0002-4120-8559 FU National Institutes of Health/National Center for Advancing Translational Sciences through UCLA CTSI Grant [UL1TR000124]; Southern California CTSI Grant [UL1TR000130]; Kaiser Permanente Southern California FX The research described was supported, in part, by the National Institutes of Health/National Center for Advancing Translational Sciences through UCLA CTSI Grant Number UL1TR000124, the Southern California CTSI Grant Number UL1TR000130, and Kaiser Permanente Southern California. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 24 TC 1 Z9 1 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 EI 1752-8062 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD DEC PY 2015 VL 8 IS 6 BP 800 EP 806 DI 10.1111/cts.12348 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DA3DL UT WOS:000367676600034 PM 26602191 ER PT J AU Bodison, SC Sankare, I Anaya, H Booker-Vaughns, J Miller, A Williams, P Norris, K AF Bodison, Stefanie C. Sankare, Ibrahima Anaya, Henry Booker-Vaughns, Juanita Miller, Aria Williams, Pluscedia Norris, Keith CA Community Engagement Workgrp TI Engaging the Community in the Dissemination, Implementation, and Improvement of Health-Related Research SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE community-partnered participatory research; community-based participatory research; community engagement; translational research; implementation science ID PARTICIPATORY RESEARCH; PARTNERED RESEARCH; POPULATION HEALTH; STRATEGIES; ENGAGEMENT; SCIENCE; INTEGRATION; EXPERIENCE; DISTRUST; BARRIERS AB To help maximize the real-world applicability of available interventions in clinical and community healthcare practice, there has been greater emphasis over the past two decades on engaging local communities in health-related research. While there have been numerous successful community-academic partnered collaborations, there continues to be a need to articulate the common barriers experienced during the evolution of these partnerships, and to provide a roadmap for best practices that engage healthcare providers, patients, families, caregivers, community leaders, healthcare systems, public agencies and academic medical centers. To this end, this paper presents a summary of a forum discussion from the 2014 Southern California Dissemination, Implementation and Improvement (DII) Science Symposium, sponsored by the University of California Los Angeles (UCLA) Clinical Translational Science Institute (CTSI), University of Southern California (USC) CTSI, and Kaiser Permanente. During this forum, a diverse group of individuals representing multiple constituencies identified four key barriers to success in community-partnered participatory research (CPPR) and discussed consensus recommendations to enhance the development, implementation, and dissemination of community health-related research. In addition, this group identified several ways in which the over 60 NIH funded Clinical and Translational Science Institutes across the country could engage communities and researchers to advance DII science. C1 [Bodison, Stefanie C.] Univ So Calif, Chan Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90095 USA. [Sankare, Ibrahima] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. [Anaya, Henry] US Dept Vet Affairs, Los Angeles, CA USA. [Booker-Vaughns, Juanita; Williams, Pluscedia] Hlth African Amer Families, Los Angeles, CA USA. [Miller, Aria] City Hope Natl Med Ctr, Natl Med Ctr, Dept Populat Sci, Ctr Community Alliance Res & Educ, Duarte, CA USA. [Williams, Pluscedia] Charles R Drew Univ, Los Angeles, CA USA. [Williams, Pluscedia] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Norris, Keith] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Bodison, SC (reprint author), Univ So Calif, Chan Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90095 USA. EM bodison@usc.edu FU National Institutes of Health/National Center for Advancing Translational Sciences through UCLA CTSI [UL1TR000124]; Southern California CTSI [UL1TR000130]; Kaiser Permanente Southern California; National Institutes of Health/National Center for Research Resources/National Center for Advancing Translational Sciences [KL2TR000131]; National Institutes of Health [2P20MD000182, 3P30AG021684] FX The research described was supported, in part, by the National Institutes of Health/National Center for Advancing Translational Sciences through UCLA CTSI Grant Number UL1TR000124, the Southern California CTSI Grant Number UL1TR000130, and Kaiser Permanente Southern California. Work on the manuscript was also supported by the National Institutes of Health/National Center for Research Resources/National Center for Advancing Translational Sciences Grant Number KL2TR000131 (SB); and National Institutes of Health Grant Numbers 2P20MD000182 (KN), 3P30AG021684 (KN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 46 TC 1 Z9 1 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 EI 1752-8062 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD DEC PY 2015 VL 8 IS 6 BP 814 EP 819 DI 10.1111/cts.12342 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DA3DL UT WOS:000367676600036 PM 26546337 ER PT J AU Wilbur, DC Nayar, R AF Wilbur, D. C. Nayar, R. TI Bethesda 2014: improving on a paradigm shift SO CYTOPATHOLOGY LA English DT Review DE gynecologic cytology; Pap test; Bethesda System ID CERVICAL-CANCER; CONSENSUS GUIDELINES; MANAGEMENT; CYTOLOGY; ABNORMALITIES; TERMINOLOGY; COLPOSCOPY; PRECURSORS; SOCIETY; SYSTEM AB The third iteration of the Bethesda System terminology manual was recently published. This update included changes in the reporting of benign endometrial cells, and guidance for special adequacy situations and for cases in which low grade squamous intraepithelial lesions are accompanied by some cells suggesting that a high grade lesion might also be present. In addition, the manual was increased in size to include more illustrations with special studies and comparisons to histology, a greatly increased reference list, and a new chapter devoted to the modern practice of risk-based management. The third edition of the Bethesda manual is meant to serve as a primary reference for the practice of gynecologic cytology designed to provide a uniform system of reporting Worldwide for clinical, teaching, and research purposes. C1 [Wilbur, D. C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wilbur, D. C.] Harvard Univ, Sch Med, Boston, MA USA. [Nayar, R.] Northwestern Univ & Northwestren Med, Feinberg Sch Med, Dept Pathol, Chicago, IL USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM dwilbur@mgh.harvard.edu NR 23 TC 1 Z9 1 U1 4 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0956-5507 EI 1365-2303 J9 CYTOPATHOLOGY JI Cytopathology PD DEC PY 2015 VL 26 IS 6 SI SI BP 339 EP 342 DI 10.1111/cyt.12300 PG 4 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DA3BW UT WOS:000367671900002 PM 26767599 ER PT J AU Sassmann, H Albrecht, C Busse-Widmann, P Hevelke, LK Kranz, J Markowitz, JT Marshall, LF Meurs, S de Soye, IH Lange, K AF Sassmann, H. Albrecht, C. Busse-Widmann, P. Hevelke, L. K. Kranz, J. Markowitz, J. T. Marshall, L. F. Meurs, S. de Soye, I. H. Lange, K. TI Psychometric properties of the German version of the Diabetes Eating Problem Survey-Revised: additional benefit of disease-specific screening in adolescents with Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article ID DISORDERS; CHILDREN; BEHAVIOR; INSULIN; MELLITUS; FEMALES; QUESTIONNAIRE; COMPLICATIONS; METAANALYSIS; INTERVIEW AB Aim To examine the psychometric properties of the German version of the abbreviated 16-item Diabetes Eating Problem Survey-Revised in a sample of young people with Type 1 diabetes. Methods A total of 246 young people, aged 11-19 years, with Type 1 diabetes from six pediatric diabetes centres in Germany were assessed using the Diabetes Eating Problem Survey-Revised. In addition, they underwent screening with two generic tools as well as the WHO five-question well-being index. A clinician's report was also obtained. Results The Diabetes Eating Problem Survey-Revised was found to have good internal consistency (Cronbach's alpha = 0.84). The Diabetes Eating Problem Survey-Revised scores significantly correlated with those provided by the nonspecific screening tools (r = 0.37, P <= 0.000 and r = 0.50, P <= 0.000 for boys and r = 0.62, P <= 0.000 and r = 0.79, P <= 0.000 for girls), indicating convergent validity. The mean (SD) total of the scores was 12.0 (9.6). Criterion validity was confirmed against HbA(1c) value, BMI standard deviation score and expert (clinician) report. Of the boys included in the study, 11 scored higher than the threshold score on the Diabetes Eating Problem Survey-Revised, of whom only three (27%) were classified as 'suspected to have a disordered eating behaviour' by their clinicians. Conclusions The Diabetes Eating Problem Survey-Revised delivered more specific information than generic screening instruments and identified more young people with eating disorders than did clinician report, especially regarding the detection of boys at risk. The results of this study support the utility of the German version of the Diabetes Eating Problem Survey-Revised to identify eating disorders in young people with Type 1 diabetes at an early stage. (German Clinical Trials Registry no.: DRKS00004699) C1 [Sassmann, H.; Hevelke, L. K.; Lange, K.] Hannover Med Sch, Med Psychol, Hannover, Germany. [Albrecht, C.] Bunter Kreis GmbH, Team Diabet, Clin Children & Juveniles, Clin Ctr Augsburg, Augsburg, Germany. [Busse-Widmann, P.] Paediat & Youth Med Clin, Dritter Orden Clin Munich, Munich, Germany. [Kranz, J.] Univ Tubingen, Childrens Hosp, Dept 3, Tubingen, Germany. [Markowitz, J. T.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Marshall, L. F.] Univ Med Ctr Schleswig Holstein Lubeck, Hosp Child & Adolescent Med, Lubeck, Germany. [Meurs, S.] Childrens Hosp Passau Dritter Orden, Social Paediat Ctr, Passau, Germany. [de Soye, I. H.] Childrens Hosp, Clin Ctr Nurnberg Sud, Nurnberg, Germany. RP Sassmann, H (reprint author), Hannover Med Sch, Med Psychol, Hannover, Germany. EM sassmann.heike@mh-hannover.de FU foundation 'Das zuckerkranke Kind' FX This work was supported in part by the foundation 'Das zuckerkranke Kind'. NR 25 TC 2 Z9 2 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD DEC PY 2015 VL 32 IS 12 BP 1641 EP 1647 DI 10.1111/dme.12788 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DA3HJ UT WOS:000367687500016 PM 25919651 ER PT J AU Hanlon, CA DeVries, W Dowdle, LT West, JA Siekman, B Li, XB George, MS AF Hanlon, Colleen A. DeVries, William Dowdle, Logan T. West, Julia A. Siekman, Bradley Li, Xingbao George, Mark S. TI A comprehensive study of sensorimotor cortex excitability in chronic cocaine users: Integrating TMS and functional MRI data SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Addiction; Brain stimulation; Electrophysiology; Recruitment curve; Cortex ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; CORTICAL EXCITABILITY; DEPENDENT PATIENTS; INHIBITION; LAMOTRIGINE; QUESTIONNAIRE; EXCITATION; THRESHOLD; LORAZEPAM AB Background: Disruptions in motor control are often overlooked features of chronic cocaine users. During a simple sensorimotor integration task, for example, cocaine users activate a larger area of cortex than controls but have lower functional connectivity between the cortex and dorsal striatum, which is further correlated with poor performance. The purpose of this study was to determine whether abnormal cortical excitability in cocaine users was related to disrupted inhibitory or excitatory mechanisms, as measured by transcranial magnetic stimulation (TMS). Methods: A battery of TMS measures were acquired from 87 individuals (50 cocaine dependent, 37 controls). Functional MM data were acquired from a subset of 28 individuals who performed a block-design finger tapping task. Results: TMS measures revealed that cocaine users had significantly higher resting motor thresholds and higher intracortical cortical facilitation (ICF) than controls. There was no between-group difference in either measure of cortical inhibition. Task-evoked BOLD signal in the motor cortex was significantly correlated with ICF in the cocaine users. There was no significant difference in brain skull distance between groups. Conclusion: These data demonstrated that cocaine users have disrupted cortical facilitation (as measured with TMS), which is related to elevated BOLD signal. Cortical inhibition, however, is largely intact. Given the relationship between ICF and glutamatergic agents, this may be a potentially fruitful and treatable target in addiction. Finally, among controls the distance from the scalp to the cortex was correlated with the motor threshold which may be a useful parameter to integrate into therapeutic TMS protocols in the future. (C) 2015 Published by Elsevier Ireland Ltd. C1 [Hanlon, Colleen A.; DeVries, William; Dowdle, Logan T.; West, Julia A.; Siekman, Bradley; Li, Xingbao; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Dowdle, Logan T.; West, Julia A.; Siekman, Bradley; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Hanlon, CA (reprint author), Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. EM hanlon@musc.edu OI Dowdle, Logan/0000-0002-1879-705X FU NIDA [K01DA027756, R01DA036617]; MUSC's CTSA from the National Center for Research Resources [UL1 RR029882] FX Funding was provided by NIDA K01DA027756 (Hanlon), R01DA036617, and MUSC's CTSA UL1 RR029882 from the National Center for Research Resources. The funding source had no further role in study design, collection, analysis, interpretation or in the decision to submit the paper for publication. NR 54 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2015 VL 157 BP 28 EP 35 DI 10.1016/j.drugalcdep.2015.07.1196 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DA5QM UT WOS:000367857600003 PM 26541870 ER PT J AU Safa, K Chandran, S Wojciechowski, D AF Safa, Kassem Chandran, Sindhu Wojciechowski, David TI Pharmacologic Targeting of Regulatory T Cells for Solid Organ Transplantation: Current and Future Prospects (vol 75, pg 1843, 2015) SO DRUGS LA English DT Correction C1 [Safa, Kassem; Wojciechowski, David] Harvard Univ, Sch Med, Div Nephrol, Boston, MA 02115 USA. [Safa, Kassem; Wojciechowski, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02115 USA. [Chandran, Sindhu] Univ Calif San Francisco, Med Ctr, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. RP Wojciechowski, D (reprint author), Harvard Univ, Sch Med, Div Nephrol, 55 Fruit St, Boston, MA 02115 USA. EM dwojciechowski@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 0012-6667 EI 1179-1950 J9 DRUGS JI Drugs PD DEC PY 2015 VL 75 IS 18 BP 2171 EP 2171 DI 10.1007/s40265-015-0501-z PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA DA2EZ UT WOS:000367609400010 PM 26553341 ER PT J AU Petrovics, G Li, H Stumpel, T Tan, SH Young, D Katta, S Li, QY Ying, K Klocke, B Ravindranath, L Kohaar, I Chen, YM Ribli, D Grote, K Zou, H Cheng, J Dalgard, CL Zhang, SM Csabai, I Kagan, J Takeda, D Loda, M Srivastava, S Scherf, M Seifert, M Gaiser, T McLeod, DG Szallasi, Z Ebner, R Werner, T Sesterhenn, IA Freedman, M Dobi, A Srivastava, S AF Petrovics, Gyorgy Li, Hua Stuempel, Tanja Tan, Shyh-Han Young, Denise Katta, Shilpa Li, Qiyuan Ying, Kai Klocke, Bernward Ravindranath, Lakshmi Kohaar, Indu Chen, Yongmei Ribli, Dezso Grote, Korbinian Zou, Hua Cheng, Joseph Dalgard, Clifton L. Zhang, Shimin Csabai, Istvan Kagan, Jacob Takeda, David Loda, Massimo Srivastava, Sudhir Scherf, Matthias Seifert, Martin Gaiser, Timo McLeod, David G. Szallasi, Zoltan Ebner, Reinhard Werner, Thomas Sesterhenn, Isabell A. Freedman, Matthew Dobi, Albert Srivastava, Shiv TI A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men SO EBIOMEDICINE LA English DT Article DE African American; Prostate cancer; Genome; LSAMP; ERG; PTEN ID SOMATIC POINT MUTATIONS; ERG ONCOPROTEIN EXPRESSION; GENERATION SEQUENCING DATA; MOLECULAR DIFFERENCES; WIDE ASSOCIATION; COPY NUMBER; LANDSCAPE; CELLS; STRATIFICATION; CARCINOGENESIS AB Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somaticmutations in CaP across ancestral groups, which have implications for precision medicine strategies. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Petrovics, Gyorgy; Li, Hua; Tan, Shyh-Han; Young, Denise; Katta, Shilpa; Ying, Kai; Ravindranath, Lakshmi; Kohaar, Indu; Chen, Yongmei; McLeod, David G.; Dobi, Albert; Srivastava, Shiv] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. [Petrovics, Gyorgy; Li, Hua; Tan, Shyh-Han; Young, Denise; Katta, Shilpa; Ying, Kai; Ravindranath, Lakshmi; Kohaar, Indu; Chen, Yongmei; McLeod, David G.; Dobi, Albert; Srivastava, Shiv] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20814 USA. [Stuempel, Tanja; Klocke, Bernward; Grote, Korbinian; Scherf, Matthias; Seifert, Martin; Werner, Thomas] Genomatix Software GmbH, D-80335 Munchene, Germany. [Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen 361102, Peoples R China. [Li, Qiyuan; Takeda, David; Loda, Massimo; Freedman, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Ribli, Dezso; Csabai, Istvan] Eotvos Lorand Univ, Dept Phys Complex Syst, H-1117 Budapest, Hungary. [Ribli, Dezso; Csabai, Istvan; Szallasi, Zoltan] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Zou, Hua; Cheng, Joseph; Ebner, Reinhard] CytoTest Inc, Rockville, MD 20850 USA. [Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Collaborat Hlth Initiat Res Program, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Zhang, Shimin; Sesterhenn, Isabell A.] Joint Pathol Ctr, Genitourinary Pathol, Silver Spring, MD 20910 USA. [Kagan, Jacob; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Takeda, David; Loda, Massimo; Freedman, Matthew] Eli & Edythe L Broad Inst, Cambridge, MA USA. [Gaiser, Timo] Heidelberg Univ, Med Fak Mannheim, Univ Med Mannheim, Inst Pathol, D-68167 Mannheim, Germany. [McLeod, David G.] Walter Reed Natl Mil Med Ctr, Urol Serv, Bethesda, MD 20814 USA. [Szallasi, Zoltan] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA 02115 USA. [Szallasi, Zoltan] Semmelweis Univ, Dept Pathol 2, Hungarian Acad Sci, Brain Metastasis Res Grp,MTA SE NAP, H-1091 Budapest, Hungary. [Werner, Thomas] Univ Michigan, Div Nephrol, Internal Med, Ann Arbor, MI 48109 USA. [Werner, Thomas] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. RP Freedman, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. EM freedman@broadinstitute.org; adobi@cpdr.org; ssrivastava@cpdr.org OI Tan, Shyh-Han/0000-0001-8250-7005; Csabai, Istvan/0000-0001-9232-9898 FU NCI NIH HHS [R01 CA162383, R01 CA162383-05] NR 57 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD DEC PY 2015 VL 2 IS 12 BP 1957 EP 1964 DI 10.1016/j.ebiom.2015.10.028 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DA1EC UT WOS:000367538100028 PM 26844274 ER PT J AU Pandharipande, PV Jeon, A Heberle, CR Dowling, EC Kong, CY Chung, DC Brugge, WR Hur, C AF Pandharipande, Pari V. Jeon, Alvin Heberle, Curtis R. Dowling, Emily C. Kong, Chung Yin Chung, Daniel C. Brugge, William R. Hur, Chin TI Screening for Pancreatic Adenocarcinoma in BRCA2 Mutation Carriers: Results of a Disease Simulation Model SO EBIOMEDICINE LA English DT Article DE Pancreatic cancer; BRCA2 mutation; Cancer screening; Simulation disease modeling ID RANDOMIZED CONTROLLED-TRIAL; HIGH-RISK; ADJUVANT CHEMOTHERAPY; OPERATIVE MORTALITY; HOSPITAL VOLUME; CANCER; RESECTION; INDIVIDUALS; GEMCITABINE; EXPERIENCE AB Background: BRCA2 mutation carriers are at increased risk for multiple cancers including pancreatic adenocarcinoma (PAC). Our goal was to compare the effectiveness of different PAC screening strategies in BRCA2 mutation carriers, from the standpoint of life expectancy. Methods: A previously published Markov model of PAC was updated and extended to incorporate key aspects of BRCA2 mutation carrier status, including competing risks of breast-and ovarian-cancer specific mortality. BRCA2 mutation carriers were modeled and analyzed as the primary cohort for the analysis. Additional higher risk BRCA2 cohorts that were stratified according to the number of first-degree relatives (FDRs) with PAC were also analyzed. For each cohort, one-time screening and annual screening were evaluated, with screening starting at age 50 in both strategies. The primary outcome was net gain in life expectancy (LE) compared to no screening. Sensitivity analysis was performed on key model parameters, including surgical mortality and MRI test performance. Findings: One-timescreening at age 50 resulted in a LE gain of 3.9 days for the primary BRCA2 cohort, and a gain of 5.8 days for thosewith BRCA2 and one FDR. Annual screening resulted in LE loss of 12.9 days for the primary cohort and 1.3 days for BRCA2 carriers with 1 FDR, but resulted in 20.6 days gained for carriers with 2 FDRs and 260 days gained for those with 3 FDRs. For patients with >= 3 FDRs, annual screening starting at an earlier age (i.e. 35-40) was optimal. Interpretation: Among BRCA2 mutation carriers, aggressive screening regimens may be ineffective unless additional indicators of elevated risk (e.g., 2 or more FDRs) are present. More clinical studies are needed to confirm these findings. Funding: American Cancer Society -NewEngland Division - Ellison Foundation Research Scholar Grant (RSG-15129-01-CPHPS). (C) 2015 The Authors. Published by Elsevier B.V. C1 [Pandharipande, Pari V.; Jeon, Alvin; Heberle, Curtis R.; Dowling, Emily C.; Kong, Chung Yin; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Pandharipande, Pari V.; Jeon, Alvin; Heberle, Curtis R.; Chung, Daniel C.; Brugge, William R.; Hur, Chin] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Pandharipande, Pari V.; Dowling, Emily C.; Kong, Chung Yin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kong, Chung Yin; Chung, Daniel C.; Brugge, William R.; Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St, Boston, MA 02114 USA. EM chur@mgh.harvard.edu OI Hur, Chin/0000-0002-2819-7576 NR 30 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD DEC PY 2015 VL 2 IS 12 BP 1980 EP 1986 DI 10.1016/j.ebiom.2015.11.005 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DA1EC UT WOS:000367538100031 PM 26844277 ER PT J AU Pun, VC Hart, JE Kabrhel, C Camargo, CA Baccarelli, AA Laden, F AF Pun, Vivian C. Hart, Jaime E. Kabrhel, Christopher Camargo, Carlos A., Jr. Baccarelli, Andrea A. Laden, Francine TI Prospective Study of Ambient Particulate Matter Exposure and Risk of Pulmonary Embolism in the Nurses' Health Study Cohort SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID AMERICAN-HEART-ASSOCIATION; DEEP-VEIN THROMBOSIS; LONG-TERM EXPOSURE; AIR-POLLUTION; UNITED-STATES; VENOUS THROMBOEMBOLISM; CARDIOVASCULAR-DISEASE; MORTALITY; WOMEN; EPIDEMIOLOGY AB BACKGROUND: Pulmonary embolism (PE) is the most serious manifestation of venous thromboembolism and a leading cause of sudden death. Several studies have suggested associations of venous thromboembolism with short-term particulate matter (PM) exposure; evidence on long-term PM and traffic exposure is mixed. OBJECTIVES: We examined the association of long-term exposure to PM2.5, PM2.5-10, and PM10 (PM with diameter of <= 2.5, 2.5-10, and <= 10 mu m) and distance to roadways with overall incident PE and with PE subtypes in a cohort of U. S. women. METHODS: The study included 115,745 women from the Nurses' Health Study, followed from 1992 through 2008. Incident PE cases were self-reported biennially. Nonidiopathic PE were cases for which the medical record revealed an underlying health condition related to PE (i. e., surgery, trauma, or malignancy); idiopathic PE were cases with no such history. We used spatiotemporal models combining spatial smoothing and geographic covariates to quantify exposure at residential addresses, and Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: PM2.5 averaged over 1month (HR= 1.22; 95% CI: 1.04, 1.44) or 12 months (HR= 1.17; 95% CI: 0.93, 1.48) was associated with incident PE, after adjusting for known risk factors and PM2.5-10. Equivalent analyses restricted to PE subtypes showed a positive association for PM2.5 with nonidiopathic PE, but not with idiopathic PE. We did not find evidence of an -association between distance to roadways and PE risk. CONCLUSIONS: We provide evidence that PM in the prior 1 and 12 months is associated with PE risk. Our results also suggest that women with underlying health conditions may be more-susceptible to PE after PM exposure. C1 [Pun, Vivian C.] Chinese Univ Hong Kong, Jockey Club Sch Publ Hlth & Primary Care, Shatin, Hong Kong, Peoples R China. [Pun, Vivian C.; Hart, Jaime E.; Baccarelli, Andrea A.; Laden, Francine] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hart, Jaime E.; Kabrhel, Christopher; Camargo, Carlos A., Jr.; Laden, Francine] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Hart, Jaime E.; Kabrhel, Christopher; Camargo, Carlos A., Jr.; Laden, Francine] Harvard Univ, Sch Med, Boston, MA USA. [Kabrhel, Christopher; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.; Baccarelli, Andrea A.; Laden, Francine] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Laden, F (reprint author), Landmark Ctr, Channing Div Network Med, 401 Pk Dr,3rd Floor West, Boston, MA 02215 USA. EM francine.laden@channing.harvard.edu OI Baccarelli, Andrea/0000-0002-3436-0640; Kabrhel, Christopher/0000-0002-8699-7176 FU National Institutes of Health [P01 CA87969, R01 ES017017, R01 HL116854, UM1 CA186107]; Global Scholarship Programme for Research Excellence-CNOOC (China National Offshore Oil Corporation) grant from the Chinese University of Hong Kong FX This work was funded by National Institutes of Health grants P01 CA87969, R01 ES017017, R01 HL116854, and UM1 CA186107. V.C.P. was supported by a Global Scholarship Programme for Research Excellence-CNOOC (China National Offshore Oil Corporation) grant from the Chinese University of Hong Kong. NR 45 TC 2 Z9 2 U1 4 U2 12 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2015 VL 123 IS 12 BP 1265 EP 1270 DI 10.1289/ehp.1408927 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DA1WS UT WOS:000367587000013 PM 25956005 ER PT J AU Bartlett, BA Mitchell, KS AF Bartlett, Brooke A. Mitchell, Karen S. TI Eating Disorders in Military and Veteran Men and Women: A Systematic Review SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Review DE eating disorders; veterans; military; women; men ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY-REPLICATION; SEXUAL TRAUMA; AFGHANISTAN VETERANS; US MILITARY; PSYCHIATRIC COMORBIDITY; CONTRIBUTING FACTORS; FEMALE VETERANS; GENDER-DIFFERENCES; HEALTH DIAGNOSES AB Objective: Eating disorders (EDs) have serious consequences for psychological and physical health. They have high mortality rates and are among the most costly disorders to treat. However, EDs remain understudied in military and veteran populations. The aim of this review was to examine prevalence estimates and associated symptomatology of EDs among military and veteran men and women and to identify factors that may put these individuals at risk for the development of an ED for the purposes of improving detection, intervention, and treatment. Method: A thorough literature review was conducted using the databases Psy-cINFO and PubMed. All articles with a focus on EDs in military/veteran samples were considered. Results: Studies reveal high prevalence estimates of EDs among military/veteran men and women. Unique features of military life may increase the risk for development of an ED, including: military sexual trauma, strict weight and physical fitness requirements, and combat exposure. A history of trauma was common in individuals diagnosed with an ED in military and veteran samples. Discussion: The high rates of EDs among military and veteran samples underscore the importance of further research, as well as the importance of screening and intervention efforts, in these understudied populations. (C) 2015 Wiley Periodicals, Inc. C1 [Bartlett, Brooke A.; Mitchell, Karen S.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Bartlett, Brooke A.; Mitchell, Karen S.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Bartlett, BA (reprint author), VA Boston, Womens Hlth Sci Div, Healthcare Syst, Natl Ctr PTSD, Boston, VA 22714 USA. EM bbartlet@bu.edu FU [K01MH093750] FX Supported by Contract grant sponsor: K01MH093750 (to K.S.M.). NR 67 TC 3 Z9 3 U1 4 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD DEC PY 2015 VL 48 IS 8 BP 1057 EP 1069 DI 10.1002/eat.22454 PG 13 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA DA2YG UT WOS:000367662500001 PM 26310193 ER PT J AU Rosen, LJ Myers, V Winickoff, JP Kott, J AF Rosen, Laura J. Myers, Vicki Winickoff, Jonathan P. Kott, Jeff TI Effectiveness of Interventions to Reduce Tobacco Smoke Pollution in Homes: A Systematic Review and Meta-Analysis SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article; Proceedings Paper CT Scientific Symposium Small Solution for Big Water-Related Problems Innovative Microarrays and Small Sensors to Cope with Water Quality and Food Security CY OCT 26-28, 2014 CL Rome, ITALY DE tobacco smoke exposure (TSE); environmental tobacco smoke (ETS); home air quality; air nicotine; respirable small particles (RSPs) ID RANDOMIZED CONTROLLED-TRIAL; SECONDHAND SMOKE; PASSIVE SMOKING; YOUNG-CHILDREN; ASTHMATIC-CHILDREN; PARENTAL SMOKING; EXPOSED CHILDREN; MATERNAL SMOKING; LATINO CHILDREN; URBAN CHILDREN AB Introduction: Smoke-free homes can help protect children from tobacco smoke exposure (TSE). The objective of this study was to conduct a meta-analysis to quantify effects of interventions on changes in tobacco smoke pollution in the home, as measured by air nicotine and particulate matter (PM). Methods: We searched MEDLINE, PubMed, Web of Science, PsycINFO, and Embase. We included controlled trials of interventions which aimed to help parents protect children from tobacco smoke exposure. Two reviewers identified relevant studies, and three reviewers extracted data. Results: Seven studies were identified. Interventions improved tobacco smoke air pollution in homes as assessed by nicotine or PM. (6 studies, N = 681, p = 0.02). Analyses of air nicotine and PM separately also showed some benefit (Air nicotine: 4 studies, N = 421, p = 0.08; PM: 3 studies, N = 340, p = 0.02). Despite improvements, tobacco smoke pollution was present in homes in all studies at follow-up. Conclusions: Interventions designed to protect children from tobacco smoke are effective in reducing tobacco smoke pollution (as assessed by air nicotine or PM) in homes, but contamination remains. The persistence of significant pollution levels in homes after individual level intervention may signal the need for other population and regulatory measures to help reduce and eliminate childhood tobacco smoke exposure. C1 [Rosen, Laura J.; Myers, Vicki] Tel Aviv Univ, Sackler Fac Med, Sch Publ Hlth, IL-69978 Ramat Aviv, Israel. [Winickoff, Jonathan P.] Massachusetts Gen Hosp, Boston, MA 02451 USA. [Winickoff, Jonathan P.] Harvard Univ, Sch Med, Boston, MA 02451 USA. [Kott, Jeff] Tel Aviv Univ, Sackler Fac Med, Sackler Sch Med, IL-69978 Ramat Aviv, Israel. EM rosenl@post.tau.ac.il; vicki_myers@hotmail.com; jwinickoff@mgh.harvard.edu; jeffreykott@gmail.com FU Flight Attendant Medical Research Institute (FAMRI) [072086_YCSA]; Sackler Faculty of Medicine at Tel Aviv University FX We thank the Flight Attendant Medical Research Institute (FAMRI) for funding for this study (Award # 072086_YCSA), and the Sackler Faculty of Medicine at Tel Aviv University for a student stipend. We thank Ruth Suhami for her assistance with the systematic review of the literature. We thank the following individuals, who provided additional information on published studies for use in this systematic review: Arlene Butz, Bruce Lanphear, Amy Kalkbrenner, Jane Khoudi, Alex Prokhorov, Sean Semple, Angela Stotts, Michelle Eakin, Sandy Liles, Mel Hovell, and Michal Ben Noach. NR 80 TC 2 Z9 2 U1 6 U2 11 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD DEC PY 2015 VL 12 IS 12 BP 16043 EP 16059 DI 10.3390/ijerph121215038 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA DA1EL UT WOS:000367539000083 PM 26694440 ER PT J AU Rosenbaum, BL Bui, E Marin, MF Holt, DJ Lasko, NB Pitman, RK Orr, SP Milad, MR AF Rosenbaum, Blake L. Bui, Eric Marin, Marie-France Holt, Daphne J. Lasko, Natasha B. Pitman, Roger K. Orr, Scott P. Milad, Mohammed R. TI Reprint of: "Demographic factors predict magnitude of conditioned fear" SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Fear conditioning; Demographics; Classical conditioning; Education; Extinction; Skin conductance ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; PSYCHOPHYSIOLOGICAL ASSESSMENT; EXTINCTION RETENTION; SEX-DIFFERENCES; HUMANS; PTSD; NEUROSCIENCE; AWARENESS; RESPONSES AB There is substantial variability across individuals in the magnitudes of their skin conductance (SC) responses during the acquisition and extinction of conditioned fear. To manage this variability, subjects may be matched for demographic variables, such as age, gender and education. However, limited data exist addressing how much variability in conditioned SC responses is actually explained by these variables. The present study assessed the influence of age, gender and education on the SC responses of 222 subjects who underwent the same differential conditioning paradigm. The demographic variables were found to predict a small but significant amount of variability in conditioned responding during fear acquisition, but not fear extinction learning or extinction recall. A larger differential change in SC during acquisition was associated with more education. Older participants and women showed smaller differential SC during acquisition. Our findings support the need to consider age, gender and education when studying fear acquisition but not necessarily when examining fear extinction learning and recall. Variability in demographic factors across studies may partially explain the difficulty in reproducing some SC findings. (C) 2015 Published by Elsevier B.V. C1 [Rosenbaum, Blake L.; Bui, Eric; Marin, Marie-France; Holt, Daphne J.; Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Bui, Eric; Marin, Marie-France; Holt, Daphne J.; Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.; Milad, Mohammed R.] Harvard Univ, Sch Med, Boston, MA USA. [Holt, Daphne J.; Milad, Mohammed R.] HST MIT Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Milad, MR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,CNY 2614, Charlestown, MA 02129 USA. EM milad@nmr.mgh.harvard.edu FU National Institute of Mental Health [1R01MH097964]; Department of Psychiatry at MGH FX This work was supported by the National Institute of Mental Health grant 1R01MH097964 and institutional funds from the Department of Psychiatry at MGH to MRM. The authors would like to thank the Translation Neuroscience team for their help preparing this manuscript. NR 42 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 EI 1872-7697 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD DEC PY 2015 VL 98 IS 3 SI SI BP 606 EP 611 DI 10.1016/j.ijpsycho.2015.11.009 PN 2 PG 6 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA DA0NI UT WOS:000367493700014 PM 26608179 ER PT J AU Charidimou, A Yeon, S Song, M AF Charidimou, Andreas Yeon, Su Song, Min TI Exploring cerebral small vessel disease research using informetrics: a first glimpse into microbleeds SO INTERNATIONAL JOURNAL OF STROKE LA English DT Letter ID IMPACT C1 [Charidimou, Andreas] Harvard Univ, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol,Stroke Res Ctr,Med Sch, Boston, MA 02114 USA. [Charidimou, Andreas] UCL Inst Neurol, London, England. [Charidimou, Andreas] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Yeon, Su; Song, Min] Yonsei Univ, Dept Lib & Informat Sci, Seoul 120749, South Korea. RP Charidimou, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM andreas.charidimou.09@ucl.ac.uk NR 8 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD DEC PY 2015 VL 10 IS 8 BP E87 EP E88 DI 10.1111/ijs.12617 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DA3CO UT WOS:000367673700002 PM 26745706 ER PT J AU Thielke, S Slatore, CG Banks, WA AF Thielke, Stephen Slatore, Christopher G. Banks, William A. TI Association Between Alzheimer Dementia Mortality Rate and Altitude in California Counties SO JAMA PSYCHIATRY LA English DT Letter ID DISEASE C1 [Thielke, Stephen; Banks, William A.] Puget Sound VA Med Ctr, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR USA. RP Thielke, S (reprint author), Puget Sound VA Med Ctr, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way,GRECC S-182, Seattle, WA 98108 USA. EM sthielke@u.washington.edu OI Slatore, Christopher/0000-0003-0958-8122 NR 6 TC 1 Z9 1 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD DEC PY 2015 VL 72 IS 12 BP 1253 EP 1254 DI 10.1001/jamapsychiatry.2015.1852 PG 2 WC Psychiatry SC Psychiatry GA DA1UY UT WOS:000367582200018 PM 26502029 ER PT J AU Panaroni, C Fulzele, K Saini, V Chubb, R Pajevic, PD Wu, JY AF Panaroni, Cristina Fulzele, Keertik Saini, Vaibhav Chubb, Rhiannon Pajevic, Paola Divieti Wu, Joy Y. TI PTH Signaling in Osteoprogenitors Is Essential for B-Lymphocyte Differentiation and Mobilization SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BONE; OSTEOPROGENITORS; B CELLS; PTH RECEPTOR; VCAM1 ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW MICROENVIRONMENT; PARATHYROID-HORMONE; ADHESION MOLECULE-1; OSTEOBLAST LINEAGE; MESENCHYMAL PROGENITORS; GROWTH-PLATE; MICE; LYMPHOPOIESIS; RECEPTOR AB Cells of the osteoblast lineage provide critical support for B lymphopoiesis in the bone marrow (BM). Parathyroid hormone (PTH) signaling in osteoblastic cells through its receptor (PPR) is an important regulator of hematopoietic stem cells; however, its role in regulation of B lymphopoiesis is not clear. Here we demonstrate that deletion of PPR in osteoprogenitors results in a significant loss of trabecular and cortical bone. PPR signaling in osteoprogenitors, but not in mature osteoblasts or osteocytes, is critical for B-cell precursor differentiation via IL-7 production. Interestingly, despite a severe reduction in B-cell progenitors in BM, mature B-lymphocytes were increased 3.5-fold in the BM of mice lacking PPR in osteoprogenitors. This retention of mature IgD(+) B cells in the BM was associated with increased expression of vascular cell adhesion molecule 1 (VCAM1) by PPR-deficient osteoprogenitors, and treatment with VCAM1 neutralizing antibody increased mobilization of B lymphocytes from mutant BM. Our results demonstrate that PPR signaling in early osteoblasts is necessary for B-cell differentiation via IL-7 secretion and for B-lymphocyte mobilization via VCAM1. (C) 2015 American Society for Bone and Mineral Research. C1 [Panaroni, Cristina; Wu, Joy Y.] Stanford Univ, Sch Med, Div Endocrinol, Stanford, CA 94305 USA. [Fulzele, Keertik; Saini, Vaibhav; Chubb, Rhiannon; Pajevic, Paola Divieti] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. RP Wu, JY (reprint author), Stanford Univ, Sch Med, Div Endocrinol, 300 Pasteur Dr,S-025, Stanford, CA 94305 USA. EM jywu1@stanford.edu FU Harvard Stem Cell Institute; National Institutes of Health [OD008466, DK079161, AR060211] FX The authors thank Dr Andrew McMahon for providing Osx1:GFP-Cre mice; Dr Tatsuya Kobayashi for providing PPRfl/fl mice; the MGH Center for Comparative Medicine and Stanford University Veterinary Services Center staff for care of the animals; the Harvard Stem Cell Institute flow cytometry core and the Stanford Shared FACS Facility; and the Ragon Institute imaging core. This work was supported by the Harvard Stem Cell Institute (JYW) and National Institutes of Health grants OD008466 to JYW and DK079161 and AR060211 to PDP. NR 55 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2015 VL 30 IS 12 BP 2273 EP 2286 DI 10.1002/jbmr.2581 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DA3JD UT WOS:000367692100016 PM 26191777 ER PT J AU Mihos, CG Santana, O AF Mihos, Christos G. Santana, Orlando TI Annuloplasty Ring Selection in Ischemic Mitral Regurgitation for Valve Repair During Coronary Artery Bypass Grafting SO JOURNAL OF CARDIAC SURGERY LA English DT Letter C1 [Mihos, Christos G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02140 USA. [Santana, Orlando] Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Miami Beach, FL USA. RP Mihos, CG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02140 USA. EM cmihos@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0886-0440 EI 1540-8191 J9 J CARDIAC SURG JI J. Card. Surg. PD DEC PY 2015 VL 30 IS 12 BP 906 EP 906 DI 10.1111/jocs.12640 PG 1 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA DA5NL UT WOS:000367849700018 PM 26377498 ER PT J AU Carneiro, JS Bento, ASA Bacic, D Nearing, BD Rajamani, S Belardinelli, L Verrier, RL AF Carneiro, Juliana Saran Alves Bento, Afonso S. Bacic, Danilo Nearing, Bruce D. Rajamani, Sridharan Belardinelli, Luiz Verrier, Richard L. TI The Selective Cardiac Late Sodium Current Inhibitor GS-458967 Suppresses Autonomically Triggered Atrial Fibrillation in an Intact Porcine Model SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE acetylcholine; atrial fibrillation; cardiac late sodium current; catecholamines; epinephrine; QT interval; ranolazine ID HEART-RATE; RANOLAZINE; ARRHYTHMIAS; REPOLARIZATION; ALTERNANS; ISCHEMIA; POTENT; ROLES; TRIAL; ONSET AB GS-967 Suppresses AF IntroductionThe anti-atrial fibrillation (AF) effects of GS-458967 (GS-967), a selective, potent inhibitor of cardiac late Na+ current (I-Na), were evaluated in a novel model of AF induction that does not require electrical stimuli. Methods and ResultsIn 6 closed-chest anesthetized pigs, AF was induced by intrapericardial acetylcholine (1 mL of 100 mM solution) followed within 1 minute by epinephrine (20 g/kg, i.v., bolus over 1 min). Effects of GS-967 (0.4 mg/kg, i.v., infused over 30 min) on inducibility and duration of AF were analyzed. Administration of acetylcholine followed by epinephrine elicited spontaneous AF that persisted for 12.03 1.22 minutes (mean +/- SEM) in all 6 pigs. Following GS-967, AF did not occur in 5 of 6 pigs when plasma concentration was 383 +/- 150 nM. In the single animal in which AF could still be induced, the arrhythmia lasted 6.3 minutes. Partial return of AF inducibility occurred in 2 of 6 animals at 90 minutes, when plasma concentration of GS-967 was 228 +/- 35 nM. GS-967 reduced the QT interval (P = 0.004), consistent with cardiac late I-Na inhibition, but did not affect heart rate, mean arterial pressure, QRS duration, or PR interval. Epinephrine infusion alone, tested in a separate group (N = 6), did not provoke AF. ConclusionSelective cardiac late I-Na inhibition with GS-967 suppresses spontaneous induction of AF in a novel model that does not require provocative electrical stimuli. Because this mode of action has only a mild on effect on contractility, it offers an advantage over contemporary anti-AF agents, which can have negative inotropic actions. C1 [Carneiro, Juliana Saran; Alves Bento, Afonso S.; Bacic, Danilo; Nearing, Bruce D.; Verrier, Richard L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Carneiro, Juliana Saran; Alves Bento, Afonso S.; Bacic, Danilo] Univ Sao Paulo, Fac Med, Sao Paulo, Brazil. [Nearing, Bruce D.; Verrier, Richard L.] Harvard Univ, Sch Med, Boston, MA USA. [Rajamani, Sridharan; Belardinelli, Luiz] Gilead Sci Inc, Foster City, CA 94404 USA. RP Verrier, RL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Harvard Thorndike Electrophysiol Inst,Sch Med, 99 Brookline Ave,RN-301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu FU "Science without Borders" (CAPES of the Brazilian Federal Government); Banco Santander Brasil; Harvard University's David Rockefeller Center for Latin American Studies; Gilead Sciences, Inc. FX Messrs. Bento and Bacic and Ms. Carneiro received support from "Science without Borders" (CAPES of the Brazilian Federal Government), Banco Santander Brasil, Dr. Miguel Srougi, and Harvard University's David Rockefeller Center for Latin American Studies.; This study was funded by a grant from Gilead Sciences, Inc., to Beth Israel Deaconess Medical Center, Boston MA, RL Verrier, P.I. Drs. Belardinelli and Rajamani are employees of Gilead Sciences, Inc. Other authors: No disclosures. NR 30 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD DEC PY 2015 VL 26 IS 12 BP 1364 EP 1369 DI 10.1111/jce.12824 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA4TT UT WOS:000367794600013 PM 26331943 ER PT J AU Mananga, ES AF Mananga, Eugene Stephane TI Theoretical approaches to control spin dynamics in solid-state nuclear magnetic resonance SO JOURNAL OF CHEMICAL SCIENCES LA English DT Article DE Average Hamiltonian theory; Floquet theory; Fer expansion; Floquet-Magnus expansion; Chebyshev expansion; Cayley method ID FLOQUET-MAGNUS EXPANSION; RADIOFREQUENCY PULSE SEQUENCES; AVERAGE HAMILTONIAN THEORY; MULTIPLE-QUANTUM DYNAMICS; DEPENDENT SCHRODINGER-EQUATION; UNIFORMLY LABELED MOLECULE; ANISOTROPY CORRELATION NMR; MAGIC-ANGLE; ROTATING SOLIDS; FER EXPANSION AB This article reviews theoretical approaches for controlling spin dynamics in solid-state nuclear magnetic resonance. We present fundamental theories in the history of NMR, namely, the average Hamiltonian and Floquet theories. We also discuss emerging theories such as the Fer and Floquet-Magnus expansions. These theories allow one to solve the time-dependent Schrodinger equation, which is still the central problem in spin dynamics of solid-state NMR. Examples from the literature that highlight several applications of these theories are presented, and particular attention is paid to numerical integrators and propagator operators. The problem of time propagation calculated with Chebychev expansion and the future development of numerical directions with the Cayley transformation are considered. The bibliography includes 190 references. C1 [Mananga, Eugene Stephane] CUNY, Dept Phys & Technol, New York, NY 10453 USA. [Mananga, Eugene Stephane] NYU, Dept Appl Phys, Polytech Sch Engn, New York, NY 11201 USA. [Mananga, Eugene Stephane] Harvard Univ, Sch Med, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging Phys, Boston, MA 02114 USA. [Mananga, Eugene Stephane] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mananga, ES (reprint author), CUNY, Dept Phys & Technol, BCC 2155 Univ Ave, New York, NY 10453 USA. EM esm041@mail.harvard.edu FU National Institute of Health (NIH) [R01HL110241, T32 EB013180] FX The author was a Research Fellow at Harvard Medical School and Massachusetts General Hospital supported by the National Institute of Health (NIH) Grants R01HL110241 and T32 EB013180. The contents of this paper are solely the responsibility of the authors and do not represent the official views of NIH. NR 175 TC 0 Z9 0 U1 3 U2 3 PU INDIAN ACAD SCIENCES PI BANGALORE PA C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA SN 0974-3626 EI 0973-7103 J9 J CHEM SCI JI J. Chem. Sci. PD DEC PY 2015 VL 127 IS 12 BP 2081 EP 2109 DI 10.1007/s12039-015-0977-9 PG 29 WC Chemistry, Multidisciplinary SC Chemistry GA DA1EY UT WOS:000367540300001 ER PT J AU Baffy, G AF Baffy, Gyoergy TI MicroRNAs in Nonalcoholic Fatty Liver Disease SO JOURNAL OF CLINICAL MEDICINE LA English DT Review DE nonalcoholic fatty liver disease; steatohepatitis; hepatocellular carcinoma; miRNA; circulating miRNA; antagomir; differential expression; transcriptome; predicted target genes ID HEPATOCELLULAR-CARCINOMA; MISSING HERITABILITY; METABOLIC SYNDROME; HEPATIC MICRORNAS; NONCODING RNAS; COMPLEX TRAITS; RAT-LIVER; EXPRESSION; STEATOHEPATITIS; ACID AB Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder. Strongly linked to obesity and diabetes, NAFLD has the characteristics of complex diseases with substantial heterogeneity. Accordingly, our ability to predict the risk of advanced NAFLD and provide efficient treatment may improve by a better understanding of the relationship between genotype and phenotype. MicroRNAs (miRNAs) play a major role in the fine-tuning of gene expression and they have recently emerged as novel biomarkers and therapeutic tools in the management of NAFLD. These short non-coding RNA sequences act by partial repression or degradation of targeted mRNAs. Deregulation of miRNAs has been associated with different stages of NAFLD, while their biological role in the pathogenesis remains to be fully understood. Systems biology analyses based on predicted target genes have associated hepatic miRNAs with molecular pathways involved in NAFLD progression such as cholesterol and lipid metabolism, insulin signaling, oxidative stress, inflammation, and pathways of cell survival and proliferation. Moreover, circulating miRNAs have been identified as promising noninvasive biomarkers of NAFLD and linked to disease severity. This rapidly growing field is likely to result in major advances in the pathomechanism, prognostication, and treatment of NAFLD. C1 [Baffy, Gyoergy] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Med, Boston, MA 02130 USA. [Baffy, Gyoergy] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02130 USA. RP Baffy, G (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Med, 150 S Huntington Ave,Room 6A-46, Boston, MA 02130 USA. EM gbaffy@bwh.harvard.edu NR 77 TC 7 Z9 7 U1 1 U2 3 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2077-0383 J9 J CLIN MED JI J. Clin. Med. PD DEC PY 2015 VL 4 IS 12 BP 1977 EP 1988 DI 10.3390/jcm4121953 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA DA3TR UT WOS:000367722300002 PM 26690233 ER PT J AU Miloslavsky, EM Sargsyan, Z Heath, JK Kohn, R Alba, GA Gordon, JA Currier, PF AF Miloslavsky, Eli M. Sargsyan, Zaven Heath, Janae K. Kohn, Rachel Alba, George A. Gordon, James A. Currier, Paul F. TI A Simulation-Based Resident-as-Teacher Program: The Impact on Teachers and Learners SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID EMERGENCY-MEDICINE; CURRICULUM; EDUCATION; FEEDBACK; FACULTY AB BACKGROUND: Residency training is charged with improving resident teaching skills. Utilizing simulation in teacher training has unique advantages such as providing a controlled learning environment and opportunities for deliberate practice. OBJECTIVE: We assessed the impact of a simulation-based resident-as-teacher (RaT) program. DESIGN: A RaT program was embedded in an existing 8-case simulation curriculum for 52 internal medicine (IM) interns. Residents participated in a workshop, then served as facilitators in the curriculum and received feedback from faculty. METHODS: Residents' teaching and feed back skills were measured using a pre- and post-program self-assessment and post-session and post-curriculum evaluations by intern learners. SETTING/PARTICIPANTS: Forty-one second-and third-year residents participated in the study August 2013 to October 2013 at a single center. RESULTS: Pre- and post-program teaching skills were assessed for 34 of 41 resident facilitators (83%) participating in 3.9 sessions on average. Partaking in the program led to improvements in resident facilitators' self-reported teaching and feedback skills across all domains. The most significant improvement was in teaching in a simulated environment (2.81 to 4.16, P < 0.001). Interns rated the curriculum highly (81% "excellent," 19% "good") and reported that resident facilitators frequently utilized debriefing techniques covered in the RaT program. CONCLUSIONS: Our simulation-based RaT program offered a unique opportunity for deliberate practice of teaching skills in a controlled environment and led to improvements in resident facilitators' teaching and feed back skills. The simulation curriculum, facilitated by residents, was well received by the intern learners. Our program design may serve as a model for the development of simulation curricula and RaT programs within IM residencies. (C) 2015 Society of Hospital Medicine C1 [Miloslavsky, Eli M.; Heath, Janae K.; Alba, George A.; Currier, Paul F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sargsyan, Zaven] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kohn, Rachel] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Miloslavsky, EM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Suite 2C, Boston, MA 02114 USA. EM emiloslavsky@mgh.harvard.edu NR 20 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD DEC PY 2015 VL 10 IS 12 BP 767 EP 772 DI 10.1002/jhm.2423 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DA3VQ UT WOS:000367728200001 PM 26173641 ER PT J AU Soni, NJ Franco, R Velez, MI Schnobrich, D Dancel, R Restrepo, MI Mayo, PH AF Soni, Nilam J. Franco, Ricardo Velez, Maria I. Schnobrich, Daniel Dancel, Ria Restrepo, Marcos I. Mayo, Paul H. TI Ultrasound in the Diagnosis and Management of Pleural Effusions SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID PARAPNEUMONIC EFFUSIONS; CHEST RADIOGRAPHY; MEDICAL ICU; THORACIC ULTRASOUND; LUNG ULTRASOUND; ACCURACY; SONOGRAPHY; ULTRASONOGRAPHY; FLUID; PNEUMOTHORAX AB We review the literature on the use of point-of-care ultrasound to evaluate and manage pleural effusions. Point-of-care ultrasound is more sensitive than physical exam and chest radiography to detect pleural effusions, and avoids many negative aspects of computerized tomography. Additionally, point-of-care ultrasound can assess pleural fluid volume and character, revealing possible underlying pathologies and guiding management. Thoracentesis performed with ultrasound guidance has lower risk of pneumothorax and bleeding complications. Future research should focus on the clinical effectiveness of point-of-care ultrasound in the routine management of pleural effusions and how new technologies may expand its clinical utility. (C) 2015 Society of Hospital Medicine C1 [Soni, Nilam J.] South Texas Vet Hlth Care Syst, Sect Hosp Med, San Antonio, TX USA. [Soni, Nilam J.; Velez, Maria I.; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Soni, Nilam J.; Velez, Maria I.; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Pulm & Crit Care Med Sect, San Antonio, TX USA. [Franco, Ricardo] Med Coll Wisconsin, Div Gen Internal Med, Milwaukee, WI 53226 USA. [Schnobrich, Daniel] Univ Minnesota, Div Gen Internal Med, Minneapolis, MN USA. [Dancel, Ria] Univ N Carolina, Div Gen Med & Epidemiol, Chapel Hill, NC USA. [Mayo, Paul H.] North Shore LIJ Med Ctr, Div Pulm Crit Care & Sleep Med, New Hyde Pk, NY USA. RP Soni, NJ (reprint author), 7703 Floyd Curl Dr,MC 7982, San Antonio, TX 78229 USA. EM sonin@uthscsa.edu FU National Heart, Lung, and Blood Institute [K23HL096054] FX Dr. Restrepo is partially supported by award number K23HL096054 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. The authors report no conflicts of interest. NR 50 TC 5 Z9 5 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD DEC PY 2015 VL 10 IS 12 BP 811 EP 816 DI 10.1002/jhm.2434 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DA3VQ UT WOS:000367728200009 PM 26218493 ER PT J AU Finn, KM Greenwald, JL AF Finn, Kathleen M. Greenwald, Jeffrey L. TI Update in Hospital Medicine: Evidence You Should Know SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID MOLECULAR-WEIGHT HEPARIN; VENOUS THROMBOEMBOLISM; CLINICAL-TRIAL; CIRRHOSIS; ENCEPHALOPATHY; THERAPY; WINDOW AB BACKGROUND: The practice of hospital medicine is complex, and the number of clinical publications each year continues to grow. To maintain best practice it is necessary for hospitalists to stay abreast of the literature, but difficult to accomplish due to time. The annual Society of Hospital Medicine meeting offers a plenary session on Updates in Hospital Medicine. This article is a summary of those papers presented at the meeting. METHODS: We reviewed articles published between January 2014 and January 2015 in the leading medical journals, searching for papers with good methodological quality, the potential to change practice, and papers that are thought provoking. The authors collectively agreed on 14 articles. The findings, cautions, and implications are discussed for each paper. RESULTS: Key findings include: a novel neprilysin inhibitor and angiotensin receptor blocker combination drug reduces mortality in patients with heart failure; the concern for acute kidney injury after venous contrast may be overstated; the Confusion Assessment Method Severity score is an important tool for prognostication in delirious patients; ramelteon shows promise for lowering incident delirium among elderly medical patients; polyethylene glycol appears effective in rapidly resolving hepatic encephalopathy; cirrhotic patients on a nonselective beta-blocker have increased mortality after they develop spontaneous bacterial peritonitis; current guidelines regarding prophylaxis against venous thromboembolism (VTE) in medical inpatients likely result in nonbeneficial use of medications; from a safety and efficacy perspective, direct oral anticoagulants perform quite well against conventional therapies in patients with VTE and atrial fibrillation, including in elderly populations; 2 new once-weekly antibiotics, dalbavancin and oritivancin, approved for skin and soft tissue infections, appear noninferior to vancomycin; offering family members of a patient undergoing cardiopulmonary resuscitation the opportunity to observe has durable impact on long-term psychological outcomes. CONCLUSIONS: This update reviews key clinical articles published in 2014, selected by the authors for their methodological quality and potential for changing the practice of inpatient physicians. All of these articles add to the body of inpatient medical knowledge and contribute to the debate on best practices. (C) 2015 Society of Hospital Medicine C1 [Finn, Kathleen M.; Greenwald, Jeffrey L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clinician Educ Serv,Dept Med, Boston, MA USA. RP Finn, KM (reprint author), Clinician Educ Serv, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM kfinn@partners.org NR 19 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD DEC PY 2015 VL 10 IS 12 BP 817 EP 826 DI 10.1002/jhm.2476 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DA3VQ UT WOS:000367728200010 PM 26352909 ER PT J AU Abdala, C Luo, P Shera, CA AF Abdala, Carolina Luo, Ping Shera, Christopher A. TI Optimizing swept-tone protocols for recording distortion-product otoacoustic emissions in adults and newborns SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID NORMAL-HEARING; FINE-STRUCTURE; SWEEPING PRIMARIES; DPOAE; PHASE; MODEL; MECHANISMS; AMPLITUDE; HUMANS; LEVEL AB Distortion-product otoacoustic emissions (DPOAEs), which are routinely used in the audiology clinic and research laboratory, are conventionally recorded with discrete tones presented sequentially across frequency. However, a more efficient technique sweeps tones smoothly across frequency and applies a least-squares-fitting (LSF) procedure to compute estimates of otoacoustic emission phase and amplitude. In this study, the optimal parameters (i.e., sweep rate and duration of the LSF analysis window) required to record and analyze swept-tone DPOAEs were tested and defined in 15 adults and 10 newborns. Results indicate that optimal recording of swept-tone DPOAEs requires use of an appropriate analysis bandwidth, defined as the range of frequencies included in each least squares fit model. To achieve this, the rate at which the tones are swept and the length of the LSF analysis window must be carefully considered and changed in concert. Additionally, the optimal analysis bandwidth must be adjusted to accommodate frequency-dependent latency shifts in the reflection-component of the DPOAE. Parametric guidelines established here are equally applicable to adults and newborns. However, elevated noise during newborn swept-tone DPOAE recordings warrants protocol adaptations to improve signal-to-noise ratio and response quality. C1 [Abdala, Carolina; Luo, Ping] Univ So Calif, Keck Sch Med, Caruso Dept Otolaryngol, Los Angeles, CA 90033 USA. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Abdala, C (reprint author), Univ So Calif, Keck Sch Med, Caruso Dept Otolaryngol, 1540 Alcazar St, Los Angeles, CA 90033 USA. EM carolina.abdala@usc.edu FU NIH NIDCD [DC 003552, DC 003687] FX This work was supported by NIH NIDCD Grant Nos. DC 003552 (C.A.) and DC 003687 (C.A.S.). The authors thank Mahnaz Ahmadi and Amanda Ortmann for their contributions to data collection. NR 29 TC 3 Z9 3 U1 1 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2015 VL 138 IS 6 BP 3785 EP 3799 DI 10.1121/1.4937611 PG 15 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA DA1DE UT WOS:000367535700045 PM 26723333 ER PT J AU Wasfy, MM Weiner, RB Wang, F Berkstresser, B Lewis, GD DeLuca, JR Hutter, AM Picard, MH Baggish, AL AF Wasfy, Meagan M. Weiner, Rory B. Wang, Francis Berkstresser, Brant Lewis, Gregory D. DeLuca, James R. Hutter, Adolph M. Picard, Michael H. Baggish, Aaron L. TI Endurance Exercise-Induced Cardiac Remodeling: Not All Sports Are Created Equal SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Endurance exercise; Cardiac remodeling; Left ventricular hypertrophy; Diastolic function ID EJECTION FRACTION; TISSUE-DOPPLER; ATHLETES HEART; UPPER LIMIT; HYPERTROPHY; DYSFUNCTION; PATTERNS; HUMANS; IMPACT AB Background: The term endurance sport (ES) is broadly used to characterize any exercise that requires maintenance of high cardiac output over extended time. However, the relative amount of isotonic (volume) versus isometric (pressure) cardiac stress varies across ES disciplines. To what degree ES-mediated cardiac remodeling varies, as a function of superimposed isometric stress, is uncertain. The aim of this study was to compare the cardiac remodeling characteristics associated with two common yet physiologically distinct forms of ES. Methods: Healthy competitive male long-distance runners (high isotonic, low isometric stress; n = 40) and rowers (high isotonic, high isometric stress; n = 40) were comparatively studied after 3 months of sport-specific exercise training with conventional and speckle-tracking two-dimensional echocardiography. Results: Rowers demonstrated dilated left ventricular (LV) volumes and elevated LV mass (i.e., eccentric LV hypertrophy), whereas runners demonstrated normal LV mass (runners, 88 +/- 11 g/m(2); rowers, 108 +/- 13 g/ m(2); P <.001) despite comparatively larger LV volumes (runners, 101 +/- 10 mL/m(2); rowers, 89 +/- 13 mL/m(2); P <.001) consistent with eccentric LV remodeling. Increasing LV mass was associated with increased reliance on early diastolic filling (LV mass vs E'/A' ratio, R = 0.47, P <.001) indicating "mass-dependent'' diastolic function. Right ventricular dilation of similar magnitude and LV systolic function, as assessed by numerous complementary indices, were similar in both groups. Conclusions: Cardiac adaptations differ significantly as a function of ES discipline. Further work is required to determine the mechanisms for this differential adaptation, to develop definitive ES discipline-specific normative values, and to evaluate the optimal therapeutic use of specific ES disciplines among patients with common cardiovascular diseases. (J Am Soc Echocardiogr 2015; 28: 1434-40.) C1 [Wasfy, Meagan M.; Weiner, Rory B.; Lewis, Gregory D.; DeLuca, James R.; Hutter, Adolph M.; Picard, Michael H.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. [Wang, Francis; Berkstresser, Brant; Baggish, Aaron L.] Harvard Univ Hlth Serv, Cambridge, MA USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, 55 Fruit St,Yawkey 5B, Boston, MA 02114 USA. EM abaggish@partners.org OI Picard, Michael/0000-0002-9264-3243 FU American Heart Association [FTF2220328] FX This study was funded in part by a research grant from the American Heart Association (FTF2220328) to Dr Baggish. NR 22 TC 3 Z9 3 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2015 VL 28 IS 12 BP 1434 EP 1440 DI 10.1016/j.echo.2015.08.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA3DV UT WOS:000367677700010 PM 26361851 ER PT J AU Bunch, H Lawney, BP Lin, YF Asaithamby, A Murshid, A Wang, YYE Chen, BPC Calderwood, SK AF Bunch, Heeyoun Lawney, Brian P. Lin, Yu-Fen Asaithamby, Aroumougame Murshid, Ayesha Wang, Yaoyu E. Chen, Benjamin P. C. Calderwood, Stuart K. TI Transcriptional elongation requires DNA break-induced signalling SO NATURE COMMUNICATIONS LA English DT Article ID DOUBLE-STRAND BREAKS; DEPENDENT PROTEIN-KINASE; RNA-POLYMERASE; TOPOISOMERASE-II; POL II; H2AX PHOSPHORYLATION; GENOME INSTABILITY; GENE-EXPRESSION; PAUSE RELEASE; DROSOPHILA AB We have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcriptional elongation in stimulus-inducible genes in humans. Our data show the enrichment of TRIM28 and gamma H2AX on serum-induced genes and the important function of DNA-PK for Pol II pause release and transcriptional activation-coupled DDR signalling on these genes. gamma H2AX accumulation decreases when P-TEFb is inhibited, confirming that DDR signalling results from transcriptional elongation. In addition, transcriptional elongation-coupled DDR signalling involves topoisomerase II because inhibiting this enzyme interferes with Pol II pause release and gamma H2AX accumulation. Our findings propose that DDR signalling is required for effective Pol II pause release and transcriptional elongation through a novel mechanism involving TRIM28, DNA-PK and topoisomerase II. C1 [Bunch, Heeyoun; Murshid, Ayesha; Calderwood, Stuart K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Lawney, Brian P.; Wang, Yaoyu E.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02130 USA. [Lin, Yu-Fen; Asaithamby, Aroumougame; Chen, Benjamin P. C.] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA. RP Bunch, H (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. EM heeyounbunch@gmail.com; scalderw@bidmc.harvard.edu OI Bunch, Heeyoun/0000-0003-0038-1985 FU US National Institute of Health (NIH) [RO1CA166677]; NIH [2RO1CA047407-21, 1RO1CA176326]; Harvard Joint Center for Radiation Therapy FX We appreciate D. J. Taatjes at the University of Colorado, Boulder for critical reading and helpful comments for the manuscript and S. Buratowski at Harvard Medical School for interest in our research and reading the manuscript. We thank M. A. Stevenson at Beth Israel Deaconess Medical Center (BIDMC) and B. D. Price at Dana Farber Cancer Institute for discussions and W. Wei laboratory in BIDMC for sharing equipment. We are grateful to T. Westerling and M. Brown for providing with ChIP-seq library construction. We thank S. Gupta and T. Volkert in the Whitehead Institute Genomic Technology Core and S. Motola and S. Levine in the MIT Biomicro Center for the generation and sequencing of the ChIP libraries. H.B. thanks M. Cross at BIDMC for administrative support and D. Bunch, D. Verrengia, K. Perkins, R. S. Baker and Brookline small group members, and P.S.C. for loving encouragement throughout the work. This study was supported by grants from the US National Institute of Health (NIH) RO1CA166677 to B.P.C.C and NIH 2RO1CA047407-21 and 1RO1CA176326 and the Harvard Joint Center for Radiation Therapy to S.K.C. and H.B. NR 59 TC 13 Z9 13 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2015 VL 6 AR 10191 DI 10.1038/ncomms10191 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA1SF UT WOS:000367575100001 PM 26671524 ER PT J AU Kim, J Singh, AK Takata, Y Lin, K Shen, JJ Lu, Y Kerenyi, MA Orkin, SH Chen, TP AF Kim, Jeesun Singh, Anup Kumar Takata, Yoko Lin, Kevin Shen, Jianjun Lu, Yue Kerenyi, Marc A. Orkin, Stuart H. Chen, Taiping TI LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice SO NATURE COMMUNICATIONS LA English DT Article ID PROPHASE I ARREST; MOUSE OOCYTES; MAMMALIAN OOCYTES; DEMETHYLASE LSD1; MEIOSIS-I; METHYLATION; GENE; RESUMPTION; MATURATION; ACTIVATION AB Mammalian oocytes are arrested at prophase I until puberty when hormonal signals induce the resumption of meiosis I and progression to meiosis II. Meiotic progression is controlled by CDK1 activity and is accompanied by dynamic epigenetic changes. Although the signalling pathways regulating CDK1 activity are well defined, the functional significance of epigenetic changes remains largely unknown. Here we show that LSD1, a lysine demethylase, regulates histone H3 lysine 4 di-methylation (H3K4me2) in mouse oocytes and is essential for meiotic progression. Conditional deletion of Lsd1 in growing oocytes results in precocious resumption of meiosis and spindle and chromosomal abnormalities. Consequently, most Lsd1-null oocytes fail to complete meiosis I and undergo apoptosis. Mechanistically, upregulation of CDC25B, a phosphatase that activates CDK1, is responsible for precocious meiotic resumption and also contributes to subsequent spindle and chromosomal defects. Our findings uncover a functional link between LSD1 and the major signalling pathway governing meiotic progression. C1 [Kim, Jeesun; Singh, Anup Kumar; Takata, Yoko; Lin, Kevin; Shen, Jianjun; Lu, Yue; Chen, Taiping] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Smithville, TX 78957 USA. [Kim, Jeesun; Singh, Anup Kumar; Lu, Yue; Chen, Taiping] Univ Texas MD Anderson Canc Ctr, Ctr Canc Epigenet, Smithville, TX 78957 USA. [Kerenyi, Marc A.; Orkin, Stuart H.] Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA 02115 USA. [Kerenyi, Marc A.; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Chen, TP (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Sci Pk,1808 Pk Rd 1C, Smithville, TX 78957 USA. EM tchen2@mdanderson.org FU Cancer Prevention and Research Institute of Texas (CPRIT) [R1108]; CPRIT Core Facility Support Award [RP120348]; Center for Cancer Epigenetics at MDACC FX We thank colleagues in the Chen laboratory at The University of Texas MD Anderson Cancer Center (MDACC) for discussions. This work is supported by a Rising Star Award (R1108 to T.C.) from the Cancer Prevention and Research Institute of Texas (CPRIT). RNA-seq experiments were supported by a CPRIT Core Facility Support Award (RP120348) and funding from the Center for Cancer Epigenetics at MDACC. NR 49 TC 5 Z9 5 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2015 VL 6 AR 10116 DI 10.1038/ncomms10116 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA1QH UT WOS:000367569900007 PM 26626423 ER PT J AU Caster, DJ Korte, EA Merchant, ML Klein, JB Wilkey, DW Rovin, BH Birmingham, DJ Harley, JB Cobb, BL Namjou, B McLeish, KR Powell, DW AF Caster, Dawn J. Korte, Erik A. Merchant, Michael L. Klein, Jon B. Wilkey, Daniel W. Rovin, Brad H. Birmingham, Dan J. Harley, John B. Cobb, Beth L. Namjou, Bahram McLeish, Kenneth R. Powell, David W. TI Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE Autoantibodies; Glomerulonephritis; Lupus nephritis; Systemic lupus erythematosus; Target antigens ID SLIT DIAPHRAGM; ACTIN REORGANIZATION; NEPHROTIC SYNDROME; STATISTICAL-MODEL; ERYTHEMATOSUS; CELLS; CYTOSKELETON; DISEASE; COMPLEX; GLOMERULONEPHRITIS AB Purpose: Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. Experimental design: Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS. Results: LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36 and 50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. Conclusion and clinical relevance: Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers. C1 [Caster, Dawn J.; Merchant, Michael L.; Klein, Jon B.; Wilkey, Daniel W.; McLeish, Kenneth R.; Powell, David W.] Univ Louisville, Dept Med, Sch Med, Louisville, KY 40202 USA. [Korte, Erik A.; Powell, David W.] Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40202 USA. [Caster, Dawn J.; Klein, Jon B.; McLeish, Kenneth R.] Robley Rex Vet Affairs Med Ctr, Louisville, KY USA. [Rovin, Brad H.; Birmingham, Dan J.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA. [Harley, John B.; Cobb, Beth L.; Namjou, Bahram] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA. [Harley, John B.; Cobb, Beth L.; Namjou, Bahram] Univ Cincinnati, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Caster, DJ (reprint author), Univ Louisville, Dept Med, Sch Med, 570 South Preston St,Baxter Res Bldg 1,102D, Louisville, KY 40202 USA. EM dawn.caster@louisville.edu RI Merchant, Michael/F-7109-2013; McLeish, Kenneth/B-9819-2013 OI McLeish, Kenneth/0000-0002-7816-3286 FU National Institutes of Health [AR063124, AI103980, AI24717, TR000077, HG006828]; Juvenile Diabetes Research Foundation [1-2011-588]; US Department of Veterans Affairs FX The authors were supported by grants from the National Institutes of Health AR063124 (to D.W.P.), AI103980 (to D.W.P. and K.R.M.), AI24717, TR000077, HG006828 (to J.B.H), and the Juvenile Diabetes Research Foundation international grant 1-2011-588 (to D.W.P.). J.B.H. and K.R.M were supported by the US Department of Veterans Affairs. The authors wish to thank Vilius Stribinskis, Ph.D., for the production of recombinant annexin A2. NR 63 TC 4 Z9 4 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1862-8346 EI 1862-8354 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD DEC PY 2015 VL 9 IS 11-12 SI SI BP 1012 EP 1020 DI 10.1002/prca.201400175 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA3UD UT WOS:000367723600006 PM 25824007 ER PT J AU Dodge, LE Williams, PL Williams, MA Missmer, SA Souter, I Calafat, AM Hauser, R AF Dodge, L. E. Williams, P. L. Williams, M. A. Missmer, S. A. Souter, I. Calafat, A. M. Hauser, R. CA EARTH Study Team TI Associations between paternal urinary phthalate metabolite concentrations and reproductive outcomes among couples seeking fertility treatment SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Phthalates; Fertility; Male reproduction; Assisted reproduction ID HUMAN SPERMATOZOAL RNAS; IN-UTERO EXPOSURE; TESTOSTERONE PRODUCTION; IDENTIFICATION; DISRUPTION; PREGNANCY; TESTIS; DI(2-ETHYLHEXYL)PHTHALATE; FAILURE; WEIGHT AB Introduction: Limited evidence suggests that male exposure to ubiquitous environmental phthalates may result in poor reproductive outcomes among female partners. Methods: This analysis included male female couples undergoing in vitro fertilization (IVF) and/or intrauterine insemination (IUI). We evaluated associations between the geometric mean of paternal specific gravity-adjusted urinary phthalate concentrations prior to the female partners' cycle and fertilization, embryo quality, implantation, and live birth using generalized linear mixed models. Results: Two-hundred eighteen couples underwent 211 IVF and 195 lUI cycles. Trends were observed between paternal urinary mono-3-carboxypropyl phthalate (MCPP; P=0.01) and mono(carboxyoctyl) phthalate (MCOP; P = 0.01) and decreased odds of implantation. MCPP and MCOP were also associated with decreased odds of live birth following IVF (P = 0.01 and P = 0.04, respectively), and monobutyl phthalate above the first quartile was significantly associated with decreased odds of live birth following IUI (P= 0.04). However, most urinary phthalate metabolites were not associated with these reproductive outcomes. Conclusion: Selected phthalates were associated with decreased odds of implantation and live birth. (C) 2015 Elsevier Inc. All rights reserved. C1 [Dodge, L. E.; Williams, P. L.; Williams, M. A.; Missmer, S. A.; Hauser, R.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Dodge, L. E.; Missmer, S. A.; Hauser, R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Williams, P. L.; Souter, I.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Missmer, S. A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Missmer, S. A.] Harvard Univ, Sch Med, Boston, MA USA. [Souter, I.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Boston, MA 02114 USA. [Calafat, A. M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Hauser, R.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Hauser, R (reprint author), 665 Huntington Ave,Bldg 1,14th Floor, Boston, MA 02115 USA. EM rhauser@hsph.harvard.edu FU National Institute of Environmental Health Sciences (NIEHS) [ES009718, ES022955, ES000002, T32ES007069] FX This work was supported by grants ES009718, ES022955, ES000002, and T32ES007069 (supported LED) from the National Institute of Environmental Health Sciences (NIEHS). The authors gratefully acknowledge Manori Silva, Ella Samandar, Jim Preau, and Tao Jia (CDC, Atlanta, GA) for measuring the urinary concentrations of the phthalate metabolites. We also acknowledge all members of the EARTH study team, specifically the Harvard T.H. Chan School of Public Health research nurses Jennifer B. Ford and Myra G. Keller, research staff Ramace Dadd and Patricia Morey, physicians and staff at Massachusetts General Hospital fertility center and a special thanks to all the study participants. NR 48 TC 3 Z9 4 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD DEC PY 2015 VL 58 BP 184 EP 193 DI 10.1016/j.reprotox.2015.09.007 PG 10 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA DA1MJ UT WOS:000367559600022 PM 26456810 ER PT J AU Kaiser, BN Haroz, EE Kohrt, BA Bolton, PA Bass, JK Hinton, DE AF Kaiser, Bonnie N. Haroz, Emily E. Kohrt, Brandon A. Bolton, Paul A. Bass, Judith K. Hinton, Devon E. TI "Thinking too much": A systematic review of a common idiom of distress SO SOCIAL SCIENCE & MEDICINE LA English DT Review DE Cultural concept of distress; Idiom of distress; Depression; Anxiety; PTSD; Ethnopsychology; Global mental health; Transcultural psychiatry ID TRAUMATIZED CAMBODIAN REFUGEES; AFGHAN SYMPTOM CHECKLIST; KEY SOMATIC COMPLAINTS; HAITI CENTRAL PLATEAU; MENTAL-HEALTH-CARE; EXPLANATORY MODELS; QUALITATIVE RESEARCH; CULTURAL SYNDROMES; NORTHERN UGANDA; DEPRESSION AB Idioms of distress communicate suffering via reference to shared ethnopsychologies, and better understanding of idioms of distress can contribute to effective clinical and public health communication. This systematic review is a qualitative synthesis of "thinking too much" idioms globally, to determine their applicability and variability across cultures. We searched eight databases and retained publications if they included empirical quantitative, qualitative, or mixed-methods research regarding a "thinking too much" idiom and were in English. In total, 138 publications from 1979 to 2014 met inclusion criteria. We examined the descriptive epidemiology, phenomenology, etiology, and course of "thinking too much" idioms and compared them to psychiatric constructs. "Thinking too much" idioms typically reference ruminative, intrusive, and anxious thoughts and result in a range of perceived complications, physical and mental illnesses, or even death. These idioms appear to have variable overlap with common psychiatric constructs, including depression, anxiety, and PTSD. However, "thinking too much" idiom's reflect aspects of experience, distress, and social positioning not captured by psychiatric diagnoses and often show wide within-cultural variation, in addition to between-cultural differences. Taken together, these findings suggest that "thinking too much" should not be interpreted as a gloss for psychiatric disorder nor assumed to be a unitary symptom or syndrome within a culture. We suggest five key ways in which engagement with "thinking too much" idioms can improve global mental health research and interventions: it (1) incorporates a key idiom of distress into measurement and screening to improve validity of efforts at identifying those in need of services and tracking treatment outcomes; (2) facilitates exploration of ethnopsychology in order to bolster cultural appropriateness of interventions; (3) strengthens public health communication to encourage engagement in treatment; (4) reduces stigma by enhancing understanding, promoting treatment-seeking, and avoiding unintentionally contributing to stigmatization; and (5) identifies a key locally salient treatment target. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Kaiser, Bonnie N.] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. [Kaiser, Bonnie N.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Kaiser, Bonnie N.] Duke Univ, Duke Global Hlth Inst, Durham, NC 27701 USA. [Haroz, Emily E.; Bass, Judith K.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. [Kohrt, Brandon A.] Duke Univ, Duke Global Hlth Inst, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Kohrt, Brandon A.] Duke Univ, Dept Cultural Anthropol, Durham, NC 27710 USA. [Bolton, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. [Hinton, Devon E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kaiser, BN (reprint author), Emory Univ, Dept Anthropol, 1557 Dickey Dr, Atlanta, GA 30322 USA. EM bfullard@gmail.com OI Kaiser, Bonnie/0000-0003-0742-1302; Bass, Judith/0000-0002-5192-628X FU National Science Foundation [0234618]; "Reducing Barriers to Mental Health Task Sharing" - NIMH [K01MH104310-01] FX The authors are grateful to Craig Hadley for his helpful feedback on an earlier draft. BNK was supported by a National Science Foundation Graduate Research Fellowship (#0234618). BAK was supported by "Reducing Barriers to Mental Health Task Sharing" funded by NIMH (K01MH104310-01). NR 135 TC 4 Z9 4 U1 5 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2015 VL 147 BP 170 EP 183 DI 10.1016/j.socscimed.2015.10.044 PG 14 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DA2PA UT WOS:000367637100022 PM 26584235 ER PT J AU Symeonides, M Murooka, TT Bellfy, LN Roy, NH Mempel, TR Thali, M AF Symeonides, Menelaos Murooka, Thomas T. Bellfy, Lauren N. Roy, Nathan H. Mempel, Thorsten R. Thali, Markus TI HIV-1-Induced Small T Cell Syncytia Can Transfer Virus Particles to Target Cells through Transient Contacts SO VIRUSES-BASEL LA English DT Article DE HIV; cell-cell fusion; syncytia; humanized mouse; 3D culture; live cell imaging ID GP41 CYTOPLASMIC TAIL; HIV-INDUCED SYNCYTIA; LYMPH-NODES; LEUKOCYTE MIGRATION; PERIPHERAL-BLOOD; ENVELOPE PROTEIN; GIANT PSEUDOPODS; DENDRITIC CELLS; IN-VIVO; FUSION AB HIV-1 Env mediates fusion of viral and target cell membranes, but it can also mediate fusion of infected (producer) and target cells, thus triggering the formation of multinucleated cells, so-called syncytia. Large, round, immobile syncytia are readily observable in cultures of HIV-1-infected T cells, but these fast growing fusion sinks are largely regarded as cell culture artifacts. In contrast, small HIV-1-induced syncytia were seen in the paracortex of peripheral lymph nodes and other secondary lymphoid tissue of HIV-1-positive individuals. Further, recent intravital imaging of lymph nodes in humanized mice early after their infection with HIV-1 demonstrated that a significant fraction of infected cells were highly mobile, small syncytia, suggesting that these entities contribute to virus dissemination. Here, we report that the formation of small, migratory syncytia, for which we provide further quantification in humanized mice, can be recapitulated in vitro if HIV-1-infected T cells are placed into 3D extracellular matrix (ECM) hydrogels rather than being kept in traditional suspension culture systems. Intriguingly, live-cell imaging in hydrogels revealed that these syncytia, similar to individual infected cells, can transiently interact with uninfected cells, leading to rapid virus transfer without cell-cell fusion. Infected cells were also observed to deposit large amounts of viral particles into the extracellular space. Altogether, these observations suggest the need to further evaluate the biological significance of small, T cell-based syncytia and to consider the possibility that these entities do indeed contribute to virus spread and pathogenesis. C1 [Symeonides, Menelaos; Roy, Nathan H.; Thali, Markus] Univ Vermont, Grad Program Cell & Mol Biol, Burlington, VT 05405 USA. [Symeonides, Menelaos; Bellfy, Lauren N.; Roy, Nathan H.; Thali, Markus] Univ Vermont, Dept Microbiol & Mol Genet, Burlington, VT 05405 USA. [Murooka, Thomas T.] Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0T5, Canada. [Murooka, Thomas T.] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0T5, Canada. [Mempel, Thorsten R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. RP Thali, M (reprint author), Univ Vermont, Grad Program Cell & Mol Biol, Burlington, VT 05405 USA. EM msymeoni@uvm.edu; thomas.murooka@umanitoba.ca; lbellfy@uvm.edu; royn@email.chop.edu; tmempel@mgh.harvard.edu; markus.thali@uvm.edu OI Symeonides, Menelaos/0000-0003-3476-9881; Thali, Markus/0000-0001-8621-2095 FU National Institutes of Allergy and Infectious Diseases and of Drug Abuse of the National Institutes of Health [5R01AI080302, R01AI097052, R01DA036298] FX We thank Jan Orenstein for comments on our observations, and Christopher Huston, Alan K. Howe, and Anna P. McLean for valuable discussions during preparation of this manuscript. We also appreciate input from numerous colleagues who provided feedback after we first presented the data at the 2014 Cold Spring Harbor Retroviruses meeting. This publication was made possible by grants 5R01AI080302 (to Markus Thali) and R01AI097052 and R01DA036298 (to Thorsten R. Mempel) from the National Institutes of Allergy and Infectious Diseases and of Drug Abuse of the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 52 TC 4 Z9 4 U1 0 U2 3 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD DEC PY 2015 VL 7 IS 12 BP 6590 EP 6603 DI 10.3390/v7122959 PG 14 WC Virology SC Virology GA DA1DO UT WOS:000367536700033 PM 26703714 ER PT J AU Elias, KM Kang, S Liu, XX Horowitz, NS Berkowitz, RS Frendl, G AF Elias, Kevin M. Kang, Stephanie Liu, Xiaoxia Horowitz, Neil S. Berkowitz, Ross S. Frendl, Gyorgy TI Anesthetic Selection and Disease-Free Survival Following Optimal Primary Cytoreductive Surgery for Stage III Epithelial Ovarian Cancer (vol 22, pg 1341, 2015) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Correction C1 [Elias, Kevin M.; Horowitz, Neil S.; Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. [Elias, Kevin M.; Kang, Stephanie; Liu, Xiaoxia; Frendl, Gyorgy] Brigham & Womens Hosp, Surg ICU Translat Res Ctr, Boston, MA 02115 USA. [Elias, Kevin M.; Frendl, Gyorgy] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Elias, Kevin M.; Horowitz, Neil S.; Berkowitz, Ross S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Elias, Kevin M.; Horowitz, Neil S.; Berkowitz, Ross S.; Frendl, Gyorgy] Harvard Univ, Sch Med, Boston, MA USA. RP Elias, KM (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol & Reprod Biol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM kelias1@partners.org OI Elias, Kevin/0000-0003-1502-5553 NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2015 VL 22 SU 3 BP S1611 EP S1611 DI 10.1245/s10434-015-4542-z PG 1 WC Oncology; Surgery SC Oncology; Surgery GA CZ7OG UT WOS:000367288100166 PM 25821001 ER PT J AU Ferrone, CR Ting, DT Shahid, M Konstantinidis, IT Sabbatino, F Goyal, L Rice-Stitt, T Mubeen, A Arora, K Bardeesy, N Miura, J Gamblin, TC Zhu, AX Borger, D Lillemoe, KD Rivera, MN Deshpande, V AF Ferrone, Cristina R. Ting, David T. Shahid, Mohammad Konstantinidis, Ioannis T. Sabbatino, Francesco Goyal, Lipika Rice-Stitt, Travis Mubeen, Aysha Arora, Kshitij Bardeesy, Nabeel Miura, John Gamblin, T. Clark Zhu, Andrew X. Borger, Darrell Lillemoe, Keith D. Rivera, Miguel N. Deshpande, Vikram TI The Ability to Diagnose Intrahepatic Cholangiocarcinoma Definitively Using Novel Branched DNA-Enhanced Albumin RNA In Situ Hybridization Technology (vol 23, pg 290, 2016) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Correction C1 [Ferrone, Cristina R.; Shahid, Mohammad; Konstantinidis, Ioannis T.; Sabbatino, Francesco; Mubeen, Aysha; Arora, Kshitij; Borger, Darrell; Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ting, David T.; Goyal, Lipika; Bardeesy, Nabeel; Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Shahid, Mohammad; Rice-Stitt, Travis; Arora, Kshitij; Rivera, Miguel N.; Deshpande, Vikram] Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. [Miura, John; Gamblin, T. Clark] Med Coll Wisconsin, Div Surg Oncol, Milwaukee, WI 53226 USA. RP Ferrone, CR (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM CFERRONE@mgh.harvard.edu; vdeshpande@partners.org RI Sabbatino, Francesco/F-4992-2014 OI Sabbatino, Francesco/0000-0001-6431-8278 NR 1 TC 0 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2015 VL 22 SU 3 BP S1609 EP S1609 DI 10.1245/s10434-015-4510-7 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA CZ7OG UT WOS:000367288100164 PM 25786746 ER PT J AU Golshan, M Losk, K Mallory, MA Camuso, K Troyan, S Lin, NU Kadish, S Bunnell, CA AF Golshan, Mehra Losk, Katya Mallory, Melissa A. Camuso, Kristen Troyan, Susan Lin, Nancy U. Kadish, Sarah Bunnell, Craig A. TI Variation in Additional Breast Imaging Orders and Impact on Surgical Wait Times at a Comprehensive Cancer Center SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID 2ND OPINIONS; MANAGEMENT; SURGERY; DELAYS; DIAGNOSIS; CARE AB Background. In the multidisciplinary care model, breast imagers frequently provide second-opinion reviews of imaging studies performed at outside institutions. However, the need for additional imaging and timeliness of obtaining these studies has yet to be established. We sought to evaluate the frequency of additional imaging orders by breast surgeons and to evaluate the impact of this supplementary imaging on timeliness of surgery. Methods. We identified 2489 consecutive women with breast cancer who underwent first definitive surgery (FDS) at our comprehensive cancer center between 2011 and 2013. The number of breast-specific imaging studies performed for each patient between initial consultation and FDS was obtained. chi(2) tests were used to quantify the proportion of patients undergoing additional imaging by surgeon. Interval time between initial consultation and additional imaging and/or biopsy was calculated. The delay of additional imaging on time to FDS was assessed by t test. Results. Of 2489 patients, 615 (24.7 %) had at least one additional breast-specific imaging study performed between initial consultation and FDS, with 222 patients undergoing additional biopsies (8.9 %). The proportion of patients receiving imaging tests by breast surgeon ranged from 15 to 39 % (p < 0.0001). Patients receiving additional imaging had statistically longer wait times to FDS for BCT (21.4-28.5 days, p < 0.0001). Conclusions. Substantial variability exists in the utilization of additional breast- specific imaging and in the timeliness of obtaining these tests among breast surgeons. Further research is warranted to assess the sources and impact of this variation on patient care, cost, and outcomes. C1 [Golshan, Mehra; Mallory, Melissa A.; Troyan, Susan] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Losk, Katya; Camuso, Kristen; Kadish, Sarah] Dana Farber Canc Inst, Dept Qual & Patient Safety, Boston, MA 02115 USA. [Lin, Nancy U.; Bunnell, Craig A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org FU NIH National Institute of Health [R25 CA089017] FX This initiative was supported in part by the NIH National Institute of Health Grant R25 CA089017. NR 21 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2015 VL 22 SU 3 BP S428 EP S434 DI 10.1245/s10434-015-4834-3 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA CZ7OG UT WOS:000367288100022 PM 26307233 ER PT J AU Sharma, G Whang, EE Ruan, DT Ito, H AF Sharma, Gaurav Whang, Edward E. Ruan, Daniel T. Ito, Hiromichi TI Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Pancreatic Adenocarcinoma: A Decision Analysis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PHASE-II TRIAL; GEMCITABINE-BASED CHEMORADIATION; SINGLE-INSTITUTION EXPERIENCE; QUALITY-OF-LIFE; CURATIVE RESECTION; PREOPERATIVE GEMCITABINE; IMPROVES SURVIVAL; FOLINIC ACID; CANCER AB Background. Neoadjuvant therapy-based protocols for potentially resectable pancreatic adenocarcinoma (PAC) have not been directly compared with adjuvant protocols in large prospective randomized trials. This study aimed to compare the efficacy of neoadjuvant versus adjuvant therapy-based management by using a formal decision analytic model. Methods. A decision analytic model was created with a Markov process to compare neoadjuvant and adjuvant chemo-and/or chemoradiation therapy-based strategies for simulated cohorts of patients with potentially resectable PAC. Base-case probabilities were derived from the published data of 21 prospective phases 2 and 3 trials (3708 patients) between 1997 and 2014. The primary outcome measures determined in an intent-to-treat fashion were overall and quality-adjusted survival rates. One- and two-way sensitivity analyses were performed to assess the effects of model uncertainty on outcomes. Results. The median overall survival and 2-year survival rates for the patients in the standard adjuvant therapy arm of the study were 20 months and 42.2 % versus 22 months and 46.8 % for those in the neoadjuvant strategy arm. Quality-adjusted survival was 18.4 and 19.8 months, respectively. Sensitivity analysis demonstrated that when recurrence-free survival after completion of neoadjuvant therapy and resection is less than 13.9 months or when the rate for progression of disease precluding resection during neoadjuvant therapy is greater than 44 %, the neoadjuvant strategy is no longer the favored option. Conclusions. The decision analytic model suggests that neoadjuvant therapy-based management improves the outcomes for patients with potentially resectable pancreatic cancer. However, the benefits in terms of overall and quality-adjusted survival are modest. C1 [Sharma, Gaurav; Whang, Edward E.; Ruan, Daniel T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Whang, Edward E.] VA Boston Healthcare Syst, Dept Surg, West Roxbury, MA USA. [Ito, Hiromichi] Michigan State Univ, Coll Human Med, Dept Surg, E Lansing, MI 48824 USA. RP Sharma, G (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. EM gsharma1@partners.org NR 39 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2015 VL 22 SU 3 BP S1229 EP S1237 DI 10.1245/s10434-015-4711-0 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA CZ7OG UT WOS:000367288100126 PM 26152276 ER PT J AU Knorr, J Soldado, F Menendez, ME Domenech, P Sanchez, M de Gauzy, JS AF Knoerr, Jorge Soldado, Francisco Menendez, Mariano E. Domenech, Pedro Sanchez, Mikel de Gauzy, Jerome Sales TI Arthroscopic Talocalcaneal Coalition Resection in Children SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID CALCANEO-STOP PROCEDURE; OSTEOTOMY; FLATFOOT; HINDFOOT; ANKLE; FOOT AB Purpose: To present the technique and outcomes of arthroscopic talocalcaneal coalition (TCC) resection in pediatric patients. Methods: We performed a prospective study of 16 consecutive feet with persistent symptomatic TCCs in 15 children. The mean age was 11.8 years (range, 8 to 15 years), and the mean follow-up period was 28 months (range, 12 to 44 months). A posterior arthroscopic TCC resection was performed. The plantar footprint, subtalar motion, pain, and the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot scale score were evaluated preoperatively and postoperatively. Preoperative computed tomography (CT) scans were used to classify the coalition according to the Rozansky classification, to measure the percentage of involvement of the surface area, and to determine the degree of hindfoot valgus. Postoperative CT scans at 1 year (n = 15) and 3 years (n = 5) were used to assess recurrences. Patient satisfaction was also evaluated. Results: The TCC distribution according to the Rozansky classification was type I in 7 cases, type II in 3, type III in 3, and type IV in 3. In all cases the arthroscopic approach enabled complete coalition resection. All patients increased by at least 1 stage in the footprint classification and showed clinical subtalar mobility after surgery. All patients showed a statistically significant improvement in pain after surgery except for 1 patient in whom complex regional pain syndrome developed (P < .001). The mean American Orthopaedic Foot & Ankle Society score was 56.8 (range, 45 to 62) preoperatively versus 90.9 (range, 36 to 100) postoperatively, showing a statistically significant increase (P < .001). Preoperative CT scans showed that all TCCs involved the medial subtalar joint facet, with mean involvement of 40.8% of the articular surface. All postoperative CT scans showed complete synostosis resections with no recurrences at final followup. At final follow-up, all patients were either satisfied (n = 4 [27%]) or extremely satisfied (n = 10 [67%]) with the outcome, except the 1 patient (7%) in whom complex regional pain syndrome developed. Conclusions: Arthroscopic TCC resection provides good outcomes (symptom relief and restoration of subtalar motion), with no recurrence of the coalition. C1 [Knoerr, Jorge; Soldado, Francisco; Domenech, Pedro] Univ Barcelona, Hosp St Joan de Deu, Dept Pediat Orthoped Surg & Microsurg, Barcelona, Spain. [Menendez, Mariano E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Sanchez, Mikel] Hosp Vhitas San Jose, Unidad Cirugia Artroscop, Vitoria, Spain. [de Gauzy, Jerome Sales] Hop Enfants, Pediat Orthoped Surg Dept, Toulouse, France. RP Knorr, J (reprint author), Hosp St Joan de Deu, Passeig St Joan de Deu 2, Barcelona 08950, Spain. EM knorr.j@chu-toulouse.fr OI Soldado, Francisco Antonio/0000-0003-1759-9868 NR 24 TC 1 Z9 1 U1 2 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 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD DEC PY 2015 VL 31 IS 12 BP 2417 EP 2423 DI 10.1016/j.arthro.2015.06.022 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CZ7YT UT WOS:000367317400020 PM 26315054 ER PT J AU Uy, GL Costa, LJ Hari, PN Zhang, MJ Huang, JX Anderson, KC Bredeson, CN Callander, NS Cornell, RF Perez, MAD Dispenzieri, A Freytes, CO Gale, RP Garfall, A Gertz, MA Gibson, J Hamadani, M Lazarus, HM Kalaycio, ME Kamble, RT Kharfan-Dabaja, MA Krishnan, AY Kumar, SK Kyle, RA Landau, HJ Lee, CH Maiolino, A Marks, DI Mark, TM Munker, R Nishihori, T Olsson, RF Ramanathan, M Rodriguez, TE Saad, AA Savani, BN Schiller, GJ Schouten, HC Schriber, JR Scott, E Seo, S Sharma, M Ganguly, S Stadtmauer, EA Tay, J To, LB Vesole, DH Vogl, DT Wagner, JL Wirk, B Wood, WA D'Souza, A AF Uy, G. L. Costa, L. J. Hari, P. N. Zhang, M-J Huang, J-X Anderson, K. C. Bredeson, C. N. Callander, N. S. Cornell, R. F. Perez, M. A. D. Dispenzieri, A. Freytes, C. O. Gale, R. P. Garfall, A. Gertz, M. A. Gibson, J. Hamadani, M. Lazarus, H. M. Kalaycio, M. E. Kamble, R. T. Kharfan-Dabaja, M. A. Krishnan, A. Y. Kumar, S. K. Kyle, R. A. Landau, H. J. Lee, C. H. Maiolino, A. Marks, D. I. Mark, T. M. Munker, R. Nishihori, T. Olsson, R. F. Ramanathan, M. Rodriguez, T. E. Saad, A. A. Savani, B. N. Schiller, G. J. Schouten, H. C. Schriber, J. R. Scott, E. Seo, S. Sharma, M. Ganguly, S. Stadtmauer, E. A. Tay, J. To, L. B. Vesole, D. H. Vogl, D. T. Wagner, J. L. Wirk, B. Wood, W. A. D'Souza, A. TI Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article ID LENALIDOMIDE THERAPY; INDUCTION THERAPY; RANDOMIZED-TRIAL; STEM-CELLS; G-CSF; CYCLOPHOSPHAMIDE; RESCUE; IMPACT; MAINTENANCE; PLERIXAFOR AB In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (auto-HCT), peripheral blood progenitor cells may be collected following mobilization with growth factor alone (GF) or cytotoxic chemotherapy plus GF (CC+GF). It is uncertain whether the method of mobilization affects post-transplant outcomes. We compared these mobilization strategies in a retrospective analysis of 968 patients with MM from the Center for International Blood and Marrow Transplant Research database who received an auto-Ha in the US and Canada between 2007 and 2012. The kinetics of neutrophil engraftment (>= 0.5 x 10(9)/L) was similar between groups (13 vs 13 days, P=0.69) while platelet engraftment (>= 20 x 10(9)/L) was slightly faster with CC+GF (19 vs 18 days, P=0.006). Adjusted 3-year PFS was 43% (95% confidence interval (CI) 38-48) in GF and 40% (95% CI 35-45) in CC+GF, P=0.33. Adjusted 3-year OS was 82% (95% CI 78-86) vs 80% (95% CI 75-84), P=0.43 and adjusted 5-year OS was 62% (95% CI 54-68) vs 60% (95% CI 52-67), P=0.76, for GF and CC+GF, respectively. We conclude that MM patients undergoing auto-Ha have similar outcomes irrespective of the method of mobilization and found no evidence that the addition of chemotherapy to mobilization contributes to disease control. C1 [Uy, G. L.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Costa, L. J.; Saad, A. A.] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Hari, P. N.; Zhang, M-J; Huang, J-X; Hamadani, M.; D'Souza, A.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Zhang, M-J] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Anderson, K. C.] Dana Farber Canc Inst, Hematol Oncol Treatment Ctr, Boston, MA 02115 USA. [Bredeson, C. N.] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada. [Bredeson, C. N.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Callander, N. S.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Cornell, R. F.; Savani, B. N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Perez, M. A. D.] Univ Nino Jesus, Serv Oncohematol, Hosp Infantil, Madrid, Spain. [Dispenzieri, A.; Gertz, M. A.; Kumar, S. K.; Kyle, R. A.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Freytes, C. O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, C. O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, R. P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England. [Garfall, A.; Stadtmauer, E. A.; Vogl, D. T.] Univ Penn, Abramson Canc Ctr, Perelman Ctr Adv Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Gibson, J.] Royal Prince Alfred Hosp, Dept Haematol, Inst Haematol, Camperdown, NSW 2050, Australia. [Lazarus, H. M.] Univ Hosp, Seidman Canc Ctr, Case Med Ctr, Cleveland, OH USA. [Kalaycio, M. E.] Cleveland Clin, Hematol Oncol & Blood Disorders, Cleveland, OH 44106 USA. [Kamble, R. T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Dept Hematol & Oncol, Houston, TX 77030 USA. [Kharfan-Dabaja, M. A.; Nishihori, T.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Krishnan, A. Y.] City Hope Natl Med Ctr, Dept Hematol Oncol, Duarte, CA 91010 USA. [Landau, H. J.] Mem Sloan Kettering Canc Ctr, Bone Marrow Transplant Serv, New York, NY 10021 USA. [Lee, C. H.; To, L. B.] Royal Adelaide Hosp, SA Pathol, Haematol & Bone Marrow Transplant Unit, Adelaide, SA 5000, Australia. [Maiolino, A.] Univ Fed Rio de Janeiro, Hosp Univ Clementinio Fraga Filho, Rio De Janeiro, Brazil. [Marks, D. I.] Univ Hosp Bristol NHS Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England. [Mark, T. M.] New York Presbyterian Hosp Cornell, Dept Med, New York, NY USA. [Munker, R.] Louisiana State Univ Hlth Shreveport, Dept Internal Med, Hematol Oncol Sect, Shreveport, LA USA. [Olsson, R. F.] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden. [Olsson, R. F.] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Ramanathan, M.] UMass Mem Med Ctr, Dept Med, Div Hematol Oncol, Worcester, MA USA. [Rodriguez, T. E.] Loyola Univ, Med Ctr, Bone Marrow Transplant Program, Chicago, IL 60611 USA. [Schiller, G. J.] Univ Calif Los Angeles, Ctr Hlth Sci, Bone Marrow Transplant Program, Los Angeles, CA 90024 USA. [Schouten, H. C.] Acad Ziekenhuis, Dept Hematol, Maastricht, Netherlands. [Schriber, J. R.] Virginia G Piper Canc Ctr, Canc Transplant Inst, Scottsdale, AZ USA. [Schriber, J. R.] Arizona Oncol, Scottsdale, AZ USA. [Scott, E.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Seo, S.] Fred Hutchinson Canc Res Ctr, Dept Vaccine & Infect Dis, Seattle, WA 98104 USA. [Sharma, M.; Wagner, J. L.] Thomas Jefferson Univ, Dept Hematol Oncol, Philadelphia, PA 19107 USA. [Ganguly, S.] Univ Kansas, Med Ctr, Div Hematol & Oncol, Blood & Marrow Transplantat, Kansas City, KS 66103 USA. [Tay, J.] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Vesole, D. H.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Wirk, B.] Seattle Canc Care Alliance, Seattle, WA USA. [Wood, W. A.] Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA. RP D'Souza, A (reprint author), Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, 9200 West Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM anitadsouza@mcw.edu OI D'Souza, Anita/0000-0002-1092-5643; Dispenzieri, Angela/0000-0001-8780-9512 FU Public Health Service Grant/National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. NR 24 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD DEC PY 2015 VL 50 IS 12 BP 1513 EP 1518 DI 10.1038/bmt.2015.190 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA DA0KR UT WOS:000367486500005 PM 26301967 ER PT J AU Klaassen, Z Howard, L Terris, MK Aronson, WJ Cooperberg, MR Amling, CL Kane, CJ Freedland, SJ AF Klaassen, Zachary Howard, Lauren Terris, Martha K. Aronson, William J. Cooperberg, Matthew R. Amling, Christopher L. Kane, Christopher J. Freedland, Stephen J. TI Does larger tumor volume explain the higher prostate specific antigen levels in black men with prostate cancer-Results from the SEARCH database SO CANCER EPIDEMIOLOGY LA English DT Article DE Prostate cancer; PSA; Race; Radical prostatectomy; Tumor volume ID AFRICAN-AMERICAN MEN; ANDROGEN RECEPTOR GENE; RADICAL PROSTATECTOMY; RACIAL-DIFFERENCES; WHITE MEN; SPECIMENS; PSA; DISEASE; RISK; CAG AB Objectives: To assess whether larger tumor volume in black men explains higher presurgical PSA levels versus white men with prostate cancer. Methods: We retrospectively analyzed 1904 men from the Shared Equal Access Regional Cancer Hospital database who underwent radical prostatectomy from 1990 to 2013. Geometric mean of tumor volume and preoperative PSA for each race were estimated from multivariable linear regression models. Results: There were 1104 (58%) white men and 800 (42%) black men. Black men were younger (60.2 vs. 62.9 years, p < 0.001) had a higher PSA (6.7 vs. 6.0 ng/mL, p < 0.001), more positive margins (47 vs. 38%, p < 0.001), and seminal vesicle invasion (13 vs. 9%, p = 0.007). White patients had higher clinical stage (p < 0.001) and greater median tumor volume (6.0 vs. 5.3 gm, p = 0.011). After multivariable adjustment (except for PSA), white men had smaller mean tumor volumes (5.2 vs. 5.8 gm, p = 0.011). When further adjusted for PSA, there was no racial difference in mean tumor volume (p = 0.34). After multivariable adjustment, black men had higher mean PSAs vs. white men (7.5 vs. 6.1 ng/mL, p < 0.001). Results were similar after further adjusting for tumor volume: black men had 16% higher mean PSAs versus white men (7.4 vs. 6.2 ng/mL, p < 0.001). Conclusions: In this study of men undergoing radical prostatectomy at multiple equal access medical centers, racial differences in tumor volume did not explain higher presurgical PSA levels in black versus white men. The exact reason for higher PSA values in black men remains unclear. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Klaassen, Zachary; Terris, Martha K.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [Howard, Lauren] Duke Univ, Med Ctr, Durham, NC USA. [Terris, Martha K.] Augusta Vet Affairs Med Ctr, Augusta, GA USA. [Aronson, William J.] West Los Angeles Vet Affairs Med Ctr, West Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Cooperberg, Matthew R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cooperberg, Matthew R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kane, Christopher J.] San Diego Vet Affairs Med Ctr, San Diego, CA USA. [Kane, Christopher J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Freedland, Stephen J.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Freedland, Stephen J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Freedland, SJ (reprint author), Cedars Sinai Med Ctr, Dept Surg, Div Urol, 8635 West 3rd St,Suite 1070W, Los Angeles, CA 90048 USA. EM stephen.freedland@cshs.org FU Department of Veterans Affairs, the National Institutes of Health (NIH) [R01CA100938]; NIH Specialized Programs of Research Excellence Grant [P50CA92131-01A1]; Georgia Cancer Coalition; NIH grant [K24CA160653] FX Research support was received from the Department of Veterans Affairs, the National Institutes of Health (NIH) (grant R01CA100938 to Dr. Aronson), NIH Specialized Programs of Research Excellence Grant P50CA92131-01A1 (to Dr. Aronson), the Georgia Cancer Coalition (to Dr. Terris), and NIH grant K24CA160653 (to Dr. Freedland). NR 30 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 1877-7821 EI 1877-783X J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD DEC PY 2015 VL 39 IS 6 BP 1066 EP 1070 DI 10.1016/j.canep.2015.09.007 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CZ9VE UT WOS:000367444300039 PM 26452418 ER PT J AU Mahoney, KM Sun, H Liao, X Hua, P Callea, M Greenfield, EA Hodi, FS Sharpe, AH Signoretti, S Rodig, SJ Freeman, GJ AF Mahoney, Kathleen M. Sun, Heather Liao, Xiaoyun Hua, Ping Callea, Marcella Greenfield, Edward A. Hodi, F. Stephen Sharpe, Arlene H. Signoretti, Sabina Rodig, Scott J. Freeman, Gordon J. TI PD-L1 Antibodies to Its Cytoplasmic Domain Most Clearly Delineate Cell Membranes in Immunohistochemical Staining of Tumor Cells SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID PROGRAMMED CELL-DEATH-1; B7 FAMILY; EXPRESSION; CANCER; ACTIVATION; CARCINOMA; BLOCKADE; LIGANDS; SAFETY; NIVOLUMAB AB Blocking the programmed death-1 (PD-1) pathway has clinical benefit in metastatic cancer and has led to the approval of the mAbs pembrolizumab and nivolumab to treat melanoma and nivolumab for non-small cell lung cancer. Expression of PD-L1 on the cell surface of either tumor cells or infiltrating immune cells is associated with a higher likelihood of response to PD-1 blockade in multiple studies. Most mAbs to PD-L1 in use are directed to its extracellular domain and immunohistochemically stain tumor tissue with a mixture of cytoplasmic and membrane staining. Cytoplasmic staining obscures the interpretation of a positive reaction on the tumor cell membrane, and thus affects the accuracy of PD-L1 scoring systems. We developed a mAb to the cytoplasmic domain of PD-L1, 405.9A11 (9A11), which is both more selective for membranous PD-L1 and more sensitive in IHC and Western blotting, compared with previous mAbs specific for the PD-L1 extracellular domain. Here, we compare immunohistochemical staining patterns of PD-L1 expression in five types of tumors, using five PD-L1 mAbs: 9A11, 7G11, and three commercially available mAbs. We demonstrate that 9A11, as well as two other cytoplasmic domain-specific mAbs, E1L3N and SP142, can clearly delineate the membrane of PD-L1-positive cells in formalin-fixed paraffin-embedded tissue and facilitate interpretation of staining results. (C)2015 AACR. C1 [Mahoney, Kathleen M.; Liao, Xiaoyun; Hua, Ping; Greenfield, Edward A.; Hodi, F. Stephen; Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mahoney, Kathleen M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol & Oncol, Boston, MA 02215 USA. [Sun, Heather; Callea, Marcella; Signoretti, Sabina; Rodig, Scott J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Liao, Xiaoyun; Hodi, F. Stephen; Rodig, Scott J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Freeman, GJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM gordon_freeman@dfci.harvard.edu FU DF/HCC Kidney Cancer [SPORE P50CA101942, U54CA163125, P01AI056299]; Claudia Adams Barr Program for Innovative Cancer Research; AACR Basic Cancer Research Fellowship [14-40-01-MAHO]; Kidney Cancer Association; Center for Immuno-Oncology, Dana-Farber Cancer Institute FX This study was supported by DF/HCC Kidney Cancer SPORE P50CA101942 (to S. Signoretti, A.H. Sharpe, and G.J. Freeman), U54CA163125, and P01AI056299 (to G.J. Freeman and A.H. Sharpe); Claudia Adams Barr Program for Innovative Cancer Research, 2014 AACR Basic Cancer Research Fellowship, grant number 14-40-01-MAHO, and the ASCO Young Investigator Award supported by Kidney Cancer Association (to K.M. Mahoney); the Center for Immuno-Oncology, Dana-Farber Cancer Institute (to F.S. Hodi and S.J. Rodig). NR 27 TC 18 Z9 18 U1 2 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD DEC PY 2015 VL 3 IS 12 BP 1308 EP 1315 DI 10.1158/2326-6066.CIR-15-0116 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA DA1LC UT WOS:000367556300004 PM 26546452 ER PT J AU Voena, C Menotti, M Mastini, C Di Giacomo, F Longo, DL Castella, B Merlo, MEB Ambrogio, C Wang, Q Minero, VG Poggio, T Martinengo, C D'Amico, L Panizza, E Mologni, L Cavallo, F Altruda, F Butaney, M Capelletti, M Inghirami, G Janne, PA Chiarle, R AF Voena, Claudia Menotti, Matteo Mastini, Cristina Di Giacomo, Filomena Longo, Dario Livio Castella, Barbara Merlo, Maria Elena Boggio Ambrogio, Chiara Wang, Qi Minero, Valerio Giacomo Poggio, Teresa Martinengo, Cinzia D'Amico, Lucia Panizza, Elena Mologni, Luca Cavallo, Federica Altruda, Fiorella Butaney, Mohit Capelletti, Marzia Inghirami, Giorgio Jaenne, Pasi A. Chiarle, Roberto TI Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; LARGE-CELL LYMPHOMA; ANTI-PD-L1 ANTIBODY; TARGETED THERAPIES; IMMUNE-RESPONSE; TYROSINE KINASE; GROWTH-FACTOR; INHIBITION; MUTATIONS; CERITINIB AB Non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase inhibitors (TKI), but the treatment is successful for only a limited amount of time; most patients experience a relapse due to the development of drug resistance. Here, we show that a vaccine against ALK induced a strong and specific immune response that both prophylactically and therapeutically impaired the growth of ALK-positive lung tumors in mousemodels. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. We found that lung tumors containing ALK rearrangements induced an immunosuppressive microenvironment, regulating the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti-PD- 1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune checkpoint blockade therapies might represent a powerful strategy for the treatment of ALK-driven NSCLC. (C)2015 AACR. C1 [Voena, Claudia; Menotti, Matteo; Mastini, Cristina; Di Giacomo, Filomena; Longo, Dario Livio; Castella, Barbara; Merlo, Maria Elena Boggio; Minero, Valerio Giacomo; Poggio, Teresa; Martinengo, Cinzia; D'Amico, Lucia; Panizza, Elena; Cavallo, Federica; Altruda, Fiorella; Inghirami, Giorgio; Chiarle, Roberto] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy. [Voena, Claudia; Menotti, Matteo; Mastini, Cristina; Di Giacomo, Filomena; Castella, Barbara; Merlo, Maria Elena Boggio; Minero, Valerio Giacomo; Poggio, Teresa; Martinengo, Cinzia; D'Amico, Lucia; Panizza, Elena; Inghirami, Giorgio; Chiarle, Roberto] Citta Salute & Sci, CERMS, Turin, Italy. [Longo, Dario Livio] Univ Turin, Mol Imaging Ctr, Turin, Italy. [Ambrogio, Chiara] Ctr Nacl Invest Oncol, Mol Oncol Program, Madrid, Spain. [Wang, Qi; Chiarle, Roberto] Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Mologni, Luca] Univ Milano Bicocca, Dept Hlth Sci, Milan, Italy. [Cavallo, Federica; Altruda, Fiorella] Univ Turin, Mol Biotechnol Ctr, Turin, Italy. [Butaney, Mohit; Capelletti, Marzia; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Butaney, Mohit; Capelletti, Marzia; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. RP Chiarle, R (reprint author), Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA. EM roberto.chiarle@childrens.harvard.edu RI Cavallo, Federica/C-5666-2011 OI Ambrogio, Chiara/0000-0003-4122-701X; Boggio Merlo, Maria Elena/0000-0002-1967-7308; Cavallo, Federica/0000-0003-4571-1060 FU FP7 ERC-StG [242965]; Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG-12023]; Koch Institute/DFCC Bridge Project Fund; Ellison Foundation Boston; Grant for Oncology Innovation by Merck-Serono; Worldwide Cancer Research [12-0216]; [R01 CA136851] FX This work has been supported by grants FP7 ERC-2009-StG (proposal no. 242965-"Lunely") to R. Chiarle; Associazione Italiana per la Ricerca sul Cancro (AIRC) grant IG-12023 to R. Chiarle; Koch Institute/DFCC Bridge Project Fund to R. Chiarle; Ellison Foundation Boston to R. Chiarle; the Grant for Oncology Innovation by Merck-Serono to R. Chiarle; Worldwide Cancer Research (former AICR) grant 12-0216 to R. Chiarle; and R01 CA136851 to P.A. Janne. NR 47 TC 4 Z9 4 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD DEC PY 2015 VL 3 IS 12 BP 1333 EP 1343 DI 10.1158/2326-6066.CIR-15-0089 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA DA1LC UT WOS:000367556300007 PM 26419961 ER PT J AU Agassandian, M Tedrow, JR Sembrat, J Kass, DJ Zhang, YZ Goncharova, EA Kaminski, N Mallampalli, RK Vuga, LJ AF Agassandian, Marianna Tedrow, John R. Sembrat, John Kass, Daniel J. Zhang, Yingze Goncharova, Elena A. Kaminski, Naftali Mallampalli, Rama K. Vuga, Louis J. TI VCAM-1 is a TGF-beta 1 inducible gene upregulated in idiopathic pulmonary fibrosis SO CELLULAR SIGNALLING LA English DT Article DE IPF; VCAM-1; Lung fibroblasts; TGF-beta 1 ID SOLUBLE ADHESION MOLECULES; INTERSTITIAL PNEUMONIAS; SYSTEMIC-SCLEROSIS; EXPRESSION; INHIBITION; THERAPY AB Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease of unknown etiology. We previously reported that high plasma levels of vascular cell adhesion molecule 1 (VCAM-1) predict mortality in IPF subjects. Here we investigated the cellular origin and potential role of VCAM-1 in regulating primary lung fibroblast behavior. VCAM-1 mRNA was significantly increased in lungs of subjects with IPF compared to lungs from control subjects (p = 0.001), and it negatively correlated with two markers of lung function, forced vital capacity (FVC) and pulmonary diffusion capacity for carbon monoxide (DLco). VCAM-1 protein levels were highly expressed in IPF subjects where it was detected in fibrotic foci and blood vessels of IPF lung. Treatment of human lung fibroblasts with TGF-beta 1 significantly increased steady-state VCAM1 mRNA and protein levels without affecting VCAM1 mRNA stability. Further, cellular depletion of VCAM-1 inhibited fibroblast cell proliferation and reduced G2/M and S phases of the cell cycle suggestive of cell cycle arrest. These effects on cell cycle progression triggered by VCAM1 depletion were associated with reductions in levels of phosphorylaed extracellular regulated kinase 1/2 and cyclin D1. Thus, these observations suggest that VCAM-1 is a TGF-beta 1 responsive mediator that partakes in fibroblast proliferation in subjects with IPF. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Agassandian, Marianna; Tedrow, John R.; Sembrat, John; Kass, Daniel J.; Zhang, Yingze; Vuga, Louis J.] Univ Pittsburgh, Sch Med, Dorothy P & Richard P Simmons Ctr Interstitial Lu, Pittsburgh, PA 15213 USA. [Agassandian, Marianna; Tedrow, John R.; Sembrat, John; Kass, Daniel J.; Zhang, Yingze; Goncharova, Elena A.; Mallampalli, Rama K.; Vuga, Louis J.] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA. [Goncharova, Elena A.] Univ Pittsburgh, Pittsburgh Heart Lung Blood & Vasc Med Inst, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. [Kaminski, Naftali] Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, New Heaven, CT USA. RP Mallampalli, RK (reprint author), NW628 Montefiore Univ Hosp, 3459 Fifth Ave, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu; vugalj@upmc.edu FU National Institutes of Health/National Heart, Lung, and Blood Institute [HL108869, HL073745, HL097376, R01HL095397, RC2HL101715, U01HL108642, P01HL114453, P50HL0894932]; Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research; US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; VA Merit Review Award FX We would like to thank Dr. Mauricio Rojas for his editorial suggestions in the manuscript. This research was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute [HL108869, HL073745, HL097376, R01HL095397, RC2HL101715, U01HL108642, P01HL114453, and P50HL0894932], and the Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research. This material is also based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development and a VA Merit Review Award. NR 36 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD DEC PY 2015 VL 27 IS 12 BP 2467 EP 2473 DI 10.1016/j.cellsig.2015.09.003 PG 7 WC Cell Biology SC Cell Biology GA DA0KQ UT WOS:000367486400015 PM 26386411 ER PT J AU Boockvar, K AF Boockvar, Kenneth TI Preserving Cognition and Attaining Ideal Anesthesia and Surgical Outcomes in Older Adults SO CLINICAL THERAPEUTICS LA English DT Editorial Material ID POSTOPERATIVE DELIRIUM; HIP FRACTURE; SEVOFLURANE; SURGERY C1 [Boockvar, Kenneth] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Boockvar, Kenneth] New Jewish Home, Res Inst Aging, New York, NY USA. [Boockvar, Kenneth] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. RP Boockvar, K (reprint author), James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. OI Boockvar, Kenneth/0000-0003-1165-5558 NR 20 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD DEC PY 2015 VL 37 IS 12 BP 2638 EP 2640 DI 10.1016/j.clinthera.2015.11.006 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CZ9MF UT WOS:000367421000004 PM 26621624 ER PT J AU Garcia, PS Duggan, EW McCullough, IL Lee, SC Fishman, D AF Garcia, Paul S. Duggan, Elizabeth W. McCullough, Ian L. Lee, Simon C. Fishman, David TI Postanesthesia Care for the Elderly Patient SO CLINICAL THERAPEUTICS LA English DT Review DE elderly; recovery; delirium; polypharmacy; anesthesia; surgery ID POSTOPERATIVE URINARY RETENTION; OBSTRUCTIVE PULMONARY-DISEASE; CONVERTING ENZYME-INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; NONCARDIAC SURGERY; ALZHEIMERS-DISEASE; UNITED-STATES; OLDER-ADULTS; SLEEP-APNEA; RESPIRATORY COMPLICATIONS AB Purpose: As the general population lives longer, the perioperative physician is more likely to encounter disease states that increase in incidence in an aging population. This review focuses on anesthetic considerations for rational drug choices during the perioperative care of elderly patients. The primary aim of the review was to identify intraoperative and postanesthetic considerations for diseases associated with advancing age; it includes highlights of the commonly impaired major organs (eg, cardiovascular, pulmonary, neurologic, renal, hepatic systems). We also outline an approach to frequent issues that arise in the immediate postsurgical period while caring for these patients. Methods: A systematic review was performed on aspects of the perioperative and postoperative periods that relate to the elderly. A list of pertinent key words was derived from the authors, and a PubMed database search was performed. Findings: The anesthesiologist must account for changes in various organ systems that affect perioperative care, including the cardiovascular, pulmonary, renal, hepatic, and central nervous systems. The pharmacokinetic principles frequently differ and are often unpredictable because of anatomic changes and decreased renal and hepatic function. The most important pharmacodynamic consideration is that elderly patients tend to exhibit an exaggerated hypoactivity after anesthesia. Published by Elsevier HS Journals, Inc. C1 [Garcia, Paul S.; Fishman, David] US Dept Vet Affairs, Atlanta VA Med Ctr, Decatur, GA USA. [Garcia, Paul S.; Duggan, Elizabeth W.; McCullough, Ian L.; Lee, Simon C.; Fishman, David] Emory Univ, Sch Med, Dept Anesthesiol, Decatur, GA 30033 USA. RP Garcia, PS (reprint author), Emory Univ, Sch Med, Dept Vet Affairs, Atlanta VA Med Ctr, 1670 Clairmont Rd NE, Decatur, GA 30033 USA. EM pgarcia@emory.edu FU James S. McDonnell Foundation; Department of Veterans Affairs [CDA BX001677] FX The authors gratefully acknowledge research support from internal departmental and institutional initiatives (Team-Based Science). Dr. Garcia's research efforts are supported in part by funding from the James S. McDonnell Foundation (www.jsmf.org) and from funding from a Career Development Award awarded by the Department of Veterans Affairs (PSG, CDA BX001677). The contents do not represent the views of the US Department of Veterans Affairs or the United States Government. NR 113 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD DEC PY 2015 VL 37 IS 12 BP 2651 EP 2665 DI 10.1016/j.clinthera.2015.10.018 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CZ9MF UT WOS:000367421000006 PM 26598176 ER PT J AU Dudzinski, DM Isselbacher, EM AF Dudzinski, David M. Isselbacher, Eric M. TI Diagnosis and Management of Thoracic Aortic Disease SO CURRENT CARDIOLOGY REPORTS LA English DT Review DE Aorta; Thoracic aorta aneurysm; Acute aortic syndrome; Aortic dissection; Intramural hematoma; Penetrating atherosclerotic ulcer ID COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; DISSECTION; ECHOCARDIOGRAPHY; METAANALYSIS; ASSOCIATION; LOSARTAN; THERAPY; SOCIETY; ADULTS AB Thoracic aortic aneurysms are typically asymptomatic and discovered incidentally on an imaging study ordered for other indications. Small aneurysms are managed with antihypertensive therapy and surveillance imaging, using either echocardiography, computed tomographic angiography (CTA), or magnetic resonance angiography (MRA). Aneurysms are repaired when the risk of rupture or dissection exceeds the risk of repair; size thresholds for repair are determined by the underlying etiology of the aneurysm, with lower thresholds for those with genetic aortopathies. In contrast to the silent and asymptomatic nature of aneurysms, acute aortic syndromes-which include aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer-are usually associated with recognizable symptoms and signs. Acute aortic syndromes involving the ascending aorta are treated with emergent surgery, whereas those involving the descending aorta are now often treated with endovascular stent-grafting techniques. After acute aortic syndromes have been successfully treated, prognosis is favorable with close follow-up that includes optimal medical management and regular surveillance imaging. C1 [Dudzinski, David M.; Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Thorac Aort Ctr, Yawkey 5, Boston, MA 02114 USA. EM ddudzinski@partners.org; eisselbacher@partners.org NR 15 TC 2 Z9 2 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD DEC PY 2015 VL 17 IS 12 AR 106 DI 10.1007/s11886-015-0655-z PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA0II UT WOS:000367480400001 PM 26468124 ER PT J AU Loucks, EB Schuman-Olivier, Z Britton, WB Fresco, DM Desbordes, G Brewer, JA Fulwiler, C AF Loucks, Eric B. Schuman-Olivier, Zev Britton, Willoughby B. Fresco, David M. Desbordes, Gaelle Brewer, Judson A. Fulwiler, Carl TI Mindfulness and Cardiovascular Disease Risk: State of the Evidence, Plausible Mechanisms, and Theoretical Framework SO CURRENT CARDIOLOGY REPORTS LA English DT Review DE Mindfulness; Cardiovascular disease; Etiology ID RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; SELF-DETERMINATION THEORY; STRESS-REDUCTION; SMOKING-CESSATION; PLANNED BEHAVIOR; WEIGHT-LOSS; DISPOSITIONAL MINDFULNESS; UPDATED GUIDELINES; PROSPECTIVE COHORT AB The purpose of this review is to provide (1) a synopsis on relations of mindfulness with cardiovascular disease (CVD) and major CVD risk factors, and (2) an initial consensus-based overview of mechanisms and theoretical framework by which mindfulness might influence CVD. Initial evidence, often of limited methodological quality, suggests possible impacts of mindfulness on CVD risk factors including physical activity, smoking, diet, obesity, blood pressure, and diabetes regulation. Plausible mechanisms include (1) improved attention control (e.g., ability to hold attention on experiences related to CVD risk, such as smoking, diet, physical activity, and medication adherence), (2) emotion regulation (e.g., improved stress response, self-efficacy, and skills to manage craving for cigarettes, palatable foods, and sedentary activities), and (3) self-awareness (e.g., self-referential processing and awareness of physical sensations due to CVD risk factors). Understanding mechanisms and theoretical framework should improve etiologic knowledge, providing customized mindfulness intervention targets that could enable greater mindfulness intervention efficacy. C1 [Loucks, Eric B.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02906 USA. [Schuman-Olivier, Zev; Desbordes, Gaelle] Harvard Univ, Sch Med, Boston, MA USA. [Schuman-Olivier, Zev] Cambridge Hlth Alliance, Cambridge, MA USA. [Britton, Willoughby B.] Brown Univ, Sch Publ Hlth, Dept Behav & Social Sci, Providence, RI 02906 USA. [Britton, Willoughby B.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Fresco, David M.] Kent State Univ, Dept Psychol Sci, Kent, OH 44242 USA. [Desbordes, Gaelle] Massachussetts Gen Hosp, Boston, MA USA. [Brewer, Judson A.] Univ Massachusetts, Dept Med, Worcester, MA 01605 USA. [Brewer, Judson A.; Fulwiler, Carl] Univ Massachusetts, Dept Psychiat, Worcester, MA 01605 USA. RP Loucks, EB (reprint author), Brown Univ, Sch Publ Hlth, Dept Epidemiol, 121 South Main St, Providence, RI 02906 USA. EM eric.loucks@brown.edu OI Fresco, David/0000-0001-6736-3912 FU National Institutes of Health (NIH) [UH2AT009145]; National Center for Complementary and Integrative Health (NCCIH); Office of Behavioral and Social Sciences Research (OBSSR) FX This publication was supported by grant number UH2AT009145 from the National Institutes of Health (NIH), specifically the National Center for Complementary and Integrative Health (NCCIH) and the Office of Behavioral and Social Sciences Research (OBSSR). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCIH, OBSSR, or the NIH. NR 134 TC 3 Z9 3 U1 17 U2 42 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD DEC PY 2015 VL 17 IS 12 AR 112 DI 10.1007/s11886-015-0668-7 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA0II UT WOS:000367480400007 PM 26482755 ER PT J AU Gencer, ZK Saydam, L Cohen, NA Cingi, C AF Gencer, Zeliha Kapusuz Saydam, Levent Cohen, Noam A. Cingi, Cemal TI N-acetylcysteine effects on sinonasal cilia function SO ENT UPDATES LA English DT Article DE N-acetylcysteine; sinonasal; cilia ID AIRWAY EPITHELIAL-CELLS; SURFACE LIQUID VOLUME; S-NITROSOGLUTATHIONE; CYSTIC-FIBROSIS; BEAT AB Objective: To evaluate the pharmacological effects of the N-acetylcysteine (NAC) on human respiratory epithelial cultures specifically addressing electrolyte transport and cilia beat frequency. 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 NAC. The best NAC concentration for ideal cilia beat frequency was found. The effects of NAC were evaluated on cilia beat frequency. After the effect of N-acetylcysteine on beat rate was found, its efficiency was investigated by ATP or IBMX to understand its mechanism of action. Changes in ciliary beat frequency were determined using the Sissons-Ammons video analysis system. Results: Maximal stimulatory effect on cilia function was evident at 10 mg/ml NAC concentration. After wash up, cilia movement were increased very dramatically. This increase of cilia beat frequency was even higher after NAC plus IBMX and NAC plus ATP washings. Conclusion: Apical application of NAC prominently stimulates cilia beat frequency and after wash up, cilia movement was increased very dramatically. After NAC use by washing with PBS in clinical efficacy can be enhanced. C1 [Gencer, Zeliha Kapusuz; Saydam, Levent] Univ Bozok, Dept Otorhinolaryngol Head & Neck Surg, Yozgat, Turkey. [Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. [Cingi, Cemal] Osmangazi Univ, Dept Otorhinolaryngol Head & Neck Surg, Eskisehir, Turkey. RP Gencer, ZK (reprint author), Univ Bozok, Dept Otorhinolaryngol Head & Neck Surg, Yozgat, Turkey. EM drzeliha19@hotmail.com NR 18 TC 0 Z9 0 U1 0 U2 0 PU DEOMED PUBL, ISTANBUL PI ISTANBUL PA GUR SOK 7-B, FIKIRTEPE 34720 KADIKOY, ISTANBUL, 00000, TURKEY SN 2149-7109 EI 2149-6498 J9 ENT UPDATES JI ENT Updates PD DEC PY 2015 VL 5 IS 3 BP 87 EP 92 DI 10.2399/jmu.2015003002 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA CZ8UJ UT WOS:000367374300001 ER PT J AU Gow, BJ Peng, CK Wayne, PM Ahn, AC AF Gow, Brian J. Peng, Chung-Kang Wayne, Peter M. Ahn, Andrew C. TI Multiscale Entropy Analysis of Center-of-Pressure Dynamics in Human Postural Control: Methodological Considerations SO ENTROPY LA English DT Review DE multiscale entropy; sample entropy; methodological; center of pressure; systematic review ID TIME-SERIES ANALYSIS; SAMPLE ENTROPY; OLDER-ADULTS; APPROXIMATE ENTROPY; COMPLEXITY; BALANCE; SIGNAL; STIMULATION; DEGRADATION; VARIABILITY AB Multiscale entropy (MSE) is a widely used metric for characterizing the nonlinear dynamics of physiological processes. Significant variability, however, exists in the methodological approaches to MSE which may ultimately impact results and their interpretations. Using publications focused on balance-related center of pressure (COP) dynamics, we highlight sources of methodological heterogeneity that can impact study findings. Seventeen studies were systematically identified that employed MSE for characterizing COP displacement dynamics. We identified five key methodological procedures that varied significantly between studies: (1) data length; (2) frequencies of the COP dynamics analyzed; (3) sampling rate; (4) point matching tolerance and sequence length; and (5) filtering of displacement changes from drifts, fidgets, and shifts. We discuss strengths and limitations of the various approaches employed and supply flowcharts to assist in the decision making process regarding each of these procedures. Our guidelines are intended to more broadly inform the design and analysis of future studies employing MSE for continuous time series, such as COP. C1 [Gow, Brian J.; Wayne, Peter M.] Harvard Univ, Brigham & Womens Hosp, Osher Ctr Integrat Med, Sch Med, Boston, MA 02215 USA. [Peng, Chung-Kang] Harvard Univ, Div Interdisciplinary Med & Biotechnol, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ahn, Andrew C.] Harvard Univ, Div Gen Med & Primary Care, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. [Ahn, Andrew C.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Ahn, AC (reprint author), Harvard Univ, Div Gen Med & Primary Care, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave, Boston, MA 02115 USA. EM bgow@partners.org; cpeng@bidmc.harvard.edu; pwayne@partners.org; aahn1@mgh.harvard.edu FU National Center for Complementary and Alternative Medicine (NCCAM): at the National Institutes of Health (NIH) [R21 AT005501-01A1]; National Center for Research Resources (NCRR) [UL1 RR025758]; Ministry of Science and Technology of Taiwan [NSC 102-2911-I-008-001] FX The authors thank Madalena D. Costa for helpful discussions regarding nonstationarities which led to the idea for computing sample entropy with an r value dependent on the time series' local (windowed) standard deviation. Andrew Ahn's work was made possible through the generous support from The Institute for Integrative Health. Peter Wayne and Brian Gow's work was made possible by grant number R21 AT005501-01A1 from the National Center for Complementary and Alternative Medicine (NCCAM: http://nccam.nih.gov/) at the National Institutes of Health (NIH: http://www.nih.gov/), and from grant number UL1 RR025758 supporting the Harvard Clinical and Translational Science Center, from the National Center for Research Resources (NCRR: http://www.nih.gov/about/almanac/organization/NCRR.htm). Chung-Kang Peng's work was supported by grant (NSC 102-2911-I-008-001) from the Ministry of Science and Technology of Taiwan. NR 45 TC 2 Z9 2 U1 3 U2 14 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1099-4300 J9 ENTROPY-SWITZ JI Entropy PD DEC PY 2015 VL 17 IS 12 BP 7926 EP 7947 DI 10.3390/e17127849 PG 22 WC Physics, Multidisciplinary SC Physics GA CZ9UX UT WOS:000367443600006 ER PT J AU Schure, MB Conte, KP Goins, RT AF Schure, Marc B. Conte, Kathleen P. Goins, R. Turner TI Unmet Assistance Need Among Older American Indians: The Native Elder Care Study SO GERONTOLOGIST LA English DT Article DE American Indians; Functional disability; Unmet assistance need; Social support ID PERSONAL ASSISTANCE; ADULTS; DISABILITY; HEALTH; CONSEQUENCES; IMPUTATION; MORTALITY; HELP AB Purpose: We examined the prevalence and correlates of unmet assistance need with respect to activities of daily living (ADLs) and instrumental activities of daily living (IADLs) among older American Indians. Design and Methods: Data for our analyses were collected in 2006-2008 as part of the Native Elder Care Study, a cross-sectional study of community-dwelling American Indians aged >= 55 years. In-person interviewer-administered surveys were used to collect data on demographic characteristics, physical functioning, mental and physical health, personal assistance needs, and psychosocial resources. Results: Among those with an assistance need, 47.8% reported an unmet need with one or more ADLs or IADLs. Significant adjusted correlates of unmet assistance need included greater number of ADL and IADL difficulties and lower levels of social support. Implications: Initiatives and programs aimed at increasing social support and augmenting informal care networks can support efforts to meet American Indian adults' personal assistance needs. C1 [Schure, Marc B.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Conte, Kathleen P.] Oregon State Univ, Sch Social & Behav Hlth Sci, Corvallis, OR 97331 USA. [Goins, R. Turner] Western Carolina Univ, Coll Hlth & Human Sci, Dept Social Work, Cullowhee, NC 28723 USA. RP Schure, MB (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Mark.Schure@va.gov RI Conte, Kathleen/G-8348-2016 OI Conte, Kathleen/0000-0002-5429-429X FU National Institute on Aging [AG022336] FX The authors receive support by award AG022336 from the National Institute on Aging. NR 35 TC 0 Z9 0 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 2015 VL 55 IS 6 BP 920 EP 928 DI 10.1093/geront/gnt211 PG 9 WC Gerontology SC Geriatrics & Gerontology GA CZ9XX UT WOS:000367452300005 PM 24451895 ER PT J AU Kujawa, SG Liberman, MC AF Kujawa, Sharon G. Liberman, M. Charles TI Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss SO HEARING RESEARCH LA English DT Article ID AUDITORY-NERVE FIBERS; HAIR CELL LOSS; SPIRAL GANGLION NEURONS; GUINEA-PIG; MAMMALIAN COCHLEA; BRAIN-STEM; INNER-EAR; OLIVOCOCHLEAR EFFERENTS; AFFERENT SYNAPSES; GLUTAMATE SYNAPSE AB The classic view of sensorineural hearing loss (SNHL) is that the "primary" targets are hair cells, and that cochlear-nerve loss is "secondary" to hair cell degeneration. Our recent work in mouse and guinea pig has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of cochlear-nerve/hair-cell synapses. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained hidden for three reasons: 1) the spiral ganglion cells, the cochlear neural elements commonly assessed in studies of SNHL, survive for years despite loss of synaptic connection with hair cells, 2) the synaptic terminals of cochlear nerve fibers are unmyelinated and difficult to see in the light microscope, and 3) the degeneration is selective for cochlear-nerve fibers with high thresholds. Although not required for threshold detection in quiet (e.g. threshold audiometry or auditory brainstem response threshold), these high-threshold fibers are critical for hearing in noisy environments. Our research suggests that 1) primary neural degeneration is an important contributor to the perceptual handicap in SNHL, and 2) in cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from spiral ganglion neurons and re-establishment of their peripheral synapses. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kujawa, Sharon G.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kujawa, Sharon G.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Kujawa, Sharon G.] Massachusetts Eye & Ear, Dept Audiol, Boston, MA USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM Charles_Liberman@meei.harvard.edu FU NIH [R01 DC0188, R01 DC08577, P30 DC 05209] FX Research supported by grants from the NIH including R01 DC0188, R01 DC08577 and P30 DC 05209. NR 101 TC 52 Z9 52 U1 11 U2 24 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 DEC PY 2015 VL 330 SI SI BP 191 EP 199 DI 10.1016/j.heares.2015.02.009 PN B PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA DA0MW UT WOS:000367492200005 PM 25769437 ER PT J AU Diercks, GR Hartnick, CJ Bates, SV AF Diercks, Gillian R. Hartnick, Christopher J. Bates, Sara V. TI Management of the critical airway when an EXIT procedure is not an option: A case report SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Congenital lymphovascular malformations; Airway; Ex utero intrapartum therapy ID UTERO INTRAPARTUM TREATMENT; OBSTRUCTION; DIAGNOSIS; NECK; HEAD AB Perinatal imaging facilitates detection of congenital head and neck masses to plan fetal procedures which secure the airway. Ex utero intrapartum therapy (EXIT) procedures are preferred to protect the neonatal airway. Herein we present a case in which a neonate with a large oropharyngeal lymphovascular malformation was delivered and the airway successfully managed without an EXIT procedure using a multidisciplinary approach. Preparations for the non-EXIT delivery and critical airway management are described. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Diercks, Gillian R.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Diercks, Gillian R.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Bates, Sara V.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Bates, Sara V.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 21 TC 0 Z9 1 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD DEC PY 2015 VL 79 IS 12 BP 2433 EP 2437 DI 10.1016/j.ijporl.2015.08.044 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA CZ9IM UT WOS:000367411300086 PM 26429602 ER PT J AU Diercks, GR Cunnane, MB Hartnick, CJ AF Diercks, Gillian R. Cunnane, Mary Beth Hartnick, Christopher J. TI Laryngeal mask airway may result in false negative imaging for carotid medialization: A case report SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE DiGeorge syndrome; Velocardiofacial syndrome; Carotid medialization; Velopharyngeal insufficiency; Pharyngeal flap; Laryngeal mask airway ID ARTERY; CHILDREN AB Chromosome 22q11.2 microdeletions result in multiple congenital abnormalities, including an increased risk of carotid medialization, which is an important consideration for preoperative planning in children with velopharyngeal insufficiency. Preoperative imaging of the neck vasculature is recommended. Here we describe a case in which a child had negative imaging studies despite the presence of a medialized carotid artery on physical examination, likely secondary to the supraglottic airway use during sedated imaging, which displaced the carotid laterally. The type of airway used should be a consideration for children undergoing sedated imaging prior to pharyngeal procedures. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Diercks, Gillian R.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Diercks, Gillian R.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Cunnane, Mary Beth] Massachusetts Eye & Ear Infirm, Dept Neuroradiol, Boston, MA 02114 USA. [Cunnane, Mary Beth] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cunnane, Mary Beth] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Diercks, GR (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM gillian_diercks@meel.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD DEC PY 2015 VL 79 IS 12 BP 2453 EP 2455 DI 10.1016/j.ijporl.2015.09.044 PG 3 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA CZ9IM UT WOS:000367411300091 PM 26482069 ER PT J AU Raol, N Diercks, G Hersh, C Hartnick, CJ AF Raol, Nikhila Diercks, Gillian Hersh, Cheryl Hartnick, Christopher J. TI Stress velopharyngeal incompetence: Two case reports and options for diagnosis and management SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Velopharyngeal incompetence; VPI; Stress VPI; Speech disorder ID CLEFT-PALATE; INSUFFICIENCY; PREVALENCE AB Stress velopharyngeal incompetence (SVPI) commonly affects brass and wind musicians. We present a series of two patients who presented with nasal air emission following prolonged woodwind instrument practice. Neither patient demonstrated audible nasal air emission during speech, but endoscopy revealed localized air escape/bubbling from different sites for each patient with instrument playing only. Both underwent tailored surgical treatment with resolution of symptoms during performance. Diagnosis of SVPI requires examination during the action that induces VPI to allow for directed management. Treatment should be targeted based on nasopharyngoscopy findings. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Raol, Nikhila; Diercks, Gillian; Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Hersh, Cheryl] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Speech Language Pathol, Boston, MA USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Christopher_hartnick@meei.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD DEC PY 2015 VL 79 IS 12 BP 2456 EP 2459 DI 10.1016/j.ijporl.2015.10.013 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA CZ9IM UT WOS:000367411300092 PM 26531005 ER PT J AU Lahey, LJ Panas, MW Mao, R Delanoy, M Flanagan, JJ Binder, SR Rebman, AW Montoya, JG Soloski, MJ Steere, AC Dattwyler, RJ Arnaboldi, PM Aucott, JN Robinson, WH AF Lahey, Lauren J. Panas, Michael W. Mao, Rong Delanoy, Michelle Flanagan, John J. Binder, Steven R. Rebman, Alison W. Montoya, Jose G. Soloski, Mark J. Steere, Allen C. Dattwyler, Raymond J. Arnaboldi, Paul M. Aucott, John N. Robinson, William H. TI Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ANTIBIOTIC-TREATMENT; ANTIBODY-RESPONSES; ERYTHEMA MIGRANS; PROTEINS; DIAGNOSIS; IDENTIFICATION; SERODIAGNOSIS; EPITOPES; DURATION; AMERICA AB The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease. C1 [Lahey, Lauren J.; Mao, Rong; Robinson, William H.] Vet Affairs Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA 94304 USA. [Lahey, Lauren J.; Mao, Rong; Robinson, William H.] Stanford Univ, Dept Med, Div Rheumatol & Immunol, Sch Med, Stanford, CA 94305 USA. [Panas, Michael W.] Stanford Univ, Dept Med, Div Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. [Delanoy, Michelle; Flanagan, John J.; Binder, Steven R.] Biorad Labs, Hercules, CA USA. [Rebman, Alison W.; Soloski, Mark J.; Aucott, John N.] Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21205 USA. [Montoya, Jose G.] Stanford Univ, Sch Med, Dept Med, Div Infect Dis & Geog Med, Palo Alto, CA 94304 USA. [Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA. [Dattwyler, Raymond J.; Arnaboldi, Paul M.] Biopeptides Corp, East Setauket, NY USA. [Dattwyler, Raymond J.; Arnaboldi, Paul M.] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA. RP Robinson, WH (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA 94304 USA. EM wrobins@stanford.edu OI Binder, Steven/0000-0003-4091-2090; Dattwyler, Raymond/0000-0002-1983-1301; Arnaboldi, Paul/0000-0002-4005-4412 FU Biopeptides Corp; Gordon and Lulie Gund Foundation; Lyme Research Alliance; Lyme Disease Research Foundation, Inc.; National Institute of Arthritis And Musculoskeletal And Skin Diseases of the National Institutes of Health [P30AR053503]; Brennan Family FX M.D., J.J.F., and S.R.B. are employees of Bio-Rad Laboratories. R.J.D. is a shareholder in Biopeptides, Corp. P.M.A. has a research appointment with Biopeptides Corp. Bio-Rad provided test materials, including microspheres and buffers, for this study. Bio-Rad and Biopeptides did not perform the data analyses or interpretation described in this report. Raw data were shared with Bio-Rad. Some of the OspC constructs are protected under U.S. patent number 7582304, and the peptides described in this study are protected under U.S. patent number 7887815 and U.S. provisional patent application no. 61/705,344. These patents could serve as a future source of funding for Biopeptides Corp.; This work was supported by funding by the Gordon and Lulie Gund Foundation, the Lyme Research Alliance (www.lymeresearchalliance.org), the Lyme Disease Research Foundation, Inc. (www.lymemd.org), the National Institute of Arthritis And Musculoskeletal And Skin Diseases of the National Institutes of Health (award number P30AR053503), and the Brennan Family. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. NR 44 TC 3 Z9 3 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2015 VL 53 IS 12 BP 3834 EP 3841 DI 10.1128/JCM.02111-15 PG 8 WC Microbiology SC Microbiology GA DA1CB UT WOS:000367532800020 PM 26447113 ER PT J AU Schofield, H Loewenstein, G Kopsic, J Volpp, KG AF Schofield, Heather Loewenstein, George Kopsic, Jessica Volpp, Kevin G. TI Comparing the effectiveness of individualistic, altruistic, and competitive incentives in motivating completion of mental exercises SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Cognitive exercises; Incentives; Social incentives; Behavioral economics; Health behaviors ID RANDOMIZED CONTROLLED-TRIAL; FINANCIAL INCENTIVES; OLDER-ADULTS; SMOKING-CESSATION; DESIGN AB This study examines the impact of individually oriented, purely altruistic, and a hybrid of competitive and cooperative monetary reward incentives on older adults' completion of cognitive exercises and cognitive function. We find that all three incentive structures approximately double the number of exercises completed during the six-week active experimental period relative to a no incentive control condition. However, the altruistic and cooperative/competitive incentives led to different patterns of participation, with significantly higher inter-partner correlations in utilization of the software, as well as greater persistence once incentives were removed. Provision of all incentives significantly improved performance on the incentivized exercises. However, results of an independent cognitive testing battery suggest no generalizable gains in cognitive function resulted from the training. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Schofield, Heather] Harvard Univ, Littauer Ctr, Dept Econ, Cambridge, MA 02138 USA. [Loewenstein, George; Kopsic, Jessica] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. [Volpp, Kevin G.] Univ Penn, Perelman Sch Med, LDI Ctr Hlth Incent & Behav Econ, CHERP,Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Schofield, H (reprint author), Univ Penn, Perelman Sch Med, 1102 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM hschof@upenn.edu; gl20@andrew.cmu.edu; jessica.kopsic@gmail.com; volpp70@mail.med.upenn.edu FU Pennsylvania Department of Health's Commonwealth Universal Research Enhancement Program; NIA FX We gratefully acknowledge financial support from the Pennsylvania Department of Health's Commonwealth Universal Research Enhancement Program and the NIA-funded joint Penn/CMU Roybal P30 Center on Behavioral Economics and Health. We also thank Lumosity and Neurotrax for generously allowing us to use their software, Matt Thompson for his outstanding website development, and Ben Cowan and ASHEcon conference participants for helpful comments. All errors are our own. NR 46 TC 1 Z9 1 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 EI 1879-1646 J9 J HEALTH ECON JI J. Health Econ. PD DEC PY 2015 VL 44 BP 286 EP 299 DI 10.1016/j.jhealeco.2015.09.007 PG 14 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CZ9HI UT WOS:000367408200020 PM 26595894 ER PT J AU Fu, LW Wei, CC Powell, PC Bradley, WE Collawn, JF Dell'Italia, LJ AF Fu, Lianwu Wei, Chih-Chang Powell, Pamela C. Bradley, Wayne E. Collawn, James F. Dell'Italia, Louis J. TI Volume overload induces autophagic degradation of procollagen in cardiac fibroblasts SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Volume overload; Cardiac fibroblast; Oxidative stress; Autophagy; Intracellular procollagen; Matrix metalloproteinase ID MATRIX-METALLOPROTEINASE ACTIVITY; OXIDATIVE STRESS; MITRAL REGURGITATION; HEART-FAILURE; MYOCARDIAL-INFARCTION; EXTRACELLULAR-MATRIX; COLLAGEN PRODUCTION; MITOCHONDRIA; INFLAMMATION; BRADYKININ AB In a pure volume overloaded (VO) heart, interstitial collagen loss is degraded by matrix metalloproteinases (MMPs) that leads to left ventricular (LV) dilatation and heart failure. Cardiac fibroblasts are the primary source of extracellular matrix proteins that connect cardiomyocytes. The goal of this study was to determine how VO affects intracellular procollagen in cardiac fibroblasts. Using the aortocaval fistula (ACF) model in Sprague-Dawley rats, we demonstrate that cardiac fibroblasts isolated from 4 and 12 wk ACF animals have decreased intracellular procollagen I compared to the fibroblasts from age-matched shams. The reduction of procollagen I is associated with increased autophagy as demonstrated by increased autophagic vacuoles and LC3-II expression. To test the relationship between autophagy and procollagen degradation, we treated adult cardiac fibroblasts with either an autophagy inducer, rapamycin, or an inhibitor, wortmannin, and found that procollagen I protein levels were decreased in fibroblasts treated with rapamycin and elevated in wortmannin-treated cells. In addition, we demonstrated that VO induces oxidative stresses in cardiac fibroblasts from 4 and 12 wk ACF rats. Treatment of cultured cardiac fibroblasts with an oxidative stress-inducing agent (DMNQ) induces autophagy and intracellular procollagen I and fibronectin degradation, which is reversed by wortmannin but not by the global MMP inhibitor (PD166793). Mechanical stretch of cardiac fibroblasts also induces oxidative stress and autophagic degradation of procollagen I and fibronectin. Our results suggest that in addition to the well-known effects of MMPs on extracellular collagen degradation in VO, there is a concurrent degradation of intracellular procollagen and fibronectin mediated by oxidative stress-induced autophagy in cardiac fibroblasts. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Fu, Lianwu; Collawn, James F.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA. [Wei, Chih-Chang; Powell, Pamela C.; Dell'Italia, Louis J.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Wei, Chih-Chang; Bradley, Wayne E.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Wei, CC (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham VA Med Ctr, 901 19th St South, Birmingham, AL 35294 USA. EM chih@uab.edu; louis.dellitalia@va.gov FU Department of Veteran Affairs for Merit Review [1BX001050-01, 1CX000993-01]; NIH [P01 HL051952] FX This work was supported by grants from Department of Veteran Affairs for Merit Review (Grant 1BX001050-01 to C.C.W. and Grant 1CX000993-01 to L.J.D.) and NIH (Grant P01 HL051952 to L.J.D). NR 34 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 2015 VL 89 BP 241 EP 250 DI 10.1016/j.yjmcc.2015.10.027 PN B PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CZ9KV UT WOS:000367417400017 PM 26596413 ER PT J AU Agsten, M Hessler, S Lehnert, S Volk, T Rittger, A Hartmann, S Raab, C Kim, DY Groemer, TW Schwake, M Alzheimer, C Huth, T AF Agsten, Marianne Hessler, Sabine Lehnert, Sandra Volk, Tilmann Rittger, Andrea Hartmann, Stephanie Raab, Christian Kim, Doo Yeon Groemer, Teja W. Schwake, Michael Alzheimer, Christian Huth, Tobias TI BACE1 modulates gating of KCNQ1 (Kv7.1) and cardiac delayed rectifier KCNQ1/KCNE1 (I-Ks) SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE KCNQ1; KCNE1; Kv7.1; BACE1; I-Ks; Cardiomyocytes ID AMYLOID PRECURSOR PROTEIN; GATED POTASSIUM CHANNELS; BETA-SECRETASE BACE1; ALZHEIMERS-DISEASE; NEURONAL-ACTIVITY; SODIUM-CHANNELS; ENZYME BACE1; SUBUNITS; KVLQT1; KCNE1 AB KCNQ1 (Kv7.1) proteins form a homotetrameric channel, which produces a voltage-dependent K+ current. Co-assembly of KCNQ1 with the auxiliary beta-subunit KCNE1 strongly up-regulates this current In cardiac myocytes, KCNQ1/E1 complexes are thought to give rise to the delayed rectifier current I-Ks, which contributes to cardiac action potential repolarization. We report here that the type I membrane protein BACE1 (beta-site APP-cleaving enzyme 1), which is best known for its detrimental role in Alzheimer's disease, but is also, as reported here, present in cardiac myocytes, serves as a novel interaction partner of KCNQ1. Using HEK293T cells as heterologous expression system to study the electrophysiological effects of BACE1 and KCNE1 on KCNQ1 in different combinations, our main findings were the following: (1) BACE1 slowed the inactivation of KCNQ1 current producing an increased initial response to depolarizing voltage steps. (2) Activation kinetics of KCNQ1/E1 currents were significantly slowed in the presence of co-expressed BACE1. (3) BACE1 impaired reconstituted cardiac I-Ks when cardiac action potentials were used as voltage commands, but interestingly augmented the I-Ks of ATP-deprived cells, suggesting that the effect of BACE1 depends on the metabolic state of the cell. (4) The electrophysiological effects of BACE1 on KCNQ1 reported here were independent of its enzymatic activity, as they were preserved when the proteolytically inactive variant BACE1 D289N was co-transfected in lieu of BACE1 or when BACE1-expressing cells were treated with the BACE1-inhibiting compound C3. (5) Co-immunoprecipitation and fluorescence recovery after photobleaching (FRAP) supported our hypothesis that BACE1 modifies the biophysical properties of I-Ks by physically interacting with KCNQ1 in a beta-subunit-like fashion. Strongly underscoring the functional significance of this interaction, we detected BACE1 in human iPSC-derived cardiomyocytes and murine cardiac tissue and observed decreased I-Ks in atrial cardiomyocytes of BACE1-deficient mice. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Agsten, Marianne; Hessler, Sabine; Lehnert, Sandra; Hartmann, Stephanie; Alzheimer, Christian; Huth, Tobias] Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, D-91054 Erlangen, Germany. [Volk, Tilmann] Univ Erlangen Nurnberg, Inst Zellulare & Mol Physiol, D-91054 Erlangen, Germany. [Rittger, Andrea; Raab, Christian; Schwake, Michael] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany. [Kim, Doo Yeon] Harvard Univ, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Groemer, Teja W.] Univ Hosp, Dept Psychiat & Psychotherapy, D-91054 Erlangen, Germany. [Schwake, Michael] Univ Bielefeld, Biochem 3, Fak Chem, D-33501 Bielefeld, Germany. RP Huth, T (reprint author), Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, Univ Str 17, D-91054 Erlangen, Germany. EM tobias.huth@fau.de OI Huth, Tobias/0000-0002-6414-8923 FU Johannes und Frieda Marohn-Stiftung; Deutsche Forschungsgemeinschaft [INST 90/675-1]; Staedtler-Stiftung; ELAN-program of the Universitatsklinikum Erlangen; National Institute of Health [1RF1AG048080-01]; Studienstiftung des deutschen Volkes FX This work was supported by the Johannes und Frieda Marohn-Stiftung (to T.H. and C.A.), the Deutsche Forschungsgemeinschaft (INST 90/675-1 FUGG to C.A.), the Staedtler-Stiftung (to C.A.), the ELAN-program of the Universitatsklinikum Erlangen (to T.H. and T.W.G.), National Institute of Health (1RF1AG048080-01 to D.Y.K.), and Studienstiftung des deutschen Volkes (to S.L. and S.Ha.). NR 46 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 2015 VL 89 BP 335 EP 348 DI 10.1016/j.yjmcc.2015.10.006 PN B PG 14 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CZ9KV UT WOS:000367417400027 PM 26454161 ER PT J AU Steenkamp, MM Suvak, MK Dickstein, BD Shea, MT Litz, BT AF Steenkamp, Maria M. Suvak, Michael K. Dickstein, Benjamin D. Shea, M. Tracie Litz, Brett T. TI EMOTIONAL FUNCTIONING IN OBSESSIVE-COMPULSIVE PERSONALITY DISORDER: COMPARISON TO BORDERLINE PERSONALITY DISORDER AND HEALTHY CONTROLS SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID ECOLOGICAL MOMENTARY ASSESSMENT; NATIONAL EPIDEMIOLOGIC SURVEY; PSYCHIATRIC OUTPATIENTS; ANTISOCIAL PERSONALITY; AFFECTIVE INSTABILITY; COMORBIDITY; DEPRESSION; BEHAVIOR; DYSREGULATION; MALTREATMENT AB Few studies have investigated emotional functioning in obsessive-compulsive personality disorder (OCPD). To explore the nature and extent of emotion difficulties in OCPD, the authors examined four domains of self-reported emotional functioning-negative affectivity, anger, emotion regulation, and emotion expressivity-in women with OCPD and compared them to a borderline personality disorder (BPD) group and a healthy control group. Data were collected as part of a larger psychophysiological experimental study on emotion regulation and personality. Compared to healthy controls, participants with OCPD reported significantly higher levels of negative affectivity, trait anger, emotional intensity, and emotion regulation difficulties. Emotion regulation difficulties included lack of emotional clarity, nonacceptance of emotional responses, and limited access to effective emotion regulation strategies. Participants with OCPD scored similarly to participants with BPD on only one variable, namely, problems engaging in goal-directed behavior when upset. Results suggest that OCPD may be characterized by notable difficulties in several emotional domains. C1 [Steenkamp, Maria M.; Dickstein, Benjamin D.; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Steenkamp, Maria M.; Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Suvak, Michael K.] Suffolk Univ, Boston, MA 02114 USA. [Shea, M. Tracie] Vet Affairs Med Ctr, Providence, RI USA. [Shea, M. Tracie] Brown Univ, Providence, RI 02912 USA. RP Litz, BT (reprint author), VA Boston Med Ctr, 150 South Huntington Ave,13B-71, Jamaica Plain, MA 02130 USA. EM brett.litz@va.gov NR 46 TC 0 Z9 0 U1 5 U2 11 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0885-579X EI 1943-2763 J9 J PERS DISORD JI J. Pers. Disord. PD DEC PY 2015 VL 29 IS 6 BP 794 EP 808 PG 15 WC Psychiatry SC Psychiatry GA CZ7LW UT WOS:000367281900005 PM 25562536 ER PT J AU Nguyen, C Mir, O Vahidy, F Wu, TC Albright, K Boehme, A Delgado, R Savitz, S AF Claude Nguyen Mir, Osman Vahidy, Farhaan Wu, Tzu-Ching Albright, Karen Boehme, Amelia Delgado, Rigoberto Savitz, Sean TI Resource Utilization for Patients with Intracerebral Hemorrhage Transferred to a Comprehensive Stroke Center SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Stroke systems; comprehensive stroke center; hemorrhagic stroke; intracerebral hemorrhage ID INTENSIVE-CARE-UNIT; MORTALITY-RATE; IMPACT; ASSOCIATION; POPULATION; OUTCOMES; COST AB Background: As a comprehensive stroke center (CSC), we accept transfer patients with intracerebral hemorrhage (ICH) in our region. CSC guidelines mandate receipt of patients with ICH for higher level of care. We determined resource utilization of patients accepted from outside hospitals compared with patients directly arriving to our center. Methods: From our stroke registry, we compared patients with primary ICH transferred to those directly arriving to our CSC from March 2011-March 2012. We compared the proportion of patients who utilized at least one of these resources: neurointensive care unit (NICU), neurosurgical intervention, or clinical trial enrollment. Results: Among the 362 patients, 210 (58%) were transfers. Transferred patients were older, had higher median Glasgow Coma Scale scores, and lower National Institutes of Health Stroke Scale scores than directly admitted patients. Transfers had smaller median ICH volumes (20.5 cc versus 15.2 cc; P = .04) and lower ICH scores (2.1 +/- 1.4 versus 1.6 +/- 1.3; P < .01). A smaller proportion of transfers utilized CSC-specific resources compared with direct admits (P = .02). Fewer transferred patients required neurosurgical intervention or were enrolled in trials. No significant difference was found in the proportion of patients who used NICU resources, although transferred patients had a significantly lower length of stay in the NICU. Average hospital stay costs were less for transferred patients than for direct admits. Conclusions: Patients with ICH transferred to our CSC underwent fewer neurosurgical procedures and had a shorter stay in the NICU. These results were reflected in the lower per-patient costs in the transferred group. Our results raise the need to analyze cost-benefits and resource utilization of transferring patients with milder ICH. (C) 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved. C1 [Claude Nguyen; Mir, Osman; Vahidy, Farhaan; Wu, Tzu-Ching; Savitz, Sean] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA. [Albright, Karen] Birmingham VA Med Ctr, GRECC, Birmingham, AL USA. [Albright, Karen] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Boehme, Amelia] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10027 USA. [Delgado, Rigoberto] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA. RP Savitz, S (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Neurol, 6431 Fannin,MSB 7-125, Houston, TX 77030 USA. EM sean.i.savitz@uth.tmc.edu FU National Institutes of Health [5 T32 NS007412-12] FX This work was supported by National Institutes of Health Training Grant 5 T32 NS007412-12. NR 20 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD DEC PY 2015 VL 24 IS 12 BP 2866 EP 2874 DI 10.1016/j.jstrokecerebrovasdis.2015.08.023 PG 9 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CZ8ZY UT WOS:000367388800029 PM 26460244 ER PT J AU Johnson, RS Fowler, JC Sikes, KA Allen, JG Oldham, JM AF Johnson, R. Scott Fowler, J. Christopher Sikes, Kristi A. Allen, Jon G. Oldham, John M. TI Treatment of Depression in Voluntary Versus Mandated Physicians SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID INVENTORY-II; ABUSE; DISORDERS; VALIDITY; OUTCOMES; CLIENTS; DRUG AB Few if any publications discuss the effectiveness of voluntary versus mandated treatment for impaired physicians. This retrospective case-control study compared the recovery rates of physicians whose treatment was mandated or coerced by either licensure boards or employers (mandated physicians) with the rates for physicians admitted voluntarily (voluntary physicians) to the Menninger Clinic's Professionals in Crisis program from 2009 through 2012. Beck Depression Inventory (BDI)-II scores served as the primary outcome measure. At the time of admission, voluntary physicians were more depressed, but the improvement rates in the voluntary and mandated groups did not differ significantly. In addition, the two groups differed neither in rates of return to the healthy range of BDI-II scores, nor in whether BDI-II scores had decreased by at least two standard deviations by the time of discharge. These findings suggest that state physician health programs can continue to mandate physicians into treatment despite concerns that mandatory treatment may be less efficacious than voluntary treatment. C1 [Johnson, R. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Sikes, Kristi A.] Cypress Creek Hosp, Houston, TX USA. [Allen, Jon G.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Psychiat, Houston, TX 77030 USA. [Allen, Jon G.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Mental Hlth Res, Houston, TX 77030 USA. [Fowler, J. Christopher] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Oldham, John M.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Clin Affairs & Dev, Houston, TX 77030 USA. [Fowler, J. Christopher] Menninger Clin, Clin Res, Houston, TX USA. [Oldham, John M.] Menninger Clin, Houston, TX USA. RP Johnson, RS (reprint author), MGH, Law & Psychiat Serv, 1 Bowdoin Sq,10th Floor, Boston, MA 02114 USA. EM RSJohnson@mgh.harvard.edu NR 27 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 EI 1943-3662 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PD DEC 1 PY 2015 VL 43 IS 4 BP 476 EP 482 PG 7 WC Law; Psychiatry SC Government & Law; Psychiatry GA CZ9MR UT WOS:000367422200010 PM 26668225 ER PT J AU Connor, Y Tekleab, S Nandakumar, S Walls, C Tekleab, Y Husain, A Gadish, O Sabbisetti, V Kaushik, S Sehrawat, S Kulkarni, A Dvorak, H Zetter, B Edelman, ER Sengupta, S AF Connor, Yamicia Tekleab, Sarah Nandakumar, Shyama Walls, Cherelle Tekleab, Yonatan Husain, Amjad Gadish, Or Sabbisetti, Venkata Kaushik, Shelly Sehrawat, Seema Kulkarni, Ashish Dvorak, Harold Zetter, Bruce Edelman, Elazer R. Sengupta, Shiladitya TI Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype SO NATURE COMMUNICATIONS LA English DT Article ID BREAST-CANCER; TUNNELING NANOTUBES; PATHOLOGICAL ANGIOGENESIS; MEMBRANE NANOTUBES; THERAPEUTIC TARGET; GROWTH-FACTOR; METASTASIS; EXPRESSION; MICRORNAS; THERAPIES AB Metastasis is a major cause of mortality and remains a hurdle in the search for a cure for cancer. Not much is known about metastatic cancer cells and endothelial cross-talk, which occurs at multiple stages during metastasis. Here we report a dynamic regulation of the endothelium by cancer cells through the formation of nanoscale intercellular membrane bridges, which act as physical conduits for transfer of microRNAs. The communication between the tumour cell and the endothelium upregulates markers associated with pathological endothelium, which is reversed by pharmacological inhibition of these nanoscale conduits. These results lead us to define the notion of 'metastatic hijack': cancer cell-induced transformation of healthy endothelium into pathological endothelium via horizontal communication through the nanoscale conduits. Pharmacological perturbation of these nanoscale membrane bridges decreases metastatic foci in vivo. Targeting these nanoscale membrane bridges may potentially emerge as a new therapeutic opportunity in the management of metastatic cancer. C1 [Connor, Yamicia; Gadish, Or; Kulkarni, Ashish; Edelman, Elazer R.; Sengupta, Shiladitya] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Connor, Yamicia; Tekleab, Yonatan; Gadish, Or; Edelman, Elazer R.] MIT, Cambridge, MA 02139 USA. [Connor, Yamicia; Tekleab, Sarah; Nandakumar, Shyama; Walls, Cherelle; Sabbisetti, Venkata; Sehrawat, Seema; Kulkarni, Ashish; Edelman, Elazer R.; Sengupta, Shiladitya] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Connor, Yamicia; Husain, Amjad; Sabbisetti, Venkata; Kulkarni, Ashish; Dvorak, Harold; Zetter, Bruce; Edelman, Elazer R.; Sengupta, Shiladitya] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Husain, Amjad; Dvorak, Harold] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Kaushik, Shelly] India Innovat Res Ctr, New Delhi 110092, India. [Zetter, Bruce] Childrens Hosp, Program Vasc Biol, Boston, MA 02115 USA. [Zetter, Bruce] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Zetter, Bruce; Sengupta, Shiladitya] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sengupta, S (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM shiladit@mit.edu OI Nandakumar, Shyama/0000-0003-0624-3452 FU NIH, a DoD-BCRP Breakthrough Award [W81XWH-14-1-0168, 1R01CA135242-01A2]; American Lung Association Innovator Award; National Institute of General Medical Sciences [T32GM007753]; [RO1 GM49039] FX We thank Michael Oh, Navjot K. Gill, Divya Bharat, Nicki Watson, Sonya Bhatia, Halley Belt, Matthew Luchette and Shyam Nathan for help with data collection, and the Center for Nanoscale Systems at Harvard University, W.M. Keck Microscopy Facility at the Whitehead Institute and the Hematologic Neoplasia Flow Cytometry Facility at the Dana-Farber Cancer Institute. S. Sengupta is supported by NIH (1R01CA135242-01A2), a DoD-BCRP Breakthrough Award (W81XWH-14-1-0168) and an American Lung Association Innovator Award. The project described was also supported by award Number T32GM007753 from the National Institute of General Medical Sciences. ERE is supported by RO1 GM49039. NR 60 TC 5 Z9 5 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2015 VL 6 AR 8671 DI 10.1038/ncomms9671 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA1XL UT WOS:000367589000001 PM 26669454 ER PT J AU Herter, JM Grabie, N Cullere, X Azcutia, V Rosetti, F Bennett, P Herter-Sprie, GS Elyaman, W Luscinskas, FW Lichtman, AH Mayadas, TN AF Herter, Jan M. Grabie, Nir Cullere, Xavier Azcutia, Veronica Rosetti, Florencia Bennett, Paul Herter-Sprie, Grit S. Elyaman, Wassim Luscinskas, Francis W. Lichtman, Andrew H. Mayadas, Tanya N. TI AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation SO NATURE COMMUNICATIONS LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ANTIGEN-PRESENTING CELLS; CRESCENTIC GLOMERULONEPHRITIS; DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSE; MICROTUBULE DYNAMICS; PERIPHERAL-TISSUES; PROTEIN AKAP450; GOLGI-APPARATUS; LYMPH-NODES AB The mechanisms driving T cell homing to lymph nodes and migration to tissue are well described but little is known about factors that affect T cell egress from tissues. Here, we generate mice with a Tcell-specific deletion of the scaffold protein A kinase anchoring protein 9 (AKAP9) and use models of inflammatory disease to demonstrate that AKAP9 is dispensable for T cell priming and migration into tissues and lymph nodes, but is required for T cell retention in tissues. AKAP9 deficiency results in increased T cell egress to draining lymph nodes, which is associated with impaired T cell re-activation in tissues and protection from organ damage. AKAP9-deficient T cells exhibit reduced microtubule-dependent recycling of TCRs back to the cell surface and this affects antigen-dependent activation, primarily by non-classical antigen-presenting cells. Thus, AKAP9-dependent TCR trafficking drives efficient T cell re-activation and extends their retention at sites of inflammation with implications for disease pathogenesis. C1 [Herter, Jan M.; Grabie, Nir; Cullere, Xavier; Azcutia, Veronica; Rosetti, Florencia; Bennett, Paul; Luscinskas, Francis W.; Lichtman, Andrew H.; Mayadas, Tanya N.] Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. [Herter, Jan M.; Grabie, Nir; Cullere, Xavier; Azcutia, Veronica; Rosetti, Florencia; Bennett, Paul; Herter-Sprie, Grit S.; Elyaman, Wassim; Luscinskas, Francis W.; Lichtman, Andrew H.; Mayadas, Tanya N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Herter-Sprie, Grit S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Elyaman, Wassim] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA. RP Mayadas, TN (reprint author), Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM tmayadas@rics.bwh.harvard.edu RI Azcutia, Veronica/A-7704-2017 OI Azcutia, Veronica/0000-0003-2160-5175 FU NIH [NHLBI PO1 HL036028]; German Research Foundation [HE-6810/1-1, HE 6897/1-1]; Else Kroner-Fresenius-Stiftung [2014_A80] FX This work was supported by grants from the NIH (NHLBI PO1 HL036028 to T.N.M., A.H.L. and F.W.L.), German Research Foundation (HE-6810/1-1 to J.M.H. and HE 6897/1-1 to G.S.H.-S.) and the Else Kroner-Fresenius-Stiftung (2014_A80 to J.M.H.). NR 70 TC 2 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2015 VL 6 AR 10182 DI 10.1038/ncomms10182 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA1RZ UT WOS:000367574500002 PM 26680259 ER PT J AU Kasar, S Kim, J Improgo, R Tiao, G Polak, P Haradhvala, N Lawrence, MS Kiezun, A Fernandes, SM Bahl, S Sougnez, C Gabriel, S Lander, ES Kim, HT Getz, G Brown, JR AF Kasar, S. Kim, J. Improgo, R. Tiao, G. Polak, P. Haradhvala, N. Lawrence, M. S. Kiezun, A. Fernandes, S. M. Bahl, S. Sougnez, C. Gabriel, S. Lander, E. S. Kim, H. T. Getz, G. Brown, J. R. TI Whole-genome sequencing reveals activation-induced cytidine deaminase signatures during indolent chronic lymphocytic leukaemia evolution SO NATURE COMMUNICATIONS LA English DT Article ID DNA-POLYMERASE-ETA; SOMATIC HYPERMUTATION; B-CELLS; HUMAN CANCER; MUTATIONAL PROCESSES; RNA-SEQ; CLUSTERED MUTATIONS; AID; EXPRESSION; GENE AB Patients with chromosome 13q deletion or normal cytogenetics represent the majority of chronic lymphocytic leukaemia (CLL) cases, yet have relatively few driver mutations. To better understand their genomic landscape, here we perform whole-genome sequencing on a cohort of patients enriched with these cytogenetic characteristics. Mutations in known CLL drivers are seen in only 33% of this cohort, and associated with normal cytogenetics and unmutated IGHV. The most commonly mutated gene in our cohort, IGLL5, shows a mutational pattern suggestive of activation-induced cytidine deaminase (AID) activity. Unsupervised analysis of mutational signatures demonstrates the activities of canonical AID (c-AID), leading to clustered mutations near active transcriptional start sites; non-canonical AID (nc-AID), leading to genome-wide non-clustered mutations, and an ageing signature responsible for most mutations. Using mutation clonality to infer time of onset, we find that while ageing and c-AID activities are ongoing, nc-AID-associated mutations likely occur earlier in tumour evolution. C1 [Kasar, S.; Improgo, R.; Fernandes, S. M.; Brown, J. R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. [Kasar, S.; Improgo, R.; Brown, J. R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Kim, J.; Tiao, G.; Polak, P.; Haradhvala, N.; Lawrence, M. S.; Kiezun, A.; Bahl, S.; Sougnez, C.; Gabriel, S.; Lander, E. S.; Getz, G.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA. [Kim, H. T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Getz, G.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Getz, G.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Getz, G.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Getz, G (reprint author), Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA. EM gadgetz@broadinstitute.org; jennifer_brown@dfci.harvard.edu FU Melton Family Fund for CLL Research; National Human Genome Research Institute [U54HG003067]; American Cancer Society [RSG-13-002-01-CCE]; Leukemia Lymphoma Society (TRP) [6289-13] FX We thank the Melton Family Fund for CLL Research and the National Human Genome Research Institute Grant U54HG003067 for funding the whole-genome sequencing and SNP arrays, respectively. B.J.R. is a clinical scholar of the Leukemia Lymphoma Society and is supported by the American Cancer Society (RSG-13-002-01-CCE) and the Leukemia Lymphoma Society (TRP#6289-13). G.G. is the Paul C. Zamecnik, MD, Chair in Oncology at Massachusetts General Hospital. We thank the Genome Sequencing Platform and Firehose Team at the Broad Institute for their help. We also thank Drs. Nicholas Chiorazzi, Catherine Wu and Dan-Avi Landau for critical review of this manuscript and Dr. Sylvan Baca for reviewing the ChainFinder results. NR 67 TC 8 Z9 9 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2015 VL 6 AR 8866 DI 10.1038/ncomms9866 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA1WA UT WOS:000367585100001 PM 26638776 ER PT J AU Wang, ZW Dai, XP Zhong, JT Inuzuka, H Wan, LX Li, XN Wang, LX Ye, XT Sun, LK Gao, DM Zou, L Wei, WY AF Wang, Zhiwei Dai, Xiangpeng Zhong, Jiateng Inuzuka, Hiroyuki Wan, Lixin Li, Xiaoning Wang, Lixia Ye, Xiantao Sun, Liankun Gao, Daming Zou, Lee Wei, Wenyi TI SCF beta(-TRCP) promotes cell growth by targeting PR-Set7/Set8 for degradation SO NATURE COMMUNICATIONS LA English DT Article ID SCF-BETA-TRCP; HISTONE METHYLTRANSFERASE SET8; UBIQUITIN LIGASE COMPLEX; 3' UNTRANSLATED REGION; MIR-502 BINDING-SITE; DNA-DAMAGE RESPONSE; F-BOX PROTEINS; S-PHASE; DEPENDENT DEGRADATION; GENOME INTEGRITY AB The Set8/PR-Set7/KMT5a methyltransferase plays critical roles in governing transcriptional regulation, cell cycle progression and tumorigenesis. Although CRL4(Cdt2) was reported to regulate Set8 stability, deleting the PIP motif only led to partial resistance to ultravioletinduced degradation of Set8, indicating the existence of additional E3 ligase(s) controlling Set8 stability. Furthermore, it remains largely undefined how DNA damage-induced kinase cascades trigger the timely destruction of Set8 to govern tumorigenesis. Here, we report that SCF beta-TRCP earmarks Set8 for ubiquitination and degradation in a casein kinase I-dependent manner, which is activated by DNA-damaging agents. Biologically, both CRL4(Cdt2) and SCF beta-TRCP-mediated pathways contribute to ultraviolet-induced Set8 degradation to control cell cycle progression, governing the onset of DNA damage-induced checkpoints. Therefore, like many critical cell cycle regulators including p21 and Cdt1, we uncover a tight regulatory network to accurately control Set8 abundance. Our studies further suggest that aberrancies in this delicate degradation pathway might contribute to aberrant elevation of Set8 in human tumours. C1 [Wang, Zhiwei; Wang, Lixia; Ye, Xiantao] Soochow Univ, Affiliated Hosp 1, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China. [Wang, Zhiwei; Wang, Lixia; Ye, Xiantao] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Collaborat Innovat Ctr Hematol, Suzhou 215123, Peoples R China. [Wang, Zhiwei; Dai, Xiangpeng; Zhong, Jiateng; Inuzuka, Hiroyuki; Wan, Lixin; Li, Xiaoning; Gao, Daming; Wei, Wenyi] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Zhong, Jiateng] Xinxiang Med Univ, Dept Pathol, Xinxiang 453000, Peoples R China. [Li, Xiaoning; Sun, Liankun] Jilin Univ, Basic Med Coll, Dept Pathophysiol, Changchun 130021, Peoples R China. [Gao, Daming] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China. [Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Canc Ctr, Boston, MA 02129 USA. RP Wang, ZW (reprint author), Soochow Univ, Affiliated Hosp 1, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China. EM zwwang@suda.edu.cn; wwei2@bidmc.harvard.edu FU NIH [GM094777, CA177910]; NSFC [81172087, 81572936]; priority academic program development of Jiangsu higher education institutions; NIH T32 training grant [5T32HL007893-18]; [AG041218] FX This work was supported in part by the NIH grants to W.W. (GM094777 and CA177910). W.W. is an ACS research scholar and a LLS research scholar. This work was also supported by grant from NSFC (81172087, 81572936) and the priority academic program development of Jiangsu higher education institutions. H.I. is supported by AG041218 and X.D. is supported by NIH T32 training grant 5T32HL007893-18. NR 48 TC 5 Z9 5 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2015 VL 6 AR 10185 DI 10.1038/ncomms10185 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA1SE UT WOS:000367575000001 PM 26666832 ER PT J AU Ding, Y Hazle, JD Mohamed, ASR Frank, SJ Hobbs, BP Colen, RR Gunn, GB Wang, JH Kalpathy-Cramer, J Garden, AS Lai, SY Rosenthal, DI Fuller, CD AF Ding, Yao Hazle, John D. Mohamed, Abdallah S. R. Frank, Steven J. Hobbs, Brian P. Colen, Rivka R. Gunn, G. Brandon Wang, Jihong Kalpathy-Cramer, Jayashree Garden, Adam S. Lai, Stephen Y. Rosenthal, David I. Fuller, Clifton D. TI Intravoxel incoherent motion imaging kinetics during chemoradiotherapy for human papillomavirus-associated squamous cell carcinoma of the oropharynx: preliminary results from a prospective pilot study SO NMR IN BIOMEDICINE LA English DT Article DE intravoxel incoherent motion imaging; HPV-associated oropharyngeal cancer; chemoradiotherapy; response assessment ID DIFFUSION-WEIGHTED MRI; NECK-CANCER; RADIATION-THERAPY; GRADIENT SENSITIZATION; TREATMENT RESPONSE; HEAD; PERFUSION; TUMORS; RADIOTHERAPY; PARAMETERS AB This study aims to identify the temporal kinetics of intravoxel incoherent motion (IVIM) MRI in patients with human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma. Patients were enrolled under an Institutional Review Board (IRB)-approved protocol as part of an ongoing prospective clinical trial. All patients underwent two MRI studies: a baseline scan before chemoradiotherapy and a mid-treatment scan 3-4 weeks after treatment initiation. Parametric maps representing pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) were generated. The Mann-Whitney U-test was used to assess the temporal variation of IVIM metrics. Bayesian quadratic discriminant analysis (QDA) was used to evaluate the extent to which mid-treatment changes in IVIM metrics could be combined to predict sites that would achieve complete response (CR) in multivariate analysis. Thirty-one patients were included in the final analysis with 59 lesions. Pretreatment ADC and D values of the CR lesions (n = 19) were significantly lower than those of non-CR lesions (n = 33). Mid-treatment ADC, D and f values were significantly higher (p < 0.0001) than pretreatment values for all lesions. Each increase in normalized Delta ADC of size 0.1 yielded a 1.45-fold increase in the odds of CR (p < 0.0003), each increase in normalized Delta D of size 0.1 yielded a 1.53-fold increase in the odds of CR (p < 0.0002), and each unit increase in Delta f yielded a 2.29-fold increase in the odds of CR (p < 0.02). Combined Delta D and Delta ADC were integrated into a multivariate prediction model and attained an AUC of 0.87 (95% confidence interval: 0.79, 0.96), as well as a sensitivity of 0.63, specificity of 0.85 and accuracy of 0.78, under leave-one-out cross-validation. In conclusion, IVIM is feasible and potentially useful in the prediction and assessment of the early response of HPV+ oropharyngeal squamous cell carcinoma to chemoradiotherapy. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Ding, Yao; Mohamed, Abdallah S. R.; Frank, Steven J.; Gunn, G. Brandon; Garden, Adam S.; Rosenthal, David I.; Fuller, Clifton D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Ding, Yao; Hazle, John D.] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA. [Mohamed, Abdallah S. R.] Univ Alexandria, Dept Clin Oncol & Nucl Med, Fac Med, Alexandria, Egypt. [Hobbs, Brian P.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Colen, Rivka R.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Wang, Jihong] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kalpathy-Cramer, Jayashree] MIT, Div Hlth Sci & Technol, Charlestown, MA USA. [Lai, Stephen Y.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Fuller, Clifton D.] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX USA. RP Fuller, CD (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Unit 0097, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM cdfuller@mdanderson.org OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618; Fuller, Clifton/0000-0002-5264-3994; Mohamed, Abdallah/0000-0003-2064-7613 FU MD Anderson Institutional Research Grant Program award; Bernard W. Biedenharn Foundation; Union for International Cancer Control/American Cancer Society; National Institutes of Health/National Cancer Institute's Paul Calabresi Clinical Oncology Award Program [K12 CA088084-06]; Clinician Scientist Loan Repayment Program [L30 CA136381-02]; SWOG/Hope Foundation; Center for Advanced Biomedical Imaging/General Electric Healthcare In-Kind Award; Center for Advanced Biomedical Imaging; Center for Radiation Oncology Research of The University of Texas MD Anderson Cancer Center Technology Development Grant; Elekta AB/MD Anderson Cancer Center Department of Radiation Oncology Seed Grant; National Institutes of Health/National Cancer Institute [P30CA016672] FX YD was partially supported by an MD Anderson Institutional Research Grant Program award and the Bernard W. Biedenharn Foundation. ASRM received salary support from the Union for International Cancer Control/American Cancer Society International Fellowships for Beginning Investigators. CDF received support from the National Institutes of Health/National Cancer Institute's Paul Calabresi Clinical Oncology Award Program (K12 CA088084-06) and Clinician Scientist Loan Repayment Program (L30 CA136381-02); the SWOG/Hope Foundation's Dr Charles A. Coltman Jr Fellowship in Clinical Trials; a Center for Advanced Biomedical Imaging/General Electric Healthcare In-Kind Award; a Center for Advanced Biomedical Imaging and Center for Radiation Oncology Research of The University of Texas MD Anderson Cancer Center Technology Development Grant; and an Elekta AB/MD Anderson Cancer Center Department of Radiation Oncology Seed Grant. This work was supported in part by the National Institutes of Health/National Cancer Institute under award number P30CA016672. These funders/supporters played no role in the study design, collection, analysis or interpretation of the data, manuscript writing or the decision to submit the report for publication. NR 47 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD DEC PY 2015 VL 28 IS 12 BP 1645 EP 1654 DI 10.1002/nbm.3412 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA CZ7XX UT WOS:000367315100004 PM 26451969 ER PT J AU Yarnykh, VL Tartaglione, EV Ioannou, GN AF Yarnykh, Vasily L. Tartaglione, Erica V. Ioannou, George N. TI Fast macromolecular proton fraction mapping of the human liver in vivo for quantitative assessment of hepatic fibrosis SO NMR IN BIOMEDICINE LA English DT Article DE magnetization transfer; quantification; hepatobiliary; fibrosis; macromolecular proton fraction; biomarker ID MAGNETIC-RESONANCE ELASTOGRAPHY; SELECTIVE INVERSION-RECOVERY; DIFFUSION-WEIGHTED MRI; CROSS-RELAXATION; TRANSIENT ELASTOGRAPHY; NONINVASIVE DIAGNOSIS; WHITE-MATTER; HUMAN BRAIN; STEADY-STATE; PARAMETERS AB The macromolecular proton fraction (MPF) is a quantitative MRI parameter determining the magnetization transfer (MT) effect in tissues, and is defined as the relative amount of immobile macromolecular protons involved in magnetization exchange with mobile water protons. MPF has the potential to provide a quantitative assessment of fibrous tissue because of the intrinsically high MPF specific for collagen. The goal of this study was to investigate the relationship between histologically determined fibrosis stage and MPF in the liver parenchyma measured using a recently developed fast single-point clinically targeted MPF mapping method. Optimal saturation parameters for single-point liver MPF measurements were determined from the analysis of liver Z spectra in vivo based on the error propagation model. Sixteen patients with chronic hepatitis C viral infection underwent 3-T MRI using an optimized liver MPF mapping protocol. Fourteen patients had prior liver biopsy with histologically staged fibrosis (METAVIR scores F0-F3) and two patients had clinically diagnosed cirrhosis (score F4 was assigned). The protocol included four breath-hold three-dimensional scans with 2 x 3 x 6-mm(3) resolution and 10 transverse sections: (1) dynamic acquisition of MT-weighted and reference images; (2) dynamic acquisition of three images for variable flip angle T-1 mapping; (3) dual-echo B-0 map; and (4) actual flip angle imaging B-1 map. The average liver MPF was determined as the mode of the MPF histograms. MPF was significantly increased in patients with clinically significant fibrosis (scores F2-F4, n = 6) relative to patients with no or mild fibrosis (scores F0-F1, n = 10): 6.49 +/- 0.36% versus 5.94 +/- 0.26%, p < 0.01 (Mann-Whitney test). MPF and fibrosis scores were strongly positively correlated, with a Spearman's rank correlation coefficient of 0.80 (p < 0.001). This study demonstrates the feasibility of fast MPF mapping of the human liver in vivo and confirms the hypothesis that MPF is increased in hepatic fibrosis and associated with fibrosis stage. MPF may be useful as a non-invasive imaging biomarker of hepatic fibrosis. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Yarnykh, Vasily L.] Univ Washington, Dept Radiol, Seattle, WA 98109 USA. [Yarnykh, Vasily L.] Tomsk State Univ, Res Inst Biol & Biophys, Tomsk 634050, Russia. [Tartaglione, Erica V.; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98109 USA. RP Yarnykh, VL (reprint author), Univ Washington, Dept Radiol, Box 358050,850 Republican St,Room 255, Seattle, WA 98109 USA. EM yarnykh@u.washington.edu RI Yarnykh, Vasily/G-8757-2016; Yarnykh, Vasiliy/N-7635-2014 OI Yarnykh, Vasily/0000-0002-1583-8979; FU National Institutes of Health [R21EB016135]; University of Washington Bridge Fund; Russian Science Foundation [14-45-00040] FX The authors acknowledge financial support from the National Institutes of Health (grant R21EB016135) for software development, University of Washington Bridge Fund for data acquisition, and the Russian Science Foundation (project no. 14-45-00040) for data analysis and manuscript preparation. NR 69 TC 2 Z9 2 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD DEC PY 2015 VL 28 IS 12 BP 1716 EP 1725 DI 10.1002/nbm.3437 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA CZ7XX UT WOS:000367315100012 PM 26503401 ER PT J AU Kazak, AE Abrams, AN Banks, J Christofferson, J DiDonato, S Grootenhuis, MA Kabour, M Madan-Swain, A Patel, SK Zadeh, S Kupst, MJ AF Kazak, Anne E. Abrams, Annah N. Banks, Jaime Christofferson, Jennifer DiDonato, Stephen Grootenhuis, Martha A. Kabour, Marianne Madan-Swain, Avi Patel, Sunita K. Zadeh, Sima Kupst, Mary Jo TI Psychosocial Assessment as a Standard of Care in Pediatric Cancer SO PEDIATRIC BLOOD & CANCER LA English DT Article DE pediatric oncology; psychosocial assessment; screening; standards of care ID QUALITY-OF-LIFE; POSTTRAUMATIC STRESS SYMPTOMS; BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; CHRONIC HEALTH CONDITIONS; CHRONICALLY ILL CHILDREN; ASSESSMENT-TOOL PAT2.0; YOUNG-ADULT SURVIVORS; LONG-TERM SURVIVORS AB This paper presents the evidence for a standard of care for psychosocial assessment in pediatric cancer. An interdisciplinary group of investigators utilized EBSCO, PubMed, PsycINFO, Ovid, and Google Scholar search databases, focusing on five areas: youth/family psychosocial adjustment, family resources, family/social support, previous history/premorbid functioning, and family structure/function. Descriptive quantitative studies, systematic reviews, and meta-analyses (n = 149) were reviewed and evaluated using grading of recommendations, assessment development, and evaluation (GRADE) criteria. There is high quality evidence to support a strong recommendation for multifaceted, systematic assessments of psychosocial health care needs of youth with cancer and their families as a standard of care in pediatric oncology. (C) 2015 Wiley Periodicals, Inc. C1 [Kazak, Anne E.; Christofferson, Jennifer; DiDonato, Stephen] Nemours Childrens Hlth Syst, Ctr Healthcare Delivery Sci, Wilmington, DE USA. [Kazak, Anne E.; Christofferson, Jennifer; DiDonato, Stephen] Nemours Childrens Hlth Syst, Ctr Pediat Traumat Stress, Wilmington, DE USA. [Kazak, Anne E.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Abrams, Annah N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abrams, Annah N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Banks, Jaime] Parent Advocate, Bethesda, MD USA. [Grootenhuis, Martha A.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands. [Kabour, Marianne] Transit Profess Ctr, Portland, OR USA. [Madan-Swain, Avi] Univ Alabama Birmingham, Childrens Alabama, Birmingham, AL USA. [Patel, Sunita K.] City Hope Med Ctr, Duarte, CA USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Zadeh, Sima] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Kupst, Mary Jo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Kazak, AE (reprint author), AI Du Pont Hosp Children, Nemours Ctr Healthcare Delivery Sci, 1701 Rockland Rd,Suite 160, Wilmington, DE 19803 USA. EM anne.kazak@nemours.org FU Mattie Miracle Foundation; National Institutes of Health; Center for Pediatric Traumatic Stress [U79SM061255] FX Grant sponsor: Mattie Miracle Foundation; Grant sponsor: National Institutes of Health and the Center for Pediatric Traumatic Stress; Grant number: U79SM061255 NR 166 TC 2 Z9 2 U1 5 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 SU 5 BP S426 EP + DI 10.1002/pbc.25730 PG 34 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CZ7OZ UT WOS:000367290000003 PM 26700916 ER PT J AU Kearney, JA Salley, CG Muriel, AC AF Kearney, Julia A. Salley, Christina G. Muriel, Anna C. TI Standards of Psychosocial Care for Parents of Children With Cancer SO PEDIATRIC BLOOD & CANCER LA English DT Article DE anxiety; childhood cancer; depression; distress; intervention; mental health; parents; pediatric oncology; psychosocial ID POSTTRAUMATIC STRESS SYMPTOMS; STEM-CELL TRANSPLANTATION; QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; RANDOMIZED CLINICAL-TRIAL; NEWLY-DIAGNOSED CANCER; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MEDICAL CONDITIONS; BRAIN-TUMOR SURVIVORS; PEDIATRIC CANCER AB Parents and caregivers of children with cancer are both resilient and deeply affected by the child's cancer. A systematic review of published research since 1995 identified 138 studies of moderate quality indicating that parent distress increases around diagnosis, then returns to normal levels. Post-traumatic symptoms are common. Distress may be impairing for vulnerable parents and may impact a child's coping and adjustment. Moderate quality evidence and expert consensus informed a strong recommendation for parents and caregivers to receive early and ongoing assessment of their mental health needs with access to appropriate interventions facilitated to optimize parent, child, and family well being. (C) 2015 Wiley Periodicals, Inc. C1 [Kearney, Julia A.; Salley, Christina G.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. [Muriel, Anna C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Muriel, Anna C.] Boston Childrens Hosp, Boston, MA USA. RP Kearney, JA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA. EM kearneyj@mskcc.org OI Kearney, Julia/0000-0003-1113-9617 FU Royal Bank of Canada Foundation FX Dr. Kearney's research study assistant time was supported by funding from the Royal Bank of Canada Foundation. NR 169 TC 3 Z9 3 U1 5 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 SU 5 BP S632 EP + DI 10.1002/pbc.25761 PG 52 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CZ7OZ UT WOS:000367290000008 PM 26700921 ER PT J AU Patenaude, AF Pelletier, W Bingen, K AF Patenaude, Andrea Farkas Pelletier, Wendy Bingen, Kristin TI Communication, Documentation, and Training Standards in Pediatric Psychosocial Oncology SO PEDIATRIC BLOOD & CANCER LA English DT Article DE documentation; interdisciplinary communication; pediatric oncology; pediatric psycho-oncology; training ID PRACTICE GUIDELINES; CHILDHOOD-CANCER; CARE; ROUNDS; CHILDREN; PARENTS; RECOMMENDATIONS; FAMILIES; LIFE; COLLABORATION AB As part of a larger effort to create standards for psychosocial care of children with cancer, we document consensus and evidence-based data on interprofessional communication, documentation, and training for professionals providing psycho-oncology services. Six databases were searched. Sixty-five articles and six guidelines and consensus-based documents were identified; 35 met inclusion criteria. Data support strong recommendations for standards of care in communication/collaboration, documentation of patient information, and training in pediatric psycho-oncology. These are areas where extensive research is unlikely to be conducted; however, professional expectations and qualifications may be further clarified and strengthened with time. (C) 2015 Wiley Periodicals, Inc. C1 [Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pelletier, Wendy] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. [Bingen, Kristin] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Patenaude, AF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM andrea_patenaude@dfci.harvard.edu NR 42 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 SU 5 BP S870 EP + DI 10.1002/pbc.25725 PG 26 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CZ7OZ UT WOS:000367290000017 PM 26700930 ER PT J AU Pelletier, W Bona, K AF Pelletier, Wendy Bona, Kira TI Assessment of Financial Burden as a Standard of Care in Pediatric Oncology SO PEDIATRIC BLOOD & CANCER LA English DT Article DE pediatric oncology; psychosocial; quality of life; support care ID OF-POCKET EXPENSES; CHILDHOOD-CANCER; ECONOMIC BURDEN; FAMILIES; CHILDREN; IMPACT; COSTS; ADOLESCENTS; PARENTS; HEALTH AB Family financial hardship has emerged as a burden of pediatric cancer treatment with negative implications for family well-being. As part of an extensive project to create evidence-based standards for the psychosocial care of children with cancer, we performed a literature review of pediatric cancer-associated financial hardship utilizing six databases, and identified 24 publications for incorporation into this review. Financial hardship during childhood cancer was found to affect a significant proportion of the population and to negatively impact family well-being. Existing literature supports a strong recommendation for assessment of financial hardship as a component of comprehensive psychosocial care in pediatric oncology. (C) 2015 Wiley Periodicals, Inc. C1 [Pelletier, Wendy] Alberta Childrens Prov Gen Hosp, Pediat Hematol Oncol Transplant Program, Calgary, AB T3B 6A8, Canada. [Bona, Kira] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Bona, Kira] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Oncol, Boston, MA USA. [Bona, Kira] Harvard Univ, Sch Med, Boston, MA USA. [Bona, Kira] Dana Farber Canc Inst, Ctr Outcomes & Populat Res, Boston, MA 02115 USA. RP Pelletier, W (reprint author), Alberta Childrens Prov Gen Hosp, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. EM Wendy.Pelletier@albertahealthservices.ca FU St. Baldrick's Foundation; National Palliative Care Research Center FX Grant sponsor: St. Baldrick's Foundation; Grant sponsor: National Palliative Care Research Center NR 24 TC 4 Z9 4 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 SU 5 BP S619 EP S631 DI 10.1002/pbc.25714 PG 13 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CZ7OZ UT WOS:000367290000007 PM 26700920 ER PT J AU Steele, AC Mullins, LL Mullins, AJ Muriel, AC AF Steele, Amii C. Mullins, Larry L. Mullins, Alexandria J. Muriel, Anna C. TI Psychosocial Interventions and Therapeutic Support as a Standard of Care in Pediatric Oncology SO PEDIATRIC BLOOD & CANCER LA English DT Article DE cancer; intervention; pediatric; psychosocial; standard of care; support ID POSTTRAUMATIC STRESS SYMPTOMS; QUALITY-OF-LIFE; CHILDHOOD-CANCER SURVIVORS; NEWLY-DIAGNOSED CANCER; YOUNG-ADULT SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; RANDOMIZED CLINICAL-TRIAL; LONG-TERM SURVIVORS; BONE-MARROW-TRANSPLANTATION; ASSESSMENT-TOOL PAT2.0 AB Research indicates that a subset of youths with childhood cancer and their parents will experience significant psychological distress throughout the course of their illness. Importantly, the existing literature indicates that psychosocial support is beneficial in decreasing symptoms of distress in these families. The aim of the current review is to determine the extent of the evidence to support a standard of psychosocial care for children and their families throughout the cancer trajectory; thus, we examined the research related to psychosocial outcomes in youth with cancer and their parents. (C) 2015 Wiley Periodicals, Inc. C1 [Steele, Amii C.] Levine Childrens Hosp, Div Pediat Hematol Oncol & Blood & Marrow Transpl, Charlotte, NC 28203 USA. [Mullins, Larry L.; Mullins, Alexandria J.] Oklahoma State Univ, Dept Psychol, Stillwater, OK 74078 USA. [Muriel, Anna C.] Dana Farber Canc Inst, Dept Child Psychiat, Boston, MA 02115 USA. RP Steele, AC (reprint author), Levine Childrens Hosp, Div Pediat Hematol Oncol & Blood & Marrow Transpl, Suite 601,Med Ctr Plaza,1001 Blythe Blvd, Charlotte, NC 28203 USA. EM Amii.Steele@carolinas.org NR 185 TC 0 Z9 0 U1 4 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 SU 5 BP S585 EP + DI 10.1002/pbc.25701 PG 34 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CZ7OZ UT WOS:000367290000006 PM 26700919 ER PT J AU Weaver, MS Heinze, KE Kelly, KP Wiener, L Casey, RL Bell, CJ Wolfe, J Garee, AM Watson, A Hinds, PS AF Weaver, Meaghann S. Heinze, Katherine E. Kelly, Katherine P. Wiener, Lori Casey, Robert L. Bell, Cynthia J. Wolfe, Joanne Garee, Amy M. Watson, Anne Hinds, Pamela S. TI Palliative Care as a Standard of Care in Pediatric Oncology SO PEDIATRIC BLOOD & CANCER LA English DT Article DE communication; family-centered care; palliative care; psychosocial support; quality of life ID QUALITY-OF-LIFE; PATIENT-REPORTED OUTCOMES; YOUNG-ADULT ONCOLOGY; ADVANCED CANCER; BRAIN-TUMORS; CHILDREN; END; DEATH; PARENTS; PERSPECTIVES AB The study team conducted a systematic review of pediatric and adolescent palliative cancer care literature from 1995 to 2015 using four databases to inform development of a palliative care psychosocial standard. A total of 209 papers were reviewed with inclusion of 73 papers for final synthesis. Revealed topics of urgent consideration include the following: symptom assessment and intervention, direct patient report, effective communication, and shared decision-making. Standardization of palliative care assessments and interventions in pediatric oncology has the potential to foster improved quality of care across the cancer trajectory for children and adolescents with cancer and their family members. (C) 2015 Wiley Periodicals, Inc. C1 [Weaver, Meaghann S.] Childrens Natl Hlth Syst, Dept Oncol, Washington, DC USA. [Weaver, Meaghann S.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Heinze, Katherine E.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Kelly, Katherine P.; Hinds, Pamela S.] Childrens Natl Hlth Syst, Dept Nursing Res & Qual Outcomes, Washington, DC USA. [Wiener, Lori] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Casey, Robert L.] Univ Colorado, Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Denver, CO 80202 USA. [Bell, Cynthia J.] Wayne State Univ, Coll Nursing, Detroit, MI 48202 USA. [Bell, Cynthia J.] Hosp Michigan Inst, Detroit, MI USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Garee, Amy M.] Nationwide Childrens Hosp, Dept Oncol, Columbus, OH USA. [Watson, Anne] Childrens Natl Hlth Syst, Dept Crit Care Med, Washington, DC USA. [Hinds, Pamela S.] George Washington Univ, Dept Pediat, Washington, DC 20052 USA. RP Weaver, MS (reprint author), St Jude Childrens Res Hosp, 262 Danny Thomas Pl,MS 260, Memphis, TN 38105 USA. EM Meaghann.Weaver@StJude.org OI Bell, Cynthia/0000-0002-9026-0986 FU Intramural NIH HHS [Z99 CA999999] NR 61 TC 4 Z9 4 U1 5 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 SU 5 BP S829 EP S833 DI 10.1002/pbc.25695 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CZ7OZ UT WOS:000367290000015 PM 26700928 ER PT J AU Wiener, L Kazak, AE Noll, RB Patenaude, AF Kupst, MJ AF Wiener, Lori Kazak, Anne E. Noll, Robert B. Patenaude, Andrea Farkas Kupst, Mary Jo TI Interdisciplinary Collaboration in Standards of Psychosocial Care SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material C1 [Wiener, Lori] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kazak, Anne E.] Nemours Childrens Hlth Syst, Wilmington, DE USA. [Kazak, Anne E.] Thomas Jefferson Univ, Sidney Kimmel Med Sch, Philadelphia, PA 19107 USA. [Noll, Robert B.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. [Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kupst, Mary Jo] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Wiener, L (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 SU 5 BP S425 EP S425 DI 10.1002/pbc.25718 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CZ7OZ UT WOS:000367290000002 PM 26700915 ER PT J AU Wiener, L Kazak, AE Noll, RB Patenaude, AF Kupst, MJ AF Wiener, Lori Kazak, Anne E. Noll, Robert B. Patenaude, Andrea Farkas Kupst, Mary Jo TI Standards for the Psychosocial Care of Children With Cancer and Their Families: An Introduction to the Special Issue SO PEDIATRIC BLOOD & CANCER LA English DT Article DE cancer; child; family; pediatric; psychosocial; standards ID RECOMMENDATIONS; GUIDELINES; CONSENSUS; ONCOLOGY; GRADE AB Pediatric oncology psychosocial professionals collaborated with an interdisciplinary group of experts and stakeholders and developed evidence-based standards for pediatric psychosocial care. Given the breadth of research evidence and traditions of clinical care, 15 standards were derived. Each standard is based on a systematic review of relevant literature and used the AGREE II process to evaluate the quality of the evidence. This article describes the methods used to develop the standards and introduces the 15 articles included in this special issue. Established standards help ensure that all children with cancer and their families receive essential psychosocial care. (C) 2015 Wiley Periodicals, Inc. C1 [Wiener, Lori] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kazak, Anne E.] Thomas Jefferson Univ, Sidney Kimmel Med Sch, Nemours Childrens Hlth Syst, Philadelphia, PA 19107 USA. [Noll, Robert B.] Univ Pittsburgh, Pittsburgh, PA USA. [Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kupst, Mary Jo] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Wiener, L (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Mattie Miracle Cancer Foundation; National Cancer Institute; Center for Pediatric Traumatic Stress [5U79SM061255-03] FX Grant sponsor: Mattie Miracle Cancer Foundation; Grant sponsor: National Cancer Institute; Grant sponsor: Center for Pediatric Traumatic Stress; Grant number: 5U79SM061255-03 NR 25 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 SU 5 BP S419 EP S424 DI 10.1002/pbc.25675 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CZ7OZ UT WOS:000367290000001 PM 26397836 ER PT J AU Hasan, NS Babson, KA Banducci, AN Bonn-Miller, MO AF Hasan, Nadeem S. Babson, Kimberly A. Banducci, Anne N. Bonn-Miller, Marcel O. TI The Prospective Effects of Perceived and Laboratory Indices of Distress Tolerance on Cannabis Use Following a Self-Guided Quit Attempt SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE distress tolerance; cannabis; marijuana; veterans; cessation ID SUBSTANCE USE DISORDERS; MARIJUANA DEPENDENCE; NEGATIVE AFFECT; WITHDRAWAL; INDIVIDUALS; VALIDATION; VALIDITY; MOTIVES; ADULTS; SCALE AB The majority of individuals who attempt to quit using cannabis do not seek formalized treatment. To better understand which malleable factors contribute to cannabis use following a self-guided quit attempt, we concurrently examined 2 measures of distress tolerance (DT) as prospective predictors of cannabis use post quit attempt. We hypothesized that veterans with higher in relation to lower levels of DT would be less likely to use cannabis following a self-guided quit attempt. In this study, we included 103 cannabis-dependent veterans (M-age = 50, 95% male, 37% White, 36% Black, 14% Hispanic, 14% other) who reported being motivated to quit using cannabis. Veterans completed 2 measures of DT, the Distress Tolerance Scale (perceived distress tolerance) and the Mirror-Tracing Persistence Task (laboratory analogue of distress tolerance). Findings indicated that veterans with greater perceived distress tolerance used less cannabis over the quit period than did veterans with less perceived distress tolerance. However, contrary to expectations, baseline performance on a laboratory analogue of distress tolerance was not related to cannabis use over the quit period. Results suggest that veterans' perceived ability to tolerate distress is an important predictor of cannabis use following a self-guided quit attempt. Thus, the Distress Tolerance Scale could serve as an important tool for helping to identify veterans at risk for cannabis use postquit. C1 [Hasan, Nadeem S.] Univ Calif Los Angeles, Counseling Serv, Los Angeles, CA USA. [Hasan, Nadeem S.] Univ Calif Los Angeles, Psychol Serv, Los Angeles, CA USA. [Babson, Kimberly A.; Banducci, Anne N.; Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Bonn-Miller, Marcel O.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Bonn-Miller, Marcel O.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Babson, KA (reprint author), VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM kimberly.babson@gmail.com OI Banducci, Anne N/0000-0003-1213-7998 FU CSRD VA [IK2 CX001023] NR 36 TC 2 Z9 2 U1 3 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 2015 VL 29 IS 4 BP 933 EP 940 DI 10.1037/adb0000132 PG 8 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA DA0BE UT WOS:000367460900012 PM 26727009 ER PT J AU Kaliyaperuma, K Sharma, AK McDonald, DG Dhindsa, JS Yount, C Singh, AK Won, JS Singh, I AF Kaliyaperuma, Kolanjiappan Sharma, Anand K. McDonald, Daniel G. Dhindsa, Jasdeep S. Yount, Caroline Singh, Avtar K. Won, Je-Seong Singh, Inderjit TI S-nitrosoglutathione-mediated STAT3 regulation in efficacy of radiotherapy and cisplatin therapy in head and neck squamous cell carcinoma SO REDOX BIOLOGY LA English DT Article DE S-Nitrosoglutathione; STAT3; NF-kappa B; Head and neck cancer; Radiotherapy; Cisplatin ID NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; CANCER-CELLS; TRANSCRIPTION FACTOR; MOLECULAR TARGETS; DRUG-RESISTANCE; VEGF EXPRESSION; RAT MODEL; NITROSYLATION AB S-nitrosoglutathione (GSNO) is an endogenous nitric oxide (NO) carrier that plays a critical role in redox based NO signaling. Recent studies have reported that GSNO regulates the activities of STAT3 and NF-kappa B via S-nitrosylation dependent mechanisms. Since STAT3 and NF-kappa B are key transcription factors involved in tumor progression, chemoresistance, and metastasis of head and neck cancer, we investigated the effect of GSNO in cell culture and mouse xenograft models of head and neck squamous cell carcinoma (HNSCC). For the cell culture studies, three HNSCC cell lines were tested (SCC1, SCC14a and SCC22a). All three cell lines had constitutively activated (phosphorylated) STAT3 (Tyr(705)). GSNO treatment of these cell lines reversibly decreased the STAT3 phosphorylation in a concentration dependent manner. GSNO treatment also decreased the basal and cytokine-stimulated activation of NF-kappa B in SCC14a cells and reduced the basal low degree of nitrotyrosine by inhibition of inducible NO synthase (iNOS) expression. The reduced STAT3/NF-kappa B activity by GSNO treatment was correlated with the decreased cell proliferation and increased apoptosis of HNSCC cells. In HNSCC mouse xenograft model, the tumor growth was reduced by systemic treatment with GSNO and was further reduced when the treatment was combined with radiation and cisplatin. Accordingly, GSNO treatment also resulted in decreased levels of phosphorylated STAT3. In summary, these studies demonstrate that GSNO treatment blocks the NF-kappa B and STAT3 pathways which are responsible for cell survival, proliferation and that GSNO mediated mechanisms complement cispaltin and radiation therapy, and thus could potentiate the therapeutic effect in HNSCC. (C) 2015 Published by Elsevier B.V. C1 [Kaliyaperuma, Kolanjiappan; Sharma, Anand K.; McDonald, Daniel G.; Yount, Caroline] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Won, Je-Seong] Med Univ S Carolina, Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson Vet Adm Med Ctr, Pathol & Lab Med Serv, Charleston, SC 29401 USA. [Dhindsa, Jasdeep S.; Singh, Inderjit] Med Univ S Carolina, Pediat, Charleston, SC 29425 USA. RP Won, JS (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, Childrens Res Inst, Room 513,173 Ashley Ave, Charleston, SC 29425 USA. EM wonj@musc.edu; singhi@musc.edu FU NIH, United States [NS-37766, NS-72511]; [BX-002829]; [BX-001062] FX In part, this research was supported by grants from VA, United States (BX-002829 and BX-001062) and NIH, United States (NS-37766 and NS-72511). NR 77 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PD DEC PY 2015 VL 6 BP 41 EP 50 DI 10.1016/j.redox.2015.07.001 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CZ8GR UT WOS:000367338700005 PM 26177470 ER PT J AU Liu, R Pulliam, DA Liu, YH Salmon, AB AF Liu, Roy Pulliam, Daniel A. Liu, Yuhong Salmon, Adam B. TI Dynamic differences in oxidative stress and the regulation of metabolism with age in visceral versus subcutaneous adipose SO REDOX BIOLOGY LA English DT Article DE Fat; Mitochondria; JNK; MAPK/ERK; Pre-adipocytes; Seahorse ID TERMINAL KINASE JNK; INSULIN-RESISTANCE; HUMAN OBESITY; TISSUE; FAT; MICE; LONGEVITY; PROTEIN; IMPACT; CARBONYLATION AB Once thought only as storage for excess nutrients, adipose tissue has been shown to be a dynamic organ implicated in the regulation of many physiological processes. There is emerging evidence supporting differential roles for visceral and subcutaneous white adipose tissue in maintaining health, although how these roles are modulated by the aging process is not clear. However, the proposed beneficial effects of subcutaneous fat suggest that targeting maintenance of this tissue could lead to healthier aging. In this study, we tested whether alterations in adipose function with age might be associated with changes in oxidative stress. Using visceral and subcutaneous adipose from C57BL16 mice, we discovered effects of both age and depot location on markers of lipolysis and adipogenesis. Conversely, accumulation of oxidative damage and changes in enzymatic antioxidant expression with age were largely similar between these two depots. The activation of each of the stress signaling pathways JNK and MAPK/ERK was relatively suppressed in subcutaneous adipose tissue suggesting reduced sensitivity to oxidative stress. Similarly, pre-adipocytes from subcutaneous adipose were significantly more resistant than visceral-derived cells to cell death caused by oxidative stress. Cellular respiration in visceral-derived cells was dramatically higher than in cells derived from subcutaneous adipose despite little evidence for differences in mitochondrial density. Together, our data identify molecular mechanisms by which visceral and subcutaneous adipose differ with age and suggest potential targetable means to preserve healthy adipose aging. Published by Elsevier B.V. C1 [Liu, Roy; Pulliam, Daniel A.; Liu, Yuhong; Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Pulliam, Daniel A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Mol Med, San Antonio, TX 78245 USA. [Salmon, Adam B.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Salmon, AB (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM salmona@uthscsa.edu FU Medical Student Training in Aging Research (MSTAR) program - American Federation for Aging Research; National Institute on Aging [T35AG038048]; Geriatric Research Education and Clinical Center of the South Texas Veterans Healthcare System; American Federation for Aging Research; San Antonio Area Foundation FX R.L. was supported throughout this project as an awardee of the Medical Student Training in Aging Research (MSTAR) program supported by the American Federation for Aging Research and the National Institute on Aging (T35AG038048). This research was supported in part by the Geriatric Research Education and Clinical Center of the South Texas Veterans Healthcare System, and funding from the American Federation for Aging Research and the San Antonio Area Foundation (to A.B.S.). Mitochondrial bio-energetic assessment was performed with resources provided by the Mitochondrial Function and Oxidative Damage Core Facility of the San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging. This work was supported using facilities and resources at the Audie L. Murphy Memorial Veterans Hospital of the South Texas Veterans Health Care System. This work does not represent the views of the Department of Veterans Affairs or the United States Government. NR 41 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PD DEC PY 2015 VL 6 BP 401 EP 408 DI 10.1016/j.redox.2015.07.014 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CZ8GR UT WOS:000367338700039 PM 26355396 ER PT J AU Xu, Y Morse, LR da Silva, RAB Wang, DH Battaglino, RA AF Xu, Yan Morse, Leslie R. Bezerra da Silva, Raquel Assed Wang, Dianhua Battaglino, Ricardo A. TI A short report: PAMM, a novel antioxidant protein, induced by oxidative stress SO REDOX BIOLOGY LA English DT Article DE PAMM; Antioxidant; Oxidative stress; Bone loss; Ovariectomy ID INDUCED OSTEOCLAST DIFFERENTIATION; DEFICIENCY BONE LOSS; CRUCIAL ROLE; OVARIECTOMY; SURVIVAL; CELLS; OSTEOBLASTS; INHIBITION; PRECURSORS; MECHANISM AB Reactive oxygen species (ROS) play a central role in estrogen deficiency-induced bone loss. We previously identified and characterized a novel member of the Peroxiredoxin (PRX) like 2 family that we called PAMM: Peroxiredoxin Activated in M-CSF stimulated Monocytes, a redox regulatory protein that modulates osteoclast differentiation in vitro. In this study, we report increased PAMM expression in H2O2-treated cells and in bones from ovariectomized (OVX) mice 4 weeks after surgery, models for oxidative stress in vitro and in vivo, respectively. We also detected increased PAMM abundance and phosphorylated Akt in OVX mice treated with estrogen. In addition, Wortmannin, a specific PI3Kinase inhibitor and Rapamycin, an inhibitor of the PI3Kinase/Akt pathway, blocked Akt phosphorylation and stimulation of PAMM expression by M-CSF. These results indicate that M-CSF-induced PAMM expression is mediated by Akt phosphorylation. Our data also suggest that estrogen-induced PAMM expression is mediated by phosphorylation of Akt. These findings point to PAMM as a potential candidate for Akt-mediated protection against oxidative stress. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Xu, Yan; Morse, Leslie R.; Battaglino, Ricardo A.] Forsyth Inst, Dept Mineralized Tissue Biol, Cambridge, MA 02142 USA. [Morse, Leslie R.] Spaulding Rehabil Hosp, Spaulding Harvard SCI Model Syst, Boston, MA 02129 USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Bezerra da Silva, Raquel Assed] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Pediat Clin Prevent & Community Dent, BR-05508 Sao Paulo, Brazil. [Xu, Yan; Wang, Dianhua] Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Peoples R China. [Battaglino, Ricardo A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Battaglino, RA (reprint author), Forsyth Inst, Dept Mineralized Tissue Biol, 245 First St, Cambridge, MA 02142 USA. EM yxu@forsyth.org; leslie.morse@mgh.harvard.edu; raquel@forp.usp.br; wangdianhuakm@126.com; rbattaglino@forsyth.or RI Morse, Leslie/C-9442-2015; battaglino, ricardo/D-2892-2015; Bezerra da Silva, Raquel /M-8655-2016 OI Morse, Leslie/0000-0002-7426-6341; Bezerra da Silva, Raquel /0000-0002-0230-1347 FU National Natural Science Foundation of China [81060074] FX We would like to give our thanks to Ms. Justine Dobeck for technical assistance and Subbiah Yoganathan for expertize with animal experimentation. This study partially received support from National Natural Science Foundation of China (81060074). NR 30 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PD DEC PY 2015 VL 6 BP 446 EP 453 DI 10.1016/j.redox.2015.09.008 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CZ8GR UT WOS:000367338700044 PM 26402163 ER PT J AU Medlock, MM AF Medlock, Morgan M. TI A Light Pierces the Darkness: A Reflection on Spirituality and Suicide SO SPIRITUALITY IN CLINICAL PRACTICE LA English DT Article DE spirituality; religion; prayer; depression; suicide AB In this reflection, the author presents the case of a 48-year-old man in the throes of a major depressive episode and crisis of faith, who survives an attempt to take his own life. His Christian religion proved critical to his recovery, as the treatment team delved into spiritual issues of guilt, shame, and the meaning of life. This article reveals the author's approach to addressing spiritual distress in psychiatric patients, a valuable resource for clinicians desiring a better understanding of how to relate to individuals with strong religious backgrounds. C1 [Medlock, Morgan M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Medlock, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,McLean Hosp, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM mmmedlock@partners.org NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 2326-4500 EI 2326-4519 J9 SPIRITUAL CLIN PRACT JI Spiritual. Clin. Pract. PD DEC PY 2015 VL 2 IS 4 BP 282 EP 284 DI 10.1037/scp0000081 PG 3 WC Psychology, Clinical SC Psychology GA DA0BJ UT WOS:000367461400006 ER PT J AU Graham, JL Shahani, L Grimes, RM Hartman, C Giordano, TP AF Graham, James L. Shahani, Lokesh Grimes, Richard M. Hartman, Christine Giordano, Thomas P. TI The Influence of Trust in Physicians and Trust in the Healthcare System on Linkage, Retention, and Adherence to HIV Care SO AIDS PATIENT CARE AND STDS LA English DT Article ID UNITED-STATES; PREVENTIVE SERVICES; PATIENT; MORTALITY; PROVIDERS; INFECTION; DISPARITIES; POPULATION; BEHAVIORS; DIAGNOSIS AB Lack of trust by the patient in the physicians or the healthcare system has been associated with poorer health outcomes. The present study was designed to determine if trust in physicians and the healthcare system among persons newly diagnosed with HIV infection was predictive of patients' subsequent linkage, retention, and adherence to HIV care. 178 newly diagnosed HIV infected patients were administered the trust-in-physicians and trust-in-healthcare system scales. Median trust-in-physicians and trust-in-healthcare system scores were compared for all the mentioned subsequent linkage, retention, and adherence to HIV care. Univariate logistic regression using the trust-in-physician scale confirmed significant association with retention in care (p=0.04), which persisted in multivariate analyses (p=0.04). No significant association was found between trust-in-physicians and linkage to care or adherence to antiretroviral therapy. Trust in the healthcare system was not associated with any of the outcomes. Patients with higher trust in physicians were more likely to be retained in HIV care. Trust at diagnosis may not be a barrier to better clinical outcomes, either because trust changes based on subsequent interactions, or because trust is not a determining feature. Interventions to improve retention in care could include improving trust in physicians or target persons with low trust in physicians. C1 [Graham, James L.] Legacy Community Hlth Serv, Houston, TX USA. [Shahani, Lokesh; Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Shahani, Lokesh; Hartman, Christine; Giordano, Thomas P.] Michael E DeBakey VA Med Ctr 152, Ctr Innovat Qual Effectiveness & Safety, Houston, TX 77030 USA. [Grimes, Richard M.] Univ Texas Hlth Sci Ctr Houston, Houston Med Sch, Houston, TX 77030 USA. RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.edu FU NIMH [R34MH074360]; AHRQ [U18HS016093]; Baylor/UT Houston Center for AIDS Research Grant [P30AI036211] FX This study is supported by NIMH Grant R34MH074360, AHRQ Grant U18HS016093, the Baylor/UT Houston Center for AIDS Research Grant P30AI036211, and the facilities and resources of the Harris Health System and the Michael E. DeBakey VA Medical Center. Dr. Giordano is a researcher at the Michael E. DeBakey VA Medical Center, Houston, TX. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 35 TC 4 Z9 5 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD DEC 1 PY 2015 VL 29 IS 12 BP 661 EP 667 DI 10.1089/apc.2015.0156 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CY7QF UT WOS:000366602800006 PM 26669793 ER PT J AU Vo, KD Yoo, AJ Gupta, A Qiao, Y Vagal, AS Hirsch, JA Yousem, DM Lum, C AF Vo, K. D. Yoo, A. J. Gupta, A. Qiao, Y. Vagal, A. S. Hirsch, J. A. Yousem, D. M. Lum, C. TI Multimodal Diagnostic Imaging for Hyperacute Stroke SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID ACUTE ISCHEMIC-STROKE; INTRAVENOUS T-PA; EARLY CT SCORE; INTRACEREBRAL HEMORRHAGE; ENDOVASCULAR THERAPY; COMPUTED-TOMOGRAPHY; CAROTID PLAQUE; ALBERTA STROKE; INDUCED NEPHROTOXICITY; ATHEROSCLEROSIS RISK AB In April 2015, the American Roentgen Ray Society and the American Society of Neuroradiology cosponsored a unique program designed to evaluate the state of the art in the imaging work-up of acute stroke. This topic has grown in importance because of the recent randomized controlled trials demonstrating the clear efficacy of endovascular stroke treatment. The authors, who were participants in that symposium, will highlight the points of emphasis in this article. C1 [Vo, K. D.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Yoo, A. J.] Texas Stroke Inst, Div Neurointervent, Plano, TX USA. [Gupta, A.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Gupta, A.] Weill Cornell Med Coll, Feil Family Brain & Mind Res Inst, New York, NY USA. [Qiao, Y.] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD USA. [Vagal, A. S.] Univ Cincinnati, Med Ctr, Dept Radiol, Cincinnati, OH 45267 USA. [Hirsch, J. A.] Massachusetts Gen Hosp, Neurolntervent Radiol, Boston, MA 02114 USA. [Yousem, D. M.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA. [Lum, C.] Univ Ottawa, Ottawa Hosp Res Inst, Intervent Neuroradiol, Ottawa, ON, Canada. RP Vo, KD (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, 510 South Kingshighway Blvd,Campus Box 8131, St Louis, MO 63110 USA. EM vok@wustl.edu FU Foundation of the American Society of Neuroradiology Scholar Award; National Institutes of Health/National Center for Advancing Translational Sciences [UUTRO0457]; NIH [K99HL106232, R00HL106232]; Clinical and Translational Science Awards [8 UL1 TR000077-05 KL2] FX Albert J. Yoo-UNRELATED: Consultancy: Neuravi*; Grants/Grants Pending. Penumbra,* Neuravi,* Comments: core imaging lab. Ajay Gupta UNRELATED: Grants/Grants Pending: Foundation of the American Society of Neuroradiology Scholar Award,* National Institutes of Health/National Center for Advancing Translational Sciences Grant No. UUTRO0457,* Comments: grants supporting research related to imaging of stroke and cerebrovascular disease. Ye Qiao-UNRELATED: Grants/Grants Pending: NIH K99HL106232 and R00HL106232. Comments: MRI imaging of intracranial atherosclerosis. Achala S. Vagal UNRELATED: Grants/Grants Pending: Clinical and Translational Science Awards 8 UL1 TR000077-05 KL2 research award,* Genentech (research grant).*Joshua A. Hirsch UNRELATED:Consultancy: Medtronic, CareFusion, Comments: Medtronic, interventional spine, ongoing; CareFusion, single episode in time; taught a spine-related course; Stock/Stock Options: Intratech, InNeuroCo, Comments: Intratech, development-stage stroke company; InNeuroCo, development-stage catheter company. David M. Yousem UNRELATED: Expert Testimony: Medicolegal consultations; Payment for Lectures (including service on Speakers Bureaus): American.College of Radiology Education Center*; Royalties: Elsevier; Payment for Development of Educational Presentations: CMEInfo.com for Hopkins Continuing Medical Education courses.* *Money paid to the institution. NR 81 TC 0 Z9 0 U1 1 U2 6 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD DEC PY 2015 VL 36 IS 12 BP 2206 EP 2213 DI 10.3174/ajnr.A4530 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CZ2RQ UT WOS:000366952700003 PM 26427831 ER PT J AU Biller, A Reuter, M Patenaude, B Homola, GA Breuer, F Bendszus, M Bartsch, AJ AF Biller, A. Reuter, M. Patenaude, B. Homola, G. A. Breuer, F. Bendszus, M. Bartsch, A. J. TI Responses of the Human Brain to Mild Dehydration and Rehydration Explored In Vivo by H-1-MR Imaging and Spectroscopy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID PROTON MR SPECTROSCOPY; ORGANIC OSMOLYTES; TISSUE WATER; VOLUME; OSMOREGULATION; CELLS; QUANTITATION; ADAPTATION; MECHANISMS; ALCOHOLISM AB BACKGROUND AND PURPOSE: As yet, there are no in vivo data on tissue water changes and associated morphometric changes involved in the osmo-adaptation of normal brains. Our aim was to evaluate osmoadaptive responses of the healthy human brain to osmotic challenges of de- and rehydration by serial measurements of brain volume, tissue fluid, and metabolites. MATERIALS AND METHODS: Serial T1-weighted and H-1-MR spectroscopy data were acquired in 15 healthy individuals at normohydration, on 12 hours of dehydration, and during 1 hour of oral rehydration. Osmotic challenges were monitored by serum measures, including osmolality and hematocrit. MR imaging data were analyzed by using Free Surfer and LCModel. RESULTS: On dehydration, serum osmolality increased by 0.67% and brain tissue fluid decreased by 1.63%, on average. MR imaging morphometry demonstrated corresponding decreases of cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus. These changes reversed during rehydration. Continuous fluid ingestion of 1 L of water for 1 hour within the scanner lowered serum osmolality by 0.96% and increased brain tissue fluid by 0.43%, on average. Concomitantly, cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus increased. Changes in brain tissue fluid were related to volume changes of the whole brain, the white matter, and hypothalamus/thalamus. Only volume changes of the hypothalamus/thalamus significantly correlated with serum osmolality. CONCLUSIONS: This is the first study simultaneously evaluating changes in brain tissue fluid, metabolites, volume, and cortical thickness. Our results reflect cellular volume regulatory mechanisms at a macroscopic level and emphasize that it is essential to control for hydration levels in studies on brain morphometry and metabolism in order to avoid confounding the findings. C1 [Biller, A.; Bendszus, M.; Bartsch, A. J.] Heidelberg Univ, Dept Neuroradiol, D-69120 Heidelberg, Germany. [Reuter, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Reuter, M.] Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Reuter, M.] Massachusetts Inst Technol Comp Sci & Al Lab, Cambridge, MA USA. [Patenaude, B.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Patenaude, B.; Bartsch, A. J.] Univ Oxford, FMRIB Ctr, Dept Clin Neurol, Oxford, England. [Homola, G. A.; Bartsch, A. J.] Univ Wurzburg, Dept Neuroradiol, D-97070 Wurzburg, Germany. [Breuer, F.] Res Ctr Magnet Resonance Bavaria, Wurzburg, Germany. RP Biller, A (reprint author), Heidelberg Univ, Dept Neuroradiol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. EM armin.biller@med.uni-heidelberg.de FU [K25 CA181632] FX Martin Reuter-RELATED: Grant: National Institutes of Health, Grant K25 CA181632.* Martin Bendszus-UNRELATED: Consultancy: Codman; Payment for Lectures (including service on Speakers Bureaus): Novartis, Guerbet, Codman, Roche. *Money paid to the institution. NR 41 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD DEC PY 2015 VL 36 IS 12 BP 2277 EP 2284 DI 10.3174/ajnr.A4508 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CZ2RQ UT WOS:000366952700013 PM 26381562 ER PT J AU Glykys, J Staley, KJ AF Glykys, Joseph Staley, Kevin J. TI Diazepam effect during early neonatal development correlates with neuronal Cl- SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article ID CATION-CHLORIDE COTRANSPORTERS; GRAMICIDIN-PERFORATED-PATCH; GAMMA-AMINOBUTYRIC-ACID; RAT HIPPOCAMPAL SLICES; IN-VITRO; INTRACELLULAR CHLORIDE; EXCITATORY ACTIONS; POSTTRAUMATIC EPILEPTOGENESIS; EPILEPTIFORM ACTIVITY; POSTNATAL MATURATION AB Objective: Although benzodiazepines and other GABA(A) receptors allosteric modulators are used to treat neonatal seizures, their efficacy may derive from actions on subcortical structures. Side effects of benzodiazepines in nonseizing human neonates include myoclonus, seizures, and abnormal movements. Excitatory actions of GABA may underlie both side effects and reduced anticonvulsant activity of benzodiazepines. Neocortical organotypic slice cultures were used to study: (1) spontaneous cortical epileptiform activity during early development; (2) developmental changes in [Cl-](i) and (3) whether diazepam's anticonvulsant effect correlated with neuronal [Cl-](i). Methods: Epileptiform activity in neocortical organotypic slice cultures was measured by field potential recordings. Cl- changes during development were assessed by multiphoton imaging of neurons transgenically expressing a Cl-sensitive fluorophore. Clinically relevant concentrations of diazepam were used to test the anticonvulsant effectiveness at ages corresponding to premature neonates through early infancy. Results: (1) Neocortical organotypic slices at days in vitro 5 (DIV5) exhibited spontaneous epileptiform activity. (2) Epileptiform event duration decreased with age. (3) There was a progressive decrease in [Cl-](i) over the same age range. (4) Diazepam was ineffective in decreasing epileptiform activity at DIV5-6, but progressively more effective at older ages through DIV15. (5) At DIV5-6, diazepam worsened epileptiform activity in 50% of the slices. Interpretation: The neocortical organotypic slice is a useful model to study spontaneous epileptiform activity. Decreasing [Cl-](i) during development correlates with decreasing duration of spontaneous epileptiform activity and increasing anticonvulsant efficacy of diazepam. We provide a potential explanation for the reports of seizures and myoclonus induction by benzodiazepines in newborn human neonates and the limited electrographic efficacy of benzodiazepines for the treatment of neonatal seizures. C1 [Glykys, Joseph; Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Glykys, Joseph; Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. RP Glykys, J (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM jglykys@mgh.harvard.edu FU NINDS NIH HHS [R01 NS040109, R01 NS074772] NR 91 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD DEC PY 2015 VL 2 IS 12 BP 1055 EP 1070 DI 10.1002/acn3.259 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CZ6WA UT WOS:000367240500002 PM 26734658 ER PT J AU Niquet, J Gezalian, M Baldwin, R Wasterlain, CG AF Niquet, Jerome Gezalian, Michael Baldwin, Roger Wasterlain, Claude G. TI Neuroprotective effects of deep hypothermia in refractory status epilepticus SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article ID TARGETED TEMPERATURE MANAGEMENT; HOSPITAL CARDIAC-ARREST; INTENSIVE-CARE-UNIT; THERAPEUTIC HYPOTHERMIA; NEONATAL ENCEPHALOPATHY; MILD HYPOTHERMIA; GENE-EXPRESSION; RISK-FACTORS; BRAIN; SEIZURES AB Objective: Pharmacoresistance develops quickly during repetitive seizures, and refractory status epilepticus (RSE) remains a therapeutic challenge. The outcome of RSE is poor, with high mortality and morbidity. New treatments are needed. Deep hypothermia (20 degrees C) is used clinically during reconstructive cardiac surgery and neurosurgery, and has proved safe and effective in those indications. We tested the hypothesis that deep hypothermia reduces RSE and its long-term consequences. Methods: We used a model of SE induced by lithium and pilocarpine and refractory to midazolam. Several EEG measures were recorded in both hypothermic (n = 17) and normothermic (n = 20) animals. Neuronal injury (by Fluoro-Jade B), cell-mediated inflammation, and breakdown of the blood-brain barrier (BBB) (by immunohistochemistry) were studied 48 h following SE onset. Results: Normothermic rats in RSE seized for 4.1 +/- 1.1 h, and at 48 h they displayed extensive neuronal injury in many brain regions, including hippocampus, dentate gyrus, amygdala, entorhinal and pyriform cortices, thalamus, caudate/putamen, and the frontoparietal neocortex. Deep hypothermia (20 degrees C) of 30 min duration terminated RSE within 12 min of initiation of hypothermia, reduced EEG power and seizure activity upon rewarming, and eliminated SE-induced neuronal injury in most animals. Normothermic rats showed widespread breakdown of the BBB, and extensive macrophage infiltration in areas of neuronal injury, which were completely absent in animals treated with hypothermia. Interpretation: These results suggest that deep hypothermia may open a new therapeutic avenue for the treatment of RSE and for the prevention of its long-term consequences. C1 [Niquet, Jerome; Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Niquet, Jerome; Gezalian, Michael; Baldwin, Roger; Wasterlain, Claude G.] Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, Los Angeles, CA USA. [Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Wasterlain, CG (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, 11301 Wilshire Blvd,Bldg 114,Room 139, West Los Angeles, CA 90073 USA. EM wasterla@ucla.edu FU BLRD VA [I01 BX000273]; NINDS NIH HHS [U01 NS074926] NR 57 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD DEC PY 2015 VL 2 IS 12 BP 1105 EP 1115 DI 10.1002/acn3.262 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CZ6WA UT WOS:000367240500005 PM 26734661 ER PT J AU Roberts-Rapp, L Ansell, P Kular, R Song, M Sokolova, I Gan, HK Papadopoulos, KP Lassman, AB Merrell, R Kumthekar, P Scott, AM Gomez, E Fischer, J Bhathena, A Holen, K Lai, R Reardon, D van den Bent, M AF Roberts-Rapp, L. Ansell, P. Kular, R. Song, M. Sokolova, I. Gan, H. K. Papadopoulos, K. P. Lassman, A. B. Merrell, R. Kumthekar, P. Scott, A. M. Gomez, E. Fischer, J. Bhathena, A. Holen, K. Lai, R. Reardon, D. van den Bent, M. TI Identifying the correct patient (pt) population for ABT-414: Biomarker assays for epidermal growth factor receptor (EGFR) in pts with glioblastoma (GBM) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Roberts-Rapp, L.; Ansell, P.; Bhathena, A.] AbbVie Inc, Discovery Oncol, N Chicago, IL USA. [Kular, R.; Song, M.; Sokolova, I.] Abbott Mol, Res & Dev, Des Plaines, IL USA. [Roberts-Rapp, L.; Gan, H. K.; Scott, A. M.] Austin Hlth, Dept Med Oncol, Melbourne, Vic, Australia. [Roberts-Rapp, L.; Gan, H. K.; Scott, A. M.] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia. [Papadopoulos, K. P.] South Texas Accelerated Res Therapeut, Clin Res, San Antonio, TX USA. [Lassman, A. B.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. [Lassman, A. B.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Merrell, R.] NorthShore Univ Hlth Syst, Kellogg Canc Ctr, Evanston, IL USA. [Kumthekar, P.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Gomez, E.; Fischer, J.] AbbVie Inc, Clin Operat Oncol, N Chicago, IL USA. [Holen, K.; Lai, R.] AbbVie Inc, Oncol Dev, N Chicago, IL USA. [Reardon, D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [van den Bent, M.] Erasmus MC, Ctr Canc, Dept Neurol Neurooncol, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 28PD BP 8 EP 9 PG 2 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700028 ER PT J AU Im, SA Chow, L Shao, Z Tripathy, D Bardia, A Hurvitz, S Harbeck, N Colleoni, M Franke, F Germa, C Hughes, G McLean, L Horan, M Lu, YS AF Im, S. -A. Chow, L. Shao, Z. Tripathy, D. Bardia, A. Hurvitz, S. Harbeck, N. Colleoni, M. Franke, F. Germa, C. Hughes, G. McLean, L. Horan, M. Lu, Y. -S. TI MONALEESA-7: a phase III, randomized, double-blind, placebo-controlled study of ribociclib (LEE011) combined with standard first-line endocrine therapy (ET) for the treatment of premenopausal women with HR+, HER2-advanced breast cancer (aBC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Im, S. -A.] Seoul Natl Univ Hosp, Coll Med, Seoul 110744, South Korea. [Chow, L.] Org Oncol & Translat Res, Translat Res, Hong Kong, Hong Kong, Peoples R China. [Shao, Z.] Fudan Univ, Shanghai Canc Ctr, Shanghai 200433, Peoples R China. [Tripathy, D.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Bardia, A.] Massachusetts Gen Hosp, Ctr Canc, Haematol Oncol, Boston, MA USA. [Hurvitz, S.] UCLA Jonsson Comprehens Canc Ctr, Clin Res Unit, Los Angeles, CA USA. [Harbeck, N.] Univ Munich, Breast Ctr, Munich, Germany. [Colleoni, M.] Ist Europeo Oncol, Div Med Senol, Milan, Italy. [Franke, F.] Hosp Caridade Ijui, Oncol, Ijui, Brazil. [Germa, C.; McLean, L.; Horan, M.] Novartis Oncol, Oncol Global Dev, E Hanover, NJ USA. [Hughes, G.] Novartis Pharma AG, Oncol Biometr & Data Management, Basel, Switzerland. [Lu, Y. -S.] Natl Taiwan Univ Hosp, Oncol, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 4 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 116TiP BP 33 EP 33 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700116 ER PT J AU Ohtsu, A Tabernero, J Bang, YJ Fuchs, CS Sun, L Wang, Z Csiki, I Koshiji, M Van Cutsem, E AF Ohtsu, A. Tabernero, J. Bang, Y. -J. Fuchs, C. S. Sun, L. Wang, Z. Csiki, I. Koshiji, M. Van Cutsem, E. TI Pembrolizumab (MK-3475) versus paclitaxel as second-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Ohtsu, A.] Natl Canc Ctr Hosp East, Exploratory Oncol Res & Clin Trial Ctr, Kashiwa, Chiba, Japan. [Tabernero, J.] Vall dHebron Univ Hosp, Med Oncol Serv, Barcelona, Spain. [Bang, Y. -J.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Fuchs, C. S.] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [Sun, L.; Wang, Z.] Merck & Co Inc, BARDS, Kenilworth, NJ USA. [Csiki, I.; Koshiji, M.] Merck & Co Inc, Clin Oncol, Kenilworth, NJ USA. [Van Cutsem, E.] Univ Hosp Leuven, Leuven Canc Inst, Gastroenterol Digest Oncol, Leuven, Belgium. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 232TiP BP 69 EP 69 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700232 ER PT J AU Van Cutsem, E Fuchs, CS Denker, AE Tabernero, J Ohtsu, A Lam, B Koshiji, M Bang, YJ AF Van Cutsem, E. Fuchs, C. S. Denker, A. E. Tabernero, J. Ohtsu, A. Lam, B. Koshiji, M. Bang, Y. -J. TI Phase 2 study of pembrolizumab (MK-3475) for recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Van Cutsem, E.] Univ Hosp Leuven, Leuven Canc Inst, Gastroenterol Digest Oncol, Leuven, Belgium. [Fuchs, C. S.] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [Denker, A. E.; Lam, B.; Koshiji, M.] Merck & Co Inc, Clin Oncol, Kenilworth, NJ USA. [Tabernero, J.] Vall dHebron Univ Hosp, Med Oncol Serv, Barcelona, Spain. [Ohtsu, A.] Natl Canc Ctr Hosp East, Exploratory Oncol Res & Clin Trial Ctr, Kashiwa, Chiba, Japan. [Bang, Y. -J.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 231TiP BP 69 EP 69 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700231 ER PT J AU Tahara, M Cohen, EEW Haddad, RI Fayette, J Licitra, LF Clement, PM Vermorken, JB Gauler, T Cupissol, D Grau, JJ Guigay, J del Campo, JM Okami, K Takahashi, S Burtness, B Cong, XJ Gibson, N Solca, F Ehrnrooth, E Machiels, JPH AF Tahara, M. Cohen, E. E. W. Haddad, R. I. Fayette, J. Licitra, L. F. Clement, P. M. Vermorken, J. B. Gauler, T. Cupissol, D. Grau, J. J. Guigay, J. del Campo, J. M. Okami, K. Takahashi, S. Burtness, B. Cong, X. J. Gibson, N. Solca, F. Ehrnrooth, E. Machiels, J. -P. H. TI PR Second-line afatinib vs methotrexate (MTX) in patients (pts) with recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC): subgroup/biomarker analysis of LUX-head and neck 1 (LUX-H&N1) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Tahara, M.] Natl Canc Ctr, Hosp East, Dept Head & Neck Med Oncol, Kashiwa, Chiba, Japan. [Cohen, E. E. W.] Univ Calif San Diego, Dept Med, Moores Canc Ctr, La Jolla, CA 92093 USA. [Haddad, R. I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Haddad, R. I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fayette, J.] Univ Lyon 1, Ctr Leon Berard, F-69365 Lyon, France. [Licitra, L. F.] Univ Lyon 1, Hosp Civils Lyon, F-69365 Lyon, France. [Licitra, L. F.] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy. [Clement, P. M.] Katholieke Univ Leuven, Dept Oncol, Leuven, Belgium. [Vermorken, J. B.] Univ Antwerp Hosp, Dept Med Oncol, Edegem, Belgium. [Gauler, T.] Univ Hosp Essen, West German Canc Ctr, Essen, Germany. [Cupissol, D.] Inst Canc Montpellier Val dAurelle, Med Oncol, Montpellier, France. [Gauler, T.] Univ Barcelona, Hosp Clin Barcelona, Barcelona 7, Spain. [Guigay, J.] Villejuif & Ctr Antoine Lacassagne, Gustave Roussy, Nice, France. [del Campo, J. M.] Hosp Univ Vall DHebron, Dept Med Oncol, Barcelona, Spain. [Okami, K.] Tokai Univ Hosp, Dept Otolaryngol, Kanagawa, Japan. [Takahashi, S.] Japanese Fdn Canc Res, Dept Med Oncol, Tokyo, Japan. [Burtness, B.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Cong, X. J.] Boehringer Ingetheim Pharmaceut Inc, Stat, Ridgefield, CT USA. [Gibson, N.] Boehringer Ingetheim Pharma GmbH & Co KG, Drug Metab & Pharmacokinet, Biberach, Germany. [Solca, F.] Boehringer Ingetheim RCV GmbH & Co KG, Pharmacol & Translat Res, Vienna, Austria. [Ehrnrooth, E.] Boehringer Ingetheim, TA Oncol, Danmark As, Denmark. [Machiels, J. -P. H.] Clin Univ St Luc, Ins Roi Albert 2, Brussels, Belgium. [Machiels, J. -P. H.] Catholic Univ Louvain, Inst Rech Clin & Experimentale Pole MIRO, B-1200 Brussels, Belgium. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 314O BP 93 EP 93 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700313 ER PT J AU Licitra, L Even, C Haddad, R Tahara, M Goswami, T Franks, A Emeribe, U Jarkowski, A Melillo, G Ferris, RL AF Licitra, L. Even, C. Haddad, R. Tahara, M. Goswami, T. Franks, A. Emeribe, U. Jarkowski, A., III Melillo, G. Ferris, R. L. TI Phase 3 study of durvalumab (MEDI4736) alone or in combination with tremelimumab versus standard of care (SoC) in platinum-resistant recurrent ormetastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): EAGLE SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Licitra, L.] Fdn IRCCS Inst Nazl Tumori, Head & Neck Canc Med Oncol Unit, Milan, Italy. [Even, C.] Inst Gustave Roussy, Head & Neck Oncol, Villejuif, France. [Haddad, R.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Tahara, M.] Natl Canc Ctr Hosp East, Head & Neck Med Oncol, Kashiwa, Chiba, Japan. [Goswami, T.; Jarkowski, A., III] AstraZeneca, Immunooncol GMD, Gaithersburg, MD USA. [Franks, A.] AstraZeneca, Clin Dev, Immunooncol, Gaithersburg, MD USA. [Emeribe, U.; Melillo, G.] AstraZeneca, Global Med Dev, Gaithersburg, MD USA. [Ferris, R. L.] Univ Pittsburgh, Inst Canc, Dept Otolaryngol, Pittsburgh, PA USA. [Ferris, R. L.] Univ Pittsburgh, Inst Canc, Canc Immunol Program, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 341TiP BP 101 EP 101 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700340 ER PT J AU Ahn, MJ Gandhi, L Hamid, O Hellmann, MD Garon, EB Ramalingam, SS Lubiniecki, GM Zhang, J Piperdi, B Hui, R AF Ahn, M. -J. Gandhi, L. Hamid, O. Hellmann, M. D. Garon, E. B. Ramalingam, S. S. Lubiniecki, G. M. Zhang, J. Piperdi, B. Hui, R. TI Risk of pneumonitis in patients with advanced NSCLC treated with pembrolizumab in KEYNOTE-001 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Ahn, M. -J.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Med, Seoul, South Korea. [Gandhi, L.] Dana Farber Canc Inst, Thorac Oncol, Boston, MA 02115 USA. [Hamid, O.] Angeles Clin & Res Inst, Res, Los Angeles, CA USA. [Hellmann, M. D.] Mem Sloan Kettering Canc Ctr, Med, New York, NY 10021 USA. [Hellmann, M. D.] Weill Cornell Med Coll, New York, NY USA. [Garon, E. B.] Univ Calif Los Angeles, David Geffen Sch Med, Med, Los Angeles, CA 90095 USA. [Ramalingam, S. S.] Emory Univ, Winship Canc Inst, Hematol & Oncol, Atlanta, GA 30322 USA. [Lubiniecki, G. M.; Piperdi, B.] Merck & Co Inc, Clin Oncol, Kenilworth, NJ USA. [Zhang, J.] Merck & Co Inc, BARDS, Kenilworth, NJ USA. [Hui, R.] Westmead Hosp, Med Oncol, Sydney, NSW, Australia. RI Zhang, Jin/E-8298-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 459P BP 140 EP 140 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700458 ER PT J AU Wolf, J Hochmair, M Kattan, JG Ang, MK Garon, EB Groen, HJM Heist, R Ohashi, K Felip, E Reguart, N Campelo, RG Soo, R Paz-Ares, L de Marinis, F Smit, EF Giovannini, M Squires, M Cui, X Zhang, Y Tan, D AF Wolf, J. Hochmair, M. Kattan, J. G. Ang, M. -K. Garon, E. B. Groen, H. J. M. Heist, R. Ohashi, K. Felip, E. Reguart, N. Garcia Campelo, R. Soo, R. Paz-Ares, L. de Marinis, F. Smit, E. F. Giovannini, M. Squires, M. Cui, X. Zhang, Y. Tan, D. TI A phase II, multicenter, four-cohort study of oral cMET inhibitor capmatinib (INC280) in patients with EGFR wild-type, advanced NSCLC who have received one or two prior lines of systemic therapy for advanced/metastatic disease SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO) CY DEC 18-21, 2015 CL Singapore, SINGAPORE SP European Soc Med Oncol C1 [Wolf, J.] Univ Hosp Cologne, Innere Med Klin, Cologne, Germany. [Hochmair, M.] Otto Wagner Spital, Dept Resp Oncol, Vienna, Austria. [Kattan, J. G.] Hotel Dieu France Hosp, Dept Hematol Oncol, Beirut, Lebanon. [Ang, M. -K.; Tan, D.] Natl Canc Ctr, Dept Med Oncol, Singapore, Singapore. [Garon, E. B.] UCLA Sch Med, David Geffen Sch Med, Los Angeles, CA USA. [Groen, H. J. M.] Univ Groningen Hosp UMCG, Dept Pulm Dis, Groningen, Netherlands. [Heist, R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ohashi, K.] Okayama Univ Hosp, Dept Med Res, Okayama, Japan. [Felip, E.] Vall Hebron Univ Hosp, Dept Oncol, Barcelona, Spain. [Reguart, N.] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain. [Garcia Campelo, R.] Hosp Univ A Coruna Corunac, Lung Canc & Thorac Tumors Dept, La Coruna, Spain. [Soo, R.] Natl Univ Canc Inst, Natl Univ Hlth Syst, Dept Haematol Oncol, Singapore, Singapore. [Paz-Ares, L.] Hosp Univ 12 Octubre, Dept Med Oncol, Madrid, Spain. [de Marinis, F.] Ist Europeo Oncol, Unita Operat Pneumol Oncol 1, Milan, Italy. [Smit, E. F.] NKI AVL, Dept Thorac Oncol, Amsterdam, Netherlands. [Giovannini, M.] Novartis Pharma AG, Oncol Clin Dev, Basel, Switzerland. [Squires, M.] Novartis Pharma AG, Oncol Correlat Sci, Basel, Switzerland. [Cui, X.] Novartis Pharmaceut, Oncol Clin Pharmacol, E Hanover, NJ USA. [Zhang, Y.] Novartis Pharmaceut, Biostat, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 SU 9 MA 478TiP BP 146 EP 146 PG 1 WC Oncology SC Oncology GA CZ5RC UT WOS:000367158700477 ER PT J AU Barth, RF Yang, WL Nakkula, RJ Byun, Y Tjarks, W Wu, LC Binns, PJ Riley, KJ AF Barth, Rolf F. Yang, Weilian Nakkula, Robin J. Byun, Youngjoo Tjarks, Werner Wu, Lai Chu Binns, Peter J. Riley, Kent J. TI Evaluation of TK1 targeting carboranyl thymidine analogs as potential delivery agents for neutron capture therapy of brain tumors SO APPLIED RADIATION AND ISOTOPES LA English DT Article; Proceedings Paper CT 16th International Congress on Neutron Capture Therapy (ICNCT) CY JUN 14-19, 2014 CL Helsinki, FINLAND DE Carboranyl thymidine analogs; N5-2OH; F98 rat glioma; BNCT ID BIOLOGICAL EVALUATION; INTRACAROTID INJECTION; SODIUM BOROCAPTATE; BARRIER DISRUPTION; ENHANCED SURVIVAL; KINASE 1; BORONOPHENYLALANINE; CANCER AB In this report we describe studies with N5-2OH, a carboranyl thymidine analog (CTA), which is a substrate for thymidine kinase 1 (TK1), using the F98 rat glioma model. In vivo BNCT studies have demonstrated that intracerebral (i.c.) osmotic pump infusion of N5-2OH yielded survival data equivalent to those obtained with i.v. administration of boronophenylalanine (BPA). The combination of N5-2OH and BPA resulted in a modest increase in MST of F98 glioma bearing rats compared to a statistically significant increase with the RG2 glioma model, as has been previously reported by us (Barth et al., 2008). This had lead us to synthesize a second generation of CTAs that have improved in vitro enzyme kinetics and in vivo tumor uptake (Agarwal et al., 2015). (C) 2015 Elsevier Ltd. All rights reserved. C1 [Barth, Rolf F.; Yang, Weilian; Nakkula, Robin J.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Byun, Youngjoo; Tjarks, Werner] Ohio State Univ, Div Med Chem & Pharmacognosy, Coll Pharm, Columbus, OH 43210 USA. [Wu, Lai Chu] Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. [Wu, Lai Chu] Ohio State Univ Hosp, Dept Internal Med, Columbus, OH 43210 USA. [Binns, Peter J.] Mt Auburn Hosp, Dept Radiol, Cambridge, MA 02138 USA. [Riley, Kent J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Barth, RF (reprint author), Ohio State Univ, Dept Pathol, 4132 Graves Hall 333 W 10th Ave, Columbus, OH 43210 USA. EM rolf.barth@osumc.edu FU NCI NIH HHS [5R01CA127935, R01 CA127935] NR 21 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD DEC PY 2015 VL 106 SI SI BP 251 EP 255 DI 10.1016/j.apradiso.2015.06.031 PG 5 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA CZ2SE UT WOS:000366954100053 PM 26282567 ER PT J AU Weisholtz, DS Root, JC Butler, T Tuscher, O Epstein, J Pan, H Protopopescu, X Goldstein, M Isenberg, N Brendel, G LeDoux, J Silbersweig, DA Stern, E AF Weisholtz, Daniel S. Root, James C. Butler, Tracy Tuescher, Oliver Epstein, Jane Pan, Hong Protopopescu, Xenia Goldstein, Martin Isenberg, Nancy Brendel, Gary LeDoux, Joseph Silbersweig, David A. Stern, Emily TI Beyond the amygdala: Linguistic threat modulates peri-sylvian semantic access cortices SO BRAIN AND LANGUAGE LA English DT Article DE Emotion; fMRI; Threat; Functional neuroimaging; Neuroanatomy; Reading ID WORD FORM AREA; FUNCTIONAL CONNECTIVITY; PERIAQUEDUCTAL GRAY; EMOTIONAL RESPONSES; FMRI DATA; BRAIN; ACTIVATION; LANGUAGE; VALENCE; CORTEX AB In this study, healthy volunteers were scanned using functional magnetic resonance imaging (fMRI) to investigate the neural systems involved in processing the threatening content conveyed via visually presented "threat words." The neural responses elicited by these words were compared to those elicited by matched neutral control words. The results demonstrate that linguistic threat, when presented in written form, can selectively engage areas of lateral temporal and inferior frontal cortex, distinct from the core language areas implicated in aphasia. Additionally, linguistic threat modulates neural activity in visceral/emotional systems (amygdala, parahippocampal gyrus and periaqueductal gray), and at earlier stages of the visual-linguistic processing stream involved in visual word form representations (ventral occipitotemporal cortex). We propose a model whereby limbic activation modulates activity at multiple nodes along the visual-linguistic-semantic processing stream, including a perisylvian "semantic access network" involved in decoding word meaning, suggesting a dynamic interplay between feedforward and feedback processes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Weisholtz, Daniel S.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Root, James C.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10065 USA. [Butler, Tracy] NYU, Langone Med Ctr, Dept Neurol, New York, NY 10016 USA. [Root, James C.; Butler, Tracy; Brendel, Gary] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA. [Tuescher, Oliver] Johannes Gutenberg Univ Mainz, Dept Psychiat & Psychotherapy, D-55131 Mainz, Germany. [Epstein, Jane] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Pan, Hong; Silbersweig, David A.; Stern, Emily] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Martin] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Isenberg, Nancy] Virginia Mason Med Ctr, Inst Neurosci, Seattle, WA 98101 USA. [LeDoux, Joseph] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Stern, Emily] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Weisholtz, DS (reprint author), Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dweisholtz@partners.org OI Isenberg, Nancy/0000-0001-8876-7801; Weisholtz, Daniel/0000-0001-6277-4894 FU National Institutes of Mental Health [R01 MH61825] FX This work was supported by a National Institutes of Mental Health grant for the study of psychotic symptoms in schizophrenia (R01 MH61825). NR 60 TC 1 Z9 1 U1 2 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD DEC PY 2015 VL 151 BP 12 EP 22 DI 10.1016/j.bandl.2015.10.004 PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA CZ5DI UT WOS:000367122300002 PM 26575986 ER PT J AU Donskov, F Michaelson, MD Puzanov, I Davis, MP Bjarnason, GA Motzer, RJ Goldstein, D Lin, X Cohen, DP Wiltshire, R Rini, BI AF Donskov, Frede Michaelson, M. Dror Puzanov, Igor Davis, Mellar P. Bjarnason, Georg A. Motzer, Robert J. Goldstein, David Lin, Xun Cohen, Darrel P. Wiltshire, Robin Rini, Brian I. TI Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients SO BRITISH JOURNAL OF CANCER LA English DT Article DE sunitinib; metastatic renal cell carcinoma; biomarkers; adverse events; multivariate; neutropenia; hypertension ID ENDOTHELIAL GROWTH-FACTOR; INTERFERON-ALPHA; TARGETED THERAPIES; PROGRESSION-FREE; CLINICAL-TRIALS; PHASE-II; CANCER; CYTOKINE; SURVIVAL; POLYMORPHISMS AB Background: Metastatic renal cell carcinoma (mRCC) prognostic models may be improved by incorporating treatment-induced toxicities. Methods: In sunitinib-treated mRCC patients (N = 770), baseline prognostic factors and treatment-induced toxicities (hypertension (systolic blood pressure >= 140mmHg), neutropenia (grade >= 2), thrombocytopenia (grade >= 2), hand-foot syndrome (grade 40), and asthenia/fatigue (grade 40)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. Results: On-treatment neutropenia and hypertension were associated with longer PFS (P = 0.0276 and P<0.0001, respectively) and OS (P = 0.0014 and P<0.0001, respectively), independent of baseline prognostic factors, including International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. By 12-week landmark analysis, neutropenia was significantly associated with longer PFS and OS (P = 0.013 and P = 0.0122, respectively) and hypertension or hand-foot syndrome with longer OS (P = 0.0036 and P = 0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63 - 0.67) for IMDC classification alone and 0.72 (95% CI: 0.70 - 0.74) when combined with hypertension and neutropenia. Considering hypertension and neutropenia (developing both vs neither) changed IMDC-predicted median OS in each IMDC risk group (favourable: 45.3 vs 19.5 months; intermediate: 32.5 vs 8.0 months; poor: 21.1 vs 4.8 months). Conclusions: On-treatment neutropenia and hypertension are independent biomarkers of sunitinib efficacy and may add prognostic accuracy to the IMDC model. C1 [Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus C, Denmark. [Michaelson, M. Dror] Massachusetts Gen Hosp, Claire & John Bertucci Ctr Genitourinary Canc, Ctr Canc, Boston, MA 02114 USA. [Puzanov, Igor] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN 37232 USA. [Davis, Mellar P.] Cleveland Clin, Taussig Canc Inst, Div Solid Tumor, Palliat Med Serv, Cleveland, OH 44195 USA. [Davis, Mellar P.] Cleveland Clin, Taussig Canc Inst, Div Solid Tumor, Support Oncol Serv, Cleveland, OH 44195 USA. [Bjarnason, Georg A.] Sunnybrook Odette Canc Ctr, Div Med Oncol, Toronto, ON M4N 3M5, Canada. [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. [Goldstein, David] Prince Wales Hosp, Dept Med Oncol, Randwick, NSW 2031, Australia. [Lin, Xun; Cohen, Darrel P.] Pfizer Oncol, La Jolla, CA 92121 USA. [Wiltshire, Robin] Pfizer Oncol, Walton Oaks, Tadworth KT20 7NS, Surrey, England. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Glickman Urol Inst, Cleveland, OH 44195 USA. RP Donskov, F (reprint author), Aarhus Univ Hosp, Dept Oncol, Norrebrogade 44, DK-8000 Aarhus C, Denmark. EM fd@oncology.au.dk OI Michaelson, Dror/0000-0001-9249-6338 FU Pfizer Inc., New York, NY, USA; Pfizer Inc. FX We thank all the participating patients and their families, as well as the investigators, research nurses, study coordinators, and operation staff. This study was sponsored by Pfizer Inc., New York, NY, USA. Medical writing support was provided by Andy Gannon at ACUMED, part of the KnowledgePoint360 Group, an Ashfield company (New York, NY, USA) with funding from Pfizer Inc. NR 41 TC 12 Z9 13 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 1 PY 2015 VL 113 IS 11 BP 1571 EP 1580 DI 10.1038/bjc.2015.368 PG 10 WC Oncology SC Oncology GA CZ5UL UT WOS:000367167400007 PM 26492223 ER PT J AU Ashack, KA Burton, KA Kilgour, JM Dellavalle, RP AF Ashack, K. A. Burton, K. A. Kilgour, J. M. Dellavalle, R. P. TI Conflicts of interest in dermatology: a medical student and mentor perspective SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID PHARMACEUTICAL-INDUSTRY; EDUCATION AB Conflict of interest (COI) in medicine is well defined, but is seldom discussed in the field of dermatology. This perspective sheds light on this topic in dermatology and provides suggestions on how better to approach COI in medical school and residency. C1 [Ashack, K. A.] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [Burton, K. A.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA. [Kilgour, J. M.] Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales. [Dellavalle, R. P.] Univ Colorado Anschutz Med Campus, Dept Dermatol, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [Dellavalle, R. P.] Univ Colorado Anschutz Med Campus, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Dellavalle, R. P.] US Dept Vet Affairs, Eastern Colorado Hlth Care Syst, Dermatol Serv, Denver, CO 80220 USA. RP Dellavalle, RP (reprint author), Univ Colorado Anschutz Med Campus, Dept Dermatol, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. EM robert.dellavalle@ucdenver.edu NR 21 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD DEC PY 2015 VL 173 IS 6 BP 1518 EP 1521 DI 10.1111/bjd.14225 PG 4 WC Dermatology SC Dermatology GA CZ6SX UT WOS:000367232300075 PM 26708549 ER PT J AU Fuzaylov, G Kelly, TL Bline, C Dunaev, A Dylewski, ML Driscoll, DN AF Fuzaylov, Gennadiy Kelly, Tara L. Bline, Cheryl Dunaev, Alexander Dylewski, Maggie L. Driscoll, Daniel N. TI Post-operative pain control for burn reconstructive surgery in a resource-restricted country with subcutaneous infusion of local anesthetics through a soaker catheter to the surgical site: Preliminary results SO BURNS LA English DT Article DE Pain control; Burn; A reconstructive surgery; Recourse-limited country; Ukraine; Split thickness skin graft; Local anesthetic infusion ID GRAFT DONOR SITE; EPIDURAL ANALGESIA; MINIMIZE PAIN; MANAGEMENT; EFFICACY; BLOCK; METAANALYSIS AB Objective: Post-operative pain can significantly affect a patient's ability to recover following surgery. In this study we introduced the concept of post-operative pain evaluation of burn patients as well as a technique for placement and use of subcutaneous catheters for continuous infusion of local anesthetic to provide analgesia following skin harvest from the lateral thigh in a hospital in resource-restricted country - Ukraine. Methods: A total of 109 patients were enrolled in this study. In the control group 64 patients received the standard post-operative pain regimen of metamizole 1 g and/or ketorolac 3%-30 mg at the discretion of the nursing staff. In the interventional group, 45 patients received the catheter infusion of local anesthetic by elastomeric pump which was placed intraoperatively; it continuously delivers a regulated flow 4-5 ml/h of procaine 0.5% for 48 h to a patient's surgical donor site with the standard pain regimen available for breakthrough pain. All patients were assessed post-operatively and in the pen-dressing change period by the nursing staff. Blood pressure, heart rate, and pain scores were documented based on the Wong-Baker Faces Pain Rating Scale. All data were analyzed using SAS version 9.3. The Student's t test and Fisher's exact test were used to assess differences between groups for continuous variables. The Mann Whitney U Test was used to examine differences in pain scores between groups. A p value of <0.05 was considered significant. Results: The median pain score immediately following surgery was 5.0 in the control group, which was significantly greater (p = 0.03) than median pain score of 4.0 for the patients receiving continuous infusion of procaine. However, there is no statistically significant difference in the median pain score (3.0 and 3.0) after the initial dressing change (p = 0.73). Conclusions: Our Ukrainian colleagues now have a method of objective pain assessment and a new technique in pain management. With assessment linked to intervention, improvement in post-operative pain can be expected. (C) 2015 Elsevier Ltd and ISBI. All rights reserved. C1 [Fuzaylov, Gennadiy] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Kelly, Tara L.; Bline, Cheryl] Massachusetts Gen Hosp, Anesthesia, Boston, MA 02114 USA. [Dunaev, Alexander] Municipal Hosp 8, Burn Ctr, Lvov, Ukraine. [Dylewski, Maggie L.] Shriners Hosp Children, Boston, MA 02114 USA. [Driscoll, Daniel N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg, Cambridge, MA USA. RP Fuzaylov, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. EM gfuzaylov@mgh.harvard.edu NR 29 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 EI 1879-1409 J9 BURNS JI Burns PD DEC PY 2015 VL 41 IS 8 BP 1811 EP 1815 DI 10.1016/j.burns.2015.06.003 PG 5 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA CZ5FK UT WOS:000367127700023 PM 26188896 ER PT J AU Keane, TM AF Keane, Terence M. TI "A Sense of Where You Are," Bowling Alone, and the Future of the Society of Clinical Psychology SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Editorial Material DE Clinical Psychology; membership; professional organizations; Society of Clinical Psychology AB Professional organizations in all specialties are experiencing membership declines largely as a function of the demands on young graduates to see benefits and advantages to membership. This response to the Robiner et al. (2015) article highlights the importance of professional organizations, what they do for the profession, and what benefits these organizations confer at the individual level. C1 [Keane, Terence M.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Keane, Terence M.] Boston Univ, Sch Med, Boston, MA 02130 USA. RP Keane, TM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM terry.keane@va.gov NR 2 TC 0 Z9 0 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0969-5893 EI 1468-2850 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD DEC PY 2015 VL 22 IS 4 BP 387 EP 389 DI 10.1111/cpsp.12120 PG 3 WC Psychology, Clinical SC Psychology GA CZ2HI UT WOS:000366925300007 ER PT J AU Mendez, MF Ringman, JM Shapira, JS AF Mendez, Mario F. Ringman, John M. Shapira, Jill S. TI Impairments in the Face- Processing Network in Developmental Prosopagnosia and Semantic Dementia SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article ID RIGHT TEMPORAL-LOBE; PROGRESSIVE PROSOPAGNOSIA; CONGENITAL PROSOPAGNOSIA; ACQUIRED PROSOPAGNOSIA; FRONTOTEMPORAL DEMENTIA; RECOGNITION DISORDERS; FACIAL IDENTITY; FUSIFORM GYRUS; NEURAL SYSTEMS; FAMILIAR FACES C1 [Mendez, Mario F.; Ringman, John M.; Shapira, Jill S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Ringman, John M.; Shapira, Jill S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Ringman, John M.; Shapira, Jill S.] Vet Affairs Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit, 691-116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu FU National Institute on Aging [R01AG034499-05] FX Supported in part by National Institute on Aging Grant #R01AG034499-05 (M.F.M.) NR 106 TC 1 Z9 1 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1543-3633 EI 1543-3641 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD DEC PY 2015 VL 28 IS 4 BP 188 EP 197 PG 10 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA CZ5HW UT WOS:000367134400002 PM 26705265 ER PT J AU Katz, M Giani, E Laffel, L AF Katz, Michelle Giani, Elisa Laffel, Lori TI Challenges and Opportunities in the Management of Cardiovascular Risk Factors in Youth With Type 1 Diabetes: Lifestyle and Beyond SO CURRENT DIABETES REPORTS LA English DT Review DE Diabetes type 1; Cardiovascular; Lifestyle; Pediatrics ID INTIMA-MEDIA THICKNESS; EXCHANGE CLINIC REGISTRY; ALL-CAUSE MORTALITY; GLYCEMIC CONTROL; ENDOTHELIAL DYSFUNCTION; ARTERIAL STIFFNESS; OBESE CHILDREN; BLOOD-PRESSURE; YOUNG-PEOPLE; COMPLICATIONS TRIAL AB Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in persons with type 1 diabetes (T1D). Specific risk factors associated with diabetes, such as hyperglycemia and kidney disease, have been demonstrated to increase the incidence and progression of CVD. Nevertheless, few data exist on the effects of traditional risk factors such as dyslipidemia, obesity, and hypertension on CVD risk in youth with T1D. Improvements in understanding and approaches to the evaluation and management of CVD risk factors, specifically for young persons with T1D, are desirable. Recent advances in noninvasive techniques to detect early vascular damage, such as the evaluation of endothelial dysfunction and aortic or carotid intima- media thickness, provide new tools to evaluate the progression of CVD in childhood. In the present review, current CVD risk factor management, challenges, and potential therapeutic interventions in youth with T1D are described. C1 [Katz, Michelle; Giani, Elisa; Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. RP Laffel, L (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet & Epidemiol Sect, One Joslin Pl, Boston, MA 02215 USA. EM Michelle.Katz@joslin.harvard.edu; Elisa.Giani@joslin.harvard.edu; lori.laffel@joslin.harvard.edu FU Johnson Johnson; Eli Lilly; Sanofi; Novo Nordisk; Roche; Bristol-Myers Squibb/AstraZeneca; Menarini; Oshad; Boehringer Ingelheim; Dexcom; Bayer FX Lori Laffel reports personal fees from Johnson & Johnson, Eli Lilly, Sanofi, Novo Nordisk, Roche, Bristol-Myers Squibb/AstraZeneca, Menarini, and Oshad; grants and personal fees from Boehringer Ingelheim and Dexcom; and grants from Bayer. NR 106 TC 2 Z9 2 U1 2 U2 11 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD DEC PY 2015 VL 15 IS 12 AR 119 DI 10.1007/s11892-015-0692-4 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ0OY UT WOS:000366806700017 PM 26520142 ER PT J AU Li, H Fan, WL Yang, J Song, SY Liu, Y Lei, P Shrestha, L Mella, G Chen, W Xu, HB AF Li, Hong Fan, Wenliang Yang, Jie Song, Shuyan Liu, Yuan Lei, Ping Shrestha, Lochan Mella, Grace Chen, Wei Xu, Haibo TI Asymmetry in cross-hippocampal connectivity in unilateral mesial temporal lobe epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Mesial temporal lobe epilepsy; Hippocampal network; Resting state functional connectivity; Brain plasticity ID VISUAL WORKING-MEMORY; ALTERED FUNCTIONAL CONNECTIVITY; RESTING STATE FMRI; PREFRONTAL CORTEX; NEUROCOGNITIVE FUNCTION; INSULAR CORTEX; BRAIN; RETRIEVAL; SCLEROSIS; NETWORKS AB Mesial temporal lobe epilepsy (mTLE) is mostly characterized by hippocampal sclerosis (HS) changes. Although considerable progress has been made in understanding the altered functional network of mTLE patients, whether one side of the abnormal hippocampal (HP) structure will affect the other healthy side of the hippocampal network is still unclear. Here, we used a seed-based method to explore the commonly alterative hippocampal network in mTLE patients by comparing the bilateral hippocampal network of unilateral mTLE patients with healthy control participants. We observed that both sides of the hippocampal network in unilateral mTLE patients were changed independent of the affected or "healthy" side, which may suggest a common plasticity network for both sides of hippocampal sclerosis mesial temporal lobe epilepsy patients. Furthermore, using the HP as the ROT, we found that the functional connectivity of the intra-HP in the left mTLE-HS group was moderately positively correlated with the duration of the disease, while a strong negative correlation between functional connectivity of the intra-HP and duration were detected in the right mTLE-HS group, which suggested that it was easier for the right HP than the left HP to communicate with the contralateral HP according to the progression of mTLE disease because the hippocampus plays different roles in the communication and compensatory mechanism associated with the contralateral side of the hemisphere. We hope that this potential relevance may help us to better characterize mTLE with hippocampal sclerosis and ultimately assist in providing a better diagnosis and more accurate invasive treatments of mTLE. (C) 2015 Elsevier B.V. All rights reserved. C1 [Li, Hong; Fan, Wenliang; Liu, Yuan; Lei, Ping; Shrestha, Lochan; Mella, Grace; Xu, Haibo] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Radiol, Wuhan 430022, Peoples R China. [Yang, Jie] Massachusetts Gen Hosp, Dept Commun Sci & Disorders, Inst Hlth Profess, Boston, MA 02114 USA. [Song, Shuyan] Huazhong Univ Sci & Technol, Educ Minist China, Key Lab Image Proc & Intelligent Control, Sch Life Sci & Technol, Wuhan 430074, Peoples R China. [Chen, Wei] Tongji Univ, Tonsil Hosp, Dept Radiol, Sch Med, Shanghai, Peoples R China. [Chen, Wei] First Peoples Hosp Yibin, Radiol & Med Imaging Ctr, Sichuan 644000, Peoples R China. [Xu, Haibo] Wuhan Univ, Zhongnan Hosp, Dept Radiol, Wuhan 430071, Peoples R China. RP Xu, HB (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Radiol, 1277 Jiefang Ave, Wuhan 430022, Peoples R China. EM 248026233@qq.com; fanwenliang168@163.com; kingsleyang@gmail.com; song_shuyan@163.com; 309105825@qq.com; leiping_rosemary@126.com; lochan.shrestha@yahoo.com; gracegloriam@gmail.com; q1530831809@qq.com; xuhaibo1120@hotmail.com FU National Natural Science Foundation of China [81171386]; Hubei Key Laboratory Foundation of Molecular Imaging [2008-69]; Hubei Natural Science Foundation [2009CDB008] FX This research was supported by the National Natural Science Foundation of China (no. 81171386), Hubei Key Laboratory Foundation of Molecular Imaging (no. 2008-69), as well as the Hubei Natural Science Foundation (no. 2009CDB008). NR 52 TC 2 Z9 2 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD DEC PY 2015 VL 118 BP 14 EP 21 DI 10.1016/j.eplepsyres.2015.10.005 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CZ0AH UT WOS:000366767000004 PM 26561924 ER PT J AU Schoeler, NE Leu, C White, J Plagnol, V Ellard, S Matarin, M Yellen, G Thiele, EA Mackay, M McMahon, JM Scheffer, IE Sander, JW Cross, JH Sisodiya, SM AF Schoeler, Natasha E. Leu, Costin White, Jon Plagnol, Vincent Ellard, Sian Matarin, Mar Yellen, Gary Thiele, Elizabeth A. Mackay, Mark McMahon, Jacinta M. Scheffer, Ingrid E. Sander, Josemir W. Cross, J. Helen Sisodiya, Sanjay M. TI Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Genetic biomarker; Ketogenic diet; KCNJ11; BAD; Epilepsy; Seizures ID GENETIC-VARIATION; CHILDHOOD EPILEPSY; DIABETES-MELLITUS; ASSOCIATION; MUTATIONS; EFFICACY; IDENTIFICATION; GLYCOLYSIS; EXPRESSION; SEIZURES AB In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: >= 50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF) >0.01, using PLINK. Response to KDT in individuals with variants with MAF < 0.01 was evaluated. 303 Individuals had KCNJ11 and 246 individuals had BAD sequencing data and diet response data. Six SNPs in KCNJ11 and two in BAD had MAF > 0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAF < 0.01. No significant results were obtained from association analyses, with either KDT response phenotype. P-values were similar when accounting for ethnicity using a stratified Cochran-Mantel-Haenszel test. There did not seem to be a consistent effect of rare variants on response to KDT, although the cohort size was too small to assess significance. Common variants in KCNJ11 and BAD do not predict response to KDT for epilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes. (C) 2015 Elsevier B.V. All rights reserved. C1 [Schoeler, Natasha E.; Leu, Costin; Matarin, Mar; Sander, Josemir W.; Sisodiya, Sanjay M.] Univ Coll London Hosp, NIHR, Biomed Res Ctr, Dept Clin & Expt Epilepsy,Inst Neurol, London WC1N 3BG, England. [Schoeler, Natasha E.; Cross, J. Helen] UCL, Inst Child Hlth, London, England. [White, Jon] UCL, Genet Inst, Dept Genet Environm & Evolut, London, England. [Plagnol, Vincent] UCL, Dept Stat Genet, London, England. [Ellard, Sian] Univ Exeter, Sch Med, Mol Genet, Exeter, Devon, England. [Yellen, Gary] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mackay, Mark; Scheffer, Ingrid E.] Royal Childrens Hosp, Melbourne, Australia. [Mackay, Mark] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [McMahon, Jacinta M.] Univ Melbourne, Epilepsy Res Ctr, Austin Hlth, Melbourne, Vic, Australia. [Scheffer, Ingrid E.] Univ Melbourne, Dept Med & Paediat, Melbourne, Vic, Australia. [Scheffer, Ingrid E.] Austin Hlth, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia. [Sander, Josemir W.; Sisodiya, Sanjay M.] Epilepsy Soc, Gerrards Cross, England. [Sander, Josemir W.] SEIN, Heemstede, Netherlands. [Cross, J. Helen] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Cross, J. Helen] Young Epilepsy, Lingfield, England. RP Schoeler, NE (reprint author), Univ Coll London Hosp, NIHR, Biomed Res Ctr, Dept Clin & Expt Epilepsy,Inst Neurol, 33 Queen Sq, London WC1N 3BG, England. EM n.schoeler.10@ucl.ac.uk RI Sander, Josemir/C-1576-2008; Matarin, Mar/F-1771-2016; OI Sander, Josemir/0000-0001-6041-9661; Matarin, Mar/0000-0002-4717-5735; Plagnol, Vincent/0000-0002-5597-9215 FU Wellcome Trust [084730]; UCL Impact Studentship in conjunction with Epilepsy Society; Epilepsy Research UK [F1206]; Epilepsy Society; Dr. Marvin Weil Epilepsy Research Fund; Eisai; GSK; WHO; EU; National Institutes of Health (NIH); UCB Pharma; Vitaflo; European Commission; Dravet Syndrome UK; Epilepsy Action; MRC; NIH; Katy Baggott Foundation FX This study was partly funded by the Wellcome Trust (084730). NES is supported by a UCL Impact Studentship in conjunction with Epilepsy Society. MM is supported by Epilepsy Research UK (F1206). JWS receives research support from Epilepsy Society, the Dr. Marvin Weil Epilepsy Research Fund, Eisai, GSK, WHO, EU FP7 and the National Institutes of Health (NIH), and has been consulted by and received fees for lectures from GSK, Eisai and UCB Pharma. JHC has received funds to the department for research into the ketogenic diet from Vitaflo. Honoraria for speaking have also been made to the department on her behalf from Nutricia. JHC and IS have written a cookery book aetocooking', funds from the sale of which will be donated to their respective departments. SMS receives research support from Epilepsy Society, The Wellcome Trust, The European Commission, Dravet Syndrome UK, Epilepsy Action, MRC, NIH and The Katy Baggott Foundation and has received research support/fees from lectures from Eisai, GSK and UCB Pharma. The remaining authors have no conflicts of interest. NR 33 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD DEC PY 2015 VL 118 BP 22 EP 28 DI 10.1016/j.eplepsyres.2015.10.003 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CZ0AH UT WOS:000366767000005 PM 26590798 ER PT J AU Hur, HC King, LP Klebanoff, MJ Hur, C Ricciotti, HA AF Hur, Hye-Chun King, Louise P. Klebanoff, Matthew J. Hur, Chin Ricciotti, Hope A. TI Fibroid morcellation: a shared clinical decision tool for mode of hysterectomy SO EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE Laparoscopic hysterectomy; Laparotomy; Morcellation; Uterine fibroids; Uterine sarcoma ID QUALITY-OF-LIFE; LAPAROSCOPIC HYSTERECTOMY; ABDOMINAL HYSTERECTOMY; CONTROLLED-TRIAL; UTERINE SARCOMA; BENIGN DISEASE; SURGERY; PREVENTION; ADHESIONS; OBSTRUCTION AB Objective: To compare risks and benefits of laparoscopic hysterectomy with morcellation versus abdominal hysterectomy without morcellation for large fibroids. Study design: We developed a shared clinical decision tool to communicate risks and benefits of laparoscopic versus abdominal hysterectomy to patients with large fibroids as mandated by the FDA. The decision tool was designed to serve as a framework for providers to counsel patients about mode of hysterectomy to facilitate shared decision-making between patient and provider. Risks and benefits were estimated from the literature, including surgical complications (venous thromboembolism, small bowel obstruction, adhesions, hernia, surgical site infections, and transfusions), uterine sarcoma risks, and quality-of-life endpoints. The shared clinical decision tool was applied to a hypothetical population of 20,000 patients with large uterine fibroids, of which 10,000 underwent laparoscopic hysterectomies and 10,000 had abdominal hysterectomies. Results: Abdominal hysterectomy would result in 50.1% more adhesions, 10.7% more hernias, 4.8% more surgical site infections, 2.8% more bowel obstructions, and 2% more venous thromboembolisms compared to laparoscopic hysterectomy. Abdominal hysterectomy would also result in longer hospital stays (2 days), slower return to work (13.6 days), greater postoperative day 3 narcotic requirements (48%), and lower SF-36 quality-of-life scores (50.4 points lower). 0.28% of fibroid hysterectomy patients would have unsuspected uterine sarcomas. Among these patients, laparoscopic hysterectomy with morcellation would have a 27% reduction in 5-year overall survival rates and a 28.8 month shorter recurrence-free survival period. Conclusion: Some evidence suggests laparoscopic hysterectomy with morcellation may result in increased risk of cancer dissemination with worse survival outcomes among uterine sarcoma patients compared to abdominal hysterectomy without morcellation, however, the current data is limited and the exact risks associated specifically with electromechanical morcellation are not conclusive. Data also supports abdominal hysterectomy would lead to a net detriment in other outcomes, with greater risks of venous thromboembolism, obstruction, hernia, adhesions, infection, and blood loss compared to laparoscopic hysterectomy. This shared clinical decision tool may aid the patient and physician in determining an optimal mode of hysterectomy for large uterine fibroids while taking account of risks and benefits as mandated by the FDA. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Hur, Hye-Chun; King, Louise P.; Ricciotti, Hope A.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Klebanoff, Matthew J.; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Hur, Hye-Chun; King, Louise P.; Hur, Chin; Ricciotti, Hope A.] Harvard Univ, Sch Med, Boston, MA USA. RP Hur, HC (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Minimally Invas Gynecol, 330 Brookline Ave, Boston, MA 02215 USA. EM hhur@bidmc.harvard.edu OI Hur, Chin/0000-0002-2819-7576 NR 29 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-2115 EI 1872-7654 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD DEC PY 2015 VL 195 BP 122 EP 127 DI 10.1016/j.ejogrb.2015.09.044 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CZ4ZS UT WOS:000367112500022 PM 26520875 ER PT J AU Simonneau, G Channick, RN Delcroix, M Galie, N Ghofrani, HA Jansa, P Le Brun, FO Mehta, S Perchenet, L Pulido, T Sastry, BKS Sitbon, O Souza, R Torbicki, A Rubin, LJ AF Simonneau, Gerald Channick, Richard N. Delcroix, Marion Galie, Nazzareno Ghofrani, Hossein-Ardeschir Jansa, Pavel Le Brun, Franck-Olivier Mehta, Sanjay Perchenet, Loic Pulido, Tomas Sastry, B. K. S. Sitbon, Olivier Souza, Rogerio Torbicki, Adam Rubin, Lewis J. TI Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID SURVIVAL; REGISTRY; EPIDEMIOLOGY; MACITENTAN; CANCER AB In SERAPHIN, a long-term, randomised, controlled trial (NCT00660179) in pulmonary arterial hypertension (PAH), macitentan significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation. We evaluated disease progression and the effect of macitentan in treatment-nave incident and prevalent cohorts. Patients allocated to placebo, or macitentan 3 mg or 10 mg were classified by time from diagnosis to enrolment as incident (<= 6 months; n=110) or prevalent (>6 months; n=157). The risk of morbidity/mortality and PAH-related death/hospitalisation was determined using Cox regression. The risk of morbidity/mortality (Kaplan-Meier estimates at month 12: 54.4% versus 26.7%; p=0.006) and PAH-related death/hospitalisation (Kaplan-Meier estimates at month 12: 47.3% versus 19.9%; p=0.006) were significantly higher for incident versus prevalent patients receiving placebo, respectively. There was no significant difference in the risk of all-cause death between incident and prevalent cohorts (p=0.587). Macitentan 10 mg significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation versus placebo in incident and prevalent cohorts. Incident patients had a higher risk for PAH progression compared with prevalent patients but not a higher risk of death. Macitentan delayed disease progression in both incident and prevalent PAH patients. C1 [Simonneau, Gerald; Sitbon, Olivier] Hop Bicetre, AP HP, Serv Pneumol, F-94270 Le Kremlin Bicetre, France. [Simonneau, Gerald; Sitbon, Olivier] Univ Paris 11, Lab Excellence Rech Medicament & Innovat Therapeu, Le Kremlin Bicetre, France. [Simonneau, Gerald; Sitbon, Olivier] Ctr Chirurg Marie Lannelongue, INSERM U 999, Le Plessis Robinson, France. [Channick, Richard N.] Massachusetts Gen Hosp, Pulm & Crit Care, Boston, MA 02114 USA. [Delcroix, Marion] Univ Hosp Gasthuisberg, Dept Pneumol, Leuven, Belgium. [Galie, Nazzareno] Bologna Univ Hosp, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy. [Ghofrani, Hossein-Ardeschir] Univ Giessen, D-35390 Giessen, Germany. [Ghofrani, Hossein-Ardeschir] Marburg Lung Ctr, Giessen, Germany. [Ghofrani, Hossein-Ardeschir] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. [Jansa, Pavel] Charles Univ Prague, Fac Med 1, Dept Med 2, Clin Dept Cardiol & Angiol, Prague, Czech Republic. [Le Brun, Franck-Olivier; Perchenet, Loic] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Mehta, Sanjay] Western Univ, Victoria Hosp, London Hlth Sci Ctr, Dept Med,Div Respirol, London, ON, Canada. [Pulido, Tomas] Ignacio Chavez Natl Heart Inst, Cardiopulm Dept, Mexico City, DF, Mexico. [Sastry, B. K. S.] CARE Hosp, Dept Cardiol, Hyderabad, Andhra Pradesh, India. [Souza, Rogerio] Univ Sao Paulo, Sch Med, Inst Heart, Dept Pulm, Sao Paulo, Brazil. [Torbicki, Adam] ECZ Otwock, Ctr Postgrad Med Educ, Dept Pulm Circulat & Thromboembol Dis, Otwock, Poland. [Rubin, Lewis J.] Univ Calif San Diego, Sch Med, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. RP Simonneau, G (reprint author), Hop Bicetre, AP HP, Serv Pneumol, 78 Rue Gen Leclerc, F-94270 Le Kremlin Bicetre, France. EM gerald.simonneau@bct.aphp.fr OI Galie, Nazzareno/0000-0003-4271-8670 FU Actelion Pharmaceuticals Ltd. FX SERAPHIN was funded by Actelion Pharmaceuticals Ltd. Medical writing support was provided by Lisa Thomas of Elements Communications Ltd (Westerham, UK) (manuscript outline), Marion James and Jonathan Viney of Apothecom Scopemedical Ltd (London, UK) (manuscript), and Anoushka Thomas of nspm ltd (Meggen, Switzerland) (manuscript), funded by Actelion Pharmaceuticals Ltd. Funding information for this article has been deposited with FundRef. NR 19 TC 9 Z9 9 U1 0 U2 6 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD DEC PY 2015 VL 46 IS 6 BP 1711 EP 1720 DI 10.1183/13993003.00364-2015 PG 10 WC Respiratory System SC Respiratory System GA CZ2QC UT WOS:000366948700025 PM 26493786 ER PT J AU Barry, CL Stuart, EA Donohue, JM Greenfield, SF Kouri, E Duckworth, K Song, ZR Mechanic, RE Chernew, ME Huskamp, HA AF Barry, Colleen L. Stuart, Elizabeth A. Donohue, Julie M. Greenfield, Shelly F. Kouri, Elena Duckworth, Kenneth Song, Zirui Mechanic, Robert E. Chernew, Michael E. Huskamp, Haiden A. TI The Early Impact Of The 'Alternative Quality Contract' On Mental Health Service Use And Spending In Massachusetts SO HEALTH AFFAIRS LA English DT Article ID CARDIOVASCULAR-DISEASE; INSURANCE PARITY; PRIMARY-CARE; DEPRESSION; ILLNESS; SYMPTOMS; MODELS; COSTS AB Accountable care using global payment with performance bonuses has shown promise in controlling spending growth and improving care. This study examined how an early model, the Alternative Quality Contract (AQC) established in 2009 by Blue Cross Blue Shield of Massachusetts (BCBSMA), has affected care for mental illness. We compared spending and use for enrollees in AQC organizations that did and did not accept financial risk for mental health with enrollees not participating in the contract. Compared with BCBSMA enrollees in organizations not participating in the AQC, we found that enrollees in participating organizations were slightly less likely to use mental health services and, among mental health services users, small declines were detected in total health care spending, but no change was found in mental health spending. The declines in probability of use of mental health services and in total health spending among mental health service users attributable to the AQC were concentrated among enrollees in organizations that accepted financial risk for behavioral health. Interviews with AQC organization leaders suggested that the contractual arrangements did not meaningfully affect mental health care delivery in the program's initial years, but organizations are now at varying stages of efforts to improve mental health integration. C1 [Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Res & Practice, Baltimore, MD 21205 USA. [Stuart, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15260 USA. [Greenfield, Shelly F.] McLean Hosp, Psychiat, Belmont, MA 02178 USA. [Kouri, Elena] Harvard Univ, Sch Med, Hlth Care Policy, Boston, MA USA. [Duckworth, Kenneth] Blue Cross & Blue Shield Massachusetts, Behav Hlth, Quincy, MA USA. [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Mechanic, Robert E.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Chernew, Michael E.; Huskamp, Haiden A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Barry, CL (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Res & Practice, Baltimore, MD 21205 USA. EM cbarry@jhu.edu OI Donohue, Julie/0000-0003-2418-6017 FU Commonwealth Fund (multi-principal investigators: Colleen Barry and Haiden Huskamp) [20130499]; National Institute on Drug Abuse [K24 DA019855] FX Preliminary results were presented at the National Institute of Mental Health's Mental Health Services Research Conference, in Bethesda, Maryland, April 2014; and at the Association for Public Policy Analysis and Management's Fall Research Conference, in Albuquerque, New Mexico, November 2014. The authors acknowledge funding support from the Commonwealth Fund (Grant No. 20130499; multi-principal investigators: Colleen Barry and Haiden Huskamp). Shelly Greenfield acknowledges support from the National Institute on Drug Abuse (Grant No. K24 DA019855). Robert Mechanic is a trustee at Atrius Health, one of the provider organizations that signed the Alternative Quality Contract with Blue Cross Blue Shield of Massachusetts (BCBSMA). The authors thank Dana Gelb Safran at BCBSMA and Jeffrey Simmons, formerly of BCBSMA, for their support of the project, and Christina Fu and Hocine Azeni of Harvard Medical School for expert programming support. The authors also thank Alisa B. Busch for her assistance in developing mental health diagnostic cohorts and comorbidity categories, as well as mental health treatment categories derived from procedure codes. NR 25 TC 4 Z9 4 U1 2 U2 7 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD DEC PY 2015 VL 34 IS 12 BP 2077 EP 2085 DI 10.1377/hlthaff.2015.0685 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CY9KB UT WOS:000366724700010 PM 26643628 ER PT J AU McCauley, MP Ramanadhan, S Viswanath, K AF McCauley, M. P. Ramanadhan, S. Viswanath, K. TI Assessing opinions in community leadership networks to address health inequalities: a case study from Project IMPACT SO HEALTH EDUCATION RESEARCH LA English DT Article ID SOCIAL DETERMINANTS; COMMUNICATION; DISPARITIES; CHALLENGES AB This study demonstrates a novel approach that those engaged in promoting social change in health can use to analyze community power, mobilize it and enhance community capacity to reduce health inequalities. We used community reconnaissance methods to select and interview 33 participants from six leadership sectors in 'Milltown', the New England city where the study was conducted. We used UCINET network analysis software to assess the structure of local leadership and NVivo qualitative software to analyze leaders' views on public health and health inequalities. Our main analyses showed that community power is distributed unequally in Milltown, with our network of 33 divided into an older, largely male and more powerful group, and a younger, largely female group with many 'grassroots' sector leaders who focus on reducing health inequalities. Ancillary network analyses showed that grassroots leaders comprise a self-referential cluster that could benefit from greater affiliation with leaders from other sectors and identified leaders who may serve as leverage points in our overall program of public agenda change to address health inequalities. Our innovative approach provides public health practitioners with a method for assessing community leaders' views, understanding subgroup divides and mobilizing leaders who may be helpful in reducing health inequalities. C1 [McCauley, M. P.] Med Coll Wisconsin, Ctr Bioeth & Med Humanities, Milwaukee, WI 53226 USA. [Ramanadhan, S.; Viswanath, K.] Harvard Univ, TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Ramanadhan, S.; Viswanath, K.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. RP McCauley, MP (reprint author), Med Coll Wisconsin, Ctr Bioeth & Med Humanities, Milwaukee, WI 53226 USA. EM mmccauley@mcw.edu FU National Cancer Institute PI of Project on Public Agenda Setting [5P50CA148596]; National Institutes of Health [3R25CA057711-18S1] FX National Cancer Institute (5P50CA148596 to K.V., PI of the Project on Public Agenda Setting); National Institutes of Health (3R25CA057711-18S1). NR 51 TC 0 Z9 0 U1 4 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 EI 1465-3648 J9 HEALTH EDUC RES JI Health Educ. Res. PD DEC PY 2015 VL 30 IS 6 BP 866 EP 881 DI 10.1093/her/cyv049 PG 16 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA CZ5UG UT WOS:000367166900004 PM 26471919 ER PT J AU Liang, TJ Block, TM McMahon, BJ Ghany, MG Urban, S Guo, JT Locarnini, S Zoulim, F Chang, KM Lok, AS AF Liang, T. Jake Block, Timothy M. McMahon, Brian J. Ghany, Marc G. Urban, Stephan Guo, Ju-Tao Locarnini, Stephen Zoulim, Fabien Chang, Kyong-Mi Lok, Anna S. TI Present and Future Therapies of Hepatitis B: From Discovery to Cure SO HEPATOLOGY LA English DT Review ID CLOSED CIRCULAR DNA; TENOFOVIR DISOPROXIL FUMARATE; TAUROCHOLATE COTRANSPORTING POLYPEPTIDE; COMPLEX THERAPEUTIC VACCINE; CHIMERIC ANTIGEN RECEPTOR; ANTIVIRAL IMMUNE-RESPONSE; LARGE SURFACE PROTEIN; D VIRUS ENTRY; T-CELLS; IN-VIVO AB Hepatitis B virus (HBV) is a significant global pathogen, infecting more than 240 million people worldwide. While treatment for HBV has improved, HBV patients often require lifelong therapies and cure is still a challenging goal. Recent advances in technologies and pharmaceutical sciences have heralded a new horizon of innovative therapeutic approaches that are bringing us closer to the possibility of a functional cure of chronic HBV infection. In this article, we review the current state of science in HBV therapy and highlight new and exciting therapeutic strategies spurred by recent scientific advances. Some of these therapies have already entered into clinical phase, and we will likely see more of them moving along the development pipeline. Conclusion: With growing interest in developing and efforts to develop more effective therapies for HBV, the challenging goal of a cure may be well within reach in the near future. C1 [Liang, T. Jake; Ghany, Marc G.] NIDDK, LDB, NIH, Bethesda, MD 20892 USA. [Block, Timothy M.] Baruch S Blumberg Inst, Doylestown, PA USA. [McMahon, Brian J.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Anchorage, AK USA. [Urban, Stephan] Univ Heidelberg Hosp, Mol Virol, Dept Infect Dis, Heidelberg, Germany. [Urban, Stephan] Univ Heidelberg Hosp, German Ctr Infect Dis, Heidelberg, Germany. [Locarnini, Stephen] Lyon Univ, Hepatol Dept, Lyon, France. [Locarnini, Stephen] Canc Res Ctr Lyon, INSERM, U1052, Lyon, France. [Zoulim, Fabien] Doherty Inst, Victorian Infect Dis Reference Lab, Melbourne, Vic, Australia. [Chang, Kyong-Mi] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Chang, Kyong-Mi] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lok, Anna S.] Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA. RP Liang, TJ (reprint author), NIDDK, LDB, NIH, Bldg 10-9B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM jliang@nih.gov FU Janssen; Oncore-Tekmira; Gilead; Bristol-Myers Squibb; Roche; Novira; Arrowhead FX Dr. Guo received grants from Janssen. Dr. Block is on the Board of and owns stock in Contravir. He received grants and holds intellectual property rights with Oncore-Tekmira. Dr. Lok consults and received grants from Gilead. She consults from GlaxoSmithKline, Merck, MYR, and Tekmira. She received grants from Bristol-Myers Squibb. Dr. Chang advises Genentech, Arbutus, and Alnylam. Dr. Zoulim consults and received grants from Roche, Gilead, and Novira. He consults for Janssen. Dr. Locarnini received royalties and holds intellectual property rights with Melbourne Health. He consults and received fees from Arrowhead. He consults for Gilead. NR 154 TC 32 Z9 33 U1 6 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD DEC PY 2015 VL 62 IS 6 BP 1893 EP 1908 DI 10.1002/hep.28025 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CZ3OF UT WOS:000367013200059 PM 26239691 ER PT J AU Nahrendorf, M Swirski, FK AF Nahrendorf, Matthias Swirski, Filip K. TI PET Imaging of Leukocytes in Patients With Acute Myocardial Infarction SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE chemokine receptor; CXCR4; inflammation; myocardial infarction; positron emission tomography ID ATHEROSCLEROSIS; CELLS; STEM C1 [Nahrendorf, Matthias] Massachusetts Gen Hosp, Dept Radiol, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@partners.org FU NHLBI NIH HHS [HL096576] NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD DEC PY 2015 VL 8 IS 12 BP 1427 EP 1429 DI 10.1016/j.jcmg.2015.10.004 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CZ6IS UT WOS:000367205100012 PM 26699111 ER PT J AU Thanos, A Esmaili, DD Eliott, D AF Thanos, Aristomenis Esmaili, Daniel D. Eliott, Dean TI Cotton-Wool Spots Associated With Mild Nonprogressive Visual Loss SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID GIANT-CELL ARTERITIS C1 [Thanos, Aristomenis; Eliott, Dean] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, Boston, MA 02114 USA. [Thanos, Aristomenis; Eliott, Dean] Harvard Univ, Sch Med, Boston, MA USA. [Esmaili, Daniel D.] Retina Vitreous Associates Med Grp, Los Angeles, CA USA. RP Eliott, D (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD DEC PY 2015 VL 133 IS 12 BP 1471 EP 1472 DI 10.1001/jamaophthalmol.2015.1967 PG 2 WC Ophthalmology SC Ophthalmology GA CZ4RV UT WOS:000367091300020 PM 26448135 ER PT J AU Stagner, AM Jakobiec, FA Iwamoto, MA AF Stagner, Anna M. Jakobiec, Frederick A. Iwamoto, Mami A. TI Invasive Squamous Cell Carcinoma With Clear Cell Change of the Eyelid Arising in a Seborrheic Keratosis SO JAMA OPHTHALMOLOGY LA English DT Letter C1 [Stagner, Anna M.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Stagner, Anna M.; Jakobiec, Frederick A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Iwamoto, Mami A.] Ophthalm Consultants Boston, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Ste 328, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 6 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD DEC PY 2015 VL 133 IS 12 BP 1476 EP 1477 DI 10.1001/jamaophthalmol.2015.3439 PG 3 WC Ophthalmology SC Ophthalmology GA CZ4RV UT WOS:000367091300022 PM 26426916 ER PT J AU de Almeida, JR Li, R Magnuson, JS Smith, RV Moore, E Lawson, G Remacle, M Ganly, I Kraus, DH Teng, MS Miles, BA White, H Duvvuri, U Ferris, RL Mehta, V Kiyosaki, K Damrose, EJ Wang, SJ Kupferman, ME Koh, Y Genden, EM Holsinger, FC AF de Almeida, John R. Li, Ryan Magnuson, J. Scott Smith, Richard V. Moore, Eric Lawson, Georges Remacle, Marc Ganly, Ian Kraus, Dennis H. Teng, Marita S. Miles, Brett A. White, Hilliary Duvvuri, Umamaheswar Ferris, Robert L. Mehta, Vikas Kiyosaki, Krista Damrose, Edward J. Wang, Steven J. Kupferman, Michael E. Koh, YoonWoo Genden, Eric M. Holsinger, F. Christopher TI Oncologic Outcomes After Transoral Robotic Surgery A Multi-institutional Study SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PAPILLOMAVIRUS-ASSOCIATED CANCERS; OROPHARYNGEAL CANCER; NECK-CANCER; FUNCTIONAL OUTCOMES; LATERAL OROPHARYNGECTOMY; TONSILLAR REGION; ORAL-CAVITY; HEAD; EXPERIENCE AB IMPORTANCE Large patient cohorts are necessary to validate the efficacy of transoral robotic surgery (TORS) in the management of head and neck cancer. OBJECTIVES To review oncologic outcomes of TORS from a large multi-institutional collaboration and to identify predictors of disease recurrence and disease-specific mortality. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of records from 410 patients undergoing TORS for laryngeal and pharyngeal cancers from January 1, 2007, through December 31, 2012, was performed. Pertinent data were obtained from 11 participating medical institutions. INTERVENTIONS Select patients received radiation therapy and/or chemotherapy before or after TORS. MAIN OUTCOMES AND MEASURES Locoregional control, disease-specific survival, and overall survival were calculated. We used Kaplan-Meier survival analysis with log-rank testing to evaluate individual variable association with these outcomes, followed by multivariate analysis with Cox proportional hazards regression modeling to identify independent predictors. RESULTS Of the 410 patients treated with TORS in this study, 364 (88.8%) had oropharyngeal cancer. Of these 364 patients, information about post-operative adjuvant therapy was known about 338: 106 (31.3) received radiation therapy alone, and 72 (21.3%) received radiation therapy with concurrent chemotherapy. Neck dissection was performed in 323 patients (78.8%). Mean follow-up time was 20 months. Local, regional, and distant recurrence occurred in 18 (4.4%), 15 (3.7%), and 10 (2.4%) of 410 patients, respectively. Seventeen (4.1%) died of disease, and 13 (3.2%) died of other causes. The 2-year locoregional control rate was 91.8% (95% CI, 87.6%-94.7%), disease-specific survival 94.5% (95% CI, 90.6%-96.8%), and overall survival 91% (95% CI, 86.5%-94.0%). Multivariate analysis identified improved survival among women (P = .05) and for patients with tumors arising in tonsil (P = .01). Smoking was associated with worse overall all-cause mortality (P = .01). Although advanced age and tobacco use were associated with locoregional recurrence and disease-specific survival, they, as well as tumor stage and other adverse histopathologic features, did not remain significant on multivariate analysis. CONCLUSIONS AND RELEVANCE This large, multi-institutional study supports the role of TORS within the multidisciplinary treatment paradigm for the treatment of head and neck cancer, especially for patients with oropharyngeal cancer. Favorable oncologic outcomes have been found across institutions. Ongoing comparative clinical trials funded by the National Cancer Institute will further evaluate the role of robotic surgery for patients with head and neck cancers. C1 [de Almeida, John R.] Princess Margaret Canc Ctr, Dept Otolaryngol Head & Neck Surg, Toronto, ON, Canada. [Li, Ryan; Kiyosaki, Krista; Damrose, Edward J.; Holsinger, F. Christopher] Stanford Univ, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Surg, Palo Alto, CA 94305 USA. [Magnuson, J. Scott; White, Hilliary] Univ Alabama Birmingham, Dept Otolaryngol Head & Neck Surg, Birmingham, AL USA. [Smith, Richard V.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, New York, NY USA. [Moore, Eric] Mayo Clin, Dept Otolaryngol Head & Neck Surg, Rochester, MN USA. [Lawson, Georges; Remacle, Marc] Catholic Univ Louvain Mont Godinne, Yvoir, Belgium. [Ganly, Ian] Mem Sloan Kettering Canc Ctr, Dept Surg Head & Neck Oncol, New York, NY 10021 USA. [Kraus, Dennis H.] North Shore Hlth Syst, New York Head & Neck Inst, New York, NY USA. [Teng, Marita S.; Miles, Brett A.; Genden, Eric M.] Icahn Sch Med Mt Sinai, Dept Otolaryngol Head & Neck Surg, New York, NY 10029 USA. [Mehta, Vikas] Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh HealthCare Syst, Dept Otolaryngol Head & Neck Surg, Pittsburgh, PA USA. [Wang, Steven J.] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. [Kupferman, Michael E.; Holsinger, F. Christopher] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Koh, YoonWoo] Yonsei Univ, Sch Med, Severance Hosp, Seoul 120749, South Korea. RP Holsinger, FC (reprint author), Stanford Univ, Dept Otolaryngol Head & Neck Surg, 875 Blake Wilbur Dr, Palo Alto, CA 94305 USA. EM holsinger@stanford.edu OI Ganly, Ian/0000-0001-7636-5426 FU Bureau of Labor Statistics, Research and Development; Department of Veterans Affairs FX This study was supported in part by funds from the Bureau of Labor Statistics, Research and Development, Department of Veterans Affairs (Dr Duvvuri). NR 35 TC 16 Z9 16 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD DEC PY 2015 VL 141 IS 12 BP 1043 EP 1051 DI 10.1001/jamaoto.2015.1508 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CZ5MJ UT WOS:000367146400003 PM 26402479 ER PT J AU Maxwell, JH Thompson, LDR Brandwein-Gensler, MS Weiss, BG Canis, M Purgina, B Prabhu, AV Lai, C Shuai, YL Carroll, WR Morlandt, A Duvvuri, U Kim, S Johnson, JT Ferris, RL Seethala, R Chiosea, SI AF Maxwell, Jessica H. Thompson, Lester D. R. Brandwein-Gensler, Margaret S. Weiss, Bernhard G. Canis, Martin Purgina, Bibianna Prabhu, Arpan V. Lai, Chi Shuai, Yongli Carroll, William R. Morlandt, Anthony Duvvuri, Umamaheswar Kim, Seungwon Johnson, Jonas T. Ferris, Robert L. Seethala, Raja Chiosea, Simion I. TI Early Oral Tongue Squamous Cell Carcinoma Sampling of Margins From Tumor Bed and Worse Local Control SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID MICROSCOPIC CUT-THROUGH; FROZEN-SECTION MARGINS; LASER MICROSURGERY; NECK-CANCER; IMPACT; HEAD; CAVITY; RESECTIONS; RATES AB IMPORTANCE Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique. OBJECTIVE To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC. DESIGN, SETTING, AND PARTICIPANTS A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pNO oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015. INTERVENTIONS In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR. MAIN OUTCOMES AND MEASURES Local recurrence. RESULTS Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin. CONCLUSIONS AND RELEVANCE The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended. C1 [Maxwell, Jessica H.; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T.; Ferris, Robert L.] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Thompson, Lester D. R.] So Calif Permanente Med Grp, Dept Pathol, Woodland Hills, CA USA. [Brandwein-Gensler, Margaret S.] Univ Alabama Birmingham, Dept Pathol, Div Anat Pathol, Birmingham, AL USA. [Brandwein-Gensler, Margaret S.] SUNY Buffalo, Dept Pathol & Anat Sci, Buffalo, NY 14260 USA. [Brandwein-Gensler, Margaret S.] Erie Cty Med Ctr & Labs, Buffalo, NY USA. [Weiss, Bernhard G.; Canis, Martin] Univ Gottingen, Dept Otorhinolaryngol Head & Neck Surg, D-37073 Gottingen, Germany. [Purgina, Bibianna; Lai, Chi] Univ Ottawa, Dept Pathol & Lab Med, Ottawa Hosp, Ottawa, ON, Canada. [Prabhu, Arpan V.; Seethala, Raja; Chiosea, Simion I.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA. [Shuai, Yongli] Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA 15213 USA. [Carroll, William R.; Morlandt, Anthony] Univ Alabama Birmingham, Dept Surg Head & Neck Oncol, Birmingham, AL USA. [Duvvuri, Umamaheswar] Vet Affairs Pittsburgh Hlth Syst, Dept Otolaryngol, Pittsburgh, PA USA. RP Chiosea, SI (reprint author), Univ Pittsburgh, Med Ctr, Dept Pathol, 200 Lothrop St,A610 Room 3, Pittsburgh, PA 15213 USA. EM chioseasi@upmc.edu RI Prabhu, Arpan/M-4193-2014; Thompson, Lester/J-8404-2016 OI Prabhu, Arpan/0000-0002-9928-2911; Thompson, Lester/0000-0003-3714-1432 FU [P30CA047904] FX This project used the University of Pittsburgh Cancer Institute Biostatistics Facility that is supported in part by award P30CA047904. NR 27 TC 6 Z9 7 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD DEC PY 2015 VL 141 IS 12 BP 1104 EP 1110 DI 10.1001/jamaoto.2015.1351 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CZ5MJ UT WOS:000367146400012 PM 26225798 ER PT J AU Andren, O Armstrong, J Berry, D Bolla, M Buyse, M Chowdhury, S Clarke, N Collette, L Cooperberg, M Denham, J Eisenberger, M Dignam, J Fizazi, K Freidlin, B Gleave, M Habibian, M Halabi, S Hayes, J James, N Jarow, J Keating, N Kantoff, P Kelloff, G Klotz, L Li, SH Lukka, H Mahal, B Mason, M Miyahara, A Nakabayashi, M Parulekar, W Philipson, T Regan, M Sandler, H Sartor, O Scardino, P Scher, H Simon, R Simons, J Small, E Soule, H Sweeney, C Sydes, M Tangen, C Thompson, I Tombal, B Widmark, A Wiegel, T Williams, S Xie, WL AF Andren, Ove Armstrong, John Berry, Donald Bolla, Michel Buyse, Marc Chowdhury, Simon Clarke, Noel Collette, Laurence Cooperberg, Matthew Denham, Jim Eisenberger, Mario Dignam, James Fizazi, Karim Freidlin, Boris Gleave, Martin Habibian, Muriel Halabi, Susan Hayes, Julia James, Nick Jarow, Jonathan Keating, Nancy Kantoff, Philip Kelloff, Gary Klotz, Laurence Li, Suhui Lukka, Himu Mahal, Brandon Mason, Malcolm Miyahara, Andrea Nakabayashi, Mari Parulekar, Wendy Philipson, Tomas Regan, Meredith Sandler, Howard Sartor, Oliver Scardino, Peter Scher, Howard Simon, Richard Simons, Jonathan Small, Eric Soule, Howard Sweeney, Christopher Sydes, Matthew Tangen, Catherine Thompson, Ian Tombal, Bertrand Widmark, Anders Wiegel, Thomas Williams, Scott Xie, Wanling CA ICECaP Working Grp TI The Development of Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BEAM RADIATION-THERAPY; ANTIGEN DOUBLING TIME; III RANDOMIZED-TRIAL; RADICAL PROSTATECTOMY; BIOCHEMICAL FAILURE; ANDROGEN SUPPRESSION; INCREASED SURVIVAL; HORMONAL-THERAPY; MORTALITY; RADIOTHERAPY AB New systemic therapies have prolonged the lives of men with metastatic castration-resistant prostate cancer (mCRPC). Use of these therapies in the adjuvant setting when the disease may be micrometastatic and potentially more sensitive to therapies may decrease mortality from prostate cancer. However, the conduct of adjuvant prostate cancer clinical trials is hampered by taking longer than a decade to reach the meaningful endpoint of overall survival (OS) and the fact that many men never die from prostate cancer, even if they relapse. A validated intermediate clinical endpoint (ICE) in prostate cancer that is a robust surrogate for OS has yet to be defined. This paper details the plans, process, and progress of the international Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group to pool individual patient data from all available clinical trials of radiation or prostatectomy for localized disease and conduct the requisite analyses to determine whether an ICE can be identified. This paper further details the challenges and the a priori statistical analytical plans and strategies to define an ICE for adjuvant prostate cancer clinical trials. In addition, a brief review of the health economic analyses to model the benefits to patients, society and manufacturers is detailed. If successful, the results from this work will provide a robust surrogate for OS that will expedite the design and conduct of future adjuvant therapy trials using new agents that have proven activity in mCRPC. Moreover, it will also define the health economic benefits to patients and societies. RP Sweeney, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,D1230, Boston, MA 02468 USA. EM christopher_sweeney@dfci.harvard.edu OI Sydes, Matthew/0000-0002-9323-1371 NR 48 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD DEC PY 2015 VL 107 IS 12 AR djv261 DI 10.1093/jnci/djv261 PG 8 WC Oncology SC Oncology GA CZ2YN UT WOS:000366970900006 ER PT J AU Cho, E Zhang, XH Townsend, MK Selhub, J Paul, L Rosner, B Fuchs, CS Willett, WC Giovannucci, EL AF Cho, Eunyoung Zhang, Xuehong Townsend, Mary K. Selhub, Jacob Paul, Ligi Rosner, Bernard Fuchs, Charles S. Willett, Walter C. Giovannucci, Edward L. TI Unmetabolized Folic Acid in Prediagnostic Plasma and the Risk for Colorectal Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POSTMENOPAUSAL WOMEN; FOLATE; FORTIFICATION; SERUM; HOMOCYSTEINE; FOOD AB Higher folate has been associated with a reduced colorectal cancer (CRC) risk, but excessive folate may promote tumor progression. The role of unmetabolized folic acid (UFA) from high folic acid consumption in carcinogenesis is largely unexplored. We evaluated prediagnostic plasma levels of UFA in relation to CRC risk in nested case-control studies (618 CRC case patients and 1207 matched control) with blood samples collected prior to folic acid fortification. UFA was detected in 21.4% of control UFA levels were not associated with CRC risk. Compared with undetectable levels, the multivariable relative risks (RRs) of CRC were 1.03 (95% confidence interval [CI] = 0.73 to 1.46) for less than 0.5 nmol/L and 1.12 (95% CI = 0.81 to 1.55) for 0.5 nmol/L or more (P-trend = .32). A positive association between UFA levels and CRC risk was observed among men (RR = 1.57, 95% CI = 0.99 to 2.49 for >= 0.5 nmol/L vs undetectable, P-interaction =.04), and a positive association was also observed among those with the methylene-tetrahydrofolate reductase (MTHFR) CT/TT genotype (RR = 2.20, 95% CI = 1.22 to 3.94 for >= 0.5 nmol/L vs undetectable, P-interaction = 0.02). In conclusion, prediagnostic plasma levels of UFA from the prefortification period were not associated with risk of CRC. C1 [Cho, Eunyoung; Zhang, Xuehong; Townsend, Mary K.; Rosner, Bernard; Willett, Walter C.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Cho, Eunyoung; Zhang, Xuehong; Townsend, Mary K.; Rosner, Bernard; Fuchs, Charles S.; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Cho, Eunyoung] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Selhub, Jacob; Paul, Ligi] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Rosner, Bernard] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cho, E (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Box G-D, Providence, RI 02912 USA. EM eunyoung_cho@brown.edu FU National Institutes of Health [CA136950, CA87969, CA49449, CA167552] FX This work was supported by research grants CA136950 (to EC), CA87969, CA49449, and CA167552 (to WCW) from the National Institutes of Health. NR 22 TC 4 Z9 4 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD DEC PY 2015 VL 107 IS 12 AR djv260 DI 10.1093/jnci/djv260 PG 4 WC Oncology SC Oncology GA CZ2YN UT WOS:000366970900005 PM 26376686 ER PT J AU Playdon, MC Bracken, MB Sanft, TB Ligibel, JA Harrigan, M Irwin, ML AF Playdon, Mary C. Bracken, Michael B. Sanft, Tara B. Ligibel, Jennifer A. Harrigan, Maura Irwin, Melinda L. TI Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID BODY-MASS INDEX; RECEIVING ADJUVANT CHEMOTHERAPY; RISK-FACTORS; LIFE-STYLE; PHYSICAL-ACTIVITY; TUMOR CHARACTERISTICS; POSTMENOPAUSAL WOMEN; POOLING PROJECT; ENERGY-BALANCE; FOLLOW-UP AB Background: Overweight and obesity are associated with breast cancer mortality. However, the relationship between postdiagnosis weight gain and mortality is unclear. We conducted a systematic review and meta-analysis of weight gain after breast cancer diagnosis and breast cancer-specific, all-cause mortality and recurrence outcomes. Methods: Electronic databases identified articles upthrough December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL (1982-present), and Web of Science. Language and publication status were unrestricted. Cohort studies and clinical trials measuring weight change after diagnosis and all-cause/breast cancer-specific mortality or recurrence were considered. Participants were women age 18 years or older with stage I-IIIC breast cancer. Fixed effects analysis summarized the association between weight gain (>= 5.0% body weight) and all-cause mortality; all tests were two-sided. Results: Twelve studies (n = 23 832) were included. Weight gain (>= 5.0%) compared with maintenance (<+/- 5.0%) was associated with increased all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.03 to 1.22, p=.01, I-2 = 55.0%). Higher risk of mortality was apparent for weight gain >= 10.0% (HR = 1.23, 95% CI = 1.09 to 1.39, p<.001); 5% to 10.0% weight gain was not associated with all-cause mortality (p=.40). The association was not statistically significant for those with a prediagnosis body mass index (BMI) of less than 25 kg/m(2) (HR = 1.14, 95% CI = 0.99 to 1.31, p=.07) or with a BMI of 25 kg/m(2) or higher (HR = 1.00, 95% CI = 0.86 to 1.16, p=.19). Weight gain of 10.0% or more was not associated with hazard of breast cancer-specific mortality (HR = 1.17, 95% CI = 1.00 to 1.38, p=.05). Conclusions: Weight gain after diagnosis of breast cancer is associated with higher all-cause mortality rates compared with maintaining body weight. Adverse effects are greater for weight gains of 10.0% or higher. C1 [Playdon, Mary C.; Bracken, Michael B.; Harrigan, Maura; Irwin, Melinda L.] Yale Univ, Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA. [Sanft, Tara B.; Irwin, Melinda L.] Yale Canc Ctr, New Haven, CT USA. [Ligibel, Jennifer A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Playdon, MC (reprint author), Yale Univ, 60 Coll St, New Haven, CT 06520 USA. EM mary.playdon@yale.edu RI Playdon, Mary/I-4050-2016 FU National Cancer Institute at the National Institutes of Health [T32 CA105666] FX This work was supported by the National Cancer Institute at the National Institutes of Health (grant number T32 CA105666 to Mary Playdon). NR 94 TC 20 Z9 21 U1 2 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD DEC PY 2015 VL 107 IS 12 AR djv275 DI 10.1093/jnci/djv275 PG 15 WC Oncology SC Oncology GA CZ2YN UT WOS:000366970900011 PM 26424778 ER PT J AU Sampson, JN Wheeler, WA Yeager, M Panagiotou, O Wang, Z Berndt, SI Lan, Q Abnet, CC Amundadottir, LT Figueroa, JD Landi, MT Mirabello, L Savage, SA Taylor, PR De Vivo, I McGlynn, KA Purdue, MP Rajaraman, P Adami, HO Ahlbom, A Albanes, D Amary, MF An, SJ Andersson, U Andriole, G Andrulis, IL Angelucci, E Ansell, SM Arici, C Armstrong, BK Arslan, AA Austin, MA Baris, D Barkauskas, DA Bassig, BA Becker, N Benavente, Y Benhamou, S Berg, C Van Den Berg, D Bernstein, L Bertrand, KA Birmann, BM Black, A Boeing, H Boffetta, P Boutron-Ruault, MC Bracci, PM Brinton, L Brooks-Wilson, AR Bueno-De-Mesquita, HB Burdett, L Buring, J Butler, MA Cai, QY Cancel-Tassin, G Canzian, F Carrato, A Carreon, T Carta, A Chan, JKC Chang, ET Chang, GC Chang, IS Chang, J Chang-Claude, J Chen, CJ Chen, CY Chen, C Chen, CH Chen, C Chen, HY Chen, KX Chen, KY Chen, KC Chen, Y Chen, YH Chen, YS Chen, YM Chien, LH Chirlaque, MD Choi, JE Choi, YY Chow, WH Chung, CC Clavel, J Clavel-Chapelon, F Cocco, P Colt, JS Comperat, E Conde, L Connors, JM Conti, D Cortessis, VK Cotterchio, M Cozen, W Crouch, S Crous-Bou, M Cussenot, O Davis, FG Ding, T Diver, WR Dorronsoro, M Dossus, L Duell, EJ Ennas, MG Erickson, RL Feychting, M Flanagan, AM Foretova, L Fraumeni, JF Freedman, ND Freeman, LEB Fuchs, C Gago-Dominguez, M Gallinger, S Gao, YT Gapstur, SM Garcia-Closas, M Garcia-Closas, R Gascoyne, RD Gastier-Foster, J Gaudet, MM Gaziano, JM Giffen, C Giles, GG Giovannucci, E Glimelius, B Goggins, M Gokgoz, N Goldstein, AM Gorlick, R Gross, M Grubb, R Gu, J Guan, P Gunter, M Guo, H Habermann, TM Haiman, CA Halai, D Hallmans, G Hassan, M Hattinger, C He, QC He, XZ Helzlsouer, K Henderson, B Henriksson, R Hjalgrim, H Hoffman-Bolton, J Hohensee, C Holford, TR Holly, EA Hong, YC Hoover, RN Horn-Ross, PL Hosain, GMM Hosgood, HD Hsiao, CF Hu, N Hu, W Hu, ZB Huang, MS Huerta, JM Hung, JY Hutchinson, A Inskip, PD Jackson, RD Jacobs, EJ Jenab, M Jeon, HS Ji, BT Jin, GF Jin, L Johansen, C Johnson, A Jung, YJ Kaaks, R Kamineni, A Kane, E Kang, CH Karagas, MR Kelly, RS Khaw, KT Kim, C Kim, HN Kim, JH Kim, JS Kim, YH Kim, YT Kim, YC Kitahara, CM Klein, AP Klein, RJ Kogevinas, M Kohno, T Kolonel, LN Kooperberg, C Kricker, A Krogh, V Kunitoh, H Kurtz, RC Kweon, SS LaCroix, A Lawrence, C Lecanda, F Lee, VHF Li, DH Li, HX Li, JH Li, YJ Li, YQ Liao, LM Liebow, M Lightfoot, T Lim, WY Lin, CC Lin, DX Lindstrom, S Linet, MS Link, BK Liu, CW Liu, JJ Liu, L Ljungberg, B Lloreta, J Di Lollo, S Lu, D Lund, E Malats, N Mannisto, S Le Marchand, L Marina, N Masala, G Mastrangelo, G Matsuo, K Maynadie, M Mckay, J McKean-Cowdin, R Melbye, M Melin, BS Michaud, DS Mitsudomi, T Monnereau, A Montalvan, R Moore, LE Mortensen, LM Nieters, A North, KE Novak, AJ Oberg, AL Offit, K Oh, IJ Olson, SH Palli, D Pao, W Park, IK Park, JY Park, KH Patino-Garcia, A Pavanello, S Peeters, PHM Perng, RP Peters, U Petersen, GM Picci, P Pike, MC Porru, S Prescott, J Prokunina-Olsson, L Qian, B Qiao, YL Rais, M Riboli, E Riby, J Risch, HA Rizzato, C Rodabough, R Roman, E Roupret, M Ruder, AM de Sanjose, S Scelo, G Schned, A Schumacher, F Schwartz, K Schwenn, M Scotlandi, K Seow, A Serra, C Serra, M Sesso, HD Setiawan, VW Severi, G Severson, RK Shanafelt, TD Shen, HB Shen, W Shin, MH Shiraishi, K Shu, XO Siddiq, A Sierrasesumaga, L Sihoe, ADL Skibola, CF Smith, A Smith, MT Southey, MC Spinelli, JJ Staines, A Stampfer, M Stern, MC Stevens, VL Stolzenberg-Solomon, RS Su, J Su, WC Sund, M Sung, JS Sung, SW Tan, W Tang, W Tardon, A Thomas, D Thompson, CA Tinker, LF Tirabosco, R Tjonneland, A Travis, RC Trichopoulos, D Tsai, FY Tsai, YH Tucker, M Turner, J Vajdic, CM Vermeulen, RCH Villano, DJ Vineis, P Virtamo, J Visvanathan, K Wactawski-Wende, J Wang, CY Wang, CL Wang, JC Wang, JW Wei, FS Weiderpass, E Weiner, GJ Weinstein, S Wentzensen, N White, E Witzig, TE Wolpin, BM Wong, MP Wu, C Wu, GP Wu, JJ Wu, TC Wu, W Wu, XF Wu, YL Wunder, JS Xiang, YB Xu, J Xu, P Yang, PC Yang, TY Ye, YQ Yin, ZH Yokota, J Yoon, HI Yu, CJ Yu, H Yu, K Yuan, JM Zelenetz, A Zeleniuch-Jacquotte, A Zhang, XC Zhang, YW Zhao, XY Zhao, ZH Zheng, H Zheng, TZ Zheng, W Zhou, BS Zhu, M Zucca, M Boca, SM Cerhan, JR Ferri, GM Hartge, P Hsiung, CA Magnani, C Miligi, L Morton, LM Smedby, KE Teras, LR Vijai, J Wang, SS Brennan, P Caporaso, NE Hunter, DJ Kraft, P Rothman, N Silverman, DT Slager, SL Chanock, SJ Chatterjee, N AF Sampson, Joshua N. Wheeler, William A. Yeager, Meredith Panagiotou, Orestis Wang, Zhaoming Berndt, Sonja I. Lan, Qing Abnet, Christian C. Amundadottir, Laufey T. Figueroa, Jonine D. Landi, Maria Teresa Mirabello, Lisa Savage, Sharon A. Taylor, Philip R. De Vivo, Immaculata McGlynn, Katherine A. Purdue, Mark P. Rajaraman, Preetha Adami, Hans-Olov Ahlbom, Anders Albanes, Demetrius Amary, Maria Fernanda An, She-Juan Andersson, Ulrika Andriole, Gerald, Jr. Andrulis, Irene L. Angelucci, Emanuele Ansell, Stephen M. Arici, Cecilia Armstrong, Bruce K. Arslan, Alan A. Austin, Melissa A. Baris, Dalsu Barkauskas, Donald A. Bassig, Bryan A. Becker, Nikolaus Benavente, Yolanda Benhamou, Simone Berg, Christine Van Den Berg, David Bernstein, Leslie Bertrand, Kimberly A. Birmann, Brenda M. Black, Amanda Boeing, Heiner Boffetta, Paolo Boutron-Ruault, Marie-Christine Bracci, Paige M. Brinton, Louise Brooks-Wilson, Angela R. Bueno-de-Mesquita, H. Bas Burdett, Laurie Buring, Julie Butler, Mary Ann Cai, Qiuyin Cancel-Tassin, Geraldine Canzian, Federico Carrato, Alfredo Carreon, Tania Carta, Angela Chan, John K. C. Chang, Ellen T. Chang, Gee-Chen Chang, I-Shou Chang, Jiang Chang-Claude, Jenny Chen, Chien-Jen Chen, Chih-Yi Chen, Chu Chen, Chung-Hsing Chen, Constance Chen, Hongyan Chen, Kexin Chen, Kuan-Yu Chen, Kun-Chieh Chen, Ying Chen, Ying-Hsiang Chen, Yi-Song Chen, Yuh-Min Chien, Li-Hsin Chirlaque, Maria-Dolores Choi, Jin Eun Choi, Yi Young Chow, Wong-Ho Chung, Charles C. Clavel, Jacqueline Clavel-Chapelon, Franoise Cocco, Pierluigi Colt, Joanne S. Comperat, Eva Conde, Lucia Connors, Joseph M. Conti, David Cortessis, Victoria K. Cotterchio, Michelle Cozen, Wendy Crouch, Simon Crous-Bou, Marta Cussenot, Olivier Davis, Faith G. Ding, Ti Diver, W. Ryan Dorronsoro, Miren Dossus, Laure Duell, Eric J. Ennas, Maria Grazia Erickson, Ralph L. Feychting, Maria Flanagan, Adrienne M. Foretova, Lenka Fraumeni, Joseph F., Jr. Freedman, Neal D. Freeman, Laura E. Beane Fuchs, Charles Gago-Dominguez, Manuela Gallinger, Steven Gao, Yu-Tang Gapstur, Susan M. Garcia-Closas, Montserrat Garcia-Closas, Reina Gascoyne, Randy D. Gastier-Foster, Julie Gaudet, Mia M. Gaziano, J. Michael Giffen, Carol Giles, Graham G. Giovannucci, Edward Glimelius, Bengt Goggins, Michael Gokgoz, Nalan Goldstein, Alisa M. Gorlick, Richard Gross, Myron Grubb, Robert, III Gu, Jian Guan, Peng Gunter, Marc Guo, Huan Habermann, Thomas M. Haiman, Christopher A. Halai, Dina Hallmans, Goran Hassan, Manal Hattinger, Claudia He, Qincheng He, Xingzhou Helzlsouer, Kathy Henderson, Brian Henriksson, Roger Hjalgrim, Henrik Hoffman-Bolton, Judith Hohensee, Chancellor Holford, Theodore R. Holly, Elizabeth A. Hong, Yun-Chul Hoover, Robert N. Horn-Ross, Pamela L. Hosain, G. M. Monawar Hosgood, H. Dean, III Hsiao, Chin-Fu Hu, Nan Hu, Wei Hu, Zhibin Huang, Ming-Shyan Huerta, Jose-Maria Hung, Jen-Yu Hutchinson, Amy Inskip, Peter D. Jackson, Rebecca D. Jacobs, Eric J. Jenab, Mazda Jeon, Hyo-Sung Ji, Bu-Tian Jin, Guangfu Jin, Li Johansen, Christoffer Johnson, Alison Jung, Yoo Jin Kaaks, Rudolph Kamineni, Aruna Kane, Eleanor Kang, Chang Hyun Karagas, Margaret R. Kelly, Rachel S. Khaw, Kay-Tee Kim, Christopher Kim, Hee Nam Kim, Jin Hee Kim, Jun Suk Kim, Yeul Hong Kim, Young Tae Kim, Young-Chul Kitahara, Cari M. Klein, Alison P. Klein, Robert J. Kogevinas, Manolis Kohno, Takashi Kolonel, Laurence N. Kooperberg, Charles Kricker, Anne Krogh, Vittorio Kunitoh, Hideo Kurtz, Robert C. Kweon, Sun-Seog LaCroix, Andrea Lawrence, Charles Lecanda, Fernando Lee, Victor Ho Fun Li, Donghui Li, Haixin Li, Jihua Li, Yao-Jen Li, Yuqing Liao, Linda M. Liebow, Mark Lightfoot, Tracy Lim, Wei-Yen Lin, Chien-Chung Lin, Dongxin Lindstrom, Sara Linet, Martha S. Link, Brian K. Liu, Chenwei Liu, Jianjun Liu, Li Ljungberg, Boerje Lloreta, Josep Di Lollo, Simonetta Lu, Daru Lund, Eiluv Malats, Nuria Mannisto, Satu Le Marchand, Loic Marina, Neyssa Masala, Giovanna Mastrangelo, Giuseppe Matsuo, Keitaro Maynadie, Marc Mckay, James McKean-Cowdin, Roberta Melbye, Mads Melin, Beatrice S. Michaud, Dominique S. Mitsudomi, Tetsuya Monnereau, Alain Montalvan, Rebecca Moore, Lee E. Mortensen, Lotte Maxild Nieters, Alexandra North, Kari E. Novak, Anne J. Oberg, Ann L. Offit, Kenneth Oh, In-Jae Olson, Sara H. Palli, Domenico Pao, William Park, In Kyu Park, Jae Yong Park, Kyong Hwa Patino-Garcia, Ana Pavanello, Sofia Peeters, Petra H. M. Perng, Reury-Perng Peters, Ulrike Petersen, Gloria M. Picci, Piero Pike, Malcolm C. Porru, Stefano Prescott, Jennifer Prokunina-Olsson, Ludmila Qian, Biyun Qiao, You-Lin Rais, Marco Riboli, Elio Riby, Jacques Risch, Harvey A. Rizzato, Cosmeri Rodabough, Rebecca Roman, Eve Roupret, Morgan Ruder, Avima M. de Sanjose, Silvia Scelo, Ghislaine Schned, Alan Schumacher, Fredrick Schwartz, Kendra Schwenn, Molly Scotlandi, Katia Seow, Adeline Serra, Consol Serra, Massimo Sesso, Howard D. Setiawan, Veronica Wendy Severi, Gianluca Severson, Richard K. Shanafelt, Tait D. Shen, Hongbing Shen, Wei Shin, Min-Ho Shiraishi, Kouya Shu, Xiao-Ou Siddiq, Afshan Sierrasesumaga, Luis Sihoe, Alan Dart Loon Skibola, Christine F. Smith, Alex Smith, Martyn T. Southey, Melissa C. Spinelli, John J. Staines, Anthony Stampfer, Meir Stern, Marianna C. Stevens, Victoria L. Stolzenberg-Solomon, Rachael S. Su, Jian Su, Wu-Chou Sund, Malin Sung, Jae Sook Sung, Sook Whan Tan, Wen Tang, Wei Tardon, Adonina Thomas, David Thompson, Carrie A. Tinker, Lesley F. Tirabosco, Roberto Tjonneland, Anne Travis, Ruth C. Trichopoulos, Dimitrios Tsai, Fang-Yu Tsai, Ying-Huang Tucker, Margaret Turner, Jenny Vajdic, Claire M. Vermeulen, Roel C. H. Villano, Danylo J. Vineis, Paolo Virtamo, Jarmo Visvanathan, Kala Wactawski-Wende, Jean Wang, Chaoyu Wang, Chih-Liang Wang, Jiu-Cun Wang, Junwen Wei, Fusheng Weiderpass, Elisabete Weiner, George J. Weinstein, Stephanie Wentzensen, Nicolas White, Emily Witzig, Thomas E. Wolpin, Brian M. Wong, Maria Pik Wu, Chen Wu, Guoping Wu, Junjie Wu, Tangchun Wu, Wei Wu, Xifeng Wu, Yi-Long Wunder, Jay S. Xiang, Yong-Bing Xu, Jun Xu, Ping Yang, Pan-Chyr Yang, Tsung-Ying Ye, Yuanqing Yin, Zhihua Yokota, Jun Yoon, Ho-Il Yu, Chong-Jen Yu, Herbert Yu, Kai Yuan, Jian-Min Zelenetz, Andrew Zeleniuch-Jacquotte, Anne Zhang, Xu-Chao Zhang, Yawei Zhao, Xueying Zhao, Zhenhong Zheng, Hong Zheng, Tongzhang Zheng, Wei Zhou, Baosen Zhu, Meng Zucca, Mariagrazia Boca, Simina M. Cerhan, James R. Ferri, Giovanni M. Hartge, Patricia Hsiung, Chao Agnes Magnani, Corrado Miligi, Lucia Morton, Lindsay M. Smedby, Karin E. Teras, Lauren R. Vijai, Joseph Wang, Sophia S. Brennan, Paul Caporaso, Neil E. Hunter, David J. Kraft, Peter Rothman, Nathaniel Silverman, Debra T. Slager, Susan L. Chanock, Stephen J. Chatterjee, Nilanjan TI Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MULTIPLE SUSCEPTIBILITY LOCI; LUNG-CANCER; FAMILIAL RISK; PANCREATIC-CANCER; SWEDEN; INDIVIDUALS; MUTATIONS; RELATIVES; LYMPHOMA; DATABASE AB Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation. 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[Clavel, Jacqueline; Monnereau, Alain] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Environm Epidemiol Canc Grp, Villejuif, France. [Cocco, Pierluigi; Rais, Marco] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy. [Comperat, Eva; Roupret, Morgan] AP HP, Pitie Salpetriere, Dept Urol, Paris, France. [Comperat, Eva] AP HP, Pitie Salpetriere, Dept Pathol, Paris, France. [Conde, Lucia; Riby, Jacques; Skibola, Christine F.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Conde, Lucia; Riby, Jacques; Skibola, Christine F.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Conde, Lucia; Riby, Jacques; Skibola, Christine F.; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Conde, Lucia; Riby, Jacques; Skibola, Christine F.; Smith, Martyn T.] BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC, Canada. [Connors, Joseph M.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Cortessis, Victoria K.] Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. [Cotterchio, Michelle] Canc Care Ontario, Toronto, ON, Canada. [Cotterchio, Michelle] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Crouch, Simon; Kane, Eleanor; Lightfoot, Tracy; Riboli, Elio; Smith, Alex] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Cussenot, Olivier] Hop Tenon, AP HP, Dept Urol, F-75970 Paris, France. [Davis, Faith G.] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada. [Ding, Ti] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China. [Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Jacobs, Eric J.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Dorronsoro, Miren] BioDonostia Res Inst, Dept Hlth, Basque Region, Spain. 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[Johansen, Christoffer] Danish Canc Soc Res Ctr, Unit Survivorship, Copenhagen, Denmark. [Johnson, Alison] Vermont Canc Registry, Burlington, VT USA. [Jung, Yoo Jin; Kang, Chang Hyun; Kim, Young Tae; Park, In Kyu] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Thorac & Cardiovasc Surg, Seoul, South Korea. [Kamineni, Aruna] Grp Hlth Res Inst, Seattle, WA USA. [Karagas, Margaret R.; Schned, Alan] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Kelly, Rachel S.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England. [Khaw, Kay-Tee] Univ Cambridge, Cambridge CB2 1TN, England. [Kim, Hee Nam] Chonnam Natl Univ, Ctr Creat Biomed Scientists, Gwangju, South Korea. [Kim, Jin Hee] Seoul Natl Univ, Grad Sch Publ Hlth, Dept Environm Hlth, Seoul, South Korea. [Kim, Jun Suk] Korea Univ, Guro Hosp, Coll Med, Dept Internal Med,Div Med Oncol, Seoul, South Korea. 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[Weiner, George J.] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA USA. [Liu, Jianjun] Genome Inst Singapore, Human Genet, Singapore, Singapore. [Liu, Li] Huazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Wuhan 430074, Peoples R China. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden. Univ Florence, Dept Surg & Translat Med, Sect Anatomopathol, Florence, Italy. [Lund, Eiluv; Weiderpass, Elisabete] Univ Tromso, Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, Tromso, Norway. Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain. [Mannisto, Satu; Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Le Marchand, Loic; Yu, Herbert] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA. Stanford Univ, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [Masala, Giovanna; Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy. 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[Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Epidemiol, Beijing 100730, Peoples R China. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. Karmanos Canc Inst, Detroit, MI USA. [Schwenn, Molly] Maine Canc Registry, Augusta, ME USA. [Serra, Consol] Univ Pompeu Fabra, Dept Ciencies Experimentals & Salut, Barcelona, Spain. [Severi, Gianluca; Vineis, Paolo] Human Genet Fdn, Turin, Italy. [Sihoe, Alan Dart Loon] Queen Mary Hosp, Div Cardiothorac Surg, Dept Surg, Hong Kong, Hong Kong, Peoples R China. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Spinelli, John J.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada. [Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Staines, Anthony] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland. [Su, Wu-Chou] Natl Cheng Kung Univ, Med Coll & Hosp, Tainan 701, Taiwan. [Sund, Malin] Umea Univ, Dept Surg & Perioperat Sci, Surg, Umea, Sweden. [Sung, Jae Sook] Korea Univ, Canc Res Inst, Seoul, South Korea. [Sung, Sook Whan] Seoul St Marys Hosp, Dept Thorac & Cardiovasc Surg, Seoul, South Korea. [Tardon, Adonina] Univ Oviedo, Inst Univ Oncol, Oviedo, Spain. [Thomas, David] St Vincents Hosp, Garvan Inst Med Res, Kinghorn Canc Ctr, Darlinghurst, NSW 2010, Australia. [Tjonneland, Anne] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece. [Tsai, Ying-Huang] Chang Gung Mem Hosp, Dept Resp Thearpy, Chiayi, Taiwan. [Turner, Jenny] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia. [Turner, Jenny] Douglass Hanly Moir Pathol, Dept Histopathol, Macquarie Pk, NSW, Australia. [Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia. [Vermeulen, Roel C. H.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Wang, Chih-Liang] Chang Gung Mem Hosp, Dept Pulm & Crit Care, Taoyuan, Taiwan. [Wang, Jiu-Cun] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China. [Wang, Junwen] Univ Hong Kong, Li Ka Shing Fac Med, Ctr Genom Sci, Hong Kong, Peoples R China. [Wang, Junwen] Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. [Wei, Fusheng; Wu, Guoping] China Natl Environm Monitoring Ctr, Beijing, Peoples R China. [Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway. [Weiderpass, Elisabete] Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland. [Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Maria Pik] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China. [Wu, Chen] Peking Union Med Coll, Beijing 100021, Peoples R China. [Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, Shanghai 200030, Peoples R China. [Xu, Jun] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. [Xu, Ping] Wuhan Iron & Steel Corp Staff Worker Hosp, Dept Oncol, Wuhan, Peoples R China. [Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan. [Yokota, Jun] Inst Predict & Personalized Med Canc IMPPC, Barcelona, Spain. [Yoon, Ho-Il] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. [Yuan, Jian-Min] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, Washington, DC USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Cerhan, James R.; Slager, Susan L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Ferri, Giovanni M.] Univ Bari, Interdisciplinary Dept Med, Bari, Italy. [Magnani, Corrado] Univ Piemonte Orientale, Dept Translat Med, CPO Piemonte & Unit Med Stat & Epidemiol, Novara, Italy. [Mirabello, Lisa] Canc Prevent & Res Inst ISPO, Environm & Occupat Epidemiol Unit, Florence, Italy. [Smedby, Karin E.] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden. [Hunter, David J.] Broad Inst Harvard, Cambridge, MA USA. [Hunter, David J.] MIT, Cambridge, MA 02139 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Sampson, JN (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,7E594, Rockville, MD 20815 USA. EM joshua.sampson@nih.gov; nilanjan.chatterjee@nih.gov RI Wang, Junwen/D-3700-2011; Qiao, You-Lin/B-4139-2012; Clavel, Jacqueline/Q-2750-2016; Hattinger, Claudia/Q-1212-2016; Beane Freeman, Laura/C-4468-2015; Kitahara, Cari/R-8267-2016; Jung, Yoojin/G-2519-2015; Kogevinas, Manolis/C-3918-2017; Brooks-Wilson, Angela/E-9399-2012; Weiderpass, Elisabete/M-4029-2016; Abnet, Christian/C-4111-2015; Purdue, Mark/C-9228-2016; Jin, Li/C-1468-2009; Savage, Sharon/B-9747-2015; de Sanjose Llongueras, Silvia/H-6339-2014; Andrulis, Irene/E-7267-2013; Gallinger, Steven/E-4575-2013; Benhamou, Simone/K-6554-2015; Krogh, Vittorio/K-2628-2016 OI Wang, Junwen/0000-0002-4432-4707; Qiao, You-Lin/0000-0001-6380-0871; Clavel, Jacqueline/0000-0002-3616-7676; Hattinger, Claudia/0000-0002-9316-5095; Beane Freeman, Laura/0000-0003-1294-4124; Joseph, Vijai/0000-0002-7933-151X; Brooks-Wilson, Angela/0000-0003-1009-6408; Weiderpass, Elisabete/0000-0003-2237-0128; Abnet, Christian/0000-0002-3008-7843; Purdue, Mark/0000-0003-1177-3108; Jin, Li/0000-0002-4546-2415; Savage, Sharon/0000-0001-6006-0740; Krogh, Vittorio/0000-0003-0122-8624 FU Intramural Research Program of the National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institutes of Health. NR 35 TC 14 Z9 14 U1 7 U2 63 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD DEC PY 2015 VL 107 IS 12 AR djv279 DI 10.1093/jnci/djv279 PG 11 WC Oncology SC Oncology GA CZ2YN UT WOS:000366970900015 PM 26464424 ER PT J AU Phillips, AB Merrill, JA AF Phillips, Andrew B. Merrill, Jacqueline A. TI Innovative use of the integrative review to evaluate evidence of technology transformation in healthcare SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Review DE Integrative review; Information technology; Health reform; Complex adaptive systems; Technology transformation ID COMPLEX ADAPTIVE SYSTEMS; ORGANIZATIONAL TRANSFORMATION; INFORMATION-TECHNOLOGY; DISCONTINUITIES; WILL AB Healthcare is in a period significant transformational activity through the accelerated adoption of healthcare technologies, new reimbursement systems that emphasize shared savings and care coordination, and the common place use of mobile technologies by patients, providers, and others. The complexity of healthcare creates barriers to transformational activity and has the potential to inhibit the desired paths toward change envisioned by policymakers. Methods for understanding how change is occurring within this complex environment are important to the evaluation of delivery system reform and the role of technology in healthcare transformation. This study examines the use on an integrative review methodology to evaluate the healthcare literature for evidence of technology transformation in healthcare. The methodology integrates the evaluation of a broad set of literature with an established evaluative framework to develop a more complete understanding of a particular topic. We applied this methodology and the framework of punctuated equilibrium (PEq) to the analysis of the healthcare literature from 2004 to 2012 for evidence of technology transformation, a time during which technology was at the forefront of healthcare policy. The analysis demonstrated that the established PEq framework applied to the literature showed considerable potential for evaluating the progress of policies that encourage healthcare transformation. Significant inhibitors to change were identified through the integrative review and categorized into ten themes that describe the resistant structure of healthcare delivery: variations in the environment; market complexity; regulations; flawed risks and rewards; change theories; barriers; ethical considerations; competition and sustainability; environmental elements, and internal elements. We hypothesize that the resistant nature of the healthcare system described by this study creates barriers to the direct consumer involvement and engagement necessary for transformational change. Future policies should be directed at removing these barriers by demanding and emphasizing open technologies and unrestricted access to data versus as currently prescribed by technology vendors, practitioners, and policies that perpetuate market equilibrium. (C) 2015 Elsevier Inc. All rights reserved. C1 [Phillips, Andrew B.; Merrill, Jacqueline A.] Columbia Univ, Sch Nursing, New York, NY 10032 USA. [Merrill, Jacqueline A.] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. RP Phillips, AB (reprint author), Massachusetts Gen Hosp, Sch Nursing, MGH Inst Hlth Profess, Partners HealthCare Syst, 36 1st Ave, Boston, MA 02129 USA. EM aphillips@mghihp.edu FU National Institute of Nursing Research [T32NR007969] FX Andrew B. Phillips received support from an institutional training grant to Columbia University from the National Institute of Nursing Research (T32NR007969). NR 46 TC 1 Z9 1 U1 4 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD DEC PY 2015 VL 58 BP 114 EP 121 DI 10.1016/j.jbi.2015.09.014 PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA CZ0JL UT WOS:000366791000013 PM 26429591 ER PT J AU Choi, MG Park, JM Kim, JH Hasan, T AF Choi, Myung-Gyu Park, Jae Myung Kim, Ju Hee Hasan, Tayyaba TI Development of molecular imaging probe through the fusion of colon cancer-specific peptide and photosensitizer SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Choi, Myung-Gyu; Park, Jae Myung] Catholic Univ Korea, Seoul St Marys Hosp, Div Gastroenterol, Dept Internal Med, Seoul, South Korea. [Choi, Myung-Gyu; Park, Jae Myung; Kim, Ju Hee] Catholic Univ Korea, Catholic Harvard Wellman Photomed Ctr, Div Gastroenterol, Dept Internal Med, Seoul, South Korea. [Hasan, Tayyaba] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Ctr Photomed, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD DEC PY 2015 VL 30 SU 4 SI SI MA 2067 BP 100 EP 101 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CX4NI UT WOS:000365677200259 ER PT J AU Corcoran, RB AF Corcoran, Ryan B. TI New therapeutic strategies for BRAF mutant colorectal cancers SO JOURNAL OF GASTROINTESTINAL ONCOLOGY LA English DT Review DE BRAF; colorectal cancer (CRC); BRAF inhibitor; clinical trials ID ACQUIRED-RESISTANCE; MEK INHIBITORS; TUMOR MICROENVIRONMENT; METASTATIC MELANOMA; 1ST-LINE TREATMENT; V600E MUTATION; COLON-CANCER; CETUXIMAB; SURVIVAL; RAF AB Oncogenic BRAF mutations are found in similar to 10% of colorectal cancers (CRCs) and predict poor prognosis. Although BRAF inhibitors have demonstrated striking efficacy in BRAF mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF mutant CRC. Over the past few years, studies have begun to define the molecular mechanisms underlying the relative resistance of BRAF mutant CRC to BRAF inhibitors, leading to the development of novel therapeutic strategies that are showing promising clinical activity in initial clinical trials. Our current understanding of the mechanisms of BRAF inhibitor resistance in BRAF mutant CRC and the therapeutic approaches currently in clinical trials for BRAF mutant CRC are reviewed herein. C1 [Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Corcoran, Ryan B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Corcoran, RB (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St,7th floor, Boston, MA 02129 USA. EM rbcorcoran@partners.org NR 49 TC 5 Z9 5 U1 0 U2 3 PU PIONEER BIOSCIENCE PUBL CO PI HONG KONG PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG, 00000, PEOPLES R CHINA SN 2078-6891 EI 2219-679X J9 J GASTROINTEST ONCOL JI J. Gastrointest. Oncol. PD DEC PY 2015 VL 6 IS 6 BP 650 EP 659 DI 10.3978/j.issn.2078-6891.2015.076 PG 10 WC Oncology SC Oncology GA CZ2AW UT WOS:000366908400011 PM 26697198 ER PT J AU Anderson, MB Goldstein, J Milano, C Morris, LD Kormos, RL Bhama, J Kapur, NK Barisal, A Garcia, J Baker, JN Silvestry, S Holman, WL Douglas, PS O'Neill, W AF Anderson, Mark B. Goldstein, James Milano, Carmelo Morris, Lynn D. Kormos, Robert L. Bhama, Jay Kapur, Navin K. Barisal, Aditya Garcia, Jose Baker, Joshua N. Silvestry, Scott Holman, William L. Douglas, Pamela S. O'Neill, William TI Benefits of a novel percutaneous ventricular assist device for right heart failure: The prospective RECOVER RIGHT study of the Impel la RP device SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE heart failure; hemodynamics; right ventricular assist device; cardiogenic shock; right ventricular failure ID MECHANICAL CIRCULATORY SUPPORT; IMPLANTATION; SYSTEM; MULTICENTER; OUTCOMES; TRIAL AB BACKGROUND: Right ventricular failure (RVF) increases morbidity and mortality. The RECOVER RIGHT study evaluated the safety and efficacy of a novel percutaneous right ventricular assist device, the Impella RP (Abiomed, Danvers, MA), in a prospective, multicenter trial. METHODS: Thirty patients with RVF refractory to medical treatment received the Impella RP device at 15 United States institutions. The study population included 2 cohorts: 18 patients with RVF after left ventricular assist device (LVAD) implantation (Cohort A) and 12 patients with RVF after cardiotomy or myocardial infarction (Cohort B). The primary end point was survival to 30 days or hospital discharge (whichever was longer). Major secondary end points included indices of safety and efficacy. RESULTS: The patients (77% male) were a mean age of 59 +/- 15 years, 53% had diabetes, 88.5% had a history of congestive heart failure, and 37.5% had renal dysfunction. Patients were on an average of 3.2 inotropes/pressors. Device delivery was achieved in all but 1 patient. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in cardiac index from 1.8 +/- 0.2 to 3.3 +/- 0.23 liters/min/m(2) (p < 0.001) and a decrease in central venous pressure from 19.2 +/- 4 to 12.6 +/- 1 mm Hg (p < 0.001). Patients were supported for an average of 3.0 +/- 1.5 days (range, 0.5-7.8 days). The overall survival at 30 days was 73.3%. All patients discharged were alive at 180 days. CONCLUSIONS: In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit. These data support its probable benefit in this gravely ill patient 'population. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Anderson, Mark B.; Morris, Lynn D.] Albert Einstein Healthcare Network, Div Cardiothorac Surg, Philadelphia, PA 19141 USA. [Anderson, Mark B.; Morris, Lynn D.] Albert Einstein Healthcare Network, Dept Cardiovasc Med, Philadelphia, PA 19141 USA. [Goldstein, James] William Beaumont Hosp, Dept Cardiovasc Med, Royal Oak, MI 48072 USA. [Milano, Carmelo] Duke Univ, Med Ctr, Dept Cardiovasc & Thorac Surg, Durham, NC USA. [Kormos, Robert L.; Bhama, Jay] Univ Pittsburgh, Med Ctr, Div Cardiothorac Surg, Artificial Heart Program, Pittsburgh, PA USA. [Kapur, Navin K.] Tufts Univ, Med Ctr, Ctr Cardiovasc, Dept Med, Boston, MA 02111 USA. [Barisal, Aditya] Ochsner Fdn, Dept Cardiothorac Surg, New Orleans, LA USA. [Garcia, Jose; Baker, Joshua N.] Massachusetts Gen Hosp, Div Cardiothorac Surg, Boston, MA 02114 USA. [Silvestry, Scott] Washington Univ, Sch Med, Div Cardiothorac Surg, St Louis, MO 63110 USA. [Holman, William L.] Univ Alabama Birmingham, Div Cardiothorac Surg, Birmingham, AL USA. [Douglas, Pamela S.] Duke Clin Res Inst, Durham, NC USA. [O'Neill, William] Henry Ford Hosp, Ctr Strucrural Heart Dis, Detroit, MI 48202 USA. RP Anderson, MB (reprint author), Albert Einstein Healthcare Network, 5501 Old York Rd, Philadelphia, PA 19141 USA. EM andersom@einstein.edu FU Abiomed (Danvers, MA) FX This study was funded by Abiomed (Danvers, MA). M.B.A. is a consultant for Abiomed. NR 14 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 2015 VL 34 IS 12 SI SI BP 1549 EP 1560 DI 10.1016/j.healun.2015.08.018 PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CZ2SU UT WOS:000366955700008 PM 26681124 ER PT J AU Garan, AR Levin, AP Topkara, V Thomas, SS Yuzefpolskaya, M Colombo, PC Takeda, K Takayama, H Naka, Y Whang, W Jorde, UP Uriel, N AF Garan, Arthur R. Levin, Allison P. Topkara, Veli Thomas, Sunu S. Yuzefpolskaya, Melana Colombo, Paolo C. Takeda, Koji Takayama, Hiroo Naka, Yoshifumi Whang, William Jorde, Ulrich P. Uriel, Nir TI Early post-operative ventricular arrhythmias in patients with continuous-flow left ventricular assist devices SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE LVAD; ventricular arrhythmia; ventricular tachycardia; ablation; right ventricular failure; ICD; suction event ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; LONG-TERM SUPPORT; QUALITY-OF-LIFE; HEART-FAILURE; THERAPY; RECIPIENTS; TRANSPLANTATION; ELECTROGRAM; PREVALENCE AB BACKGROUND: Ventricular arrhythmias (VAs) are common in patients with a continuous-flow left ventricular assist device (CF-LVAD). The causes and clinical significance of early post-operative VAs have not previously been characterized in these patients. The purpose of this study was to assess the incidence, precipitants, and clinical impact of early VAs in patients supported by CF-LVADs. METHODS: Patients with a long-term CF-LVAD receiving care between January 1, 2012, and March 1, 2014, were enrolled and followed prospectively. Implantable cardioverter-defibrillators (ICDs) were interrogated at baseline and throughout the follow-up period. VA was defined as ventricular tachycardia or ventricular fibrillation lasting >30 seconds or effectively terminated by appropriate ICD tachytherapy or external defibrillation. The primary end-point was the occurrence of early VAs (within 30 days of surgery). Secondary end-points were right ventricular (RV) failure and need for VA ablation. RESULTS: There were 162 patients enrolled, and 38 (23.5%) experienced at least 1 early VA. Predictors of early VA were a history of pre-operative VAs, non-ischemic cardiomyopathy, and older age. Several conditions frequently encountered in the early post-operative period were identified as possible precipitants for VA episodes. Early VAs were associated with post-operative RV failure, particularly when patients received shocks instead of anti-tachycardia pacing. CONCLUSIONS: Early VAs are common and are associated with RV failure. ICD shocks, but not antitachycardia pacing, for early VAs are associated with acute worsening of RV failure. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Garan, Arthur R.; Levin, Allison P.; Topkara, Veli; Yuzefpolskaya, Melana; Colombo, Paolo C.; Whang, William] Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY 10032 USA. [Thomas, Sunu S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA 02115 USA. [Takeda, Koji; Takayama, Hiroo; Naka, Yoshifumi] Columbia Univ, Med Ctr, Dept Surg, Div Cardiothorac Surg, New York, NY 10032 USA. [Jorde, Ulrich P.] Montefiore Med Ctr, Dept Med, Div Cardiol, New York, NY USA. [Uriel, Nir] Univ Chicago, Med Ctr, Dept Med, Div Cardiol, Chicago, IL 60637 USA. RP Garan, AR (reprint author), Columbia Univ, Med Ctr, Dept Med, Div Cardiol, 622 West 168th St,PH-12, New York, NY 10032 USA. EM arg2024@cumc.columbia.edu NR 20 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 2015 VL 34 IS 12 SI SI BP 1611 EP 1616 DI 10.1016/j.healun.2015.05.018 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CZ2SU UT WOS:000366955700015 PM 26212658 ER PT J AU La Muraglia, GM O'Neil, MJ Madariaga, ML Michel, SG Mordecai, KS Allan, JS Madsen, JC Hanekamp, IM Preffer, FI AF La Muraglia, G. M., II O'Neil, M. J. Madariaga, M. L. Michel, S. G. Mordecai, K. S. Allan, J. S. Madsen, J. C. Hanekamp, I. M. Preffer, F. I. TI A novel approach to measuring cell-mediated lympholysis using quantitative flow and imaging cytometry SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Cell-mediated lympholysis; Cytotoxic lymphocyte; Major histocompatibility complex; Chromium-51; Imaging flow cytometry; Transplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; LYMPHOCYTES KILL; IN-VITRO; T-CELLS; TRANSPLANTATION; ASSAY; CYTOTOXICITY; TOLERANCE; PROLIFERATION AB In this study, we established a novel isotope-free approach for the detection of cell-mediated lympholysis (CML) in MHC defined peripheral blood mononuclear cells (PBMCs) using multiparameter flow and imaging cytometry. CML is an established in vitro assay to detect the presence of cytotoxic effector T-lymphocytes precursors (CTLp). Current methods employed in the identification of CTLp in the context of transplantation are based upon the quantification of chromium (Cr-51) released from target cells. In order to adapt the assay to flow cytometry, primary porcine PBMC targets were labeled with eFluor670 and incubated with major histocompatibility complex (MHC) mismatched effector cytotoxic lymphocytes (CTLs). With this method, we were able to detect target-specific lysis that was comparable to that observed with the Cr-51-based assay. In addition, the use of quantitative cell imaging demonstrates the presence of accessory cells involved in the cytotoxic pathway. This innovative technique improves upon the standard Cr-51 release assay by eliminating the need for radioisotopes and provides enhanced characterization of the interactions between effector and target cells. This technique has wide applicability to numerous experimental and clinical models involved with effector-cell interactions. (C) 2015 Elsevier B.V. All rights reserved. C1 [La Muraglia, G. M., II; O'Neil, M. J.; Madariaga, M. L.; Michel, S. G.; Allan, J. S.; Madsen, J. C.; Hanekamp, I. M.] Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. [Mordecai, K. S.; Preffer, F. I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Allan, J. S.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Madsen, J. C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. RP Hanekamp, IM (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. EM preffer@helix.mgh.harvard.edu FU NIH [1S10OD012027]; ASTS-Novartis Scientist Scholarship Grant; International Society for Heart and Lung Transplantation; National Heart, Lung, and Blood Institute of the National Institutes of Health [F32HL117540] FX Dr. Preffer is supported by NIH grant 1S10OD012027. Dr. Michel is a recipient of the 2013 ASTS-Novartis Scientist Scholarship Grant. Dr. Madariaga is an Edward D. Churchill Surgical Research Fellow, Massachusetts General Hospital and a recipient of a fellowship from the International Society for Heart and Lung Transplantation and a National Research Service Award from the National Heart, Lung, and Blood Institute of the National Institutes of Health (F32HL117540). We acknowledge C06RR020135-01 for construction of the facility utilized for production and maintenance of miniature swine. We would also like to acknowledge Dr. Douglas Hayden for his invaluable guidance in biostatistics. NR 27 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 EI 1872-7905 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC PY 2015 VL 427 BP 85 EP 93 DI 10.1016/j.jim.2015.10.005 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA CZ5FE UT WOS:000367127100012 PM 26516062 ER PT J AU Aydil, U Duvvuri, U Kizil, Y Koybasioglu, A AF Aydil, U. Duvvuri, U. Kizil, Y. Koybasioglu, A. TI Tumour-node-metastasis staging of human papillomavirus negative upper aerodigestive tract cancers: a critical appraisal SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Review DE Neoplasm Staging; Head and Neck Neoplasms; Larynx; Mouth; Lymphatic Metastasis ID SQUAMOUS-CELL CARCINOMA; EARLY GLOTTIC CARCINOMA; ANTERIOR COMMISSURE INVOLVEMENT; PRIMARY SUBGLOTTIC CANCER; CAROTID-ARTERY RESECTION; ORAL TONGUE CARCINOMA; EXTRACAPSULAR SPREAD; PROGNOSTIC-FACTORS; RADIATION-THERAPY; LARYNGEAL-CANCER AB Objective: The tumour-node-metastasis staging system has a dynamic structure that is continuously being updated as scientific data develops. This review discusses some suggested revisions on tumour-node-metastasis staging of human papillomavirus negative upper aerodigestive tract cancers. Methods: The seventh edition of The American Joint Committee on Cancer Staging Manual was reviewed and important issues that could be considered for revision were identified and discussed. Results: According to our assessment of the oncological outcomes of previous studies, the following factors should be considered for revision: anterior commissure involvement and subglottic extension in laryngeal cancers; underlying bone involvement in hard palate and upper alveolar ridge cancers; tumour thickness in oral cancers; and extracapsular spread and carotid artery involvement in neck metastases. Conclusion: Sufficient data on the prognostic importance of these issues have been reported. Suggested revisions in line with current knowledge on the clinical behaviour of upper aerodigestive tract cancers would improve the relevancy of staging. C1 [Aydil, U.; Kizil, Y.] Gazi Univ, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, TR-06500 Ankara, Turkey. [Koybasioglu, A.] Mem Ankara Hosp, Dept Otorhinolaryngol Head & Neck Surg, Ankara, Turkey. [Duvvuri, U.] Univ Pittsburgh, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Pittsburgh, PA 15260 USA. [Duvvuri, U.] Vet Affairs Pittsburgh Hlth Syst, Otolaryngol Sect, Pittsburgh, PA USA. RP Aydil, U (reprint author), Gazi Univ, Tip Faku, KBB AD, TR-06500 Ankara, Turkey. EM utkuaydil@yahoo.com NR 101 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0022-2151 EI 1748-5460 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD DEC PY 2015 VL 129 IS 12 BP 1148 EP 1155 DI 10.1017/S0022215115002686 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA CZ6ZR UT WOS:000367250200002 PM 26446522 ER PT J AU Choi, YE Park, E AF Choi, Young Eun Park, Eunmi TI Curcumin enhances poly(ADP-ribose) polymerase inhibitor sensitivity to chemotherapy in breast cancer cells SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Curcumin; PARP inhibitor; Breast cancer cells; Homologous-recombination repair; Chemotherapy ID MAMMALIAN-CELLS; REPAIR; MICE; BLEOMYCIN; CISPLATIN; TUMORS AB Poly(ADP-ribose) polymerase (PARP) inhibitor has shown promising responses in homologous recombination (HR) repair-deficient cancer cells. More specifically, targeting HR pathway in combination with PARP inhibitor has been an effective chemotherapy strategy by so far. Curcumin has been recognized as anticancer agents for several types of cancers. Here, we demonstrate that curcumin inhibits a critical step in HR pathway, Rad51 foci formation, and accumulates gamma-H2AX levels in MDA-MB-231 breast cancer cells. Curcumin also directly reduces HR and induces cell death with cotreatment of PARP inhibitor in MDA-MB-231 breast cancer cells. Moreover, curcumin, when combined with ABT-888, could effectively delayed breast tumor formation in vivo. Our study indicates that cotreatment of curcumin and PARP inhibitor might be useful for the combination chemotherapy for aggressive breast cancer treatment as a natural bioactive compound. (C) 2015 Elsevier Inc. All rights reserved. C1 [Choi, Young Eun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Park, Eunmi] Hannam Univ, Sch Life Sci & Nanotechnol, Dept Food & Nutr, Daejeon 305811, South Korea. RP Park, E (reprint author), Hannam Univ, Sch Life Sci & Nanotechnol, Dept Food & Nutr, 461-6 Jeonmin Dong, Daejeon 305811, South Korea. EM eunmi_park@hnu.kr FU Basic Science Research Program through the National Research of Korea (NRF) - Ministry of Science, ICT Future Planing [2015R1C1A1A02037579] FX This research was supported by Basic Science Research Program through the National Research of Korea (NRF) funded by the Ministry of Science, ICT & Future Planing (Grant No. 2015R1C1A1A02037579). NR 25 TC 0 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD DEC PY 2015 VL 26 IS 12 BP 1442 EP 1447 DI 10.1016/j.jnutbio.2015.07.015 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA CZ0HL UT WOS:000366785600005 PM 26350251 ER PT J AU Wang, XF Ma, DWL Kang, JX Kulka, M AF Wang, Xiaofeng Ma, David W. L. Kang, Jing X. Kulka, Marianna TI n-3 Polyunsaturated fatty acids inhibit Fc epsilon receptor I-mediated mast cell activation SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE n-3 Polyunsaturated fatty acids; Mast cell; Fc epsilon RI; Signal transduction; Lipid rafts ID LIPID RAFTS; ARACHIDONIC-ACID; MEMBRANE FLUIDITY; TRANSGENIC MICE; FAT-1 MICE; OMEGA-3-FATTY-ACIDS; ASTHMA; INVOLVEMENT; HISTAMINE; RESPONSES AB In vivo models show that n-3 polyunsaturated fatty acids (PUFA) inhibit some of the processes associated with allergic inflammation but the direct effect of n-3 PUFA on mast cells, the major effector cells in allergy, is poorly understood. We sought to determine the effect and mechanism of n-3 PUFA on Fc a receptor I (Fc epsilon RI)-mediated signal transduction and mast cell activation. Bone marrow-derived mast cells (BMMC) were differentiated from bone marrow obtained from C57BL/6 wild-type (WT) and fat-1 transgenic mice. The fat-1 mice express fatty acid n-3 desaturase and produce endogenous n-3 PUFA. For comparison, exogenous n-3 PUFA were supplemented to WT BMMC and human mast cell (LAD2) cultures. Fat-1 BMMC released less beta-hexosaminidase (beta-hex) and cysteinyl leukotrienes and produced less tumor necrosis factor and chemokine (C-C motif) ligand 2. n-3 PUFA supplementation reduced LAD2 and BMMC degranulation (beta-hex release) following FceRI activation. Fat-1 BMMC expressed less constitutive Lyn and linker of activated T cells (LAT), and Fc epsilon RI-mediated phosphorylation of Lyn, spleen tyrosine kinase and LAT were reduced in fat-1 BMMC. Although the expression of surface and whole cell REM was similar in WT and fat-1 BMMC, unstimulated fat-1 BMMC showed reduced Fc epsilon RI localization to lipid rafts, and stimulation with antigen resulted in aberrant REM shuttling to the rafts. Our results show that n-3 PUFA suppress Fc epsilon RI-mediated activation of mast cells, which results in reduced mediator release. This effect is associated with a decrease in LAT and Lyn expression as well as abnormal shuttling of FceRI to lipid rafts. Crown Copyright (C) 2015 Published by Elsevier Inc. All rights reserved. C1 [Wang, Xiaofeng] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB, Canada. [Ma, David W. L.] Univ Guelph, Coll Biol Sci, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada. [Kang, Jing X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Kulka, Marianna] Natl Inst Nanotechnol, Edmonton, AB, Canada. RP Kulka, M (reprint author), Natl Res Council Canada, Natl Inst Nanotechnol, 11421 Saskatchewan Dr, Edmonton, AB T6G 2M9, Canada. EM marianna.kulka@nrc-cnrc.gc.ca FU National Breast Cancer Foundation; Canadian Institutes of Health Research FX This work was supported by the National Breast Cancer Foundation and Canadian Institutes of Health Research. We gratefully acknowledge Dr. Adriana Catalli, Steven Locke and Andrew Breeze for their technical support. NR 49 TC 1 Z9 1 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD DEC PY 2015 VL 26 IS 12 BP 1580 EP 1588 DI 10.1016/j.jnutbio.2015.07.027 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA CZ0HL UT WOS:000366785600019 PM 26363927 ER PT J AU Fernandes, KPS Souza, NHC Mesquita-Ferrari, RA da Silva, DDT Rocha, LA Alves, AN Sousa, KD Bussadori, SK Hamblin, MR Nunes, FD AF Santos Fernandes, Kristianne Porta Costa Souza, Nadhia Helena Mesquita-Ferrari, Raquel Agnelli Teixeira da Silva, Daniela de Fatima Rocha, Lilia Alves Alves, Agnelo Neves Sousa, Kaline de Brito Bussadori, Sandra Kalil Hamblin, Michael R. Nunes, Fabio Daumas TI Photobiomodulation with 660-nm and 780-nm laser on activated J774 macrophage-like cells: Effect on M1 inflammatory markers SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE Cytokines; Inflammatory markers; Photobiomodulation; LLLT; M1-activated macrophages; J774 cells ID MESSENGER-RNA EXPRESSION; SKELETAL-MUSCLE REPAIR; TIBIALIS ANTERIOR MUSCLE; TISSUE-REPAIR; STIMULATED MACROPHAGES; HUMAN MONOCYTES; LIGHT THERAPY; NITRIC-OXIDE; TNF-ALPHA; RATS AB M1 profile macrophages exert a major influence on initial tissue repair process. Few days after the occurrence of injury, macrophages in the injured region exhibit a M2 profile, attenuate the effects of the M1 population, and stimulate the reconstruction of the damaged tissue. The different effects of macrophages in the healing process suggest that these cells could be the target of therapeutic interventions. Photobiomodulation has been used to accelerate tissue repair, but little is known regarding its effect on macrophages. In the present study, J774 macrophages were activated to simulate the M1 profile and irradiated with two different sets of laser parameters (780 nm, 70 mW, 2.6 J/cm(2), 1.5 s and 660 nm, 15 mW, 7.5 J/cm(2), 20 s). IL-6, TNF-alpha, iNOS and COX-2 gene and protein expression were analyzed by RT-qPCR and ELISA. Both lasers were able to reduce TNF-alpha and iNOS expression, and TNF-alpha and COX-2 production, although the parameters used for 780 nm laser provided an additional decrease. 660 nm laser parameters resulted in an up-regulation of IL-6 expression and production. These findings imply a distinct, time-dependent modulation by the two different sets of laser parameters, suggesting that the best modulation may involve more than one combination of parameters. (C) 2015 Elsevier B.V. All rights reserved. C1 [Santos Fernandes, Kristianne Porta; Mesquita-Ferrari, Raquel Agnelli; Teixeira da Silva, Daniela de Fatima; Sousa, Kaline de Brito; Bussadori, Sandra Kalil] Univ Nove Julho UNINOVE, Postgrad Program Biophoton Appl Hlth Sci, BR-01504001 Sao Paulo, SP, Brazil. [Santos Fernandes, Kristianne Porta; Rocha, Lilia Alves; Nunes, Fabio Daumas] Univ Sao Paulo, Sch Dent, Dept Oral Pathol, BR-05508000 Sao Paulo, SP, Brazil. [Costa Souza, Nadhia Helena; Mesquita-Ferrari, Raquel Agnelli; Alves, Agnelo Neves; Bussadori, Sandra Kalil] Univ Nave Julho UNINOVE, Postgrad Program Rehabil Sci, BR-01504001 Sao Paulo, SP, Brazil. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Fernandes, KPS (reprint author), Univ Nove Julho UNINOVE, Postgrad Program Biophoton Appl Hlth Sci, 249 Vergueiro St, BR-01504001 Sao Paulo, SP, Brazil. EM kristianneporta@gmail.com; nadhiacosta@gmail.com; raquel.mesquita@gmail.com; fatesi@uol.com.br; lilia_mail81@yahoo.com.br; agnelonevesalves@gmail.com; kaline.bsousa@gmail.com; sandra.skb@gmail.com; hamblin@helix.mgh.harvard.edu; fadnunes@usp.br RI Ferrari, Raquel/I-4419-2016; Fernandes, Kristianne/I-4417-2016; OI Nunes, Fabio/0000-0002-7785-6785 FU Sao Paulo Research Foundation (FAPESP) [2011/14474-9, 2013/23051-0]; Coordination for the Improvement of Higher Education Personnel (CAPES/PROSUP) [33092010004P5]; National Council for Technological and Scientific Development (CNPq) [303662/2012-3]; US NIH [R01AI050875] FX The authors would like to thank the Brazilian funding agencies Sao Paulo Research Foundation (FAPESP, grant no 2011/14474-9 and grant no 2013/23051-0) and Coordination for the Improvement of Higher Education Personnel (CAPES/PROSUP) (33092010004P5) for financial support. KPS Fernandes was supported by the National Council for Technological and Scientific Development (CNPq, grant no 303662/2012-3). MR Hamblin was supported by US NIH grant R01AI050875. NR 55 TC 4 Z9 4 U1 2 U2 8 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD DEC PY 2015 VL 153 BP 344 EP 351 DI 10.1016/j.jphotobiol.2015.10.015 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CY9ZR UT WOS:000366765400042 PM 26519828 ER PT J AU Cooper, Z Mitchell, SL Gorges, RJ Rosenthal, RA Lipsitz, SR Kelley, AS AF Cooper, Zara Mitchell, Susan L. Gorges, Rebecca J. Rosenthal, Ronnie A. Lipsitz, Stuart R. Kelley, Amy S. TI Predictors of Mortality Up to 1 Year After Emergency Major Abdominal Surgery in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE major abdominal surgery; 1-year mortality; surgical complications; geriatric surgery; emergency surgery ID SELF-REPORTED HEALTH; LONG-TERM OUTCOMES; SURGICAL OUTCOMES; DECISION-MAKING; RISK-FACTORS; MORBIDITY; IMPACT; AGE; DIVERTICULITIS; POPULATION AB ObjectivesTo identify factors associated with mortality in older adults 30, 180, and 365days after emergency major abdominal surgery. DesignA retrospective study linked to Medicare claims from 2000 to 2010. SettingHealth and Retirement Study (HRS). ParticipantsMedicare beneficiaries aged 65.5 enrolled in the HRS from 2000 to 2010 with at least one urgent or emergency major abdominal surgery and a core interview from the HRS within 3years before surgery. MeasurementsSurvival analysis was used to describe all-cause mortality 30, 180, and 365days after surgery. Complementary log-log regression was used to identify participant characteristics and postoperative events associated with poorer survival. ResultsFour hundred individuals had one of the urgent or emergency surgeries of interest, 24% of whom were aged 85 and older, 50% had coronary artery disease, 48% had cancer, 33% had congestive heart failure, and 37% experienced a postoperative complication. Postoperative mortality was 20% at 30days, 31% at 180days, and 34% at 365days. Of those aged 85 and older, 50% were dead 1year after surgery. After multivariate adjustment including postoperative complications, dementia (hazard ratio (HR)=2.02, 95% confidence interval (CI)=1.24-3.31), hospitalization within 6months before surgery (HR=1.63, 95% CI=1.12-2.28), and complications (HR=3.45, 95% CI=2.32-5.13) were independently associated with worse 1-year survival. ConclusionOverall mortality is high in many older adults up to 1year after undergoing emergency major abdominal surgery. The occurrence of a complication is the clinical factor most strongly associated with worse survival. C1 [Cooper, Zara] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Cooper, Zara; Lipsitz, Stuart R.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Mitchell, Susan L.] Inst Aging Res, Hebrew Senior Life, Boston, MA USA. [Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Gorges, Rebecca J.; Kelley, Amy S.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Rosenthal, Ronnie A.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Kelley, Amy S.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Cooper, Z (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM zcooper@partners.org FU Jahnigen Career Development Award from American Geriatrics Society; National Institute on Aging (NIA) Grants [1R03AG042361-01]; Mid-Career Mentoring Award [K24AG033640]; Paul B. Beeson Career Development Award in Aging NIA [K23AG040774]; American Federation for Aging Research FX Dr. Cooper is supported by a Jahnigen Career Development Award from the American Geriatrics Society and National Institute on Aging (NIA) Grants for Early Medical/Surgical Specialists' Transition to Aging Research Grant 1R03AG042361-01. Dr. Mitchell is supported by Mid-Career Mentoring Award K24AG033640. Dr. Kelley is supported by Paul B. Beeson Career Development Award in Aging NIA K23AG040774 and the American Federation for Aging Research. NR 34 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2015 VL 63 IS 12 BP 2572 EP 2579 DI 10.1111/jgs.13785 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CZ6EF UT WOS:000367193300020 PM 26661929 ER PT J AU Hanlon, JT Semla, TP Schmader, KE AF Hanlon, Joseph T. Semla, Todd P. Schmader, Kenneth E. TI Alternative Medications for Medications in the Use of High-Risk Medications in the Elderly and Potentially Harmful Drug-Disease Interactions in the Elderly Quality Measures SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE inappropriate medications; Beers Criteria; medication management ID RANDOMIZED CONTROLLED-TRIAL; HEALTHY MENOPAUSAL WOMEN; VULVO-VAGINAL ATROPHY; OLDER-PEOPLE; PHARMACOLOGICAL MANAGEMENT; POSTMENOPAUSAL WOMEN; PARKINSONS-DISEASE; HOT FLASHES; DEMENTIA; CRITERIA AB The National Committee for Quality Assurance (NCQA) and the Pharmacy Quality Alliance (PQA) use the American Geriatrics Society (AGS) Beers Criteria to designate the quality measure Use of High-Risk Medications in the Elderly (HRM). The Centers for Medicare and Medicaid Services (CMS) use the HRM measure to monitor and evaluate the quality of care provided to Medicare beneficiaries. NCQA additionally uses the AGS Beers Criteria to designate the quality measure Potentially Harmful Drug-Disease Interactions in the Elderly. Medications included in these measures may be harmful to elderly adults and negatively affect a healthcare plan's quality ratings. Prescribers, pharmacists, patients, and healthcare plans may benefit from evidence-based alternative medication treatments to avoid these problems. Therefore the goal of this work was to develop a list of alternative medications to those included in the two measures. The authors conducted a comprehensive literature review from 2000 to 2015 and a search of their personal files. From the evidence, they prepared a list of drug-therapy alternatives with supporting references. A reference list of nonpharmacological approaches was also provided when appropriate. NCQA, PQA, the 2015 AGS Beers Criteria panel, and the Executive Committee of the AGS reviewed the drug therapy alternatives and nonpharmacological approaches. Recommendations by these groups were incorporated into the final list of alternatives. The final product of drug-therapy alternatives to medications included in the two quality measures and some nonpharmacological resources will be useful to health professionals, consumers, payers, and health systems that care for older adults. C1 [Hanlon, Joseph T.] Univ Pittsburgh, Dept Med, Div Geriatr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Geriatr Pharmaceut Outcomes & Gero Informat Res &, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Hanlon, Joseph T.] Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Semla, Todd P.] Pharm Benefits Management Serv, Dept Vet Affairs, Hines, IL USA. [Semla, Todd P.] Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, Sch Med, Div Geriatr,Dept Med, Durham, NC 27710 USA. [Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. RP Hanlon, JT (reprint author), Amer Geriatr Soc, Special Projects & Governance, 40 Fulton St,18th Floor, New York, NY 10038 USA. EM msamuel@americangeriatrics.org FU National Institute of Aging [P30AG024827, R01AG037451, P30AG028716]; Donoghue Foundation grant; Department of Veterans Affairs Health Services Research and Development Service Merit Award [IIR12-379, IIR14-297] FX Dr. Hanlon is supported by National Institute of Aging grants P30AG024827 and R01AG037451, a Donoghue Foundation grant, and Department of Veterans Affairs Health Services Research and Development Service Merit Awards IIR12-379 and IIR14-297. Dr. Schmader is supported by National Institute on Aging Grant P30AG028716. NR 40 TC 14 Z9 14 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2015 VL 63 IS 12 BP e8 EP e18 DI 10.1111/jgs.13807 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CZ6EF UT WOS:000367193300002 PM 26447889 ER PT J AU Steinman, MA Beizer, JL DuBeau, CE Laird, RD Lundebjerg, NE Mulhausen, P AF Steinman, Michael A. Beizer, Judith L. DuBeau, Catherine E. Laird, Rosemary D. Lundebjerg, Nancy E. Mulhausen, Paul TI How to Use the American Geriatrics Society 2015 Beers Criteria-A Guide for Patients, Clinicians, Health Systems, and Payors SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID POTENTIALLY INAPPROPRIATE MEDICATION; OLDER-PEOPLE; EXPLICIT CRITERIA; ADULTS; CARE; PERSPECTIVE; EVENTS; EUROPE; MISUSE; COSTS AB The Beers Criteria are a valuable tool for clinical care and quality improvement but may be misinterpreted and implemented in ways that cause unintended harms. This article describes the intended role of the 2015 American Geriatrics Society (AGS) Beers Criteria and provides guidance on how patients, clinicians, health systems, and payors should use them. A key theme underlying these recommendations is to use common sense and clinical judgment in applying the 2015 AGS Beers Criteria and to remain mindful of nuances in the criteria. The criteria serve as a warning light to identify medications that have an unfavorable balance of benefits and harms in many older adults, particularly when compared with pharmacological and nonpharmacological alternatives. However, there are situations in which use of medications included in the criteria can be appropriate. As such, the 2015 AGS Beers Criteria work best not only when they identify potentially inappropriate medications, but also when they educate clinicians and patients about the reasons those medications are included and the situations in which their use may be more or less problematic. The criteria are designed to support, rather than supplant, good clinical judgment. C1 [Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Beizer, Judith L.] St Johns Univ, Coll Pharm & Hlth Sci, Queens, NY USA. [DuBeau, Catherine E.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [DuBeau, Catherine E.] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA USA. [DuBeau, Catherine E.] Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA. [Laird, Rosemary D.] Florida Hosp, Winter Pk, FL USA. [Lundebjerg, Nancy E.] Amer Geriatr Soc, New York, NY USA. [Mulhausen, Paul] Telligen, W Des Moines, IA USA. RP Steinman, MA (reprint author), 4150 Clement St,SFVAMC Box 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU NIA NIH HHS [K24 AG049057] NR 33 TC 9 Z9 9 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2015 VL 63 IS 12 BP e1 EP e7 DI 10.1111/jgs.13701 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CZ6EF UT WOS:000367193300001 PM 26446776 ER PT J AU Gradishar, WJ Anderson, BO Balassanian, R Blair, SL Burstein, HJ Cyr, A Elias, AD Farrar, WB Forero, A Giordano, SH Goetz, M Goldstein, LJ Hudis, CA Isakoff, SJ Marcom, PK Mayer, IA McCormick, B Moran, M Patel, SA Pierce, LJ Reed, EC Salerno, KE Schwartzberg, LS Smith, KL Smith, ML Soliman, H Somlo, G Telli, M Ward, JH Shead, DA Kumar, R AF Gradishar, William J. Anderson, Benjamin O. Balassanian, Ron Blair, Sarah L. Burstein, Harold J. Cyr, Amy Elias, Anthony D. Farrar, William B. Forero, Andres Giordano, Sharon Hermes Goetz, Matthew Goldstein, Lori J. Hudis, Clifford A. Isakoff, Steven J. Marcom, P. Kelly Mayer, Ingrid A. McCormick, Beryl Moran, Meena Patel, Sameer A. Pierce, Lori J. Reed, Elizabeth C. Salerno, Kilin E. Schwartzberg, Lee S. Smith, Karen Lisa Smith, Mary Lou Soliman, Hatem Somlo, George Telli, Melinda Ward, John H. Shead, Dottie A. Kumar, Rashmi TI Breast Cancer, Version 1.2016 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PERTUZUMAB PLUS TRASTUZUMAB; DOUBLE-BLIND; POSTMENOPAUSAL WOMEN; PREOPERATIVE THERAPY; OVARIAN SUPPRESSION; 1ST-LINE TREATMENT; NEOADJUVANT; TRIAL; ANASTROZOLE; LETROZOLE AB These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor-positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them. C1 [Gradishar, William J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Anderson, Benjamin O.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Balassanian, Ron] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Blair, Sarah L.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Burstein, Harold J.] Dana Farber Brigham & Womens Canc Ctr, Milford, MA USA. [Cyr, Amy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Cyr, Amy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Elias, Anthony D.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Farrar, William B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Farrar, William B.] Solove Res Inst, Columbus, OH USA. [Forero, Andres] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Giordano, Sharon Hermes] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Goetz, Matthew] Mayo Clin, Ctr Canc, Rochester, MN USA. [Goldstein, Lori J.; Patel, Sameer A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Hudis, Clifford A.; McCormick, Beryl] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Marcom, P. Kelly] Duke Canc Inst, Durham, NC USA. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Moran, Meena] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Pierce, Lori J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Reed, Elizabeth C.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Salerno, Kilin E.] Roswell Pk Canc Inst, Buffalo, NY USA. [Schwartzberg, Lee S.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Smith, Karen Lisa] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Smith, Mary Lou] Res Advocacy Network, New York, NY USA. [Soliman, Hatem] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Somlo, George] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Telli, Melinda] Stanford Canc Inst, Stanford, CA USA. [Ward, John H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Shead, Dottie A.; Kumar, Rashmi] Natl Comprehens Canc Network, Washington, DC USA. RP Gradishar, WJ (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. FU Eisai; Bristol-Myers Squibb; Genentech BioOncology; Merck; Novartis Oncology; Novocure; Boehringer Ingelheim Pharmaceuticals, Inc. FX Supported by an educational grant from Eisai; a contribution from Exelixis Inc.; educational grants from Bristol-Myers Squibb, Genentech BioOncology, Merck, Novartis Oncology, Novocure; and by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. NR 28 TC 19 Z9 20 U1 1 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2015 VL 13 IS 12 BP 1475 EP 1485 PG 11 WC Oncology SC Oncology GA CZ3RG UT WOS:000367021100005 PM 26656517 ER PT J AU Carroll, PR Parsons, JK Andriole, G Bahnson, RR Barocas, DA Castle, EP Catalona, WJ Dahl, DM Davis, JW Epstein, JI Etzioni, RB Farrington, T Hemstreet, GP Kawachi, MH Lange, PH Loughlin, KR Lowrance, W Maroni, P Mohler, J Morgan, TM Nadler, RB Poch, M Scales, C Shaneyfelt, TM Smaldone, MC Sonn, G Sprenke, P Vickers, AJ Wake, R Shead, DA Freedman-Cass, D AF Carroll, Peter R. Parsons, J. Kellogg Andriole, Gerald Bahnson, Robert R. Barocas, Daniel A. Castle, Erik P. Catalona, William J. Dahl, Douglas M. Davis, John W. Epstein, Jonathan I. Etzioni, Ruth B. Farrington, Thomas Hemstreet, George P., III Kawachi, Mark H. Lange, Paul H. Loughlin, Kevin R. Lowrance, William Maroni, Paul Mohler, James Morgan, Todd M. Nadler, Robert B. Poch, Michael Scales, Chuck Shaneyfelt, Terrence M. Smaldone, Marc C. Sonn, Geoffrey Sprenke, Preston Vickers, Andrew J. Wake, Robert Shead, Dorothy A. Freedman-Cass, Deborah TI Prostate Cancer Early Detection, Version 2.2015 Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID DIGITAL RECTAL EXAMINATION; BRCA2 MUTATION CARRIERS; RANDOMIZED CONTROLLED-TRIAL; ULTRASOUND-GUIDED BIOPSY; AFRICAN-AMERICAN MEN; MOLECULAR URINE TEST; HEALTH INDEX PHI; PERCENT FREE-PSA; SCREENING TRIAL; FOLLOW-UP AB Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease. C1 [Carroll, Peter R.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Parsons, J. Kellogg] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Andriole, Gerald] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Andriole, Gerald] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Bahnson, Robert R.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bahnson, Robert R.] Solove Res Inst, Columbus, OH USA. [Barocas, Daniel A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Castle, Erik P.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Catalona, William J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Dahl, Douglas M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Davis, John W.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Epstein, Jonathan I.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Etzioni, Ruth B.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Farrington, Thomas] Prostate Hlth Educ Network, Boston, MA USA. [Hemstreet, George P., III] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Kawachi, Mark H.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Lange, Paul H.] Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Loughlin, Kevin R.] Dana Farber Brigham & Womens Canc Ctr, Milford, MA USA. [Lowrance, William] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Maroni, Paul] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Mohler, James] Roswell Pk Canc Inst, Buffalo, NY USA. [Morgan, Todd M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Nadler, Robert B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Poch, Michael] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Scales, Chuck] Duke Canc Inst, Durham, NC USA. [Shaneyfelt, Terrence M.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Smaldone, Marc C.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Sonn, Geoffrey] Stanford Canc Ctr, Stanford, CA USA. [Sprenke, Preston] Smilow Canc Hosp, Yale Canc Ctr, New York, NY USA. [Vickers, Andrew J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Wake, Robert] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP Carroll, PR (reprint author), UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. NR 206 TC 11 Z9 11 U1 3 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2015 VL 13 IS 12 BP 1534 EP 1561 PG 28 WC Oncology SC Oncology GA CZ3RG UT WOS:000367021100010 PM 26656522 ER PT J AU Gregorio, LL Wu, CL Busaba, NY AF Gregorio, Luciano L. Wu, Chin-Lee Busaba, Nicolas Y. TI Lobular Capillary Hemangioma Formation: An Unusual Complication of Submucous Resection With Power Instrumentation of the Inferior Turbinate SO LARYNGOSCOPE LA English DT Article DE Turbinates; hemangioma; capillary hemangioma; sinus surgery ID CAVITY AB Submucous resection with powered instrumentation (SRPI) is an effective surgical method to achieve inferior turbinate (IT) reduction with minimal morbidity. We describe a series of two cases of capillary hemangioma (pyogenic granuloma) that developed in the posterior third of the IT as a late complication after SRPI. C1 [Gregorio, Luciano L.; Busaba, Nicolas Y.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Gregorio, Luciano L.; Busaba, Nicolas Y.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gregorio, Luciano L.] Univ Fed Sao Paulo, Dept Otolaryngol Head & Neck Surg, Sao Paulo, Brazil. RP Gregorio, LL (reprint author), 145 Pinckney St,Apt 325, Boston, MA 02114 USA. EM luciano_gregorio@meei.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2015 VL 125 IS 12 BP 2653 EP 2655 DI 10.1002/lary.25355 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CZ6CC UT WOS:000367187700017 PM 26403945 ER PT J AU Deschler, DG Herr, MW Kmiecik, JR Sethi, R Bunting, G AF Deschler, Daniel G. Herr, Marc W. Kmiecik, Joann R. Sethi, Rosh Bunting, Glenn TI Tracheoesophageal Voice After Total Laryngopharyngectomy Reconstruction: Jejunum Versus Radial Forearm Free Flap SO LARYNGOSCOPE LA English DT Article DE Total laryngopharyngectomy; jejunal free flap; radial forearm free flap; tracheoesophageal voice; quality of life ID ANTEROLATERAL THIGH FLAP; PHARYNGOESOPHAGEAL RECONSTRUCTION; FUNCTIONAL OUTCOMES; CERVICAL ESOPHAGUS; TOTAL LARYNGECTOMY; SWALLOWING OUTCOMES; RESTORATION; SPEECH; EXPERIENCE; PROSTHESIS AB Objective/Hypothesis: Tracheoesophageal (TE) voice restoration after laryngopharyngectomy with jejunal (Jej) flap and radial forearm flap (RFF) reconstruction has been successfully completed and studied for both techniques, but no direct comparisons exist. We undertook this study to directly compare TE voice in patients with total laryngopharyngectomy (TLP) reconstruction using the Jej and the RFF in a comprehensive and rigorous manner. Study Design: Retrospective cohort study. Methods: Forty patients after total laryngectomy or TLP were grouped by pharyngeal closure method: 18 primary closure (STL), 10 jejunal flap (TLP-Jej), and 12 radial forearm flap (TLP-RFF). Voice recordings underwent objective acoustic analysis and blinded subjective assessment by trained and naive listeners. Quality-of-life (QOL) assessments were obtained in all subjects using general health, disease-specific, and voice-specific survey tools. Results: All studies groups had similar demographics. Acoustic analysis demonstrated no differences in fundamental frequency or intensity levels. Subjective assessment demonstrated statistically significant inferior voice function of the reconstructed patients (TLP-Jej and TLP-RFF) compared to STL subjects for nearly all parameters tested by both naive and trained listeners. No differences were noted between TLP-Jej and TLP-RFF subjects for any of the parameters evaluated. Overall, trained listeners assessed TE voice more favorably compared to naive listeners in a significant manner. The three QOL surveys revealed no significant differences between TLP-Jej and TLP-RFF subjects. Conclusion: Tracheoesophageal voice in TLP-Jej and TLP-RFF subjects was equivalent but inferior to STL subjects. Reconstructed subjects had no differences in general, disease-specific, and voice-specific quality of life. C1 [Deschler, Daniel G.; Sethi, Rosh; Bunting, Glenn] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Herr, Marc W.] Brooke Army Med Ctr, Dept Otolaryngol Head & Neck Surg, San Antonio, TX USA. [Kmiecik, Joann R.] Cleveland Clin, Head & Neck Inst, Cleveland, OH 44106 USA. RP Deschler, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg,Acad Affairs, 243 Charles St, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu FU Synthes Grant from The American Head and Neck Society FX Partial financial support for this study was provided by the Synthes Grant awarded from The American Head and Neck Society. The authors have no additional funding, financial relationships, or conflicts of interest to disclose. NR 50 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2015 VL 125 IS 12 BP 2715 EP 2721 DI 10.1002/lary.25404 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CZ6CC UT WOS:000367187700027 PM 26198802 ER PT J AU Creighton, FX Bhattacharyya, N AF Creighton, Francis X., Jr. Bhattacharyya, Neil TI Does Septoplasty Performed at the Same Time as Oropharyngeal Surgery Increase Complication Rates? SO LARYNGOSCOPE LA English DT Article DE Oropharyngeal surgery; septoplasty; surgical outcomes ID OBSTRUCTIVE SLEEP-APNEA; UVULOPALATOPHARYNGOPLASTY; NASAL AB Objectives/Hypothesis: To determine whether septoplasty when combined with ambulatory oropharyngeal surgery increases postoperative complications. Study Design: Cross-sectional analysis of multistate ambulatory surgery and hospital databases. Methods: Ambulatory adult septoplasty and oropharyngeal surgical procedures (tonsillectomy and uvulopalatoplasty [UPPP]) were extracted from the state ambulatory surgery databases for New York, Florida, Iowa, and California for 2010-2011. Cases with concurrent sinus surgery were excluded. Cases were linked to the state emergency department databases and the state inpatient databases to identify revisits within 14 days. The rates of unplanned revisits and postoperative bleeding were determined and compared among groups undergoing solely oropharyngeal surgery versus groups undergoing oropharyngeal surgery combined with septoplasty. Results: Among 26,280 tonsillectomies alone versus 1,002 tonsillectomies1septoplasty, rates for unplanned revisits and hemorrhage were 13.2% and 12.8% (P=.66) and 4.9% and 7.0% (P=.003), respectively. Among 2,598 UPPPs alone versus 1,343 UPPPs+septoplasty, rates for revisits and hemorrhage were 11.4% versus 10.1% (P=.242) and 3.5% versus 3.8% (P=0.683), respectively. Among 389 UPPP/tonsillectomies versus 164 UPPP/tonsillectomies+septoplasty, rates for revisits and hemorrhage were 11.8% versus 8.5% (P=.256) and 3.9% versus 6.1% (P=.247), respectively. Among all cases and groups, there were mortalities only in the UPPP alone group. Conclusions: The addition of septoplasty to oropharyngeal ambulatory surgical procedures does not significantly increase the rate of unplanned revisits or postoperative hemorrhage except in the case of septoplasty added to tonsillectomy, with a small percentage increase in hemorrhage rate. Combining septoplasty with ambulatory oropharyngeal surgery is clinically reasonable in adults. C1 [Creighton, Francis X., Jr.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Sch Med, Boston, MA 02114 USA. [Creighton, Francis X., Jr.; Bhattacharyya, Neil] Harvard Univ, Dept Otolaryngol, Sch Med, Boston, MA 02114 USA. RP Creighton, FX (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM Francis_Creighton@meei.harvard.edu NR 9 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2015 VL 125 IS 12 BP 2828 EP 2831 DI 10.1002/lary.25494 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CZ6CC UT WOS:000367187700046 PM 26297935 ER PT J AU Wu, CW Chai, YJ Dionigi, G Chiang, FY Liu, XL Sun, H Randolph, GW Tufano, RP Kim, HY AF Wu, Che-Wei Chai, Young Jun Dionigi, Gianlorenzo Chiang, Feng-Yu Liu, Xiaoli Sun, Hui Randolph, Gregory W. Tufano, Ralph P. Kim, Hoon Yub TI Recurrent Laryngeal Nerve Safety Parameters of the Harmonic Focus During Thyroid Surgery: Porcine Model Using Continuous Monitoring SO LARYNGOSCOPE LA English DT Article DE Recurrent laryngeal nerve; energy-based devices; Harmonic Focus; electrophysiologic monitoring; thyroid surgery; nerve thermal injury ID CONVENTIONAL HEMOSTASIS; SCALPEL; INJURY; CANCER; STIMULATION; DEVICES; TISSUE; KNOT; RLN AB Objectives/Hypothesis: The Harmonic Focus (HF) is one of the most popular energy-based devices. The aim of this study was to provide recurrent laryngeal nerve (RLN) functional data that define the safety parameters of the HF during thyroidectomy. Study Design: Prospective porcine model using continuous electrophysiologic monitoring. Methods: Ten piglets were used. At varying distances from the RLN, the HF was activated (activation study). The HF was also applied directly on the RLN after activation on sternocleidomastoid muscle for 10 seconds with different cooling times (cooling study). Results: In the activation study, there was no adverse electromyography (EMG) event at more than 1 mm distance. In the cooling study, there was no adverse EMG event after a 10-second cooling period. When the HF was cooled on the sternocleidomastoid muscle, there was no adverse EMG event after 2 seconds cooling time. Conclusions: The safe distance of the HF was 1 mm, and it should be cooled for more than 10 seconds or 2 seconds after cooling on muscle. The HF should be used in a standardized manner to avoid RLN injury. C1 [Wu, Che-Wei; Chiang, Feng-Yu] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan. [Wu, Che-Wei; Chiang, Feng-Yu] Kaohsiung Med Univ, Fac Med, Coll Med, Kaohsiung, Taiwan. [Chai, Young Jun] Seoul Natl Univ, Dept Surg, Boramae Med Ctr, Seoul, South Korea. [Dionigi, Gianlorenzo] Univ Insubria, Endocrine Surg Res Ctr, Dept Surg Sci, Varese Como, Varese, Italy. [Liu, Xiaoli; Sun, Hui] Jilin Univ, China Japan Union Hosp, Dept Thyroid & Parathyroid Surg, Changchun 130023, Jilin, Peoples R China. [Liu, Xiaoli; Sun, Hui] Jilin Prov Key Lab Surg Translat Med, Changchun 130023, Jilin, Peoples R China. [Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Sch Med,Div Thyroid & Parathyroid Surg, Boston, MA 02114 USA. [Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Div Surg Oncol, Sch Med,Dept Surg, Boston, MA 02114 USA. [Tufano, Ralph P.] Johns Hopkins, Sch Med, Div Head & Neck Endocrine Surg, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. [Kim, Hoon Yub] Korea Univ, Coll Med, Dept Surg, KUMC Thyroid Ctr,Korea Univ Hosp, Seoul 136705, South Korea. RP Kim, HY (reprint author), Korea Univ, Coll Med, Dept Surg, 126-1 Anam Dong, Seoul 136705, South Korea. EM hoonyubkim@gmail.com OI dionigi, gianlorenzo/0000-0003-0864-6087; Wu, Che-Wei/0000-0003-1052-5348; Chai, Young Jun/0000-0001-8830-3433 FU Kaohsiung Medical University Hospital [KMUH 103-3T07, 103-3R36]; Ministry of Science and Technology, Taiwan [MOST 103-2314-B-037-037- MY2] FX This study was supported by grants from the Kaohsiung Medical University Hospital (KMUH 103-3T07, 103-3R36), and the Ministry of Science and Technology, Taiwan (MOST 103-2314-B-037-037- MY2). NR 35 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2015 VL 125 IS 12 BP 2838 EP 2845 DI 10.1002/lary.25412 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CZ6CC UT WOS:000367187700048 PM 26198968 ER PT J AU Mhozya, H Bintabara, D Kibusi, S Neilson, E Mpondo, BC AF Mhozya, H. Bintabara, D. Kibusi, S. Neilson, E. Mpondo, B. C. TI Late-stage disease at presentation to an HIV clinic in eastern Tanzania: A retrospective cross-sectional study SO MALAWI MEDICAL JOURNAL LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; INFECTION; COUNTRIES; CARE AB Background Late presentation and delayed treatment initiation is associated with poor outcomes in patients with HIV. Little is known about the stage at which HIV patients present at HIV clinics in Tanzania. Aim: This study aimed at determining the proportion of HIV patients presenting with WHO clinical stages 3 and 4 disease, and the level of immunity at the time of enrollment at the care and treatment center. Methods A retrospective cross-sectional study was conducted among 366 HIV-infected adults attending HIV clinic at Mwananyamala Hospital in Dar es Salaam, Tanzania. Data were obtained from the care and treatment clinic database. Results Late stage disease at the time of presentation was found in 276 (75.4%) of the patients; out of whom 153 (41.8%) presented with CD4 count < 200 cells/ul and 229 (62.6%) presented with WHO clinical stage 3 or 4 at the time of clinic enrollment. Strategies to improve early diagnosis and treatment initiation should be improved. C1 [Mhozya, H.] Buguruni Hlth Ctr, Dar Es Salaam, Tanzania. [Neilson, E.; Mpondo, B. C.] Univ Dodoma, Coll Hlth Sci, Sch Med, Dodoma, Tanzania. [Bintabara, D.; Kibusi, S.] Univ Dodoma, Coll Hlth Sci, Sch Nursing & Publ Hlth, Dodoma, Tanzania. [Neilson, E.] Massachusetts Gen Hosp, Peace Corps SEED Global Hlth Serv Partnership, Ctr Global Hlth, Boston, MA 02114 USA. RP Mpondo, BC (reprint author), Univ Dodoma, Coll Hlth Sci, Dept Internal Med, Sch Med, Dodoma, Tanzania. EM boniempondo@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 0 PU MED COLL MALAWI PI CHICHIRI PA MALAWAI MEDICAL JOURNAL, PRIVATE BAG 360, CHICHIRI, BLANTYRE 3 00000, MALAWI SN 1995-7262 EI 1995-7270 J9 MALAWI MED J JI Malawi Med. J. PD DEC PY 2015 VL 27 IS 4 BP 125 EP 127 DI 10.4314/mmj.v27i4.2 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CZ5ZT UT WOS:000367181600002 PM 26952140 ER PT J AU Stockler-Ipsiroglu, S Apatean, D Battini, R DeBrosse, S Dessoffy, K Edvardson, S Eichler, F Johnston, K Koeller, DM Nouioua, S Tazir, M Verma, A Dowling, MD Wierenga, KJ Wierenga, AM Zhang, V Wong, LJC AF Stockler-Ipsiroglu, Sylvia Apatean, Delia Battini, Roberta DeBrosse, Suzanne Dessoffy, Kimberley Edvardson, Simon Eichler, Florian Johnston, Katherine Koeller, David M. Nouioua, Sonia Tazir, Meriem Verma, Ashok Dowling, Monica D. Wierenga, Klaas J. Wierenga, Andrea M. Zhang, Victor Wong, Lee-Jun C. TI Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE GATM; Cerebral creatine deficiency; Myopathy; Intellectual disability ID CREATINE DEFICIENCY; ARGININE/GLYCINE AMIDINOTRANSFERASE; INBORN ERROR; METABOLISM; DISEASE; HOMOARGININE; BRAIN AB Background: Arginine:glycine aminotransferase (AGAT) (GATM) deficiency is an autosomal recessive inborn error of creative synthesis. Objective: We performed an international survey among physicians known to treat patients with AGAT deficiency, to assess clinical characteristics and long-term outcomes of this ultra-rare condition. Results: 16 patients from 8 families of 8 different ethnic backgrounds were included. 1 patient was asymptomatic when diagnosed at age 3 weeks. 15 patients diagnosed between 16 months and 25 years of life had intellectual disability/developmental delay (IDD). 8 patients also had myopathy/proximal muscle weakness. Common biochemical denominators were low/undetectable guanidinoacetate (GAA) concentrations in urine and plasma, and low/undetectable cerebral creatine levels. 3 families had protein truncation/null mutations. The rest had missense and splice mutations. Treatment with creatine monohydrate (100-800 mg/kg/day) resulted in almost complete restoration of brain creatine levels and significant improvement of myopathy. The 2 patients treated since age 4 and 16 months had normal cognitive and behavioral development at age 10 and 11 years. Late treated patients had limited improvement of cognitive functions. Conclusion: AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GM and cerebral creatine levels (via brain MRS), and by GATM gene sequencing. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Stockler-Ipsiroglu, Sylvia; Apatean, Delia] Univ British Columbia, Dept Pediat, Div Biochem Dis, Vancouver, BC V6H 3V4, Canada. [Stockler-Ipsiroglu, Sylvia] BC Childrens Hosp, Child & Family Res Inst, Vancouver, BC, Canada. [Battini, Roberta] IRCCS Fdn Stella Maris, Dept Dev Neurosci, Pisa, Italy. [DeBrosse, Suzanne; Dessoffy, Kimberley] Univ Hosp Case Med Ctr, Ctr Med Genet, Cleveland, OH USA. [Edvardson, Simon] Hadassah Hebrew Univ, Med Ctr, Pediat Neurol Unit, Jerusalem, Israel. [Eichler, Florian] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. [Johnston, Katherine] Permanent Med Grp, Dept Genet, San Francisco, CA USA. [Koeller, David M.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Nouioua, Sonia; Tazir, Meriem] Univ Alger, CHU Mustapha Bacha, Serv Neurol, Algiers, Algeria. [Nouioua, Sonia; Tazir, Meriem] Univ Alger, CHU Mustapha Bacha, Lab Neurosci, Algiers, Algeria. [Verma, Ashok] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Dowling, Monica D.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Wierenga, Klaas J.; Wierenga, Andrea M.] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Norman, OK 73019 USA. [Zhang, Victor; Wong, Lee-Jun C.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Stockler-Ipsiroglu, S (reprint author), Univ British Columbia, British Columbia Childrens Hosp, Child & Family Res Inst, Dept Pediat,Div Biochem Dis, K3-204-4480 Oak St, Vancouver, BC V6H 3V4, Canada. EM sstockler@cw.bc.ca FU BC Children's Hospital Foundation through TIDE-BC FX Funding support: BC Children's Hospital Foundation through TIDE-BC (www.tidebc.org). NR 24 TC 4 Z9 4 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2015 VL 116 IS 4 BP 252 EP 259 DI 10.1016/j.ymgme.2015.10.003 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA CZ7KH UT WOS:000367277800005 PM 26490222 ER PT J AU Gold, MC McLaren, JE Reistetter, J Smyk-Pearson, S Ladell, K Swarbrick, GM Yu, YYL Hansen, TH Lund, O Nielsen, M Lewinsohn, DA Price, DA Lewinsohn, DM AF Gold, Marielle C. McLaren, James E. Reistetter, Joe Smyk-Pearson, Sue Ladell, Kristin Swarbrick, Gwendolyn M. Yu, Yik Y. L. Hansen, Ted H. Lund, Ole Nielsen, Morten Lewinsohn, Deborah A. Price, David A. Lewinsohn, David M. TI MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T-cell receptor usage SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Antigen Processing and Presentation CY JUN 10-13, 2014 CL Philadelphia, PA C1 [Gold, Marielle C.; Reistetter, Joe; Smyk-Pearson, Sue; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Pulm & Crit Care Med, Portland, OR 97239 USA. [Gold, Marielle C.; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR 97239 USA. [Gold, Marielle C.; Lewinsohn, Deborah A.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Mol Microbiol & Immunol, Portland, OR 97239 USA. [McLaren, James E.; Ladell, Kristin; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales. [Swarbrick, Gwendolyn M.; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Pediat, Portland, OR 97239 USA. [Yu, Yik Y. L.; Hansen, Ted H.] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. [Lund, Ole; Nielsen, Morten] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Nielsen, Morten] Univ Nacl San Martin, Inst Invest Biotecnol, Buenos Aires, DF, Argentina. EM smykpearson@ohsu.edu; swarbric@ohsu.edu; lund@cbs.dtu.dk; mniel@cbs.dtu.dk; lewinsde@ohsu.edu RI Ladell, Kristin/C-8301-2013; Price, David/C-7876-2013; Lund, Ole/F-4437-2014; Nielsen, Morten/E-7754-2011 OI Ladell, Kristin/0000-0002-9856-2938; Price, David/0000-0001-9416-2737; Lund, Ole/0000-0003-1108-0491; Nielsen, Morten/0000-0001-7885-4311 NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2015 VL 68 IS 2 BP 134 EP 134 PN A PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA CZ0AO UT WOS:000366767700022 ER PT J AU Kourjian, G Xu, Y Mondesire-Crump, I Vaithilingam, A Shimada, M Gourdain, P Le Gall, S AF Kourjian, Georgio Xu, Yang Mondesire-Crump, Ijah Vaithilingam, Archana Shimada, Mariko Gourdain, Pauline Le Gall, Sylvie TI Sequence-specific alterations of epitope production and presentation by HIV protease inhibitors SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Antigen Processing and Presentation CY JUN 10-13, 2014 CL Philadelphia, PA C1 [Kourjian, Georgio; Xu, Yang; Mondesire-Crump, Ijah; Vaithilingam, Archana; Shimada, Mariko; Gourdain, Pauline; Le Gall, Sylvie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. EM gkourjian@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2015 VL 68 IS 2 BP 158 EP 159 PN A PG 2 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA CZ0AO UT WOS:000366767700094 ER PT J AU McMurtrey, C Harriff, M Liles, L Swarbrick, G Bardet, W Canfield, ET Jackson, K Lewinsohn, D Lewinsohn, D Hildebrand, W AF McMurtrey, Curtis Harriff, Melanie Liles, Lauren Swarbrick, Gwendolyn Bardet, Wilfried Canfield, Elizabeth T. Jackson, Ken Lewinsohn, Deborah Lewinsohn, David Hildebrand, William TI Identification of Mtb peptides presented by the HLA-Ib molecule HLA-E SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Antigen Processing and Presentation CY JUN 10-13, 2014 CL Philadelphia, PA C1 [McMurtrey, Curtis; Liles, Lauren; Bardet, Wilfried; Jackson, Ken; Hildebrand, William] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73140 USA. [Harriff, Melanie; Swarbrick, Gwendolyn; Canfield, Elizabeth T.; Lewinsohn, Deborah; Lewinsohn, David] Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. EM William-hildebrand@ouhsc.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2015 VL 68 IS 2 BP 158 EP 158 PN A PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA CZ0AO UT WOS:000366767700092 ER PT J AU Harriff, MJ Moita, LF Canfield, ET Grant, WF Burr, A Lewinsohn, DM AF Harriff, Melanie J. Moita, Luis F. Canfield, Elizabeth T. Grant, Wilmon F. Burr, Ansen Lewinsohn, David M. TI Identification of key determinants of MR1 vesicular trafficking and antigen presentation SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Antigen Processing and Presentation CY JUN 10-13, 2014 CL Philadelphia, PA C1 [Harriff, Melanie J.; Canfield, Elizabeth T.; Burr, Ansen; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR 97239 USA. [Harriff, Melanie J.; Canfield, Elizabeth T.; Grant, Wilmon F.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Pulm & Crit Care Med, Portland, OR 97239 USA. [Moita, Luis F.] Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal. [Lewinsohn, David M.] Oregon Hlth & Sci Univ, Mol Microbiol & Immunol, Portland, OR 97239 USA. EM harriffm@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2015 VL 68 IS 2 BP 159 EP 159 PN A PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA CZ0AO UT WOS:000366767700095 ER PT J AU Grant, WF Harriff, MJ Canfield, ET Lewinsohn, DM AF Grant, Wilmon F. Harriff, Melanie J. Canfield, Elizabeth T. Lewinsohn, David M. TI HLA-E dependent antigen processing at the Mycobacterium tuberculosis phagosome SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Antigen Processing and Presentation CY JUN 10-13, 2014 CL Philadelphia, PA C1 [Grant, Wilmon F.; Harriff, Melanie J.; Canfield, Elizabeth T.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Pulm & Crit Care Med, Portland, OR 97239 USA. [Harriff, Melanie J.; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR 97239 USA. EM lewinsod@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2015 VL 68 IS 2 BP 160 EP 160 PN A PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA CZ0AO UT WOS:000366767700099 ER PT J AU Hensley, K Harris-White, ME AF Hensley, Kenneth Harris-White, Marni E. TI Redox regulation of autophagy in healthy brain and neurodegeneration SO NEUROBIOLOGY OF DISEASE LA English DT Review DE Autophagy; Alzheimer's disease; Beclin; Brain; Lanthionine; LC3; Neuroinflammation; Nrf2/Keap1; Redox biology; Reactive oxygen species; Sequestosome ID RESPONSE MEDIATOR PROTEIN-2; AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE; MOUSE MODEL; OXIDATIVE STRESS; AMYLOID-BETA; PATHWAY; COMPLEX; MICE; NRF2 AB Autophagy and redox biochemistry are two major sub disciplines of cell biology which are both coming to be appreciated for their paramount importance in the etiology of neurodegenerative diseases including Alzheimer's disease (AD). Thus far, however, there has been relatively little exploration of the interface between autophagy and redox biology. Autophagy normally recycles macro-molecular aggregates produced through oxidative-stress mediated pathways, and also may reduce the mitochondria(production of reactive oxygen species through recycling of old and damaged mitochondria. Conversely, dysfunction in autophagy initiation, progression or clearance is evidenced to increase aggregation-prone proteins in neural and extraneural tissues. Redox mechanisms of autophagy regulation have been documented at the level of cross-talk between the Nrf2/Keap1 oxidant and electrophilic defense pathway and p62/sequestosome-1 (SQSTM1)-associated autophagy, at least in extraneural tissue; but other mechanisms of redox autophagy regulation doubtless remain to be discovered and the relevance of such processes to maintenance of neural homeostasis remains to be determined. This review summarizes current knowledge regarding the relationship of redox signaling, autophagy control, and oxidative stress as these phenomena relate to neurodegenerative disease. AD is specifically addressed as an example of the theme and as a promising indication for new therapies that act through engagement of autophagy pathways. To exemplify one such novel therapeutic entity, data is presented that the antioxidant and neurotrophic agent lanthionine ketimine-ethyl ester (LIKE) affects autophagy pathway proteins including beclin-1 in the 3xTg-AD model of Alzheimer's disease where the compound has been shown to reduce pathological features and cognitive dysfunction. (C) 2015 Elsevier Inc. All rights reserved. C1 [Hensley, Kenneth] Univ Toledo, Toledo, OH 43614 USA. [Harris-White, Marni E.] Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Harris-White, Marni E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Hensley, K (reprint author), Univ Toledo, Hlth Sci Campus,3000 Arlington Ave, Toledo, OH 43614 USA. EM Kenneth.hensley@utoledo.edu; Marni@ucla.edu FU University of Toledo Foundation Biomedical Innovation Award; Veterans Administration Merit funding; Muscular Dystrophy Association [MDA217526]; National Institutes of Health [NS082283] FX This work was supported in part by the University of Toledo Foundation Biomedical Innovation Award (KH); Veterans Administration Merit funding (MHW); a grant from the Muscular Dystrophy Association (MDA217526; KH); and the National Institutes of Health (NS082283; KH). KH is the inventor on U.S. patent 7,683,055 (other patents pending) covering composition and use of lanthionine ketimine derivatives including lanthionine ketimine-ester (LICE) and holds equity in a company engaged in commercial development of the technology. NR 68 TC 17 Z9 18 U1 4 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2015 VL 84 SI SI BP 50 EP 59 DI 10.1016/j.nbd.2015.03.002 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CZ3UK UT WOS:000367029300005 PM 25771170 ER PT J AU Harris-White, ME Ferbas, KG Johnson, MF Eslami, P Poteshkina, A Venkova, K Christov, A Hensley, K AF Harris-White, Marni E. Ferbas, Kathie G. Johnson, Ming F. Eslami, Pirooz Poteshkina, Aleksandra Venkova, Kalina Christov, Alexandar Hensley, Kenneth TI A cell-penetrating ester of the neural metabolite lanthionine ketimine stimulates autophagy through the mTORC1 pathway: Evidence for a mechanism of action with pharmacological implications for neurodegenerative pathologies SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Autophagy; mTOR complex (mTORC); CRMP2; DPYSL2; Lanthionine ketimine ID RESPONSE MEDIATOR PROTEIN-2; CENTRAL-NERVOUS-SYSTEM; C-LIKE PROTEIN-1; ALZHEIMERS-DISEASE; MOUSE MODEL; MUSCULAR-DYSTROPHY; OXIDATIVE STRESS; BRAIN; RAPAMYCIN; PHOSPHORYLATION AB Autophagy is a fundamental cellular recycling process vulnerable to compromise in neurodegeneration. We now report that a cell-penetrating neurotrophic and neuroprotective derivative of the central nervous system (CNS) metabolite, lanthionine ketimine (LK), stimulates autophagy in RG2 glioma and SH-SY5Y neuroblastoma cells at concentrations within or below pharmacological levels reported in previous mouse studies. Autophagy stimulation was evidenced by increased lipidation of microtubule-associated protein 1 light chain 3 (LC3) both in the absence and presence of bafilomycin-A1 which discriminates between effects on autophagic flux versus blockage of autophagy clearance. LIKE treatment caused changes in protein level or phosphorylation state of multiple autophagy pathway proteins including mTOR; p70S6 kinase; unc-51-like-kinase-1 (ULK1); beclin-1 and LC3 in a manner essentially identical to effects observed after rapamycin treatment. The LICE site of action was near mTOR because neither LIKE nor the mTOR inhibitor rapamycin affected tuberous sclerosis complex (TSC) phosphorylation status upstream from mTOR. Confocal immunofluorescence imaging revealed that LICE specifically decreased mTOR (but not TSC2) colocalization with LAMP2(+) lysosomes in RG2 cells, a necessary event for mTORC1-mediated autophagy suppression, whereas rapamycin had no effect. Suppression of the LK-binding adaptor protein CRMP2 (collapsin response mediator protein-2) by means of shRNA resulted in diminished autophagy flux, suggesting that the LIKE action on mTOR localization may occur through a novel mechanism involving CRMP2-mediated intracellular trafficking. These findings clarify the mechanism-of-action for LIKE in preclinical models of CNS disease, while suggesting possible roles for natural lanthionine metabolites in regulating CNS autophagy. (C) 2015 Elsevier Inc All rights reserved. C1 [Harris-White, Marni E.; Ferbas, Kathie G.; Johnson, Ming F.; Eslami, Pirooz; Poteshkina, Aleksandra] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Harris-White, Marni E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ferbas, Kathie G.] Pepperdine Univ, Seaver Coll, Div Nat Sci, Malibu, CA 90265 USA. [Venkova, Kalina; Christov, Alexandar; Hensley, Kenneth] Univ Toledo, Med Ctr, Dept Pathol, Toledo, OH 43614 USA. [Hensley, Kenneth] Univ Toledo, Med Ctr, Dept Neurosci, Toledo, OH 43614 USA. RP Hensley, K (reprint author), 3000 Arlington Ave, Toledo, OH 43614 USA. EM Kenneth.hensley@utoledo.edu OI Harris-White, Marni/0000-0001-8994-3715 FU University of Toledo Foundation Biomedical Innovation Award; Veterans Administration Merit funding; Muscular Dystrophy Association [MDA217526]; National Institutes of Health [NS082283] FX This work was supported in part by the University of Toledo Foundation Biomedical Innovation Award (KH); Veterans Administration Merit funding (MHW); a grant from the Muscular Dystrophy Association (MDA217526; KH); and the National Institutes of Health (NS082283; KH). KH is the inventor of U.S. patent 7,683,055 covering composition and use of lanthionine ketimine derivatives including lanthionine ketimine-ester (LKE) and holds equity in a company engaged in commercial development of the technology. NR 53 TC 6 Z9 6 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2015 VL 84 SI SI BP 60 EP 68 DI 10.1016/j.nbd.2015.03.007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CZ3UK UT WOS:000367029300006 PM 25779968 ER PT J AU Arimon, M Takeda, S Post, KL Svirsky, S Hyman, BT Berezovska, O AF Arimon, Muriel Takeda, Shuko Post, Kathryn L. Svirsky, Sarah Hyman, Bradley T. Berezovska, Oksana TI Oxidative stress and lipid peroxidation are upstream of amyloid pathology SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Oxidative stress; Lipid peroxidation; Alzheimer's disease; Microdialysis; Amyloid beta; gamma-Secretase; Presenilin; 4-Hydroxynonenal ID FAMILIAL ALZHEIMERS-DISEASE; MILD COGNITIVE IMPAIRMENT; GAMMA-SECRETASE; BETA-PEPTIDE; IN-VIVO; PROTEOMIC IDENTIFICATION; PRESENILIN MUTATIONS; TALKING POINT; MOUSE MODEL; BRAIN AB Oxidative stress is a common feature of the aging process and of many neurodegenerative disorders, including Alzheimer's disease. Understanding the direct causative relationship between oxidative stress and amyloid pathology, and determining the underlying molecular mechanisms is crucial for the development of more effective therapeutics for the disease. By employing microdialysis technique, we report local increase in the amyloid-beta(42) levels and elevated amyloid-beta(42/40) ratio in the interstitial fluid within 6 h of direct infusion of oxidizing agents into the hippocampus of living and awake wild type mice. The increase in the amyloid-beta(42/40) ratio correlated with the pathogenic conformational change of the amyloid precursor protein-cleaving enzyme, presenilin1/gamma-secretase. Furthermore, we found that the product of lipid peroxidation 4-hydroxynonenal, binds to both nicastrin and BACE, differentially affecting gamma- and beta-secretase activity, respectively. The present study demonstrates a direct cause-and-effect correlation between oxidative stress and altered amyloid-beta production, and provides a molecular mechanism by which naturally occurring product of lipid peroxidation may trigger generation of toxic amyloid-beta(42) species. (C) 2015 Elsevier Inc All rights reserved. C1 [Arimon, Muriel; Takeda, Shuko; Post, Kathryn L.; Svirsky, Sarah; Hyman, Bradley T.; Berezovska, Oksana] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA. RP Berezovska, O (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIND, 114 16th St, Charlestown, MA 02129 USA. EM OBerezovska@partners.org RI Arimon, Muriel/I-4054-2015 OI Arimon, Muriel/0000-0002-0894-3324 FU National Institutes of Health [AG044486, AG15379]; BrightFocus foundation; MGH ECOR Postdoctoral Fellowship Award FX We would like to thank Dr. Alberto Serrano-Pozo, MD,PhD, for helpful discussions. This work was supported by National Institutes of Health grants [AG044486 and AG15379 to O.B.]; funding from BrightFocus foundation [O.B.], and the MGH ECOR Postdoctoral Fellowship Award [Fund for Medical Discovery to M.A.]. NR 59 TC 10 Z9 10 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2015 VL 84 SI SI BP 109 EP 119 DI 10.1016/j.nbd.2015.06.013 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CZ3UK UT WOS:000367029300011 PM 26102023 ER PT J AU Hone-Blanchet, A Ciraulo, DA Pascual-Leone, A Fecteau, S AF Hone-Blanchet, Antoine Ciraulo, Domenic A. Pascual-Leone, Alvaro Fecteau, Shirley TI Noninvasive brain stimulation to suppress craving in substance use disorders: Review of human evidence and methodological considerations for future work SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Craving; Substance use disorders; Non-invasive brain stimulation; Transcranial magnetic stimulation; Transcranial electric stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; DORSOLATERAL PREFRONTAL CORTEX; RANDOMIZED CONTROLLED-TRIAL; DORSAL ANTERIOR CINGULATE; HF-RTMS SESSION; DECISION-MAKING; DRUG-ADDICTION; FUNCTIONAL CONNECTIVITY; ALCOHOL DEPENDENCE; CIGARETTE-SMOKING AB Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of noninvasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of noninvasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects' characteristics. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Hone-Blanchet, Antoine; Fecteau, Shirley] Univ Laval, Ctr Rech Inst Univ Sante Mentale Quebec, Ctr Interdisciplinaire Rech Readaptat & Integrat, Fac Med,Lab Canada Res,Chair Cognit Neuroplast, Quebec City, PQ G1V 0A6, Canada. [Pascual-Leone, Alvaro; Fecteau, Shirley] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. [Pascual-Leone, Alvaro; Fecteau, Shirley] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Translat Cognit Neurol, Boston, MA 02215 USA. [Ciraulo, Domenic A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Fecteau, S (reprint author), Univ Laval, Ctr Rech Inst Univ Sante Mentale Quebec, Ctr Interdisciplinaire Rech Readaptat & Integrat, Fac Med,Lab Canada Res,Chair Cognit Neuroplast, 1050 Ave Med, Quebec City, PQ G1V 0A6, Canada. EM Shirley.fecteau@fmed.ulaval.ca FU Centre Interdisciplinaire de Recherche en Readaptation et Integration Sociale; Fonds de la Recherche du Quebec, Sante; Sidney R. Baer Jr. Foundation; National Institutes of Health [R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, UL1 RR025758]; Harvard Catalyst\The Harvard Clinical and Translational Science Center (NCRR); Harvard Catalyst\The Harvard Clinical and Translational Science Center (NCATS NIH) [8KL2TR000168-05]; National Science and Engineering Research Council; Canada Research Chairs FX This work was supported by a scholarship from Centre Interdisciplinaire de Recherche en Readaptation et Integration Sociale and Fonds de la Recherche du Quebec, Sante to AHB, grants from the Sidney R. Baer Jr. Foundation, the National Institutes of Health (R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, UL1 RR025758), and Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NCRR and the NCATS NIH 8KL2TR000168-05) to APL, and grants from the National Science and Engineering Research Council and Canada Research Chairs to SF. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Institutes of Health or the Sidney R. Baer Jr. Foundation. NR 128 TC 4 Z9 4 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD DEC PY 2015 VL 59 BP 184 EP 200 DI 10.1016/j.neubiorev.2015.10.001 PG 17 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CZ1NS UT WOS:000366873200013 PM 26449761 ER PT J AU Fofaria, NM Frederick, DT Sullivan, RJ Flaherty, KT Srivastava, SK AF Fofaria, Neel M. Frederick, Dennie T. Sullivan, Ryan J. Flaherty, Keith T. Srivastava, Sanjay K. TI Overexpression of Mcl-1 confers resistance to BRAF(V600E) inhibitors alone and in combination with MEK1/2 inhibitors in melanoma SO ONCOTARGET LA English DT Article DE BRAF inhibitors; de novo and acquired resistance; MEK1/2 inhibitors; Mcl-1; combination therapy ID PANCREATIC TUMOR-GROWTH; SMALL-MOLECULE INHIBITOR; CELLS IN-VITRO; ACQUIRED-RESISTANCE; CANCER CELLS; MALIGNANT-MELANOMA; TARGETING MCL-1; BRAF INHIBITORS; RAS MUTATIONS; BREAST-CANCER AB Melanoma harboring BRAF mutations frequently develop resistance to BRAF inhibitors, limiting the impact of treatment. Here, we establish a mechanism of resistance and subsequently identified a suitable drug combination to overcome the resistance. Single treatment of BRAF mutant melanoma cell lines with vemurafenib or dabrafenib (BRAF inhibitors) alone or in combination with trametinib (MEK1/2 inhibitor) resulted in overexpression of Mcl-1. Overexpression of Mcl-1 in A375 and SK-MEL-28 by transfection completely blocked BRAF and MEK1/2 inhibitor-mediated inhibition of cell survival and apoptosis. Melanoma cells resistant to BRAF inhibitors showed massive expression of Mcl-1 as compared to respective sensitive cell lines. Silencing of Mcl-1 using siRNA completely sensitized resistant melanoma cells to growth suppression and induction of apoptosis by BRAF inhibitors. In vivo, vemurafenib resistant A375 xenografts implanted in athymic nude mice showed substantial tumor growth inhibition when treated with a combination of vemurafenib and Mcl-1 inhibitor or siRNA. Immunohistochemistry and western blot analyses demonstrated enhanced expression of Mcl-1 and activation of ERK1/2 in vemurafenib-resistant tumors whereas level of Mcl-1 or p-ERK1/2 was diminished in the tumors of mice treated with either of the combination. Biopsied tumors from the patients treated with or resistant to BRAF inhibitors revealed overexpression of Mcl-1. These results suggest that the combination of BRAF inhibitors with Mcl-1 inhibitor may have therapeutic advantage to melanoma patients with acquired resistance to BRAF inhibitors alone or in combination with MEK1/2 inhibitors. C1 [Fofaria, Neel M.; Srivastava, Sanjay K.] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Amarillo, TX 79106 USA. [Fofaria, Neel M.; Srivastava, Sanjay K.] Texas Tech Univ, Hlth Sci Ctr, Canc Biol Ctr, Amarillo, TX USA. [Frederick, Dennie T.; Sullivan, Ryan J.; Flaherty, Keith T.] Harvard Univ, Sch Med, Boston, MA USA. [Frederick, Dennie T.; Sullivan, Ryan J.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Div Med Oncol, Boston, MA USA. RP Srivastava, SK (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Amarillo, TX 79106 USA. EM sanjay.srivastava@ttuhsc.edu FU National Cancer Institute [CA129038] FX This work was supported in part by R01 grant CA129038 (to S.K.S.) awarded by National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 2 Z9 2 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC 1 PY 2015 VL 6 IS 38 BP 40535 EP 40556 PG 22 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CY0SF UT WOS:000366115500013 PM 26497853 ER PT J AU Silva, PS Dela Cruz, AJ Ledesma, MG van Hemert, J Radwan, A Cavallerano, JD Aiello, LM Sun, JK Aiello, LP AF Silva, Paolo S. Dela Cruz, Amanda J. Ledesma, Migil G. van Hemert, Jano Radwan, Ajlan Cavallerano, Jerry D. Aiello, Lloyd M. Sun, Jennifer K. Aiello, Lloyd Paul TI Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography SO OPHTHALMOLOGY LA English DT Article ID RETINAL MICROANEURYSM COUNTS; PROGRESSION; PHOTOGRAPHY; ABNORMALITIES; ONSET AB Purpose: To assess whether the presence of peripheral nonperfusion on ultrawide field (UWF) fluorescein angiography (FA) is associated with diabetic retinopathy (DR) severity and the presence of predominantly peripheral lesions (PPLs). Design: Single-site, cross-sectional, retrospective study. Participants: Sixty-eight eyes of 37 diabetic subjects with or without DR and no history of prior panretinal laser photocoagulation. Methods: Both 200 degrees UWF images and UWF FA images were acquired at the same visit. Early Treatment Diabetic Retinopathy Study (ETDRS) templates were overlaid digitally based on disc and macula location onto stereographically projected UWF images. Images were evaluated for the presence of PPLs, defined as more than 50% of the graded lesion located outside the ETDRS field in each of the 5 extended fields. The UWF-FA images were evaluated by 2 masked, independent graders for extent of retinal nonperfusion area (NPA) and nonperfusion index (NPI; nonperfused/total gradable area). Main Outcome Measures: Association of NPA and NPI with DR severity and presence of PPLs. Results: Distribution of DR severity was as follows: no DR, 8.8% eyes; mild nonproliferative DR (NPDR), 17.6%; moderate NPDR, 32.4%; severe NPDR, 17.6%; proliferative DR (PDR), 19.1%; and high-risk PDR, 4.4%; with PPL present in 61.8%. There was strong intragrader (r = 0.95) and intergrader (r = 0.86) agreement for NPA. Presence of PPLs was associated with increased NPA (191.8 mm(2) vs. 306.1 mm(2); P = 0.0019) and NPI (0.25 vs. 0.43; P = 0.0003). These relationships remained significant after adjusting for DR severity and diabetes duration. In eyes without PDR (n = 52), increasing NPA and NPI was associated with worsening DR (NPA, P = 0.001; NPI, P = 0.0003). NPA and NPI were not associated with clinically significant macular edema (NPA, P = 0.99; NPI, P = 0.67), nor correlated with visual acuity (NPA, r = 0.14, P = 0.23; NPI, r = 0.24, P = 0.05). Conclusions: Following a standardized protocol, the evaluation of UWF FA for NPA and NPI is reproducible. Both parameters are correlated highly with the presence of PPLs and DR severity. Given that the presence and extent of PPLs have been associated with increased risks of DR progression, the clinical identification of PPLs may reflect closely the extent of nonperfusion and ischemia, thus accounting for the increased risk of progression. (C) 2015 by the American Academy of Ophthalmology. C1 [Silva, Paolo S.; Radwan, Ajlan; Cavallerano, Jerry D.; Aiello, Lloyd M.; Sun, Jennifer K.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Silva, Paolo S.; Radwan, Ajlan; Cavallerano, Jerry D.; Aiello, Lloyd M.; Sun, Jennifer K.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Silva, Paolo S.; Dela Cruz, Amanda J.; Ledesma, Migil G.] Univ Philippines, Teleophthalmol & Image Reading Ctr, Philippine Eye Res Inst, Natl Inst Hlth, Manila, Philippines. [van Hemert, Jano] Optos Plc, Dunfermline, Fife, Scotland. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu FU National Academy of Science and Technology, Taguig City, Philippines; Amelia Peabody Charitable Fund (Boston, Massachusetts); Massachusetts Lions Eye Research Fund (Belmont, Massachusetts) FX Supported in part by the National Academy of Science and Technology, Taguig City, Philippines (Outstanding Young Scientist Grant to P.S.S.); the Amelia Peabody Charitable Fund (Boston, Massachusetts); and the Massachusetts Lions Eye Research Fund (Belmont, Massachusetts) to the Joslin Diabetes Center. NR 28 TC 2 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2015 VL 122 IS 12 BP 2465 EP 2472 DI 10.1016/j.ophtha.2015.07.034 PG 8 WC Ophthalmology SC Ophthalmology GA CZ4EZ UT WOS:000367057500025 PM 26350546 ER PT J AU Kanick, SC Davis, SC Zhao, Y Sheehan, KL Hasan, T Maytin, EV Pogue, BW Chapman, MS AF Kanick, S. C. Davis, S. C. Zhao, Y. Sheehan, K. L. Hasan, T. Maytin, E. V. Pogue, B. W. Chapman, M. S. TI Pre-treatment protoporphyrin IX concentration in actinic keratosis lesions may be a predictive biomarker of response to aminolevulinic-acid based photodynamic therapy SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY LA English DT Article DE Photodynamic therapy; Actinic keratosis; Optical dosimetry ID 5-AMINOLEVULINIC ACID; METHYL-AMINOLEVULINATE; SHORT INCUBATION; IN-VIVO; HUMAN SKIN; FOLLOW-UP; FLUORESCENCE; ACCUMULATION; MULTICENTER; SCALP AB Background: Although aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy (PDT) is an effective FDA-approved therapy for actinic keratosis (AK), a substantial fraction of patients (up to 25%) do not respond to treatment. This study examined the feasibility of using pre-treatment measurements of PpIX concentration in AK lesions to predict response of ALA-PpIX PDT. Methods: A non-invasive fiber-optic fluorescence spectroscopy system was used to measure PpIX concentration in patients undergoing standard-of-care ALA-PDT for AK. All patients provided assessments of pain at the time of treatment (n = 70), and a subset reported pain and erythema 48-76 h after treatment (n=13). Results: PpIX concentration was significantly higher in lesions of patients reporting high levels of pain (VAS score >= 5) immediately after treatment vs. patients reporting pain scores below VAS = 5 (p < 0.022) (n = 70). However, pain was not an exclusive indicator of PpIX concentration as many patients with low PpIX concentration reported high pain. In a subpopulation of patients surveyed in the days after treatment (n = 13), PpIX concentration measured on the day of treatment was uncorrelated with pain-reported immediately after treatment (r = 0.17, p < 0.57), but positive correlations were found between PpIX concentration and patient-reported pain (r = 0.55, p < 0.051) and erythema (r = 0.58, p < 0.039) in the 48-72 h following treatment. Conclusions: These data suggest that in vivo optical measurements of PpIX concentration acquired before light delivery may be an objective predictor of response to ALA-PpIX PDT. Identification of non-responding patients on the day of treatment could facilitate the use of interventions that may improve outcomes. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Kanick, S. C.; Davis, S. C.; Zhao, Y.; Pogue, B. W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Kanick, S. C.; Davis, S. C.; Pogue, B. W.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. [Sheehan, K. L.; Pogue, B. W.; Chapman, M. S.] Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03766 USA. [Hasan, T.; Maytin, E. V.; Pogue, B. W.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Maytin, E. V.] Cleveland Clin, Biomed Engn, Cleveland, OH 44106 USA. RP Kanick, SC (reprint author), Dartmouth Coll, Thayer Sch Engn, 14 Engn Dr, Hanover, NH 03755 USA. EM stephen.c.kanick@dartmouth.edu FU National Institute of Health/National Cancer Institute [P01CA084203, K25CA164248]; SYNERGY pilot award from Dartmouth Hitchcock Medical Center FX This work was supported by the National Institute of Health/National Cancer Institute grants P01CA084203 and K25CA164248, and funded in part by a SYNERGY pilot award from Dartmouth Hitchcock Medical Center. NR 42 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-1000 EI 1873-1597 J9 PHOTODIAGN PHOTODYN JI Photodiagnosis Photodyn. Ther. PD DEC PY 2015 VL 12 IS 4 BP 561 EP 566 DI 10.1016/j.pdpdt.2015.10.006 PG 6 WC Oncology SC Oncology GA CZ1OU UT WOS:000366876000002 PM 26480810 ER PT J AU Blevins, JE Baskin, DG AF Blevins, James E. Baskin, Denis G. TI Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans SO PHYSIOLOGY & BEHAVIOR LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society for the Study of Ingestive Behavior CY JUL 29-AUG 02, 2014 CL Seattle, WA DE Obesity; Food intake; Energy expenditure; Oxytocin ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; BROWN ADIPOSE-TISSUE; CAUSES WEIGHT-LOSS; HUMAN GASTROINTESTINAL-TRACT; SUGAR-SWEETENED BEVERAGES; MESSENGER-RNA EXPRESSION; RECEPTOR-DEFICIENT MICE; PRADER-WILLI-SYNDROME; HIGH-AFFINITY BINDING; INDUCED OBESE RATS AB The fact that more than 78 million adults in the US are considered overweight or obese highlights the need to develop new, effective strategies to treat obesity and its associated complications, including type 2 diabetes, kidney disease and cardiovascular disease. While the neurohypophyseal peptide oxytocin (OT) is well recognized for its peripheral effects to stimulate uterine contraction during parturition and milk ejection during lactation, release of OT within the brain is implicated in prosocial behaviors and in the regulation of energy balance. Previous findings indicate that chronic administration of OT decreases food intake and weight gain or elicits weight loss in diet-induced obese (DIO) mice and rats. Furthermore, chronic systemic treatment with OT largely reproduces the effects of central administration to reduce weight gain in DIO and genetically obese rodents at doses that do not appear to result in tolerance. These findings have now been recently extended to more translational models of obesity showing that chronic subcutaneous or intranasal OT treatment is sufficient to elicit body weight loss in DIO nonhuman primates and pre-diabetic obese humans. This review assesses the potential use of OT as a therapeutic strategy for treatment of obesity in rodents, nonhuman primates, and humans, and identifies potential mechanisms that mediate this effect. Published by Elsevier Inc. C1 [Blevins, James E.; Baskin, Denis G.] VA Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Blevins, James E.; Baskin, Denis G.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Blevins, JE (reprint author), VA Puget Sound Hlth Care Syst, Res 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu OI Blevins, James/0000-0002-7587-0380 FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA); California National Primate Research Center (CNPRC) Pilot Award [0D011107]; Department of VA Merit Review Research Program; VA Senior Research Career Scientist award FX This review is based on work presented in the symposium titled, "OT in Energy Balance Control" during the XXIInd Annual Meeting of the Society for the Study of Ingestive Behavior, July 29-August 2, 2014, in Seattle, WA. This material is based upon work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA). The research in our laboratory has been supported by the California National Primate Research Center (CNPRC) Pilot Award (core grant #0D011107) and the Department of VA Merit Review Research Program. DGB is the recipient of a VA Senior Research Career Scientist award. We also acknowledge the contributions of Dr. Christian Roth and Dr. Karen Bales for their review of this manuscript. In addition, we acknowledge Zachary Roberts for his technical assistance with Fig. 1. NR 242 TC 9 Z9 9 U1 7 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 1 PY 2015 VL 152 SI SI BP 438 EP 449 DI 10.1016/j.physbeh.2015.05.023 PN B PG 12 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA CZ2SB UT WOS:000366953800016 PM 26013577 ER PT J AU Schuster, RM Mermelstein, RJ Hedeker, D AF Schuster, Randi Melissa Mermelstein, Robin J. Hedeker, Donald TI Acceptability and Feasibility of a Visual Working Memory Task in an Ecological Momentary Assessment Paradigm SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE visual working memory; ecological momentary assessment; neurocognition ID PERFORMANCE ASSESSMENT TEST; SHORT-TERM-MEMORY; NEUROPSYCHOLOGICAL ASSESSMENT; VIRTUAL ENVIRONMENT; INITIAL VALIDATION; REACTION-TIME; ORGANIZATION; INFORMATION; CAPACITY; VALIDITY AB Neuropsychological performance, has historically been measured in laboratory settings using standardized assessments. However, these methods may be inherently limited in generalizability. This concern may be mitigated with paradigms such as ecological momentary assessment (EMA). We evaluated the initial feasibility and acceptability of administering a visual working memory (VWM) task on handheld computers across l MA study week among adolescents/young adults (N = 39). Participants also completed standardized laboratory neurocognitive measures to determine the extent to which ['MA VWM performance mapped onto scores obtained in traditional testing enviromnents. Compliance with the EMA protocol was high as participants responded to 87% of random prompts across the study week. As expected, ['MA VWM performance was positively associated with laboratory measures of auditory and VWM, and these relationships persisted after adjusting for predicted intelligence. Further, discriminant validity tests showed that ['MA VWM was not linked with laboratory scores of verbal abilities and processing speed. These data provide initial evidence on the convergent and discriminant validity of interpretations from this novel, ecologically valid neurocognitive approach. Future studios will aim to further establish the psychometric properties of this (and similar) tasks and investigate how momentary fluctuations in VWM correspond with contextual influences (e.g., substance use, mood) and clinical outcomes. C1 [Schuster, Randi Melissa] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Schuster, Randi Melissa] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mermelstein, Robin J.] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Mermelstein, Robin J.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL USA. [Hedeker, Donald] Univ Illinois, Dept Publ Hlth Sci, Chicago, IL USA. RP Schuster, RM (reprint author), 60 Staniford St, Boston, MA 02114 USA. EM rschuster@mgh.harvard.edu FU National Cancer Institute (NCI) [P01CA098262] FX This publication was made possible by the National Cancer Institute (NCI; P01CA098262, PI: R.J.M.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCI or the National Institutes of Health. We thank Kathi Diviak and John O'Keefe for their work recruiting and maintaining study participants. NR 40 TC 1 Z9 1 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2015 VL 27 IS 4 BP 1463 EP 1470 DI 10.1037/pas0000138 PG 8 WC Psychology, Clinical SC Psychology GA CZ0UG UT WOS:000366820900030 PM 25894710 ER PT J AU Santo, L Siu, KT Raje, N AF Santo, Loredana Siu, Ka Tat Raje, Noopur TI Targeting Cyclin-Dependent Kinases and Cell Cycle Progression in Human Cancers SO SEMINARS IN ONCOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; RNA-POLYMERASE-II; ADVANCED BREAST-CANCER; INHIBITOR DINACICLIB MK-7965; HISTONE GENE-TRANSCRIPTION; PHARMACODYNAMIC END-POINTS; MULTIPLE-MYELOMA; PHASE-I; LUNG-CANCER; RETINOBLASTOMA PROTEIN AB Uncontrolled cell division is a defining characteristic of cancer cells. Cyclin-dependent kinases (Cdks) are critical regulators of cell cycle progression. Deregulated Cdk activities as a result of gene amplification, translocation, or point mutations of Cdks or cyclins, have been reported in a majority of human cancers. These kinases, therefore, represent potential therapeutic targets for the treatment of cancer. In this review, we offer an overview of Cdk functions in driving cell cycle. progression and transcriptional regulation, a highlight of the DNA damage checkpoints, and an outline of the most relevant Cdk inhibitors currently in clinical trials with an emphasis on the Cdk inhibitors used for treatment of multiple myeloma. (C) 2015 Elsevier Inc. All rights reserved. C1 [Santo, Loredana; Siu, Ka Tat; Raje, Noopur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Div Hematol & Oncol, Boston, MA 02115 USA. RP Raje, N (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, POB 216,55 Fruit St, Boston, MA 02114 USA. EM NRAJE@mgh.harvard.edu NR 136 TC 13 Z9 14 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2015 VL 42 IS 6 BP 788 EP 800 DI 10.1053/j.seminoncol.2015.09.024 PG 13 WC Oncology SC Oncology GA CZ1MN UT WOS:000366870000003 PM 26615126 ER PT J AU Grilli, MD Verfaellie, M AF Grilli, Matthew D. Verfaellie, Mieke TI Supporting the self-concept with memory: insight from amnesia SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE self; personal semantics; episodic memory; amnesia ID AUTOBIOGRAPHICAL MEMORY; EPISODIC MEMORY; COGNITIVE NEUROSCIENCE; DECLARATIVE MEMORY; KNOWLEDGE; RETRIEVAL; PATIENT; NEUROPSYCHOLOGY; CONSTRUCTION; IDENTITY AB We investigated the extent to which personal semantic memory supports the self-concept in individuals with medial temporal lobe amnesia and healthy adults. Participants completed eight 'I Am' self-statements. For each of the four highest ranked self-statements, participants completed an open-ended narrative task, during which they provided supporting information indicating why the I Am statement was considered self-descriptive. Participants then completed an episodic probe task, during which they attempted to retrieve six episodic memories for each of these self-statements. Supporting information was scored as episodic, personal semantic or general semantic. In the narrative task, personal semantic memory predominated as self-supporting information in both groups. The amnesic participants generated fewer personal semantic memories than controls to support their self-statements, a deficit that was more pronounced for trait relative to role self-statements. In the episodic probe task, the controls primarily generated unique event memories, but the amnesic participants did not. These findings demonstrate that personal semantic memory, in particular autobiographical fact knowledge, plays a critical role in supporting the self-concept, regardless of the accessibility of episodic memories, and they highlight potential differences in the way traits and roles are supported by personal memory. C1 [Grilli, Matthew D.] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Grilli, MD (reprint author), Vet Adm Med Ctr Jamaica Plain, VA Boston Healthcare Syst, 150 South Huntington Ave 116B, Boston, MA 02130 USA. EM matthew.grilli@va.gov FU Clinical Science Research and Development Service, Department of Veterans Affairs [IO1CX000925] FX This work was supported by: Clinical Science Research and Development Service, Department of Veterans Affairs grant IO1CX000925. NR 44 TC 3 Z9 3 U1 4 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD DEC PY 2015 VL 10 IS 12 BP 1684 EP 1692 DI 10.1093/scan/nsv056 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CZ6DV UT WOS:000367192300009 PM 25964501 ER PT J AU Uchida, M Biederman, J Gabrieli, JDE Micco, J de Los Angeles, C Brown, A Kenworthy, T Kagan, E Whitfield-Gabrieli, S AF Uchida, Mai Biederman, Joseph Gabrieli, John D. E. Micco, Jamie de Los Angeles, Carlo Brown, Ariel Kenworthy, Tara Kagan, Elana Whitfield-Gabrieli, Susan TI Emotion regulation ability varies in relation to intrinsic functional brain architecture SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE fMRI; resting state; reappraisal; amygdala; medial prefrontal cortex ID EVENT-RELATED FMRI; DEFAULT MODE; PREFRONTAL CORTEX; MAJOR DEPRESSION; NEGATIVE AFFECT; TRAIT ANXIETY; CONNECTIVITY; DYSREGULATION; DISORDER; AMYGDALA AB This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. C1 [Uchida, Mai; Biederman, Joseph; Micco, Jamie; Kenworthy, Tara; Kagan, Elana] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02114 USA. [Gabrieli, John D. E.; de Los Angeles, Carlo; Brown, Ariel; Whitfield-Gabrieli, Susan] MIT, Poitras Ctr Affect Disorders Res, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Gabrieli, John D. E.; de Los Angeles, Carlo; Brown, Ariel; Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Whitfield-Gabrieli, S (reprint author), MIT, McGovern Inst Brain Res, 43 Vassar St,46-4041, Cambridge, MA 02139 USA. EM swg@mit.edu FU Tommy Fuss Fund; MGH Pediatric Psychopharmacology Council Fund; Poitras Center for Affective Disorders Research at McGovern Institute for Brain Research FX This work was supported by the Tommy Fuss Fund, the MGH Pediatric Psychopharmacology Council Fund, and the Poitras Center for Affective Disorders Research at the McGovern Institute for Brain Research. NR 46 TC 1 Z9 1 U1 4 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD DEC PY 2015 VL 10 IS 12 BP 1738 EP 1748 DI 10.1093/scan/nsv059 PG 11 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CZ6DV UT WOS:000367192300014 PM 25999363 ER PT J AU Terai, H Tan, L Beauchamp, EM Hatcher, JM Liu, QS Meyerson, M Gray, NS Hammerman, PS AF Terai, Hideki Tan, Li Beauchamp, Ellen M. Hatcher, John M. Liu, Qingsong Meyerson, Matthew Gray, Nathanael S. Hammerman, Peter S. TI Characterization of DDR2 Inhibitors for the Treatment of DDR2 Mutated Nonsmall Cell Lung Cancer SO ACS CHEMICAL BIOLOGY LA English DT Article ID KINASE INHIBITORS; TARGETED THERAPY; MUTATIONS; COLLAGEN; IDENTIFICATION; GENE; ACTIVATION; DASATINIB; SRC; DISCOVERY AB Despite advances in precision medicine approaches over the past decade, the majority of nonsmall cell lung cancers (NSCLCs) are refractory to treatment with targeted small molecule inhibitors. Previous work has identified mutations in the Discoidin Domain Receptor 2 (DDR2) kinase as potential therapeutic targets in NSCLCs. While DDR2 is potently targeted by several multitargeted kinase inhibitors, most notably dasatinib, toxicity has limited the clinical application of anti-DDR2 therapy. Here, we have characterized compound 1 and other tool compounds demonstrating selectivity for DDR2 and show that while these compounds inhibit DDR2 in lung cancer model systems, they display limited antiproliferative activity in DDR2 mutated cell lines as compared to dual DDR2/SRC inhibitors. We show that DDR2 and SRC are binding partners, that SRC activity is tied to DDR2 activation, and that dual inhibition of both DDR2 and SRC leads to enhanced suppression of DDR2 mutated lung cancer cell lines. These results support the further evaluation of dual SRC/DDR2 targeting in NSCLC, and we report a tool compound, compound 5, which potently inhibits both SRC and DDR2 with a distinct selectivity profile as compared to dasatinib. C1 [Terai, Hideki; Beauchamp, Ellen M.; Meyerson, Matthew; Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tan, Li; Hatcher, John M.; Liu, Qingsong; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Tan, Li; Hatcher, John M.; Liu, Qingsong; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Meyerson, Matthew; Hammerman, Peter S.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM Nathanael_gray@dfci.harvard.edu; Peter_hammerman@dfci.harvard.edu FU NCI [P01 CA154303, K08 CA163677] FX This work was supported in part by NCI P01 CA154303 (M.M. and N.S.G.) and K08 CA163677 (P.S.H.). NR 50 TC 6 Z9 6 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD DEC PY 2015 VL 10 IS 12 BP 2687 EP 2696 DI 10.1021/acschembio.5b00655 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CZ1OO UT WOS:000366875400004 PM 26390252 ER PT J AU Martinez-Ramirez, S Romero, JR Shoamanesh, A McKee, AC Van Etten, E Pontes-Neto, O Macklin, EA Ayres, A Auriel, E Himali, JJ Beiser, AS DeCarli, C Stein, TD Alvarez, VE Frosch, MP Rosand, J Greenberg, SM Gurol, ME Seshadri, S Viswanathan, A AF Martinez-Ramirez, Sergi Romero, Jose-Rafael Shoamanesh, Ashkan McKee, Ann C. Van Etten, Ellis Pontes-Neto, Octavio Macklin, Eric A. Ayres, Alison Auriel, Eitan Himali, Jayandra J. Beiser, Alexa S. DeCarli, Charles Stein, Thor D. Alvarez, Victor E. Frosch, Matthew P. Rosand, Jonathan Greenberg, Steven M. Gurol, M. Edip Seshadri, Sudha Viswanathan, Anand TI Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage SO ALZHEIMERS & DEMENTIA LA English DT Article DE Cerebral amyloid angiopathy; Microbleed; Intracerebral hemorrhage; Boston criteria; Sensitivity; Specificity; Predictive value; Likelihood ratio ID CEREBRAL AMYLOID ANGIOPATHY; CLINICAL-DIAGNOSIS; BOSTON CRITERIA; ROTTERDAM-SCAN; RISK-FACTORS; PREVALENCE; DISEASE; MRI; POPULATION; TOPOGRAPHY AB Introduction: The Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH. Methods: We identified individuals aged. 55 years having brain magnetic resonance imaging (MRI) and pathological assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study [FHS]). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria. Results: We included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 +/- 8.5 and 83.4 +/- 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with >= 2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of "probable CAA" (>= 2 strictly lobar MBs) was 87.5% (95% confidence interval [CI], 60.4-97.8) and 25% (95% CI, 13.2-78) in hospital and general populations, respectively. Discussion: Strictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Martinez-Ramirez, Sergi; Shoamanesh, Ashkan; Van Etten, Ellis; Pontes-Neto, Octavio; Ayres, Alison; Auriel, Eitan; Greenberg, Steven M.; Gurol, M. Edip; Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Martinez-Ramirez, Sergi] Autonomous Univ Barcelona, Escola Postgrau, Barcelona, Spain. [Romero, Jose-Rafael; McKee, Ann C.; Beiser, Alexa S.; Alvarez, Victor E.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Romero, Jose-Rafael; Shoamanesh, Ashkan; McKee, Ann C.; Himali, Jayandra J.; Beiser, Alexa S.; Seshadri, Sudha] NHLBIs Framingham Heart Study, Framingham, MA USA. [McKee, Ann C.; Stein, Thor D.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [McKee, Ann C.; Stein, Thor D.] VA Boston Healthcare Syst, US Dept Vet Affairs, Boston, MA USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Himali, Jayandra J.; Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [Alvarez, Victor E.] Boston Univ, Alzheimer Dis Ctr, Ctr Study Traumat Encephalopathy, Boston, MA 02215 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Neuropathol Serv, Charlestown, MA USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Martinez-Ramirez, S (reprint author), Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. EM srmartinez@mgh.harvard.edu RI Pontes-Neto, Octavio/G-4294-2012; Gurol, Edip/J-2279-2014; OI Pontes-Neto, Octavio/0000-0003-0317-843X; Gurol, Edip/0000-0002-2169-4457; Seshadri, Sudha/0000-0001-6135-2622; Macklin, Eric/0000-0003-1618-3502; Beiser, Alexa/0000-0001-8551-7778; /0000-0003-1391-9481 FU National Institute of Neurological Disorders and Stroke [R01NS070834, R01 NS17950]; National Institute on Aging-Massachusetts General Hospital [5P50AG005134-30]; Framingham Heart Study's National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institute on Aging [R01 AG16495, AG08122, AG033193, AG031287, K23AG038444, P30AG13846]; NIH [1RO1 HL64753, R01 HL076784, 1 R01 AG028321]; Department of Veterans Affairs -Framingham Heart Study FX The authors thank Teresa Gomez-Isla and Jamary Oliveira-Filho for their highly valuable comments and suggestions on the study design and execution. This work (design and conduct of the study and collection and management of the data) was financially supported by: -grants from the National Institute of Neurological Disorders and Stroke (R01NS070834) and the National Institute on Aging (5P50AG005134-30)-Massachusetts General Hospital. -the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195) and grants from the National Institute of Neurological Disorders and Stroke (R01 NS17950), the National Institute on Aging (R01 AG16495; AG08122; AG033193; AG031287; K23AG038444; and P30AG13846); NIH grant (1RO1 HL64753; R01 HL076784; and 1 R01 AG028321), and the Department of Veterans Affairs -Framingham Heart Study. NR 41 TC 18 Z9 18 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD DEC PY 2015 VL 11 IS 12 BP 1480 EP 1488 DI 10.1016/j.jalz.2015.04.009 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CY9IW UT WOS:000366721600009 PM 26079413 ER PT J AU Ithapu, VK Singh, V Okonkwo, OC Chappell, RJ Dowling, NM Johnson, SC AF Ithapu, Vamsi K. Singh, Vikas Okonkwo, Ozioma C. Chappell, Richard J. Dowling, N. Maritza Johnson, Sterling C. CA Alzheimer's Dis Neuroimaging TI Imaging-based enrichment criteria using deep learning algorithms for efficient clinical trials in mild cognitive impairment SO ALZHEIMERS & DEMENTIA LA English DT Article DE Clinical trials; Sample enrichment; Deep learning; Alzheimer's disease ID ALZHEIMERS-DISEASE; SAMPLE-SIZE; BIOMARKER; CLASSIFICATION; VARIABILITY; DEMENTIA AB The mild cognitive impairment (MCI) stage of Alzheimer's disease (AD) may be optimal for clinical trials to test potential treatments for preventing or delaying decline to dementia. However, MCI is heterogeneous in that not all cases progress to dementia within the time frame of a trial and some may not have underlying AD pathology. Identifying those MCIs who are most likely to decline during a trial and thus most likely to benefit from treatment will improve trial efficiency and power to detect treatment effects. To this end, using multimodal, imaging-derived, inclusion criteria may be especially beneficial. Here, we present a novel multimodal imaging marker that predicts future cognitive and neural decline from [F-18] fluorodeoxyglucose positron emission tomography (PET), amyloid florbetapir PET, and structural magnetic resonance imaging, based on a new deep learning algorithm (randomized denoising autoencoder marker, rDAm). Using ADNI2 MCI data, we show that using rDAm as a trial enrichment criterion reduces the required sample estimates by at least five times compared with the no-enrichment regime and leads to smaller trials with high statistical power, compared with existing methods. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Ithapu, Vamsi K.; Singh, Vikas] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA. [Ithapu, Vamsi K.; Singh, Vikas; Okonkwo, Ozioma C.; Dowling, N. Maritza; Johnson, Sterling C.] Univ Wisconsin, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Singh, Vikas; Chappell, Richard J.; Dowling, N. Maritza] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Okonkwo, Ozioma C.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Madison, WI USA. [Johnson, Sterling C.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI USA. RP Ithapu, VK (reprint author), Univ Wisconsin, Dept Comp Sci, 1210 W Dayton St, Madison, WI 53706 USA. EM ithapu@wisc.edu FU NIH [R01 AG040396, R01 AG021155]; NSF CAREER award [1252725]; Wisconsin Partnership Program; UW ADRC [P50 AG033514]; UW ICTR [1UL1RR025011] FX NIH R01 AG040396; NSF CAREER award 1252725; NIH R01 AG021155; Wisconsin Partnership Program; UW ADRC P50 AG033514; UW ICTR 1UL1RR025011. NR 28 TC 2 Z9 2 U1 5 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD DEC PY 2015 VL 11 IS 12 BP 1489 EP 1499 DI 10.1016/j.jalz.2015.01.010 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CY9IW UT WOS:000366721600010 PM 26093156 ER PT J AU Koyner, JL Coca, SG Thiessen-Philbrook, H Patel, UD Shlipak, MG Garg, AX Parikh, CR AF Koyner, Jay L. Coca, Steven G. Thiessen-Philbrook, Heather Patel, Uptal D. Shlipak, Michael G. Garg, Amit X. Parikh, Chirag R. CA TRIBE AKI Consortium TI Urine Biomarkers and Perioperative Acute Kidney Injury: The Impact of Preoperative Estimated GFR SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Urine biomarkers; interleukin 18 (IL-18); liver-type fatty acid binding protein (L-FABP); acute renal failure (ARF); acute kidney injury (AKI); perioperative AKI; effect modification; estimated glomerular filtration rate (eGFR); prognosis; cardiac surgery; surgical complication ID GELATINASE-ASSOCIATED LIPOCALIN; GLOMERULAR-FILTRATION-RATE; CYCLE ARREST BIOMARKERS; ACUTE-RENAL-FAILURE; CARDIAC-SURGERY; PREDICT PROGRESSION; CRITICALLY-ILL; POOR OUTCOMES; PERFORMANCE; VALIDATION AB Background: The interaction between baseline kidney function and the performance of biomarkers of acute kidney injury (AKI) on the development of AKI is unclear. Study Design: Post hoc analysis of prospective cohort study. Setting & Participants: The 1,219 TRIBE-AKI Consortium adult cardiac surgery cohort participants. Predictor: Unadjusted postoperative urinary biomarkers of AKI measured within 6 hours of surgery. Outcome: AKI was defined as AKI Network stage 1 (any AKI) or higher, as well as a doubling of serum creatinine level from the preoperative value or the need for post-operative dialysis (severe AKI). Measurements: Stratified analyses by preoperative estimated glomerular filtration rate (eGFR) <= 60 versus >60 mL/min/1.73 m(2). Results: 180 (42%) patients with preoperative eGFRs <= 60 mL/min/1.73 m(2) developed clinical AKI compared with 246 (31%) of those with eGFRs >60 mL/min/1.73 m(2) (P < 0.001). For log(2)-transformed biomarker concentrations, there was a significant interaction between any AKI and baseline eGFR for interleukin 18 (P = 0.007) and borderline significance for liver-type fatty acid binding protein (P = 0.06). For all biomarkers, the adjusted relative risk (RR) point estimates for the risk for any AKI were higher in those with elevated baseline eGFRs compared with those with eGFRs <= 60 mL/min/1.73 m(2). However, the difference in magnitude of these risks was low (adjusted RRs were 1.04 [95% CI, 0.99-1.09] and 1.11 [95% CI, 1.07-1.15] for those with preoperative eGFRs <= 60 mL/min/1.73 m(2) and those with higher eGFRs, respectively). Although no biomarker displayed an interaction for baseline eGFR and severe AKI, log(2)-transformed interleukin 18 and kidney injury molecule 1 had significant adjusted RRs for severe AKI in those with and without baseline eGFRs <= 60 mL/min/1.73 m(2). Limitations: Limited numbers of patients with severe AKI and post-operative dialysis. Conclusions: The association between early postoperative AKI urinary biomarkers and AKI is modified by preoperative eGFR. The degree of this modification and its impact on the biomarker-AKI association is small across biomarkers. Our findings suggest that distinct biomarker cutoffs for those with and without a preoperative eGFR <= 60 mL/min/1.73 m(2) is not necessary. Published by Elsevier Inc. C1 [Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Nephrol Sect, Dept Med, Chicago, IL 60637 USA. [Coca, Steven G.; Parikh, Chirag R.] Yale Univ, Sch Med, Dept Internal Med, Clin Epidemiol Res Ctr, New Haven, CT 06510 USA. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Patel, Uptal D.] Duke Univ, Sch Med, Durham, NC USA. [Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Parikh, CR (reprint author), Yale Univ, Program Appl Translat Res, 60 Temple St,Ste 6C, New Haven, CT 06510 USA. EM chirag.parikh@yale.edu FU National Institutes of Health (NIH) [R01HL085757]; NIH Career Development Awards [K23DK081616, K23DK080132]; NIH [K24DK090203, U01DK082185] FX This study was supported by the National Institutes of Health (NIH; R01HL085757 to Dr Parikh) to fund the TRIBE-AKI Consortium to study novel biomarkers of AKI in cardiac surgery. Drs Koyner and Coca have been supported by NIH Career Development Awards (K23DK081616 and K23DK080132, respectively). Dr Parikh is supported by the NIH (K24DK090203). Drs Coca, Garg, and Parikh are also members of the NIH-sponsored Assess, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Consortium (U01DK082185). Urine biomarker assays were donated by Abbott Diagnostics (IL-18 and NGAL) and Sekisui Diagnostics LLC (cystatin C, KIM-1, and L-FABP). The granting agencies, Abbott Diagnostics, and Sekisui Diagnostics Inc, did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. NR 29 TC 4 Z9 4 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2015 VL 66 IS 6 BP 1006 EP 1014 DI 10.1053/j.ajkd.2015.07.027 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CZ0ZP UT WOS:000366835700016 PM 26386737 ER PT J AU Stanton, RC AF Stanton, Robert C. TI In Reply to 'Restricting Metformin in CKD: Continued Caution Warranted' SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Letter ID KIDNEY-DISEASE C1 [Stanton, Robert C.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2015 VL 66 IS 6 BP 1102 EP 1102 DI 10.1053/j.ajkd.2015.09.012 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CZ0ZP UT WOS:000366835700027 PM 26593315 ER PT J AU Kramar, A Negrier, S Sylvester, R Joniau, S Mulders, P Powles, T Bex, A Bonnetain, F Bossi, A Bracarda, S Bukowski, R Catto, J Choueiri, TK Crabb, S Eisen, T El Demery, M Fitzpatrick, J Flamand, V Goebell, PJ Gravis, G Houede, N Jacqmin, D Kaplan, R Malavaud, B Massard, C Melichar, B Mourey, L Nathan, P Pasquier, D Porta, C Pouessel, D Quinn, D Ravaud, A Rolland, F Schmidinger, M Tombal, B Tosi, D Vauleon, E Volpe, A Wolter, P Escudier, B Filleron, T AF Kramar, A. Negrier, S. Sylvester, R. Joniau, S. Mulders, P. Powles, T. Bex, A. Bonnetain, F. Bossi, A. Bracarda, S. Bukowski, R. Catto, J. Choueiri, T. K. Crabb, S. Eisen, T. El Demery, M. Fitzpatrick, J. Flamand, V. Goebell, P. J. Gravis, G. Houede, N. Jacqmin, D. Kaplan, R. Malavaud, B. Massard, C. Melichar, B. Mourey, L. Nathan, P. Pasquier, D. Porta, C. Pouessel, D. Quinn, D. Ravaud, A. Rolland, F. Schmidinger, M. Tombal, B. Tosi, D. Vauleon, E. Volpe, A. Wolter, P. Escudier, B. Filleron, T. CA DATECAN Renal Can Grp TI Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project(aEuro) SO ANNALS OF ONCOLOGY LA English DT Review DE clinical trials; DATECAN; recommendations; renal cell cancer; time-to-event end points ID BREAST-CANCER; FREE SURVIVAL; CARCINOMA; FUTURE AB Background: In this report, results from a panel of expert in the area of renal cell cancer (RCC) have come up with a consensus for defining selected time-to-event end points in RCC. It should now be easier to compare results from studies when evaluating therapies in both the adjuvant and advanced disease setting.In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. Materials and methods: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. Results: Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). Conclusions: The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons. C1 [Kramar, A.] Ctr Oscar Lambret, Methodol & Biostat Unit, F-59020 Lille, France. [Kramar, A.; Filleron, T.] SIRIC ONCO LILLE, Lille, France. [Negrier, S.] Univ Lyon 1, Ctr Leon Berard, Dept Med Oncol, F-69365 Lyon, France. [Sylvester, R.] EORTC Headquarters, Dept Biostat, Brussels, Belgium. [Joniau, S.] Univ Hosp Leuven, Dept Urol, Leuven, Belgium. [Mulders, P.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Powles, T.] Queen Mary Univ London, Barts Canc Inst, Barts Expt Canc Med Ctr, London, England. [Bex, A.] Netherlands Canc Inst Antoni Van Leeuwenhoekzieke, Dept Urol, Amsterdam, Netherlands. [Bonnetain, F.] Univ Hosp Besancon, Methodol & Qual Life Oncol Unit, Besancon, France. [Bossi, A.; Massard, C.; Escudier, B.] Inst Gustave Roussy, Dept Radiat Oncol, Villejuif, France. [Bracarda, S.] Osped San Donato, Dept Oncol, Arezzo, Italy. [Bukowski, R.] Cleveland Clin, Taussig Canc Ctr, Dept Immunol, Cleveland, OH 44106 USA. [Catto, J.] Univ Sheffield, Acad Urol Unit, Sheffield, S Yorkshire, England. [Choueiri, T. K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Kidney Canc Ctr, Boston, MA 02115 USA. [Crabb, S.] Univ Southampton, Fac Med, Canc Sci Unit, Southampton SO9 5NH, Hants, England. [Eisen, T.] Cambridge Univ Hlth Partners, Dept Oncol, Cambridge, England. [El Demery, M.] Univ Nimes Hosp, Dept Med Oncol, F-30006 Nimes, France. [Fitzpatrick, J.] Mater Misericordiae Univ Hosp, Div Surg, Dublin 7, Ireland. [Fitzpatrick, J.] Univ Coll Dublin, Dublin 2, Ireland. [Flamand, V.] Univ Lille2 Nord France, Dept Urol, Lille, France. [Goebell, P. J.] Univ Erlangen Nurnberg, Dept Urol, D-91054 Erlangen, Germany. [Gravis, G.] Inst Paoli Calmettes, Dept Med Oncol, Marseille, France. [Houede, N.] CHU Caremeau, Dept Med Oncol, Nimes, France. [Jacqmin, D.] CHRU, Dept Urol, Strasbourg, France. [Kaplan, R.] UCL, MRC Clin Trials Unit, London, England. [Malavaud, B.] CHU, Dept Urol, Toulouse, France. [Melichar, B.] Palacky Univ, Med Sch & Teaching Hosp, Dept Oncol, CR-77147 Olomouc, Czech Republic. [Mourey, L.] Inst Univ Canc Oncopole, Inst Claudius Regaud, Dept Med Oncol, Toulouse, France. [Nathan, P.] Mt Vernon Canc Ctr, Dept Med Oncol, Northwood, Middx, England. [Pasquier, D.] Ctr Oscar Lambret, Dept Acad Radiat Oncol, F-59020 Lille, France. [Porta, C.] Fdn IRCCS Policlin San Matteo, Dept Med Oncol, Pavia, Italy. [Pouessel, D.] Hop St Louis, AP HP, Dept Med Oncol, Paris, France. [Quinn, D.] USC Norris Comprehens Canc Ctr & Hosp, Div Oncol, Los Angeles, CA USA. [Ravaud, A.] Hop St Andre, Dept Med Oncol, Bordeaux, France. [Rolland, F.] Inst Cancerol Ouest Rene Gauducheau, Dept Med Oncol, Nantes, France. [Schmidinger, M.] Med Univ Vienna, Div Clin Oncol, Dept Med 1, Vienna, Austria. [Schmidinger, M.] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Tombal, B.] Clin Univ St Luc, Dept Urol, B-1200 Brussels, Belgium. [Tosi, D.] Inst Reg Canc Val dAurelle, Dept Med Oncol, Montpellier, France. [Vauleon, E.] Ctr Eugene Marquis, Dept Med Oncol, Rennes, France. [Volpe, A.] Univ Piemonte Orientale, Maggiore Carita Hosp, Div Urol, Novara, Italy. [Wolter, P.] Univ Hosp Leuven, Leuven Canc Inst, Dept Gen Med Oncol, Leuven, Belgium. RP Filleron, T (reprint author), Inst Univ Canc Toulouse Oncopole, Bur Essais Clin Cellule Biostat, Inst Claudius Regaud, 1 Ave Irene Joliot Curie, F-31059 Toulouse 9, France. EM filleron.thomas@iuct-oncopole.fr RI filleron, thomas/C-3554-2014 OI filleron, thomas/0000-0003-0724-0659 FU Medical Research Council [MC_U122861326, MC_UU_12023/4] NR 20 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 IS 12 BP 2392 EP 2398 DI 10.1093/annonc/mdv380 PG 7 WC Oncology SC Oncology GA CY4JP UT WOS:000366374700005 PM 26371288 ER PT J AU Lambertini, M Ceppi, M Poggio, F Peccatori, FA Azim, HA Ugolini, D Pronzato, P Loibl, S Moore, HCF Partridge, AH Bruzzi, P Del Mastro, L AF Lambertini, M. Ceppi, M. Poggio, F. Peccatori, F. A. Azim, H. A., Jr. Ugolini, D. Pronzato, P. Loibl, S. Moore, H. C. F. Partridge, A. H. Bruzzi, P. Del Mastro, L. TI Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies SO ANNALS OF ONCOLOGY LA English DT Review DE luteinizing hormone-releasing hormone agonists; fertility preservation; ovarian function preservation; breast cancer; premenopausal patients ID ADJUVANT CHEMOTHERAPY; YOUNG-WOMEN; PREMENOPAUSAL WOMEN; PROGNOSTIC IMPACT; CONTROLLED-TRIAL; CLINICAL-TRIALS; FAILURE; AMENORRHEA; TAMOXIFEN; THERAPY AB Background: This meta-analysis assessed the role of luteinizing hormone-releasing hormone agonists (LHRHa) to prevent chemotherapy-induced premature ovarian failure (POF) and fertility in premenopausal breast cancer women. Temporary ovarian suppression with LHRHa during chemotherapy is associated with a significant reduction in the risk of POF and a higher pregnancy rate, with no negative impact on prognosis.The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS). Methods: A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models. Results: A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I-2 = 47.1%, P-heterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I-2 = 0.0%, P-heterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I-2 = 0.0%, P-heterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I-2 = 68.0%, P-heterogeneity = 0.044). Conclusion: Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis. C1 [Lambertini, M.; Poggio, F.; Pronzato, P.] IRCCS AOU San Martino IST, Dept Med Oncol, UO Oncol Med 2, I-16132 Genoa, Italy. [Ceppi, M.; Bruzzi, P.] IRCCS AOU San Martino IST, Clin Epidemiol Unit, I-16132 Genoa, Italy. [Peccatori, F. A.] European Inst Oncol, Dept Gynecol Oncol, Fertil & Procreat Unit, Milan, Italy. [Azim, H. A., Jr.] Univ Libre Bruxelles, Inst Jules Bordet, Dept Med, BrEAST Data Ctr, Brussels, Belgium. [Ugolini, D.] Univ Genoa, Dept Internal Med, Clin Epidemiol Unit, IRCCS AOU San Martino IST, I-16126 Genoa, Italy. [Loibl, S.] GBG, Neu Isenburg, Germany. [Loibl, S.] Sana Klinikum Offenbach, Offenbach, Germany. [Moore, H. C. F.] Cleveland Clin Fdn, Taussig Canc Inst, Cleveland, OH 44195 USA. [Partridge, A. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Del Mastro, L.] IRCCS AOU San Martino IST, Dept Med Oncol, UO Sviluppo Terapie Innovat, I-16132 Genoa, Italy. RP Del Mastro, L (reprint author), IRCCS AOU San Martino IST, Dept Med Oncol, UO Sviluppo Terapie Innovat, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. EM lucia.delmastro@hsanmartino.it OI Bruzzi, Paolo/0000-0002-7874-2077; Lambertini, Matteo/0000-0003-1797-5296; Del Mastro, Lucia/0000-0002-9546-5841 NR 55 TC 18 Z9 18 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 IS 12 BP 2408 EP 2419 DI 10.1093/annonc/mdv374 PG 12 WC Oncology SC Oncology GA CY4JP UT WOS:000366374700007 PM 26347105 ER PT J AU Munzone, E Giobbie-Hurder, A Gusterson, BA Mallon, E Viale, G Thurlimann, B Ejlertsen, B MacGrogan, G Bibeau, F Lelkaitis, G Price, KN Gelber, RD Coates, AS Goldhirsch, A Colleoni, M AF Munzone, E. Giobbie-Hurder, A. Gusterson, B. A. Mallon, E. Viale, G. Thurlimann, B. Ejlertsen, B. MacGrogan, G. Bibeau, F. Lelkaitis, G. Price, K. N. Gelber, R. D. Coates, A. S. Goldhirsch, A. Colleoni, M. CA Int Breast Canc Study Grp BIG 1-98 Collaborative Grp TI Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial SO ANNALS OF ONCOLOGY LA English DT Article DE letrozole; tamoxifen; mucinous; tubular; cribriform; breast cancer ID INTERNATIONAL EXPERT CONSENSUS; POSTMENOPAUSAL WOMEN; TUBULAR CARCINOMA; HIGHLIGHTS; PROGNOSIS; LESIONS; INDEX AB In the BIG 1-98 clinical trial of 4922 postmenopausal women treated with 5 years of letrozole or tamoxifen for endocrine-responsive breast cancer, 183 had the rare histotypes mucinous or tubular/cribriform. These women had better outcomes than those with other histotypes. The magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with these rare histotypes. Background: We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial. Patients and methods: The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or letrozole) included 4922 women, of whom 4091 had central pathology review. Histotype groups were defined as: mucinous (N = 100), tubular/cribriform (N = 83), ductal (N = 3257), and other (N = 651). Of 183 women with either mucinous or tubular/cribriform tumors, 96 were randomly assigned to letrozole and 87 to tamoxifen. Outcomes assessed were disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Median follow-up in the analytic cohort was 8.1 years. Results: Women with tubular/cribriform breast cancer had the best outcomes for all end points compared with the other three histotypes, and had less breast cancer recurrence (97.5% 5-year BCFI) than those with mucinous (93.5%), ductal (88.9%), or other (89.9%) histotypes. Patients with mucinous or tubular/cribriform carcinoma had better DRFI (5-year rates 97.8% and 98.8%, respectively) than those with ductal (90.9%) or other (92.1%) carcinomas. Within the subgroup of women with special histotypes, we observed a nonsignificant increase in the hazard of breast cancer recurrence with letrozole [hazard (letrozole versus tamoxifen): 3.31, 95% confidence interval 0.94-11.7; P = 0.06]. Conclusions: Women with mucinous or tubular/cribriform breast cancer have better outcomes than those with other histotypes, although the observation is based on a limited number of events. In postmenopausal women with these histotypes, the magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with mucinous or tubular/cribriform disease. Clinicaltrials. gov: NCT00004205. C1 [Munzone, E.] European Inst Oncol, Div Med Senol, I-20141 Milan, Italy. [Giobbie-Hurder, A.; Gelber, R. D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG, Ctr Stat, Boston, MA 02115 USA. [Gusterson, B. A.] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland. [Mallon, E.] So Gen Hosp, Glasgow G51 4TF, Lanark, Scotland. [Viale, G.] European Inst Oncol, Dept Pathol & Lab Med, IBCSG Cent Pathol Lab, I-20141 Milan, Italy. [Viale, G.] Univ Milan, Milan, Italy. [Thurlimann, B.] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thurlimann, B.] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Ejlertsen, B.] Rigshosp, Danish Breast Canc Cooperat Grp DBCG, DK-2100 Copenhagen, Denmark. [MacGrogan, G.] Inst Bergonie, Dept Pathol, Bordeaux, France. [Bibeau, F.] Val dAurelle Canc Inst, Dept Pathol, Montpellier, France. [Lelkaitis, G.] Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark. [Price, K. N.] IBCSG, Ctr Stat, Boston, MA USA. [Gelber, R. D.] Harvard Univ, Frontier Sci & Technol Res Fdn, Sch Med, Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Coates, A. S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, A. S.] Univ Sydney, Sydney, NSW 2006, Australia. [Goldhirsch, A.] European Inst Oncol, Program Breast Hlth, I-20141 Milan, Italy. RP Munzone, E (reprint author), European Inst Oncol, Div Med Senol, Via Ripamonti 435, I-20141 Milan, Italy. EM elisabetta.munzone@ieo.it NR 26 TC 0 Z9 0 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2015 VL 26 IS 12 BP 2442 EP 2449 DI 10.1093/annonc/mdv391 PG 8 WC Oncology SC Oncology GA CY4JP UT WOS:000366374700011 PM 26387144 ER PT J AU Hom, J Goldstein, G AF Hom, Jim Goldstein, Gerald TI Introduction to the Special Issue: A Tribute to Ralph M. Reitan SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Editorial Material C1 [Hom, Jim] Neuropsychol Ctr, Plano, TX 75074 USA. [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, VISN IV MIRECC, Pittsburgh, PA USA. RP Hom, J (reprint author), Neuropsychol Ctr, Plano, TX 75074 USA. EM jhom@neuropsych.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2015 VL 30 IS 8 BP 721 EP 723 DI 10.1093/arclin/acv068 PG 3 WC Psychology, Clinical; Psychology SC Psychology GA CY4HD UT WOS:000366368300001 PM 26590071 ER PT J AU Goldstein, G AF Goldstein, Gerald TI Ralph Reitan and Biological Intelligence SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article ID BRAIN-DAMAGE; LESIONS C1 [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, VISN IV MIRECC, Pittsburgh, PA 15260 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, VISN IV MIRECC, Pittsburgh, PA 15260 USA. EM ggold@nb.net NR 23 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2015 VL 30 IS 8 BP 733 EP 739 DI 10.1093/arclin/acv069 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA CY4HD UT WOS:000366368300003 PM 26590073 ER PT J AU Park, M Kulkarni, A Beatty, A Ganz, P Regan, M Vittinghoff, E Whooley, M AF Park, Meyeon Kulkarni, Ameya Beatty, Alexis Ganz, Peter Regan, Mathilda Vittinghoff, Eric Whooley, Mary TI Soluble endothelial cell selective adhesion molecule and cardiovascular outcomes in patients with stable coronary disease: A report from the Heart and Soul Study SO ATHEROSCLEROSIS LA English DT Article DE Atherosclerosis; Endothelium; Kidney disease; Cardiovascular mortality ID GLOMERULAR-FILTRATION-RATE; ARTERY-DISEASE; CYSTATIN-C; THROMBUS FORMATION; SERUM CREATININE; EVENTS; MORTALITY; ALBUMINURIA; ASSOCIATION; FAILURE AB Background and Aims: Endothelial cell-selective adhesion molecule (ESAM) is selectively expressed on vascular endothelium and is postulated to play a role in atherogenesis. We investigated the association of serum soluble ESAM (sESAM) levels with subsequent cardiovascular outcomes in patients with stable ischemic heart disease. Methods: We measured sESAM levels in 981 patients with stable coronary disease enrolled between September 2000 and December 2002 in a prospective cohort study. Poisson regression models were used to define the relationship between baseline sESAM levels and cardiovascular outcomes, including myocardial infarction, heart failure hospitalization, and mortality. Results: There were 293 occurrences of the composite endpoint over a median follow-up of 8.9 years. After adjusting for demographic and clinical risk factors, participants in the highest sESAM quartile (compared to the lower three sESAM quartiles) had a higher rate of the composite endpoint (incident rate ratio (IRR) 1.52 (95% CI 1.16-1.99) as well as of its individual components: myocardial infarction (IRR 1.64 (1.06-2.55)), heart failure hospitalizations (IRR 1.96 (1.32-2.81)), and death (IRR 1.5 (1.2-1.89)). These associations were no longer significant after adjustment for estimated glomerular filtration rate. Conclusions: sESAM levels associate with myocardial infarction, heart failure, and death after adjustment for demographic and clinical risk factors, but not after adjustment for kidney function. sESAM may be involved in the pathogenesis of concurrent kidney and cardiovascular disease. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Park, Meyeon] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Kulkarni, Ameya] Kaiser Permanente, Mclean, VA USA. [Beatty, Alexis; Ganz, Peter] Univ Washington, VA Puget Sound Hlth Care Syst, Div Cardiol, Seattle, WA 98195 USA. [Ganz, Peter] San Francisco Gen Hosp, San Francisco, CA USA. [Regan, Mathilda; Whooley, Mary] San Francisco VA Hosp, Dept Med, San Francisco, CA USA. [Whooley, Mary] UCSF, Dept Med, San Francisco, CA USA. [Vittinghoff, Eric; Whooley, Mary] UCSF, Dept Epidemiol & Biostat, San Francisco, CA USA. RP Park, M (reprint author), 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA. EM meyeon.park@ucsf.edu FU Meyeon Park's NIH/NIDDK [K23 DK099238]; Department of Veteran Affairs (Epidemiology Merit Review Program), Washington, DC; National Heart, Lung, and Blood Institute, Bethesda, MD [R01 HL-079235]; Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), Princeton, NJ; American Federation for Aging Research (Paul Beeson Faculty Scholars in Aging Research Program), New York, NY; Ischemia Research and Education Foundation, South San Francisco, CA FX This work was supported by Meyeon Park's NIH/NIDDK K23 DK099238. The Heart and Soul Study was funded by the Department of Veteran Affairs (Epidemiology Merit Review Program), Washington, DC; grant R01 HL-079235 from the National Heart, Lung, and Blood Institute, Bethesda, MD; the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), Princeton, NJ; the American Federation for Aging Research (Paul Beeson Faculty Scholars in Aging Research Program), New York, NY; and the Ischemia Research and Education Foundation, South San Francisco, CA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2015 VL 243 IS 2 BP 546 EP 552 DI 10.1016/j.atherosclerosis.2015.10.092 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CY6QO UT WOS:000366534100028 PM 26523992 ER PT J AU Crawford, ED Petrylak, DP Higano, CS Kibel, AS Kantoff, PW Small, EJ Shore, ND Ferrari, A AF Crawford, E. David Petrylak, Daniel P. Higano, Celestia S. Kibel, Adam S. Kantoff, Philip W. Small, Eric J. Shore, Neal D. Ferrari, Anna TI Optimal timing of sipuleucel-T treatment in metastatic castration-resistant prostate cancer SO CANADIAN JOURNAL OF UROLOGY LA English DT Review DE prosta tic neoplasms; sipuleucel-T ID CELLULAR IMMUNOTHERAPY; PHASE-III; SURVIVAL; TRIAL; ANTIGEN; IMPACT; INDUCTION; VACCINES; THERAPY; TIME AB Introduction: Numerous treatments are approved for metastatic castration-resistant prostate cancer (mCRPC), including sipuleucel-T, an FDA-approved immunotherapy. Materials and methods: In this paper we review recent data providing insights into the mechanism of action of sipuleucel-T which suggests sipuleucel-T may be most effective when administered to mCRPC patients with a low burden of disease. Published and presented data from the sipuleucel-T clinical trials NeoACT (NCT00715104), IMPACT (NCT00065442), ProACT (NCT00715078), PROTECT (NCT00779402), OpenACT (NCT00901342), STAMP (NCT01487863) and STAND (NCT01431391), individually or across trials, were included in this review. Results: Overall, a growing body of evidence supports the concept that sipuleucel-T, like some other immunotherapies, has long term effects that result in an overall survival benefit. mCRPC patients with a low tumor burden may derive a greater therapeutic benefit, since the immune response may be more robust when the disease is less advanced and immunosuppressive effects from the tumor or traditional therapies may be less marked. In addition, treatment with sipuleucel-T in early mCRPC does not preclude subsequent treatment with other approved mCRPC therapies. Conclusions: Collectively, clinical data to date suggest the optimal timing for sipuleucel-T treatment may be early in the mCRPC treatment paradigm. C1 [Crawford, E. David] Univ Colorado Anschutz Med Campus, Aurora, CO 80045 USA. [Petrylak, Daniel P.] Yale Canc Ctr, Genitourinary Oncol Program, New Haven, CT USA. [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA. [Higano, Celestia S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Kibel, Adam S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Small, Eric J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shore, Neal D.] Atlantic Urol Clin, Myrtle Beach, SC USA. [Ferrari, Anna] Rutgers Canc Inst New Jersey, Dept Med Oncol, New Brunswick, NJ USA. RP Crawford, ED (reprint author), Univ Colorado Anschutz Med Campus, Aurora, CO 80045 USA. FU Dendreon FX EDC has acted as a consultant and advisor to Dendreon. DPP, CSH, ASK, NDS and AF have received research support from Dendreon, and have served on advisory boards for Dendreon. ASK and AF are principal investigators on Dendreon-sponsored clinical trials. PWK has served on advisory boards for Dendreon. EJS has no disclosures. NR 32 TC 0 Z9 0 U1 0 U2 1 PU CANADIAN J UROLOGY PI ST LAURENT PA 2330 WARD ST, STE 604, ST LAURENT, QUEBEC H4M 2V6, CANADA SN 1195-9479 J9 CAN J UROL JI Can. J. Urol. PD DEC PY 2015 VL 22 IS 6 BP 8048 EP 8055 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CZ0GR UT WOS:000366783600003 PM 26688132 ER PT J AU Pusztaszeri, MP Krane, JF Faquin, WC AF Pusztaszeri, Marc P. Krane, Jeffrey F. Faquin, William C. TI BRAF testing and thyroid FNA SO CANCER CYTOPATHOLOGY LA English DT Article ID FINE-NEEDLE-ASPIRATION; GENE-EXPRESSION CLASSIFIER; BRAF(V600E) MUTATION ANALYSIS; CARCINOMA FOLLICULAR VARIANT; V600E MUTATION; INDETERMINATE CYTOLOGY; SINGLE-INSTITUTION; MOLECULAR ANALYSIS; PROGNOSTIC VALUE; DIAGNOSTIC-VALUE C1 [Pusztaszeri, Marc P.] Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland. [Krane, Jeffrey F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Krane, Jeffrey F.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 219, Boston, MA 02114 USA. EM wfaquin@partners.org NR 66 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC PY 2015 VL 123 IS 12 BP 689 EP 695 DI 10.1002/cncy.21614 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA CY5FP UT WOS:000366433800003 PM 26335367 ER PT J AU Lowe, AC Pignon, JC Carvo, I Drage, MG Constantine, NM Jones, N Kroll, Y Frank, DA Signoretti, S Cibas, ES AF Lowe, Alarice C. Pignon, Jean-Christophe Carvo, Ingrid Drage, Michael G. Constantine, Natalie M. Jones, Nichole Kroll, Yasmin Frank, David A. Signoretti, Sabina Cibas, Edmund S. TI Young investigator challenge: Application of cytologic techniques to circulating tumor cell specimens: Detecting activation of the oncogenic transcription factor STAT3 SO CANCER CYTOPATHOLOGY LA English DT Article DE circulating tumor cell (CTC); cytological techniques; cytology; immunocytochemistry; signal transducer and activator of transcription 3 (STAT3) ID METASTATIC BREAST-CANCER; PROSTATE-CANCER; PROGRESSION; SURVIVAL AB BACKGROUNDThe circulating tumor cell (CTC) field is rapidly advancing with the advent of continuously improving technologies for enriching these rare neoplastic cells from blood. CTC enumeration provides prognostic information, and CTC characterization has the potential to provide more useful information for the clinical decision-making process in this era of personalized medicine and targeted therapeutics. Proof-of-principle studies have shown that CTC samples can be characterized with a variety of techniques in the research laboratory environment. The goal of the current study was to validate routine cytologic techniques and immunohistochemical markers in CTC samples in a clinical cytology laboratory, using inducible phosphorylated signal transducer and activator of transcription 3 (pSTAT3) as a clinically important example and Ki-67 as a positive control. METHODSWhole blood from noncancer patients was spiked with breast cancer cell lines with constitutive or inducible pSTAT3 expression and underwent CTC processing in the CellSearch system. The resulting CTC samples were subjected to various cytologic/immunocytochemical techniques and were compared with non-CTC-processed cultured cell controls. RESULTSCTC-processed samples showed a morphology comparable to that of controls in cytospin, ThinPrep, and cell block preparations. Immunocytochemistry for Ki-67 and pSTAT3 provided biological information from CTC samples, showing uniform Ki-67 staining across all samples, pSTAT3 positivity in the constitutive and induced cells, and an absence of pSTAT3 expression in the noninduced cells, as expected. CONCLUSIONSCTC samples can be processed in the cytology laboratory with routine methods. CTC morphologic and immunophenotypic analysis can be easily integrated into the existing clinical workflow, moving the field closer to a true peripheral blood liquid biopsy for cancer patients. Cancer (Cancer Cytopathol) 2015;123:696-705. (c) 2015 American Cancer Society. Circulating tumor cells represent an emerging sample type for targetable biomarkers. This study shows that cytomorphologic and immunophenotypic analysis can be performed on circulating tumor cell specimens with routine cytologic methods. C1 [Lowe, Alarice C.; Pignon, Jean-Christophe; Carvo, Ingrid; Drage, Michael G.; Constantine, Natalie M.; Signoretti, Sabina; Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lowe, Alarice C.; Drage, Michael G.; Frank, David A.; Signoretti, Sabina; Cibas, Edmund S.] Harvard Univ, Sch Med, Boston, MA USA. [Jones, Nichole; Kroll, Yasmin; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Lowe, AC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM aclowe@partners.org NR 22 TC 2 Z9 3 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC PY 2015 VL 123 IS 12 BP 696 EP 705 DI 10.1002/cncy.21640 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA CY5FP UT WOS:000366433800004 PM 26671736 ER PT J AU Weiner, RB DeLuca, JR Wang, F Lin, J Wasfy, MM Berkstresser, B Stohr, E Shave, R Lewis, GD Hutter, AM Picard, MH Baggish, AL AF Weiner, Rory B. DeLuca, James R. Wang, Francis Lin, Jeffrey Wasfy, Meagan M. Berkstresser, Brant Stoehr, Eric Shave, Rob Lewis, Gregory D. Hutter, Adolph M., Jr. Picard, Michael H. Baggish, Aaron L. TI Exercise-Induced Left Ventricular Remodeling Among Competitive Athletes A Phasic Phenomenon SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE exercise; echocardiography; hypertrophy, left ventricular; longitudinal studies; myocardium ID BLOOD-PRESSURE; ENDURANCE; HYPERTROPHY; IMPACT; MECHANICS; TORSION; HUMANS; HEART; ECHOCARDIOGRAPHY; ADAPTATION AB Background- Contemporary understanding of exercise-induced cardiac remodeling is based on cross-sectional data and relatively short duration longitudinal studies. Temporal progression of exercise-induced cardiac remodeling remains incompletely understood. Methods and Results-A longitudinal repeated-measures study design using 2-dimensional and speckle-tracking echocardiography was used to examine acute augmentation phase (AAP; 90 days) and more extended chronic maintenance phase (39 months) left ventricular (LV) structural and functional adaptations to endurance exercise training among competitive male rowers (n=12; age 18.60.5 years). LV mass was within normal limits at baseline (93 +/- 9 g/m(2)), increased after AAP (105 +/- 7 g/m(2); P=0.001), and further increased after chronic maintenance phase (113 +/- 10 g/m(2); P<0.001 for comparison to post-AAP). AAP LV hypertrophy was driven by LV dilation (LV end-diastolic volume, 9 +/- 3 mL/m(2); P=0.004) with stable LV wall thickness (LV wall thickness, 0.3 +/- 0.1 mm; P=0.63). In contrast, chronic maintenance phase LV hypertrophy was attributable to LV wall thickening ( LV wall thickness, 1.1 +/- 0.4 mm; P=0.004) with stable LV chamber volumes (LV end-diastolic volume, 1 +/- 1 mL/m(2); P=0.48). Early diastolic peak tissue velocity increased during AAP (-11.7 +/- 1.9 versus -13.6 +/- 1.3 cm/s; P<0.001) and remained similarly increased after chronic maintenance phase. Conclusions-In a small sample of competitive endurance athletes, exercise-induced cardiac remodeling follows a phasic response with increases in LV chamber size, early diastolic function, and systolic twist in an acute augmentation phase of exercise training. This is followed by a chronic phase of adaptation characterized by increasing wall thickness and regression in LV twist. Training duration is a determinant of exercise-induced cardiac remodeling and has implications for the assessment of myocardial structure and function in athletes. C1 [Weiner, Rory B.; DeLuca, James R.; Lin, Jeffrey; Wasfy, Meagan M.; Lewis, Gregory D.; Hutter, Adolph M., Jr.; Picard, Michael H.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. [Weiner, Rory B.; Wang, Francis; Berkstresser, Brant; Baggish, Aaron L.] Harvard Univ Hlth Serv, Cambridge, MA USA. [Stoehr, Eric; Shave, Rob] Cardiff Metropolitan Univ, Cardiff Sch Sport, Cardiff, S Glam, Wales. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org OI Shave, Rob/0000-0002-0283-037X; Picard, Michael/0000-0002-9264-3243 FU American Heart Association [09FTF2220328] FX This work was supported by the American Heart Association (09FTF2220328 to Dr Baggish). NR 28 TC 5 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD DEC PY 2015 VL 8 IS 12 AR e003651 DI 10.1161/CIRCIMAGING.115.003651 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CY9TG UT WOS:000366748600001 ER PT J AU Arnold, SV Spertus, JA Vemulapalli, S Dai, DD O'Brien, SM Baron, SJ Kirtane, AJ Mack, MJ Green, P Reynolds, MR Rumsfeld, JS Cohen, DJ AF Arnold, Suzanne V. Spertus, John A. Vemulapalli, Sreekanth Dai, Dadi O'Brien, Sean M. Baron, Suzanne J. Kirtane, Ajay J. Mack, Michael J. Green, Philip Reynolds, Matthew R. Rumsfeld, John S. Cohen, David J. TI Association of Patient-Reported Health Status With Long-Term Mortality After Transcatheter Aortic Valve Replacement Report From the STS/ACC TVT Registry SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article ID HIGH-RISK PATIENTS; CITY CARDIOMYOPATHY QUESTIONNAIRE; HEART-FAILURE; MYOCARDIAL-INFARCTION; OUTCOMES; IMPLANTATION; STENOSIS; TRIAL; RELIABILITY; PREDICTORS C1 [Arnold, Suzanne V.; Spertus, John A.; Baron, Suzanne J.; Cohen, David J.] St Lukes Mid Amer Heart Inst, Dept Med, Kansas City, MO 64111 USA. [Arnold, Suzanne V.; Spertus, John A.; Baron, Suzanne J.; Cohen, David J.] Univ Missouri Kansas City, Kansas City, MO USA. [Vemulapalli, Sreekanth; Dai, Dadi; O'Brien, Sean M.] Duke Univ, Dept Med, Durham, NC USA. [Kirtane, Ajay J.; Green, Philip] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Dept Med, New York, NY 10027 USA. [Mack, Michael J.] Baylor Scott & White Hlth, Dept Cardiovasc Dis, Plano, TX USA. [Reynolds, Matthew R.] Lahey Hosp & Med Ctr, Dept Med, Boston, MA USA. [Reynolds, Matthew R.] Harvard Clin Res Inst, Boston, MA USA. [Rumsfeld, John S.] Denver VA Med Ctr, Dept Med, Denver, CO USA. RP Arnold, SV (reprint author), St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM suz.v.arnold@gmail.com FU American College of Cardiology's National Cardiovascular Data Registry (NCDR); National Heart, Lung, and Blood Institute [K23 HL116799, K23 HL12114] FX The Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry is an initiative of the STS and the ACC. This research was supported by the American College of Cardiology's National Cardiovascular Data Registry (NCDR). The study sponsors were not involved in the design and conduct of the study; analysis and interpretation of the data; preparation of the article; or decision to submit the article for publication. Dr Arnold is supported by a Career Development Grant Award (K23 HL116799) from the National Heart, Lung, and Blood Institute. Dr Green is supported by a Career Development Grant Award (K23 HL12114) from the National Heart, Lung, and Blood Institute. NR 29 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD DEC PY 2015 VL 8 IS 12 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY9VI UT WOS:000366754000001 ER PT J AU Wang, LX Lin, L Feng, Y Fernandes, TL Asnis, P Hosseini, A Li, GA AF Wang, Lianxin Lin, Lin Feng, Yong Fernandes, Tiago Lazzaretti Asnis, Peter Hosseini, Ali Li, Guoan TI Anterior cruciate ligament reconstruction and cartilage contact forces-A 3D computational simulation SO CLINICAL BIOMECHANICS LA English DT Article DE Anterior cruciate ligament reconstruction; Biomechanics; Computational model; Contact force ID FEMORAL TUNNEL PLACEMENT; HUMAN KNEE-JOINT; DOUBLE-BUNDLE; ACL RECONSTRUCTION; 3-DIMENSIONAL MODEL; PATELLAR TENDON; GRAFT FUNCTION; IN-VITRO; OSTEOARTHRITIS; SINGLE AB Background: Clinical outcome studies showed a high incidence of knee osteoarthritis after anterior cruciate ligament reconstruction. Abnormal joint kinematics and loading conditions were assumed as risking factors. However, little is known on cartilage contact forces after the surgery. Methods: A validated computational model was used to simulate anatomic and transtibial single-bundle anterior cruciate ligament reconstructions. Two graft fixation angles (0 degrees and 30 degrees) were simulated for each reconstruction. Biomechanics of the knee was investigated in intact, anterior cruciate ligament deficient and reconstructed conditions when the knee was subjected to 134 N anterior load and 400 N quadriceps load at 0 degrees, 30 degrees, 60 degrees and 90 degrees of flexion. The tibial translation and rotation, graft forces, medial and lateral contact forces were calculated. Findings: When the graft was fixed at 0 degrees, the anatomic reconstruction resulted in slightly larger lateral contact force at 0 degrees compared to the intact knee while the transtibial technique led to higher contact force at both 0 degrees and 30 degrees under the muscle load. When graft was fixed at 30 degrees, the anatomic reconstruction overstrained the knee at 0 degrees with larger contact forces, while the transtibial technique resulted in slightly larger contact forces at 30 degrees. Interpretation: This study suggests that neither the anatomic nor the transtibial reconstruction can consistently restore normal knee biomechanics at different flexion angles. The anatomic reconstruction may better restore anteroposterior stability and contact force with the graft fixed at 0 degrees. The transtibial technique may better restore knee anteroposterior stability and articular contact force with the graft fixed at 30 degrees of flexion. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Wang, Lianxin; Lin, Lin; Feng, Yong; Fernandes, Tiago Lazzaretti; Asnis, Peter; Hosseini, Ali; Li, Guoan] Massachusetts Gen Hosp, Dept Orthoped Surg, Bioengn Lab, Boston, MA 02114 USA. [Wang, Lianxin; Lin, Lin; Feng, Yong; Fernandes, Tiago Lazzaretti; Asnis, Peter; Hosseini, Ali; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wang, Lianxin] Jilin Univ, China Japan Union Hosp, Dept Orthoped Stugery, Changchun 130023, Jilin Province, Peoples R China. [Lin, Lin] Peking Univ, Hosp 3, Inst Sports Med, Beijing 100191, Peoples R China. [Feng, Yong] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Orthoped Surg, Shanghai 200233, Peoples R China. [Fernandes, Tiago Lazzaretti] Univ Sao Paulo, Sch Med, Hosp Clin, Inst Orthoped & Traumatol, BR-05403010 Sao Paulo, Brazil. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Bioengn Lab, 55 Fruit St, Boston, MA 02114 USA. EM Li.Guoan@mgh.harvard.edu RI Fernandes, Tiago/B-9107-2017 OI Fernandes, Tiago/0000-0002-6665-3608 FU National Institute of Health [R01AR055612]; China Scholarship Council FX This work was supported by National Institute of Health Grant (R01AR055612) and China Scholarship Council. NR 41 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 EI 1879-1271 J9 CLIN BIOMECH JI Clin. Biomech. PD DEC PY 2015 VL 30 IS 10 BP 1175 EP 1180 DI 10.1016/j.clinbiomech.2015.08.007 PG 6 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA CZ0JF UT WOS:000366790400025 PM 26320976 ER PT J AU Crisp, JG Takhar, SS Moran, GJ Krishnadasan, A Dowd, SE Finegold, SM Summanen, PH Talan, DA AF Crisp, Jonathan G. Takhar, Sukhjit S. Moran, Gregory J. Krishnadasan, Anusha Dowd, Scot E. Finegold, Sydney M. Summanen, Paula H. Talan, David A. CA EMERGEncy ID Net Study Grp TI Inability of Polymerase Chain Reaction, Pyrosequencing, and Culture of Infected and Uninfected Site Skin Biopsy Specimens to Identify the Cause of Cellulitis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE cellulitis; culture; polymerase chain reaction; PCR; pyrosequencing ID RESISTANT STAPHYLOCOCCUS-AUREUS; FINE-NEEDLE-ASPIRATION; SOFT-TISSUE INFECTIONS; ANTIBACTERIAL PROPERTIES; EMERGENCY-DEPARTMENT; DIAGNOSIS; ERYSIPELAS; MANAGEMENT; ADULTS; PCR AB Background. The cause of cellulitis is unclear. Streptococcus pyogenes, and to a lesser extent, Staphylococcus aureus, are presumed pathogens. Methods. We conducted a study of adults with acute cellulitis without drainage presenting to a US emergency department research network. Skin biopsy specimens were taken from the infected site and a comparable uninfected site on the opposite side of the body. Microbiology was evaluated using quantitative polymerase chain reaction (PCR), pyrosequencing, and standard culture techniques. To determine the cause, the prevalence and quantity of bacterial species at the infected and uninfected sites were compared. Results. Among 50 subjects with biopsy specimens from infected and uninfected sites, culture rarely identified a bacterium. Among 49 subjects with paired specimens from infected and uninfected sites tested with PCR, methicillin- susceptible S. aureus was identified in 20 (41%) and 17 (34%), respectively. Pyrosequencing identified abundant atypical bacteria in addition to streptococci and staphylococci. Among 49 subjects with paired specimens tested by pyrosequencing, S. aureus was identified from 11 (22%) and 15 (31%) and streptococci from 15 (31%) and 20 (41%) of the specimens, respectively. Methicillin-resistant S. aureus was not found by culture or PCR, and S. pyogenes was not identified by any technique. Conclusions. The bacterial cause of cellulitis cannot be determined by comparing the prevalence and quantity of pathogens from infected and uninfected skin biopsy specimens using current molecular techniques. Methicillin-susceptible S. aureus was detected but not methicillin-resistant S. aureus or S. pyogenes from cellulitis tissue specimens. For now, optimal treatment will need to be guided by clinical trials. Noninfectious causes should also be explored. C1 [Crisp, Jonathan G.; Moran, Gregory J.; Krishnadasan, Anusha; Talan, David A.] Olive View UCLA Med Ctr, Dept Emergency Med, Los Angeles, CA USA. [Moran, Gregory J.; Talan, David A.] Olive View UCLA Med Ctr, Dept Med, Div Infect Dis, Los Angeles, CA USA. [Finegold, Sydney M.; Summanen, Paula H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Infect Dis,VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Takhar, Sukhjit S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med,Div Infect Dis, Boston, MA 02115 USA. [Takhar, Sukhjit S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Infect Dis, Boston, MA 02115 USA. [Dowd, Scot E.] MR DNA, Shallowater, TX USA. RP Talan, DA (reprint author), Olive View UCLA Med Ctr, 14445 Olive View Dr, Sylmar, CA 91342 USA. EM dtalan@ucla.edu OI Rothman, Richard/0000-0002-1017-9505 FU Centers for Disease Control and Prevention [U01/CI000353-0] FX This work was supported by the Centers for Disease Control and Prevention (cooperative agreement U01/CI000353-0). NR 51 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2015 VL 61 IS 11 BP 1679 EP 1687 DI 10.1093/cid/civ655 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CY5RF UT WOS:000366464200008 PM 26240200 ER PT J AU Abad, CL Safdar, N AF Abad, C. L. Safdar, N. TI The Reemergence of Measles SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Review DE Acute viral illness; Acute viral illness of childhood; Measles; Measles vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; MUMPS-RUBELLA VACCINE; UNITED-STATES; YOUNG-ADULTS; CLINICAL CHARACTERISTICS; MEDIASTINAL EMPHYSEMA; CONTROLLED-TRIAL; LIVE MEASLES; CHILDREN; IMMUNIZATION AB Measles, or rubeola, is a highly infectious, acute viral illness of childhood that is considered eliminated in the USA but has reemerged in the past few years. Globally, an estimated 20 million cases of measles continue to occur, and it remains a leading cause of death among young children. It is rare in the USA and other first world countries, but numerous outbreaks have occurred in the USA recently, due to a combination of factors including poor vaccine coverage and importation of cases among travelers returning from endemic areas. The diagnosis of measles is usually made clinically, when an individual presents with a constellation of symptoms including cough, coryza, conjunctivitis, high fever, and an erythematous maculopapular rash in a cephalocaudal distribution. Complications are common and include otitis media, pneumonia, encephalitis, and rarely death. A measles vaccine is available in two doses and provides excellent protection against the disease. Despite this, vaccination coverage, especially among young adults, remains poor. Given its resurgence in the USA and other countries, interventions are urgently needed to address low vaccination rates and vaccine hesitancy. Measles awareness should also be a priority among young clinicians, who may have never seen a case or are not familiar with the disease. C1 [Abad, C. L.] Univ Philippines, Philippine Gen Hosp, Dept Med, Pasig, Philippines. [Safdar, N.] Univ Wisconsin, Sch Med, William S Middleton Mem Vet Hosp, Madison, WI 53703 USA. [Safdar, N.] Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. RP Safdar, N (reprint author), Univ Wisconsin, Sch Med, William S Middleton Mem Vet Hosp, Madison, WI 53703 USA. EM ns2@medicine.wisc.edu NR 95 TC 3 Z9 3 U1 3 U2 31 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD DEC PY 2015 VL 17 IS 12 AR 51 DI 10.1007/s11908-015-0506-5 PG 8 WC Infectious Diseases SC Infectious Diseases GA CZ0PA UT WOS:000366807000003 PM 26446612 ER PT J AU Xiong, Y Sheen, J AF Xiong, Yan Sheen, Jen TI Novel links in the plant TOR kinase signaling network SO CURRENT OPINION IN PLANT BIOLOGY LA English DT Review ID MESSENGER-RNA TRANSLATION; TRANSCRIPTIONAL REGULATION; CHLAMYDOMONAS-REINHARDTII; PHOSPHOPROTEOME REVEALS; RAPAMYCIN KINASE; S6 KINASE; TARGET; ARABIDOPSIS; GROWTH; MTOR AB Nutrient and energy sensing and signaling mechanisms constitute the most ancient and fundamental regulatory networks to control growth and development in all life forms. The target of rapamycin (TOR) protein kinase is modulated by diverse nutrient, energy, hormone and stress inputs and plays a central role in regulating cell proliferation, growth, metabolism and stress responses from yeasts to plants and animals. Recent chemical, genetic, genomic and metabolomic analyses have enabled significant progress toward molecular understanding of the TOR signaling network in multicellular plants. This review discusses the applications of new chemical tools to probe plant TOR functions and highlights recent findings and predictions on TOR-mediate biological processes. Special focus is placed on novel and evolutionarily conserved TOR kinase effectors as positive and negative signaling regulators that control transcription, translation and metabolism to support cell proliferation, growth and maintenance from embryogenesis to senescence in the plant system. C1 [Xiong, Yan] Chinese Acad Sci, Shanghai Ctr Plant Stress Biol, Shanghai 200032, Peoples R China. [Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. EM sheen@molbio.mgh.harvard.edu FU NIH grant; WJC Special Project RDA-Korea; Chinese Academy of Sciences FX We apologize for limited literature coverage due to space limitation. The projects on the plant TOR signaling network have been supported by the NIH grants and WJC Special Project RDA-Korea to J.S. Y.X. is supported by Chinese Academy of Sciences. NR 60 TC 13 Z9 13 U1 14 U2 41 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5266 EI 1879-0356 J9 CURR OPIN PLANT BIOL JI Curr. Opin. Plant Biol. PD DEC PY 2015 VL 28 BP 83 EP 91 DI 10.1016/j.pbi.2015.09.006 PG 9 WC Plant Sciences SC Plant Sciences GA CZ0FN UT WOS:000366780600013 PM 26476687 ER PT J AU Cheezum, MK Subramaniyam, PS Bittencourt, MS Hulten, EA Ghoshhajra, BB Shah, NR Forman, DE Hainer, J Leavitt, M Padmanabhan, R Skali, H Dorbala, S Hoffmann, U Abbara, S Di Carli, MF Gewirtz, H Blankstein, R AF Cheezum, Michael K. Subramaniyam, Prem Srinivas Bittencourt, Marcio S. Hulten, Edward A. Ghoshhajra, Brian B. Shah, Nishant R. Forman, Daniel E. Hainer, Jon Leavitt, Marcia Padmanabhan, Ram Skali, Hicham Dorbala, Sharmila Hoffmann, Udo Abbara, Suhny Di Carli, Marcelo F. Gewirtz, Henry Blankstein, Ron TI Prognostic value of coronary CTA vs. exercise treadmilltesting: results from the Partners registry SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE exercise testing; coronary computed tomographic angiography; prognosis; major adverse cardiac events; coronary artery disease ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; INTERNATIONAL MULTICENTER REGISTRY; STABLE ANGINA-PECTORIS; ISCHEMIC-HEART-DISEASE; ARTERY-DISEASE; CHEST-PAIN; CARDIAC CT; MYOCARDIAL-INFARCTION; EXTRACARDIAC FINDINGS; CLINICAL-OUTCOMES AB Aims We sought to compare the complementary prognostic value of exercise treadmill testing (ETT) and coronary computed tomographic angiography (CTA) among patients referred for both exams. Methods and results We studied 582 patients without known coronary artery disease (CAD) who were clinically referred for ETT and CTA within 6 months. Patients were followed for cardiovascular (CV) death, non-fatal myocardial infarction (MI), or late revascularization (. 90 days), stratified by Duke Treadmill Score (DTS) and CAD severity (>= 50% stenosis). Mean age was 54 +/- 13 years (63% male). In median follow-up of 40 months, there were 3 CV deaths, 7 non-fatal MIs, and 26 late revascularizations. ETT was inconclusive in 23%, positive in 31%, and negative in 46%. CTA demonstrated no CAD in 37%, non-obstructive CAD in 28%, and obstructive CAD in 35%. Among low-risk ETT patients (n = 326), there were 3 MI, 10 late revascularizations, and the frequent presence of non-obstructive (32%, n = 105) and obstructive CAD (27%, n = 88). When present, ETT features (i.e. angina, DTS, ischaemic electrocardiogram changes, and exercise capacity) individually failed to predict CV death/MI after adjustment for Morise score. Conversely, both obstructive CAD [HR 4.9 (1.0-23.3), P = 0.048] and CAD extent by segment involvement score >4 [HR 3.9 (1.0-15.2), P = 0.049] predicted increased risk for CV death or MI. Conclusion Patients with a low-risk ETT have an excellent prognosis at 40 months, despite the frequent presence of non-obstructive (32%) and obstructive (27%) CAD. In patients with an intermediate-to high-risk ETT (DTS,5), CTA can provide incremental risk stratification for future CV events. C1 [Cheezum, Michael K.; Bittencourt, Marcio S.; Hulten, Edward A.; Shah, Nishant R.; Forman, Daniel E.; Hainer, Jon; Skali, Hicham; Dorbala, Sharmila; Di Carli, Marcelo F.; Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Dept Med,Sch Med, Noninvas Cardiovasc Imaging Program,Cardiovasc Di, Boston, MA 02115 USA. [Cheezum, Michael K.; Bittencourt, Marcio S.; Hulten, Edward A.; Shah, Nishant R.; Forman, Daniel E.; Hainer, Jon; Skali, Hicham; Dorbala, Sharmila; Di Carli, Marcelo F.; Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Dept Radiol,Sch Med, Noninvas Cardiovasc Imaging Program,Cardiovasc Di, Boston, MA 02115 USA. [Subramaniyam, Prem Srinivas; Leavitt, Marcia; Padmanabhan, Ram; Gewirtz, Henry] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA 02115 USA. [Bittencourt, Marcio S.; Ghoshhajra, Brian B.] Univ Sao Paulo, Div Internal Med, Ctr Clin & Epidemiol Res, Sao Paulo, Brazil. [Hulten, Edward A.] Walter Reed Natl Mil Med Ctr, Div Med, Serv Cardiol, Bethesda, MD USA. [Hulten, Edward A.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Hoffmann, Udo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Abbara, Suhny] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. RP Blankstein, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Med,Sch Med, Noninvas Cardiovasc Imaging Program,Cardiovasc Di, 75 Francis St,Shapiro Room 5096, Boston, MA 02115 USA. EM rblankstein@partners.org RI Bittencourt, Marcio/C-1444-2011 OI Bittencourt, Marcio/0000-0002-3711-1754 FU NHLBI NIH HHS [T32 HL094301, K24 HL113128, T32 HL076136] NR 35 TC 5 Z9 5 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 EI 2047-2412 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD DEC PY 2015 VL 16 IS 12 BP 1338 EP 1346 DI 10.1093/ehjci/jev087 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY7KD UT WOS:000366586300010 PM 25899714 ER PT J AU Minami, Y Ong, DS Uemura, S Wang, Z Aguirre, AD Mukhopadhyay, S Soeda, T Vergallo, R Jia, HB Tian, JW Hu, SN Kim, SJ Park, CB Dauerman, HL Lee, S Jang, IK AF Minami, Yoshiyasu Ong, Daniel S. Uemura, Shiro Wang, Zhao Aguirre, Aaron D. Mukhopadhyay, Shankha Soeda, Tsunenari Vergallo, Rocco Jia, Haibo Tian, Jinwei Hu, Sining Kim, Soo Joong Park, Chang-Bum Dauerman, Harold L. Lee, Stephen Jang, Ik-Kyung TI Impacts of lesion angle on incidence and distribution of acute vessel wall injuries and strut malapposition after drug-eluting stent implantation assessed by optical coherence tomography SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE Optical coherence tomography; Drug-eluting stent; Post-stent complication ID THROMBUS FORMATION; CLINICAL-OUTCOMES; NATURAL-HISTORY; TISSUE PROLAPSE; CORONARY STENT; SHEAR-STRESS; FOLLOW-UP; PREDICTORS; DISSECTION; GEOMETRY AB Aims To investigate the impact of lesion angle on the incidence and distribution of acute vessel wall injuries and incomplete stent apposition (ISA) following second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Several ex vivo studies demonstrated that angled arterial walls are exposed to imbalanced mechanical stress from deployed stents. Methods and results We included 243 lesions treated with a single DES (148 everolimus-eluting stent and 95 zotarolimus-eluting stent). Angled lesions were defined as lesions with angle >= 45 degrees onan angiogram(n = 58). The vessel wall injuries and ISA were evaluated by OCT. The results were compared with non-angled lesions (<45 degrees, n = 185). The incidence of instent dissection, thrombus, and ISA was significantly higher in the angled group than in the non-angled group (84.5 vs. 63.2%, P < 0.01; 55.2 vs. 35.1%, P < 0.01; 75.9 vs. 44.9%, P < 0.001, respectively). In the angled group, the normalized tissue protrusion volume around the centreofangle(6.59 +/- 6.81, mm(3) x 10(2)) washigher than in the distal sub-segment (2.21 +/- 2.87, mm(3) x 10(2), P < 0.001), in the proximal sub-segment (4.14 +/- 5.34, mm(3) x 10(2), P = 0.02), and in the non-angled group (3.30 +/- 2.81, mm(3) x 10(2), P < 0.001). The incidence of major adverse cardiac events within 12 months was similar between the groups. Conclusions Angled coronary lesions had a higher incidence rate of OCT-detected vessel wall injuries and ISA compared with non-angled lesions following second-generation DES implantation. Further studies are needed to understand the long-term clinical significance of these findings. C1 [Minami, Yoshiyasu; Ong, Daniel S.; Mukhopadhyay, Shankha; Soeda, Tsunenari; Vergallo, Rocco; Jia, Haibo; Tian, Jinwei; Hu, Sining; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [Wang, Zhao] MIT, Cambridge, MA 02139 USA. [Aguirre, Aaron D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Jia, Haibo; Tian, Jinwei; Hu, Sining] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Kim, Soo Joong; Jang, Ik-Kyung] Kyung Hee Univ Hosp, Seoul, South Korea. [Park, Chang-Bum] Kyung Hee Univ Hosp Gangdong, Seoul, South Korea. [Dauerman, Harold L.] Univ Vermont, Burlington, VT USA. [Lee, Stephen] Queen Mary Hosp, Pok Fu Lam, Hong Kong, Peoples R China. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@mgh.harvard.edu RI Wang, Zhao/E-3515-2015 OI Wang, Zhao/0000-0002-3628-5699 FU Italian Society of Cardiology Award for Research Abroad; National Natural Science Foundation of China [81200076, 81300201]; China Postdoctoral Science Foundation [2013M531074]; Heilongjiang Postdoctoral Science Foundation [LBH-Z12180] FX R.V. was funded in part by the 2013 Italian Society of Cardiology Award for Research Abroad. H.J. received a grant from the National Natural Science Foundation of China (81200076). J.T. has received a grant from the National Natural Science Foundation of China (81300201), a grant from China Postdoctoral Science Foundation (2013M531074), and a grant from Heilongjiang Postdoctoral Science Foundation (LBH-Z12180). NR 29 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 EI 2047-2412 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD DEC PY 2015 VL 16 IS 12 BP 1390 EP 1398 DI 10.1093/ehjci/jev108 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY7KD UT WOS:000366586300018 PM 25925215 ER PT J AU Rocca, HPL Eurlings, L Richards, AM Januzzi, JL Pfisterer, ME Dahlstrom, U Pinto, YM Karlstrom, P Erntell, H Berger, R Persson, H O'Connor, CM Moertl, D Gaggin, HK Frampton, CM Nicholls, MG Troughton, RW AF Brunner-La Rocca, Hans-Peter Eurlings, Luc Richards, A. Mark Januzzi, James L. Pfisterer, Matthias E. Dahlstrom, Ulf Pinto, Yigal M. Karlstrom, Patric Erntell, Hans Berger, Rudolf Persson, Hans O'Connor, Christopher M. Moertl, Deddo Gaggin, Hanna K. Frampton, Christopher M. Nicholls, M. Gary Troughton, Richard W. TI Which heart failure patients profit from natriuretic peptide guided therapy? A meta-analysis from individual patient data of randomized trials SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Biomarkers; Co-morbidity; Treatment response; Heart failure with preserved ejection fraction ID PRESERVED EJECTION FRACTION; STANDARD MEDICAL THERAPY; ELDERLY-PATIENTS; TIME-CHF; PEP-CHF; MORTALITY; MANAGEMENT; ASSOCIATION; PREVALENCE; GUIDELINES AB AimsPrevious analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear. Methods and resultsTo determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) 45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P < 0.02). Age (74 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02). Conclusion The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients. C1 [Brunner-La Rocca, Hans-Peter; Eurlings, Luc] Maastricht Univ Med Ctr, Dept Cardiol, NL-6202 AZ Maastricht, Netherlands. [Richards, A. Mark; Frampton, Christopher M.; Nicholls, M. Gary; Troughton, Richard W.] Univ Otago Christchurch, Christchurch Hosp, Dept Med, Christchurch, New Zealand. [Richards, A. Mark] Natl Univ Heart Ctr Singapore, Singapore, Singapore. [Januzzi, James L.; Gaggin, Hanna K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pfisterer, Matthias E.] Univ Basel Hosp, Dept Cardiol, CH-4031 Basel, Switzerland. [Dahlstrom, Ulf] Linkoping Univ, Dept Cardiol, Linkoping, Sweden. [Dahlstrom, Ulf] Linkoping Univ, Dept Med & Hlth Sci, Dept Cardiol, Linkoping, Sweden. [Pinto, Yigal M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Karlstrom, Patric] Cty Hosp Ryhov, Div Cardiol, Dept Med, Jonkoping, Sweden. [Erntell, Hans; Persson, Hans] Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden. [Berger, Rudolf] Med Univ Vienna, Dept Cardiol, Vienna, Austria. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Moertl, Deddo] LKH, Dept Cardiol, St Polten, Austria. RP Rocca, HPL (reprint author), Maastricht Univ Med Ctr, Dept Cardiol, POB 5800, NL-6202 AZ Maastricht, Netherlands. EM hp.brunnerlarocca@mumc.nl NR 31 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD DEC PY 2015 VL 17 IS 12 BP 1252 EP 1261 DI 10.1002/ejhf.401 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY4YV UT WOS:000366415700010 ER PT J AU Felker, GM Mentz, RJ Teerlink, JR Voors, AA Pang, PS Ponikowski, P Greenberg, BH Filippatos, G Davison, BA Cotter, G Prescott, MF Hua, TA Lopez-Pintado, S Severin, T Metra, M AF Felker, G. Michael Mentz, Robert J. Teerlink, John R. Voors, Adriaan A. Pang, Peter S. Ponikowski, Piotr Greenberg, Barry H. Filippatos, Gerasimos Davison, Beth A. Cotter, Gad Prescott, Margaret F. Hua, Tsushung A. Lopez-Pintado, Sara Severin, Thomas Metra, Marco TI Serial high sensitivity cardiac troponin T measurement in acute heart failure: insights from the RELAX-AHF study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE High-sensitivity cardiac troponin T; Acute heart failure; Outcomes; mortality; Dyspnoea ID SERELAXIN; BIOMARKERS; OUTCOMES AB AimsTroponin elevation is common in acute heart failure (AHF) and may be useful for prognostication; however, available data are mixed and many previous studies used older, less sensitive assays. We examined the association between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and outcomes in RELAX-AHF. Methods and resultsHs-cTnT was measured at baseline and days 2, 5, and 14. We assessed the relationship between baseline, peak and peak change hs-cTnT with dyspnoea relief by visual analogue scale, cardiovascular death, or HF/renal hospitalization to 60days and cardiovascular mortality to 180days. Models were adjusted for clinical variables and treatment assignment. Whether baseline troponin status affected the treatment effect of serelaxin was assessed using interactions terms. In 1074 patients, the median baseline troponin was 0.033 mu g/L, and 90% of patients were above the 99th upper reference limit (URL). Patients with hs-cTnT >median were more likely to be men with ischaemic heart disease, worse renal function, and higher N-terminal pro-brain natriuretic peptide. Higher baseline or peak hs-cTnT and greater peak change were associated with worse outcomes independent of adjustment for covariates, but relationships were generally strongest for 180-day cardiovascular mortality (hazard ratio per doubling of baseline hs-cTnT=1.36, 95% confidence interval 1.15-1.60). Troponin was most strongly associated with death from heart failure or from other cardiovascular causes. The treatment effect of serelaxin did not differ by baseline troponin levels. ConclusionHs-cTnT was elevated above the 99% URL in the majority of AHF patients. Baseline, peak, and peak change hs-cTnT were associated with worse outcomes, with the strongest relationship with 180-day cardiovascular mortality. C1 [Felker, G. Michael; Mentz, Robert J.] Duke Clin Res Inst, Durham, NC 27710 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Pang, Peter S.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Greenberg, Barry H.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Filippatos, Gerasimos] Athens Univ Hosp, Athens, Greece. [Davison, Beth A.; Cotter, Gad] Momentum Res Inc, Durham, NC USA. [Prescott, Margaret F.; Hua, Tsushung A.] Novartis Pharmaceut, E Hanover, NJ USA. [Lopez-Pintado, Sara] Columbia Univ, New York, NY USA. [Severin, Thomas] Novartis Pharma AG, Basel, Switzerland. [Metra, Marco] Univ Brescia, Brescia, Italy. RP Felker, GM (reprint author), Duke Clin Res Inst, DUMC Box 3850, Durham, NC 27710 USA. EM michael.felker@duke.edu NR 13 TC 13 Z9 13 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD DEC PY 2015 VL 17 IS 12 BP 1262 EP 1270 DI 10.1002/ejhf.341 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY4YV UT WOS:000366415700011 PM 26333655 ER PT J AU Schizas, D Mylonas, KS Economopoulos, KP Tasigiorgos, S Patouras, D Karavokyros, I Liakakos, T AF Schizas, D. Mylonas, K. S. Economopoulos, K. P. Tasigiorgos, S. Patouras, D. Karavokyros, I. Liakakos, T. TI Laparoscopic surgery for gastric cancer: a systematic review SO EUROPEAN SURGERY-ACTA CHIRURGICA AUSTRIACA LA English DT Review DE Gastric cancer; Laparoscopy; Surgery; Lymph node excision ID ASSISTED DISTAL GASTRECTOMY; LYMPH-NODE DISSECTION; QUALITY-OF-LIFE; OPEN SUBTOTAL GASTRECTOMY; BILLROTH-I GASTRECTOMY; CLAVIEN-DINDO CLASSIFICATION; RANDOMIZED CLINICAL-TRIAL; 5 YEARS EXPERIENCE; RESPIRATORY-FUNCTION; SURGICAL OUTCOMES AB Background The objective of this paper is to systematically review current literature on laparoscopic surgery for gastric cancer in terms of current indications and feasibility as well as short-term and long-term postoperative outcomes. Methods A systematic review was conducted with respect to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using PubMed and is up-to-date until January 1, 2014. Results A total of 99 papers matched the inclusion criteria and comprised of 92 case-control studies and 7 randomized controlled trials (RCTs). The majority of these papers focused on short-term outcomes of laparoscopy-assisted distal gastrectomy (LADG), which are superior compared to open distal gastrectomy (ODG). Lymphadenectomy extent, morbidity, and mortality rates as well as disease-free and overall survival did not differ significantly between LADG and ODG groups. Finally, the implementation of laparoscopic gastrectomy was assessed in advanced gastric carcinoma, obese, and elderly patients. Conclusions This systematic review revealed that laparoscopic surgery is safe and effective for the treatment of gastric cancer. LADG offers better short-term and similar long-term results to ODG. Well-designed multicenter RCTs are needed to better understand the limitations of oncologic laparoscopic gastrectomy. C1 [Mylonas, K. S.] Aristotle Univ Thessaloniki, Fac Hlth Sci, Sch Med, Thessaloniki 54124, Greece. [Schizas, D.; Mylonas, K. S.; Economopoulos, K. P.; Tasigiorgos, S.; Patouras, D.] Soc Jr Doctors, Surg Working Grp, Athens, Greece. [Schizas, D.; Karavokyros, I.; Liakakos, T.] Univ Athens, Dept Surg 1, Athens, Greece. [Economopoulos, K. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Mylonas, KS (reprint author), Aristotle Univ Thessaloniki, Fac Hlth Sci, Sch Med, Kyriakidi St 1, Thessaloniki 54124, Greece. EM ksmylonas@gmail.com OI Economopoulos, Konstantinos/0000-0003-4856-0405; Mylonas, Konstantinos/0000-0002-2356-6694 NR 125 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1682-8631 EI 1682-4016 J9 EUR SURG JI Eur. Surg. PD DEC PY 2015 VL 47 IS 6 BP 286 EP 302 DI 10.1007/s10353-015-0350-8 PG 17 WC Surgery SC Surgery GA CY7ZE UT WOS:000366627300002 ER PT J AU Long, SR Wang, ZQ Jiang, P Liu, RD Qi, X Liu, P Ren, HJ Shi, HN Cui, J AF Long, Shao Rong Wang, Zhong Quan Jiang, Peng Liu, Ruo Dan Qi, Xin Liu, Pei Ren, Hui Jun Shi, Hai Ning Cui, Jing TI Characterization and functional analysis of Trichinella spiralis Nudix hydrolase SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Trichinella spiralis; Nudix hydrolases; Enzyme activity; Molecular function; Invasion ID INTESTINAL EPITHELIAL-CELLS; PROTEIN-PROTEIN INTERACTIONS; REAL-TIME PCR; PROTECTIVE IMMUNITY; IN-VITRO; HUMAN TRICHINOSIS; BALB/C MICE; LARVAE; INFECTION; CYTOTOXICITY AB Trichinella spiralis Nudix hydrolase (TsNd) was identified by screening a T7 phage display cDNA library from T spiralis intestinal infective larvae (ILL), and vaccination of mice with recombinant TsNd protein (rTsNd) or TsNd DNA vaccine produced a partial protective immunity. The aim of this study was to identify the characteristics and biological functions of TsNd in the process of invasion and development of T. spiralis larvae. Transcription and expression of TsNd gene at all developmental stages of T. spiralis were observed by qPCR and immunofluorescent test (IFT). The rTsNd had the Nd enzymatic activity to dGTP, NAD, NADP and CoA. Its kinetic properties on the preferred substrate dGTP were calculated, and the V-max, K-m, and k(cat)/K-m values at pH 8.0 were 3.19 mu M min(-1) mu g(-1), 370 mu M, and 144 s(-1) M-1, respectively, in reaction matrix containing 5 mM Zn2+ and 2 mM DTT. The rTsNd was active from 25 degrees C to 50 degrees C, with optimal activity at 37 degrees C. rTsNd was able to bind specifically to mouse intestinal epithelial cells (IECs) and promoted the larval invasion of IECs, whereas anti-rTsNd antibodies inhibited the larval invasion of IECs in a dose-dependent manner. Anti-rTsNd antibodies could kill T spiralis infective larvae by an ADCC-mediated mechanism. Our results showed that the rTsNd protein was able to interact with host IECs, had the Nudix hydrolasing activity and the enzymatic activity appeared to be essential indispensable for the T spiralis larval invasion, development and survival in host. (C) 2015 Elsevier Inc. All rights reserved. C1 [Long, Shao Rong; Wang, Zhong Quan; Jiang, Peng; Liu, Ruo Dan; Qi, Xin; Liu, Pei; Ren, Hui Jun; Cui, Jing] Zhengzhou Univ, Coll Med, Dept Parasitol, Zhengzhou 450052, Peoples R China. [Shi, Hai Ning] Massachusetts Gen Hosp, Dept Immunol, Charlestown, MA 02129 USA. [Shi, Hai Ning] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Cui, J (reprint author), Zhengzhou Univ, Coll Med, Dept Parasitol, Zhengzhou 450052, Peoples R China. EM wangzq@zzu.edu.cn; cuij@zzu.edu.cn FU National Natural Science Foundation of China [81371843, 81271860, 81471981] FX We would like to thank Prof. Hai Ling Qiao, Na Gao and Ms. Jun Zhou from the Department of Clinical Pharmacology, Medical College of Zhengzhou University, for their technical assistance in the HPLC analysis. We are also grateful to Prof. Yuan Fang Ma and Prof. Jun Zhang from the Medical College of Henan University, who provided the C2C12 cells. This work was supported by the National Natural Science Foundation of China (No. 81371843, 81271860, and 81471981). NR 42 TC 0 Z9 0 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 EI 1090-2449 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 2015 VL 159 BP 264 EP 273 DI 10.1016/j.exppara.2015.10.009 PG 10 WC Parasitology SC Parasitology GA CY5JC UT WOS:000366442900032 PM 26545353 ER PT J AU Suzuki, M Bandoski, C Bartlett, JD AF Suzuki, Maiko Bandoski, Cheryl Bartlett, John D. TI Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Fluorosis; Ameloblast; ROS; Oxidative damage; JNK Sirtuin; Autophagy ID ENDOPLASMIC-RETICULUM STRESS; N-ACETYLCYSTEINE PROTECTS; DNA-DAMAGE; DENTAL FLUOROSIS; UNCOUPLING PROTEIN-2; EPITHELIAL-CELLS; ENAMEL FORMATION; SODIUM-FLUORIDE; BIOGENIC-AMINES; MUCOSAL CELLS AB Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (gamma H2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators gamma H2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and gamma H2AX were increased compared to those in controls (0 ppm fluoride). These results suggest that fluoride-induced ROS generation causes mitochondrial damage and DNA damage, which may lead to impairment of ameloblast function. To counteract this impairment, SIRT1/autophagy is induced via JNK signaling to protect cells/ameloblasts from fluoride induced oxidative damage that may cause dental fluorosis. (C) 2015 Elsevier Inc. All rights reserved. C1 [Bartlett, John D.] Forsyth Inst, Dept Mineralized Tissue Biol, Cambridge, MA 02142 USA. Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Mineralized Tissue Biol, 245 First St, Cambridge, MA 02142 USA. EM jbartlett@forsyth.org FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [R01DE018106] FX We thank Justine Dobeck for histology expertise and Dr. Malcolm L. Snead for generously providing us with LS8 cells. Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award R01DE018106. NR 68 TC 8 Z9 9 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2015 VL 89 BP 369 EP 378 DI 10.1016/j.freeradbiomed.2015.08.015 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CY4CI UT WOS:000366355800034 PM 26431905 ER PT J AU Xia, N Zhang, Q Wang, ST Gu, L Yang, HM Liu, L Bakshi, R Yang, H Zhang, H AF Xia, Ning Zhang, Qian Wang, Shu Ting Gu, Li Yang, Hui Min Liu, Li Bakshi, Rachit Yang, Hui Zhang, Hong TI Blockade of metabotropic glutamate receptor 5 protects against DNA damage in a rotenone-induced Parkinson's disease model SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Metabotropic glutamate receptor 5; DNA damage; 8-0HdG [Ca2+](i); ER; Trx2; ERK; PD ID SUBSTANTIA-NIGRA; OXIDATIVE DAMAGE; ENDOPLASMIC-RETICULUM; COMET ASSAY; MOUSE MODEL; NEURONS; GLUTATHIONE; EXPRESSION; REPAIR; BRAIN AB Glutamate excitotoxicity contributes to the development of Parkinson's disease (PD) and pharmacological blockade of metabotropic glutamate receptor 5 (mGluR5) has beneficial anti-akinetic effects in animal models of PD; however, the mechanism by which these antagonists alleviate PD symptoms is largely unknown. In our study, the effects of mGluR5 inhibition on DNA damage were investigated in a rotenone-induced model of PD. We first found that the selective mGluR5 antagonist, 2-methyl-6(phenylethynyl) pyridine, prevented rotenone-induced DNA damage in MN9D dopaminergic neurons through a mechanism involving the downregulation of intracellular calcium release which was associated with a reduction in endoplasmic reticulum stress and reactive oxygen species (ROS)-related mitochondrial dysfunction. Interestingly, the ROS-related mitochondrial dysfunction was accompanied by an increase in expression of the antioxidant protein, Trx2. Treatment of cells with the calcium chelating agent 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or the ROS scavenger N-acetyl-L-cysteine, also reduced rotenone-induced DNA damage, while transfection of a dominant-negative form of Trx2 increased it. In addition, mGluR5 inhibition altered the expression profiles of proteins involved in DNA repair activity. Specifically, the expression of phosphorylated ERK (p-ERK) and CREB, as well as APE1 and Rad51 were elevated after rotenone stimulation and were subsequently downregulated following blockade of mGluR5. These findings were confirmed in vivo in a rotenone-induced rat model of PD. Inhibition of mGluR5 protected against neurotoxicity by mitigating oxidative stress-related DNA damage associated with 8-hydroxy-2'-deoxyguanosine production and also reduced p-ERK activity and Trx2 expression. These findings provide a novel link between mGluR5 and DNA damage in a model of PD, and reveal a potential mechanism by which mGluR5 mediates DNA damage in neurodegenerative diseases. (C) 2015 Elsevier Inc. All rights reserved. C1 [Xia, Ning; Zhang, Qian; Wang, Shu Ting; Gu, Li; Yang, Hui Min; Liu, Li; Yang, Hui; Zhang, Hong] Capital Med Univ, Dept Neurobiol, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China. [Xia, Ning; Zhang, Qian; Wang, Shu Ting; Gu, Li; Yang, Hui Min; Liu, Li; Yang, Hui; Zhang, Hong] Capital Med Univ, Key Lab Neurodegenerat Dis, Minist Educ, Beijing 100069, Peoples R China. [Bakshi, Rachit] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. RP Zhang, H (reprint author), Capital Med Univ, Dept Neurobiol, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China. EM hzhang@ccmu.edu.cn FU National Natural Science Foundation of the People's Republic of China [81171886, 81372587]; Beijing Municipal Natural Science Foundation [7132018]; Beijing City Board of Education Development Project [KZ201310025021]; Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipality [IDHT20140514] FX This work was supported by the National Natural Science Foundation of the People's Republic of China (81171886; 81372587), Beijing Municipal Natural Science Foundation (No. 7132018), Beijing City Board of Education Development Project (KZ201310025021), and the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipality (No. IDHT20140514). NR 51 TC 2 Z9 2 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2015 VL 89 BP 567 EP 580 DI 10.1016/j.freeradbiomed.2015.09.017 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CY4CI UT WOS:000366355800052 PM 26454081 ER PT J AU Bigelow, CA Horowitz, NS Goodman, A Growdon, WB del Carmen, M Kaimal, A AF Bigelow, Catherine A. Horowitz, Neil S. Goodman, Annekathryn Growdon, Whitfield B. del Carmen, Marcela Kaimal, Anjali TI Cervical Cancer Diagnosed in Pregnancy: Management and Outcomes SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Bigelow, Catherine A.; Horowitz, Neil S.; Goodman, Annekathryn; Growdon, Whitfield B.; del Carmen, Marcela; Kaimal, Anjali] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 585 EP 585 DI 10.1016/j.ygyno.2015.09.025 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900039 ER PT J AU Pepin, KJ Rauh-Hain, JA Meyer, LA Clemmer, J Lu, KH Rice, LW Uppal, S Schorge, JO del Carmen, MG AF Pepin, Kristen J. Rauh-Hain, J. Alejandro Meyer, Larissa A. Clemmer, Joel Lu, Karen H. Rice, Laurel W. Uppal, Shitanshu Schorge, John O. del Carmen, Marcela G. TI Management and Outcomes for Elderly Women with High-Grade Endometrial Cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Pepin, Kristen J.; Rauh-Hain, J. Alejandro; Meyer, Larissa A.; Clemmer, Joel; Lu, Karen H.; Rice, Laurel W.; Uppal, Shitanshu; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 587 EP 587 DI 10.1016/j.ygyno.2015.09.031 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900044 ER PT J AU Buskwofie, A Rauh-Hain, JA Esselen, K Clark, RM Muto, M Feltmate, C Berkowitz, R Growdon, WB Goodman, AK Borutall, DM Schorge, JO Horowitz, N del Carmen, MG AF Buskwofie, Ama Rauh-Hain, J. Alejandro Esselen, Katharine Clark, Rachel M. Muto, Michael Feltmate, Colleen Berkowitz, Ross Growdon, Whitfield B. Goodman, A. K. Borutall, David M. Schorge, John O. Horowitz, Neil del Carmen, Marcela G. TI Intraperitoneal Therapy for Ovarian Cancer: Toxicity Profile Associated with GOG-172 vs Modified GOG-172 in the Brigham and Women's Hospital and Massachusetts General Hospital Population SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Brigham & Womens Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 588 EP 588 DI 10.1016/j.ygyno.2015.09.034 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900047 ER PT J AU Manuel, MM Cho, LP Damato, AL Tempany, C Viswanathan, AN AF Manuel, M. M. Cho, L. P. Damato, A. L. Tempany, C. Viswanathan, A. N. TI Clinical Outcomes of High-Dose-Rate (HDR) Gynecologic Brachytherapy Using Real-Time 3-Tesla Magnetic Resonance (MR) Guidance SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Harvard Univ, Brigham & Womens Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 588 EP 589 DI 10.1016/j.ygyno.2015.09.035 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900048 ER PT J AU Joseph, NT Pepin, KJ Rauh-Hain, JA Schorge, JO AF Joseph, Naima T. Pepin, Kristen J. Rauh-Hain, J. Alejandro Schorge, John O. TI Mass General Ovarian Cancer Outcomes: A Comparispn with the MRC CHORUS Trial SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Joseph, Naima T.; Pepin, Kristen J.; Rauh-Hain, J. Alejandro; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 589 EP 590 DI 10.1016/j.ygyno.2015.09.038 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900051 ER PT J AU Starbuck, K Eavarone, D Prendergast, J da Silva, APG DeSander, J Behrens, J Rueda, B Foster, R AF Starbuck, K. Eavarone, D. Prendergast, J. da Silva, A. P. G. DeSander, J. Behrens, J. Rueda, B. Foster, R. TI Eradicating ovarian cancer stem cells by targeting the tumor-associated carbohydrate antigen sialyl Tn SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Starbuck, K.; Eavarone, D.; Prendergast, J.; da Silva, A. P. G.; DeSander, J.; Behrens, J.; Rueda, B.; Foster, R.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 590 EP 590 DI 10.1016/j.ygyno.2015.09.040 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900053 ER PT J AU Dorney, KM Growdon, WB Clemmer, J Rauh-Hain, JA Hall, TL Diver, E Boruta, D del Carmen, MG Goodman, AK Schorge, JO Horowitz, N Clark, RM AF Dorney, K. M. Growdon, W. B. Clemmer, J. Rauh-Hain, J. A. Hall, T. L. Diver, E. Boruta, D. del Carmen, M. G. Goodman, A. K. Schorge, J. O. Horowitz, N. Clark, R. M. TI Patient, Treatment and Discharge Factors associated with Hospital Readmission within 30 days after Surgery for Vulvar Cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Brigham & Womens Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 593 EP 594 DI 10.1016/j.ygyno.2015.09.050 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900063 ER PT J AU Melamed, A Rauh-Hain, JA Clemmer, JT del Carmen, MG Borutaii, DM Schorge, JO AF Melamed, Alexander Rauh-Hain, Jose A. Clemmer, Joel T. del Carmen, Marcela G. Borutaii, David M. Schorge, John O. TI Laparoscopic Staging for Stage I Ovarian Cancer: An Analysis of the National Cancer Database SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Melamed, Alexander; Rauh-Hain, Jose A.; Clemmer, Joel T.; del Carmen, Marcela G.; Borutaii, David M.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 593 EP 593 DI 10.1016/j.ygyno.2015.09.048 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900061 ER PT J AU Diver, EJ Hernandez, SF Scaltriti, M Rueda, BR Growdon, WB AF Diver, E. J. Hernandez, S. F. Scaltriti, M. Rueda, B. R. Growdon, W. B. TI Targeting HER2 and PI3K in Uterine Serous Cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Diver, E. J.; Hernandez, S. F.; Scaltriti, M.; Rueda, B. R.; Growdon, W. B.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 596 EP 596 DI 10.1016/j.ygyno.2015.09.059 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900070 ER PT J AU Diver, EJ Rauh-Hain, JA Meyer, LA Clemmer, J Lu, KH del Carmen, MG Schorge, JO AF Diver, E. J. Rauh-Hain, J. A. Meyer, L. A. Clemmer, J. Lu, K. H. del Carmen, M. G. Schorge, J. O. TI Patterns of Care, Predictors and Outcomes of Chemotherapy for Uterine Serous Carcinoma: A population-based analysis SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Diver, E. J.; Rauh-Hain, J. A.; Meyer, L. A.; Clemmer, J.; Lu, K. H.; del Carmen, M. G.; Schorge, J. O.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 597 EP 598 DI 10.1016/j.ygyno.2015.09.064 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900075 ER PT J AU Growdon, W Hernandez, SF Chisholm, S Borger, D Foster, R Rueda, BR AF Growdon, Whitfield Hernandez, Silvia F. Chisholm, Sarah Borger, Darrell Foster, Rosemary Rueda, Bo R. TI Ridaforolimus improves the anti-tumor activity of dual HER2 blockade in uterine serous carcinoma in vivo models with HER2 gene amplification and a gain of function mutation in PIK3CA SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 597 EP 597 DI 10.1016/j.ygyno.2015.09.062 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900073 ER PT J AU Hall, TR Clark, R del Carmen, MG Russo, A Oliva, E Rauh-Hain, JA Schorge, JO Boruta, DM AF Hall, T. R. Clark, R. del Carmen, M. G. Russo, A. Oliva, E. Rauh-Hain, J. A. Schorge, J. O. Boruta, D. M. TI Staging Lymphadenectomy in Low Grade Endometrial Cancer: A Prospective Cohort Study Utilizing a Standard Algorithm SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Hall, T. R.; Clark, R.; del Carmen, M. G.; Russo, A.; Oliva, E.; Rauh-Hain, J. A.; Schorge, J. O.; Boruta, D. M.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 598 EP 599 DI 10.1016/j.ygyno.2015.09.067 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900078 ER PT J AU Starbuck, KD Rauh-Hain, JA Clemmer, J Schorge, JO del Carmen, MG AF Starbuck, Kristen D. Rauh-Hain, J. Alejandro Clemmer, Joel Schorge, John O. del Carmen, Marcela G. TI Patterns of Care, Predictors and Outcomes of Chemotherapy for Uterine Carcinosarcoma: A population-based analysis SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Starbuck, Kristen D.; Rauh-Hain, J. Alejandro; Clemmer, Joel; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2015 VL 139 IS 3 BP 598 EP 598 DI 10.1016/j.ygyno.2015.09.065 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CY7WB UT WOS:000366618900076 ER PT J AU Swenson, ER AF Swenson, Erik R. TI On Receiving the Baton SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Editorial Material C1 [Swenson, Erik R.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. [Swenson, Erik R.] Univ Washington, Seattle, WA 98195 USA. RP Swenson, ER (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 EI 1557-8682 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD DEC 1 PY 2015 VL 16 IS 4 BP 270 EP 270 DI 10.1089/ham.2015.29006.ers PG 1 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA CY8XX UT WOS:000366693100002 PM 26544799 ER PT J AU Roy, A Ni, J Skibo, J Rankin, S Dobyns, WB Kalume, F Baker, SJ Zhao, J Millen, KJ AF Roy, Achira Ni, Jing Skibo, Jonathan Rankin, Sherri Dobyns, William B. Kalume, Franck Baker, Suzanne J. Zhao, Jean Millen, Kathleen J. TI Modeling human PIK3CA-related congenital brain overgrowth and epilepsy in mice SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT Joint Meeting of the 20th Biennial Meeting of the International-Society-for-Developmental-Neuroscience / 5th Annual NeuroDevNet Brain Development Conference CY JUL 19-24, 2014 CL Montreal, CANADA SP Int Soc Dev Neuroscience C1 [Roy, Achira; Skibo, Jonathan; Dobyns, William B.; Kalume, Franck; Millen, Kathleen J.] Seattle Childrens Res Inst, Seattle, WA USA. [Ni, Jing; Zhao, Jean] Dana Farber Canc Inst, Boston, MA USA. [Rankin, Sherri; Baker, Suzanne J.] St Jude Childrens Res Hosp, Boston, MA USA. FU NINDS NIH HHS [R01 NS072441] NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 EI 1873-474X J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2015 VL 47 SI SI BP 46 EP 46 DI 10.1016/j.ijdevneu.2015.04.131 PN A PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA CY6QT UT WOS:000366534600121 PM 26531452 ER PT J AU Pasinetti, GM AF Pasinetti, Giulio Maria TI Insulin resistance and obesity in childhood and long term consequences during aging SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT Joint Meeting of the 20th Biennial Meeting of the International-Society-for-Developmental-Neuroscience / 5th Annual NeuroDevNet Brain Development Conference CY JUL 19-24, 2014 CL Montreal, CANADA SP Int Soc Dev Neuroscience C1 [Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Educ & Clin Ctr, Geriatr Res, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 EI 1873-474X J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2015 VL 47 SI SI BP 88 EP 88 DI 10.1016/j.ijdevneu.2015.04.241 PN A PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA CY6QT UT WOS:000366534600231 PM 26531563 ER PT J AU Aaronson, EL Marsh, RH Guha, M Schuur, JD Rouhani, SA AF Aaronson, Emily L. Marsh, Regan H. Guha, Moytrayee Schuur, Jeremiah D. Rouhani, Shada A. TI Emergency department quality and safety indicators in resource-limited settings: an environmental survey SO INTERNATIONAL JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ESSENTIAL-TRAUMA-CARE; HEALTH-ORGANIZATIONS GUIDELINES; DEVELOPING-COUNTRIES; MEDICINE; DELPHI; WORLD; TIME; CAPABILITIES; PERFORMANCE; CHILDREN AB Background: As global emergency care grows, practical and effective performance measures are needed to ensure high quality care. Our objective was to systematically catalog and classify metrics that have been used to measure the quality of emergency care in resource-limited settings. Methods: We searched MEDLINE, Embase, CINAHL, and the gray literature using standardized terms. The references of included articles were also reviewed. Two researchers screened titles and abstracts for relevance; full text was then reviewed by three researchers. A structured data extraction tool was used to identify and classify metrics into one of six Institute of Medicine (IOM) quality domains (safe, timely, efficient, effective, equitable, patient-centered) and one of three of Donabedian's structure/process/outcome categories. A fourth expert reviewer blinded to the initial classifications re-classified all indicators, with a weighted kappa of 0.89. Results: A total of 1705 articles were screened, 95 received full text review, and 34 met inclusion criteria. One hundred eighty unique metrics were identified, predominantly process (57 %) and structure measures (27 %); 16 % of metrics were related to outcomes. Most metrics evaluated the effectiveness (52 %) and timeliness (28 %) of care, with few addressing the patient centeredness (11 %), safety (4 %), resource-efficiency (3 %), or equitability (1 %) of care. Conclusions: The published quality metrics in emergency care in resource-limited settings primarily focus on the effectiveness and timeliness of care. As global emergency care is built and strengthened, outcome-based measures and those focused on the safety, efficiency, and equitability of care need to be developed and studied to improve quality of care and resource utilization. C1 [Aaronson, Emily L.; Marsh, Regan H.; Schuur, Jeremiah D.; Rouhani, Shada A.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Aaronson, Emily L.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Aaronson, Emily L.; Marsh, Regan H.; Schuur, Jeremiah D.; Rouhani, Shada A.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Guha, Moytrayee] Brigham & Womens Hosp, Ctr Clin Excellence, Boston, MA 02115 USA. [Aaronson, Emily L.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Aaronson, EL (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM eaaronson@partners.org NR 55 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 1865-1372 EI 1865-1380 J9 INT J EMERG MED JI Int. J. Emergency Medicine PD DEC PY 2015 VL 8 IS 1 AR 39 DI 10.1186/s12245-015-0088-x PG 7 WC Emergency Medicine SC Emergency Medicine GA CY8DA UT WOS:000366637600039 PM 26520848 ER PT J AU Arbelaez, C Patino, A AF Arbelaez, Christian Patino, Andres TI State of emergency medicine in Colombia SO INTERNATIONAL JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Colombia; EM; International EM development; Residency education AB Colombia is an upper-middle-income country with a population of 45 million people and one of the best national healthcare and medical education systems in South America. However, its widely diverse and difficult terrains hinder healthcare delivery to rural areas, creating disparities in healthcare access and outcomes between the urban and rural settings. Currently, emergency medical care is overwhelmingly provided by general practitioners without residency training, who obtain specialty consultations based on the medical/surgical condition identified. A few emergency medicine (EM) residency programs have sprouted over the last two decades in renowned academic institutions in the largest cities, producing high-quality EM specialists. With the establishment of EM as a specialty in 2005 and increasing recognition of the specialty, there has been an increasing demand for EM specialists in cities, which is only slowly being met by the current residencies. The critical challenges for EM in Colombia are both, establishing itself as a well-recognized specialty - by increasing academic production and reaching a critical mass of and unity among EM specialists - and providing the highest quality and safest emergency care to the people of Colombia - by improving capacity both in emergency departments and in the regional and national emergency response systems. Historically, the establishment of EM as a strongly organized specialty in other countries has spanned decades (e.g., the United States), and Colombia has been making significant progress in a similar trajectory. C1 [Arbelaez, Christian] Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Progra, Boston, MA 02115 USA. [Patino, Andres] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Progra, Boston, MA 02115 USA. RP Arbelaez, C (reprint author), Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Progra, 75 Francis St, Boston, MA 02115 USA. EM carbelaez@partners.org OI Patino, Andres/0000-0002-4599-4016 NR 5 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 1865-1372 EI 1865-1380 J9 INT J EMERG MED JI Int. J. Emergency Medicine PD DEC PY 2015 VL 8 IS 1 AR 9 DI 10.1186/s12245-015-0057-4 PG 6 WC Emergency Medicine SC Emergency Medicine GA CY8DA UT WOS:000366637600009 PM 25897343 ER PT J AU Bustos, Y Castro, J Wen, LS Sullivan, AF Chen, DK Camargo, CA AF Bustos, Yury Castro, Jenny Wen, Leana S. Sullivan, Ashley F. Chen, Dinah K. Camargo, Carlos A., Jr. TI Emergency department characteristics and capabilities in Bogota, Colombia SO INTERNATIONAL JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE International emergency medicine; Bogota; Colombia; Emergency department classification; Health policy; Emergency department crowding AB Background: Emergency departments (EDs) are a critical, yet heterogeneous, part of international emergency care. The National ED Inventories (NEDI) survey has been used in multiple countries as a standardized method to benchmark ED characteristics. We sought to describe the characteristics, resources, capabilities, and capacity of EDs in the densely populated capital city of Bogota, Colombia. Methods: Bogota EDs accessible to the general public 24/7 were surveyed using the 23-item NEDI survey used in several other countries (www.emnet-nedi.org). ED staff were asked about ED characteristics with reference to calendar year 2011. Results: Seventy EDs participated (82 % response). Most EDs (87 %) were located in hospitals, and 83 % were independent hospital departments. The median annual ED visit volume was approximately 50,000 visits. Approximately 90 % (95 % confidence interval (CI) 80-96 %) had a contiguous layout, with medical and surgical care provided in one area. Almost all EDs saw both adults and children (91 %), while 6 % saw only adults and 3 % saw only children. Availability of technological and consultant resources in EDs was variable. Nearly every ED had cardiac monitoring (99 %, 95 % CI 92-100 %), but less than half had a dedicated CT scanner (39 %, 95 % CI 28-52 %). While most EDs were able to treat trauma 24/7 (81 %, 95 % CI 69-89 %), few could manage oncological (22 %, 95 % CI 13-34 %) or dental (3 %, 95 % CI 0-11 %) emergencies 24/7. The typical ED length-of-stay was between 1 and 6 h in 59 % of EDs (95 % CI, 46-70 %), while most others reported that patients remained for >6 h (39 %). Almost half of respondents (46 %, 95 % CI 34-59 %) reported their ED was over capacity. Conclusions: Bogota EDs have high annual visit volumes and long length-of-stay, and half are over capacity. To meet the emergency care needs of people in Bogota and other large cities, Colombia should consider improving urban ED capacity and training more emergency medicine specialists capable of efficiently staffing its large and crowded EDs. C1 [Bustos, Yury] Univ Rosario, Dept Emergency Med, Bogota, Colombia. [Castro, Jenny] Univ Rosario, Dept Emergency Med, Hosp Univ Mayor Mederi, Bogota, Colombia. [Wen, Leana S.] Georgetown Washington Univ, Dept Emergency Med, Sch Med, Washington, DC USA. [Sullivan, Ashley F.; Chen, Dinah K.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Bustos, Y (reprint author), Univ Rosario, Dept Emergency Med, Carrera 24 63C-69, Bogota, Colombia. EM yury.bustos@urosario.edu.co NR 19 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 1865-1372 EI 1865-1380 J9 INT J EMERG MED JI Int. J. Emergency Medicine PD DEC PY 2015 VL 8 IS 1 AR 30 DI 10.1186/s12245-015-0079-y PG 8 WC Emergency Medicine SC Emergency Medicine GA CY8DA UT WOS:000366637600030 ER PT J AU Mbanjumucyo, G Devos, E Pulfrey, S Epino, HM AF Mbanjumucyo, Gabin Devos, Elizabeth Pulfrey, Simon Epino, Henry M. TI State of emergency medicine in Rwanda 2015: an innovative trainee and trainer model SO INTERNATIONAL JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Rwanda; Emergency medicine; Postgraduate training; Global health; International emergency medicine; Trainer; Trainee; Emergency department AB The 1994 Rwandan war and genocide left more than 1 million people dead; millions displaced; and the country's economic, social, and health infrastructure destroyed. Despite remaining one of the poorest countries in the world, Rwanda has made remarkable gains in health, social, and economic development over the last 20 years, but modern emergency care has been slow to progress. Rwanda has recently established the Human Resources for Health program to rapidly build capacity in multiple sectors of its healthcare delivery system, including emergency medicine. This project involves multiple medical and surgical residencies, nursing programs, allied health professional trainings, and hospital administrative support. A real strength of the program is that trainers work with international faculty at Rwanda's referral hospital, but also as emergency medicine specialty trainers when returning to their respective district hospitals. Rwanda's first emergency medicine trainees are playing a unique and important role in the implementation of emergency care systems and education in the country's district hospitals. While there has been early vital progress in building emergency medicine's foundations in Rwanda, there remains much work to be done. This will be accomplished with careful planning and strong commitment from the country's healthcare and emergency medicine leaders. C1 [Mbanjumucyo, Gabin] Masaka Dist Hosp, Dept Emergency Med, Kigali, Rwanda. [Mbanjumucyo, Gabin; Devos, Elizabeth; Pulfrey, Simon] Univ Teaching Hosp Kigali, Kigali, Rwanda. [Devos, Elizabeth] Univ Florida, Coll Med Jacksonville, Dept Emergency Med, Jacksonville, FL USA. [Pulfrey, Simon] Univ British Columbia, St Pauls Hosp, Dept Emergency Med, Vancouver, BC V5Z 1M9, Canada. [Epino, Henry M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Mbanjumucyo, G (reprint author), Masaka Dist Hosp, Dept Emergency Med, POB 3472, Kigali, Rwanda. EM mgabin5@gmail.com NR 5 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 1865-1372 EI 1865-1380 J9 INT J EMERG MED JI Int. J. Emergency Medicine PD DEC PY 2015 VL 8 IS 1 AR 20 DI 10.1186/s12245-015-0067-2 PG 3 WC Emergency Medicine SC Emergency Medicine GA CY8DA UT WOS:000366637600020 PM 26101554 ER PT J AU Grover, S Chadha, M Rengan, R Williams, TR Morris, ZS Morgan, DAL Tripuraneni, P Hu, K Viswanathan, AN AF Grover, Surbhi Chadha, Manjeet Rengan, Ramesh Williams, Tim R. Morris, Zachary S. Morgan, David A. L. Tripuraneni, Prabhakar Hu, Kenneth Viswanathan, Akila N. TI Education and Training Needs in Radiation Oncology in India: Opportunities for Indo-US Collaborations SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID CANCER; BURDEN AB Purpose: To conduct a survey of radiation oncologists in India, to better understand specific educational needs of radiation oncology in India and define areas of collaboration with US institutions. Methods and Materials: A 20-question survey was distributed to members of the Association of Indian Radiation Oncologists and the Indian Brachytherapy Society between November 2013 and May 2014. Results: We received a total of 132 responses. Over 50% of the physicians treat more than 200 patients per day, use 2-dimensional or 3-dimensional treatment planning techniques, and approximately 50% use image guided techniques. For education needs, most respondents agreed that further education in intensity modulated radiation therapy, image guided radiation therapy, stereotactic radiation therapy, biostatistics, and research methods for medical residents would be useful areas of collaboration with institutions in the United States. Other areas of collaboration include developing a structured training module for nursing, physics training, and developing a second-opinion clinic for difficult cases with faculty in the United States. Conclusion: Various areas of potential collaboration in radiation oncology education were identified through this survey. These include the following: establishing education programs focused on current technology, facilitating exchange programs for trainees in India to the United States, promoting training in research methods, establishing training modules for physicists and oncology nurses, and creating an Indo-US. Tumor Board. It would require collaboration between the Association of Indian Radiation Oncologists and the American Society for Radiation Oncology to develop these educational initiatives. (C) 2015 Elsevier Inc. All rights reserved. C1 [Grover, Surbhi] Univ Penn, Dept Radiat Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chadha, Manjeet] Icahn Sch Med Mt Sinai, Mt Sinai Beth Israel Hlth Syst, New York, NY 10029 USA. [Rengan, Ramesh] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. [Williams, Tim R.] Boca Raton Reg Hosp, Lynn Canc Inst, Dept Radiat Oncol, Boca Raton, FL USA. [Morris, Zachary S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Human Oncol, Seattle, WA USA. [Morgan, David A. L.] Sherwood Forest Hosp NHS Trust, Breast Serv, Sutton In Ashfield, Notts, England. [Tripuraneni, Prabhakar] Scripps Green Hosp, Dept Radiat Oncol, La Jolla, CA USA. [Hu, Kenneth] NYU, Lagone Med Ctr, Dept Radiat Oncol, New York, NY USA. [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Grover, S (reprint author), Univ Penn, Dept Radiat Oncol, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM Surbhi.grover@uphs.upenn.edu OI Morris, Zachary/0000-0001-5558-3547 FU National Institutes of Health [R21 167800] FX A.V. receives support from National Institutes of Health grant R21 167800. NR 10 TC 1 Z9 1 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2015 VL 93 IS 5 BP 957 EP 960 DI 10.1016/j.ijrobp.2015.08.009 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CY7FC UT WOS:000366572800004 PM 26581132 ER PT J AU Mak, KS Chen, YH Catalano, PJ Punglia, RS Wong, JS Truong, L Bellon, JR AF Mak, Kimberley S. Chen, Yu-Hui Catalano, Paul J. Punglia, Rinaa S. Wong, Julia S. Linh Truong Bellon, Jennifer R. TI Dosimetric Inhomogeneity Predicts for Long-Term Breast Pain After Breast-Conserving Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID QUALITY-OF-LIFE; INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; CANCER RADIOTHERAPY; SYSTEMIC TREATMENT; RISK-FACTORS; SURGERY; WOMEN; SYMPTOMS AB Purpose: The objective of this cross-sectional study was to characterize long-term breast pain in patients undergoing breast-conserving surgery and radiation (BCT) and to identify predictors of this pain. Methods and Materials: We identified 355 eligible patients with Tis-T2N0M0 breast cancer who underwent BCT in 2007 to 2011, without recurrent disease. A questionnaire derived from the Late Effects Normal Tissue Task Force (LENT) Subjective, Objective, Management, Analytic (SOMA) scale was mailed with 7 items detailing the severity, frequency, duration, and impact of ipsilateral breast pain over the previous 2 weeks. A logistic regression model identified predictors of long-term breast pain based on questionnaire responses and patient, disease, and treatment characteristics. Results: The questionnaire response rate was 80% (n=285). One hundred thirty-five patients (47%) reported pain in the treated breast, with 19 (14%) having pain constantly or at least daily; 15 (11%) had intense pain. The pain interfered with daily activities in 11 patients (8%). Six patients (4%) took analgesics for breast pain. Fourteen (10%) thought that the pain affected their quality of life. On univariable analysis, volume of breast tissue treated to >= 105% of the prescribed dose (odds ratio [OR] 1.001 per cc, 95% confidence interval [CI] 1.000-1.002; P=.045), volume treated to >= 110% (OR 1.009 per cc, 95% CI 1.002-1.016; P=.012), hormone therapy use (OR 1.95, 95% CI 1.12-3.39; P=.02), and other sites of pain (OR 1.79, 95% CI 1.05-3.07; P=.03) predicted for long-term breast pain. On multivariable analysis, volume >= 110% (OR 1.01 per cc, 95% CI 1.003-1.017; P=.007), shorter time since treatment (OR 0.98 per month, 95% CI 0.96- 0.998; P=.03), and hormone therapy (OR 1.84, 95% CI 1.05-3.25; P=.03) were independent predictors of pain. Conclusion: Long-term breast pain was common after BCT. Although nearly half of patients had pain, most considered it tolerable. Dosimetric inhomogeneity independently predicted for pain and should be minimized to the greatest extent possible. (C) 2015 Elsevier Inc. C1 [Mak, Kimberley S.] Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Chen, Yu-Hui; Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Punglia, Rinaa S.; Wong, Julia S.; Linh Truong; Bellon, Jennifer R.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. RP Bellon, JR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM jbellon@LROC.harvard.edu NR 33 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2015 VL 93 IS 5 BP 1087 EP 1095 DI 10.1016/j.ijrobp.2014.05.021 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CY7FC UT WOS:000366572800022 PM 25084611 ER PT J AU Kerlikowske, K AF Kerlikowske, Karla TI Progress Toward Consensus on Breast Cancer Screening Guidelines and Reducing Screening Harms SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID WOMEN AB IMPORTANCE Breast cancer is a leading cause of premature mortality among US women. Early detection has been shown to be associated with reduced breast cancer morbidity and mortality. OBJECTIVE To update the American Cancer Society (ACS) 2003 breast cancer screening guideline for women at average risk for breast cancer. PROCESS The ACS commissioned a systematic evidence review of the breast cancer screening literature to inform the update and a supplemental analysis of mammography registry data to address questions related to the screening interval. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. EVIDENCE SYNTHESIS Screening mammography in women aged 40 to 69 years is associated with a reduction in breast cancer deaths across a range of study designs, and inferential evidence supports breast cancer screening for women 70 years and older who are in good health. Estimates of the cumulative lifetime risk of false-positive examination results are greater if screening begins at younger ages because of the greater number of mammograms, as well as the higher recall rate in younger women. The quality of the evidence for overdiagnosis is not sufficient to estimate a lifetime risk with confidence. Analysis examining the screening interval demonstrates more favorable tumor characteristics when premenopausal women are screened annually vs biennially. Evidence does not support routine clinical breast examination as a screeningmethod for women at average risk. RECOMMENDATIONS The ACS recommends that women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation). Women aged 45 to 54 years should be screened annually (qualified recommendation). Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (qualified recommendation). Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation). Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (qualified recommendation). The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation). CONCLUSIONS AND RELEVANCE These updated ACS guidelines provide evidence-based recommendations for breast cancer screening for women at average risk of breast cancer. These recommendations should be considered by physicians and women in discussions about breast cancer screening. C1 [Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM karla.kerlikowske@ucsf.edu FU National Cancer Institute [P01CA154292] FX This work was supported by grant P01CA154292 from the National Cancer Institute. NR 5 TC 3 Z9 3 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD DEC PY 2015 VL 175 IS 12 BP 1970 EP 1971 DI 10.1001/jamainternmed.2015.6466 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CY3TE UT WOS:000366332000021 PM 26502319 ER PT J AU Romo, RD Lee, SJ Miao, YH Boscardin, WJ Smith, AK AF Romo, Rafael D. Lee, Sei J. Miao, Yinghui Boscardin, W. John Smith, Alexander K. TI Subjective, Objective, and Observed Long-term Survival: A Longitudinal Cohort Study SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID OLDER-ADULTS C1 [Romo, Rafael D.; Lee, Sei J.; Boscardin, W. John; Smith, Alexander K.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Romo, Rafael D.; Lee, Sei J.; Miao, Yinghui; Smith, Alexander K.] San Francisco VA Med Ctr, Geriatr & Extended Care, San Francisco, CA 94121 USA. RP Romo, RD (reprint author), San Francisco VA Med Ctr, Geriatr & Extended Care, 4150 Clement St 181G, San Francisco, CA 94121 USA. EM rafael.romo@ucsf.edu FU NIA NIH HHS [1K23AG040772, K23 AG040772, P30 AG044281] NR 6 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD DEC PY 2015 VL 175 IS 12 BP 1986 EP + DI 10.1001/jamainternmed.2015.5542 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CY3TE UT WOS:000366332000028 PM 26502331 ER PT J AU Chatterjee, P Venkataramani, AS Martin, EG AF Chatterjee, Paula Venkataramani, Atheendar S. Martin, Erika G. TI Organ Donation and New Policies: Do We Need to Act Less Generally and More Locally? Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Chatterjee, Paula] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chatterjee, Paula; Venkataramani, Atheendar S.] Harvard Univ, Sch Med, Boston, MA USA. [Venkataramani, Atheendar S.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Martin, Erika G.] SUNY Albany, Nelson A Rockefeller Inst Govt, Albany, NY 12222 USA. [Martin, Erika G.] SUNY Albany, Dept Publ Adm & Policy, Rockefeller Coll Publ Affairs & Policy, Albany, NY 12222 USA. RP Martin, EG (reprint author), SUNY Albany, Dept Publ Adm & Policy, Rockefeller Coll Publ Affairs & Policy, 1400 Washington Ave,Milne 300E, Albany, NY 12222 USA. EM emartin@albany.edu NR 4 TC 0 Z9 0 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD DEC PY 2015 VL 175 IS 12 BP 2000 EP 2000 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CY3TE UT WOS:000366332000040 PM 26641362 ER PT J AU Ghaoui, R Cooper, ST Lek, M Jones, K Corbett, A Reddel, S Needham, M Liang, C Waddell, LB Nicholson, G O'Grady, G Kaur, S Ong, R Davis, M Sue, CM Laing, NG North, KN MacArthur, DG Clarke, NF AF Ghaoui, Roula Cooper, Sandra T. Lek, Monkol Jones, Kristi Corbett, Alastair Reddel, StephenW. Needham, Merrilee Liang, Christina Waddell, Leigh B. Nicholson, Garth O'Grady, Gina Kaur, Simranpreet Ong, Royston Davis, Mark Sue, Carolyn M. Laing, Nigel G. North, Kathryn N. MacArthur, Daniel G. Clarke, Nigel F. TI Use of Whole-Exome Sequencing for Diagnosis of Limb-Girdle Muscular Dystrophy Outcomes and Lessons Learned SO JAMA NEUROLOGY LA English DT Article ID TARGETED CAPTURE; BETHLEM MYOPATHY; II DEFICIENCY; MUTATIONS; DISEASE; PHENOTYPE; GENE; WEAKNESS; GENOME; TOOL AB IMPORTANCE To our knowledge, the efficacy of transferring next-generation sequencing from a research setting to neuromuscular clinics has never been evaluated. OBJECTIVE To translate whole-exome sequencing (WES) to clinical practice for the genetic diagnosis of a large cohort of patients with limb-girdle muscular dystrophy (LGMD) for whom protein-based analyses and targeted Sanger sequencing failed to identify the genetic cause of their disorder. DESIGN, SETTING, AND PARTICIPANTS We performed WES on 60 families with LGMDs (100 exomes). Data analysis was performed between January 6 and December 19, 2014, using the x Browse bioinformatics interface (Broad Institute). Patients with LGMD were ascertained retrospectively through the Institute for Neuroscience and Muscle Research Biospecimen Bank between 2006 and 2014. Enrolled patients had been extensively investigated via protein studies and candidate gene sequencing and remained undiagnosed. Patients presented with more than 2 years of muscle weakness and with dystrophic or myopathic changes present in muscle biopsy specimens. MAIN OUTCOMES AND MEASURES The diagnostic rate of LGMD in Australia and the relative frequencies of the different LGMD subtypes. Our central goals were to improve the genetic diagnosis of LGMD, investigate whether the WES platform provides adequate coverage of known LGMD-related genes, and identify new LGMD-related genes. RESULTS With WES, we identified likely pathogenic mutations in known myopathy genes for 27 of 60 families. Twelve families had mutations in known LGMD-related genes. However, 15 families had variants in disease-related genes not typically associated with LGMD, highlighting the clinical overlap between LGMD and other myopathies. Common causes of phenotypic overlap were due to mutations in congenital muscular dystrophy-related genes (4 families) and collagen myopathy-related genes (4 families). Less common myopathies included metabolic myopathy (2 families), congenital myasthenic syndrome (DOK7), congenital myopathy (ACTA1), tubular aggregate myopathy (STIM1), myofibrillar myopathy (FLNC), and mutation of CHD7, usually associated with the CHARGE syndrome. Inclusion of family members increased the diagnostic efficacy of WES, with a diagnostic rate of 60% for "trios" (an affected proband with both parents) vs 40% for single probands. A follow-up screening of patients whose conditions were undiagnosed on a targeted neuromuscular disease-related gene panel did not improve our diagnostic yield. CONCLUSIONS AND RELEVANCE With WES, we achieved a diagnostic success rate of 45.0% in our difficult-to-diagnose cohort of patients with LGMD. We expand the clinical phenotypes associated with known myopathy genes, and we stress the importance of accurate clinical examination and histopathological results for interpretation of WES, with many diagnoses requiring follow-up review and ancillary investigations of biopsy specimens or serum samples. C1 [Ghaoui, Roula; Cooper, Sandra T.; Jones, Kristi; Waddell, Leigh B.; O'Grady, Gina; Kaur, Simranpreet; Clarke, Nigel F.] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Kids Res Inst, Westmead, NSW 2145, Australia. [Ghaoui, Roula; Cooper, Sandra T.; Jones, Kristi; Waddell, Leigh B.; O'Grady, Gina; Kaur, Simranpreet; Clarke, Nigel F.] Univ Sydney, Sydney Med Sch, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Corbett, Alastair; Reddel, StephenW.] Concord Gen Repatriat Hosp, Dept Neurol, Sydney, NSW, Australia. [Needham, Merrilee] Univ Western Australia, Western Australian Neurosci Res Inst, Perth, WA 6009, Australia. [Liang, Christina; Sue, Carolyn M.] Royal N Shore Hosp, Dept Neurol, Sydney, NSW, Australia. [Nicholson, Garth] Univ Sydney, ANZAC Res Inst, Sydney, NSW 2006, Australia. [Nicholson, Garth] Concord Hosp, Mol Med Lab, Sydney, NSW, Australia. [Ong, Royston; Laing, Nigel G.] Univ Western Australia, Med Res Ctr, Harry Perkins Inst Med Res, Perth, WA 6009, Australia. [Davis, Mark] Pathwest Lab Med, Dept Diagnost Gen, Perth, WA, Australia. [North, Kathryn N.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. RP Ghaoui, R (reprint author), Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Kids Res Inst, Hawkesbury Rd, Westmead, NSW 2145, Australia. EM roula.ghaoui@health.nsw.gov.au RI North, Kathryn/K-6476-2012 OI North, Kathryn/0000-0003-0841-8009 FU Australian National Health and Medical Research Council [APP1074954, APP1031893, APP1022707, APP1035828, APP1048814, APP1048816, APP108433]; Muscular Dystrophy New South Wales; National Human Genome Research Institute of the National Institutes of Health [U54 HG003067] FX This work was supported by Australian National Health and Medical Research Council grant APP1074954 (Dr Ghaoui), grants APP1031893 and APP1022707 (Drs North, Laing, and Clarke), grant APP1035828 (Dr Clarke), grants APP1048814 and APP1048816 (Dr Cooper), and grant APP108433 (Dr Sue); by the Muscular Dystrophy New South Wales (Dr Ghaoui); and by the National Human Genome Research Institute of the National Institutes of Health (Medical Sequencing Program grant U54 HG003067 to Eric S. Lander, PhD, director of the Broad Institute and principal investigator of the National Human Genome Research Institute grant). NR 40 TC 23 Z9 26 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD DEC PY 2015 VL 72 IS 12 BP 1424 EP 1432 DI 10.1001/jamaneurol.2015.2274 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CY8EG UT WOS:000366641000007 PM 26436962 ER PT J AU Yaghi, S Boehme, AK Dibu, J Guerrero, CRL Ali, S Martin-Schild, S Sands, KA Noorian, AR Blum, CA Chaudhary, S Schwamm, LH Liebeskind, DS Marshall, RS Willey, JZ AF Yaghi, Shadi Boehme, Amelia K. Dibu, Jamil Guerrero, Christopher R. Leon Ali, Syed Martin-Schild, Sheryl Sands, Kara A. Noorian, Ali Reza Blum, Christina A. Chaudhary, Shuchi Schwamm, Lee H. Liebeskind, David S. Marshall, Randolph S. Willey, Joshua Z. TI Treatment and Outcome of Thrombolysis-Related Hemorrhage A Multicenter Retrospective Study SO JAMA NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; SYMPTOMATIC INTRACEREBRAL HEMORRHAGE; HEALTH-CARE PROFESSIONALS; INTRACRANIAL HEMORRHAGE; MANAGEMENT; ASSOCIATION; GUIDELINES; TRIAL; SCORE AB IMPORTANCE Treatments for symptomatic intracerebral hemorrhage (sICH) are based on expert opinion, with limited data available on efficacy. OBJECTIVE To better understand the natural history of thrombolysis-related sICH, with a focus on the efficacy of various treatments used. DESIGN, SETTING, AND PARTICIPANTS Multicenter retrospective study between January 1, 2009, and April 30, 2014, at 10 primary and comprehensive stroke centers across the United States. Participants were all patients with sICH, using the definition by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), which included a parenchymal hematoma type 2 and at least a 4-point increase in the National Institutes of Health Stroke Scale score. MAIN OUTCOMES AND MEASURES The primary outcome was in-hospital mortality, and the secondary outcome was hematoma expansion, defined as a 33% increase in the hematoma volume on follow-up imaging. RESULTS Of 3894 patients treated with intravenous recombinant tissue plasminogen activator (rtPA) within 41/2 hours after symptom onset of ischemic stroke, 128 (3.3%) had sICH. The median time from initiation of rtPA therapy to sICH diagnosis was 470 minutes (range, 30-2572 minutes), and the median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes). The in-hospital mortality rate was 52.3%(67 of 128), and 26.8%(22 of 82) had hematoma expansion. In the multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality (odds ratio, 3.6; 95% CI, 1.2-10.6). Severe hypofibrinogenemia (fibrinogen level, <150mg/dL) was associated with hematoma expansion, occurring in 36.3% (8 of 22) of patients without hematoma expansion vs in 25.0%(15 of 60) of patients with hematoma expansion (P = .01), highlighting a role for cryoprecipitate in reversing rtPA coagulopathy. CONCLUSIONS AND RELEVANCE In this study, treatment of postthrombolysis sICH did not significantly reduce the likelihood of in-hospital mortality or hematoma expansion. Shortening the time to diagnosis and treatment may be a key variable in improving outcomes of patients with sICH. C1 [Yaghi, Shadi; Boehme, Amelia K.; Marshall, Randolph S.; Willey, Joshua Z.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Dibu, Jamil] Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. [Guerrero, Christopher R. Leon] Washington Univ, Dept Neurol, St Louis, MO USA. [Ali, Syed] Univ Arkansas Med Sci, Dept Neurol, Fayetteville, AR USA. [Martin-Schild, Sheryl] Tulane Univ, Dept Neurol, New Orleans, LA 70118 USA. [Sands, Kara A.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA. [Noorian, Ali Reza; Liebeskind, David S.] Univ Calif Los Angeles, Dept Neurol, UCLA Acute Stroke Investigators, Los Angeles, CA 90024 USA. [Blum, Christina A.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Chaudhary, Shuchi] Univ Oklahoma, Dept Neurol, Norman, OK 73019 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Yaghi, S (reprint author), Brown Univ, Dept Neurol, 593 Eddy St,Ambulatory Patient Ctr Room 530, Providence, RI 02903 USA. EM syaghi@lifespan.org FU Stroke Trials Network (StrokeNet) of the National Institute of Neurological Disorders and Stroke FX Dr Yaghi reported receiving funding from the Stroke Trials Network (StrokeNet) of the National Institute of Neurological Disorders and Stroke. Dr Liebeskind reported being a consultant for Stryker and Covidien. Dr Willey reported being a consultant for HeartWare Inc. No other disclosures were reported. NR 19 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD DEC PY 2015 VL 72 IS 12 BP 1451 EP 1457 DI 10.1001/jamaneurol.2015.2371 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CY8EG UT WOS:000366641000010 PM 26501741 ER PT J AU Willette, AA Burns, CM Bendlin, BB AF Willette, Auriel A. Burns, Christine M. Bendlin, Barbara B. TI Insulin Resistance and APOE e4 SO JAMA NEUROLOGY LA English DT Letter ID ADULTS C1 [Willette, Auriel A.] Iowa State Univ, Ames, IA USA. [Burns, Christine M.] US Dept Vet Affairs, Albuquerque, NM USA. [Bendlin, Barbara B.] Univ Wisconsin, Madison, WI 53792 USA. RP Bendlin, BB (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Ctr Clin Sci, Sect J5-1M,600 Highland Ave, Madison, WI 53792 USA. EM bbb@medicine.wisc.edu FU NIA NIH HHS [P50 AG033514] NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD DEC PY 2015 VL 72 IS 12 BP 1536 EP + PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CY8EG UT WOS:000366641000028 PM 26658975 ER PT J AU Stevens, WW Lee, RJ Schleimer, RP Cohen, NA AF Stevens, Whitney W. Lee, Robert J. Schleimer, Robert P. Cohen, Noam A. TI Chronic rhinosinusitis pathogenesis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Chronic rhinosinusitis; nasal polyps; mucociliary clearance; epithelial cells; inflammation; microbiome ID HUMAN NASAL-MUCOSA; INNATE LYMPHOID-CELLS; TASTE RECEPTOR T2R38; ANTIMICROBIAL PEPTIDE LL-37; UPPER RESPIRATORY-INFECTION; HUMAN AIRWAY EPITHELIA; SURFACTANT PROTEIN-A; CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; STAPHYLOCOCCUS-AUREUS AB There are a variety of medical conditions associated with chronic sinonasal inflammation, including chronic rhinosinusitis (CRS) and cystic fibrosis. In particular, CRS can be divided into 2 major subgroups based on whether nasal polyps are present or absent. Unfortunately, clinical treatment strategies for patients with chronic sinonasal inflammation are limited, in part because the underlying mechanisms contributing to disease pathology are heterogeneous and not entirely known. It is hypothesized that alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier, and tissue remodeling all contribute to the chronic inflammatory and tissue-deforming processes characteristic of CRS. Additionally, the host innate and adaptive immune responses are also significantly activated and might be involved in pathogenesis. Recent advancements in the understanding of CRS pathogenesis are highlighted in this review, with special focus placed on the roles of epithelial cells and the host immune response in patients with cystic fibrosis, CRS without nasal polyps, or CRS with nasal polyps. C1 [Stevens, Whitney W.; Schleimer, Robert P.] Northwestern Univ, Dept Med, Div Allergy Immunol, Feinberg Sch Med, Chicago, IL 60611 USA. [Schleimer, Robert P.] Northwestern Univ, Dept Otolaryngol, Feinberg Sch Med, Chicago, IL 60611 USA. [Lee, Robert J.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA USA. [Lee, Robert J.] Univ Penn, Dept Physiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Cohen, Noam A.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. RP Schleimer, RP (reprint author), Div Allergy Immunol, 240 E Huron St,McGaw Rm M-318, Chicago, IL 60611 USA. EM rpschleimer@northwestern.edu OI Cohen, Noam/0000-0002-9462-3932; Lee, Robert/0000-0001-5826-6686 FU USPHS grants [R01DC013588, R21DC013886, R03DC013862]; National Institutes of Health [T32 AI083216, R01 AI104733]; Ernest S. Bazley Foundation; Chronic Rhinosinusitis Integrative Studies Program [U19-AI106683]; RLG Foundation FX Some of the research described in this review and effort directed towards writing the review was supported by USPHS grants R01DC013588, R21DC013886 (to N.A.C.), and R03DC013862 (to R.J.L.); National Institutes of Health grants T32 AI083216 and R01 AI104733 (to R.P.S.); the Ernest S. Bazley Foundation (to R.P.S.); the Chronic Rhinosinusitis Integrative Studies Program U19-AI106683 (to R.P.S.), and a philanthropic contribution from the RLG Foundation (to N.A.C.). NR 159 TC 13 Z9 15 U1 2 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2015 VL 136 IS 6 BP 1442 EP 1453 DI 10.1016/j.jaci.2015.10.009 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA CX9RZ UT WOS:000366044300002 PM 26654193 ER PT J AU Hamilos, DL AF Hamilos, Daniel L. TI Drivers of chronic rhinosinusitis: Inflammation versus infection SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Chronic rhinosinusitis; nasal polyposis; T(H)2 inflammation; innate; adaptive ID THYMIC STROMAL LYMPHOPOIETIN; NASAL POLYPS; EOSINOPHILIC INFLAMMATION; CHRONIC SINUSITIS; EPITHELIAL-CELLS; IMMUNE-RESPONSE; EXPRESSION; INTERLEUKIN-33; MODEL; SUPERANTIGENS AB Studies of the underlying cause or causes of chronic rhinosinusitis (CRS) over the past 20 or more years have expanded from a focus on systemic immune and allergic mechanisms to an intense search for the underlying drivers of mucosal inflammation. These drivers involve mucosal inflammatory pathways that become activated by allergens, microbial stimuli, or poorly understood exogenous or endogenous stimuli. The holy grail in the study of CRS is to identify specific drivers of mucosal inflammation and translate these into more effective treatment for CRS. Certain deficiencies in local innate immunity have been described in patients with CRS that predispose to increased sinus mucosal bacterial colonization/infection, including deficient local production of antimicrobial lactoferrin and deficient functioning of the bitter taste receptor TAS2R38. Conversely, certain innate factors, namely IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), are elaborated by sinus epithelial cells in response to microbial stimulation or airway injury and promote local T(H)2 inflammation. The precise physiologic role of these factors in innate or adaptive immunity is unclear, although IL-33 might function as an alarmin triggered by damage-associated molecular patterns. The cytokines IL-25 and TSLP, similarly promote proinflammatory tissue responses. Another feature of epithelial dysregulation in patients with CRS is overproduction of eosinophil-promoting C-C chemokines by sinus epithelium, perhaps driven in part through innate stimuli, as well as T(H)2 cytokines, such as IL-13. Strategies to reduce the microbial stimulation of maladaptive T(H)2 inflammation or to suppress the local elaboration of T(H)2-promoting epithelial factors, such as IL-33, have potential therapeutic benefit in patients with CRS, although the extent to which this is realized in patient care remains limited at present. This rostrum will summarize my views on the major microbial drivers of mucosal inflammation and dysregulation of innate T(H)2-promoting factors in patients with CRS based on recent experimental data. C1 [Hamilos, Daniel L.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Hamilos, DL (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Bullfinch 422,55 Fruit St, Boston, MA 02114 USA. EM dhamilos@partners.org FU Sanofi; Regeneron; Merck FX D. L. Hamilos has received consultancy fees from Sanofi and Regeneron; has received research support from Merck; and receives royalties from UpToDate. NR 46 TC 7 Z9 7 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2015 VL 136 IS 6 BP 1454 EP 1459 DI 10.1016/j.jaci.2015.10.011 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA CX9RZ UT WOS:000366044300003 PM 26654194 ER PT J AU Hou, LF Cooley, J Swanson, R Ong, PC Pike, RN Bogyo, M Olson, ST Remold-O'Donnell, E AF Hou, Lifei Cooley, Jessica Swanson, Richard Poh Chee Ong Pike, Robert N. Bogyo, Matthew Olson, Steven T. Remold-O'Donnell, Eileen TI The protease cathepsin L regulates Th17 cell differentiation SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Th17 cells; Cathepsins; SerpinB1; Asparagine endopeptidase; Autoimmune disorders ID T-CELLS; ASPARAGINYL ENDOPEPTIDASE; IN-VIVO; INHIBITORS; T(H)17; SERPINB1; LINEAGE; PROTEINASES; HOMEOSTASIS; MECHANISM AB Previously we reported that IL-17(+) T cells, primarily IL-17(+) gamma delta cells, are increased in mice lacking the protease inhibitor serpinB1 (serpinb1(-/-) mice). Here we show that serpinB1-deficient CD4 cells exhibit a cell-autonomous and selective deficiency in suppressing T helper 17 (Th17) cell differentiation. This suggested an opposing role for one or more protease in promoting Th17 differentiation. We found that several SerpinB1-inhibitable cysteine cathepsins are induced in Th17 cells, most prominently cathepsin L (catL); this was verified by peptidase assays, active site labeling and Western blots. Moreover, Th17 differentiation was suppressed by both broad cathepsin inhibitors and catL selective inhibitors. CatL is present in Th17 cells as single chain (SC)- and two-chain (TC)-forms. Inhibiting asparagine endopeptidase (AEP) blocked conversion of SC-catL to TC-catL and increased generation of serpinb1(-/-) Th17 cells, but not wild-type Th17 cells. These findings suggest that SC-catL is biologically active in promoting Th17 generation and is counter-regulated by serpinB1 and secondarily by AEP. Thus, in addition to regulation by cytokines and transcription factors, differentiation of CD4 cells to Th17 cells is actively regulated by a catL-serpinB1-AEP module. Targeting this protease regulatory module could be an approach to treating Th17 cell-driven autoimmune disorders. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Hou, Lifei; Cooley, Jessica; Remold-O'Donnell, Eileen] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Remold-O'Donnell, Eileen] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Hou, Lifei; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Swanson, Richard; Olson, Steven T.] Univ Illinois, Dept Periodont, Chicago, IL 60612 USA. [Poh Chee Ong; Pike, Robert N.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. [Bogyo, Matthew] Stanford Univ, Sch Med, Dept Pathol, Palo Alto, CA 94305 USA. RP Hou, LF (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM lifei.hou@childrens.harvard.edu; eileen.remold-odonnell@childrens.harvard.edu OI Pike, Robert/0000-0002-2083-0269 FU NIH [R01 HL066548, R21 AI103407, R37 HL39888]; Boston Children's Hospital FX We thank Guo-Ping Shi for providing reagents and advice, Thomas Reinheckel and Johanna Joyce for providing ctsh-/- mice, Dieter Bromme for cathepsin V, Phillip Bird for initial discussions and material and Norma Gerard for use of CFX96 Real-Time System. This work was supported by NIH R01 HL066548, R21 AI103407 and an RRRC award from Boston Children's Hospital (to E.R.O) and NIH R37 HL39888 (to S.T.O.). NR 31 TC 2 Z9 2 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 EI 1095-9157 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 2015 VL 65 BP 56 EP 63 DI 10.1016/j.jaut.2015.08.006 PG 8 WC Immunology SC Immunology GA CZ0EY UT WOS:000366779100006 PM 26343333 ER PT J AU Hartling, L Guise, JM Kato, E Anderson, J Belinson, S Berliner, E Dryden, DM Featherstone, R Mitchell, MD Motu'apuaka, M Noorani, H Paynter, R Robinson, KA Schoelles, K Umscheid, CA Whitlock, E AF Hartling, Lisa Guise, Jeanne-Marie Kato, Elisabeth Anderson, Johanna Belinson, Suzanne Berliner, Elise Dryden, Donna M. Featherstone, Robin Mitchell, Matthew D. Motu'apuaka, Makalapua Noorani, Hussein Paynter, Robin Robinson, Karen A. Schoelles, Karen Umscheid, Craig A. Whitlock, Evelyn TI A taxonomy of rapid reviews links report types and methods to specific decision-making contexts SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Review DE Systematic reviews; Rapid reviews; Methodology; Interviews; Stakeholders; Automation ID SYSTEMATIC REVIEWS; PRODUCTS; MAKERS AB Objectives: Describe characteristics of rapid reviews and examine the impact of methodological variations on their reliability and validity. Study Design and Setting: We conducted a literature review and interviews with organizations that produce rapid reviews or related products to identify methods, guidance, empiric evidence, and current practices. Results: We identified 36 rapid products from 20 organizations (production time, 5 minutes to 8 months). Methods differed from systematic reviews at all stages. As time frames increased, methods became more rigorous; however, restrictions on database searching, inclusion criteria, data extracted, and independent dual review remained. We categorized rapid products based on extent of synthesis. "Inventories" list what evidence is available. "Rapid responses" present best available evidence with no formal synthesis. "Rapid reviews" synthesize the quality of and findings from the evidence. "Automated approaches" generate meta-analyses in response to user-defined queries. Rapid products rely on a close relationship with end users and support specific decisions in an identified time frame. Limited empiric evidence exists comparing rapid and systematic reviews. Conclusions: Rapid products have tremendous methodological variation; categorization based on time frame or type of synthesis reveals patterns. The similarity across rapid products lies in the close relationship with the end user to meet time-sensitive decision-making needs. (C) 2015 Elsevier Inc. All rights reserved. C1 [Hartling, Lisa; Dryden, Donna M.; Featherstone, Robin] Univ Alberta, Dept Pediat, Edmonton, AB, Canada. [Guise, Jeanne-Marie; Anderson, Johanna; Motu'apuaka, Makalapua; Paynter, Robin] Portland VA Res Fdn, Sci Resource Ctr, AHRQ Effect Hlth Care Program, Portland VA Med Ctr, Portland, OR USA. [Kato, Elisabeth; Berliner, Elise] Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD USA. [Belinson, Suzanne; Noorani, Hussein] Blue Cross Blue Shield Assoc, Off Clin Affairs, Chicago, IL USA. [Mitchell, Matthew D.; Schoelles, Karen; Umscheid, Craig A.] Univ Penn, ECRI Inst, Penn Med AHRQ EPC, Philadelphia, PA 19104 USA. [Mitchell, Matthew D.; Schoelles, Karen; Umscheid, Craig A.] Univ Penn, Ctr Evidence Based Practice, Philadelphia, PA 19104 USA. [Mitchell, Matthew D.; Schoelles, Karen; Umscheid, Craig A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Robinson, Karen A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Whitlock, Evelyn] Kaiser Permanente Res Affiliates, Portland, OR USA. RP Hartling, L (reprint author), 4-472 ECHA,11405-87 Ave, Edmonton, AB T6G IC9, Canada. EM hartling@ualberta.ca RI Featherstone, Robin/J-5165-2014; OI Featherstone, Robin/0000-0003-2517-2258; Paynter, Robin/0000-0002-6969-4261 FU Agency for Healthcare Research and Quality (AHRQ), Rockville, Maryland [290-2012-00013-I, 290-2012-00010-I, 290-2012-00011-I, 290-2012-00015-I, 290-2012-00007-I, 290201200004C] FX This manuscript is based on a project conducted by a working group with the Evidence-based Practice Center Program supported by the Agency for Healthcare Research and Quality (AHRQ), Rockville, Maryland through contracts to the following Evidence-based Practice Centers: University of Alberta (290-2012-00013-I), Blue Cross Blue Shield (290-2012-00010-I), ECRI- Penn (290-2012-00011-I), Kaiser (290-2012-00015-I), The Johns Hopkins University (290-2012-00007-I), and the Scientific Resource Center for the EPC Program (290201200004C). The findings and conclusions in this manuscript are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. No statement in this manuscript should be construed as an official position of AHRQ or of the US Department of Health and Human Services. NR 21 TC 5 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 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2015 VL 68 IS 12 BP 1451 EP 1462 DI 10.1016/j.jclinepi.2015.05.036 PG 12 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CY6TR UT WOS:000366542200010 PM 26278023 ER PT J AU Smith, CD Rattner, DW AF Smith, C. Daniel Rattner, David W. TI 25th Anniversary State-of-the-Art Expert Discussion With David W. Rattner, MD, on NOTES SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES LA English DT Editorial Material C1 [Rattner, David W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM DRATTNER@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1092-6429 EI 1557-9034 J9 J LAPAROENDOSC ADV S JI J. Laparoendosc. Adv. Surg. Tech. PD DEC 1 PY 2015 VL 25 IS 12 BP 961 EP 965 DI 10.1089/lap.2015.29004.rat PG 5 WC Surgery SC Surgery GA CY8NC UT WOS:000366664400001 ER PT J AU Iezzoni, LI Wint, AJ Smeltzer, SC Ecker, JL AF Iezzoni, Lisa I. Wint, Amy J. Smeltzer, Suzanne C. Ecker, Jeffrey L. TI Physical Accessibility of Routine Prenatal Care for Women with Mobility Disability SO JOURNAL OF WOMENS HEALTH LA English DT Article ID HEALTH-CARE; BREAST-CANCER; PREGNANCY; ACCESS; IMPAIRMENTS; DIAGNOSIS; REVIEWS AB Background: Routine prenatal care includes physical examinations and weight measurement. Little is known about whether access barriers to medical diagnostic equipment, such as examination tables and weight scales, affect prenatal care among pregnant women with physical disabilities. Methods: We conducted 2-hour, in-depth telephone interviews with 22 women using a semistructured, open-ended interview protocol. All women had significant mobility difficulties before pregnancy and had delivered babies within the prior 10 years. We recruited most participants through social networks. We sorted interview transcript texts using used NVivo software and conducted conventional content analyses to identify major themes. Results: Interviewee's mean (standard deviation) age was 34.8 (5.3) years. Most were white, well-educated, and higher income; 8 women had spinal cord injuries, 4 cerebral palsy, and 10 had other conditions; 18 used wheeled mobility aids. Some women's obstetricians had height adjustable examination tables, which facilitated transfers for physical examinations. Other women had difficulty transferring onto fixed height examination tables and were examined while sitting in their wheelchairs. Family members and/or clinical staff sometimes assisted with transfers; some women reported concerns about transfer safety. No women reported being routinely weighed on an accessible weight scale by their prenatal care clinicians. A few were never weighed during their pregnancies. Conclusions: Inaccessible examination tables and weight scales impede some pregnant women with physical disabilities from getting routine prenatal physical examinations and weight measurement. This represents substandard care. Adjustable height examination tables and wheelchair accessible weight scales could significantly improve care and comfort for pregnant women with physical disabilities. C1 [Iezzoni, Lisa I.; Wint, Amy J.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ecker, Jeffrey L.] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. [Smeltzer, Suzanne C.] Villanova Univ, Coll Nursing, Ctr Nursing Res, Villanova, PA 19085 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@mgh.harvard.edu RI Dey, Kamalesh/E-6568-2017 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development in the U.S. National Institutes of Health [1R21HD068756-02] FX This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development in the U.S. National Institutes of Health (Grant No. 1R21HD068756-02). NR 31 TC 3 Z9 3 U1 1 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD DEC 1 PY 2015 VL 24 IS 12 BP 1006 EP 1012 DI 10.1089/jwh.2015.5385 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA CY5LB UT WOS:000366448000009 PM 26484689 ER PT J AU Vadvala, H Engel, LC Ghoshhajra, BB AF Vadvala, Harshna Engel, Leif-Christopher Ghoshhajra, Brian B. TI Letter to the Editor Regarding "Ruling Out Coronary Artery Disease in Women with Atypical Chest Pain: Results of Calcium Score Combined with Coronary Computed Tomography Angiography, and Associated Radiation Exposure" SO JOURNAL OF WOMENS HEALTH LA English DT Letter C1 [Vadvala, Harshna; Engel, Leif-Christopher; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ghoshhajra, BB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM bghoshhajra@partners.org NR 2 TC 0 Z9 0 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD DEC 1 PY 2015 VL 24 IS 12 BP 1050 EP 1050 DI 10.1089/jwh.2015.5524 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA CY5LB UT WOS:000366448000015 PM 26506133 ER PT J AU Whitaker, RM Stallons, LJ Kneff, JE Alge, JL Harmon, JL Rahn, JJ Arthur, JM Beeson, CC Chan, SL Schnellmann, RG AF Whitaker, Ryan M. Stallons, L. Jay Kneff, Joshua E. Alge, Joseph L. Harmon, Jennifer L. Rahn, Jennifer J. Arthur, John M. Beeson, Craig C. Chan, Sherine L. Schnellmann, Rick G. TI Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury SO KIDNEY INTERNATIONAL LA English DT Article DE acute kidney injury; ischemia/reperfusion; mitochondria ID CARDIAC-SURGERY; DISEASE; RISK; AKI; PROGRESSION; DIAGNOSIS; RECOVERY; OUTCOMES; BIOGENESIS; SEVERITY AB Recent studies show the importance of mitochondrial dysfunction in the initiation and progression of acute kidney injury (AKI). However, no biomarkers exist linking renal injury to mitochondrial function and integrity. To this end, we evaluated urinary mitochondrial DNA (UmtDNA) as a biomarker of renal injury and function in humans with AKI following cardiac surgery. mtDNA was isolated from the urine of patients following cardiac surgery and quantified by quantitative PCR. Patients were stratified into no AKI, stable AKI, and progressive AKI groups based on Acute Kidney Injury Network (AKIN) staging. UmtDNA was elevated in progressive AKI patients and was associated with progression of patients with AKI at collection to higher AKIN stages. To evaluate the relationship of UmtDNA to measures of renal mitochondrial integrity in AKI, mice were subjected to sham surgery or varying degrees of ischemia followed by 24 h of reperfusion. UmtDNA increased in mice after 10-15 min of ischemia and positively correlated with ischemia time. Furthermore, UmtDNA was predictive of AKI in the mouse model. Finally, UmtDNA levels were negatively correlated with renal cortical mtDNA and mitochondrial gene expression. These translational studies demonstrate that UmtDNA is associated with recovery from AKI following cardiac surgery by serving as an indicator of mitochondrial integrity. Thus UmtDNA may serve as valuable biomarker for the development of mitochondrial-targeted therapies in AKI. C1 [Whitaker, Ryan M.; Stallons, L. Jay; Kneff, Joshua E.; Harmon, Jennifer L.; Rahn, Jennifer J.; Beeson, Craig C.; Chan, Sherine L.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Alge, Joseph L.; Arthur, John M.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Arthur, John M.; Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu OI Alge, Joseph/0000-0002-2491-1066 FU NIDDK NIH HHS [F30 DK096964]; NIGMS NIH HHS [T32 GM008716, R01 GM084147] NR 46 TC 3 Z9 3 U1 3 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2015 VL 88 IS 6 BP 1336 EP 1344 DI 10.1038/ki.2015.240 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CY4RG UT WOS:000366395300019 PM 26287315 ER EF