FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Roh, EK Ali, M Lu, MT Bradshaw, SH AF Roh, Ellen K. Ali, Mohammed Lu, Michael T. Bradshaw, Scott H. TI Case 2-2016: An 84-Year-Old Woman with Chest Pain, Dyspnea, and a Rash SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MULTIPLE-MYELOMA; CARDIAC AMYLOIDOSIS; CONGO RED; BLEEDING DISORDERS; CARDIOMYOPATHY; CD19 C1 [Roh, Ellen K.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Ali, Mohammed] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lu, Michael T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bradshaw, Scott H.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Roh, Ellen K.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Ali, Mohammed] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lu, Michael T.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Bradshaw, Scott H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Roh, EK (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 19 TC 0 Z9 0 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 21 PY 2016 VL 374 IS 3 BP 264 EP 274 DI 10.1056/NEJMcpc1502149 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DB3IS UT WOS:000368404800012 PM 26789875 ER PT J AU Garcia, JA Sweeney, C AF Garcia, Jorge A. Sweeney, Christopher TI Chemohormonal Therapy in Hormone-Sensitive Prostate Cancer REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ANDROGEN DEPRIVATION C1 [Garcia, Jorge A.] Cleveland Clin, Cleveland, OH 44106 USA. [Sweeney, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Garcia, JA (reprint author), Cleveland Clin, Cleveland, OH 44106 USA. EM christopher_sweeney@dfci.harvard.edu NR 2 TC 0 Z9 0 U1 2 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 21 PY 2016 VL 374 IS 3 BP 287 EP 287 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DB3IS UT WOS:000368404800021 PM 26789883 ER PT J AU Branda, JA Robbins, GK Hooper, DC AF Branda, John A. Robbins, Gregory K. Hooper, David C. TI Case 28-2015: A Man with Febrile Symptoms after Traveling from Liberia REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Branda, John A.; Robbins, Gregory K.; Hooper, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Branda, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 21 PY 2016 VL 374 IS 3 BP 294 EP 294 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DB3IS UT WOS:000368404800035 ER PT J AU Ghani, MU Zhou, ZX Ren, LQ Wong, M Li, YH Zheng, B Yang, K Liu, H AF Ghani, Muhammad U. Zhou, Zhongxing Ren, Liqiang Wong, Molly Li, Yuhua Zheng, Bin Yang, Kai Liu, Hong TI Investigation of spatial resolution characteristics of an in vivo microcomputed tomography system SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article DE Spatial resolution; MicroCT; MTF; Geometric magnification; X-ray; Interpolation ID COMPUTED-TOMOGRAPHY; MICRO-CT AB The spatial resolution characteristics of an in vivo microcomputed tomography (CT) system was investigated in the in-plane (x-y), cross plane (z) and projection imaging modes. The microCT system utilized in this study employs a flat panel detector with a 127 mu m pixel pitch, a microfocus x-ray tube with a focal spot size ranging from 5-30 mu m, and accommodates three geometric magnifications (M) of 1.72, 2.54 and 5.10. The in-plane modulation transfer function (MTF) curves were measured as a function of the number of projections, geometric magnification (M), detector binning and reconstruction magnification (M-Recon). The in plane cutoff frequency (10% MTF) ranged from 2.31 lp/mm (M=1.72, 2 x 2 binning) to 12.56 lp/mm (M=5.10, 1 x 1 binning) and a bar pattern phantom validated those measurements. A slight degradation in the spatial resolution was observed when comparing the image reconstruction with 511 and 918 projections, whose effect was visible at the lower frequencies. Small value of M-Recon has little or no impact on the in-plane spatial resolution owning to a stable system. Large value of M-Recon has implications on the spatial resolution and it was evident when comparing the bar pattern images reconstructed with M-Recon = 1.25 and 2.5. The cross plane MTF curves showed that the spatial resolution increased as the slice thickness decreased. The cutoff frequencies in the projection imaging mode yielded slightly higher values as compared to the in-plane and cross plane modes at all the geometric magnifications (M). At M=5.10, the cutoff resolution of the projection and cross plane on an ultra-high contrast resolution bar chip phantom were 14.9 lp/mm and 13-13.5 lp/mm. Due to the finite focal spot size of the x-ray tube, the detector blur and the reconstruction kernel functions, the system's spatial resolution does not reach the limiting spatial resolution as defined by the Nyquist's detector criteria with an ideal point source. The geometric magnification employed in the microCTs provide a tradeoff between field of view and spatial resolution for a wide range of applications. (C) 2015 Elsevier B.V. All rights reserved. C1 [Ghani, Muhammad U.; Zhou, Zhongxing; Ren, Liqiang; Wong, Molly; Li, Yuhua; Zheng, Bin; Liu, Hong] Univ Oklahoma, Ctr Biomed Engn, Norman, OK 73019 USA. [Ghani, Muhammad U.; Zhou, Zhongxing; Ren, Liqiang; Wong, Molly; Li, Yuhua; Zheng, Bin; Liu, Hong] Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA. [Zhou, Zhongxing] Tianjin Univ, Sch Precis & Optoelect Engn, Tianjin 300072, Peoples R China. [Yang, Kai] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Liu, H (reprint author), Univ Oklahoma, Ctr Biomed Engn, Norman, OK 73019 USA. EM liu@ou.edu RI Ghani, Muhammad/P-5473-2016 FU NIH [R01 CA193378]; University of Oklahoma Charles and Peggy Stephenson Cancer Center - Oklahoma Tobacco Settlement Endowment Trust; Charles and Jean Smith Chair endowment fund FX This research was supported in part by the NIH under grant R01 CA193378, and supported in part by a grant from the University of Oklahoma Charles and Peggy Stephenson Cancer Center funded by the Oklahoma Tobacco Settlement Endowment Trust. We would like to acknowledge the support of Charles and Jean Smith Chair endowment fund as well. NR 26 TC 4 Z9 4 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 EI 1872-9576 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD JAN 21 PY 2016 VL 807 BP 129 EP 136 DI 10.1016/j.nima.2015.11.007 PG 8 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA CX3JX UT WOS:000365596200018 PM 26640309 ER PT J AU Abu Zaid, MI Fung, C Williams, A Sesso, HD Kerns, SL Feldman, DR Hamilton, RJ Vaughn, DJ Beard, C Liu, H Fossa, SD Einhorn, LH Travis, LB AF Abu Zaid, Mohammad Issam Fung, Chunkit Williams, AnnaLynn Sesso, Howard D. Kerns, Sarah L. Feldman, Darren R. Hamilton, Robert James Vaughn, David J. Beard, Clair Liu, Hai Fossa, Sophie D. Einhorn, Lawrence H. Travis, Lois B. CA Platinum Study Grp TI Cardiovascular disease (CVD) risk factors and health behaviors following cisplatin-based chemotherapy (CHEM): A multi-institutional study of testicular cancer survivors (TCS) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Indiana Univ Sch Med, Indianapolis, IN 46202 USA. Wilmot Canc Ctr, Rochester, NY USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Oslo, Oslo Univ Hosp, Oslo, Norway. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 129 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500124 ER PT J AU Baker, KS Ambrose, K Arvey, SR Casillas, JN Ganz, PA Jacobs, LA McCabe, MS Overholser, L Partridge, AH Rajotte, EJ Risendal, BC Rosenstein, D Syrjala, K AF Baker, Kevin Scott Ambrose, Kelly Arvey, Sarah R. Casillas, Jacqueline N. Ganz, Patricia A. Jacobs, Linda A. McCabe, Mary S. Overholser, Linda Partridge, Ann H. Rajotte, Emily Jo Risendal, Betsy C. Rosenstein, Donald Syrjala, Karen TI Financial and work related impact of cancer in young adult (YA) survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. Livestrong Fdn, Austin, TX USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Univ Colorado, Sch Med, Denver, CO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 15 PG 2 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500016 ER PT J AU Bober, SL Blackmon, JE Recklitis, CJ Wright, AA AF Bober, Sharon L. Blackmon, Jaime E. Recklitis, Christopher J. Wright, Alexi A. TI Preliminary results from the Sexual Therapy and Rehabilitation after Treatment for Ovarian Cancer (START-OC) study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 [Bober, Sharon L.; Blackmon, Jaime E.; Recklitis, Christopher J.; Wright, Alexi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 127 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500122 ER PT J AU Case-Eads, S Travis, LB Fung, C Sesso, HD Feldman, DR Vaughn, DJ Hamilton, RJ Johnson, E Peterson, DR Fossa, SD Einhorn, LH Beard, C AF Case-Eads, Somer Travis, Lois B. Fung, Chunkit Sesso, Howard D. Feldman, Darren R. Vaughn, David J. Hamilton, Robert James Johnson, Eileen Peterson, Derick R. Fossa, Sophie D. Einhorn, Lawrence H. Beard, Clair TI Psychotropic and stimulant medication (PSM) use among testicular cancer survivors (TCS): A multi-institutional clinical study of 680 patients given cisplatin-based chemotherapy (CHEM) (NCI 1R01 CA157823-02). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Indiana Univ, Indianapolis, IN 46204 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Wilmot Canc Ctr, Rochester, NY USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Oslo, Oslo Univ Hosp, Oslo, Norway. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 242 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500230 ER PT J AU Cuddy, A Van Loon, K You, YN Hu, CY Francescatti, AB Greenberg, CC Venook, AP Schrag, D Chang, GJ AF Cuddy, Amanda Van Loon, Katherine You, Y. Nancy Hu, Chung-Yuan Francescatti, Amanda Beth Greenberg, Caprice Christian Venook, Alan P. Schrag, Deborah Chang, George J. TI How clinicians make decisions regarding surveillance and treatment of colorectal cancer (CRC) patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Amer Coll Surg, Chicago, IL USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 263 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500250 ER PT J AU D'Agostino, NM Edelstein, K Zhang, N Recklitis, CJ Brinkman, TM Srivastava, D Leisenring, WM Robison, LL Armstrong, GT Krull, KR AF D'Agostino, Norma Mammone Edelstein, Kim Zhang, Nan Recklitis, Christopher J. Brinkman, Tara M. Srivastava, Deokumar Leisenring, Wendy M. Robison, Leslie L. Armstrong, Gregory T. Krull, Kevin R. TI Predicting patterns of distress in adult survivors of childhood cancer: A latent profile analysis from the Childhood Cancer Survivor Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 210 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500200 ER PT J AU Donovan, HAS Horn, C Campbell, G Hagan, T Bovbjerg, DH AF Donovan, Heidi A. S. Horn, Charles Campbell, Grace Hagan, Teresa Bovbjerg, Dana H. TI Associations between peripheral neuropathy and nausea/vomiting in survivors of ovarian cancer: Evidence of persistent vagal neuropathies? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Pittsburgh, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 165 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500156 ER PT J AU Fair, DB Kirchhoff, AC Nipp, RD Leisenring, WM Nathan, PC Oeffinger, KC Armstrong, GT Robison, LL Park, E AF Fair, Douglas Beaty Kirchhoff, Anne C. Nipp, Ryan David Leisenring, Wendy M. Nathan, Paul C. Oeffinger, Kevin C. Armstrong, Gregory T. Robison, Leslie L. Park, Elyse TI Impact of health care costs on utilization of needed health care in the Childhood Cancer Survivor Study (CCSS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Huntsman Canc Inst, Salt Lake City, UT USA. Univ Utah, Dept Pediat, Salt Lake City, UT USA. Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. Mongan Hlth Inst Publ Policy, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 20 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500021 ER PT J AU Greenzang, K Cronin, A Mack, JW AF Greenzang, Katie Cronin, Angel Mack, Jennifer W. TI Parental preparedness for late effects in survivors of childhood cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Childrens Canc & Blood Disorders Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 85 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500082 ER PT J AU Hagan, T Cohen, SM Rosenzweig, MQ Zorn, KK Stone, C Donovan, HAS AF Hagan, Teresa Cohen, Susan M. Rosenzweig, Margaret Quinn Zorn, Kristin Kelley Stone, Clement Donovan, Heidi A. S. TI The female self-advocacy in cancer survivorship scale: Validating a new measure to support patient voice and engagement. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. Magee Womens Hosp UPMC, Pittsburgh, PA USA. Univ Pittsburgh, Sch Educ, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 96 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500093 ER PT J AU Kerns, SL Fung, C Williams, A Abu Zaid, MI Sesso, HD Feldman, DR Hamilton, RJ Vaughn, DJ Beard, C Liu, H Herrmann, D Sahasrabudhe, DM Fossa, SD Einhorn, LH Travis, LB AF Kerns, Sarah L. Fung, Chunkit Williams, AnnaLynn Abu Zaid, Mohammad Issam Sesso, Howard D. Feldman, Darren R. Hamilton, Robert James Vaughn, David J. Beard, Clair Liu, Hai Herrmann, David Sahasrabudhe, Deepak M. Fossa, Sophie D. Einhorn, Lawrence H. Travis, Lois B. CA Platinum Study Grp TI Cumulative burden of morbidity (CBM) among testicular cancer survivors (TCS) in the Platinum study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Wilmot Canc Ctr, Rochester, NY USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Indiana Univ Sch Med, Indianapolis, IN 46202 USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. Univ Oslo, Oslo Univ Hosp, Oslo, Norway. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 106 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500103 ER PT J AU Ligibel, JA Barry, WT Ruddy, KJ Greaney, M Rosenberg, SM Sprunck-Harrild, K Morgan, E Walsh, S Emmons, K Partridge, AH AF Ligibel, Jennifer A. Barry, William Thomas Ruddy, Kathryn Jean Greaney, Mary Rosenberg, Shoshana M. Sprunck-Harrild, Kim Morgan, Evan Walsh, Sarah Emmons, Karen Partridge, Ann H. TI Impact of Young and Strong on physical activity in young breast cancer survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Rhode Isl, Kingston, RI 02881 USA. Kaiser, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 175 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500166 ER PT J AU Ligibel, JA Barry, WT Ruddy, KJ Greaney, M Rosenberg, SM Sprunck-Harrild, K Morgan, E Walsh, S Emmons, K Partridge, AH AF Ligibel, Jennifer A. Barry, William Thomas Ruddy, Kathryn Jean Greaney, Mary Rosenberg, Shoshana M. Sprunck-Harrild, Kim Morgan, Evan Walsh, Sarah Emmons, Karen Partridge, Ann H. TI Physical activity and weight patterns in a study cohort of young breast cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Rhode Isl, Kingston, RI 02881 USA. Kaiser, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 166 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500157 ER PT J AU Moe, EL Borsch, C Garg, B Dobek, JC Doggett, R Graff, JN Beer, TM Winters-Stone, KM AF Moe, Esther L. Borsch, Carolyn Garg, Bharti Dobek, Jessica C. Doggett, Rumen Graff, Julie Nicole Beer, Tomasz M. Winters-Stone, Kerri M. TI Falls and frailty in prostate cancer survivors on androgen deprivation therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Oregon State Univ, Corvallis, OR 97331 USA. OHSU Knight Canc Inst, Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 134 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500128 ER PT J AU Rosenberg, SM Ligibel, JA Meyerhardt, JA Jacobsen, ED Garber, JE Nekhlyudov, L Bunnell, CA Walsh, S Partridge, AH AF Rosenberg, Shoshana M. Ligibel, Jennifer A. Meyerhardt, Jeffrey A. Jacobsen, Eric D. Garber, Judy Ellen Nekhlyudov, Larissa Bunnell, Craig A. Walsh, Sarah Partridge, Ann H. TI Developing infrastructure to improve research and care for cancer survivors: A pilot study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 61 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500058 ER PT J AU Vazquez, DA Rosenberg, SM Gelber, SI Ruddy, KJ Morgan, E Recklitis, CJ Come, SE Schapira, L Partridge, AH AF Vazquez, Danny A. Rosenberg, Shoshana M. Gelber, Shari I. Ruddy, Kathryn Jean Morgan, Evan Recklitis, Christopher J. Come, Steven E. Schapira, Lidia Partridge, Ann H. TI Post-traumatic stress disorder in young breast cancer survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 202 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500192 ER PT J AU Yung, RL Giobbie-Hurder, A Shockro, L O'Connor, K Campbell, N Kasper, J Overmoyer, B Mayer, EL Tolaney, SM Partridge, AH Ligibel, JA AF Yung, Rachel Lynn Giobbie-Hurder, Anita Shockro, Laura O'Connor, Keelin Campbell, Nancy Kasper, Jocelyn Overmoyer, Beth Mayer, Erica L. Tolaney, Sara M. Partridge, Ann H. Ligibel, Jennifer A. TI A randomized trial of a clinic-based weight loss intervention in cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Cancer Survivorship Symposium on Advancing Care and Research CY JAN 15-16, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Waban, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 SU S MA 167 PG 1 WC Oncology SC Oncology GA DO9MA UT WOS:000378109500158 ER PT J AU Maraldo, MV Ng, AK AF Maraldo, Maja V. Ng, Andrea K. TI Minimizing Cardiac Risks With Contemporary Radiation Therapy for Hodgkin Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID INTENSITY-MODULATED RADIOTHERAPY; INVOLVED-NODE RADIOTHERAPY; INSPIRATION BREATH-HOLD; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; CARDIOVASCULAR-DISEASE; CHILDHOOD-CANCER; PROTON THERAPY; HEART-DISEASE; PHASE-II; STAGE-II C1 [Maraldo, Maja V.] Univ Copenhagen, Copenhagen, Denmark. [Ng, Andrea K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Ng, Andrea K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Maraldo, MV (reprint author), Univ Copenhagen, Copenhagen, Denmark. NR 40 TC 3 Z9 3 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 BP 208 EP 210 DI 10.1200/JCO.2015.64.6588 PG 3 WC Oncology SC Oncology GA DJ6NV UT WOS:000374331100006 PM 26628476 ER PT J AU Yabroff, KR Dowling, EC Guy, GP Banegas, MP Davidoff, A Han, XS Virgo, KS McNeel, TS Chawla, N Blanch-Hartigan, D Kent, EE Li, CY Rodriguez, JL de Moor, JS Zheng, ZY Jemal, A Ekwueme, DU AF Yabroff, K. Robin Dowling, Emily C. Guy, Gery P., Jr. Banegas, Matthew P. Davidoff, Amy Han, Xuesong Virgo, Katherine S. McNeel, Timothy S. Chawla, Neetu Blanch-Hartigan, Danielle Kent, Erin E. Li, Chunyu Rodriguez, Juan L. de Moor, Janet S. Zheng, Zhiyuan Jemal, Ahmedin Ekwueme, Donatus U. TI Financial Hardship Associated With Cancer in the United States: Findings From a Population-Based Sample of Adult Cancer Survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; MEDICAL-CARE; INSURANCE STATUS; ECONOMIC BURDEN; COST; DIAGNOSIS; TOXICITY; STAGE; CHEMOTHERAPY; ONCOLOGISTS AB Purpose To estimate the prevalence of financial hardship associated with cancer in the United States and identify characteristics of cancer survivors associated with financial hardship. Methods We identified 1,202 adult cancer survivors diagnosed or treated at >= 18 years of age from the 2011 Medical Expenditure Panel Survey Experiences With Cancer questionnaire. Material financial hardship was measured by ever (1) borrowing money or going into debt, (2) filing for bankruptcy, (3) being unable to cover one's share of medical care costs, or (4) making other financial sacrifices because of cancer, its treatment, and lasting effects of treatment. Psychological financial hardship was measured as ever worrying about paying large medical bills. We examined factors associated with any material or psychological financial hardship using separate multivariable logistic regression models stratified by age group (18 to 64 and >= 65 years). Results Material financial hardship was more common in cancer survivors age 18 to 64 years than in those >= 65 years of age (28.4% v 13.8%; P < .001), as was psychological financial hardship (31.9% v 14.7%, P < .001). In adjusted analyses, cancer survivors age 18 to 64 years who were younger, female, nonwhite, and treated more recently and who had changed employment because of cancer were significantly more likely to report any material financial hardship. Cancer survivors who were uninsured, had lower family income, and were treated more recently were more likely to report psychological financial hardship. Among cancer survivors >= 65 years of age, those who were younger were more likely to report any financial hardship. Conclusion Cancer survivors, especially the working-age population, commonly experience material and psychological financial hardship. (C) 2015 by American Society of Clinical Oncology C1 [Yabroff, K. Robin; Banegas, Matthew P.; Chawla, Neetu; Blanch-Hartigan, Danielle; Kent, Erin E.; de Moor, Janet S.] NCI, Bethesda, MD 20892 USA. [McNeel, Timothy S.] Informat Management Serv Inc, Calverton, MD USA. [Dowling, Emily C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blanch-Hartigan, Danielle] Bentley Univ, Waltham, MA USA. [Guy, Gery P., Jr.; Li, Chunyu; Rodriguez, Juan L.; Ekwueme, Donatus U.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Han, Xuesong; Zheng, Zhiyuan; Jemal, Ahmedin] Amer Canc Soc, Atlanta, GA 30329 USA. [Virgo, Katherine S.] Emory Univ, Atlanta, GA 30322 USA. [Davidoff, Amy] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Chawla, Neetu] Kaiser Permanente No Calif, Oakland, CA USA. RP Yabroff, KR (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Rockville, MD 20892 USA. EM robin.yabroff@hhs.gov FU Celgene FX Celgene (I) NR 55 TC 9 Z9 9 U1 2 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2016 VL 34 IS 3 BP 259 EP U125 DI 10.1200/JCO.2015.62.0468 PG 16 WC Oncology SC Oncology GA DJ6NV UT WOS:000374331100014 PM 26644532 ER PT J AU Koole, O Denison, JA Menten, J Tsui, S Wabwire-Mangen, F Kwesigabo, G Mulenga, M Auld, A Agolory, S Mukadi, YD van Praag, E Torpey, K Williams, S Kaplan, J Zee, A Bangsberg, DR Colebunders, R AF Koole, Olivier Denison, Julie A. Menten, Joris Tsui, Sharon Wabwire-Mangen, Fred Kwesigabo, Gideon Mulenga, Modest Auld, Andrew Agolory, Simon Mukadi, Ya Diul van Praag, Eric Torpey, Kwasi Williams, Seymour Kaplan, Jonathan Zee, Aaron Bangsberg, David R. Colebunders, Robert TI Reasons for Missing Antiretroviral Therapy: Results from a Multi-Country Study in Tanzania, Uganda, and Zambia SO PLOS ONE LA English DT Article ID HIV PATIENTS; REPORTED ADHERENCE; FOOD INSECURITY; SUPPORT; AFRICA; ADULTS; HAART; QUESTIONNAIRE; DETERMINANTS; METAANALYSIS AB Objectives To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence. Methods Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (>= 18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients' medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months. Results Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2-7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1-1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms. Conclusions Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes. C1 [Koole, Olivier] London Sch Hyg & Trop Med, Dept Clin Res, London WC1, England. [Koole, Olivier; Menten, Joris; Colebunders, Robert] Inst Trop Med, Dept Clin Sci, B-2000 Antwerp, Belgium. [Denison, Julie A.; Tsui, Sharon; Mukadi, Ya Diul; van Praag, Eric; Torpey, Kwasi] FHI 360, Social & Behav Hlth Sci, Durham, NC USA. [Denison, Julie A.; Tsui, Sharon] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Wabwire-Mangen, Fred] Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda. [Kwesigabo, Gideon] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Mulenga, Modest] Trop Dis Res Ctr, Ndola, Zambia. [Auld, Andrew; Agolory, Simon; Williams, Seymour; Kaplan, Jonathan; Zee, Aaron] Ctr Dis Control & Prevent, Div Global HIV AIDS, Atlanta, GA USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Colebunders, Robert] Univ Antwerp, Epidemiol & Social Med, B-2020 Antwerp, Belgium. RP Koole, O (reprint author), London Sch Hyg & Trop Med, Dept Clin Res, London WC1, England.; Koole, O (reprint author), Inst Trop Med, Dept Clin Sci, B-2000 Antwerp, Belgium. EM olivier.koole@lshtm.ac.uk OI Auld, Andrew/0000-0001-5089-9163 FU President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC); Health Resources&Services Administration (HRSA) [2006-N-08428, FHI 360] FX This research has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) and the Health Resources&Services Administration (HRSA) under the terms of the contract no. 2006-N-08428 with FHI 360. The CDC provided technical input into the study design, data collection, data analysis, data interpretation, and writing of the manuscript. NR 53 TC 3 Z9 3 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 20 PY 2016 VL 11 IS 1 AR e0147309 DI 10.1371/journal.pone.0147309 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB5BW UT WOS:000368529100076 PM 26788919 ER PT J AU Minikel, EV Vallabh, SM Lek, M Estrada, K Samocha, KE Sathirapongsasuti, JF McLean, CY Tung, JY Yu, LPC Gambetti, P Blevins, J Zhang, SL Cohen, Y Chen, W Yamada, M Hamaguchi, T Sanjo, N Mizusawa, H Nakamura, Y Kitamoto, T Collins, SJ Boyd, A Will, RG Knight, R Ponto, C Zerr, I Kraus, TFJ Eigenbrod, S Giese, A Calero, M de Pedro-Cuesta, J Haik, S Laplanche, JL Bouaziz-Amar, E Brandel, JP Capellari, S Parchi, P Poleggi, A Ladogana, A O'Donnell-Luria, AH Karczewski, KJ Marshall, JL Boehnke, M Laakso, M Mohlke, KL Kahler, A Chambert, K McCarroll, S Sullivan, PF Hultman, CM Purcell, SM Sklar, P van der Lee, SJ Rozemuller, A Jansen, C Hofman, A Kraaij, R van Rooij, JGJ Ikram, MA Uitterlinden, AG van Duijn, CM Daly, MJ MacArthur, DG AF Minikel, Eric Vallabh Vallabh, Sonia M. Lek, Monkol Estrada, Karol Samocha, Kaitlin E. Sathirapongsasuti, J. Fah McLean, Cory Y. Tung, Joyce Y. Yu, Linda P. C. Gambetti, Pierluigi Blevins, Janis Zhang, Shulin Cohen, Yvonne Chen, Wei Yamada, Masahito Hamaguchi, Tsuyoshi Sanjo, Nobuo Mizusawa, Hidehiro Nakamura, Yosikazu Kitamoto, Tetsuyuki Collins, Steven J. Boyd, Alison Will, Robert G. Knight, Richard Ponto, Claudia Zerr, Inga Kraus, Theo F. J. Eigenbrod, Sabina Giese, Armin Calero, Miguel de Pedro-Cuesta, Jesus HaiK, Stephane Laplanche, Jean-Louis Bouaziz-Amar, Elodie Brandel, Jean-Philippe Capellari, Sabina Parchi, Piero Poleggi, Anna Ladogana, Anna O'Donnell-Luria, Anne H. Karczewski, Konrad J. Marshall, Jamie L. Boehnke, Michael Laakso, Markku Mohlke, Karen L. Kahler, Anna Chambert, Kimberly McCarroll, Steven Sullivan, Patrick F. Hultman, Christina M. Purcell, Shaun M. Sklar, Pamela van der Lee, Sven J. Rozemuller, Annemieke Jansen, Casper Hofman, Albert Kraaij, Robert van Rooij, Jeroen G. J. Ikram, M. Arfan Uitterlinden, Andre G. van Duijn, Cornelia M. Daly, Mark J. MacArthur, Daniel G. CA Exome Aggregation Consortium ExAC TI Quantifying prion disease penetrance using large population control cohorts SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; STRAUSSLER-SCHEINKER-DISEASE; PROTEIN GENE MUTATION; FATAL FAMILIAL INSOMNIA; UNCOMMON POLYMORPHISM RATHER; TRANSGENIC MOUSE MODEL; AMYLOID PRECURSOR GENE; PRNP GENE; POINT MUTATION; R208H MUTATION AB More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance-the probability that a carrier of the purported disease-causing genotype will indeed develop the disease-is generally unknown. We assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence. Although some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from < 0.1 to similar to 100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, a finding that supports the safety of therapeutic suppression of prion protein expression. C1 [Minikel, Eric Vallabh; Vallabh, Sonia M.; Lek, Monkol; Estrada, Karol; Samocha, Kaitlin E.; O'Donnell-Luria, Anne H.; Karczewski, Konrad J.; Marshall, Jamie L.; Daly, Mark J.; MacArthur, Daniel G.] Broad Inst Massachusetts Inst Technol MIT & Harva, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Minikel, Eric Vallabh; Lek, Monkol; Estrada, Karol; Samocha, Kaitlin E.; O'Donnell-Luria, Anne H.; Karczewski, Konrad J.; Marshall, Jamie L.; Daly, Mark J.; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Minikel, Eric Vallabh; Vallabh, Sonia M.; Samocha, Kaitlin E.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Minikel, Eric Vallabh; Vallabh, Sonia M.] Prion Alliance, Cambridge, MA 02139 USA. [Sathirapongsasuti, J. Fah; McLean, Cory Y.; Tung, Joyce Y.; Yu, Linda P. C.] 23&Me Inc, Res, Mountain View, CA 94041 USA. [Gambetti, Pierluigi; Blevins, Janis; Cohen, Yvonne; Chen, Wei] Natl Pr Dis Pathol Surveillance Ctr, Cleveland, OH 44106 USA. [Zhang, Shulin] Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Yamada, Masahito; Hamaguchi, Tsuyoshi] Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol Aging, Kanazawa, Ishikawa 9208640, Japan. [Sanjo, Nobuo] Tokyo Med & Dent Univ, Grad Sch, Dept Neurol & Neurol Sci, Tokyo 1138519, Japan. [Mizusawa, Hidehiro] Natl Ctr Neurol & Psychiat, Natl Ctr Hosp, Tokyo 1878551, Japan. [Nakamura, Yosikazu] Jichi Med Univ, Dept Publ Hlth, Shimotsuke 3290498, Japan. [Kitamoto, Tetsuyuki] Tohoku Univ, Grad Sch Med, Dept Neurol Sci, Sendai, Miyagi 9808575, Japan. [Collins, Steven J.; Boyd, Alison] Univ Melbourne, Australian Natl Creutzfeldt Jakob Dis Registry, Parkville, Vic 3010, Australia. [Will, Robert G.; Knight, Richard] Western Gen Hosp, Natl Creutzfeldt Jakob Dis Res & Surveillance Uni, Edinburgh EH4 2XU, Midlothian, Scotland. [Ponto, Claudia; Zerr, Inga] Univ Gottingen, Natl Reference Ctr Surveillance Human Transmissib, D-37073 Gottingen, Germany. [Kraus, Theo F. J.; Eigenbrod, Sabina; Giese, Armin] Univ Munich, Ctr Neuropathol & Pr Res ZNP, Marchioninistr 15, D-81377 Munich, Germany. [Calero, Miguel; de Pedro-Cuesta, Jesus] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain. [HaiK, Stephane; Brandel, Jean-Philippe] Sorbonne Univ, CNRS UMR 7225, INSERM U1127, F-75013 Paris, France. [HaiK, Stephane; Brandel, Jean-Philippe] Univ Paris 06, UMR S 1127, Inst Cerveau & Moelle Epiniere, F-75013 Paris, France. [HaiK, Stephane; Brandel, Jean-Philippe] Grp Hosp Pitie Salpetriere, AP HP, Cellule Natl Reference Malad Creutzfeldt Jakob, F-75013 Paris, France. [Laplanche, Jean-Louis; Bouaziz-Amar, Elodie] Hop Lariboisiere, AP HP, Serv Biochim & Biol Mol, F-75010 Paris, France. [Capellari, Sabina; Parchi, Piero] Inst Neurol Sci, IRCCS, I-40123 Bologna, Italy. [Capellari, Sabina; Parchi, Piero] Univ Bologna, Dept Biomed & Neuromotor Sci, I-40126 Bologna, Italy. [Poleggi, Anna; Ladogana, Anna] Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. [O'Donnell-Luria, Anne H.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. [Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio 70210, Finland. [Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Mohlke, Karen L.; Sullivan, Patrick F.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA. [Kahler, Anna; Sullivan, Patrick F.; Hultman, Christina M.] Karolinska Inst, SE-17177 Stockholm, Sweden. [McCarroll, Steven] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [van der Lee, Sven J.; Hofman, Albert; Ikram, M. Arfan; Uitterlinden, Andre G.; van Duijn, Cornelia M.] Erasmus Med Ctr MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Rozemuller, Annemieke; Jansen, Casper] Univ Med Ctr, Dept Pathol, Dutch Surveillance Ctr Pr Dis, NL-3584 CX Utrecht, Netherlands. [Kraaij, Robert; van Rooij, Jeroen G. J.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. RP Minikel, EV; MacArthur, DG (reprint author), Broad Inst Massachusetts Inst Technol MIT & Harva, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Minikel, EV; MacArthur, DG (reprint author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.; Minikel, EV (reprint author), Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. EM eminikel@broadinstitute.org; macarthur@atgu.mgh.harvard.edu RI Giese, Armin/F-3271-2010; Ladogana, Anna/K-1415-2016; Ruderfer, Douglas/M-5795-2016; Calero, Miguel/H-5691-2015; Parchi, Piero/L-9833-2015; LAPLANCHE, Jean-Louis/S-8707-2016; OI Giese, Armin/0000-0002-8238-4102; Ruderfer, Douglas/0000-0002-2365-386X; Calero, Miguel/0000-0001-5366-3324; Parchi, Piero/0000-0002-9444-9524; O'Donnell-Luria, Anne/0000-0001-6418-9592; Karczewski, Konrad/0000-0003-2878-4671; Ware, James/0000-0002-6110-5880 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences of the NIH [U54DK105566, R01GM104371]; Broad Institute NextGen funds; Prion Alliance sundry funds; National Science Foundation Graduate Research Fellowship Program [2015214731]; Centers for Disease Control and Prevention [UR8/CCU515004]; Research Committee of Prion Disease and Slow Virus Infection; Research Committee of Surveillance and Infection Control of Prion Disease of the Ministry of Health, Labour and Welfare of Japan; Institut National de veille Sanitaire; Robert Koch Institute/Federal Ministry of Health [1369-341]; Department of Health; Scottish Executive; Commonwealth Department of Health; National Health and Medical Research Council Practitioner Fellowship [APP1005816]; Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research-Netherlands Consortium for Healthy Aging [050-060-810]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; Complementation Project of the Biobanking and Biomolecular Research Infrastructure Netherlands [CP2010-41]; Netherlands Organisation for Health Research and Development (ZonMw Middelgroot) [91111025]; Netherlands Organization for the Health Research and Development; Research Institute for Diseases in the Elderly; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (Directorate-General for Science, Research and Development); Municipality of Rotterdam; Erasmus MC; Erasmus University, Rotterdam FX Research reported in this publication was partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of General Medical Sciences of the NIH (awards U54DK105566 and R01GM104371), by Broad Institute NextGen funds, and by Prion Alliance sundry funds. S.M.V. is supported by the National Science Foundation Graduate Research Fellowship Program (grant 2015214731). U.S. prion surveillance work was conducted under Centers for Disease Control and Prevention (contract UR8/CCU515004). Japanese prion surveillance work was supported by a grant-in-aid from the Research Committee of Prion Disease and Slow Virus Infection and the Research Committee of Surveillance and Infection Control of Prion Disease of the Ministry of Health, Labour and Welfare of Japan. The French prion surveillance network is supported by the Institut National de veille Sanitaire. The German prion surveillance work was supported by Robert Koch Institute/Federal Ministry of Health (grant 1369-341). The UK National Creutzfeldt Jakob Disease Research and Surveillance Unit is supported by the Department of Health and the Scottish Executive. The Australian National Creutzfeldt-Jakob Disease Registry is funded by the Commonwealth Department of Health. S.J.C. is supported by a National Health and Medical Research Council Practitioner Fellowship (identification number APP1005816). Contributions at Erasmus Medical Center (MC) were supported by Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research-sponsored Netherlands Consortium for Healthy Aging (project 050-060-810); by the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; by a Complementation Project of the Biobanking and Biomolecular Research Infrastructure Netherlands (www.bbmri.nl; project number CP2010-41); and by Erasmus MC and Erasmus University, Rotterdam, Netherlands Organisation for Health Research and Development (ZonMw Middelgroot #91111025), Netherlands Organization for the Health Research and Development, the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (Directorate-General for Science, Research and Development), and the Municipality of Rotterdam. NR 178 TC 23 Z9 23 U1 4 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 20 PY 2016 VL 8 IS 322 AR 322ra9 DI 10.1126/scitranslmed.aad5169 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DB4VI UT WOS:000368511300005 PM 26791950 ER PT J AU Sudore, R Le, GM McMahan, R Feuz, M Katen, M Barnes, DE AF Sudore, Rebecca Le, Gem M. McMahan, Ryan Feuz, Mariko Katen, Mary Barnes, Deborah E. TI The advance care planning PREPARE study among older Veterans with serious and chronic illness: study protocol for a randomized controlled trial (vol 16, 570, 2015) SO TRIALS LA English DT Correction C1 [Sudore, Rebecca; Le, Gem M.; Barnes, Deborah E.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Sudore, Rebecca; McMahan, Ryan; Feuz, Mariko; Katen, Mary] San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. [Le, Gem M.] Univ Calif San Francisco, San Francisco Gen Hosp, Ctr Vulnerable Populat, Div Gen Internal Med, San Francisco, CA 94110 USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Sudore, R (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, 3333 Calif St Suite 380, San Francisco, CA 94143 USA. EM rebecca.sudore@ucsf.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD JAN 20 PY 2016 VL 17 AR 42 DI 10.1186/s13063-016-1182-y PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DB3HA UT WOS:000368399700006 PM 26791078 ER PT J AU McQuaid, HN Muir, MF Taggart, LE McMahon, SJ Coulter, JA Hyland, WB Jain, S Butterworth, KT Schettino, G Prise, KM Hirst, DG Botchway, SW Currell, FJ AF McQuaid, Harold N. Muir, Mark F. Taggart, Laura E. McMahon, Stephen J. Coulter, Jonathan A. Hyland, Wendy B. Jain, Suneil Butterworth, Karl T. Schettino, Giuseppe Prise, Kevin M. Hirst, David G. Botchway, Stanley W. Currell, Fred J. TI Imaging and radiation effects of gold nanoparticles in tumour cells SO SCIENTIFIC REPORTS LA English DT Article ID MONTE-CARLO-SIMULATION; NUCLEAR-PORE COMPLEX; DOSE ENHANCEMENT; LIQUID WATER; X-RAYS; RADIOSENSITIZATION; THERAPY; ENERGY; DNA; LOCALIZATION AB Gold nanoparticle radiosensitization represents a novel technique in enhancement of ionising radiation dose and its effect on biological systems. Variation between theoretical predictions and experimental measurement is significant enough that the mechanism leading to an increase in cell killing and DNA damage is still not clear. We present the first experimental results that take into account both the measured biodistribution of gold nanoparticles at the cellular level and the range of the product electrons responsible for energy deposition. Combining synchrotron-generated monoenergetic X-rays, intracellular gold particle imaging and DNA damage assays, has enabled a DNA damage model to be generated that includes the production of intermediate electrons. We can therefore show for the first time good agreement between the prediction of biological outcomes from both the Local Effect Model and a DNA damage model with experimentally observed cell killing and DNA damage induction via the combination of X-rays and GNPs. However, the requirement of two distinct models as indicated by this mechanistic study, one for short-term DNA damage and another for cell survival, indicates that, at least for nanoparticle enhancement, it is not safe to equate the lethal lesions invoked in the local effect model with DNA damage events. C1 [McQuaid, Harold N.; Currell, Fred J.] Queens Univ Belfast, Sch Math & Phys, Ctr Plasma Phys, Belfast BT7 1NN, Antrim, North Ireland. [Muir, Mark F.] Camlin Technol Ltd, Lisburn BT28 2EX, North Ireland. [Taggart, Laura E.; McMahon, Stephen J.; Jain, Suneil; Butterworth, Karl T.; Prise, Kevin M.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland. [McMahon, Stephen J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [McMahon, Stephen J.] Harvard Univ, Sch Med, Boston, MA USA. [Coulter, Jonathan A.; Hirst, David G.] Queens Univ Belfast, Sch Pharm, Belfast BT9 7BL, Antrim, North Ireland. [Hyland, Wendy B.; Jain, Suneil] Belfast Hlth & Social Care Trust, Northern Ireland Canc Ctr, Belfast BT9 7AB, Antrim, North Ireland. [Schettino, Giuseppe] Natl Phys Lab, Teddington TW11 0LW, Middx, England. [Botchway, Stanley W.] Rutherford Appleton Lab, Sci & Technol Facil Council, Cent Laser Facil, Didcot OX11 0QX, Oxon, England. RP Currell, FJ (reprint author), Queens Univ Belfast, Sch Math & Phys, Ctr Plasma Phys, Belfast BT7 1NN, Antrim, North Ireland. EM f.j.currell@qub.ac.uk RI Prise, Kevin/N-7872-2015; OI Prise, Kevin/0000-0001-6134-7946; jain, suneil/0000-0001-7429-4791 FU Medical Research Council [G0502183] NR 38 TC 6 Z9 6 U1 7 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 20 PY 2016 VL 6 AR 19442 DI 10.1038/srep19442 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB2PR UT WOS:000368352000001 PM 26787230 ER PT J AU Wilson, NR Olm-Shipman, AJ Acevedo, DS Palaniyandi, K Hall, EG Kosa, E Stumpff, KM Smith, GJ Pitstick, L Liao, EC Bjork, BC Czirok, A Saadi, I AF Wilson, Nathan R. Olm-Shipman, Adam J. Acevedo, Diana S. Palaniyandi, Kanagaraj Hall, Everett G. Kosa, Edina Stumpff, Kelly M. Smith, Guerin J. Pitstick, Lenore Liao, Eric C. Bjork, Bryan C. Czirok, Andras Saadi, Irfan TI SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination SO SCIENTIFIC REPORTS LA English DT Article ID TUBE CLOSURE; CRANIOFACIAL DEVELOPMENT; MESENCHYMAL TRANSITION; EMBRYONIC LETHALITY; MOUSE MUTANTS; DEFECTS; MICE; GENE; ACTIVATION; MIGRATION AB Cranial neural crest cells (CNCCs) delaminate from embryonic neural folds and migrate to pharyngeal arches, which give rise to most mid-facial structures. CNCC dysfunction plays a prominent role in the etiology of orofacial clefts, a frequent birth malformation. Heterozygous mutations in SPECC1L have been identified in patients with atypical and syndromic clefts. Here, we report that in SPECC1L-knockdown cultured cells, staining of canonical adherens junction (AJ) components, beta-catenin and E-cadherin, was increased, and electron micrographs revealed an apico-basal diffusion of AJs. To understand the role of SPECC1L in craniofacial morphogenesis, we generated a mouse model of Specc1l deficiency. Homozygous mutants were embryonic lethal and showed impaired neural tube closure and CNCC delamination. Staining of AJ proteins was increased in the mutant neural folds. This AJ defect is consistent with impaired CNCC delamination, which requires AJ dissolution. Further, PI3K-AKT signaling was reduced and apoptosis was increased in Specc1l mutants. In vitro, moderate inhibition of PI3K-AKT signaling in wildtype cells was sufficient to cause AJ alterations. Importantly, AJ changes induced by SPECC1L-knockdown were rescued by activating the PI3K-AKT pathway. Together, these data indicate SPECC1L as a novel modulator of PI3K-AKT signaling and AJ biology, required for neural tube closure and CNCC delamination. C1 [Wilson, Nathan R.; Olm-Shipman, Adam J.; Acevedo, Diana S.; Palaniyandi, Kanagaraj; Hall, Everett G.; Kosa, Edina; Stumpff, Kelly M.; Smith, Guerin J.; Czirok, Andras; Saadi, Irfan] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA. [Pitstick, Lenore; Bjork, Bryan C.] Midwestern Univ, Dept Biochem, Downers Grove, IL 60515 USA. [Liao, Eric C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Div Plast & Reconstruct Surg, Boston, MA USA. RP Saadi, I (reprint author), Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA. EM isaadi@kumc.edu OI Saadi, Irfan/0000-0002-6250-6651 FU National Institutes of Health Center of Biomedical Research Excellence (COBRE) grant (National Institute of General Medical Sciences) [P20 GM104936]; Kansas IDeA Network for Biomedical Research Excellence grant (National Institute of General Medical Sciences) [P20 GM103418]; Kansas Intellectual and Developmental Disabilities Research Center grant (P30 Eunice Kennedy Shriver National Institute of Child Health and Human Development) [HD 002528]; COBRE grant [P20 GM104936]; NIH [S10RR027564] FX This project was supported in part by the National Institutes of Health Center of Biomedical Research Excellence (COBRE) grant (National Institute of General Medical Sciences P20 GM104936, I.S.), Kansas IDeA Network for Biomedical Research Excellence grant (National Institute of General Medical Sciences P20 GM103418, I.S.), Kansas Intellectual and Developmental Disabilities Research Center grant (P30 Eunice Kennedy Shriver National Institute of Child Health and Human Development, HD 002528, I.S.). We wish to acknowledge the Electron Microscopy Research Lab (EMRL) facility for assistance with the electron microscopy. The EMRL is also supported in part by COBRE grant P20 GM104936. The JEOL JEM-1400 TEM used in the study was purchased with funds from NIH grant S10RR027564. NR 51 TC 1 Z9 1 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 20 PY 2016 VL 6 AR 17735 DI 10.1038/srep17735 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB2OG UT WOS:000368348300001 PM 26787558 ER PT J AU Bahram, F Hydbring, P Tronnersjo, S Zakaria, SM Frings, O Fahlen, S Nilsson, H Goodwin, J von der Lehr, N Su, YT Luscher, B Castell, A Larsson, LG AF Bahram, Fuad Hydbring, Per Tronnersjo, Susanna Zakaria, Siti Mariam Frings, Oliver Fahlen, Sara Nilsson, Helen Goodwin, Jacob von der Lehr, Natalie Su, Yingtao Luescher, Bernhard Castell, Alina Larsson, Lars-Gunnar TI Interferon-gamma-induced p27(KIP1) binds to and targets MYC for proteasome-mediated degradation SO ONCOTARGET LA English DT Article DE oncogene; tumor suppressor gene; ubiquitin-proteasome system; interferon-gamma; the cancer genome atlas ID C-MYC; CDK INHIBITORS; CELL-CYCLE; POSTTRANSLATIONAL REGULATION; INDUCED-DIFFERENTIATION; PROTEIN STABILITY; U-937 MONOBLASTS; BREAST-CANCER; IFN-GAMMA; P27 AB The Myc oncoprotein is tightly regulated at multiple levels including ubiquitin-mediated protein turnover. We recently demonstrated that inhibition of Cdk2-mediated phosphorylation of Myc at Ser-62 pharmacologically or through interferon (IFN)-gamma-induced expression of p27(Kip1) (p27) repressed Myc's activity to suppress cellular senescence and differentiation. In this study we identified an additional activity of p27 to interfere with Myc independent of Ser-62 phosphorylation. p27 is required and sufficient for IFN-gamma-induced turnover of Myc. p27 interacted with Myc in the nucleus involving the C-termini of the two proteins, including Myc box 4 of Myc. The C-terminus but not the Cdk2 binding fragment of p27 was sufficient for inducing Myc degradation. Protein expression data of The Cancer Genome Atlas breast invasive carcinoma set revealed significantly lower Myc protein levels in tumors with highly expressed p27 lacking phosphorylation at Thr-157 - a marker for active p27 localized in the nucleus. Further, these conditions correlated with favorable tumor stage and patient outcome. This novel regulation of Myc by IFN-gamma/p27(KIP1) potentially offers new possibilities for therapeutic intervention in tumors with deregulated Myc. C1 [Bahram, Fuad; Hydbring, Per; Tronnersjo, Susanna; Zakaria, Siti Mariam; Fahlen, Sara; Nilsson, Helen; Goodwin, Jacob; Su, Yingtao; Castell, Alina; Larsson, Lars-Gunnar] Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden. [Bahram, Fuad; von der Lehr, Natalie] Swedish Univ Agr Sci, Dept Plant Biol & Forest Genet, SE-75007 Uppsala, Sweden. [Frings, Oliver] Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, SE-17176 Stockholm, Sweden. [Luescher, Bernhard] Rhein Westfal TH Aachen, Inst Biochem & Mol Biol, Sch Med, D-52057 Aachen, Germany. [Bahram, Fuad] Moreinx AB, S-75185 Uppsala, Sweden. [Hydbring, Per] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Tronnersjo, Susanna] GE Healthcare, S-75323 Uppsala, Sweden. [Fahlen, Sara] Karolinska Inst, Swedish Med Nanosci Ctr, Dept Neurosci, S-17177 Stockholm, Sweden. [Nilsson, Helen] Lund Univ, Ctr Mol Pathol, Lund, Sweden. [von der Lehr, Natalie] NatScience, S-75237 Uppsala, Sweden. [Su, Yingtao] Anxun Int Co Ltd, Hong Kong, Hong Kong, Peoples R China. RP Larsson, LG (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden. EM Lars-Gunnar.Larsson@ki.se FU Swedish Cancer Society; Swedish Research Council; Swedish Childhood Cancer Society; Human Frontiers Science Program; Karolinska Institutet Foundations FX This work was supported by the Swedish Cancer Society, the Swedish Research Council, the Swedish Childhood Cancer Society, Human Frontiers Science Program and the Karolinska Institutet Foundations. NR 67 TC 1 Z9 1 U1 3 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 19 PY 2016 VL 7 IS 3 BP 2837 EP 2854 PG 18 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DD5GV UT WOS:000369951800051 PM 26701207 ER PT J AU Singhal, SK Usmani, N Michiels, S Metzger-Filho, O Saini, KS Kovalchuk, O Parliament, M AF Singhal, Sandeep K. Usmani, Nawaid Michiels, Stefan Metzger-Filho, Otto Saini, Kamal S. Kovalchuk, Olga Parliament, Matthew TI Towards understanding the breast cancer epigenome: a comparison of genome-wide DNA methylation and gene expression data SO ONCOTARGET LA English DT Article DE DNA methylation; breast cancer; epigenetics; expression; microarray ID MOLECULAR SUBTYPES; EPIGENETIC MARK; RANDOM FORESTS; HUMAN-DISEASE; 5-HYDROXYMETHYLCYTOSINE; PATTERNS; 5-METHYLCYTOSINE; PROFILES; CPG; CARCINOGENESIS AB Until recently, an elevated disease risk has been ascribed to a genetic predisposition, however, exciting progress over the past years has discovered alternate elements of inheritance that involve epigenetic regulation. Epigenetic changes are heritably stable alterations that include DNA methylation, histone modifications and RNA-mediated silencing. Aberrant DNA methylation is a common molecular basis for a number of important human diseases, including breast cancer. Changes in DNA methylation profoundly affect global gene expression patterns. What is emerging is a more dynamic and complex association between DNA methylation and gene expression than previously believed. Although many tools have already been developed for analyzing genome-wide gene expression data, tools for analyzing genome-wide DNA methylation have not yet reached the same level of refinement. Here we provide an in-depth analysis of DNA methylation in parallel with gene expression data characteristics and describe the particularities of low-level and high-level analyses of DNA methylation data. Low-level analysis refers to pre-processing of methylation data (i.e. normalization, transformation and filtering), whereas high-level analysis is focused on illustrating the application of the widely used class comparison, class prediction and class discovery methods to DNA methylation data. Furthermore, we investigate the influence of DNA methylation on gene expression by measuring the correlation between the degree of CpG methylation and the level of expression and to explore the pattern of methylation as a function of the promoter region. C1 [Singhal, Sandeep K.; Usmani, Nawaid; Parliament, Matthew] Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB, Canada. [Michiels, Stefan] Inst Gustave Roussy, Serv Biostat & Epidemiol, Villejuif, France. [Michiels, Stefan] Univ Paris 11, INSERM, CESP, U1018, Villejuif, France. [Metzger-Filho, Otto] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Saini, Kamal S.] Quantum Hlth Analyt SPRL, Liege, Belgium. [Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Kovalchuk, Olga] Canada Canc & Aging Res Labs Ltd, Lethbridge, AB, Canada. RP Parliament, M (reprint author), Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB, Canada.; Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada.; Kovalchuk, O (reprint author), Canada Canc & Aging Res Labs Ltd, Lethbridge, AB, Canada. EM olga.kovalchuk@uleth.ca; matthew.parliament@albertahealthservices.ca RI Michiels, Stefan/L-1516-2013 OI Michiels, Stefan/0000-0002-6963-2968 NR 77 TC 0 Z9 0 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 19 PY 2016 VL 7 IS 3 BP 3002 EP 3017 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DD5GV UT WOS:000369951800062 PM 26657508 ER PT J AU Singh, JA Schleck, C Harmsen, WS Lewallen, DG AF Singh, Jasvinder A. Schleck, Cathy Harmsen, W. Scott Lewallen, David G. TI Validation of the Mayo Hip Score: construct validity, reliability and responsiveness to change SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Validation; Mayo hip score; Mayo hip questionnaire; Total hip arthroplasty; Total hip replacement; Validity; Responsiveness; Minimal clinically meaningful difference; MCID; Revision risk; Reliability ID REPLACEMENT CLINICAL-TRIALS; KNEE ARTHROPLASTY; OUTCOME MEASURES; HARRIS HIP; PREDICTORS; COMORBIDITY AB Background: Previous studies have provided the initial evidence for construct validity and test-retest reliability of the Mayo Hip Score. Instruments used for Total Hip Arthroplasty (THA) outcomes assessment should be valid, reliable and responsive to change. Our main objective was to examine the responsiveness to change, association with subsequent revision and the construct validity of the Mayo hip score. Methods: Discriminant ability was assessed by calculating effect size (ES), standardized response mean (SRM) and Guyatt's responsiveness index (GRI). Minimal clinically important difference (MCII) and moderate improvement thresholds were calculated. We assessed construct validity by examining association of scores with preoperative patient characteristics and correlation with Harris hip score, and assessed association of scores with the risk of subsequent revision. Results: Five thousand three hundred seven provided baseline data; of those with baseline data, 2,278 and 2,089 (39 %) provided 2- and 5-year data, respectively. Large ES, SRM and GRI ranging 2.66-2.78, 2.42-2.61 and 1.67-1.88 were noted for Mayo hip scores with THA, respectively. The MCII and moderate improvement thresholds were 22.4-22.7 and 39.4-40.5 respectively. Hazard ratios of revision surgery were higher with lower final score or less improvement in Mayo hip score at 2-years and borderline significant/non-significant at 5-years, respectively: (1) score <= 55 with hazard ratios of 2.24 (95 % CI, 1.45, 3.46; p = 0.0003) and 1.70 (95 % CI, 1.00, 2.92; p = 0.05) of implant revision subsequently, compared to 72-80 points; (2) no improvement or worsening score with hazard ratios 3.94 (95 % CI, 1.50, 10.30; p = 0.005) and 2.72 (95 % CI, 0.85,8.70; p = 0.09), compared to improvement >50-points. Mayo hip score had significant positive correlation with younger age, male gender, lower BMI, lower ASA class and lower Deyo-Charlson index (p <= 0.003 for each) and with Harris hip scores (p < 0.001). Conclusions: Mayo Hip Score is valid, sensitive to change and associated with future risk of revision surgery in patients with primary THA. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Dept Orthoped Surg, Sch Med, Rochester, MN USA. [Schleck, Cathy; Harmsen, W. Scott] Mayo Clin, Sch Med, Dept Biostat, Rochester, MN USA. [Singh, Jasvinder A.; Lewallen, David G.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Univ Alabama Birmingham, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Mayo Clin, Dept Orthoped Surg, Sch Med, Rochester, MN USA.; Singh, JA (reprint author), Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Department of Orthopedic Surgery, Mayo Clinic School of Medicine, Rochester, MN, USA FX We thank Youlonda Lochler for her assistance in data abstraction from the Mayo Clinic Total Joint Registry for this project. This material is the result of work supported by the Department of Orthopedic Surgery, Mayo Clinic School of Medicine, Rochester, MN, USA. JAS is also supported by the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, USA. NR 26 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD JAN 19 PY 2016 VL 17 AR 39 DI 10.1186/s12891-016-0868-3 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA DB4IC UT WOS:000368475700001 PM 26785640 ER PT J AU Kim, SA Inamura, K Yamauchi, M Nishihara, R Mima, K Sukawa, Y Li, TT Yasunari, M Morikawa, T Fitzgerald, KC Fuchs, CS Wu, KN Chan, AT Zhang, XH Ogino, S Qian, ZR AF Kim, Sun A. Inamura, Kentaro Yamauchi, Mai Nishihara, Reiko Mima, Kosuke Sukawa, Yasutaka Li, Tingting Yasunari, Mika Morikawa, Teppei Fitzgerald, Kathryn C. Fuchs, Charles S. Wu, Kana Chan, Andrew T. Zhang, Xuehong Ogino, Shuji Qian, Zhi Rong TI Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis SO BRITISH JOURNAL OF CANCER LA English DT Article DE colorectum; epithelial-mesenchymal transition; neoplasm invasiveness ID ISLAND METHYLATOR PHENOTYPE; ADVANCED COLORECTAL-CANCER; POPULATION-BASED SAMPLE; MICROSATELLITE INSTABILITY; BETA-CATENIN; PROGNOSTIC-SIGNIFICANCE; BORDER CONFIGURATION; RECTAL-CANCER; BRAF MUTATION; COLON-CANCER AB Background: Loss of CDH1 (E-cadherin) expression in cancer cells may promote cell migration and invasion. Therefore, we hypothesised that loss of CDH1 expression in colorectal carcinoma might be associated with aggressive features and clinical outcome. Methods: Utilising molecular pathological epidemiology database of 689 rectal and colon cancer cases in the Nurses' Health Study and the Health Professionals Follow-up Study, we assessed tumour CDH1 expression by immunohistochemistry. Multivariate logistic regression analysis was conducted to assess association of CDH1 loss with tumour growth pattern (expansile-intermediate vs infiltrative) and lymph node metastasis and distant metastasis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and PIK3CA, BRAF and KRAS mutations. Mortality according to CDH1 status was assessed using Cox proportional hazards model. Results: Loss of tumour CDH1 expression was observed in 356 cases (52%), and associated with infiltrative tumour growth pattern (odds ratio (OR), 2.02; 95% confidence interval (CI), 1.23-3.34; P = 0.006) and higher pN stage (OR, 1.73; 95% CI, 1.23-2.43; P = 0.001). Tumour CDH1 expression was not significantly associated with distant metastasis or prognosis. Conclusions: Loss of CDH1 expression in colorectal cancer is associated with infiltrative tumour growth pattern and lymph node metastasis. C1 [Kim, Sun A.; Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko; Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Fuchs, Charles S.; Ogino, Shuji; Qian, Zhi Rong] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave M420, Boston, MA 02215 USA. [Kim, Sun A.; Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko; Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Fuchs, Charles S.; Ogino, Shuji; Qian, Zhi Rong] Harvard Univ, Sch Med, 450 Brookline Ave M420, Boston, MA 02215 USA. [Inamura, Kentaro] NCI, Lab Human Carcinogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Nishihara, Reiko; Wu, Kana] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, 655 Huntington Ave Bldg 2,Room 213, Boston, MA 02115 USA. [Li, Tingting] Chinese Peoples Liberat Army Gen Hosp, Dept Geriatr Gastroenterol, 28 Fuxing Rd, Beijing 100853, Peoples R China. [Morikawa, Teppei] Tokyo Univ Hosp, Dept Pathol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. [Fitzgerald, Kathryn C.; Ogino, Shuji] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, 655 Huntington Ave, Boston, MA 02115 USA. [Fuchs, Charles S.; Chan, Andrew T.; Zhang, Xuehong] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 29 Wigglesworth St, Boston, MA 02120 USA. [Fuchs, Charles S.; Chan, Andrew T.; Zhang, Xuehong] Harvard Univ, Sch Med, 29 Wigglesworth St, Boston, MA 02120 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,GRJ-722, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, 55 Fruit St,GRJ-722, Boston, MA 02114 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 29 Wigglesworth St, Boston, MA 02120 USA. [Ogino, Shuji] Harvard Univ, Sch Med, 29 Wigglesworth St, Boston, MA 02120 USA. RP Ogino, S; Qian, ZR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave M420, Boston, MA 02215 USA.; Ogino, S; Qian, ZR (reprint author), Harvard Univ, Sch Med, 450 Brookline Ave M420, Boston, MA 02215 USA.; Ogino, S (reprint author), Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, 655 Huntington Ave, Boston, MA 02115 USA.; Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 29 Wigglesworth St, Boston, MA 02120 USA.; Ogino, S (reprint author), Harvard Univ, Sch Med, 29 Wigglesworth St, Boston, MA 02120 USA. EM shuji_ogino@dfci.harvard.edu; zhirong_qian@dfci.harvard.edu FU U.S. National Institutes of Health (NIH) [K07 CA190673, R01 CA137178, K24 DK098311, P50 CA127003, R01 CA151993, R35 CA197735, P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552]; Paula and Russell Agrusa Fund for Colorectal Cancer Research; Friends of the Dana-Farber Cancer Institute; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Asan Medical Center, Korea; Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad; Takashi Tsuruo Memorial Fund, Japan; Uehara Memorial Foundation, Japan FX This work was supported by U.S. National Institutes of Health (NIH) grants (K07 CA190673 to RN; R01 CA137178 and K24 DK098311 to ATC; P50 CA127003 to CSF; R01 CA151993 and R35 CA197735 to SO; P01 CA87969 and UM1 CA186107 to Meir J Stampfer, Nurse's Health Study; P01 CA55075 and UM1 CA167552 to Walter C Willett, Health Professional's Follow-up Study); grants from the Paula and Russell Agrusa Fund for Colorectal Cancer Research, the Friends of the Dana-Farber Cancer Institute, the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. SAK was supported by an early exchange postdoctoral fellowship grant from Asan Medical Center, Korea. KI was supported by a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad and by Takashi Tsuruo Memorial Fund, Japan. KM was supported by a fellowship grant from the Uehara Memorial Foundation, Japan. ATC is a Damon Runyon Clinical Investigator. We would like to thank the participants and staff of the Nurses' Health Study and the Health Professionals Follow-up Study for their valuable contributions, as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Use of standardised official symbols: We use HUGO (Human Genome Organisation)-approved official symbols for genes and gene products, including BRAF; CDH1 (so-called E-cadherin); CTNNB1 (catenin (cadherin-associated protein), beta 1, 88kDa; so-called beta-catenin); KRAS; and PIK3CA; all of which are described at www.genenames.org. NR 38 TC 2 Z9 3 U1 5 U2 6 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 JAN 19 PY 2016 VL 114 IS 2 BP 199 EP 206 DI 10.1038/bjc.2015.347 PG 8 WC Oncology SC Oncology GA DB5NV UT WOS:000368561800010 PM 26742007 ER PT J AU Garcia-Albeniz, X Rudolph, A Hutter, C White, E Lin, Y Rosse, SA Figueiredo, JC Harrison, TA Jiao, S Brenner, H Casey, G Hudson, TJ Thornquist, M Le Marchand, L Potter, J Slattery, ML Zanke, B Baron, JA Caan, BJ Chanock, SJ Berndt, SI Stelling, D Fuchs, CS Hoffmeister, M Butterbach, K Du, MM Gauderman, WJ Gunter, MJ Lemire, M Ogino, S Lin, J Hayes, RB Haile, RW Schoen, RE SWarnick, G Jenkins, MA Thibodeau, SN Schumacher, FR Lindor, NM Kolonel, LN Hopper, JL Gong, J Seminara, D Pflugeisen, BM Ulrich, CM Qu, CH Duggan, D Cotterchio, M Campbell, PT Carlson, CS Newcomb, PA Giovannucci, E Hsu, L Chan, AT Peters, U Chang-Claude, J AF Garcia-Albeniz, Xabier Rudolph, Anja Hutter, Carolyn White, Emily Lin, Yi Rosse, Stephanie A. Figueiredo, Jane C. Harrison, Tabitha A. Jiao, Shuo Brenner, Hermann Casey, Graham Hudson, Thomas J. Thornquist, Mark Le Marchand, Loic Potter, John Slattery, Martha L. Zanke, Brent Baron, John A. Caan, Bette J. Chanock, Stephen J. Berndt, Sonja I. Stelling, Deanna Fuchs, Charles S. Hoffmeister, Michael Butterbach, Katja Du, Mengmeng Gauderman, W. James Gunter, Marc J. Lemire, Mathieu Ogino, Shuji Lin, Jennifer Hayes, Richard B. Haile, Robert W. Schoen, Robert E. SWarnick, Greg Jenkins, Mark A. Thibodeau, Stephen N. Schumacher, Fredrick R. Lindor, Noralane M. Kolonel, Laurence N. Hopper, John L. Gong, Jian Seminara, Daniela Pflugeisen, Bethann M. Ulrich, Cornelia M. Qu, Conghui Duggan, David Cotterchio, Michelle Campbell, Peter T. Carlson, Christopher S. Newcomb, Polly A. Giovannucci, Edward Hsu, Li Chan, Andrew T. Peters, Ulrike Chang-Claude, Jenny TI CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk SO BRITISH JOURNAL OF CANCER LA English DT Article DE GWAS; colorectal cancer; menopausal hormone therapy; polymorphisms; gene-environment interaction; cytochrome P450 ID GENOME-WIDE ASSOCIATION; GENE-ENVIRONMENT INTERACTION; POSTMENOPAUSAL HORMONE-THERAPY; COLON-CANCER; SUSCEPTIBILITY LOCI; REPLACEMENT THERAPY; RECTAL-CANCER; WOMEN; HEALTH; METAANALYSIS AB Background: Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT. Methods: We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test. Results: The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs) = 0.61 (0.52-0.72), P = 4.8 x 10(-9)). The secondary analysis also identified this interaction (Cocktail test OR = 0.64 (0.52-0.78), P = 1.2 x 10(-5) (alpha threshold = 3.1 x 10(-4)). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively. Conclusions: Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis. C1 [Garcia-Albeniz, Xabier; Fuchs, Charles S.; Ogino, Shuji; Giovannucci, Edward] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Garcia-Albeniz, Xabier; Lin, Jennifer; Giovannucci, Edward; Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Rudolph, Anja; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Hutter, Carolyn; Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [White, Emily; Lin, Yi; Rosse, Stephanie A.; Harrison, Tabitha A.; Jiao, Shuo; Thornquist, Mark; Potter, John; Stelling, Deanna; Du, Mengmeng; SWarnick, Greg; Gong, Jian; Ulrich, Cornelia M.; Carlson, Christopher S.; Newcomb, Polly A.; Hsu, Li; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [White, Emily; Lin, Yi; Rosse, Stephanie A.; Harrison, Tabitha A.; Jiao, Shuo; Thornquist, Mark; Potter, John; Stelling, Deanna; Du, Mengmeng; SWarnick, Greg; Gong, Jian; Carlson, Christopher S.; Newcomb, Polly A.; Hsu, Li; Peters, Ulrike] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA. [Figueiredo, Jane C.; Casey, Graham; Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Brenner, Hermann; Hoffmeister, Michael; Butterbach, Katja] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Brenner, Hermann; Ulrich, Cornelia M.] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany. [Brenner, Hermann; Ulrich, Cornelia M.] Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Brenner, Hermann] German Canc Consortium DKTK, D-69120 Heidelberg, Germany. [Hudson, Thomas J.; Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Epidemiol Program, Ctr Canc, Honolulu, HI 96813 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT 84132 USA. [Zanke, Brent] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON K1Y 4E9, Canada. [Baron, John A.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA. [Caan, Bette J.] Kaiser Permanente, Div Res, Med Care Program, Oakland, CA 94612 USA. [Chanock, Stephen J.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Fuchs, Charles S.; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Gauderman, W. James] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Gunter, Marc J.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England. [Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY 10016 USA. [Haile, Robert W.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA 15213 USA. [Jenkins, Mark A.; Hopper, John L.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic 3010, Australia. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med, Scottsdale, AZ 85259 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Pathol, Scottsdale, AZ 85259 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Genet, Scottsdale, AZ 85259 USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA. [Pflugeisen, Bethann M.; Qu, Conghui] Fred Hutchinson Canc Res Ctr, Dept Canc Prevent, Seattle, WA 98109 USA. [Ulrich, Cornelia M.] Univ Utah, Dept Populat Sci, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Duggan, David] Translat Genom Res Inst Tgen, Phoenix, AZ 85004 USA. [Cotterchio, Michelle] Canc Care Ontario, Prevent & Canc Control, Toronto, ON M5G 2L7, Canada. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, UCCH, D-20246 Hamburg, Germany. RP Chan, AT (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Chang-Claude, J (reprint author), German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.; Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA.; Peters, U (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA. EM achan@partners.org; upeters@fhcrc.org; j.chang-claude@dkfz.de RI Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; OI Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Hayes, Richard/0000-0002-0918-661X; Hoffmeister, Michael/0000-0002-8307-3197 FU National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; NCI [R25 CA094880, P30 CA008748]; National Institutes of Health (RFA) [CA-95-011]; National Cancer Institute, National Institutes of Health [U01 CA122839]; National Institutes of Health: Australasian Colorectal Cancer Family Registry [U01 CA097735]; National Institutes of Health: Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; National Institutes of Health: Seattle Colorectal Cancer Family Registry [U01 CA074794]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Institutes of Health [U01 CA074783, R01 CA48998, R01 CA137178, P01 CA 087969, P50 CA 127003, R37 CA54281, P01 CA033619, R01 CA63464]; GL2 grant from the Ontario Research Fund; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research, through Ontario Ministry of Research and Innovation; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) [Z01 CP 010200, U01 HG004446, U01 HG 004438]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201 100046C, HHSN268201100001C, HHSN268201100002C, HHSN2 68201100003C, HHSN268201100004C, HHSN271201100004C]; ASISA Fellowship; SEOM (Sociedad Espanola de Oncologia Medica) grant; NIDDK [K24DK098311]; [HL115606]; [R35 CA197735] FX DACHS: we thank all participants and cooperating clinicians, and Ute Handte-Daub, Renate Hettler-Jensen, Utz Benscheid, Muhabbet Celik and Ursula Eilber for excellent technical assistance. GECCO: we would like to thank all those at the GECCO Coordinating Center for helping bring together the data and people that made this project possible. NHS: we would like to acknowledge Patrice Soule and Hardeep Ranu of the Dana Farber Harvard Cancer Center High-Throughput Polymorphism Core who assisted in the genotyping for NHS under the supervision of Dr Immaculata Devivo and Dr David Hunter, Qin (Carolyn) Guo and Lixue Zhu who assisted in programming for NHS. We would like to thank the participants and staff of the Nurses' Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WY. PLCO: we thank Drs Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute; the Screening Center investigators and staff or the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial; Mr Tom Riley and staff, Information Management Services, Inc.; Ms Barbara O'Brien and staff, Westat, Inc.; and Drs Bill Kopp, Wen Shao and staff, SAIC-Frederick. Most importantly, we acknowledge the study participants for their contributions to making this study possible. PMH: we would like to thank the study participants and staff of the Hormones and Colon Cancer study. WHI: we thank the WHI investigators and staff for their dedication, and the study participants for making the programme possible. A full listing of WHI investigators can be found at: https://cleo.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20 Investigator%20Short%20List.pdf. Funding details are as follows: GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045). Mengmeng Du is supported by grants R25 CA094880 and P30 CA008748 from NCI. CCFR: National Institutes of Health (RFA # CA-95-011) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome-wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFRs, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the CFR. The following Colon CFR centres contributed data to this manuscript and were supported by National Institutes of Health: Australasian Colorectal Cancer Family Registry (U01 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783) and Seattle Colorectal Cancer Family Registry (U01 CA074794). DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). DALS: National Institutes of Health (R01 CA48998 to MLS); NHS is supported by the National Institutes of Health (R01 CA137178, P01 CA 087969 and P50 CA 127003). MEC: National Institutes of Health (R37 CA54281, P01 CA033619 and R01 CA63464).; OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. As subset of ARCTIC, OFCCR is supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. TJH and BZ are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. In addition, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS, Colon CGEMS pancreatic cancer scan (PanScan) and the Lung Cancer and Smoking study. The prostate and PanScan study data sets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207v.1p1 and phs000206.v3.p2, respectively, and the lung data sets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093 v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446 and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH: National Institutes of Health (R01 CA076366 to PAN). VITAL: National Institutes of Health (K05 CA154337). WHI: The WHI programme is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201 100046C, HHSN268201100001C, HHSN268201100002C, HHSN2 68201100003C, HHSN268201100004C and HHSN271201100004C. XG-A is a recipient of an ASISA Fellowship and SEOM (Sociedad Espanola de Oncologia Medica) grant. ATC is a Damon Runyon Clinical Investigator and is also supported by NIDDK K24DK098311. WJG is supported by grant #HL115606. SO is supported by grant R35 CA197735. NR 54 TC 2 Z9 2 U1 2 U2 7 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 JAN 19 PY 2016 VL 114 IS 2 BP 221 EP 229 DI 10.1038/bjc.2015.443 PG 9 WC Oncology SC Oncology GA DB5NV UT WOS:000368561800013 PM 26766742 ER PT J AU O'Donoghue, ML Bhatt, DL Stone, GW Steg, PG Gibson, CM Hamm, CW Price, MJ Prats, J Liu, T Deliargyris, EN Mahaffey, KW White, HD Harrington, RA AF O'Donoghue, Michelle L. Bhatt, Deepak L. Stone, Gregg W. Steg, Ph. Gabriel Gibson, C. Michael Hamm, Christian W. Price, Matthew J. Prats, Jayne Liu, Tiepu Deliargyris, Efthymios N. Mahaffey, Kenneth W. White, Harvey D. Harrington, Robert A. CA CHAMPION PHOENIX Investigators TI Efficacy and Safety of Cangrelor in Women Versus Men During Percutaneous Coronary Intervention Insights From the Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PHOENIX) Trial SO CIRCULATION LA English DT Article DE ADP receptor antagonist; cangrelor; clopidogrel; percutaneous coronary intervention ID RANDOMIZED CONTROLLED-TRIALS; ASSOCIATION TASK-FORCE; COLLABORATIVE METAANALYSIS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RECEPTOR ANTAGONIST; PRACTICE GUIDELINES; AMERICAN-COLLEGE; SEX; ASPIRIN AB Background Cangrelor is an intravenous ADP receptor antagonist that leads to potent and reversible inhibition of platelet aggregation. The relative safety and efficacy of some antiplatelet drugs in women has been disputed. Methods and Results The Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PHOENIX) trial randomized 11145 patients undergoing elective or urgent percutaneous coronary intervention to cangrelor or clopidogrel. The primary efficacy end point was the composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was GUSTO severe bleeding at 48 hours. Of subjects analyzed, 3051 (28%) were female. Cangrelor reduced the odds of the primary end point by 35% in women (adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.48-0.89) and by 14% in men (OR, 0.86; 95% CI, 0.70-1.05; P interaction=0.23) compared with clopidogrel. Cangrelor reduced the odds of stent thrombosis by 61% in women (OR, 0.39; 95% CI, 0.20-0.77) and 16% in men (OR, 0.84; 95% CI, 0.53-1.33; P interaction=0.11). The odds of severe bleeding were similar in both women and men treated with cangrelor (0.3% versus 0.2%, P=0.30 [women]; 0.1% versus 0.1%, P=0.41 [men]; P interaction=0.88) versus clopidogrel. Cangrelor increased the odds of moderate bleeding in women (0.9% versus 0.3%, P=0.02), but not in men (0.2% versus 0.2%, P=0.68; P interaction=0.040). The net clinical benefit (primary efficacy and safety end point) favored cangrelor in both women (OR, 0.68; 95% CI, 0.50-0.92) and men (OR, 0.87; 95% CI, 0.71-1.06; P interaction=0.26). Conclusions In CHAMPION PHOENIX, cangrelor reduced the odds of major adverse cardiovascular events and stent thrombosis in women and men and appeared to offer greater net clinical benefit than clopidogrel. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01156571. C1 [O'Donoghue, Michelle L.; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. [Stone, Gregg W.] Columbia Univ, Med Ctr, New York, NY USA. [Stone, Gregg W.] Cardiovasc Res Fdn, New York, NY USA. [Steg, Ph. Gabriel] Univ Paris Diderot, FACT, DHU FIRE, Sorbonne Paris Cite, Paris, France. [Steg, Ph. Gabriel] HUPNVS, LVTS INSERM U1148, Hop Bichat, AP HP, Paris, France. [Steg, Ph. Gabriel] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, NHLI, London, England. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Hamm, Christian W.] Kerckhoff Heart & Thorax Ctr, Bad Nauheim, Germany. [Price, Matthew J.] Scripps Clin, La Jolla, CA 92037 USA. [Price, Matthew J.] Scripps Translat Sci Inst, La Jolla, CA USA. [Prats, Jayne; Liu, Tiepu; Deliargyris, Efthymios N.] Medicines Co, Parsippany, NJ USA. [Mahaffey, Kenneth W.; Harrington, Robert A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [White, Harvey D.] Green Lane Cardiovasc Serv, Auckland, New Zealand. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM modonoghue@partners.org FU Medicines Company FX The CHAMPION PHOENIX trial was funded by The Medicines Company. NR 27 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 19 PY 2016 VL 133 IS 3 BP 248 EP 255 DI 10.1161/CIRCULATIONAHA.115.017300 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DB5FV UT WOS:000368540900004 PM 26762525 ER PT J AU Lindvall, C Chatterjee, NA Chang, YC Chernack, B Jackson, VA Singh, JP Metlay, JP AF Lindvall, Charlotta Chatterjee, Neal A. Chang, Yuchiao Chernack, Betty Jackson, Vicki A. Singh, Jagmeet P. Metlay, Joshua P. TI National Trends in the Use of Cardiac Resynchronization Therapy With or Without Implantable Cardioverter-Defibrillator SO CIRCULATION LA English DT Article DE cardiac resynchronization therapy; cardiac resynchronization therapy devices; defibrillators; implantable; electric countershock; heart failure ID LEFT-VENTRICULAR DYSFUNCTION; CHRONIC HEART-FAILURE; ASSOCIATION TASK-FORCE; DEVICE-BASED THERAPY; PRIMARY PREVENTION; RHYTHM ABNORMALITIES; RISK STRATIFICATION; ADMINISTRATIVE DATA; PRACTICE GUIDELINES; COST-EFFECTIVENESS AB Background Candidates for cardiac resynchronization therapy (CRT) receive either a biventricular pacemaker or a biventricular pacemaker with an implantable cardioverter-defibrillator (CRT-D). Optimal device selection remains challenging because the benefit of implantable cardioverter-defibrillator therapy may not be uniform, particularly in patients at competing risk of nonsudden death. Methods and Results In this serial cross-sectional study using the National Inpatient Sample database, we identified 311086 admissions associated with CRT implant between 2006 to 2012. CRT-D was the most common device type (86.1%), including in patients 75 years of age with 5 Elixhauser comorbidities (75.5%). Multivariate predictors of CRT-D implant included demographic, clinical, and geographic factors: prior ventricular arrhythmia (rate ratio [RR], 1.14; 95% CI, 1.13-1.14), ischemic heart disease (RR, 1.11; 95% CI, 1.10-1.11), male sex (RR, 1.10; 95% CI, 1.09-1.10), black race (RR, 1.06; 95% CI: 1.04-1.07), and Northeast geographic region (RR, 1.06; 95% CI, 1.04-1.09). There was significant interhospital variation in the use of CRT-D (10-90 percentile range, 72.9%-98.0% CRT-D). Conclusions The majority of patients in this contemporary US cohort underwent implantation of CRT-D. Predictors of CRT-D implant included demographic, clinical, and geographic factors. In patient subgroups predicted to have an attenuated benefit from implantable cardioverter-defibrillator therapy (older adults with multiple comorbidities), CRT-D remained the dominant device type. An improved understanding of the determinants of device selection may aid in decision making and ultimately better align patient risk with device benefit at the time of CRT implantation. C1 [Lindvall, Charlotta; Jackson, Vicki A.] Massachusetts Gen Hosp, Dept Med, Div Palliat Care, Boston, MA 02114 USA. [Lindvall, Charlotta; Chang, Yuchiao; Metlay, Joshua P.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Chatterjee, Neal A.; Singh, Jagmeet P.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Lindvall, Charlotta; Chang, Yuchiao; Chernack, Betty; Jackson, Vicki A.; Singh, Jagmeet P.; Metlay, Joshua P.] Harvard Univ, Sch Med, Boston, MA USA. RP Lindvall, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Med Sch,Div Palliat Care, 55 Fruit St,Founders 600, Boston, MA 02114 USA. EM clindvall@mgh.harvard.edu FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NCRR and NCATS, NIH) [UL1 TR001102]; Harvard University FX This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NCRR and NCATS, NIH Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. NR 48 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 19 PY 2016 VL 133 IS 3 BP 273 EP 281 DI 10.1161/CIRCULATIONAHA.115.018830 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DB5FV UT WOS:000368540900007 PM 26635400 ER PT J AU Agarwal, S Loder, S Brownley, C Cholok, D Mangiavini, L Li, J Breuler, C Sunga, HH Li, SL Ranganathan, K Peterson, J Tompkins, R Herndon, D Xiao, WZ Jumlongras, D Olsen, BR Davis, TA Mishina, Y Schipani, E Levi, B AF Agarwal, Shailesh Loder, Shawn Brownley, Cameron Cholok, David Mangiavini, Laura Li, John Breuler, Christopher Sunga, Hsiao H. Li, Shuli Ranganathan, Kavitha Peterson, Joshua Tompkins, Ronald Herndon, David Xiao, Wenzhong Jumlongras, Dolrudee Olsen, Bjorn R. Davis, Thomas A. Mishina, Yuji Schipani, Ernestina Levi, Benjamin TI Inhibition of Hif1 alpha prevents both trauma-induced and genetic heterotopic ossification SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIF1 alpha; heterotopic ossification; cartilage; mesenchymal condensation; Prx ID HYPOXIA-INDUCIBLE FACTOR; HUMAN SKELETAL-MUSCLE; BONE-FORMATION; GROWTH-FACTOR; RISK-FACTORS; IN-VIVO; HIF-1-ALPHA; PX-478; RECEPTOR; CANCER AB Pathologic extraskeletal bone formation, or heterotopic ossification (HO), occurs following mechanical trauma, burns, orthopedic operations, and in patients with hyperactivating mutations of the type I bone morphogenetic protein receptor ACVR1 (Activin type 1 receptor). Extraskeletal bone forms through an endochondral process with a cartilage intermediary prompting the hypothesis that hypoxic signaling present during cartilage formation drives HO development and that HO precursor cells derive from a mesenchymal lineage as defined by Paired related homeobox 1 (Prx). Here we demonstrate that Hypoxia inducible factor-1 alpha (Hif1 alpha), a key mediator of cellular adaptation to hypoxia, is highly expressed and active in three separate mouse models: trauma-induced, genetic, and a hybrid model of genetic and trauma-induced HO. In each of these models, Hif1 alpha expression coincides with the expression of master transcription factor of cartilage, Sox9 [(sex determining region Y)-box 9]. Pharmacologic inhibition of Hif1 alpha using PX-478 or rapamycin significantly decreased or inhibited extraskeletal bone formation. Importantly, de novo soft-tissue HO was eliminated or significantly diminished in treated mice. Lineage-tracing mice demonstrate that cells forming HO belong to the Prx lineage. Burn/tenotomy performed in lineage-specific Hif1 alpha knockout mice (Prx-Cre/Hif1 alpha(fl:fl)) resulted in substantially decreased HO, and again lack of de novo soft-tissue HO. Genetic loss of Hif1 alpha in mesenchymal cells marked by Prx-cre prevents the formation of the mesenchymal condensations as shown by routine histology and immunostaining for Sox9 and PDGFR alpha. Pharmacologic inhibition of Hif1 alpha had a similar effect on mesenchymal condensation development. Our findings indicate that Hif1 alpha represents a promising target to prevent and treat pathologic extraskeletal bone. C1 [Agarwal, Shailesh; Loder, Shawn; Brownley, Cameron; Cholok, David; Li, John; Breuler, Christopher; Sunga, Hsiao H.; Li, Shuli; Ranganathan, Kavitha; Peterson, Joshua; Levi, Benjamin] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Mangiavini, Laura; Schipani, Ernestina] Univ Michigan, Dept Orthoped Surg, Ann Arbor, MI 48109 USA. [Tompkins, Ronald] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Herndon, David] Shriners Hosp Children, Dept Surg, Galveston, TX 77555 USA. [Herndon, David] Univ Texas Med Branch, Galveston, TX 77555 USA. [Xiao, Wenzhong] Stanford Univ, Dept Surg, Genome Technol Ctr, Palo Alto, CA 94305 USA. [Jumlongras, Dolrudee; Olsen, Bjorn R.] Harvard Univ, Sch Dent, Dept Dev Biol, Boston, MA 02115 USA. [Davis, Thomas A.] Naval Med Res Ctr, Regenerat Med Dept, Silver Spring, MD 20910 USA. [Mishina, Yuji] Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. RP Schipani, E (reprint author), Univ Michigan, Dept Orthoped Surg, Ann Arbor, MI 48109 USA. EM eschipan@med.umich.edu; blevi@umich.edu RI Mangiavini, Laura/K-6340-2016 OI Mangiavini, Laura/0000-0003-1892-1249 FU NIH [P30 CA046592, R01 DE020843, U54GM062119, R01 AR036820, P01 AR048564]; Coller Society Research Fellowship; National Institutes of Health (NIH) Loan Repayment Program; Plastic Surgery Foundation; NIH F32 Fellowship; Howard Hughes Medical Institute Medical Fellows Program; Department of Defense [W81XWH-11-2-0073]; NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR065403-02]; NIH/National Institute of General Medical Sciences [K08GM109105-0]; Plastic Surgery Foundation National Endowment Award; Association for Academic Surgery Roslyn Award; American Association for the Surgery of Trauma Research & Education Foundation Scholarship [DOD: W81XWH-14-DMRDP-CRMRP-NMSIRA]; American Association of Plastic Surgery Research Fellowship; DOD [W81XWH-14-2-0010, 602115HP.3720.001.A1014] FX We thank the Department of Radiology at The University of Michigan for the use of The Center for Molecular Imaging and the Tumor Imaging Core which are supported in part by NIH Grant P30 CA046592. This work was supported in part by a Coller Society Research Fellowship (to S.A.); National Institutes of Health (NIH) Loan Repayment Program (S.A.); the Plastic Surgery Foundation (S.A.); NIH F32 Fellowship (to S.A. and K.R.); the Howard Hughes Medical Institute Medical Fellows Program (S. Loder); NIH Grant R01 DE020843 (to Y.M.); Department of Defense Grant W81XWH-11-2-0073 (to Y.M.); NIH Grant U54GM062119 (to R.T.); NIH Grants R01 AR036820 and P01 AR048564 (to B.R.O.); and NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant R01AR065403-02 (to E.S.). B.L. received funding from NIH/National Institute of General Medical Sciences Grant K08GM109105-0, Plastic Surgery Foundation National Endowment Award, the Association for Academic Surgery Roslyn Award, American Association for the Surgery of Trauma Research & Education Foundation Scholarship, DOD: W81XWH-14-DMRDP-CRMRP-NMSIRA and American Association of Plastic Surgery Research Fellowship. Some of the authors are employees of the United States Government. This work was prepared as part of their official duties. Title 17 U.S.C. 105 provides that "Copyright protection under this title is not available for any work of the United States Government." Title 17 U.S.C 101 defined a US Government work as a work prepared by a military service member or employees of the United States Government as part of that person's official duties. The opinions or assertions contained in this paper are the private views of the authors and are not to be construed as reflecting the views, policy or positions of the Department of the Navy, Department of Defense nor the United States Government. This work was partially supported by DOD work units W81XWH-14-2-0010 and 602115HP.3720.001.A1014. NR 37 TC 6 Z9 7 U1 3 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 2016 VL 113 IS 3 BP E338 EP E347 DI 10.1073/pnas.1515397113 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB4BX UT WOS:000368458800013 PM 26721400 ER PT J AU He, TH Li, K Roberts, MS Spaulding, AC Ayer, T Grefenstette, JJ Chhatwal, J AF He, Tianhua Li, Kan Roberts, Mark S. Spaulding, Anne C. Ayer, Turgay Grefenstette, John J. Chhatwal, Jagpreet TI Prevention of Hepatitis C by Screening and Treatment in US Prisons SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID VIRUS-INFECTION; COST-EFFECTIVENESS; UNITED-STATES; COHORT; HEALTH; SOFOSBUVIR; RECOMMENDATIONS; POPULATIONS; TELAPREVIR; LEDIPASVIR AB Background: The prevalence of hepatitis C virus (HCV) in U.S. prisoners is high; however, HCV testing and treatment are rare. Infected inmates released back into society contribute to the spread of HCV in the general population. Routine hepatitis screening of inmates followed by new therapies may reduce ongoing HCV transmission. Objective: To evaluate the health and economic effect of HCV screening and treatment in prisons on the HCV epidemic in society. Design: Agent-based microsimulation model of HCV transmission and progression of HCV disease. Data Sources: Published literature. Target Population: Population in U.S. prisons and general community. Time Horizon: 30 years. Perspective: Societal. Interventions: Risk-based and universal opt-out hepatitis C screening in prisons, followed by treatment in a portion of patients. Outcome Measures: Prevention of HCV transmission and associated disease in prisons and society, costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and total prison budget. Results of Base-Case Analysis: Implementing risk-based and opt-out screening could diagnose 41 900 to 122 700 new HCV cases in prisons in the next 30 years. Compared with no screening, these scenarios could prevent 5500 to 12 700 new HCV infections caused by released inmates, wherein about 90% of averted infections would have occurred outside of prisons. Screening could also prevent 4200 to 11 700 liver-related deaths. The ICERs of screening scenarios were $19 600 to $29 200 per QALY, and the respective first-year prison budget was $900 to $1150 million. Prisons would require an additional 12.4% of their current health care budget to implement such interventions. Results of Sensitivity Analysis: Results were sensitive to the time horizon, and ICERs otherwise remained less than $50 000 per QALY. Limitation: Data on transmission network, reinfection rate, and opt-out HCV screening rate are lacking. Conclusion: Universal opt-out HCV screening in prisons is highly cost-effective and would reduce HCV transmission and HCV-associated diseases primarily in the outside community. Investing in U.S. prisons to manage hepatitis C is a strategic approach to address the current epidemic. C1 Univ Pittsburgh, Pittsburgh, PA USA. Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China. Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Georgia Inst Technol, H Milton Stewart Sch Ind & Syst Engn, Atlanta, GA 30332 USA. [Chhatwal, Jagpreet] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chhatwal, J (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM jagchhatwal@mgh.harvard.edu FU National Center for Advancing Translational Sciences of the National Institutes of Health [KL2TR000146]; China Scholarship Council FX In part by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number KL2TR000146. Dr. He's effort was supported by the China Scholarship Council. NR 43 TC 10 Z9 10 U1 6 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 19 PY 2016 VL 164 IS 2 BP 84 EP 92 DI 10.7326/M15-0617 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DB0CI UT WOS:000368175800012 PM 26595252 ER PT J AU Emanuel, EJ Ubel, PA Kessler, JB Meyer, G Muller, RW Navathe, AS Patel, P Pearl, R Rosenthal, MB Sacks, L Sen, AP Sherman, P Volpp, KG AF Emanuel, Ezekiel J. Ubel, Peter A. Kessler, Judd B. Meyer, Gregg Muller, Ralph W. Navathe, Amol S. Patel, Pankaj Pearl, Robert Rosenthal, Meredith B. Sacks, Lee Sen, Aditi P. Sherman, Paul Volpp, Kevin G. TI Using Behavioral Economics to Design Physician Incentives That Deliver High-Value Care SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PAY-FOR-PERFORMANCE; METAANALYSIS; DEFAULTS; QUALITY AB Behavioral economics provides insights about the development of effective incentives for physicians to deliver high-value care. It suggests that the structure and delivery of incentives can shape behavior, as can thoughtful design of the decision-making environment. This article discusses several principles of behavioral economics, including inertia, loss aversion, choice overload, and relative social ranking. Whereas these principles have been applied to motivate personal health decisions, retirement planning, and savings behavior, they have been largely ignored in the design of physician incentive programs. Applying these principles to physician incentives can improve their effectiveness through better alignment with performance goals. Anecdotal examples of successful incentive programs that apply behavioral economics principles are provided, even as the authors recognize that its application to the design of physician incentives is largely untested, and many outstanding questions exist. Application and rigorous evaluation of infrastructure changes and incentives are needed to design payment systems that incentivize high-quality, cost-conscious care. C1 [Emanuel, Ezekiel J.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Leonard Davis Inst, CHIBE,Univ Penn Hlth Syst, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Ubel, Peter A.] Duke Univ, Sanford Sch Publ Policy, Durham, NC 27708 USA. [Meyer, Gregg] Partners Healthcare Syst, Boston, MA 02199 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Sacks, Lee] Advocate Phys Partners, Chicago, IL USA. [Pearl, Robert] Permanente Med Grp Inc, Oakland, CA 94612 USA. Grp Hlth, Seattle, WA USA. RP Emanuel, EJ (reprint author), Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, 122 Coll Hall, Philadelphia, PA 19104 USA. EM vp-global@upenn.edu FU Commonwealth Fund FX In part by The Commonwealth Fund. The funding source reviewed the manuscript but did not make any fundamental alterations. NR 38 TC 18 Z9 18 U1 3 U2 14 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 19 PY 2016 VL 164 IS 2 BP 114 EP + DI 10.7326/M15-1330 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DB0CI UT WOS:000368175800015 PM 26595370 ER PT J AU Shekelle, P AF Shekelle, Paul TI In patients with type 2 diabetes and CV disease, empagliflozin reduced a composite of CV events at 3.1 years SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Shekelle, Paul] Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. RP Shekelle, P (reprint author), Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 19 PY 2016 VL 164 IS 2 BP JC2 EP JC2 DI 10.7326/ACPJC-2015-163-12-002 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DB0CI UT WOS:000368175800001 PM 26784492 ER PT J AU Watson, CT Roussos, P Garg, P Ho, DJ Azam, N Katsel, PL Haroutunian, V Sharp, AJ AF Watson, Corey T. Roussos, Panos Garg, Paras Ho, Daniel J. Azam, Nidha Katsel, Pavel L. Haroutunian, Vahram Sharp, Andrew J. TI Genome-wide12 DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer's disease SO GENOME MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; HUMAN PREFRONTAL CORTEX; GENE-EXPRESSION; HUMAN BRAIN; NEUROFIBRILLARY TANGLES; STEM-CELLS; RISK; LOCI; AGE; VARIANTS AB Background: Alzheimer's disease affects similar to 13 % of people in the United States 65 years and older, making it the most common neurodegenerative disorder. Recent work has identified roles for environmental, genetic, and epigenetic factors in Alzheimer's disease risk. Methods: We performed a genome-wide screen of DNA methylation using the Illumina Infinium HumanMethylation450 platform on bulk tissue samples from the superior temporal gyrus of patients with Alzheimer's disease and non-demented controls. We paired a sliding window approach with multivariate linear regression to characterize Alzheimer's disease-associated differentially methylated regions (DMRs). Results: We identified 479 DMRs exhibiting a strong bias for hypermethylated changes, a subset of which were independently associated with aging. DMR intervals overlapped 475 RefSeq genes enriched for gene ontology categories with relevant roles in neuron function and development, as well as cellular metabolism, and included genes reported in Alzheimer's disease genome-wide and epigenome-wide association studies. DMRs were enriched for brain-specific histone signatures and for binding motifs of transcription factors with roles in the brain and Alzheimer's disease pathology. Notably, hypermethylated DMRs preferentially overlapped poised promoter regions, marked by H3K27me3 and H3K4me3, previously shown to co-localize with aging-ssociated hypermethylation. Finally, the integration of DMR-associated single nucleotide polymorphisms with Alzheimer's disease genome-wide association study risk loci and brain expression quantitative trait loci highlights multiple potential DMRs of interest for further functional analysis. Conclusion: We have characterized changes in DNA methylation in the superior temporal gyrus of patients with Alzheimer's disease, highlighting novel loci that facilitate better characterization of pathways and mechanisms underlying Alzheimer's disease pathogenesis, and improve our understanding of epigenetic signatures that may contribute to the development of disease. C1 [Watson, Corey T.; Roussos, Panos; Garg, Paras; Ho, Daniel J.; Azam, Nidha; Sharp, Andrew J.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Roussos, Panos; Katsel, Pavel L.; Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Roussos, Panos; Haroutunian, Vahram] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN 3, Bronx, NY USA. [Katsel, Pavel L.; Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. RP Sharp, AJ (reprint author), Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. EM andrew.sharp@mssm.edu RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU Alzheimer's Association [2012ALZNIRG69983, NIRG-340998]; NIH [DA033660, HG006696, HD073731, MH097018, R01AG050986, AG05138, HHSN271291300031]; March of Dimes [6-FY13-92]; Brain Behavior Research Foundation [20540]; Veterans Affairs Merit grant [BX002395] FX This work was supported by a New Investigator Research Grant from the Alzheimer's Association (2012ALZNIRG69983) to AJS; NIH grants DA033660, HG006696, HD073731, and MH097018 to AJS; research grant 6-FY13-92 from the March of Dimes to AJS; NIH grant R01AG050986 to PR; a Brain Behavior Research Foundation grant 20540 to PR; an Alzheimer's Association grant NIRG-340998 to PR; a Veterans Affairs Merit grant BX002395 to PR; and NIH grants AG05138 and HHSN271291300031 to VH. The authors thank Dr. Zachary Kaminsky for useful discussion regarding the estimation of neuronal/glial cell proportions from bulk tissue methylation profiles. NR 105 TC 5 Z9 5 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PD JAN 19 PY 2016 VL 8 AR 5 DI 10.1186/s13073-015-0258-8 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA DB0YP UT WOS:000368234900001 PM 26787419 ER PT J AU Hondowicz, BD An, D Schenkel, JM Kim, KS Steach, HR Krishnamurty, AT Keitany, GJ Garza, EN Fraser, KA Moon, JJ Altemeier, WA Masopust, D Pepper, M AF Hondowicz, Brian D. An, Dowon Schenkel, Jason M. Kim, Karen S. Steach, Holly R. Krishnamurty, Akshay T. Keitany, Gladys J. Garza, Esteban N. Fraser, Kathryn A. Moon, James J. Altemeier, William A. Masopust, David Pepper, Marion TI Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma SO IMMUNITY LA English DT Article ID DUST MITE ALLERGEN; FOLLICULAR HELPER-CELL; CD4 T-CELLS; TRANSCRIPTION FACTOR; TH2 DIFFERENTIATION; LYMPHOCYTE EGRESS; LUNG; INFECTION; INFLAMMATION; MICE AB Exposure to inhaled allergens generates T helper 2 (Th2) CD4(+) T cells that contribute to episodes of inflammation associated with asthma. Little is known about allergen-specific Th2 memory cells and their contribution to airway inflammation. We generated reagents to understand how endogenous CD4(+) T cells specific for a house dust mite (HDM) allergen form and function. After allergen exposure, HDM-specific memory cells persisted as central memory cells in the lymphoid organs and tissue-resident memory cells in the lung. Experimental blockade of lymphocyte migration demonstrated that lung-resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4(+) T cells. Investigation into the differentiation of pathogenic Trm cells revealed that interleukin-2 (IL-2) signaling was required for residency and directed a program of tissue homing migrational cues. These studies thus identify IL-2-dependent resident Th2 memory cells as drivers of lung allergic responses. C1 [Hondowicz, Brian D.; Kim, Karen S.; Steach, Holly R.; Krishnamurty, Akshay T.; Keitany, Gladys J.; Garza, Esteban N.; Pepper, Marion] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98109 USA. [An, Dowon; Altemeier, William A.] Univ Washington, Sch Med, Ctr Lung Biol, Seattle, WA 98109 USA. [Schenkel, Jason M.; Fraser, Kathryn A.; Masopust, David] Univ Minnesota, Sch Med, Ctr Immunol, Dept Microbiol, Minneapolis, MN 55455 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Moon, James J.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Charlestown, MA 02129 USA. [Moon, James J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Pepper, M (reprint author), Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98109 USA. EM mpepper@uw.edu OI Steach, Holly/0000-0003-0018-3129; moon, james/0000-0001-8071-1491 FU NCI NIH HHS [P30 CA077598]; NIAID NIH HHS [U19 AI095261, R01 AI084913, R01 AI108626, T32 AI106677] NR 58 TC 11 Z9 11 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JAN 19 PY 2016 VL 44 IS 1 BP 155 EP 166 DI 10.1016/j.immuni.2015.11.004 PG 12 WC Immunology SC Immunology GA DB2NU UT WOS:000368347000020 PM 26750312 ER PT J AU Godec, J Tan, Y Liberzon, A Tamayo, P Bhattacharya, S Butte, AJ Mesirov, JP Haining, WN AF Godec, Jernej Tan, Yan Liberzon, Arthur Tamayo, Pablo Bhattacharya, Sanchita Butte, Atul J. Mesirov, Jill P. Haining, W. Nicholas TI Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation SO IMMUNITY LA English DT Article ID SET ENRICHMENT ANALYSIS; CD8(+) T-CELLS; GENE-EXPRESSION; MATRIX FACTORIZATION; B-CELLS; DISCOVERY; PROFILES; GENOMICS; DATABASE; MODELS AB Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of similar to 5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems. C1 [Godec, Jernej; Haining, W. Nicholas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Godec, Jernej] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Tan, Yan; Liberzon, Arthur; Tamayo, Pablo; Mesirov, Jill P.; Haining, W. Nicholas] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Tan, Yan; Mesirov, Jill P.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Bhattacharya, Sanchita; Butte, Atul J.] Univ Calif San Francisco, Inst Computat Hlth Sci, San Francisco, CA 94158 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Haining, WN (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu FU Infrastructure and Opportunity Grant from the Human Immunology Project Consortium [U19 AI090023]; NIAID Bioinformatics Support Contract [HHSN272201200028C, R01CA154480, R01CA121941, R01GM074024, U54CA112962]; Cancer Research Institute Predoctoral Emphasis Pathway in Tumor Immunology FX We would like to thank Arlene H. Sharpe, William Kim, and Aravind Subramanian for useful discussions. This work was supported by an Infrastructure and Opportunity Grant from the Human Immunology Project Consortium (to A.J.B., J.P.M., and W.N.H.), by U19 AI090023 to W.N.H.; NIAID Bioinformatics Support Contract HHSN272201200028C to A.J.B.; R01CA154480, R01CA121941, R01GM074024, and U54CA112962 to P.T. and J.P.M.; and the Cancer Research Institute Predoctoral Emphasis Pathway in Tumor Immunology to J.G. NR 40 TC 16 Z9 16 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JAN 19 PY 2016 VL 44 IS 1 BP 194 EP 206 DI 10.1016/j.immuni.2015.12.006 PG 13 WC Immunology SC Immunology GA DB2NU UT WOS:000368347000023 PM 26795250 ER PT J AU Quill, TE Back, AL Block, SD AF Quill, Timothy E. Back, Anthony L. Block, Susan D. TI Responding to Patients Requesting Physician-Assisted Death Physician Involvement at the Very End of Life SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID SUICIDE; CARE C1 [Quill, Timothy E.] Univ Rochester, Med Ctr, Palliat Care Div, Dept Med, Rochester, NY 14642 USA. [Back, Anthony L.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Back, Anthony L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Back, Anthony L.] Univ Washington, Cambia Palliat Care Ctr Excellence, Seattle, WA 98195 USA. [Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Block, Susan D.] Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Ariadne Labs, Boston, MA 02115 USA. RP Quill, TE (reprint author), Univ Rochester, Med Ctr, Ctr Eth, POB 687,601 Elmwood Ave,Room G-7824, Rochester, NY 14642 USA. EM timothy_quill@urmc.rochester.edu NR 7 TC 8 Z9 8 U1 2 U2 31 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 19 PY 2016 VL 315 IS 3 BP 245 EP 246 DI 10.1001/jama.2015.16210 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DB2WN UT WOS:000368371400011 PM 26784762 ER PT J AU Odejide, OO AF Odejide, Oreofe O. TI A Policy Prescription for Hospice Care SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CANCER C1 [Odejide, Oreofe O.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02215 USA. RP Odejide, OO (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. EM oreofe_odejide@dfci.harvard.edu NR 8 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 19 PY 2016 VL 315 IS 3 BP 257 EP 258 DI 10.1001/jama.2015.18424 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DB2WN UT WOS:000368371400017 PM 26784768 ER PT J AU Wright, AA Keating, NL Ayanian, JZ Chrischilles, EA Kahn, KL Ritchie, CS Weeks, JC Earle, CC Landrum, MB AF Wright, Alexi A. Keating, Nancy L. Ayanian, John Z. Chrischilles, Elizabeth A. Kahn, Katherine L. Ritchie, Christine S. Weeks, Jane C. Earle, Craig C. Landrum, Mary B. TI Family Perspectives on Aggressive Cancer Care Near the End of Life SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OF-LIFE; SURVEILLANCE CONSORTIUM; MEDICARE BENEFICIARIES; ETHNIC-DIFFERENCES; OUTCOMES RESEARCH; MENTAL-HEALTH; LUNG-CANCER; DEATH; HOSPICE; QUALITY AB IMPORTANCE Patients with advanced-stage cancer are receiving increasingly aggressive medical care near death, despite growing concerns that this reflects poor-quality care. OBJECTIVE To assess the association of aggressive end-of-life care with bereaved family members' perceptions of the quality of end-of-life care and patients' goal attainment. DESIGN, SETTING, AND PARTICIPANTS Interviews with 1146 family members of Medicare patients with advanced-stage lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance study (a multiregional, prospective, observational study) who died by the end of 2011 (median, 144.5 days after death; interquartile range, 85.0-551.0 days). EXPOSURES Claims-based quality measures of aggressive end-of-life care (ie, intensive care unit [ICU] admission or repeated hospitalizations or emergency department visits during the last month of life; chemotherapy <= 2 weeks of death; no hospice or <= 3 days of hospice services; and deaths occurring in the hospital). MAIN OUTCOMES AND MEASURES Family member-reported quality rating of "excellent" for end-of-life care. Secondary outcomes included patients' goal attainment (ie, end-of-life care congruent with patients' wishes and location of death occurred in preferred place). RESULTS Of 1146 patients with cancer (median age, 76.0 years [interquartile range, 65.0-87.0 years]; 55.8% male), bereaved family members reported excellent end-of-life care for 51.3%. Family members reported excellent end-of-life care more often for patients who received hospice care for longer than 3 days (58.8% [352/599]) than those who did not receive hospice care or received 3 or fewer days (43.1% [236/547]) (adjusted difference, 16.5 percentage points [95% CI, 10.7 to 22.4 percentage points]). In contrast, family members of patients admitted to an ICU within 30 days of death reported excellent end-of-life care less often (45.0% [68/151]) than those who were not admitted to an ICU within 30 days of death (52.3% [520/995]) (adjusted difference, -9.4 percentage points [95% CI, -18.2 to -0.6 percentage points]). Similarly, family members of patients who died in the hospital reported excellent end-of-life care less often (42.2% [194/460]) than those who did not die in the hospital (57.4% [394/686]) (adjusted difference, -17.0 percentage points [95% CI, -22.9 to -11.1 percentage points]). Family members of patients who did not receive hospice care or received 3 or fewer days were less likely to report that patients died in their preferred location (40.0% [152/380]) than those who received hospice care for longer than 3 days (72.8% [287/394]) (adjusted difference, -34.4 percentage points [95% CI, -41.7 to -27.0 percentage points]). CONCLUSIONS AND RELEVANCE Among family members of older patients with fee-for service Medicare who died of lung or colorectal cancer, earlier hospice enrollment, avoidance of ICU admissions within 30 days of death, and death occurring outside the hospital were associated with perceptions of better end-of-life care. These findings are supportive of advance care planning consistent with the preferences of patients. C1 [Wright, Alexi A.; Weeks, Jane C.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. [Keating, Nancy L.; Landrum, Mary B.] Harvard Univ, Dept Hlth Care Policy, Sch Med, Boston, MA 02215 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Ayanian, John Z.] Univ Michigan, Inst Healthcare Policy & Innovat, Div Gen Med, Ann Arbor, MI 48109 USA. [Ayanian, John Z.] Univ Michigan, Sch Publ Hlth, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA. [Ayanian, John Z.] Univ Michigan, Gerald R Ford Sch Publ Policy, Ann Arbor, MI 48109 USA. [Chrischilles, Elizabeth A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA. [Kahn, Katherine L.] Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA. [Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Wright, AA (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, 450 Brookline Ave,Dana 1133, Boston, MA 02215 USA. EM alexi_wright@dfci.harvard.edu FU National Cancer Institute [R01 CA91753, 5U01CA093344-08, K24 CA181510]; Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium [U01 CA093344, U01 CA093324, U01 CA093332, U01 CA093348, U01 CA093329, U01 CA093339, U01 CA093326, R01 CA1604021]; [K07 166210] FX This work was supported by grant R01 CA91753 from the National Cancer Institute (awarded to Dr Earle) and grants U01 CA093344 (awarded to Dana-Farber Cancer Institute), U01 CA093324 (awarded to Harvard Medical School and Northern California Cancer Center), U01 CA093332 (awarded to Dana-Farber Cancer Institute and Cancer Research Network), U01 CA093348 (awarded to RAND Corporation and University of California, Los Angeles), U01 CA093329 (awarded to University of Alabama, Birmingham), U01 CA093339 (awarded to University of Iowa), U01 CA093326 (awarded to the University of North Carolina), and R01 CA1604021 (awarded to Dr Keating) from the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium. CanCORS II work was funded by grant 5U01CA093344-08 from the National Cancer Institute (awarded to the CanCORS Consortium Statistical Coordinating Center). Dr Wright is supported by grant K07 166210 and Dr Keating is supported by K24 CA181510 from the National Cancer Institute. NR 31 TC 15 Z9 16 U1 5 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 19 PY 2016 VL 315 IS 3 BP 284 EP 292 DI 10.1001/jama.2015.18604 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DB2WN UT WOS:000368371400025 PM 26784776 ER PT J AU Lewis, GD Ngo, D Hemnes, AR Farrell, L Domos, C Pappagianopoulos, PP Dhakal, BP Souza, A Shi, X Pugh, ME Beloiartsev, A Sinha, S Clish, CB Gerszten, RE AF Lewis, Gregory D. Ngo, Debby Hemnes, Anna R. Farrell, Laurie Domos, Carly Pappagianopoulos, Paul P. Dhakal, Bishnu P. Souza, Amanda Shi, Xu Pugh, Meredith E. Beloiartsev, Arkadi Sinha, Sumita Clish, Clary B. Gerszten, Robert E. TI Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE exercise; hemodynamics; metabolism; pulmonary circulation ID SYSTOLIC HEART-FAILURE; INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY; DYSREGULATED ARGININE METABOLISM; SICKLE-CELL-DISEASE; ARTERIAL-HYPERTENSION; PLASMA SEROTONIN; EXERCISE; MORTALITY; PRESSURE; CATECHOLAMINES AB BACKGROUND Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. OBJECTIVES This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. METHODS We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). RESULTS In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [Delta PQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine-nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and Delta PQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. CONCLUSIONS Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization. (C) 2016 by the American College of Cardiology Foundation. C1 [Lewis, Gregory D.; Farrell, Laurie; Domos, Carly; Dhakal, Bishnu P.; Shi, Xu; Beloiartsev, Arkadi; Sinha, Sumita; Gerszten, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Div,Dept Med, Boston, MA USA. [Lewis, Gregory D.; Ngo, Debby; Pappagianopoulos, Paul P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. [Lewis, Gregory D.; Souza, Amanda; Clish, Clary B.; Gerszten, Robert E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Hemnes, Anna R.; Pugh, Meredith E.] Vanderbilt Univ, Pulm Unit, Nashville, TN 37235 USA. [Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM glewis@partners.org; rgerszten@partners.org FU National Institutes of Health (NIH) (Bethesda, Maryland) [1R01 HL098280, R01 DK081572]; Leducq Foundation; Clinical and Translational Science Award from the National Center for Advancing Translational Sciences (Bethesda, Maryland) [UL1TR000445]; NIH (Bethesda, Maryland) [K23HL091106, R01 HL131029, R01 HL119154]; American Heart Association (AHA) grant (Dallas, Texas) [15GPSGC24800006]; Hassenfeld Clinical Scholar Award (Boston, Massachusetts); AHA Established Investigator Award (Dallas, Texas) FX This work was supported by National Institutes of Health (NIH) grants 1R01 HL098280 and R01 DK081572 (Bethesda, Maryland) and the Leducq Foundation. The project was also supported by Clinical and Translational Science Award No. UL1TR000445 (Dr. Hemnes and Dr. Pugh) from the National Center for Advancing Translational Sciences (Bethesda, Maryland). Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the NIH. Dr. Lewis was supported by NIH grants K23HL091106, NIH R01 HL131029, and NIH R01 HL119154 (Bethesda, Maryland), American Heart Association (AHA) grant 15GPSGC24800006 (Dallas, Texas), and the Hassenfeld Clinical Scholar Award (Boston, Massachusetts). Dr. Pugh has served as an advisory board member for Gilead. Dr. Gerszten was supported by an AHA Established Investigator Award (Dallas, Texas). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 39 TC 9 Z9 9 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 19 PY 2016 VL 67 IS 2 BP 174 EP 189 DI 10.1016/j.jacc.2015.10.072 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA9FO UT WOS:000368114400009 PM 26791065 ER PT J AU Dehmer, GJ Jennings, J Madden, RA Malenka, DJ Masoudi, FA McKay, CR Ness, DL Rao, SV Resnic, FS Ring, ME Rumsfeld, JS Shelton, ME Simanowith, MC Slattery, LE Weintraub, WS Lovett, A Normand, SL AF Dehmer, Gregory J. Jennings, Jonathan Madden, Ruth A. Malenka, David J. Masoudi, Frederick A. McKay, Charles R. Ness, Debra L. Rao, Sunil V. Resnic, Frederic S. Ring, Michael E. Rumsfeld, John S. Shelton, Marc E. Simanowith, Michael C. Slattery, Lara E. Weintraub, William S. Lovett, Ann Normand, Sharon-Lise TI The National Cardiovascular Data Registry Voluntary Public Reporting Program An Interim Report From the NCDR Public Reporting Advisory Group SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE health care reform; outcomes; quality ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; MORTALITY RISK PREDICTION; SURGERY REPORT CARDS; HOSPITAL PERFORMANCE; ADMINISTRATIVE DATA; CLINICAL-OUTCOMES; QUALITY; IMPACT; CONSEQUENCES AB Public reporting of health care data continues to proliferate as consumers and other stakeholders seek information on the quality and outcomes of care. Medicare's Hospital Compare website, the U.S. News & World Report hospital rankings, and several state-level programs are well known. Many rely heavily on administrative data as a surrogate to reflect clinical reality. Clinical data are traditionally more difficult and costly to collect, but more accurately reflect patients' clinical status, thus enhancing the validity of quality metrics. We describe the public reporting effort being launched by the American College of Cardiology and partnering professional organizations using clinical data from the National Cardiovascular Data Registry (NCDR) programs. This hospital-level voluntary effort will initially report process of care measures from the percutaneous coronary intervention (CathPCI) and implantable cardioverter-defibrillator (ICD) registries of the NCDR. Over time, additional process, outcomes, and composite performance metrics will be reported. (C) 2016 by the American College of Cardiology Foundation. C1 [Dehmer, Gregory J.] Texas A&M Hlth Sci Ctr, Baylor Scott & White Hlth, Div Cardiol, Temple, TX USA. [Jennings, Jonathan] Hosp Corp Amer, Nashville, TN USA. [Madden, Ruth A.] Cleveland Clin, Dept Cardiovasc Med, Cardiac Electrophysiol & Pacing Sect, Cleveland, OH 44106 USA. [Malenka, David J.] Dartmouth Hitchcock Med Ctr, Div Cardiol, Lebanon, NH 03766 USA. [Masoudi, Frederick A.] Univ Colorado, Div Cardiol, Denver, CO 80202 USA. [McKay, Charles R.] Harbor UCLA Med Ctr, Dept Med Cardiol, Torrance, CA 90509 USA. [Ness, Debra L.] Natl Partnership Women & Families, Washington, DC USA. [Rao, Sunil V.] Duke Clin Res Inst, Durham, NC USA. [Resnic, Frederic S.] Tufts Univ, Sch Med, Lahey Hosp, Cardiol Div, Burlington, MA USA. [Resnic, Frederic S.] Tufts Univ, Sch Med, Med Ctr, Burlington, MA USA. [Ring, Michael E.] Providence Sacred Heart Med Ctr, Spokane, WA USA. [Rumsfeld, John S.] Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. [Shelton, Marc E.] Prairie Cardiovasc, Springfield, IL USA. [Simanowith, Michael C.; Slattery, Lara E.] Amer Coll Cardiol, Washington, DC USA. [Weintraub, William S.] Ctr Heart & Vasc Hlth, Christiana Care Hlth Serv, Newark, DE USA. [Lovett, Ann; Normand, Sharon-Lise] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lovett, Ann; Normand, Sharon-Lise] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Dehmer, GJ (reprint author), Baylor Scott & White Hlth, Div Cardiol, MS 33-ST156,2401 South 31st St, Temple, TX 76508 USA. EM gdehmer@sw.org NR 52 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 19 PY 2016 VL 67 IS 2 BP 205 EP 215 DI 10.1016/j.jacc.2015.11.001 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA9FO UT WOS:000368114400013 PM 26603176 ER PT J AU Mananga, ES AF Mananga, Eugene Stephane TI On the Fer expansion: Applications in solid-state nuclear magnetic resonance and physics SO PHYSICS REPORTS-REVIEW SECTION OF PHYSICS LETTERS LA English DT Review ID ANGLE-SPINNING NMR; FLOQUET-MAGNUS EXPANSION; AVERAGE HAMILTONIAN THEORY; RADIOFREQUENCY PULSE SEQUENCES; LINEAR-DIFFERENTIAL EQUATIONS; ANISOTROPY CORRELATION NMR; CHEMICAL-SHIFT ANISOTROPY; TIME-ORDERED PRODUCTS; BLOCH-SIEGERT SHIFT; HIGH-RESOLUTION NMR AB Theoretical approaches are useful and powerful tools for more accurate and efficient spin dynamics simulation to understand experiments and devising new RF pulse sequence in nuclear magnetic resonance. Solid-state NMR is definitely a timely topic or area of research, and not many papers on the respective theories are available in the literature of nuclear magnetic resonance or physics reports. This report presents the power and the salient features of the promising theoretical approach called Fer expansion that is helpful to describe the evolution of the spin system in nuclear magnetic resonance. The report presents a broad view of algorithms of spin dynamics based on the Fer expansion which provides procedures to control and describe the spin dynamics in solid-state NMR. Significant applications of the Fer expansion are illustrated in NMR and in physics such as classical physics, nonlinear dynamics systems, celestial mechanics and dynamical astronomy, hydrodynamics, nuclear, atomic, molecular physics, and quantum mechanics, quantum field theory, high energy physics, electromagnetism. The aim of this report is to bring to the attention of the spin dynamics community, the bridge that exists between solid-state NMR and other related fields of physics and applied mathematics. (C) 2015 Elsevier B.V. All rights reserved. C1 [Mananga, Eugene Stephane] Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. [Mananga, Eugene Stephane] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Dept Radiol, Div Nucl Med & Mol Imaging Phys, 55 Fruit St, Boston, MA 02114 USA. RP Mananga, ES (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA.; Mananga, ES (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Dept Radiol, Div Nucl Med & Mol Imaging Phys, 55 Fruit St, Boston, MA 02114 USA. EM esm041@mail.harvard.edu FU National Institute of Health (NIH) of USA [R01-HL110241, T32 EB013180] FX Eugene S. Mananga acknowledges assistance from Harvard University, Harvard Medical School (HMS), Massachusetts General Hospital (MGH), and the National Institute of Health (NIH) of USA, under Grants R01-HL110241 and T32 EB013180. The author particularly thanks the Division of Nuclear Medicine and the Department of Radiology for allowing him to work partially on this NMR and Physics Report during his NIHT32 tenure time at Harvard and Massachusetts General Hospital. The author is grateful for encouragement and fruitful discussions with Professor Dr. Eduard B. Fel'dman (Academy of Sciences of the Soviet Union, USSR) for reading the manuscript and providing very useful advises particularly in the context of Provotorov's theory. The author recognizes that the idea of writing a general review on various theories used to control the spin dynamics in the field of nuclear magnetic resonance came to his mind for the first time while he was a Postdoctoral Research Associate at the National High Magnetic Field Laboratory of USA, working on the application of Solid-State Nuclear Magnetic Resonance to Structural Biology and Membrane Proteins. The author was first introduced to solid-state nuclear magnetic resonance by Prof. Steven Greenbaum (City University of New York - Hunter College) during his graduate work on "High Pressure NMR" [310,311]. During and after his graduate studies, the author has benefited from enlightening discussions, mentorship, and strong support from Prof. Joel Gersten (City College of New York). Special thanks for that, as much as for the kind of hospitality extended to him during his graduate studies at City College of the City University of New York. The author is also grateful to Emeritus University Distinguished Professor of Physics, Herman Z. Cummins (City College of New York), for giving him advanced tutoring on modern physics topics during the preparation of the "hard Physics" qualifying exam of the Graduate Center. The author also gives special thanks to Dr. Thibault Charpentier (French Atomic Energy Commission, CEA-Saclay) for useful discussions and introducing him to the field of Floquet theory during his work at CEA-Saclay. The author had his first interest to the technique of average Hamiltonian theory (AHT) while working with Dr. Gregory Boutis (City University of New York). The author thanks his collaborator, Prof. Bingwen Hu (Shanghai Key Laboratory of Magnetic Resonance at East China Normal University) for helpful discussions. Advices and intellectual support from Prof. Dennis Brown, Prof. Frederic Fahey, and Prof. Arkadiusz Sitek (Harvard University, Massachusetts General Hospital, and Boston Children Hospital) are acknowledged. Physics teaching support from Prof. Lorcan Folan and Prof. Valery Sheverev (New York University) are also acknowledged. Friendly discussions with Drs. Jalil Moghaddasi, Joseph Malinsky, Michele Vittadello, Christopher Renner, and George Bennett (City University of New York, HC, MEC, BCC) are appreciated. The author also thanks Dr. Gael De Paepe (French Atomic Energy Commission, CEA-Grenoble) for providing him his preprint article on TSAR Finally, the author thanks fruitful and illuminating lectures (Edward Witten, Philip Anderson, etc.) on condensed matter theory during the 2015 summer school (Princeton University and the Institute of Advanced Studies). The contents of this paper are solely the responsibility of the author and do not represent the official views of NIH/HMS/MGH. NR 299 TC 1 Z9 1 U1 4 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0370-1573 EI 1873-6270 J9 PHYS REP JI Phys. Rep.-Rev. Sec. Phys. Lett. PD JAN 18 PY 2016 VL 608 BP 1 EP 41 DI 10.1016/j.physrep.2015.10.006 PG 41 WC Physics, Multidisciplinary SC Physics GA DC9SY UT WOS:000369562500001 ER PT J AU D'Andrea, AD AF D'Andrea, Alan D. TI Targeting DNA repair in ovarian cancer therapy SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Ctr DNA Damage & Repair, 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA IA04 PG 1 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300140 ER PT J AU Doberstein, K Karst, A Etemadmoghadam, D Jones, P Dunn, G Hahn, W Bowtell, D Drapkin, R AF Doberstein, Kai Karst, Alison Etemadmoghadam, Dariush Jones, Paul Dunn, Gavin Hahn, William Bowtell, David Drapkin, Ronny TI Identifying potential targets in Cyclin E-amplified tumors SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Doberstein, Kai; Drapkin, Ronny] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Karst, Alison; Jones, Paul; Dunn, Gavin; Hahn, William] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Etemadmoghadam, Dariush; Bowtell, David] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA PR05 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300160 ER PT J AU Elias, KM Emori, M Brown, M Drapkin, R AF Elias, Kevin M. Emori, Megan Brown, Myles Drapkin, Ronny TI The PAX8 cistrome in benign and malignant Mullerian epithelia. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Elias, Kevin M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Emori, Megan; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Drapkin, Ronny] Univ Penn, Philadelphia, PA 19104 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA A69 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300057 ER PT J AU Gjyshi, A Mendoza-Fandino, G Woods, N Tyrer, J Lawrenson, K Buckley, M Shen, H Carvalho, R Seo, JH Phelan, C Freedman, M Goode, E Sellers, T Gayther, S Pharoah, P Monteiro, A AF Gjyshi, Anxhela Mendoza-Fandino, Gustavo Woods, Nicholas Tyrer, Jonathan Lawrenson, Kate Buckley, Melissa Shen, Howard Carvalho, Renato Seo, Ji-Heui Phelan, Catherine Freedman, Matthew Goode, Ellen Sellers, Thomas Gayther, Simon Pharoah, Paul Monteiro, Alvaro TI MYC distal enhancers underlie ovarian cancer susceptibility in the 8q24.21 locus SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Gjyshi, Anxhela; Mendoza-Fandino, Gustavo; Buckley, Melissa; Carvalho, Renato; Phelan, Catherine; Sellers, Thomas; Monteiro, Alvaro] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Canc Epidemiol Program, Tampa, FL 33612 USA. [Woods, Nicholas] Univ S Florida, Morsani Coll Med, Dept Oncol Sci, Tampa, FL USA. [Tyrer, Jonathan; Pharoah, Paul] Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Lawrenson, Kate; Shen, Howard; Gayther, Simon] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Seo, Ji-Heui; Freedman, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Goode, Ellen] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA PR15 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300166 ER PT J AU Harrell, MI Norquist, BM Walsh, T Brady, MF Lee, MK Hershberg, R Kalli, KR Lankes, H Konnick, EQ Pritchard, CC Monk, BJ Chan, JK Burger, R Kaufmann, SH Birrer, MJ Swisher, EM AF Harrell, Maria I. Norquist, Barbara M. Walsh, Tom Brady, Mark F. Lee, Ming K. Hershberg, Robert Kalli, Kimberly R. Lankes, Heather Konnick, Eric Q. Pritchard, Colin C. Monk, Bradley J. Chan, John K. Burger, Robert Kaufmann, Scott H. Birrer, Michael J. Swisher, Elizabeth M. TI Old age and chemotherapy contribute to the selection of PPM1D somatic mosaic mutations in ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Harrell, Maria I.; Norquist, Barbara M.; Walsh, Tom; Lee, Ming K.; Konnick, Eric Q.; Pritchard, Colin C.; Swisher, Elizabeth M.] Univ Washington, Seattle, WA 98195 USA. [Brady, Mark F.; Lankes, Heather] NRG Oncol, Buffalo, NY USA. [Hershberg, Robert] VentiRx, Seattle, WA USA. [Kalli, Kimberly R.; Kaufmann, Scott H.] Mayo Clin, Rochester, MN USA. [Monk, Bradley J.] St Josephs Hosp, Phoenix, AZ USA. [Chan, John K.] Palo Alto Sutter Hlth, Calif Pacific Med Ctr, San Francisco, CA USA. [Burger, Robert] Univ Penn, Philadelphia, PA 19104 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA B71 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300128 ER PT J AU Iavarone, C Zervantonakis, I Chen, HY Palakurthi, SS Liu, JF Matulonis, UA Drapkin, RI Mills, GB Leverson, JD Sampath, D Brugge, JS AF Iavarone, Claudia Zervantonakis, Ioannis Chen, Hsing-Yu Palakurthi, Sangeetha S. Liu, Joyce Fu Matulonis, Ursula A. Drapkin, Ronny I. Mills, Gordon B. Leverson, Joel D. Sampath, Deepak Brugge, Joan S. TI Design of effective combination therapies for high-grade serous ovarian cancer using patient-derived xenograft models. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Iavarone, Claudia; Zervantonakis, Ioannis; Chen, Hsing-Yu; Brugge, Joan S.] Harvard Univ, Sch Med, Ludwig Ctr Harvard, Dept Cell Biol, Boston, MA USA. [Palakurthi, Sangeetha S.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Liu, Joyce Fu; Matulonis, Ursula A.] Dana Farber Canc Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Drapkin, Ronny I.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Leverson, Joel D.] AbbVie, Oncol Dev, Chicago, IL USA. [Sampath, Deepak] Genentech Inc, Translat Oncol, San Francisco, CA 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA B48 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300107 ER PT J AU Iwanicki, MP Chen, HY Zervantonakis, I Novak, M Muranen, T Ince, TA Drapkin, R Brugge, JS AF Iwanicki, Marcin P. Chen, Hsing-Yu Zervantonakis, Ioannis Novak, Marian Muranen, Taru Ince, Tan A. Drapkin, Ronny Brugge, Joan S. TI Mutant p53 drives early events in fallopian tube tumorigenesis through mesenchyme-associated autocrine production of matrix that supports survival and mesothelial intercalation. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Iwanicki, Marcin P.; Chen, Hsing-Yu; Zervantonakis, Ioannis; Muranen, Taru; Brugge, Joan S.] Harvard Univ, Sch Med, Boston, MA USA. [Novak, Marian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ince, Tan A.] Univ Miami, Miami, FL USA. [Drapkin, Ronny] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA PR12 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300165 ER PT J AU Matulonis, UA Hodi, S Dranoff, G Campos, S Penson, R Soiffer, R Butler, M AF Matulonis, Ursula Anne Hodi, Stephen Dranoff, Glenn Campos, Susana Penson, Richard Soiffer, Robert Butler, Marcus TI Long-term survival and outcome update on patients (pts) with recurrent ovarian cancer who received Ipilimumab post GVAX vaccine SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Matulonis, Ursula Anne; Hodi, Stephen; Campos, Susana; Soiffer, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dranoff, Glenn] Novartis Pharmaceut, Cambridge, MA USA. [Penson, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Butler, Marcus] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA B72 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300129 ER PT J AU Norquist, BM Brady, MF Harrell, MI Walsh, TD Lee, MK Gulsuner, S Bernards, SS Casadei, S Burger, RA Davidson, SA Mannel, RS DiSilvestro, PA Lankes, HA Ramirez, NC King, MC Birrer, MJ Swisher, EM AF Norquist, Barbara M. Brady, Mark F. Harrell, Maria I. Walsh, Tom D. Lee, Ming K. Gulsuner, Suleyman Bernards, Sarah S. Casadei, Silvia Burger, Robert A. Davidson, Susan A. Mannel, Robert S. DiSilvestro, Paul A. Lankes, Heather A. Ramirez, Nilsa C. King, Mary Claire Birrer, Michael J. Swisher, Elizabeth M. TI Mutations in homologous recombination genes and response to treatment in GOG 218: An NRG Oncology Study. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Norquist, Barbara M.; Harrell, Maria I.; Walsh, Tom D.; Lee, Ming K.; Gulsuner, Suleyman; Bernards, Sarah S.; Casadei, Silvia; King, Mary Claire; Swisher, Elizabeth M.] Univ Washington, Seattle, WA 98195 USA. [Brady, Mark F.; Lankes, Heather A.] Roswell Pk Canc Ctr, Buffalo, NY USA. [Burger, Robert A.] Univ Penn, Philadelphia, PA 19104 USA. [Davidson, Susan A.] Univ Colorado, Denver, CO 80202 USA. [Mannel, Robert S.] Univ Oklahoma, Oklahoma City, OK USA. [DiSilvestro, Paul A.] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Ramirez, Nilsa C.] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA A12 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300011 ER PT J AU Pepin, D Sosulski, A Horn, H Zhang, LH Coletti, C Vathipadiekal, V Castro, CM Birrer, MJ Nagano, O Saya, H Lage, K Donahoe, PK AF Pepin, David Sosulski, Amanda Horn, Heiko Zhang, Lihua Coletti, Caroline Vathipadiekal, Vinod Castro, Cesar M. Birrer, Michael J. Nagano, Osamu Saya, Hidekuyi Lage, Kasper Donahoe, Patricia K. TI Cell surface expression of CD44v8-10 is associated with good prognosis while cleaved extracellular domain is a marker of poor prognosis in high-grade serous epithelial ovarian cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Pepin, David; Sosulski, Amanda; Horn, Heiko; Zhang, Lihua; Coletti, Caroline; Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.; Lage, Kasper; Donahoe, Patricia K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nagano, Osamu; Saya, Hidekuyi] Keio Univ, Sch Med, Tokyo, Japan. RI Nagano, Osamu/J-5874-2013 OI Nagano, Osamu/0000-0002-7630-142X 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA B26 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300088 ER PT J AU Walker, SR Zhang, YX Bartel, K Kroll, Y Frank, DA AF Walker, Sarah R. Zhang, Yixi Bartel, Katarina Kroll, Yasmin Frank, David A. TI Targeting transcriptional networks for ovarian cancer therapy. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Walker, Sarah R.; Zhang, Yixi; Bartel, Katarina; Kroll, Yasmin; Frank, David A.] 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA A46 PG 1 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300037 ER PT J AU Wulf, GM Juvekar, A Cantley, LC Matulonis, UA AF Wulf, Gerburg M. Juvekar, Ashish Cantley, Lewis C. Matulonis, Ursula A. TI PI3K-and PARP-inhibitors for the treatment of women cancers SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Wulf, Gerburg M.; Juvekar, Ashish] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Cantley, Lewis C.] Weill Cornell Canc Ctr, New York, NY USA. [Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 SU 2 MA IA08 PG 1 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300143 ER PT J AU de Vries, PS Chasman, DI Sabater-Lleal, M Chen, MH Huffman, JE Steri, M Tang, WH Teumer, A Marioni, RE Grossmann, V Hottenga, JJ Trompet, S Muller-Nurasyid, M Zhao, JH Brody, JA Kleber, ME Guo, XQ Wang, JJ Auer, PL Attia, JR Yanek, LR Ahluwalia, TS Lahti, J Venturini, C Tanaka, T Bielak, LF Joshi, PK Rocanin-Arjo, A Kolcic, I Navarro, P Rose, LM Oldmeadow, C Riess, H Mazur, J Basu, S Goel, A Yang, Q Ghanbari, M Willemsen, G Rumley, A Fiorillo, E de Craen, AJM Grotevendt, A Scott, R Taylor, KD Delgado, GE Yao, J Kifley, A Kooperberg, C Qayyum, R Lopez, LM Berentzen, TL Raikkonen, K Mangino, M Bandinelli, S Peyser, PA Wild, S Tregouet, DA Wright, AF Marten, J Zemunik, T Morrison, AC Sennblad, B Tofler, G de Maat, MPM de Geus, EJC Lowe, GD Zoledziewska, M Sattar, N Binder, H Volker, U Waldenberger, M Khaw, KT Mcknight, B Huang, J Jenny, NS Holliday, EG Qi, LH Mcevoy, MG Becker, DM Starr, JM Sarin, AP Hysi, PG Hernandez, DG Jhun, MA Campbell, H Hamsten, A Rivadeneira, F Mcardle, WL Slagboom, PE Zeller, T Koenig, W Psaty, BM Haritunians, T Liu, JM Palotie, A Uitterlinden, AG Stott, DJ Hofman, A Franco, OH Polasek, O Rudan, I Morange, PE Wilson, JF Kardia, SLR Ferrucci, L Spector, TD Eriksson, JG Hansen, T Deary, IJ Becker, LC Scott, RJ Mitchell, P Marz, W Wareham, NJ Peters, A Greinacher, A Wild, PS Jukema, JW Boomsma, DI Hayward, C Cucca, F Tracy, R Watkins, H Reiner, AP Folsom, AR Ridker, PM O'Donnell, CJ Smith, NL Strachan, DP Dehghan, A AF de Vries, Paul S. Chasman, Daniel I. Sabater-Lleal, Maria Chen, Ming-Huei Huffman, Jennifer E. Steri, Maristella Tang, Weihong Teumer, Alexander Marioni, Riccardo E. Grossmann, Vera Hottenga, Jouke J. Trompet, Stella Mueller-Nurasyid, Martina Zhao, Jing Hua Brody, Jennifer A. Kleber, Marcus E. Guo, Xiuqing Wang, Jie Jin Auer, Paul L. Attia, John R. Yanek, Lisa R. Ahluwalia, Tarunveer S. Lahti, Jari Venturini, Cristina Tanaka, Toshiko Bielak, Lawrence F. Joshi, Peter K. Rocanin-Arjo, Ares Kolcic, Ivana Navarro, Pau Rose, Lynda M. Oldmeadow, Christopher Riess, Helene Mazur, Johanna Basu, Saonli Goel, Anuj Yang, Qiong Ghanbari, Mohsen Willemsen, Gonneke Rumley, Ann Fiorillo, Edoardo de Craen, Anton J. M. Grotevendt, Anne Scott, Robert Taylor, Kent D. Delgado, Graciela E. Yao, Jie Kifley, Annette Kooperberg, Charles Qayyum, Rehan Lopez, Lorna M. Berentzen, Tina L. Raikkonen, Katri Mangino, Massimo Bandinelli, Stefania Peyser, Patricia A. Wild, Sarah Tregouet, David-Alexandre Wright, Alan F. Marten, Jonathan Zemunik, Tatijana Morrison, Alanna C. Sennblad, Bengt Tofler, Geoffrey de Maat, Moniek P. M. de Geus, Eco J. C. Lowe, Gordon D. Zoledziewska, Magdalena Sattar, Naveed Binder, Harald Voelker, Uwe Waldenberger, Melanie Khaw, Kay-Tee Mcknight, Barbara Huang, Jie Jenny, Nancy S. Holliday, Elizabeth G. Qi, Lihong Mcevoy, Mark G. Becker, Diane M. Starr, John M. Sarin, Antti-Pekka Hysi, Pirro G. Hernandez, Dena G. Jhun, Min A. Campbell, Harry Hamsten, Anders Rivadeneira, Fernando Mcardle, Wendy L. Slagboom, P. Eline Zeller, Tanja Koenig, Wolfgang Psaty, Bruce M. Haritunians, Talin Liu, Jingmin Palotie, Aarno Uitterlinden, Andre G. Stott, David J. Hofman, Albert Franco, Oscar H. Polasek, Ozren Rudan, Igor Morange, Pierre-Emmanuel Wilson, James F. Kardia, Sharon L. R. Ferrucci, Luigi Spector, Tim D. Eriksson, Johan G. Hansen, Torben Deary, Ian J. Becker, Lewis C. Scott, Rodney J. Mitchell, Paul Maerz, Winfried Wareham, Nick J. Peters, Annette Greinacher, Andreas Wild, Philipp S. Jukema, J. Wouter Boomsma, Dorret I. Hayward, Caroline Cucca, Francesco Tracy, Russell Watkins, Hugh Reiner, Alex P. Folsom, Aaron R. Ridker, Paul M. O'Donnell, Christopher J. Smith, Nicholas L. Strachan, David P. Dehghan, Abbas TI A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; CIRCULATING FIBRINOGEN; GENETIC ARCHITECTURE; VARIANTS; DESIGN; HEMOSTASIS; RESOURCE; HEALTH AB Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including similar to 120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration. C1 [de Vries, Paul S.; Ghanbari, Mohsen; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Dehghan, Abbas] Erasmus MC, Dept Epidemiol, Wytemaweg 80, Rotterdam, Netherlands. [de Maat, Moniek P. M.] Erasmus MC, Dept Hematol, Wytemaweg 80, Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Wytemaweg 80, Rotterdam, Netherlands. [Chasman, Daniel I.; Rose, Lynda M.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Chasman, Daniel I.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sabater-Lleal, Maria; Sennblad, Bengt; Hamsten, Anders] Karolinska Inst, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Dept Med, Stockholm, Sweden. [Sennblad, Bengt] Karolinska Inst, Sci Life Lab, Stockholm, Sweden. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Chen, Ming-Huei; Huffman, Jennifer E.; Yang, Qiong; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Populat Sci Branch, Div Intramural Res,NIH, Framingham, MA USA. [Huffman, Jennifer E.; Navarro, Pau; Wright, Alan F.; Marten, Jonathan; Wilson, James F.; Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.; Lopez, Lorna M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.] Univ Edinburgh, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland. [Joshi, Peter K.; Wild, Sarah] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Joshi, Peter K.; Campbell, Harry; Polasek, Ozren; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Steri, Maristella; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Cagliari, Italy. [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Basu, Saonli] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Teumer, Alexander] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Grotevendt, Anne] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Voelker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Greinacher, Andreas] Univ Med Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany. [Marioni, Riccardo E.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Grossmann, Vera; Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, D-55122 Mainz, Germany. [Mazur, Johanna; Binder, Harald] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Med Biostat Epidemiol & Informat, D-55122 Mainz, Germany. [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 2, Prevent Cardiol & Prevent Med, D-55122 Mainz, Germany. [Hottenga, Jouke J.; Willemsen, Gonneke; de Geus, Eco J. C.; Boomsma, Dorret I.] Vrije Univ Amsterdam, Netherlands Twin Register, Dept Biol Psychol, Amsterdam, Netherlands. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Trompet, Stella; de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Riess, Helene; Waldenberger, Melanie; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Waldenberger, Melanie] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Munich, Germany. [Mueller-Nurasyid, Martina; Koenig, Wolfgang; Peters, Annette] Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany. [Zhao, Jing Hua; Scott, Robert; Wareham, Nick J.] Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit, Cambridge, England. [Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Clin Gerontol Unit, Cambridge, England. [Brody, Jennifer A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Mcknight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med Epidemiol & Hlth Serv, Seattle, WA 98195 USA. [Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Kleber, Marcus E.; Delgado, Graciela E.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany. [Guo, Xiuqing; Taylor, Kent D.; Yao, Jie] Univ Calif Los Angeles, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Guo, Xiuqing] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Dept Pediat, Torrance, CA 90509 USA. [Wang, Jie Jin; Kifley, Annette; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst Med Res, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2006, Australia. [Auer, Paul L.] Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA. [Attia, John R.; Oldmeadow, Christopher] Hunter Med Res Inst, Publ Hlth Stream, New Lambton Hts, Australia. [Scott, Rodney J.] Hunter Med Res Inst, Informat Based Med Program, New Lambton Hts, Australia. [Attia, John R.; Oldmeadow, Christopher] Univ Newcastle, Sch Med & Publ Hlth, New Lambton Hts, Australia. [Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, New Lambton Hts, Australia. [Yanek, Lisa R.; Qayyum, Rehan; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Ahluwalia, Tarunveer S.; Hansen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn,Ctr Basic Metab Res, Copenhagen, Denmark. [Ahluwalia, Tarunveer S.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark. [Ahluwalia, Tarunveer S.] Gentofte Univ Hosp, Danish Pediat Asthma Ctr, Copenhagen, Denmark. [Lahti, Jari; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Sarin, Antti-Pekka; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Lahti, Jari; Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Venturini, Cristina] UCL, Inst Opthalmol, London, England. [Venturini, Cristina; Mangino, Massimo; Hysi, Pirro G.; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Bielak, Lawrence F.; Peyser, Patricia A.; Jhun, Min A.; Kardia, Sharon L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Rocanin-Arjo, Ares; Tregouet, David-Alexandre] INSERM, Unite Mixte Rech Sante UMR S 1166, F-75013 Paris, France. [Rocanin-Arjo, Ares; Tregouet, David-Alexandre] Univ Paris 06, Sorbonne Univ, UMR S 1166, Team Genom & Pathophysiol Cardiovasc Dis, F-75013 Paris, France. [Rocanin-Arjo, Ares; Tregouet, David-Alexandre] Inst Cardiometab & Nutr ICAN, F-75013 Paris, France. [Kolcic, Ivana] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia. [Zemunik, Tatijana] Univ Split, Sch Med, Dept Biol, Split, Croatia. [Polasek, Ozren] Univ Split, Ctr Global Hlth, Fac Med, Dept Publ Hlth, Split, Croatia. [Goel, Anuj; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Radcliffe Dept Med, Dept Cardiovasc Med, Oxford, England. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Ghanbari, Mohsen] Mashhad Univ Med Sci, Sch Med, Dept Genet, Mashhad, Iran. [Rumley, Ann; Lowe, Gordon D.; Stott, David J.; Smith, Nicholas L.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Kooperberg, Charles; Liu, Jingmin; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Lopez, Lorna M.] Beaumont Hosp, Educ & Res Ctr, Royal Coll Surg Ireland, Dept Psychiat, Dublin 9, Ireland. [Lopez, Lorna M.] Univ Coll Dublin, Ctr Proteome Res, Conway Inst, Dublin 2, Ireland. [Berentzen, Tina L.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Copenhagen, Denmark. [Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy. [Morrison, Alanna C.] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Tofler, Geoffrey] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [de Geus, Eco J. C.] Vrije Univ Amsterdam, EMGO Inst, Amsterdam, Netherlands. [de Geus, Eco J. C.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland. [Huang, Jie] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England. [Jenny, Nancy S.; Tracy, Russell] Univ Vermont, Coll Med, Ctr Clin & Translat Sci, Dept Pathol & Lab Med, Colchester, VT USA. [Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Hunter Med Res Inst, Publ Hlth Stream, Newcastle, NSW 2300, Australia. [Mcevoy, Mark G.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. [Qi, Lihong] Univ Calif Davis, Dept Publ Hlth Sci, Div Biostat, Davis, CA USA. [Sarin, Antti-Pekka] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Hernandez, Dena G.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Mcardle, Wendy L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Zeller, Tanja] Univ Med Ctr Hamburg Eppendorf, Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Zeller, Tanja] German Ctr Cardiovasc Res DZHK, Partner Site Hamburg, Hamburg, Germany. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Koenig, Wolfgang] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Haritunians, Talin] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA. [Morange, Pierre-Emmanuel] La Timone Hosp, Haematol Lab, F-13385 Marseille, France. [Morange, Pierre-Emmanuel] INSERM, UMR S 1062, Nutr Obes & Risk Thrombosis, F-13385 Marseille, France. [Morange, Pierre-Emmanuel] Aix Marseille Univ, UMR S 1062, Nutr Obes & Risk Thrombosis, F-13385 Marseille, France. [Eriksson, Johan G.] Natl Inst Hlth & Welfare, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Maerz, Winfried] Synlab Serv LLC, Synlab Acad, Mannheim, Germany. [Maerz, Winfried] Med Univ Graz, Chem Lab Diagnost, Inst Clin Med, Graz, Austria. [Wild, Philipp S.] German Ctr Cardiovasc Res DZHK, Partner Site RheinMain, Mainz, Germany. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Reiner, Alex P.] Univ Washington, Seattle, WA 98195 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, NHLBI, Div Intramural Res, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Dept Vet Affairs, Seattle, WA USA. [Strachan, David P.] St Georges Univ London, Populat Hlth Res Inst, London, England. RP Dehghan, A (reprint author), Erasmus MC, Dept Epidemiol, Wytemaweg 80, Rotterdam, Netherlands. EM a.dehghan@erasmusmc.nl RI Waldenberger, Melanie/B-5355-2014; Tregouet, David-Alexandre/E-3961-2016; mangino, massimo/F-5134-2011; Peters, Annette/A-6117-2011; Slagboom, P. Eline/R-4790-2016; Polasek, Ozren/B-6002-2011; Kolcic, Ivana/E-2713-2017; OI Watkins, Hugh/0000-0002-5287-9016; Lahti, Jari/0000-0002-4310-5297; Waldenberger, Melanie/0000-0003-0583-5093; mangino, massimo/0000-0002-2167-7470; Slagboom, P. Eline/0000-0002-2875-4723; Polasek, Ozren/0000-0002-5765-1862; Kolcic, Ivana/0000-0001-7918-6052; Kleber, Marcus/0000-0003-0663-7275; Raikkonen, Katri/0000-0003-3124-3470; de Geus, Eco/0000-0001-6022-2666; Dehghan, Abbas/0000-0001-6403-016X; Sabater Lleal, Maria/0000-0002-0128-379X; Peters, Annette/0000-0001-6645-0985 FU National Heart, Lung and Blood Institute [R01HL105756, HL087660, HL100245, HL043851, HL080467]; National Heart, Lung and Blood Institute (NHLBI) [R01HL105756, R01HL087641, R01HL59367, R01HL086694, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL103612, R01HL120393, N01-HC-65226]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02, 076113/B/04/Z, 075491/Z/04]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); Juvenile Diabetes Research Foundation International; National Institute for Health Research Cambridge Biomedical Research Centre; European Commission Framework Programme 6 [018996]; French Ministry of Research; Australian National Health AMP; Medical Research Council, Canberra Australia [974159, 211069, 457349, 512423, 475604, 529912, 529923]; Wellcome Trust, UK; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [R01AG023629]; National Center for Advancing Translational Sciences; CTSI grant [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center [DK063491]; Medical Research Council (UK); European Commission Framework 6 project EUROSPAN [LSHG-CT-2006-018947]; Republic of Croatia Ministry of Science, Education and Sports [108-1080315-0302]; Cancer Research UK; European Union; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; National Heart, Lung, and Blood Institute's (NHLBI's) Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; National Institute on Aging and National Institute for Neurological Disorders and Stroke [R01 AG033193, NS017950]; National Institutes of Health/National Heart, Lung and Blood Institute [U01 HL72518, HL097698, HL59684, HL071025-01A1]; National Institutes of Health/National Institute of Nursing Research [NR0224103]; National Institutes of Health/National Center for Research Resources [M01-RR000052]; GENDINOB project; government of Rhineland-Palatinate ('Stiftung Rheinland-Pfalz fur Innovation') [AZ 961-386261/733]; research program 'Wissen schafft Zukunft' of Johannes Gutenberg-University of Mainz; research program 'Center for Translational Vascular Biology (CTVB)' of the Johannes Gutenberg-University of Mainz; Boehringer Ingelheim; PHILIPS Medical Systems; Federal Ministry of Education and Research [BMBF 01EO1003, 01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Academy of Finland; Finnish Diabetes Research Society; Folkhalsan Research Foundation; Novo Nordisk Foundation; Finska Lakaresallskapet; Signe and Ane Gyllenberg Foundation; University of Helsinki; Ministry of Education; Ahokas Foundation; Emil Aaltonen Foundation; Italian Ministry of Health [ICS110.1/RF97.71]; US National Institute on Aging [263 MD 9164, 263 MD 821336]; Intramural Research Program of the NIH, National Institute on Aging; Helmholtz Zentrum Munchen; German Research Center for Environmental Health, Neuherberg, Germany; German Federal Ministry of Education and Research (BMBF); state of Bavaria; German National Genome Research Network (NGFNPlus) [01GS0834]; University of Ulm; Munich Center of Health Sciences (MC Health) as part of LMU innovative; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F019394/1, LBC1921]; Age UK [LBC1936]; Engineering and Physical Sciences Research Council (EPSRC); Economic and Social Research Council (ESRC); Medical Research Council (MRC); sixth Framework Program (integrated project Bloodomics) [LSHM-CT-2004-503485]; seventh Framework Program (Atheroremo) of the European Union [201668]; seventh Framework Program (RiskyCAD) of the European Union [305739]; INTERREG IV Oberrhein Program [A28]; European Regional Development Fund (ERDF); Wissenschaftsoffensive TMO; Program Hospitalier de Recherche Clinique; Region Ile de France; Pierre and Marie Curie University; ICAN Institute for Cardiometabolism and Nutrition [ANR-10-IAHU-05]; Netherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, addiction-31160008, middelgroot-911-09-032, Spinozapremie 56-464-14192]; Center for Medical Systems Biology (CSMB, NWO Genomics); NBIC/BioAssist/RK [2008.024]; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL) [184.021.007]; VU University's Institute for Health and Care Research (EMGO+); Neuroscience Campus Amsterdam (NCA); European Science Foundation (ESF) [EU/QLRT-2001-01254]; European Community's Seventh Framework Program, ENGAGE [HEALTH-F4-2007-201413]; European Science Council (ERC Advanced) [230374]; Rutgers University Cell and DNA Repository [NIMH U24 MH068457-06]; Avera Institute, Sioux Falls, South Dakota (USA); National Institutes of Health (NIH) [R01D0042157-01A, MH081802, 1RC2 MH089951]; Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health; BiG Grid; Dutch e-Science Grid; NWO; Chief Scientist Office of the Scottish Government; Royal Society; MRC Human Genetics Unit; Arthritis Research UK; European Community Sixth Framework Program [LSHM-CT-2007-037273]; AstraZeneca; Swedish Research Council; Knut and Alice Wallenberg Foundation; Swedish Heart-Lung Foundation; Torsten and Ragnar Soderberg Foundation; Strategic Cardiovascular and Diabetes Programs of Karolinska Institutet; Stockholm County Council; Foundation for Strategic Research; BHF Centre of Research Excellence, Oxford; Swedish Heart-Lung Foundation [20130399]; Ake Wiberg and Tore Nilssons foundations; Magnus Bergvall Foundation; Foundation for Old Servants; European Union's Seventh Framework Programme [HEALTH-F2-2009-223004]; Netherlands Consortium of Healthy Aging [NGI: 05060810]; Scottish Executive Chief Scientist Office, Health Services Research Committee [CZG/4/306]; Research Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; NWO grant (veni) [916.12.154]; EUR Fellowship; NIA [NO1-AG-1-2109]; Sardinian Autonomous Region [7/2009, cRP3-154]; FaReBio2011 'Farmaci e Reti Biotecnologiche di Qualita'; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg West Pomerania; Leibniz Supercomputing Centre of the Bavarian Academy of Sciences and Humanities (HLRB project) [h1231]; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania [03IS2061A]; National Institute for Health Research (NIHR) Clinical Research Facility at Guy's AMP; St Thomas' NHS Foundation Trust; NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR; National Cancer Institute [CA047988]; Donald W. Reynolds Foundation; Fondation Leducq; Amgen; National Heart, Lung and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Women's Health Initiative Sequencing Project [NHLBI RC2 HL102924]; Genetics and Epidemiology of Colorectal Cancer Consortium [NCI CA137088]; Genomics and Randomized Trials Network [NHGRI U01-HG005152]; NCI training grant [R25CA094880]; King's College London FX Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung and Blood Institute grant R01HL105756. ARIC is carried out as a collaborative study supported by National Heart, Lung and Blood Institute (NHLBI) contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402 and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by grant number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. B58C acknowledges use of phenotype and genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. Genotyping for the B58C-WTCCC subset was funded by the Wellcome Trust grant 076113/B/04/Z. The B58C-T1DGC genotyping utilized resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. B58C-T1DGC GWAS data were deposited by the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, which is funded by Juvenile Diabetes Research Foundation International, the Wellcome Trust and the National Institute for Health Research Cambridge Biomedical Research Centre; the CIMR is in receipt of a Wellcome Trust Strategic Award (079895). The B58C-GABRIEL genotyping was supported by a contract from the European Commission Framework Programme 6 (018996) and grants from the French Ministry of Research. BMES has been supported by the Australian National Health & Medical Research Council, Canberra Australia (grant numbers 974159, 211069, 457349, 512423, 475604, 529912 and the funding for Centre for Clinical Research Excellence in Translational Clinical Research in Eye Diseases, CCRE in TCR-Eye, grant ID 529923); in addition, funding by the Wellcome Trust, UK (to A. Viswanathan, P. McGuffin, P. Mitchell, F. Topouzis and P. Foster) has supported the genotyping costs of the entire BMES population. This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086 and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612 and R01HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124 and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The CROATIA-Split study was funded by grants from the Medical Research Council (UK), European Commission Framework 6 project EUROSPAN (contract no.; r LSHG-CT-2006-018947) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). The CROATIA-Korcula study was funded by grants from the Medical Research Council (UK), European Commission Framework 6 project EUROSPAN (Contract no. LSHG-CT-2006-018947) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). The CROATIA-Vis study was funded by grants from the Medical Research Council (UK) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). The EPIC Norfolk Study is funded by program grants from the Medical Research Council UK and Cancer Research UK, and by additional support from the European Union, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and the Wellcome Trust. FHS was partially supported by the National Heart, Lung, and Blood Institute's (NHLBI's) Framingham Heart Study (contract no. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (contract no. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Partial investigator support was provided by the National Institute of Diabetes and Digestive and Kidney Diseases K24 DK080140 (J.B. Meigs), the National Institute on Aging and National Institute for Neurological Disorders and Stroke R01 AG033193, NS017950 (S Seshadri). GeneSTAR was supported by grants from the National Institutes of Health/National Heart, Lung and Blood Institute (U01 HL72518, HL097698, HL59684 and HL071025-01A1), the National Institutes of Health/National Institute of Nursing Research (NR0224103) and the National Institutes of Health/National Center for Research Resources (M01-RR000052) to the Johns Hopkins General Clinical Research Center. The Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, grant numbers HL087660 and HL100245 from National Heart, Lung, Blood Institute. Tarunveer Singh Ahluwalia received his post-doctoral research funding from GENDINOB project and acknowledges the same. The Gutenberg Health Study is funded through the government of Rhineland-Palatinate ('Stiftung Rheinland-Pfalz fur Innovation', contract AZ 961-386261/733), the research programs 'Wissen schafft Zukunft' and 'Center for Translational Vascular Biology (CTVB)' of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including an unrestricted grant for the Gutenberg Health Study. V.G. and P.S.W. are funded by the Federal Ministry of Education and Research (BMBF 01EO1003). Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska Lakaresallskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation. The InCHIANTI study baseline (1998-2000) was supported as a 'targeted project' (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the US National Institute on Aging (contracts: 263 MD 9164 and 263 MD 821336); this research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.; r The KORA studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF) and by the state of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFNPlus, project number 01GS0834) and through additional funds from the University of Ulm. Furthermore, the research was supported within the Munich Center of Health Sciences (MC Health) as part of LMU innovative. The whole genome association study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC; Ref. BB/F019394/1). The LBC1936 research was supported by Age UK. The LBC1921 data collection was funded by the BBSRC. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), Economic and Social Research Council (ESRC) and Medical Research Council (MRC) is gratefully acknowledged. LURIC has received funding from the sixth Framework Program (integrated project Bloodomics, grant no.: LSHM-CT-2004-503485) and from the seventh Framework Program (Atheroremo, grant agreement number 201668 and RiskyCAD, grant agreement number 305739) of the European Union as well as from the INTERREG IV Oberrhein Program (Project A28, Genetic mechanisms of cardiovascular diseases) with support from the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive TMO. The MARTHA project was supported by grants from the Program Hospitalier de Recherche Clinique. Statistical analyses of the MARTHA dataset were performed using the C2BIG computing cluster, funded by the Region Ile de France, Pierre and Marie Curie University, and the ICAN Institute for Cardiometabolism and Nutrition (ANR-10-IAHU-05). MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and RR-024156. Funding for CARe genotyping was provided by NHLBI Contract N01-HC-65226. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. NTR: funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 904-61-193,480-04-004, 400-05-717, addiction-31160008, middelgroot-911-09-032, Spinozapremie 56-464-14192, Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007).; r VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the European Science Foundation (ESF, EU/QLRT-2001-01254), the European Community's Seventh Framework Program (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC Advanced, 230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2 MH089951). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, the MRC Human Genetics Unit, Arthritis Research UK and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. PROCARDIS was supported by the European Community Sixth Framework Program (LSHM-CT-2007-037273), AstraZeneca, the British Heart Foundation, the Wellcome Trust (contract no. 075491/Z/04), the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Soderberg Foundation, the Strategic Cardiovascular and Diabetes Programs of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council. Jemma C. Hopewell and Robert Clarke acknowledge support from the BHF Centre of Research Excellence, Oxford. M. Sabater-Lleal is supported by the Swedish Heart-Lung Foundation (20130399), and acknowledges funding from Ake Wiberg and Tore Nilssons foundations. B. Sennblad acknowledges funding from the Magnus Bergvall Foundation and the Foundation for Old Servants. PROSPER-PHASE received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. HEALTH-F2-2009-223004. For a part of the genotyping we received funding from the Netherlands Consortium of Healthy Aging (NGI: 05060810). Measurement of serum fibrinogen was supported by a grant from the Scottish Executive Chief Scientist Office, Health Services Research Committee grant number CZG/4/306. This work was performed as part of an ongoing collaboration of the PROSPER study group in the universities of Leiden, Glasgow and Cork. Professor Dr J.W.J. is an Established Clinical Investigator of the Netherlands Heart Foundation (2001 D 032). The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (no. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project no. 050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. A. D. is supported by NWO grant (veni, 916.12.154) and the EUR Fellowship.; r The SardiNIA ('ProgeNIA') team was supported by contract NO1-AG-1-2109 from the NIA. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging, by Sardinian Autonomous Region (L.R. no. 7/2009) grant cRP3-154, and by grant FaReBio2011 'Farmaci e Reti Biotecnologiche di Qualita'. SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg West Pomerania. Computing resources have been made available by the Leibniz Supercomputing Centre of the Bavarian Academy of Sciences and Humanities (HLRB project h1231). The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG and the Cache Campus program of the InterSystems GmbH. This work is also part of the research project Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED consortium is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania (03IS2061A). TwinsUK was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) Clinical Research Facility at Guy's & St Thomas' NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. Tim Spector is an NIHR senior Investigator and is holder of an ERC Advanced Principal Investigator award. SNP Genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. The WGHS is supported by HL043851 and HL080467 from the National Heart, Lung and Blood Institute and CA047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. The WHI program is funded by the National Heart, Lung and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Genotyping and analysis were supported through the Women's Health Initiative Sequencing Project (NHLBI RC2 HL102924), the Genetics and Epidemiology of Colorectal Cancer Consortium (NCI CA137088), the Genomics and Randomized Trials Network (NHGRI U01-HG005152), and an NCI training grant (R25CA094880). NR 56 TC 3 Z9 3 U1 7 U2 14 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 JAN 15 PY 2016 VL 25 IS 2 BP 358 EP 370 DI 10.1093/hmg/ddv454 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DG5VU UT WOS:000372148200014 PM 26561523 ER PT J AU Ledreux, A Boger, HA Hinson, VK Cantwell, K Granholm, AC AF Ledreux, Aurelie Boger, Heather A. Hinson, Vanessa K. Cantwell, Kelsey Granholm, Ann-Charlotte TI BDNF levels are increased by aminoindan and rasagiline in a double lesion model of Parkinson's disease SO BRAIN RESEARCH LA English DT Article DE Parkinson's disease; Dopamine; Norepinephrine; Monoamine oxidase inhibitors; Cognition; Neuroprotection ID DOPA-INDUCED DYSKINESIA; NEUROTROPHIC FACTOR; MONOAMINE-OXIDASE; LOCUS-CERULEUS; NEURODEGENERATIVE DISORDERS; SIGNALING PATHWAY; SUBSTANTIA-NIGRA; SH-SY5Y CELLS; MOTOR; SELEGILINE AB The anti-Parkinsonian drug rasagiline is a selective, irreversible inhibitor of monoamine oxidase and is used in the treatment of Parkinson's disease (PD). Its postulated neuroprotective effects may be attributed to MAO inhibition, or to its propargylamine moiety. The major metabolite of rasagiline, aminoindan, has shown promising neuroprotective properties in vitro but there is a paucity of studies investigating in vivo effects of this compound. Therefore, we examined neuroprotective effects of rasagiline and its metabolite aminoindan in a double lesion model of PD. Male Fisher 344 rats received i.p. injections of the noradrenergic neurotoxin DSP-4 and intra-striatal stereotaxic microinjections of the dopamine neurotoxin 6-OHDA. Saline, rasagiline or aminoindan (3 mg/kg/day s.c.) were delivered via Alzet minipumps for 4 weeks. Rats were then tested for spontaneous locomotion and a novel object recognition task. Following behavioral testing, brain tissue was processed for ELISA measurements of growth factors and immunohistochemistry. Double-lesioned rats treated with rasagiline or aminoindan had reduced behavioral deficits, both in motor and cognitive tasks compared to saline-treated double-lesioned rats. BDNF levels were significantly increased in the hippocampus and striatum of the rasagiline- and aminoindan-lesioned groups compared to the saline-treated lesioned group. Double-lesioned rats treated with rasagiline or aminoindan exhibited a sparing in the mitochondrial marker Hsp60, suggesting mitochondrial involvement in neuroprotection. Tyrosine hydroxylase (TH) immunohistochemistry revealed a sparing of TH-immunoreactive terminals in double-lesioned rats treated with rasagiline or aminoindan in the striatum, hippocampus, and substantia nigra. These data provide evidence of neuroprotection by aminoindan and rasagiline via their ability to enhance BDNF levels. Published by Elsevier B.V. C1 [Ledreux, Aurelie; Boger, Heather A.; Granholm, Ann-Charlotte] Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave, Charleston, SC 29425 USA. [Ledreux, Aurelie; Boger, Heather A.; Granholm, Ann-Charlotte] Med Univ S Carolina, Ctr Aging, Charleston, SC 29425 USA. [Hinson, Vanessa K.] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. [Hinson, Vanessa K.] Ralph H Johnson VA Med Ctr, Neurol Serv, Charleston, SC USA. [Cantwell, Kelsey] Coll Charleston, Psychol, Charleston, SC 29401 USA. [Cantwell, Kelsey] Coll Charleston, Program Neurosci, Charleston, SC 29401 USA. RP Granholm, AC (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave, Charleston, SC 29425 USA. EM granholm@musc.edu FU TEVA Pharmaceuticals FX This work was made possible by a Grant from TEVA Pharmaceuticals, and a Medical Accuracy Review was conducted by Teva. The authors would like to thank Mr. Alfred Moore, Ms. Claudia Umphlet, and Ms. Laura Columbo for expert technical support for this project. NR 56 TC 0 Z9 0 U1 2 U2 10 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 JAN 15 PY 2016 VL 1631 BP 34 EP 45 DI 10.1016/j.brainres.2015.11.028 PG 12 WC Neurosciences SC Neurosciences & Neurology GA DD7IK UT WOS:000370096700004 PM 26607251 ER PT J AU Khurshid, S Keaney, J Ellinor, PT Lubitz, SA AF Khurshid, Shaan Keaney, John Ellinor, Patrick T. Lubitz, Steven A. TI A Simple and Portable Algorithm for Identifying Atrial Fibrillation in the Electronic Medical Record SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ISCHEMIC-STROKE; RISK-FACTORS; FOLLOW-UP; ANTICOAGULATION; COHORT AB Atrial fibrillation (AF) is common and increases stroke risk and mortality. Many knowledge gaps remain with respect to practice patterns and outcomes. Electronic medical records (EMRs) may serve as powerful research tools if AF status can be properly ascertained. We sought to develop an algorithm for identifying subjects with and without AF in the EMR and compare it to previous methods. Using a hospital network EMR (n = 5,737,846), we randomly selected 8,200 subjects seen at a large academic medical center in January 2014 to derive and validate 7 AF classification schemas (4 cases and 3 controls) to construct a composite AF algorithm. In an independent sample of 172,138 subjects, we compared this algorithm against published AF classification methods. In total, we performed manual adjudication of AF in 700 subjects. Three AF schemas (AF1, AF2, and AF4) achieved positive predictive value (PPV) >0.9. Two control schemas achieved PPV>0.9 (control 1 and control 3). A combination algorithm AF1, AF2, and AF4 (PPV 88%; 8.2% classified) outperformed published classification methods including >1 outpatient International Statistical Classification of Diseases, Ninth Revision code or 1 outpatient code with an electrocardiogram demonstrating AF (PPV 82%; 5.9% classified), =1 inpatient International Statistical Classification of Diseases, Ninth Revision code or electrocardiogram demonstrating AF (PPV 88%; 6.1% classified), or the intersection of these (PPV 84%; 7.4% classified). When applied simultaneously, the case and control algorithms classified 98.4% of the cohort with zero disagreement. In conclusion, we derived a parsimonious and portable algorithm to identify subjects with and without AF with high sensitivity. If broadly applied, this algorithm can provide optimal power for EMR-based AF research. Copyright (C) 2016 Elsevier Inc. All rights reserved. C1 [Khurshid, Shaan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Keaney, John; Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Keaney, John; Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Dept Cardiol, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.; Lubitz, SA (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM slubitz@mgh.harvard.edu FU NIH (Bethesda, MD) [2R01HL092577, R01HL104156, K24HL105780]; Duke Charitable Foundation Clinical Scientist Development Award [2014105]; American Heart Association Established Investigator Award [13EIA14220013]; Fondation Leducq [14CVD01]; [K23HL114724] FX Dr. Lubitz receives grant K23HL114724, and Dr. Ellinor receives grants 2R01HL092577, R01HL104156, and K24HL105780 from the NIH (Bethesda, MD). Dr. Lubitz received a Doris Duke Charitable Foundation Clinical Scientist Development Award 2014105 and Dr. Ellinor received an American Heart Association Established Investigator Award 13EIA14220013 and by support from the Fondation Leducq 14CVD01. NR 14 TC 2 Z9 2 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2016 VL 117 IS 2 BP 221 EP 225 DI 10.1016/j.amjcard.2015.10.031 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DC6TE UT WOS:000369351700009 PM 26684516 ER PT J AU Shah, RV Kato, S Roujol, S Murthy, V Beilm, S Kashem, A Basha, T Jang, J Eisman, AS Eisman, AS Manning, WJ Nezafat, R AF Shah, Ravi V. Kato, Shingo Roujol, Sebastien Murthy, Venkatesh Beilm, Steven Kashem, Abyaad Basha, Tamer Jang, Jihye Eisman, Aaron S. Eisman, Aaron S. Manning, Warren J. Nezafat, Reza TI Native Myocardial T-1 as a Biomarker of Cardiac Structure in Non-Ischemic Cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MAGNETIC-RESONANCE; DILATED CARDIOMYOPATHY; RESYNCHRONIZATION THERAPY; T1; FIBROSIS; DISEASE; QUANTIFICATION; ASSOCIATION; LOCATION; SHMOLLI AB Diffuse myocardial fibrosis is involved in the pathology of nonischemic cardiomyopathy (NIC). Recently, the application of native (noncontrast) myocardial T-1 measurement has been proposed as a method for characterizing diffuse interstitial fibrosis. To determine the association of native T-1 with myocardial structure and function, we prospectively studied 39 patients with NIC (defined as left ventricular ejection fraction (LVEF) <= 50% without cardiac magnetic resonance (CMR) evidence of previous infarction) and 27 subjects with normal LVEF without known overt cardiovascular disease. T-1, T-2, and extracellular volume fraction (ECV) were determined over 16 segments across the base, mid, and apical left ventricular (LV). NIC participants (57 +/- 15 years) were predominantly men (74%), with a mean LVEF 34 +/- 10%. Subjects with NIC had a greater native T-1 (1,131 +/- 51 vs 1,069 +/- 29 ms; p <0.0001), a greater ECV (0.28 +/- 0.04 vs 0.25 +/- 0.02, p = 0.002), and a longer myocardial T-2 (52 +/- 8 vs 47 +/- 5 ms; p = 0.02). After multivariate adjustment, a lower global native T-1 time in NIC was associated with a greater LVEF (beta = -0.59, p = 0.0003), greater right ventricular ejection fraction (beta = -0.47, p = 0.006), and smaller left atrial volume index (beta = 0.51, p = 0.001). The regional distribution of native myocardial T-1 was similar in patients with and without NIC. In NIC, native myocardial T-1 is elevated in all myocardial segments, suggesting a global (not regional) abnormality of myocardial tissue composition. In conclusion, native T-1 may represent a rapid, noncontrast alternative to ECV for delineating myocardial tissue remodeling in NIC. (C) 2016 Elsevier Inc. All rights reserved. C1 [Shah, Ravi V.; Kato, Shingo; Roujol, Sebastien; Beilm, Steven; Kashem, Abyaad; Basha, Tamer; Jang, Jihye; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. [Manning, Warren J.; Nezafat, Reza] Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. [Murthy, Venkatesh] Univ Michigan, Dept Med & Radiol, Ann Arbor, MI 48109 USA. [Eisman, Aaron S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Shah, RV (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. EM rshah1@bidmc.harvard.edu NR 23 TC 1 Z9 1 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2016 VL 117 IS 2 BP 282 EP 288 DI 10.1016/j.amjcard.2015.10.046 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DC6TE UT WOS:000369351700019 PM 26684511 ER PT J AU Nagy, N Barad, C Graham, HK Hotta, R Cheng, LS Fejszak, N Goldstein, AM AF Nagy, Nandor Barad, Csilla Graham, Hannah K. Hotta, Ryo Cheng, Lily S. Fejszak, Nora Goldstein, Allan M. TI Sonic hedgehog controls enteric nervous system development by patterning the extracellular matrix SO DEVELOPMENT LA English DT Article DE Enteric nervous system; Sonic hedgehog; Patched; Ptch; Epithelium; Extracellular matrix; Enteric neural crest cells; Hirschsprung disease; Chick; Quail; Mouse ID NEURAL CREST CELLS; CHICK-EMBRYO; MIGRATION; GUT; HINDGUT; DIFFERENTIATION; EXPRESSION; MICE; VERSICAN; GDNF AB The enteric nervous system (ENS) develops from neural crest cells that migrate along the intestine, differentiate into neurons and glia, and pattern into two plexuses within the gut wall. Inductive interactions between epithelium and mesenchyme regulate gut development, but the influence of these interactions on ENS development is unknown. Epithelial-mesenchymal recombinations were constructed using avian hindgut mesenchyme and non-intestinal epithelium from the bursa of Fabricius. These recombinations led to abnormally large and ectopically positioned ganglia. We hypothesized that sonic hedgehog (Shh), a secreted intestinal epithelial protein not expressed in the bursa, mediates this effect. Inhibition of Shh signaling, by addition of cyclopamine or a function-blocking antibody, resulted in large, ectopic ganglia adjacent to the epithelium. Shh overexpression, achieved in ovo using Shh-encoding retrovirus and in organ culture using recombinant protein, led to intestinal aganglionosis. Shh strongly induced the expression of versican and collagen type IX, whereas cyclopamine reduced expression of these chondroitin sulfate proteoglycans that are known to be inhibitory to neural crest cell migration. Shh also inhibited enteric neural crest-derived cell (ENCC) proliferation, promoted neuronal differentiation, and reduced expression of Gdnf, a key regulator of ENS formation. Ptc1 and Ptc2 were not expressed by ENCCs, and migration of isolated ENCCs was not inhibited by Shh protein. These results suggest that epithelial-derived Shh acts indirectly on the developing ENS by regulating the composition of the intestinal microenvironment. C1 [Nagy, Nandor; Graham, Hannah K.; Hotta, Ryo; Cheng, Lily S.; Goldstein, Allan M.] Harvard Univ, Sch Med, Dept Pediat Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nagy, Nandor; Barad, Csilla; Fejszak, Nora] Semmelweis Univ, Dept Human Morphol & Dev Biol, Fac Med, H-1094 Budapest, Hungary. RP Nagy, N (reprint author), Harvard Univ, Sch Med, Dept Pediat Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA.; Nagy, N (reprint author), Semmelweis Univ, Dept Human Morphol & Dev Biol, Fac Med, H-1094 Budapest, Hungary. EM nagy.nandor@med.semmelweis-univ.hu FU National Institutes of Health (NIH)-NIDDK [R01DK080914]; American Pediatric Surgical Association Foundation; Bolyai Fellowship of the Hungarian Academy of Sciences FX This work was supported by the National Institutes of Health (NIH)-NIDDK [R01DK080914] and the American Pediatric Surgical Association Foundation. N.N. was supported by a Bolyai Fellowship of the Hungarian Academy of Sciences. Deposited in PMC for release after 12 months. NR 62 TC 3 Z9 3 U1 3 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD JAN 15 PY 2016 VL 143 IS 2 BP 264 EP 275 DI 10.1242/dev.128132 PG 12 WC Developmental Biology SC Developmental Biology GA DC8WJ UT WOS:000369500200009 PM 26674309 ER PT J AU Liu, ES Raimann, A Chae, BT Martins, JS Baccarini, M Demay, MB AF Liu, Eva S. Raimann, Adalbert Chae, Byongsoo Timothy Martins, Janaina S. Baccarini, Manuela Demay, Marie B. TI c-Raf promotes angiogenesis during normal growth plate maturation SO DEVELOPMENT LA English DT Article DE c-Raf; Growth plate; Chondrocyte apoptosis; VEGF; Angiogenesis; Mouse ID ENDOCHONDRAL BONE-FORMATION; HYPERTROPHIC CHONDROCYTES; EMBRYONIC LETHALITY; RAF/MEK/ERK PATHWAY; APOPTOSIS; VEGF; EXPRESSION; DIFFERENTIATION; ACTIVATION; MICE AB Extracellular phosphate plays a key role in growth plate maturation by inducing Erk1/2 (Mapk3/1) phosphorylation, leading to hypertrophic chondrocyte apoptosis. The Raf kinases induce Mek1/2 (Map2k1/2) and Erk1/2 phosphorylation; however, a role for Raf kinases in endochondral bone formation has not been identified. Ablation of both A-Raf (Araf) and B-Raf (Braf) in chondrocytes does not alter growth plate maturation. Because c-Raf (Raf1) phosphorylation is increased by extracellular phosphate and c-Raf is the predominant isoform expressed in hypertrophic chondrocytes, chondrocyte-specific c-Raf knockout mice (c-Raf(f/f); ColII-Cre(+)) were generated to define a role for c-Raf in growth plate maturation. In vivo studies demonstrated that loss of c-Raf in chondrocytes leads to expansion of the hypertrophic layer of the growth plate, with decreased phospho-Erk1/2 immunoreactivity and impaired hypertrophic chondrocyte apoptosis. However, cultured hypertrophic chondrocytes from these mice did not exhibit impairment of phosphate-induced Erk1/2 phosphorylation. Studies performed to reconcile the discrepancy between the in vitro and in vivo hypertrophic chondrocyte phenotypes revealed normal chondrocyte differentiation in c-Raf(f/f); ColII-Cre(+) mice and lack of compensatory increase in the expression of A-Raf and B-Raf. However, VEGF (Vegfa) immunoreactivity in the hypertrophic chondrocytes of c-Raf(f/f); ColII-Cre(+) mice was significantly reduced, associated with increased ubiquitylation of VEGF protein. Thus, c-Raf plays an important role in growth plate maturation by regulating vascular invasion, which is crucial for replacement of terminally differentiated hypertrophic chondrocytes by bone. C1 [Liu, Eva S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 75 Francis St, Boston, MA 02115 USA. [Liu, Eva S.; Raimann, Adalbert; Chae, Byongsoo Timothy; Martins, Janaina S.; Demay, Marie B.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Liu, Eva S.; Raimann, Adalbert; Martins, Janaina S.; Demay, Marie B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raimann, Adalbert] Med Univ Vienna, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria. [Baccarini, Manuela] Univ Vienna, Dept Microbiol Immunobiol & Genet, Ctr Mol Biol, Max F Perutz Labs, Doktor Bohr Gasse 9, A-1030 Vienna, Austria. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.; Demay, MB (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM demay@helix.mgh.harvard.edu OI Baccarini, Manuela/0000-0002-3033-391X FU National Institutes of Health [P30 AR066261, R01 AR061376, T32 DK007529, F32 AR065386]; European Society for Paediatric Endocrinology FX This work was supported by National Institutes of Health grants [P30 AR066261 and R01 AR061376 to M.B.D.; T32 DK007529 and F32 AR065386 to E.S.L.], and a Research Fellowship from the European Society for Paediatric Endocrinology (to A.R.). Deposited in PMC for release after 12 months. NR 38 TC 4 Z9 4 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD JAN 15 PY 2016 VL 143 IS 2 BP 348 EP 355 DI 10.1242/dev.127142 PG 8 WC Developmental Biology SC Developmental Biology GA DC8WJ UT WOS:000369500200017 PM 26657770 ER PT J AU Philip, A Desai, A Nguyen, PA Bimey, P Colavecchia, A Karralli, R Smith, L Lorimer, D Burgess, G Munch, K Daniel, N Lionetti, J Garey, KW AF Philip, Achsah Desai, Avani Phouc Anne Nguyen Bimey, Patrick Colavecchia, Anthony Karralli, Rusol Smith, Lindsey Lorimer, Dirk Burgess, Gwen Munch, Kyle Daniel, Nelvin Lionetti, Jason Garey, Kevin W. TI Evaluating pharmacy leader development through the seven action logics SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article AB Purpose. Pharmacy leader development over time was analyzed using the seven action logics. Methods. As part of an ongoing leadership seminar series, students were required to select a visionary pharmacy leader and conduct a structured interview to evaluate pharmacy leaders' action logics. A standardized questionnaire comprising 13 questions was created by the class. Questions addressed leadership qualities during the leaders' early years, education years, and work years. Transcripts were then coded by two separate trained investigators based on the leader's stage of life to provide a score for each action logic individually over time. Kappa coefficient was used to evaluate interrater agreement. Results. A total of 14 leaders were interviewed. All leaders were currently employed and had won national awards for their contributions to pharmacy practice. Overall, there was 82% agreement between the two evaluators' scores for the various characteristics. Action logics changed based on the leaders' life stage. Using aggregate data from all leader interviews, a progression from lower-order action logics (opportunist, diplomat, expert) to higher -order action logics (strategist, alchemist) was found. Ten leaders (71%) were diplomats during their early years. Six leaders (43%) were experts during their education years, and 4 (29%) were strategists or alchemists. During the third life stage analyzed (the work years), 6 leaders (43%) were strategists, and 2 were alchemists. During their work years, all leaders had a percentage of their answers coded as alchemist (range, 5-22%). Conclusion. Throughout their professional careers, pharmacy leaders continually develop skills through formal education and mentorship that follow action logics. C1 [Philip, Achsah] Med Univ Southern Carolina, Charleston, SC USA. [Desai, Avani] DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Phouc Anne Nguyen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bimey, Patrick] Josephs Hosp, Tampa, FL USA. [Colavecchia, Anthony] Houston Methodist Hosp, Houston, TX USA. [Karralli, Rusol] Apexus, Irving, TX USA. [Smith, Lindsey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lorimer, Dirk] Childrens Hosp, Houston, TX USA. [Burgess, Gwen] Baptist Hosp Southeast Texas, Beaumont, TX USA. [Munch, Kyle] Kingwood Med Ctr, Kingwood, TX USA. [Daniel, Nelvin] Univ Texas Med Branch, Galveston, TX 77555 USA. [Lionetti, Jason] Harris Hlth Syst, Houston, TX USA. [Garey, Kevin W.] Univ Houston, Coll Pharm, Houston, TX 77030 USA. RP Garey, KW (reprint author), Univ Houston, Coll Pharm, Houston, TX 77030 USA. EM kgarey@uh.edu NR 9 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 EI 1535-2900 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JAN 15 PY 2016 VL 73 IS 2 BP 82 EP 85 DI 10.2146/ajhp150162 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB8HL UT WOS:000368757700012 PM 26721538 ER PT J AU Jaykumar, AB Caceres, PS Sablaban, I Tannous, BA Ortiz, PA AF Jaykumar, Ankita Bachhawat Caceres, Paulo S. Sablaban, Ibrahim Tannous, Bakhos A. Ortiz, Pablo A. TI Real-time monitoring of NKCC2 endocytosis by total internal reflection fluorescence (TIRF) microscopy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE Na-K-2Cl; trafficking; biotin ligase BirA; single molecule; apical membrane ID THICK ASCENDING LIMBS; NA+-K+-2CL(-) COTRANSPORTER NKCC2; IN-VIVO; METABOLIC BIOTINYLATION; MAMMALIAN-CELLS; BIOTIN LIGASE; ENDOPLASMIC-RETICULUM; BACTERIAL EXPRESSION; SURFACE EXPRESSION; CL-COTRANSPORTER AB The apical Na-K-2Cl cotransporter (NKCC2) mediates NaCl reabsorption by the thick ascending limb (TAL). The amount of NKCC2 at the apical membrane of TAL cells is determined by exocytic delivery, recycling, and endocytosis. Surface biotinylation allows measurement of NKCC2 endocytosis, but it has low time resolution and does not allow imaging of the dynamic process of endocytosis. We hypothesized that total internal reflection fluorescence (TIRF) microscopy imaging of labeled NKCC2 would allow monitoring of NKCC2 endocytosis in polarized Madin-Darby canine kidney (MDCK) and TAL cells. Thus we generated a NKCC2 construct containing a biotin acceptor domain (BAD) sequence between the transmembrane domains 5 and 6. Once expressed in polarized MDCK or TAL cells, surface NKCC2 was specifically biotinylated by exogenous biotin ligase (BirA). We also demonstrate that expression of a secretory form of BirA in TAL cells induces metabolic biotinylation of NKCC2. Labeling biotinylated surface NKCC2 with fluorescent streptavidin showed that most apical NKCC2 was located within small discrete domains or clusters referred to as "puncta" on the TIRF field. NKCC2 puncta were observed to disappear from the TIRF field, indicating an endocytic event which led to a decrease in the number of surface puncta at a rate of 1.18 +/- 0.16%/min in MDCK cells, and a rate 1.09 +/- 0.08%/min in TAL cells (n = 5). Treating cells with a cholesterol-chelating agent (methyl-beta-cyclodextrin) completely blocked NKCC2 endocytosis. We conclude that TIRF microscopy of labeled NKCC2 allows the dynamic imaging of individual endocytic events at the apical membrane of TAL cells. C1 [Jaykumar, Ankita Bachhawat; Caceres, Paulo S.; Sablaban, Ibrahim; Ortiz, Pablo A.] Henry Ford Hosp, Hypertens & Vasc Res, Detroit, MI 48202 USA. [Jaykumar, Ankita Bachhawat; Caceres, Paulo S.; Ortiz, Pablo A.] Wayne State Univ, Dept Physiol, Detroit, MI USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Boston, MA USA. RP Ortiz, PA (reprint author), Henry Ford Hosp, E&R Bldg,Rm 7038,2799 West Grand Blvd, Detroit, MI 48202 USA. EM portiz1@hfhs.org FU National Institutes of Health (NIH) [P01 HL090550]; American Heart Association; NIH/NINDS [P30NS045776] FX This work was supported in part by National Institutes of Health (NIH) Grant P01 HL090550 (P. A. Ortiz). P. Caceres was supported in part by a Pre-doctoral fellowship grant from the American Heart Association. We thank MGH vector core (funded by NIH/NINDS P30NS045776 to BAT) for the generation of lentivirus vectors obtained from our collaborator, B. A. Tannous. NR 48 TC 2 Z9 2 U1 5 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN 15 PY 2016 VL 310 IS 2 BP F183 EP F191 DI 10.1152/ajprenal.00104.2015 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA DC2TS UT WOS:000369070100010 PM 26538436 ER PT J AU Bernstein, BE AF Bernstein, Bradley E. TI Epigenetic mechanisms of tumor initiation and evolution SO CANCER RESEARCH LA English DT Meeting Abstract CT American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer CY SEP 24-27, 2015 CL Atlanta, GA SP Amer Assoc Canc Res C1 [Bernstein, Bradley E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bernstein, Bradley E.] Harvard Univ, Sch Med, Broad Inst Harvard & MIT, Boston, MA 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 JAN 15 PY 2016 VL 76 SU 2 MA IA01 DI 10.1158/1538-7445.CHROMEPI15-IA01 PG 1 WC Oncology SC Oncology GA DC0TN UT WOS:000368930800047 ER PT J AU Krajewska, M Moore, NF Chipumuro, E Zhang, TH Marco, E Hatheway, C Sharma, B Kwiatkowski, N Yuan, GC Young, RA Gray, NS George, RE AF Krajewska, Malgorzata Moore, Nathan F. Chipumuro, Edmond Zhang, Tinghu Marco, Eugenio Hatheway, Clark Sharma, Bandana Kwiatkowski, Nicholas Yuan, Guo-Cheng Young, Richard A. Gray, Nathanael S. George, Rani E. TI Targeting super-enhancer driven oncogene transcription through cyclin-dependent kinase inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract CT American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer CY SEP 24-27, 2015 CL Atlanta, GA SP Amer Assoc Canc Res C1 [Krajewska, Malgorzata; Moore, Nathan F.; Chipumuro, Edmond; Zhang, Tinghu; Marco, Eugenio; Hatheway, Clark; Sharma, Bandana; Gray, Nathanael S.; George, Rani E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kwiatkowski, Nicholas; Yuan, Guo-Cheng; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 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 JAN 15 PY 2016 VL 76 SU 2 MA PR04 DI 10.1158/1538-7445.CHROMEPI15-PR04 PG 2 WC Oncology SC Oncology GA DC0TN UT WOS:000368930800062 ER PT J AU Labbe, DP Zadra, G Ebot, EM Lin, CY Reyes, JM Cacciatore, S Cotter, M Creech, AL Jaffe, JD Kantoff, PW Bradner, JE Mucci, LA Loda, M Brown, M AF Labbe, David P. Zadra, Giorgia Ebot, Ericka M. Lin, Charles Y. Reyes, Jaime M. Cacciatore, Stefano Cotter, Maura Creech, Amanda L. Jaffe, Jacob D. Kantoff, Philip W. Bradner, James E. Mucci, Lorelei A. Loda, Massimo Brown, Myles TI High-fat diet enhances MYC-driven prostate cancer through epigenomic and metabolomic rewiring SO CANCER RESEARCH LA English DT Meeting Abstract CT American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer CY SEP 24-27, 2015 CL Atlanta, GA SP Amer Assoc Canc Res C1 [Labbe, David P.; Zadra, Giorgia; Lin, Charles Y.; Reyes, Jaime M.; Cotter, Maura; Kantoff, Philip W.; Bradner, James E.; Loda, Massimo; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ebot, Ericka M.; Mucci, Lorelei A.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Cacciatore, Stefano] Univ London Imperial Coll Sci Technol & Med, London, England. [Creech, Amanda L.; Jaffe, Jacob D.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 3 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 JAN 15 PY 2016 VL 76 SU 2 MA A10 DI 10.1158/1538-7445.CHROMEPI15-A10 PG 2 WC Oncology SC Oncology GA DC0TN UT WOS:000368930800006 ER PT J AU Yankeelov, TE Mankoff, DA Schwartz, LH Lieberman, FS Buatti, JM Mountz, JM Erickson, BJ Fennessy, FMM Huang, W Kalpathy-Cramer, J Wahl, RL Linden, HM Kinahan, PE Zhao, BS Hylton, NM Gillies, RJ Clarke, L Nordstrom, R Rubin, DL AF Yankeelov, Thomas E. Mankoff, David A. Schwartz, Lawrence H. Lieberman, Frank S. Buatti, John M. Mountz, James M. Erickson, Bradley J. Fennessy, Fiona M. M. Huang, Wei Kalpathy-Cramer, Jayashree Wahl, Richard L. Linden, Hannah M. Kinahan, Paul E. Zhao, Binsheng Hylton, Nola M. Gillies, Robert J. Clarke, Laurence Nordstrom, Robert Rubin, Daniel L. TI Quantitative Imaging in Cancer Clinical Trials SO CLINICAL CANCER RESEARCH LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; TUMOR RESPONSE; APPARENT DIFFUSION; LUNG-CANCER; VOLUME; PET; INFRASTRUCTURE; WHITEPAPERS; ONCOLOGY; CRITERIA AB As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies. (C) 2016 AACR. C1 [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Radiol, Inst Imaging Sci, Nashville, TN USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Radiol Sci, Nashville, TN USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Phys, Nashville, TN 37235 USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Canc Biol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Mankoff, David A.] Univ Penn, Perelman Sch Med, Radiol Nucl Med, Philadelphia, PA 19104 USA. [Schwartz, Lawrence H.; Zhao, Binsheng] Columbia Univ, Dept Radiol, New York, NY USA. [Lieberman, Frank S.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Lieberman, Frank S.] Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA USA. [Lieberman, Frank S.] Univ Pittsburgh, Dept Med Oncol, Pittsburgh, PA USA. [Buatti, John M.] Univ Iowa, Dept Radiat Oncol, Iowa City, IA USA. [Buatti, John M.] Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. [Buatti, John M.] Univ Iowa, Dept Neurosurg, Iowa City, IA USA. [Mountz, James M.] Univ Pittsburgh, Dept Radiol, Div Nucl Med, Pittsburgh, PA 15260 USA. [Erickson, Bradley J.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Fennessy, Fiona M. M.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Huang, Wei] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97201 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Sch Med, Boston, MA USA. [Wahl, Richard L.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Linden, Hannah M.] Univ Washington, Dept Med, Seattle, WA USA. [Kinahan, Paul E.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Hylton, Nola M.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Gillies, Robert J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Radiol, Tampa Bay, FL USA. [Clarke, Laurence; Nordstrom, Robert] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. [Rubin, Daniel L.] Stanford Univ, Dept Radiol & Med, Palo Alto, CA 94304 USA. RP Yankeelov, TE (reprint author), Univ Texas Austin, Dept Biomed Engn, 107 W Dean Keeton St,Stop C0800, Austin, TX 78712 USA. EM thomas.yankeelov@utexas.edu FU NIH [U01CA142565, U01CA190254, U01CA140207, U01CA140230, U01CA140206, U01CA160045, U01CA151261, U01CA154602, U01CA154601, U01CA140204, U01CA148131, U01CA151235, U01CA143062, U01CA142555] FX This work was supported by the NIH under award numbers U01CA142565 (to T.E. Yankeelov), U01CA190254 (to D.A. Mankoff), U01CA140207 (to L.H. Schwartz), U01CA140230 (to F.S. Lieberman and J.M. Mountz), U01CA140206 (to J.M. Buatti), U01CA160045 (to B.J. Erickson), U01CA151261 (to F.M.M. Fennessy), U01CA154602 (to W. Huang), U01CA154601 (to J. Kalpathy-Cramer), U01CA140204 (to R.L. Wahl), U01CA148131 (to H.M. Linden and P. Kinahan), U01CA151235 (to N.M. Hylton), U01CA143062 (to R.J. Gillies), and U01CA142555 (to D.L. Rubin). NR 31 TC 7 Z9 7 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 284 EP 290 DI 10.1158/1078-0432.CCR-14-3336 PG 7 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500004 PM 26773162 ER PT J AU Moeini, A Sia, D Bardeesy, N Mazzaferro, V Llovet, JM AF Moeini, Agrin Sia, Daniela Bardeesy, Nabeel Mazzaferro, Vincenzo Llovet, Josep M. TI Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Review ID GROWTH-FACTOR RECEPTOR; HUMAN HEPATOCELLULAR-CARCINOMA; HEPATIC PROGENITOR CELLS; B-VIRUS-INFECTION; RISK-FACTORS; EXTRAHEPATIC CHOLANGIOCARCINOMA; UNITED-STATES; HEPATOCYTE DIFFERENTIATION; MUTATIONAL LANDSCAPE; THERAPEUTIC TARGETS AB Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous hepatobiliary neoplasm with poor prognosis and limited therapeutic options. The incidence of this neoplasm is growing globally. One third of iCCA tumors are amenable to surgical resection, but most cases are diagnosed at advanced stages with chemotherapy as the only established standard of practice. No molecular therapies are currently available for the treatment of this neoplasm. The poor understanding of the biology of iCCA and the lack of known oncogenic addiction loops has hindered the development of effective targeted therapies. Studies with sophisticated animal models defined IDH mutation as the first gatekeeper in the carcinogenic process and led to the discovery of striking alternative cellular origins. RNA- and exome-sequencing technologies revealed the presence of recurrent novel fusion events (FGFR2 and ROS1 fusions) and somatic mutations in metabolic (IDH1/2) and chromatin-remodeling genes (ARID1A, BAP1). These latest advancements along with known mutations in KRAS/BRAF/EGFR and 11q13 high-level amplification have contributed to a better understanding of the landscape of molecular alterations in iCCA. More than 100 clinical trials testing molecular therapies alone or in combination with chemotherapy including iCCA patients have not reported conclusive clinical benefits. Recent discoveries have shown that up to 70% of iCCA patients harbor potential actionable alterations that are amenable to therapeutic targeting in early clinical trials. Thus, the first biomarker-driven trials are currently underway. (C)2015 AACR. C1 [Moeini, Agrin; Sia, Daniela; Llovet, Josep M.] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Liver Canc Translat Res Lab,Liver Unit,CIBERehd, Barcelona, Catalonia, Spain. [Moeini, Agrin; Sia, Daniela; Llovet, Josep M.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Med, Liver Canc Program,Div Liver Dis, New York, NY 10029 USA. [Sia, Daniela; Mazzaferro, Vincenzo] Natl Canc Inst, IRCCS Fdn, Dept Surg, Gastrointestinal Surg & Liver Transplantat Unit, I-20133 Milan, Italy. [Bardeesy, Nabeel] Harvard Univ, Ctr Canc, Ctr Regenerat Med, Boston, MA USA. [Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain. RP Llovet, JM (reprint author), Univ Barcelona, Hosp Clin, BCLC Grp, Liver Unit,IDIBAPS,CIBERehd, Rosello 149, E-08036 Barcelona, Catalonia, Spain. EM jmllovet@clinic.cat RI Mazzaferro, Vincenzo/C-2726-2017 OI Mazzaferro, Vincenzo/0000-0002-4013-8085 FU Spanish National Health Institute (FPI program) [BES-2011-046915]; ILCA-Bayer Fellowship; V Foundation Translational Award; TargetCancer Foundation; NIH [R01CA136567-02, P50CA1270003]; AIRC (Italian Association for Cancer Research); 5x 1000 Milan-INT institutional grant in hepato-oncology; Samuel Waxman Cancer Research Foundation; Asociacion Espanola Contra el Cancer; Spanish National Health Institute [SAF-2013-41027]; European Commission HEP-CAR grant [667273-2] FX A. Moeini is supported by a fellowship from Spanish National Health Institute (FPI program, BES-2011-046915). D. Sia is supported by the ILCA-Bayer Fellowship. N. Bardeesy holds the Gallagher Endowed Chair in Gastrointestinal Cancer Research at Massachusetts General Hospital and is supported by a V Foundation Translational Award, the TargetCancer Foundation, and the NIH under award numbers R01CA136567-02 and P50CA1270003. V. Mazzaferro is partially supported by the AIRC (Italian Association for Cancer Research) and a 5x 1000 Milan-INT institutional grant in hepato-oncology. J.M Llovet is supported by grants from the Samuel Waxman Cancer Research Foundation, Asociacion Espanola Contra el Cancer, Spanish National Health Institute (SAF-2013-41027), and a European Commission HEP-CAR grant (667273-2). NR 81 TC 10 Z9 13 U1 7 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 291 EP 300 DI 10.1158/1078-0432.CCR-14-3296 PG 10 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500005 PM 26405193 ER PT J AU Wilson, MA Zhao, FM Khare, S Roszik, J Woodman, SE D'Andrea, K Wubbenhorst, B Rimm, DL Kirkwood, JM Kluger, HM Schuchter, LM Lee, SJ Flaherty, KT Nathanson, KL AF Wilson, Melissa A. Zhao, Fengmin Khare, Sanika Roszik, Jason Woodman, Scott E. D'Andrea, Kurt Wubbenhorst, Bradley Rimm, David L. Kirkwood, John M. Kluger, Harriet M. Schuchter, Lynn M. Lee, Sandra J. Flaherty, Keith T. Nathanson, Katherine L. TI Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CUTANEOUS MALIGNANT-MELANOMA; REFRACTORY SOLID TUMORS; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; MULTIKINASE INHIBITOR; KINASE INHIBITORS; LUNG-CANCER; CELL-LINES; PHASE-III AB Purpose: Copy number alterations have been shown to be involved in melanoma pathogenesis. The randomized phase III clinical trial E2603: carboplatin, paclitaxel, +/- sorafenib (CP vs. CPS) offers a large collection of tumor samples to evaluate association of somatic mutations, genomic alterations, and clinical outcomes, prior to current FDA-approved therapies. Experimental Design: Copy number and mutational analysis on 119 pretreatment samples was performed. Results: CPS therapy was associated with improved progression-free survival (PFS) compared with CP in patients with tumors with RAF1 (cRAF) gene copy gains (HR, 0.372; P = 0.025) or CCND1 gene copy gains (HR, 0.45; P = 0.035). CPS therapy was associated with improved overall survival (OS) compared with CP in patients with tumors with KRAS gene copy gains (HR, 0.25; P = 0.035). BRAF gene copy gain and MET amplification were more common in samples with V600K versus V600E mutations (P < 0.001), which was validated in The Cancer Genome Atlas (TCGA) dataset. Conclusions: We observed improved treatment response with CPS in patients with melanoma whose tumors have RAF1 (cRAF), KRAS, or CCND1 amplification, all of which can be attributed to sorafenib targeting CRAF. These genomic alterations should be incorporated in future studies for evaluation as biomarkers. (C)2015 AACR. C1 [Wilson, Melissa A.; Schuchter, Lynn M.] Univ Penn, Perelman Sch Med, Dept Med, Hematol Oncol, Philadelphia, PA 19104 USA. [Zhao, Fengmin; Lee, Sandra J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Khare, Sanika; D'Andrea, Kurt; Wubbenhorst, Bradley; Nathanson, Katherine L.] Univ Penn, Perelman Sch Med, Dept Med, Translat Med & Human Genet, Philadelphia, PA 19104 USA. [Roszik, Jason; Woodman, Scott E.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Roszik, Jason; Woodman, Scott E.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Kirkwood, John M.] Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA USA. [Kluger, Harriet M.] Yale Canc Ctr, Sect Med Oncol, New Haven, CT USA. [Kirkwood, John M.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Wilson, Melissa A.] NYU, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, Div Hematol & Med Oncol, New York, NY USA. RP Nathanson, KL (reprint author), Univ Penn, Perelman Sch Med, 351 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM knathans@exchange.upenn.edu OI Wilson, Melissa/0000-0002-5391-7838 FU Public Health Service Grants [CA23318, CA66636, CA21115, CA15488, CA14958, CA39229]; National Cancer Institute, NIH; NIH [CA115756, CA118871]; Department of Health and Human Services; NCI Cancer Center Research Training Program [T32 CA009615] FX This study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA15488, CA14958, CA39229 and from the National Cancer Institute, NIH, and the Department of Health and Human Services. This research was funded in part by a NCI Cancer Center Research Training Program Grant T32 CA009615 (PI: Dr. John Maris; M.A. Wilson), NIH Grant CA115756 (H.M. Kluger), and CA118871 (K.L. Nathanson, K.T. Flaherty). NR 44 TC 2 Z9 2 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 374 EP 382 DI 10.1158/1078-0432.CCR-15-1162 PG 9 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500014 PM 26307133 ER PT J AU Koch, R Aung, T Vogel, D Chapuy, B Wenzel, D Becker, S Sinzig, U Venkataramani, V von Mach, T Jacob, R Truemper, L Wulf, GG AF Koch, Raphael Aung, Thiha Vogel, Daniel Chapuy, Bjoern Wenzel, Dirk Becker, Sabrina Sinzig, Ursula Venkataramani, Vivek von Mach, Tobias Jacob, Ralf Truemper, Lorenz Wulf, Gerald G. TI Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ABC TRANSPORTER A3; B-CELL LYMPHOMA; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; CARCINOMA-CELLS; P-GLYCOPROTEIN; MODULATES SUSCEPTIBILITY; LUNG-CANCER; EXPRESSION AB Purpose: Although R-CHOP-based immunochemotherapy cures significant proportions of patients with aggressive B-cell lymphoma, tumor cell susceptibility to chemotherapy varies, with mostly fatal outcome in cases of resistant disease. We and others have shown before that export of cytostatic drugs contributes to drug resistance. Now we provide a novel approach to overcome exosome-mediated drug resistance in aggressive B-cell lymphomas. Experimental Design: We used well-established centrifugation protocols to purify exosomes from DLBCL cell lines and detected anthracyclines using FACS and HPLC. We used shRNA knockdown of ABCA3 to determine ABCA3 dependence of chemotherapy susceptibility and monitored ABCA3 expression after indomethacin treatment using qPCR. Finally, we established an in vivo assay using a chorioallantoic membrane (CAM) assay to determine the synergy of anthracycline and indomethacin treatment. Results: We show increased efficacy of the anthracycline doxorubicin and the anthracenedione pixantrone by suppression of exosomal drug resistance with indomethacin. B-cell lymphoma cells in vitro efficiently extruded doxorubicin and pixantrone, in part compacted in exosomes. Exosomal biogenesis was critically dependent on the expression of the ATP-transporter A3 (ABCA3). Genetic or chemical depletion of ABCA3 augmented intracellular retention of both drugs and shifted the subcellular drug accumulation to prolonged nuclear retention. Indomethacin increased the cytostatic efficacy of both drugs against DLBCL cell lines in vitro and in vivo in a CAM assay. Conclusions: We propose pretreatment with indomethacin toward enhanced antitumor efficacy of anthracyclines and anthracenediones. (C) 2015 AACR. C1 [Koch, Raphael; Aung, Thiha; Vogel, Daniel; Becker, Sabrina; Sinzig, Ursula; Venkataramani, Vivek; Truemper, Lorenz; Wulf, Gerald G.] Univ Gottingen, Dept Hematol & Oncol, Robert Koch Str 40, D-37075 Gottingen, Germany. [Koch, Raphael; Chapuy, Bjoern] Dana Farber Canc Inst, Boston, MA 02115 USA. [Aung, Thiha] Univ Gottingen, Dept Trauma Surg Plast & Reconstruct Surg, Div Plast Surg, D-37073 Gottingen, Germany. [Wenzel, Dirk] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany. [von Mach, Tobias] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. [Jacob, Ralf] Univ Marburg, Dept Cell Biol & Cell Pathol, Marburg, Germany. RP Wulf, GG (reprint author), Univ Gottingen, Dept Hematol & Oncol, Robert Koch Str 40, D-37075 Gottingen, Germany. EM gerald.wulf@med.uni-goettingen.de FU Deutsche Forschungsgemeinschaft; University Medicine Goettingen FX FACS and cell sorting were performed in the Flow Cytometry Core Facility at the University of Goettingen. We are grateful to Jorg Wilting for support with the CAM assays. This work was supported by the Deutsche Forschungsgemeinschaft (DFG Wu 310/3-1 to G.G.W.) and by the University Medicine Goettingen (Jacob-Henle program grant to T.A., Forschungsforderung to R.K. and V.V.). NR 46 TC 3 Z9 4 U1 4 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 395 EP 404 DI 10.1158/1078-0432.CCR-15-0577 PG 10 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500016 PM 26369630 ER PT J AU Sabbatino, F Villani, V Yearley, JH Deshpande, V Cai, L Konstantinidis, IT Moon, C Nota, S Wang, YY Al-Sukaini, A Zhu, AX Goyal, L Ting, DT Bardeesy, N Hong, TS Castillo, CFD Tanabe, KK Lillemoe, KD Ferrone, S Ferrone, CR AF Sabbatino, Francesco Villani, Vincenzo Yearley, Jennifer H. Deshpande, Vikram Cai, Lei Konstantinidis, Ioannis T. Moon, Christina Nota, Sjoerd Wang, Yangyang Al-Sukaini, Ahmad Zhu, Andrew X. Goyal, Lipika Ting, David T. Bardeesy, Nabeel Hong, Theodore S. Castillo, Carlos Fernandez-Del Tanabe, Kenneth K. Lillemoe, Keith D. Ferrone, Soldano Ferrone, Cristina R. TI PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ADVANCED MELANOMA; LIGAND 1; PROGNOSTIC-FACTORS; MALIGNANT-CELLS; DR EXPRESSION; CANCER; SURVIVAL; ANTIBODY; SAFETY AB Purpose: More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells. Experimental Design: Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated. Results: Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8(-) T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease. Conclusions: ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression. (C)2015 AACR. C1 [Sabbatino, Francesco; Villani, Vincenzo; Cai, Lei; Konstantinidis, Ioannis T.; Wang, Yangyang; Al-Sukaini, Ahmad; Castillo, Carlos Fernandez-Del; Tanabe, Kenneth K.; Lillemoe, Keith D.; Ferrone, Soldano; Ferrone, Cristina R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Yearley, Jennifer H.; Moon, Christina] Merck Res Labs, Palo Alto, CA USA. [Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Nota, Sjoerd; Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. [Zhu, Andrew X.; Goyal, Lipika; Ting, David T.; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr, Boston, MA USA. [Hong, Theodore S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Ferrone, CR (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WACC 460, Boston, MA 02114 USA. EM cferrone@mgh.harvard.edu RI Sabbatino, Francesco/F-4992-2014; OI Sabbatino, Francesco/0000-0001-6431-8278; Ting, David/0000-0002-3261-2322 FU Cholangiocarcinoma Foundation; Institute for Pancreatic Cancer Research; Public Health Service (PHS) - NCI [R21 CA 164756]; Fondazione Umberto Veronesi; Centro per la Comunicazione e la Ricerca of the Collegio Ghislieri of Pavia FX This work was supported by a grant from the Cholangiocarcinoma Foundation, a grant from the Andrew L. Warshaw, M.D., Institute for Pancreatic Cancer Research, the Public Health Service (PHS) grant R21 CA 164756, awarded by the NCI and generous donations from patients and their families affected by chlolangiocarcinoma. F. Sabbatino is the recipient of a Post-Doctoral Fellowship awarded by the Fondazione Umberto Veronesi. V. Villani is the recipient of a Research Fellowship from the Centro per la Comunicazione e la Ricerca of the Collegio Ghislieri of Pavia. NR 38 TC 6 Z9 7 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 470 EP 478 DI 10.1158/1078-0432.CCR-15-0715 PG 9 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500023 PM 26373575 ER PT J AU Schill, EM Lake, JI Tusheva, OA Nagy, N Bery, SK Foster, L Avetisyan, M Johnson, SL Stenson, WF Goldstein, AM Heuckeroth, RO AF Schill, Ellen Merrick Lake, Jonathan I. Tusheva, Olga A. Nagy, Nandor Bery, Saya K. Foster, Lynne Avetisyan, Marina Johnson, Stephen L. Stenson, William F. Goldstein, Allan M. Heuckeroth, Robert O. TI Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Enteric nervous system development; Gene-environment interactions; Migration ID CREST-DERIVED CELLS; HIRSCHSPRUNG-DISEASE; NEURAL CREST; RHO-GTPASES; IN-VITRO; RET-PROTOONCOGENE; GENE DISRUPTION; NEURITE GROWTH; AXONAL GROWTH; PAR COMPLEX AB Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-assodated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/- mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children. (C) 2015 Elsevier Inc. All rights reserved. C1 [Schill, Ellen Merrick; Lake, Jonathan I.; Tusheva, Olga A.; Avetisyan, Marina] Washington Univ, Sch Med, Dept Pediat, 660 South Euclid Ave, St Louis, MO 63110 USA. [Nagy, Nandor; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Surg, Sch Med, 55 Fruit St, Boston, MA 02114 USA. [Nagy, Nandor] Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1085 Budapest, Hungary. [Bery, Saya K.] Univ Penn, Dept Pediat, Childrens Hosp, Philadelphia Res Inst,Abramson Res Ctr, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. [Bery, Saya K.] Univ Penn, Perelman Sch Med, Abramson Res Ctr, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. [Foster, Lynne; Stenson, William F.] Washington Univ, Sch Med, Dept Internal Med, 660 South Euclid Ave, St Louis, MO 63110 USA. [Johnson, Stephen L.] Washington Univ, Sch Med, Dept Genet, 660 South Euclid Ave, St Louis, MO 63110 USA. RP Heuckeroth, RO (reprint author), Univ Penn, Abramson Res Ctr, Perelman Sch Med, Childrens Hosp,Philadelphia Res Inst, Suite 11161,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM Heuckerothr@email.chop.edu FU Irma and Norman Braman Endowment; Suzi and Scott Lustgarten Center Endowment; Children's Hospital of Philadelphia Research Institute; Children's Discovery Institute of Washington University and St. Louis Children's Hospital [CH-II-1008-123, CH-II-2010-390, MD-II-2013-269]; United States National Institutes of Health (NIH) [RO1 DK087715, RO1 GM059688, R37 DK33165, RO1 DK080914]; Burroughs Wellcome Fund Clinical Scientist Award in Translational Research [1008525]; NIH [F30 DK100101]; NIH Medical Scientist Training Program Training [T32 GM07200] FX We thank Dr. Tatyana Svitkina for insightful guidance about the actin cytoskeleton, Dr. Allen Mitchell for sharing unpublished data about medicine use in early pregnancy, Ryo Hotta, Ming Fu, Elizabeth Wright-Jin, Rajarshi Sengupta, and Alisha Jamil, and the Mouse Genetics Core at Washington University School of Medicine for assistance and advice. This work was supported by Irma and Norman Braman Endowment (ROH), Suzi and Scott Lustgarten Center Endowment (ROH), The Children's Hospital of Philadelphia Research Institute (ROH), The Children's Discovery Institute of Washington University and St. Louis Children's Hospital (Grant nos. CH-II-1008-123, CH-II-2010-390, MD-II-2013-269) (ROH), United States National Institutes of Health (NIH) grants RO1 DK087715 (ROH), RO1 GM059688 (SLJ), R37 DK33165 (WFS), RO1 DK080914 (AMG), Burroughs Wellcome Fund Clinical Scientist Award in Translational Research (Grant no. 1008525) (ROH), NIH F30 DK100101 (EMS) and by the NIH Medical Scientist Training Program Training Grant T32 GM07200. NR 81 TC 8 Z9 8 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2016 VL 409 IS 2 BP 473 EP 488 DI 10.1016/j.ydbio.2015.09.023 PG 16 WC Developmental Biology SC Developmental Biology GA DC3MB UT WOS:000369122300014 PM 26586201 ER PT J AU Swenson, ER AF Swenson, Erik R. TI Pharmacology of acute mountain sickness: old drugs and newer thinking SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE hypoxia; acid-base; acute mountain sickness; carbonic anhydrase; acetazolamide; aquaporin; radical oxygen species; corticosteroid; dexamethasone; hypoxia inducible factor; sympathetic nervous system; cytokine ID BLOOD-BRAIN-BARRIER; ALTITUDE PULMONARY-EDEMA; SOLUBLE ADENYLYL-CYCLASE; CARBONIC-ANHYDRASE INHIBITION; GLUCOCORTICOID-RECEPTOR; CEREBRAL EDEMA; IN-VITRO; INTRACEREBRAL HEMORRHAGE; AQUAPORIN-4 EXPRESSION; NEUROEPITHELIAL BODIES AB Pharmacotherapy in acute mountain sickness (AMS) for the past half century has largely rested on the use of carbonic anhydrase (CA) inhibitors, such as acetazolamide, and corticosteroids, such as dexamethasone. The benefits of CA inhibitors are thought to arise from their known ventilatory stimulation and resultant greater arterial oxygenation from inhibition of renal CA and generation of a mild metabolic acidosis. The benefits of corticosteroids include their broad-based anti-inflammatory and anti-edemagenic effects. What has emerged from more recent work is the strong likelihood that drugs in both classes act on other pathways and signaling beyond their classical actions to prevent and treat AMS. For the CA inhibitors, these include reduction in aquaporinmediated transmembrane water transport, anti-oxidant actions, vasodilation, and anti-inflammatory effects. In the case of corticosteroids, these include protection against increases in vascular endothelial and blood-brain barrier permeability, suppression of inflammatory cytokines and reactive oxygen species production, and sympatholysis. The loci of action of both classes of drug include the brain, but may also involve the lung as revealed by benefits that arise with selective administration to the lungs by inhalation. Greater understanding of their pluripotent actions and sites of action in AMS may help guide development of better drugs with more selective action and fewer side effects. C1 [Swenson, Erik R.] Univ Washington, Div Pulm & Crit Care Med, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), Univ Washington, Div Pulm & Crit Care Med, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM eswenson@u.washington.edu NR 159 TC 8 Z9 8 U1 2 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN 15 PY 2016 VL 120 IS 2 BP 204 EP 215 DI 10.1152/japplphysiol.00443.2015 PG 12 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA DC2ML UT WOS:000369050700013 PM 26294748 ER PT J AU Amato, KR Wang, S Tan, L Hastings, AK Song, WQ Lovly, CM Meador, CB Ye, F Lu, PC Balko, JM Colvin, DC Cates, JM Pao, W Gray, NS Chen, J AF Amato, Katherine R. Wang, Shan Tan, Li Hastings, Andrew K. Song, Wenqiang Lovly, Christine M. Meador, Catherine B. Ye, Fei Lu, Pengcheng Balko, Justin M. Colvin, Daniel C. Cates, Justin M. Pao, William Gray, Nathanael S. Chen, Jin TI EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer SO CANCER RESEARCH LA English DT Article ID RECEPTOR TYROSINE KINASE; TARGETED THERAPY; METASTATIC PROGRESSION; TUMOR ANGIOGENESIS; CELL-MIGRATION; GENE-MUTATIONS; GEFITINIB; ACTIVATION; ERLOTINIB; ADENOCARCINOMAS AB Despite the success of treating EGFR-mutant lung cancer patients with EGFR tyrosine kinase inhibitors (TKI), all patients eventually acquire resistance to these therapies. Although various resistance mechanisms have been described, there are currently no FDA-approved therapies that target alternative mechanisms to treat lung tumors with acquired resistance to first-line EGFR TKI agents. Here we found that EPHA2 is over-expressed in EGFR TKI-resistant tumor cells. Loss of EPHA2 reduced the viability of erlotinib-resistant tumor cells harboring EGFR(T790M) mutations in vitro and inhibited tumor growth and progression in an inducible EGFR(L858R_T790M)-mutant lung cancer model in vivo. Targeting EPHA2 in erlotinib-resistant cells decreased S6K1-mediated phosphorylation of cell death agonist BAD, resulting in reduced tumor cell proliferation and increased apoptosis. Furthermore, pharmacologic inhibition of EPHA2 by the small-molecule inhibitor ALW-II-41-27 decreased both survival and proliferation of erlotinib-resistant tumor cells and inhibited tumor growth in vivo. ALW-II-41-27 was also effective in decreasing viability of cells with acquired resistance to the third-generation EGFR TKI AZD9291. Collectively, these data define a role for EPHA2 in the maintenance of cell survival of TKI-resistant, EGFR-mutant lung cancer and indicate that EPHA2 may serve as a useful therapeutic target in TKI-resistant tumors. (C) 2016 AACR. C1 [Amato, Katherine R.; Lovly, Christine M.; Meador, Catherine B.; Balko, Justin M.; Pao, William; Chen, Jin] Vanderbilt Univ, Dept Canc Biol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Wang, Shan; Song, Wenqiang; Chen, Jin] Vanderbilt Univ, Div Rheumatol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Tan, Li; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tan, Li; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Hastings, Andrew K.; Balko, Justin M.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Lovly, Christine M.; Cates, Justin M.; Pao, William; Chen, Jin] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA. [Ye, Fei; Lu, Pengcheng] Vanderbilt Univ, Dept Biostat, 221 Kirkland Hall, Nashville, TN 37235 USA. [Colvin, Daniel C.] Vanderbilt Univ, Inst Imaging Sci, 221 Kirkland Hall, Nashville, TN 37235 USA. [Chen, Jin] Vanderbilt Univ, Dept Cell & Dev Biol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Chen, Jin] Tennessee Valley Healthcare Syst, Vet Affairs Med Ctr, Nashville, TN USA. RP Chen, J (reprint author), Vanderbilt Univ, Sch Med, T-3702E MCN,1161 21st Ave South, Nashville, TN 37232 USA. EM jin.chen@vanderbilt.edu RI Cates, Justin/D-5927-2014 OI Cates, Justin/0000-0002-7336-5196 FU Department of Veterans Affairs through a VA Merit Award; Department of Defense [W81XWH-14-1-0181]; NIH [R01 CA95004, CA177681, CA173469, CA121210, P01 CA129243, U54 CA143798, F31 CA167878, CA68485, DK20593, DK58404, DK59637, EY08126]; Damon Runyon Clinical Investigator Award; LUNGevity Career Development Award; Melley Family Scholarship; VICC Thoracic Center; Astra Zeneca; NCI Cancer Center Support Grant [P30 CA068485] FX This work was supported by the Department of Veterans Affairs through a VA Merit Award (J. Chen), the Department of Defense (W81XWH-14-1-0181; J. Chen), NIH grants R01 CA95004, CA177681 (J. Chen), CA173469 (N. Gray), CA121210 (C. Lovly), P01 CA129243 (C. Lovly), U54 CA143798 (C. Lovly), F31 CA167878 (K. Amato), a Damon Runyon Clinical Investigator Award (C. Lovly), a LUNGevity Career Development Award (C. Lovly), a Melley Family Scholarship (C. Meador), a pilot project grant from the VICC Thoracic Center (J. Chen), and funds from Astra Zeneca (C. Lovly). Confocal experiments were performed through the use of the VUMC Cell Imaging Shared Resource, supported by NIH grants CA68485, DK20593, DK58404, DK59637, and EY08126. This work was also supported by the NCI Cancer Center Support Grant (P30 CA068485) utilizing the Translational Pathology, Flow Cytometry, and Small Animal Imaging Shared Resources. NR 50 TC 8 Z9 9 U1 2 U2 11 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 JAN 15 PY 2016 VL 76 IS 2 BP 305 EP 318 DI 10.1158/0008-5472.CAN-15-0717 PG 14 WC Oncology SC Oncology GA DB6MB UT WOS:000368628000015 PM 26744526 ER PT J AU De Rienzo, A Archer, MA Yeap, BY Dao, N Sciaranghella, D Sideris, AC Zheng, YF Holman, AG Wang, YYE Dal Cin, PS Fletcher, JA Rubio, R Croft, L Quackenbush, J Sugarbaker, PE Munir, KJ Battilana, JR Gustafson, CE Chirieac, LR Ching, SM Wong, J Tay, LC Rudd, S Hercus, R Sugarbaker, DJ Richards, WG Bueno, R AF De Rienzo, Assunta Archer, Michael A. Yeap, Beow Y. Dao, Nhien Sciaranghella, Daniele Sideris, Antonios C. Zheng, Yifan Holman, Alexander G. Wang, Yaoyu E. Dal Cin, Paola S. Fletcher, Jonathan A. Rubio, Renee Croft, Larry Quackenbush, John Sugarbaker, Peter E. Munir, Kiara J. Battilana, Jesse R. Gustafson, Corinne E. Chirieac, Lucian R. Ching, Soo Meng Wong, James Tay, Liang Chung Rudd, Stephen Hercus, Robert Sugarbaker, David J. Richards, William G. Bueno, Raphael TI Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma SO CANCER RESEARCH LA English DT Article ID T-CELL LYMPHOMA; GERMLINE BAP1 MUTATIONS; SOMATIC MUTATIONS; CANCER; RHOA; GENOME; GENE; NF2; POLYMORPHISMS; EXPRESSION AB Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may adva nce the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P < 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepithe-liod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. (C) 2015 AACR. C1 [De Rienzo, Assunta; Archer, Michael A.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne E.; Richards, William G.; Bueno, Raphael] Brigham & Womens Hosp, Thorac Surg Oncol Lab, 75 Francis St, Boston, MA 02115 USA. [De Rienzo, Assunta; Archer, Michael A.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne E.; Richards, William G.; Bueno, Raphael] Brigham & Womens Hosp, Int Mesothelioma Program, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. [De Rienzo, Assunta; Archer, Michael A.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne E.; Richards, William G.; Bueno, Raphael] Brigham & Womens Hosp, Lung Ctr, 75 Francis St, Boston, MA 02115 USA. [De Rienzo, Assunta; Archer, Michael A.; Yeap, Beow Y.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Dal Cin, Paola S.; Fletcher, Jonathan A.; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne E.; Chirieac, Lucian R.; Richards, William G.; Bueno, Raphael] Harvard Univ, Sch Med, Boston, MA USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Holman, Alexander G.; Wang, Yaoyu E.; Rubio, Renee; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Holman, Alexander G.; Wang, Yaoyu E.; Rubio, Renee; Quackenbush, John] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Dal Cin, Paola S.; Fletcher, Jonathan A.; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Croft, Larry; Ching, Soo Meng; Wong, James; Tay, Liang Chung; Rudd, Stephen; Hercus, Robert] Malaysian Genom Resource Ctr, Kuala Lumpur, Malaysia. [Sugarbaker, David J.] Baylor Coll Med, Debakey Dept Surg, Houston, TX 77030 USA. RP De Rienzo, A (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM aderienzo@partners.org FU Mesothelioma Applied Research Foundation; NCI [RO1CA120528]; International Mesothelioma Program at Brigham and Women's Hospital FX This work was supported by grants from the Mesothelioma Applied Research Foundation (A. De Rienzo), from the NCI (RO1CA120528 to R. Bueno), and the International Mesothelioma Program at Brigham and Women's Hospital. NR 46 TC 3 Z9 3 U1 1 U2 5 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 JAN 15 PY 2016 VL 76 IS 2 BP 319 EP 328 DI 10.1158/0008-5472.CAN-15-0751 PG 10 WC Oncology SC Oncology GA DB6MB UT WOS:000368628000016 PM 26554828 ER PT J AU Sacco, A Roccaro, AM Ma, DD Shi, JT Mishima, Y Moschetta, M Chiarini, M Munshi, N Handin, RI Ghobria, IM AF Sacco, Antonio Roccaro, Aldo M. Ma, Dongdong Shi, Jiantao Mishima, Yuji Moschetta, Michele Chiarini, Marco Munshi, Nikhil Handin, Robert I. Ghobria, Irene M. TI Cancer Cell Dissemination and Homing to the Bone Marrow in a Zebrafish Model SO CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA; GROWTH-FACTOR; TUMOR PROGRESSION; DRUG-RESISTANCE; MICROENVIRONMENT; ADHESION; INTERLEUKIN-6; ANGIOGENESIS; TRANSCRIPTS; INHIBITION AB Advancement of many solid tumors and hematologic malignancies is frequently characterized by dissemination and homing of cancer cells to the bone marrow (BM). Methods to quantitatively characterize these key steps of the metastatic cascade in mammalian models are currently limited and do not offer opportunities to perform rapid, large-scale genomic, or drug screening. Because of their optical clarity, we used zebrafish to develop an in vivo model of cancer cell dissemination and homing to the BM. We performed intracardiac injection of multiple myeloma (MM) cells derived from human BM or cell lines and monitored their migration to the caudal hematopoietic tissue (CHT), the region where hematopoiesis occurs in the zebrafish embryo, which recapitulates a BM-like niche. Transcriptomic analyses confirmed that MM cells homing to the CHT displayed gene-expression differences compared with MM cells outside of the CHT, including significant enrichment for genes known to regulate interleukin-6 (IL6) signaling, cell adhesion, and angiogenesis. Collectively, our findings point to the zebrafish as a valuable model in which to study cancer cell homing to the hematopoietic niche and to establish a screening platform for the identification of factors and mechanisms contributing to the early steps of bone metastasis. (C) 2016 AACR. C1 [Sacco, Antonio; Roccaro, Aldo M.; Shi, Jiantao; Mishima, Yuji; Moschetta, Michele; Chiarini, Marco; Munshi, Nikhil; Ghobria, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Roccaro, Aldo M.; Chiarini, Marco; Handin, Robert I.] CREA, Spedali Civili Brescia, Ctr Ric Oncoematol AIL, Brescia, Italy. [Ma, Dongdong] Harvard Univ, Brigham & Womens Hosp, Div Hematol, Sch Med, Boston, MA 02115 USA. RP Ghobria, IM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.; Handin, RI (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Fifth Floor,Karp Family Res Bldg,One Blackfan Cir, Cambridge, MA 02138 USA. EM rhandin@partners.org; irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; Chiarini, Marco/K-4983-2016 OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128; Chiarini, Marco/0000-0003-1000-0461 NR 43 TC 3 Z9 3 U1 1 U2 4 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 JAN 15 PY 2016 VL 76 IS 2 BP 463 EP 471 DI 10.1158/0008-5472.CAN-15-1926 PG 9 WC Oncology SC Oncology GA DB6MB UT WOS:000368628000029 PM 26744527 ER PT J AU Korthuis, PT McGinnis, KA Kraemer, KL Gordon, AJ Skanderson, M Justice, AC Crystal, S Goetz, MB Gibert, CL Rimland, D Fiellin, LE Gaither, JR Wang, K Asch, SM McInnes, DK Ohl, ME Bryant, K Tate, JP Duggal, M Fiellin, DA AF Korthuis, Philip Todd McGinnis, Kathleen A. Kraemer, Kevin L. Gordon, Adam J. Skanderson, Melissa Justice, Amy C. Crystal, Stephen Goetz, Matthew Bidwell Gibert, Cynthia L. Rimland, David Fiellin, Lynn E. Gaither, Julie R. Wang, Karen Asch, Steven M. McInnes, Donald Keith Ohl, Michael E. Bryant, Kendall Tate, Janet P. Duggal, Mona Fiellin, David A. CA Veterans Aging Cohort Study TI Quality of HIV Care and Mortality Rates in HIV-Infected Patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE alcohol; quality of health care; HIV; health care; opioid-related disorders ID HUMAN-IMMUNODEFICIENCY-VIRUS; VETERANS AGING COHORT; OF-CARE; PERFORMANCE-MEASURES; ANTIRETROVIRAL THERAPY; ALCOHOL-CONSUMPTION; UNHEALTHY ALCOHOL; UNITED-STATES; SYSTEM; TRANSFORMATION AB Background. The Patient Protection and Affordable Care Act encourages healthcare systems to track quality-of-care measures; little is known about their impact on mortality rates. The objective of this study was to assess associations between HIV quality of care and mortality rates. Methods. A longitudinal survival analysis of the Veterans Aging Cohort Study included 3038 human immunodeficiency virus (HIV)-infected patients enrolled between June 2002 and July 2008. The independent variable was receipt of >= 80% of 9 HIV quality indicators (QIs) abstracted from medical records in the 12 months after enrollment. Overall mortality rates through 2014 were assessed from the Veterans Health Administration, Medicare, and Social Security National Death Index records. We assessed associations between receiving >= 80% of HIV QIs and mortality rates using Kaplan-Meier survival analysis and adjusted Cox proportional hazards models. Results were stratified by unhealthy alcohol and illicit drug use. Results. The majority of participants were male (97.5%) and black (66.8%), with a mean (standard deviation) age of 49.0 (8.8) years. Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug use. During 24 805 person-years of follow-up (mean [standard deviation], 8.2 [3.3] years), those who received >= 80% of QIs experienced lower age-adjusted mortality rates (adjusted hazard ratio, 0.75; 95% confidence interval,.65-.86). Adjustment for disease severity attenuated the association. Conclusions. Receipt of >= 80% of select HIV QIs is associated with improved survival in a sample of predominantly male, black, HIV-infected patients but was insufficient to overcome adjustment for disease severity. Interventions to ensure high-quality care and address underlying chronic illness may improve survival in HIV-infected patients. C1 [Korthuis, Philip Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15260 USA. [McGinnis, Kathleen A.; Kraemer, Kevin L.; Skanderson, Melissa] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Gordon, Adam J.] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Div Gen Internal Med, 930 Scaife Hall, Pittsburgh, PA 15260 USA. [Justice, Amy C.; Fiellin, Lynn E.; Wang, Karen; Tate, Janet P.; Fiellin, David A.] Yale Univ, Sch Med, Ctr Interdisciplinary Res AIDS, Div Gen Internal Med, New Haven, CT USA. [Gaither, Julie R.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Justice, Amy C.; Tate, Janet P.] Vet Aging Cohort Study Coordinating Ctr, West Haven, CT USA. [Duggal, Mona] VA Connecticut Care Syst, West Haven, CT USA. [Crystal, Stephen] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, 30 Coll Ave, New Brunswick, NJ 08903 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst & David Geffen, Los Angeles, CA 90024 USA. [Asch, Steven M.] VA Greater Palo Alto Healthcare Syst, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Stanford, CA 94305 USA. [Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Rimland, David] VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [McInnes, Donald Keith] Boston Univ, Boston, MA 02215 USA. [Ohl, Michael E.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Bryant, Kendall] NIAAA, HIV AIDS Res, Rockville, MD 20852 USA. [Duggal, Mona] Postgrad Inst Med Educ & Res, Chandigarh, India. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu OI Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502 FU National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U24-AA020794, NIAAA U01-AA020790, NIAAA R01-AA022886]; NIH, National Institute on Drug Abuse [K23 DA019809] FX This work was supported by the National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA; grants U24-AA020794, NIAAA U01-AA020790, and NIAAA R01-AA022886) and the NIH, National Institute on Drug Abuse (grant K23 DA019809). NR 38 TC 5 Z9 5 U1 3 U2 8 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 JAN 15 PY 2016 VL 62 IS 2 BP 233 EP 239 DI 10.1093/cid/civ762 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DB6JW UT WOS:000368622300022 PM 26338783 ER PT J AU Parasuram, R Mills, CL Wang, ZX Somasundaram, S Beuning, PJ Ondrechen, MJ AF Parasuram, Ramya Mills, Caitlyn L. Wang, Zhouxi Somasundaram, Saroja Beuning, Penny J. Ondrechen, Mary Jo TI Local structure based method for prediction of the biochemical function of proteins: Applications to glycoside hydrolases SO METHODS LA English DT Article DE Protein function prediction; Structurally Aligned Local Sites of Activity (SALSA); Glycoside hydrolases; Six-hairpin glycosidases; Concanavalin A-like lectin/glucanase ID XYLOGLUCAN OLIGOSACCHARIDES; FUNCTION ANNOTATION; STRUCTURE ALIGNMENT; CRYSTAL-STRUCTURE; INTERACTION SITES; 3D STRUCTURES; RESIDUES; GLUCOAMYLASE; DATABASE; SERVER AB Thousands of protein structures of unknown or uncertain function have been reported as a result of high-throughput structure determination techniques developed by Structural Genomics (SG) projects. However, many of the putative functional assignments of these SG proteins in the Protein Data Bank (PDB) are incorrect. While high-throughput biochemical screening techniques have provided valuable functional information for limited sets of SG proteins, the biochemical functions for most SG proteins are still unknown or uncertain. Therefore, computational methods for the reliable prediction of protein function from structure can add tremendous value to the existing SG data. In this article, we show how computational methods may be used to predict the function of SG proteins, using examples from the six-hairpin glycosidase (6-HG) and the concanavalin A-like lectin/glucanase (CAL/G) superfamilies. Using a set of predicted functional residues, obtained from computed electrostatic and chemical properties for each protein structure, it is shown that these superfamilies may be sorted into functional families according to biochemical function. Within these superfamilies, a total of 18 SG proteins were analyzed according to their predicted, local functional sites: 13 from the 6-HG superfamily, five from the CAL/G superfamily. Within the 6-HG superfamily, an uncharacterized protein BACOVA_03626 from Bacteroides ovatus (PDB 3ON6) and a hypothetical protein BT3781 from Bacteroides thetaiotaomicron (PDB 2P0V) are shown to have very strong active site matches with exo-alpha-1,6-mannosidases, thus likely possessing this function. Also in this superfamily, it is shown that protein BH0842, a putative glycoside hydrolase from Bacillus halodurans (PDB 2RDY), has a predicted active site that matches well with a known alpha-L-galactosidase. In the CAL/G superfamily, an uncharacterized glycosyl hydrolase family 16 protein from Mycobacterium smegmatis (PDB 3RQ0) is shown to have local structural similarity at the predicted active site with the known members of the GH16 family, with the closest match to the endoglucanase subfamily. The method discussed herein can predict whether an SG protein is correctly or incorrectly annotated and can sometimes provide a reliable functional annotation. Examples of application of the method across folds, comparing active sites between two proteins of different structural folds, are also given. (C) 2015 Elsevier Inc. All rights reserved. C1 [Parasuram, Ramya; Mills, Caitlyn L.; Wang, Zhouxi; Somasundaram, Saroja; Beuning, Penny J.; Ondrechen, Mary Jo] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Ondrechen, Mary Jo] 360 Huntington Ave, Boston, MA 02115 USA. [Parasuram, Ramya] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. [Wang, Zhouxi] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38 A,Room 5S508,8600 Rockville Pike, Bethesda, MD 20894 USA. RP Ondrechen, MJ (reprint author), 360 Huntington Ave, Boston, MA 02115 USA. EM mjo@neu.edu FU National Science Foundation [MCB-1158176, CHE-1305655]; American Cancer Society [RSG-12-161-01-DMC]; Math Works; PhRMA Foundation FX This work is supported by the National Science Foundation under grant numbers MCB-1158176 and CHE-1305655 (PJB, MJO), the American Cancer Society under Research Scholar Grant RSG-12-161-01-DMC (PJB), Math Works, and the PhRMA Foundation (fellowship to CLM). We also thank Dr. Srinivas Somarowthu and Dr. Pengcheng Yin for their kind assistance. NR 58 TC 1 Z9 1 U1 3 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD JAN 15 PY 2016 VL 93 BP 51 EP 63 DI 10.1016/j.ymeth.2015.11.010 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DB5LI UT WOS:000368555200007 PM 26564235 ER PT J AU Jiang, DH Xiao, XQ Fu, TS Mashaghi, A Liu, QH Hong, JX AF Jiang, Donghong Xiao, Xiangqian Fu, Tongsheng Mashaghi, Alireza Liu, Qinghuai Hong, Jiaxu TI Transient Tear Film Dysfunction after Cataract Surgery in Diabetic Patients SO PLOS ONE LA English DT Article ID DRY EYE DISEASE; PHOTOREFRACTIVE KERATECTOMY; REFRACTIVE SURGERY; PHACOEMULSIFICATION; SENSATION; MELLITUS; OUTCOMES; LASIK AB Purpose Diabetes mellitus is an increasingly common systemic disease. Many diabetic patients seek cataract surgery for a better visual acuity. Unlike in the general population, the influence of cataract surgery on tear film function in diabetic patients remains elusive. The aim of this study was to evaluate the tear function in diabetic and nondiabetic patients following cataract surgery. Methods In this prospective, interventional case series, 174 diabetic patients without dry eye syndrome (DES) and 474 age-matched nondiabetic patients as control who underwent phacoemulsification were enrolled at two different eye centers between January 2011 and January 2013. Patients were followed up at baseline and at 7 days, 1 month, and 3 months postoperatively. Ocular symptom scores (Ocular Surface Disease Index, OSDI) and tear film function including tear film stability (tear film break-up time, TBUT), corneal epithelium integrity (corneal fluorescein staining, CFS), and tear secretion (Schirmer's I test, SIT) were evaluated. Results In total, 83.9% of the diabetic patients (146 cases with 185 eyes) and 89.0% of the nondiabetic patients (422 cases with 463 eyes) completed all check-ups after the interventions (P = 0.095). The incidence of DES was 17.1% in the diabetic patients and 8.1% in the nondiabetic patients at 7 days after cataract surgery. In the diabetic patients, the incidence of DES remained 4.8% at 1 month postoperatively and decreased to zero at 3 months after surgery. No DES was diagnosed in nondiabetic patients at either the 1-month or 3-month follow-up. Compared with the baseline, the diabetic patients had worse symptom scores and lower TBUT values at 7 days and 1 month but not at 3 months postoperatively. In the nondiabetic patients, symptom scores and TBUT values had returned to preoperative levels at 1-month check-up. CFS scores and SIT values did not change significantly postoperatively in either group (P = 0.916 and P = 0.964, respectively). Conclusions Diabetic patients undergoing cataract surgery are prone to DES. Ocular symptoms and tear film stability are transiently worsened in diabetic patients and are restored more slowly than those in nondiabetic patients. C1 [Jiang, Donghong; Xiao, Xiangqian] Second People Hosp, Dept Ophthalmol, Taixing, Peoples R China. [Fu, Tongsheng] People Hosp, Dept Ophthalmol, Yangzhong, Peoples R China. [Hong, Jiaxu] Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Ophthalmol & Visual Sci, Shanghai 200433, Peoples R China. [Liu, Qinghuai] Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing, Jiangsu, Peoples R China. [Mashaghi, Alireza; Hong, Jiaxu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Hong, Jiaxu] State Hlth Minist, Key Lab Myopia, Shangha, Peoples R China. [Hong, Jiaxu] Key Lab Visual Impairment & Restorat Shanghai, Shangha, Peoples R China. [Hong, Jiaxu] Xiamen Univ, Sch Life Sci, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen, Fujian, Peoples R China. RP Hong, JX (reprint author), Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Ophthalmol & Visual Sci, Shanghai 200433, Peoples R China.; Liu, QH (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing, Jiangsu, Peoples R China.; Hong, JX (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA.; Hong, JX (reprint author), State Hlth Minist, Key Lab Myopia, Shangha, Peoples R China.; Hong, JX (reprint author), Key Lab Visual Impairment & Restorat Shanghai, Shangha, Peoples R China.; Hong, JX (reprint author), Xiamen Univ, Sch Life Sci, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen, Fujian, Peoples R China. EM liuqh0545@126.com; jiaxu_hong@163.com OI Liu, Qinghuai/0000-0003-1605-1964 FU Key Clinic Medicine Research Program, the Ministry of Health, China [201302015]; National Science and Technology Research Program, the Ministry of Science and Technology, China [2012BAI08B01]; National Natural Science Foundation of China [81170817, 81200658, 81300735, 81270978, U1205025, 81330022]; Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai [13441900900, 13430720400]; Chinese Postdoctoral Fund [XMU135890]; New Technology Joint Research Project in Shanghai Hospitals [SHDC12014114] FX The authors were supported by grants from the Key Clinic Medicine Research Program, the Ministry of Health, China (201302015); the National Science and Technology Research Program, the Ministry of Science and Technology, China (2012BAI08B01); the National Natural Science Foundation of China (81170817, 81200658, 81300735, 81270978, U1205025, and 81330022); the Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai (13441900900, 13430720400); the Chinese Postdoctoral Fund (XMU135890); and the New Technology Joint Research Project in Shanghai Hospitals (SHDC12014114). The sponsor or funding organization had no role in the design or conduct of this research. NR 34 TC 0 Z9 0 U1 5 U2 8 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 JAN 15 PY 2016 VL 11 IS 1 AR e0146752 DI 10.1371/journal.pone.0146752 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB6ME UT WOS:000368628300032 PM 26771186 ER PT J AU Kim, CS Vanture, S Cho, M Klapperich, CM Wang, C Huang, FW AF Kim, Chloe S. Vanture, Sarah Cho, Margaret Klapperich, Catherine M. Wang, Catharine Huang, Franklin W. TI Awareness, Interest, and Preferences of Primary Care Providers in Using Point-of-Care Cancer Screening Technology SO PLOS ONE LA English DT Article ID BREAST; PREVENTION; BARRIERS AB Well-developed point-of-care (POC) cancer screening tools have the potential to provide better cancer care to patients in both developed and developing countries. However, new medical technology will not be adopted by medical providers unless it addresses a population's existing needs and end-users' preferences. The goals of our study were to assess primary care providers' level of awareness, interest, and preferences in using POC cancer screening technology in their practice and to provide guidelines to biomedical engineers for future POC technology development. A total of 350 primary care providers completed a one-time self-administered online survey, which took approximately 10 minutes to complete. A $50 Amazon gift card was given as an honorarium for the first 100 respondents to encourage participation. The description of POC cancer screening technology was provided in the beginning of the survey to ensure all participants had a basic understanding of what constitutes POC technology. More than half of the participants (57%) stated that they heard of the term "POC technology" for the first time when they took the survey. However, almost all of the participants (97%) stated they were either "very interested" (68%) or "some-what interested" (29%) in using POC cancer screening technology in their practice. Demographic characteristics such as the length of being in the practice of medicine, the percentage of patients on Medicaid, and the average number of patients per day were not shown to be associated with the level of interest in using POC. These data show that there is a great interest in POC cancer screening technology utilization among this population of primary care providers and vast room for future investigations to further understand the interest and preferences in using POC cancer technology in practice. Ensuring that the benefits of new technology outweigh the costs will maximize the likelihood it will be used by medical providers and patients. C1 [Kim, Chloe S.; Vanture, Sarah; Cho, Margaret; Klapperich, Catherine M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Wang, Catharine] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. [Huang, Franklin W.] Harvard Univ, Sch Med, Boston, MA USA. [Huang, Franklin W.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Klapperich, CM (reprint author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.; Huang, FW (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Huang, FW (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM catherin@bu.edu; Franklin_Huang@dfci.harvard.edu OI Wang, Catharine/0000-0001-8584-2781 FU National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIBIB-NIH) [5-U54-EB015403] FX Research reported in this paper was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIBIB-NIH) under the grant number: 5-U54-EB015403. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The authors thank Dr. Mangione for his helpful comments during the survey design phase. Research reported in this paper was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIBIB-NIH) under the grant number: 5-U54-EB015403. NR 21 TC 1 Z9 1 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 15 PY 2016 VL 11 IS 1 AR e0145215 DI 10.1371/journal.pone.0145215 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB6ME UT WOS:000368628300005 PM 26771309 ER PT J AU Reichardt, P Demetri, GD Gelderblom, H Rutkowski, P Im, SA Gupta, S Kang, YK Schoffski, P Schuette, J Soulieres, D Blay, JY Goldstein, D Fly, K Huang, X Corsaro, M Lechuga, MJ Martini, JF Heinrich, MC AF Reichardt, Peter Demetri, George D. Gelderblom, Hans Rutkowski, Piotr Im, Seock-Ah Gupta, Sudeep Kang, Yoon-Koo Schoffski, Patrick Schuette, Jochen Soulieres, Denis Blay, Jean-Yves Goldstein, David Fly, Kolette Huang, Xin Corsaro, Massimo Lechuga, Maria Jose Martini, Jean-Francois Heinrich, Michael C. TI Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial SO BMC CANCER LA English DT Article DE Sunitinib; Imatinib; GIST; KIT; KIT mutation; Imatinib-resistant GIST; Overall survival; Progression-free survival ID TYROSINE KINASE INHIBITOR; IMATINIB RESISTANCE; ACQUIRED-RESISTANCE; IN-VIVO; ACTIVATION; EFFICACY; SU11248; GENE; MECHANISMS; GENOTYPE AB Background: Several small studies indicated that the genotype of KIT or platelet-derived growth factor receptor-a (PDGFRA) contributes in part to the level of clinical effectiveness of sunitinib in gastrointestinal stromal tumor (GIST) patients. This study aimed to correlate KIT and PDGFRA mutational status with clinical outcome metrics (progression-free survival [PFS], overall survival [OS], objective response rate [ORR]) in a larger international patient population. Methods: This is a non-interventional, retrospective analysis in patients with imatinib-resistant or intolerant GIST who were treated in a worldwide, open-label treatment-use study (Study 1036; NCT00094029) in which sunitinib was administered at a starting dose of 50 mg/day on a 4-week-on, 2-week-off schedule. Molecular status was obtained in local laboratories with tumor samples obtained either pre-imatinib, post-imatinib/pre-sunitinib, or post-sunitinib treatment, and all available data were used in the analyses regardless of collection time. The primary analysis compared PFS in patients with primary KIT exon 11 versus exon 9 mutations (using a 2-sided log-rank test) and secondary analyses compared OS (using the same test) and ORR (using a 2-sided Pearson X-2 test) in the same molecular subgroups. Results: Of the 1124 sunitinib-treated patients in the treatment-use study, 230 (20 %) were included in this analysis, and baseline characteristics were similar between the two study populations. Median PFS was 7.1 months. A significantly better PFS was observed in patients with a primary mutation in KIT exon 9 (n = 42) compared to those with a primary mutation in exon 11 (n = 143; hazard ratio = 0.59; 95 % confidence interval, 0.39-0.89; P = 0.011), with median PFS times of 12.3 and 7.0 months, respectively. Similarly, longer OS and higher ORR were observed in patients with a primary KIT mutation in exon 9 versus exon 11. The data available were limited to investigate the effects of additional KIT or PDGFRA mutations on the efficacy of sunitinib treatment. Conclusions: This large retrospective analysis confirms the prognostic significance of KIT mutation status in patients with GIST. This analysis also confirms the effectiveness of sunitinib as a post-imatinib therapy, regardless of mutational status. C1 [Reichardt, Peter] HELIOS Klinikum Berlin Buch, Dept Interdisciplinary Oncol, D-13125 Berlin, Germany. [Demetri, George D.] Ludwig Ctr Harvard, Boston, MA USA. [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelderblom, Hans] Leiden Univ, Med Ctr, Leiden, Netherlands. [Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, Piotr] Inst Oncol, Warsaw, Poland. [Im, Seock-Ah] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul Natl Univ Hosp, Seoul, South Korea. [Gupta, Sudeep] Tata Mem Hosp, Bombay, Maharashtra, India. [Kang, Yoon-Koo] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. [Schoffski, Patrick] Katholieke Univ Leuven, Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium. [Schoffski, Patrick] Katholieke Univ Leuven, Expt Oncol Lab, Leuven, Belgium. [Schuette, Jochen] Hamatoonkol Schwerpunktpraxis, Dusseldorf, Germany. [Soulieres, Denis] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Blay, Jean-Yves] Univ Lyon 1, Ctr Leon Berard, F-69365 Lyon, France. [Goldstein, David] Prince Wales Hosp, Sydney, NSW, Australia. [Fly, Kolette] Pfizer Oncol, Groton, CT USA. [Huang, Xin; Martini, Jean-Francois] Pfizer Oncol, La Jolla, CA USA. [Corsaro, Massimo; Lechuga, Maria Jose] Pfizer Oncol, Milan, Italy. [Heinrich, Michael C.] VA Portland Hlth Care Syst, Portland, OR USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Reichardt, P (reprint author), HELIOS Klinikum Berlin Buch, Dept Interdisciplinary Oncol, Schwanebecker Chaussee 50, D-13125 Berlin, Germany. EM peter.reichardt@helios-kliniken.de RI Blay, Jean-Yves/N-3966-2016; OI Blay, Jean-Yves/0000-0001-7190-120X; Rutkowski, Piotr/0000-0002-8920-5429 FU Pfizer Inc.; Ludwig Center at Harvard; Pan-Mass Challenge via Team Paul's Posse; Russo Family Fund for GIST research; Gastrointestinal Cancer SPORE Grant at Dana-Farber Cancer Institute from the US National Cancer Institute [1P50CA127003-05] FX We would like to thank all of the participating patients and their families, as well as the investigators, research nurses, study coordinators, and operations staff. This study was sponsored by Pfizer Inc. Support for this work, in part, was also provided to George D. Demetri from the following sources: Ludwig Center at Harvard, The Pan-Mass Challenge via Team Paul's Posse, the Russo Family Fund for GIST research, and Gastrointestinal Cancer SPORE Grant 1P50CA127003-05 at Dana-Farber Cancer Institute from the US National Cancer Institute. Medical writing support was provided by Andy Gannon and Ryan Woodrow at ACUMED (R) (New York, NY, USA), an Ashfield company, part of UDG Healthcare plc, with funding from Pfizer Inc. NR 39 TC 1 Z9 1 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JAN 15 PY 2016 VL 16 AR 22 DI 10.1186/s12885-016-2051-5 PG 10 WC Oncology SC Oncology GA DA8SW UT WOS:000368077400002 PM 26772734 ER PT J AU Brandao, DF Strasser-Weippl, K Goss, PE AF Brandao, Denise Froes Strasser-Weippl, Kathrin Goss, Paul E. TI Prolactin and breast cancer: The need to avoid undertreatment of serious psychiatric illnesses in breast cancer patients: A review SO CANCER LA English DT Review DE antidepressive agents; antipsychotic agents; breast neoplasms; depression; prolactin ID POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; PLASMA PROLACTIN; DEPRESSION; RISK; MORTALITY; RECEPTOR; GROWTH; COHORT; DRUGS AB Hyperprolactinemia, defined as a sustained elevation of prolactin (PRL) levels greater than 530 mIU/L in women and greater than 424 mIU/L in men, has been implicated for a long time in breast cancer etiology and prognosis. Elevated PRL values (approximately 2-3 times higher than the reference values) are a common adverse effect of antipsychotic medications, especially with first-generation drugs, and most antipsychotics carry a standard warning regarding PRL elevations on their US product labels. These associations foster undertreatment of serious psychiatric illnesses in both otherwise healthy patients and cancer patients. This review assesses both the preclinical and clinical evidence that has led to the hypothesis of PRL's role in breast cancer risk or breast cancer progression. It is concluded that taken together, the published data are unconvincing and insufficient to deprive cancer patients in general and breast cancer patients specifically of potentially effective antipsychotic or antidepressant medications for serious psychiatric indications. We thus call on revised medication guidelines to avoid the existing undertreatment of serious psychiatric illnesses among cancer patients based on an unproven contraindication to psychiatric medications. Cancer 2016;122:184-188. (c) 2015 American Cancer Society. This review discusses the evidence for a role of hyperprolactinemia in breast cancer risk and prognosis. New guidelines are needed for antipsychotic and antidepressant medications among cancer patients. C1 [Brandao, Denise Froes; Goss, Paul E.] Massachusetts Gen Hosp, Avon Int Breast Canc Res Program, Ctr Canc, Boston, MA 02114 USA. [Brandao, Denise Froes; Goss, Paul E.] Global Canc Inst, Boston, MA USA. [Brandao, Denise Froes] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol & Hematol, Vienna, Austria. [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@mgh.harvard.edu NR 40 TC 3 Z9 3 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2016 VL 122 IS 2 BP 184 EP 188 DI 10.1002/cncr.29714 PG 5 WC Oncology SC Oncology GA DA7UK UT WOS:000368009600006 ER PT J AU Jordan, JT Gerstner, ER Batchelor, TT Cahill, DP Plotkin, SR AF Jordan, Justin T. Gerstner, Elizabeth R. Batchelor, Tracy T. Cahill, Daniel P. Plotkin, Scott R. TI Glioblastoma care in the elderly SO CANCER LA English DT Review DE elderly; glioblastoma; neuro-oncology; O(6)-methylguanine-DNA methyltransferase (MGMT) ID RADIOTHERAPY PLUS CONCOMITANT; NEWLY-DIAGNOSED GLIOBLASTOMA; OLDER PATIENTS; ADJUVANT TEMOZOLOMIDE; CLINICAL-TRIAL; PROMOTER METHYLATION; RADIATION-THERAPY; PHASE-3 TRIAL; MULTIFORME; MGMT AB Glioblastoma is common among elderly patients, a group in which comorbidities and a poor prognosis raise important considerations when designing neuro-oncologic care. Although the standard of care for nonelderly patients with glioblastoma includes maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide, the safety and efficacy of these modalities in elderly patients are less certain given the population's underrepresentation in many clinical trials. The authors reviewed the clinical trial literature for reports on the treatment of elderly patients with glioblastoma to provide evidence-based guidance for practitioners. In elderly patients with glioblastoma, there is a survival advantage for those who undergo maximal safe resection, which likely includes an incremental benefit with increasing completeness of resection. Radiotherapy extends survival in selected patients, and hypofractionation appears to be more tolerable than standard fractionation. In addition, temozolomide chemotherapy is safe and extends the survival of patients with tumors that harbor O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation. The combination of standard radiation with concurrent and adjuvant temozolomide has not been studied in this population. Although many questions remain unanswered regarding the treatment of glioblastoma in elderly patients, the available evidence provides a framework on which providers may base individual treatment decisions. The importance of tumor biomarkers is increasingly apparent in elderly patients, for whom the therapeutic efficacy of any treatment must be weighed against its potential toxicity. MGMT promoter methylation status has specifically demonstrated utility in predicting the efficacy of temozolomide and should be considered in treatment decisions when possible. Cancer 2016;122:189-197. (c) 2015 American Cancer Society. Glioblastoma is most common in elderly patients, yet most clinical trials for glioblastoma exclude patients of advanced age. Understanding data specific to this important population is critical for the practicing oncologist to make informed decisions regarding care. C1 [Jordan, Justin T.; Gerstner, Elizabeth R.; Batchelor, Tracy T.; Plotkin, Scott R.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Jordan, JT (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey Bldg,Suite 9E, Boston, MA 02114 USA. EM jtjordan@mgh.harvard.edu OI Cahill, Daniel/0000-0003-2552-6546 FU Merck Company; Roche; Kirin Pharmaceuticals; Novartis; Proximagen; Agenus; Spectrum; Amgen; Up to Date Inc; Robert Michael Educational Institute LLC; Educational Concepts Group; Research to Practice; Oakstone Medical Publishing; Imedex; Champion Biotechnology; Champion Advance Medical; Pfizer; Astra Zeneca; Millennium; Vertex FX Dr. Batchelor reports pharmaceutical consulting fees from Merck & Company, Roche, Kirin Pharmaceuticals, Novartis, Proximagen, Agenus, Spectrum, and Amgen; fees for continuing medical education lectures/materials from Up to Date Inc, Robert Michael Educational Institute LLC, Educational Concepts Group, Research to Practice, Oakstone Medical Publishing, and Imedex; other consulting fees from Champions Biotechnology and Advance Medical; and research support from Pfizer, Astra Zeneca, and Millennium outside the submitted work. Dr. Cahill reports personal fees from Merck & Company and Vertex and nonfinancial support from Merck & Company outside the submitted work. NR 42 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2016 VL 122 IS 2 BP 189 EP 197 DI 10.1002/cncr.29742 PG 9 WC Oncology SC Oncology GA DA7UK UT WOS:000368009600007 PM 26618888 ER PT J AU Pashankar, F Hale, JP Dang, H Krailo, M Brady, WE Rodriguez-Galindo, C Nicholson, JC Murray, MJ Bilmire, DF Stoneham, S Arul, GS Olson, TA Stark, D Shaikh, F Amatruda, JF Covens, A Gershenson, DM Frazier, AL AF Pashankar, Farzana Hale, Juliet P. Dang, Ha Krailo, Mark Brady, William E. Rodriguez-Galindo, Carlos Nicholson, James C. Murray, Matthew J. Bilmire, Deborah F. Stoneham, Sara Arul, G. Suren Olson, Thomas A. Stark, Daniel Shaikh, Furqan Amatruda, James F. Covens, Allan Gershenson, David M. Frazier, A. Lindsay TI Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative SO CANCER LA English DT Article DE adult; chemotherapy; ovarian immature teratoma; pediatric ID PEDIATRIC-ONCOLOGY-GROUP; CHILDRENS CANCER GROUP; EXPERIENCE; CHILDHOOD; THERAPY; TRIAL AB BACKGROUNDThere is a debate regarding the management of ovarian immature teratomas (ITs). In adult women, postoperative chemotherapy is standard except for stage I, grade 1 disease, whereas surgery alone is standard in pediatric patients. To determine the role of chemotherapy, a pooled analysis of pediatric and adult clinical trials was conducted. METHODSData from 7 pediatric trials and 2 adult trials were merged in the Malignant Germ Cell International Collaborative data set. Four trials included patients with newly diagnosed pure ovarian ITs and were selected (Pediatric Oncology Group/Children's Cancer Group Intergroup Study (INT 0106), Second UKCCSG Germ Cell Tumor Study (GC2), Gynecologic Oncology Group (GOG 0078 and GOG 0090). Adult and pediatric trials were analyzed separately. The primary outcome measures were event-free survival (EFS) and overall survival (OS). RESULTSOne hundred seventy-nine patients were included (98 pediatric patients and 81 adult patients). Ninety pediatric patients were treated with surgery alone, whereas all adult patients received chemotherapy. The 5-year EFS and OS were 91% and 99%, respectively, for the pediatric cohort and 87% and 93%, respectively, for the adults. There were no relapses in grade 1 patients, regardless of the stage or age. Only 1 adult patient with a grade 2 IT relapsed. Among grade 3 patients, the 5-year EFS was 0.92 (0.72-0.98) for stage I/II and 0.52 (0.22-0.75) for stage III in the pediatric cohort (P = .005) and 0.91 (0.69-0.98) for stage I/II and 0.65 (0.39-0.83) for stage III/IV in the adult cohort (P = .01). Postoperative chemotherapy did not decrease relapses in the pediatric cohort. CONCLUSIONSThe grade was the most important risk factor for relapse in ovarian ITs. Among grade 3 patients, the stage was significantly associated with relapse. Adjuvant chemotherapy did not decrease relapses in the pediatric cohort; its role in adults remains unresolved. Cancer 2016;122:230-237. (c) 2015 American Cancer Society. Grade is the most important risk factor for relapse in ovarian immature teratomas, and no relapses have been found in patients with grade 1 tumors, regardless of the stage or age. Postoperative adjuvant chemotherapy does not decrease the risk of relapse in pediatric patients, but its role in adults remains unclear. C1 [Pashankar, Farzana] Yale Univ, Sch Med, New Haven, CT 06524 USA. [Hale, Juliet P.] Royal Victoria Infirm, Newcastle Upon Tyne Hosp Trust, Dept Paediat Oncol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Dang, Ha] Childrens Oncol Grp, Monrovia, CA USA. [Krailo, Mark] Univ So Calif, Los Angeles, CA USA. [Brady, William E.] Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Boston Childrens Hosp, Boston, MA USA. [Nicholson, James C.; Murray, Matthew J.] Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England. [Bilmire, Deborah F.] Riley Hosp Children, Indianapolis, IN USA. [Stoneham, Sara] Univ Coll London Hosp Trusts, Childrens & Young Persons Canc Serv, London, England. [Arul, G. Suren] Birmingham Childrens Hosp NHS Fdn Trust, Birmingham, W Midlands, England. [Olson, Thomas A.] Emory Univ, Aflac Canc Ctr, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Stark, Daniel] Leeds Inst Oncol, Leeds Inst Canc Studies & Pathol, Leeds, W Yorkshire, England. [Stark, Daniel] St James Univ Hosp, Leeds, W Yorkshire, England. [Shaikh, Furqan; Covens, Allan] Univ Toronto, Toronto, ON, Canada. [Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Amatruda, James F.] Childrens Med Ctr, Dallas, TX 75235 USA. [Gershenson, David M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Pashankar, F (reprint author), Yale Univ, Sch Med, 333 Cedar St,LMP 2073, New Haven, CT 06524 USA. EM farzana.pashankar@yale.edu FU Bridging the Gap Fund; Dana-Farber Cancer Institute; Katie Walker Cancer Trust; Teenage Cancer Trust; William and Guy Forbeck Foundation FX This study was supported by the Bridging the Gap Fund, the Dana-Farber Cancer Institute, the Katie Walker Cancer Trust, the Teenage Cancer Trust, and the William and Guy Forbeck Foundation. NR 18 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2016 VL 122 IS 2 BP 230 EP 237 DI 10.1002/cncr.29732 PG 8 WC Oncology SC Oncology GA DA7UK UT WOS:000368009600012 PM 26485622 ER PT J AU Recklitis, CJ Blackmon, JE Chang, G AF Recklitis, Christopher J. Blackmon, Jaime E. Chang, Grace TI Screening young adult cancer survivors for distress with the Distress Thermometer: Comparisons with a structured clinical diagnostic interview SO CANCER LA English DT Article DE anxiety; cancer survivors; depression; Distress Thermometer; Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders; 4th Edition (SCID); validation ID LONG-TERM SURVIVORS; CHILDHOOD-CANCER; PSYCHOLOGIC DISTRESS; NATIONAL-SURVEY; DEPRESSION; ANXIETY; VALIDATION; HEALTH; METAANALYSIS; INSTRUMENTS AB BACKGROUNDThe validity of the Distress Thermometer (DT) as a screen for psychological distress in young adult cancer survivors was assessed by comparing it with the results of a psychiatric diagnostic interview, the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) (SCID), to evaluate the accuracy of the DT and identify optimal cutoff scores for this population. METHODSA total of 247 survivors aged 18 to 40 years completed the DT and SCID. Based on the SCID, participants were classified as having: 1)1 SCID diagnoses; 2) significant symptoms, but no SCID diagnosis; or 3) no significant SCID symptoms. Receiver operating characteristic analyses determined the sensitivity and specificity of all possible DT cutoff scores for detecting survivors with a SCID diagnosis, and subsequently for survivors with significant SCID symptoms or a SCID diagnosis. RESULTSThe recommended DT cutoff score of 5 failed to identify 31.81% of survivors with a SCID diagnosis (sensitivity of 68.18% and specificity of 78.33%), and 32.81% of survivors with either significant SCID symptoms or a SCID diagnosis. No alternative DT cutoff score met the criteria for acceptable sensitivity (85%) and specificity (75%). CONCLUSIONSThe DT does not reliably identify young adult cancer survivors with psychiatric problems identified by a gold standard structured psychiatric interview. Therefore, the DT should not be used as a stand-alone psychological screen in this population. Cancer 2016;122:296-303. (c) 2015 American Cancer Society. In a study of 247 young adult cancer survivors, conventional cutoff scores on the Distress Thermometer (DT) failed to identify 18% to 30% of survivors with a psychiatric disorder identified by a structured diagnostic interview. Alternative DT cutoff scores did not demonstrate a balance of sensitivity and specificity suited to clinical screening, indicating that the DT should not be used as a stand-alone screen in this population. C1 [Recklitis, Christopher J.; Blackmon, Jaime E.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02215 USA. [Recklitis, Christopher J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Chang, Grace] VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA USA. [Chang, Grace] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Psychiat, Boston, MA USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SW-320C, Boston, MA 02215 USA. EM Christopher_Recklitis@dfci.harvard.edu FU National Cancer Institute [1R21CA161315] FX Funded by the National Cancer Institute (grant 1R21CA161315 to Christopher Recklitis). NR 38 TC 3 Z9 3 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2016 VL 122 IS 2 BP 296 EP 303 DI 10.1002/cncr.29736 PG 8 WC Oncology SC Oncology GA DA7UK UT WOS:000368009600019 PM 26457669 ER PT J AU Mandal, CC Das, F Ganapathy, S Harris, SE Choudhury, GG Ghosh-Choudhury, N AF Mandal, Chandi C. Das, Falguni Ganapathy, Suthakar Harris, Stephen E. Choudhury, Goutam Ghosh Ghosh-Choudhury, Nandini TI Bone Morphogenetic Protein-2 ( BMP-2) Activates NFATc1 Transcription Factor via an Autoregulatory Loop Involving Smad/Akt/Ca2+ Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KAPPA-B LIGAND; GLYCOGEN-SYNTHASE KINASE-3; EFFECTOR T-CELLS; OSTEOBLAST DIFFERENTIATION; OSTEOCLAST DIFFERENTIATION; PHOSPHATIDYLINOSITOL 3-KINASE; RECEPTOR ACTIVATOR; NF-ATC; GENE-TRANSCRIPTION; EXPRESSION AB Background: Mutations in NFATc1 and BMP-2 genes result in bone abnormalities in mice. Results: BMP-2 activates intracellular Ca2+ release, thus activating calcineurin phosphatase to induce NFATc1 expression involving canonical Smad and noncanonical PI 3-kinase in osteoblasts. Conclusion: BMP-2-stimulated Ca-2 -calcineurin-NFATc1 axis potentiates osteoblast differentiation. Significance: NFATc1 autoregulates its expression in response to BMP-2 in osteoblasts. C1 [Choudhury, Goutam Ghosh; Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Vet Affairs Res, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Mandal, Chandi C.; Ganapathy, Suthakar; Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Das, Falguni; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Harris, Stephen E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. RP Ghosh-Choudhury, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. EM choudhury@uthscsa.edu FU Veterans Affairs Merit Review grants; National Institutes of Health [RO1 AR52425, RO1 DK50190]; Cancer Prevention Research Institute of Texas fellowship; Veterans Affairs Senior Research Career Scientist Award FX This work was supported in part by Veterans Affairs Merit Review grants and National Institutes of Health Grant RO1 AR52425 (to N.G.-C.)and National Institutes of Health Grant RO1 DK50190 and Veterans Affairs Merit Review grants (to G.G.C.). The authors do not have any conflict of interests. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Recipient of a Cancer Prevention Research Institute of Texas fellowship. Present address: Dept. of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer 305801, India.; Recipient of a Veterans Affairs Senior Research Career Scientist Award. NR 49 TC 1 Z9 1 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 2016 VL 291 IS 3 BP 1148 EP 1161 DI 10.1074/jbc.M115.668939 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA8PR UT WOS:000368068300011 PM 26472929 ER PT J AU Watts, LT Long, JA Boggs, RC Manga, H Huang, SL Shen, Q Duong, TQ AF Watts, Lora Talley Long, Justin Alexander Boggs, Robert Cole Manga, Hemanth Huang, Shiliang Shen, Qiang Duong, Timothy Q. TI Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE behavioral outcomes; CCI; methylene blue; mitochondria; MRI; TBI ID DIFFUSE AXONAL INJURY; SEVERE HEAD-INJURIES; WHITE-MATTER INJURY; CYCLOSPORINE-A; OXIDATIVE STRESS; IN-VIVO; DAMAGE; NEUROPROTECTION; RAT; ISCHEMIA AB Traumatic brain injury (TBI) remains a primary cause of death and disability in both civilian and military populations worldwide. There is a critical need for the development of neuroprotective agents that can circumvent damage and provide functional recovery. We previously showed that methylene blue (MB), a U.S. Food and Drug Administration-grandfathered drug with energy-enhancing and antioxidant properties, given 1 and 3h post-TBI, had neuroprotective effects in rats. This study aimed to further investigate the neuroprotection of delayed MB treatment (24h postinjury) post-TBI as measured by lesion volume and functional outcomes. Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic resonance imaging and behavioral studies were performed at 1 and 3h and 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. We found that delaying MB treatment 24h postinjury still minimized lesion volume and functional deficits, compared to vehicle-treated animals. The data further support the potential for MB as a neuroprotective treatment, especially when medical teatment is not readily available. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored. C1 [Watts, Lora Talley; Long, Justin Alexander; Boggs, Robert Cole; Manga, Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Watts, Lora Talley; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Div Res, San Antonio, TX USA. RP Watts, LT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wattsl@uthscsa.edu FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01 NS45879]; Clinical Translational Science Awards (CTSA) [TL1, KL2, 8UL1TR000149, TL1TR001119, TR001118]; Mike Hogg Fund FX This work was supported, in part, by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01 NS45879; to T.Q.D.), a TL1 grant (to J.A.L.) and KL2 (to L.T.W.) through the Clinical Translational Science Awards (CTSA; parent grant 8UL1TR000149, TL1TR001119, and TR001118), and the Mike Hogg Fund (to L.T.W.). NR 56 TC 2 Z9 2 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JAN 15 PY 2016 VL 33 IS 2 BP 194 EP 202 DI 10.1089/neu.2015.3904 PG 9 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DA7PH UT WOS:000367995800005 ER PT J AU Isokuortti, H Iverson, GL Kataja, A Brander, A Ohman, J Luoto, TM AF Isokuortti, Harri Iverson, Grant L. Kataja, Anneli Brander, Antti Ohman, Juha Luoto, Teemu M. TI Who Gets Head Trauma or Recruited in Mild Traumatic Brain Injury Research? SO JOURNAL OF NEUROTRAUMA LA English DT Article DE brain injury; comorbidity; concussion; head injury; patient recruitment ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; WHITE-MATTER INTEGRITY; MAJOR DEPRESSIVE DISORDER; TENSOR IMAGING FINDINGS; PSYCHIATRIC-DISORDERS; COGNITIVE IMPAIRMENT; EMERGENCY-DEPARTMENT; EXECUTIVE FUNCTION; SUBSTANCE-ABUSE; WORKING-MEMORY AB Mild traumatic brain injury (mTBI) is a public health problem. Outcome from mTBI is heterogeneous in part due to pre-injury individual differences that typically are not well described or understood. Pre-injury health characteristics of all consecutive patients (n=3023) who underwent head computed tomography due to acute head trauma in the emergency department of Tampere University Hospital, Finland, between August 2010 and July 2012 were examined. Patients were screened to obtain a sample of working age adults with no pre-injury medical or mental health problems who had sustained a pure mTBI. Of all patients screened, 1990 (65.8%) fulfilled the mTBI criteria, 257 (8.5%) had a more severe TBI, and 776 (25.7%) had a head trauma without obvious signs of brain injury. Injury-related data and participant-related data (e.g., age, sex, diagnosed diseases, and medications) were collected from hospital records. The most common pre-injury diseases were circulatory (39.4%-43.2%), neurological (23.7%-25.2%), and psychiatric (25.8%-27.5%) disorders. Alcohol abuse was present in 18.4%-26.8%. The most common medications were for cardiovascular (33.1%-36.6%), central nervous system (21.4%-30.8%), and blood clotting and anemia indications (21.5%-22.6%). Of the screened patients, only 2.5% met all the enrollment criteria. Age, neurological conditions, and psychiatric problems were the most common reasons for exclusion. Most of the patients sustaining an mTBI have some pre-injury diseases or conditions that could affect clinical outcome. By excluding patients with pre-existing conditions, the patients with known risk factors for poor outcome remain poorly studied. C1 [Isokuortti, Harri] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Iverson, Grant L.] Harvard Univ, Dept Phys Med & Rehabil, Sch Med, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] MassGen Hosp Children, Sports Concuss Program, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Kataja, Anneli; Brander, Antti] Tampere Univ Hosp, Dept Radiol, Tampere, Finland. [Ohman, Juha] Tampere Univ Hosp, Dept Neurosci & Rehabil, Tampere, Finland. [Luoto, Teemu M.] Tampere Univ Hosp, Dept Neurosurg, Tampere, Finland. RP Isokuortti, H (reprint author), Univ Tampere, Sch Med, Tampereen Yliopisto 33014, Finland. EM harri.isokuortti@gmail.com OI Ohman, Juha/0000-0002-6592-1367 FU INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium - Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD] FX The authors thank research assistants Anne Simi and Marika Suopanki-Ervasti for their contribution in data collection. GLI notes that he was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program (X81XWH-07-CC-CSDoD). This study was conducted as part of the first author's PhD thesis research program. NR 76 TC 2 Z9 2 U1 2 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JAN 15 PY 2016 VL 33 IS 2 BP 232 EP 241 DI 10.1089/neu.2015.3888 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DA7PH UT WOS:000367995800009 PM 26054639 ER PT J AU Madani, N AF Madani, Navid TI Visa rules imperil collaboration SO SCIENCE LA English DT Letter C1 [Madani, Navid] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA. [Madani, Navid] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02215 USA. RP Madani, N (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA. EM Navid_Madani@dfci.harvard.edu NR 6 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 15 PY 2016 VL 351 IS 6270 BP 234 EP 234 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA9AM UT WOS:000368098600026 PM 26816368 ER PT J AU Masuda, T Wang, X Maeda, M Canver, MC Sher, F Funnell, APW Fisher, C Suciu, M Martyn, GE Norton, LJ Zhu, C Kurita, R Nakamura, Y Xu, J Higgs, DR Crossley, M Bauer, DE Orkin, SH Kharchenko, PV Maeda, T AF Masuda, Takeshi Wang, Xin Maeda, Manami Canver, Matthew C. Sher, Falak Funnell, Alister P. W. Fisher, Chris Suciu, Maria Martyn, Gabriella E. Norton, Laura J. Zhu, Catherine Kurita, Ryo Nakamura, Yukio Xu, Jian Higgs, Douglas R. Crossley, Merlin Bauer, Daniel E. Orkin, Stuart H. Kharchenko, Peter V. Maeda, Takahiro TI Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin SO SCIENCE LA English DT Article ID GAMMA-GLOBIN GENE; ERYTHROID-CELLS; TRANSGENIC MICE; ERYTHROBLASTS; PROTEINS; DISEASE; TARGET AB Genes encoding human beta-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal g-globin genes and maintains the nucleosome density necessary for g-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies. C1 [Masuda, Takeshi; Maeda, Manami; Zhu, Catherine; Maeda, Takahiro] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA. [Wang, Xin; Kharchenko, Peter V.] Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA 02115 USA. [Canver, Matthew C.; Sher, Falak; Xu, Jian; Bauer, Daniel E.; Orkin, Stuart H.] Harvard Univ, Sch Med, Div Hematol Oncol, Dept Pediat Oncol,Dana Farber Canc Inst,Boston Ch, Boston, MA 02115 USA. [Funnell, Alister P. W.; Martyn, Gabriella E.; Norton, Laura J.; Crossley, Merlin] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia. [Fisher, Chris; Suciu, Maria; Higgs, Douglas R.] Univ Oxford, Weatherall Inst Mol Med, Med Res Council, Mol Haematol Unit, Oxford, England. [Kurita, Ryo; Nakamura, Yukio] RIKEN BioResource Ctr, Cell Engn Div, Tsukuba, Ibaraki, Japan. [Nakamura, Yukio] Univ Tsukuba, Comprehens Human Sci, Tsukuba, Ibaraki, Japan. [Xu, Jian] Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Res Inst, Dallas, TX 75390 USA. [Orkin, Stuart H.] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kharchenko, PV (reprint author), Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA 02115 USA. EM peter.kharchenko@post.harvard.edu; tmaeda@partners.org RI Nakamura, Yukio/A-5263-2016; OI Wang, Xin/0000-0002-5122-2418 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Predoctoral National Research Service Award [F30DK103359-01A1]; NIDDK Career Development Award [K08DK093705]; Doris Duke Charitable Foundation Innovations in Clinical Research Award [2013137]; NIH [P01HL032262, P30DK049216, 5K25AG037596, R01 AI084905, R56 DK105001]; Ellison Medical Foundation [AG-NS-0965-12]; American Society of Hematology Bridge Program grant FX We thank P. Jarolim, D. Dorfman, and other members of BWH Hematology laboratory for help on HPLC analysis; J. Hughes, J. Eglinton, J. Sharp, C. Babbs, K. di Gleria, D. Chen, and P. Schupp for technical support and assistance; E. Lamar for critical reading of the manuscript; and S-U. Lee, H. Yi, Y. Ishikawa and other members of the Maeda lab for help and advice. Supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Predoctoral National Research Service Award for M.D./Ph.D. Fellowship F30DK103359-01A1 (M.C.C.), NIDDK Career Development Award K08DK093705 and Doris Duke Charitable Foundation Innovations in Clinical Research Award 2013137 (D.E.B.), NIH grants P01HL032262 and P30DK049216 (Center of Excellence in Molecular Hematology) (S.H.O.), NIH grant 5K25AG037596 and Ellison Medical Foundation grant AG-NS-0965-12 (P.V.K.), and NIH grants R01 AI084905 and R56 DK105001 and an American Society of Hematology Bridge Program grant (T. Maeda). All reagents described in this manuscript (mouse models, plasmids) are available to the scientific community upon request. Sequencing data are available at the NCBI Gene Expression Omnibus (GEO accession number GSE74977). T. Masuda, M. Maeda, and T. Maeda are contributors to a patent application filed on behalf of Brigham and Women's Hospital related to therapeutic targeting of LRF/NuRD interaction. NR 24 TC 13 Z9 13 U1 7 U2 22 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 15 PY 2016 VL 351 IS 6270 BP 285 EP 289 DI 10.1126/science.aad3312 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA9AM UT WOS:000368098600043 PM 26816381 ER PT J AU Garcia, RG Valenza, G Tomaz, C Barbieri, R AF Garcia, Ronald G. Valenza, Gaetano Tomaz, Carlos Barbieri, Riccardo TI Relationship between cardiac vagal activity and mood congruent memory bias in major depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Major depression; Emotional memory; Autonomic nervous system; Vagus nerve; Heart rate variability; Point-process ID HEART-RATE-VARIABILITY; AUTONOMIC FUNCTION; POLYVAGAL THEORY; BIPOLAR PATIENTS; INDIVIDUALS; PERSPECTIVE; DYNAMICS; STIMULI; STATES; SCALE AB Background: Previous studies suggest that autonomic reactivity during encoding of emotional information could modulate the neural processes mediating mood-congruent memory. In this study, we use a point-process model to determine dynamic autonomic tone in response to negative emotions and its influence on long-term memory of major depressed subjects. Methods: Forty-eight patients with major depression and 48 healthy controls were randomly assigned to either neutral or emotionally arousing audiovisual stimuli. An adaptive point-process algorithm was applied to compute instantaneous estimates of the spectral components of heart rate variability [Low frequency (LF), 0.04-0.15 Hz; High frequency (HF), 0.15-0.4 Hz]. Three days later subjects were submitted to a recall test. Results: A significant increase in HF power was observed in depressed subjects in response to the emotionally arousing stimulus (p=0.03). The results of a multivariate analysis revealed that the HF power during the emotional segment of the stimulus was independently associated with the score of the recall test in depressed subjects, after adjusting for age, gender and educational level (Coef. 0.003, 95%Cl, 0.0009-0.005, p = 0.008). Limitations: These results could only be interpreted as responses to elicitation of specific negative emotions, the relationship between HF changes and encoding/recall of positive stimuli should be further examined. Conclusions: Alterations on parasympathetic response to emotion are involved in the mood-congruent cognitive bias observed in major depression. These findings are clinically relevant because it could constitute the mechanism by which depressed patients maintain maladaptive patterns of negative information processing that trigger and sustain depressed mood. (C) 2015 Elsevier B.V. All rights reserved. C1 [Garcia, Ronald G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA USA. [Garcia, Ronald G.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med,Div Womens Hlth, Boston, MA 02115 USA. [Garcia, Ronald G.] Univ Santander UDES, Sch Med, Masira Res Inst, Bucaramanga, Colombia. [Valenza, Gaetano] Univ Pisa, Sch Engn, Res Ctr E Piaggio, Pisa, Italy. [Valenza, Gaetano; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Tomaz, Carlos] Univ Brasilia, Lab Neurosci & Behav, Brasilia, DF, Brazil. [Tomaz, Carlos] Univ CEUMA, Neurosci Res Grp, Sao Luis, MA, Brazil. RP Garcia, RG (reprint author), Martinos Ctr Biomed Imaging, CNY 149-2301,13th St, Charlestown, MA 02129 USA. EM rgarcia@nmr.mgh.harvard.edu OI Garcia, Ronald Gerardo/0000-0002-8325-9944 FU Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital; National Institute of Mental Health (NIMH) [NIMH R01 MH090291, R21-MH103468]; Colombian Institute for the Development of Science and Technology "Colciencias" [6566-408-20391] FX This study was supported by the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital; the National Institute of Mental Health (NIMH Grants NIMH R01 MH090291, R21-MH103468) and the Colombian Institute for the Development of Science and Technology "Colciencias" (Grant No. 6566-408-20391). NR 32 TC 0 Z9 0 U1 4 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN 15 PY 2016 VL 190 BP 19 EP 25 DI 10.1016/j.jad.2015.09.075 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CY5QT UT WOS:000366463000005 PM 26480207 ER PT J AU Rudolph, JL Fonda, JR Hunt, PR McGlinchey, RE Milberg, WP Reynolds, MW Yonan, C AF Rudolph, James L. Fonda, Jennifer R. Hunt, Phillip R. McGlinchey, Regina E. Milberg, William P. Reynolds, Matthew W. Yonan, Charles TI Association of Pseudobulbar Affect symptoms with quality of life and healthcare costs in Veterans with traumatic brain injury SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Pseudobulbar Affect; Health-related quality of life; Traumatic brain injury; Post-traumatic stress disorder; Emotional lability; Health care cost ID POSTTRAUMATIC-STRESS-DISORDER; IRAQ; AFGHANISTAN; PATHOPHYSIOLOGY; COMORBIDITY; PREVALENCE; DIAGNOSES; LABILITY; COMBAT; SCALE C1 [Rudolph, James L.; Fonda, Jennifer R.; McGlinchey, Regina E.; Milberg, William P.] VA Boston Healthcare Syst, GRECC, Boston, MA 02130 USA. [Rudolph, James L.; Fonda, Jennifer R.; McGlinchey, Regina E.; Milberg, William P.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA 02130 USA. [Rudolph, James L.] Providence VA Med Ctr, Ctr Innovat Geriatr Serv, Providence, RI USA. [Fonda, Jennifer R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Hunt, Phillip R.; Reynolds, Matthew W.] Evidera, Hlth Econ & Epidemiol, Lexington, MA USA. [McGlinchey, Regina E.; Milberg, William P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Yonan, Charles] Avanir Pharmaceut Inc, Hlth Econ & Outcomes Res, Aliso Viejo, CA USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, GRECC TRACTS JP 182, 150 South Huntington Ave, Boston, MA 02130 USA. EM James.Rudolph@va.gov RI McGlinchey, Regina/R-1971-2016 FU Avanir Pharmaceuticals, Inc. FX Funding and editorial support were provided by Avanir Pharmaceuticals, Inc. Evidera provided support for the protocol and manuscript preparation, in collaboration with VA investigators. VA Boston Healthcare System and the Translational Research Center for TBI and Stress Disorders (TRACTS), which is a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C), are acknowledged for providing overall and infrastructural support. NR 27 TC 1 Z9 1 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN 15 PY 2016 VL 190 BP 150 EP 155 DI 10.1016/j.jad.2015.10.003 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CY5QT UT WOS:000366463000024 PM 26519634 ER PT J AU Black, AC Cooney, NL Justice, AC Fiellin, LE Pietrzak, RH Lazar, CM Rosen, MI AF Black, Anne C. Cooney, Ned L. Justice, Amy C. Fiellin, Lynn E. Pietrzak, Robert H. Lazar, Christina M. Rosen, Marc I. TI Momentary assessment of PTSD symptoms and sexual risk behavior in male OEF/OIF/OND Veterans SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE PTSD; Veterans; Sexual risk; HIV; Substance use; EMA ID POSTTRAUMATIC-STRESS-DISORDER; RESIDENTIAL-TREATMENT; HIV-INFECTION; PREVALENCE; ALCOHOL; COMBAT AB Background: Post-traumatic stress disorder (PTSD) in Veterans is associated with increased sexual risk behaviors, but the nature of this association is not well understood. Typical PTSD measurement deriving a summary estimate of symptom severity over a period of time precludes inferences about symptom variability, and whether momentary changes in symptom severity predict risk behavior. Methods: We assessed the feasibility of measuring daily PTSD symptoms, substance use, and high-risk sexual behavior in Veterans using ecological momentary assessment (EMA). Feasibility indicators were survey completion, PTSD symptom variability, and variability in rates of substance use and sexual risk behavior. Nine male Veterans completed web-based questionnaires by cell phone three times per day for 28 days. Results: Median within-day survey completion rates maintained near 90%, and PTSD symptoms showed high within-person variability, ranging up to 59 points on the 80-point scale. Six Veterans reported alcohol or substance use, and substance users reported use of more than one drug. Eight Veterans reported 1 to 28 high-risk sexual events. Heightened PTSD-related negative affect and externalizing behaviors preceded high-risk sexual events. Greater PTSD symptom instability was associated with having multiple sexual partners in the 28-day period. Limitations: These results are preliminary, given this small sample size, and multiple comparisons, and should be verified with larger Veteran samples. Conclusions: Results support the feasibility and utility of using of EMA to better understand the relationship between PTSD symptoms and sexual risk behavior in Veterans. Specific antecedent-risk behavior patterns provide promise for focused clinical interventions. Published by Elsevier B.V. C1 [Black, Anne C.; Cooney, Ned L.; Justice, Amy C.; Fiellin, Lynn E.; Pietrzak, Robert H.; Lazar, Christina M.; Rosen, Marc I.] Yale Univ, Sch Med, New Haven, CT 06519 USA. [Justice, Amy C.] Yale Univ, Sch Publ Hlth, New Haven, CT 06519 USA. [Black, Anne C.; Cooney, Ned L.; Justice, Amy C.; Pietrzak, Robert H.; Lazar, Christina M.; Rosen, Marc I.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Pietrzak, Robert H.] US Dept Vet Affairs, Natl Ctr PTSD, White River Jct, VT USA. RP Black, AC (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave 116A-4, West Haven, CT 06516 USA. EM anne.black@yale.edu; ned.cooney@va.gov; amy.justice2@va.gov; lynn.fiellin@yale.edu; robert.pietrzak@yale.edu; christina.lazar@yale.edu; marc.rosen@yale.edu OI Justice, Amy/0000-0003-0139-5502 FU VA VISN-1 Pain Research, Informatics, Multi-morbidities, and Education (PRIME) Center; LIPS [96-008]; National Institute on Drug Abuse (NIDA); [R21 DA039038] FX This study was funded by the VA VISN-1 Pain Research, Informatics, Multi-morbidities, and Education (PRIME) Center; LIPS #96-008 and National Institute on Drug Abuse (NIDA); R21 DA039038 (ACB). NR 24 TC 0 Z9 0 U1 5 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN 15 PY 2016 VL 190 BP 424 EP 428 DI 10.1016/j.jad.2015.10.039 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CY5QT UT WOS:000366463000062 PM 26551400 ER PT J AU Bruno, N ter Maaten, JM Ovchinnikova, ES Vegter, EL Valente, MAE van der Meer, P de Boer, RA van der Harst, P Schmitter, D Metra, M O'Connor, CM Ponikowski, P Teerlink, JR Cotter, G Davison, B Cleland, JG Givertz, MM Bloomfield, DM Dittrich, HC Pinto, YM van Veldhuisen, DJ Hillege, HL Berezikov, E Voors, AA AF Bruno, Noemi ter Maaten, Jozine M. Ovchinnikova, Ekaterina S. Vegter, Eline L. Valente, Mattia A. E. van der Meer, Peter de Boer, Rudolf A. van der Harst, Pim Schmitter, Daniela Metra, Marco O'Connor, Christopher M. Ponikowski, Piotr Teerlink, John R. Cotter, Gad Davison, Beth Cleland, John G. Givertz, Michael M. Bloomfield, Daniel M. Dittrich, Howard C. Pinto, Yigal M. van Veldhuisen, Dirk J. Hillege, Hans L. Berezikov, Eugene Voors, Adriaan A. TI MicroRNAs relate to early worsening of renal function in patients with acute heart failure SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Circulating microRNA; Acute heart failure; Worsening renal function ID ISCHEMIA-REPERFUSION INJURY; ACUTE KIDNEY INJURY; EXPRESSION; DISEASE; BIOMARKERS; METAANALYSIS; PLAYERS; HFREF; HFPEF AB Background: Deregulation of microRNAs (miRNAs) may be involved in the pathogenesis of heart failure (HF) and renal disease. Our aim is to describe miRNA levels related to early worsening renal function in acute HF patients. Method and results: We studied the association between 12 circulating miRNAs and Worsening Renal Function (WRF; defined as an increase in the serum creatinine level of 0.3 mg per deciliter or more from admission to day 3), absolute change in creatinine and Neutrophil Gelatinase Associated Lipocalin (NGAL) from admission to day 3 in 98 patients hospitalized for acute HF. At baseline, circulating levels of all miRNAs were lower in patients with WRF, with statistically significant decreased levels of miR-199a-3p, miR-423-3p, and miR-let-7i-5p (p-value < 0.05). The increase in creatinine during the first 3 days of hospitalization was significantly associated with lower levels of miR-199a-3p, miR-27a-3p, miR-652-3p, miR-423-5p, and miR-let-7i-5p, while the increase in NGAL was significantly associated with lower levels of miR-18a-5p, miR-106a-5p, miR-223-3p, miR-199a-3p and miR-423-3p. MiR-199a-3p was the strongest predictor of WRF, with an Odds Ratio of 1.48 (1.061-2.065; p-value = 0.021) and a C-index of 0.701. Conclusions: Our results show that the levels of circulating miRNAs at hospital admission for acute HF were consistently lower in patients who developed worsening of renal function. MiR-199a-3p was the best predictor of WRF in these patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Bruno, Noemi; ter Maaten, Jozine M.; Vegter, Eline L.; Valente, Mattia A. E.; van der Meer, Peter; de Boer, Rudolf A.; van der Harst, Pim; van Veldhuisen, Dirk J.; Hillege, Hans L.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Ovchinnikova, Ekaterina S.; Berezikov, Eugene] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, Groningen, Netherlands. [Schmitter, Daniela] Momentum Res Inc, Allschwil, Switzerland. [Metra, Marco] Univ Brescia, Dept Cardiol, Brescia, Italy. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Cotter, Gad; Davison, Beth] Momentum Res, Durham, NC USA. [Cleland, John G.] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, Natl Heart & Lung Inst, London, England. [Cleland, John G.] Univ London Imperial Coll Sci Technol & Med, Harefield Hosp, Natl Heart & Lung Inst, London, England. [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Dittrich, Howard C.] Univ Iowa, Carver Coll Med, Cardiovasc Res Ctr, Iowa City, IA USA. [Pinto, Yigal M.] Univ Amsterdam, Amsterdam, Netherlands. RP Voors, AA (reprint author), Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Berezikov, Eugene/0000-0002-1145-2884; Cleland, John/0000-0002-1471-7016 FU Dutch Heart Foundation: Approaching Heart Failure By Translational Research Of RNA Mechanisms (ARENA); NovaCardia FX This study was supported by a Grant from the Dutch Heart Foundation: Approaching Heart Failure By Translational Research Of RNA Mechanisms (ARENA). The PROTECT trial was supported by NovaCardia, a subsidiary of Merck. NR 33 TC 3 Z9 4 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD JAN 15 PY 2016 VL 203 BP 564 EP 569 DI 10.1016/j.ijcard.2015.10.217 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CZ3MC UT WOS:000367007200145 PM 26569364 ER PT J AU Halim, SA Clare, RM Newby, LK Lokhnygina, Y Schweiger, MJ Hof, AW Hochman, JS James, SK White, HD Widimsky, P Betriu, A Bode, C Giugliano, RP Harrington, RA Zeymer, U AF Halim, Sharif A. Clare, Robert M. Newby, L. Kristin Lokhnygina, Yuliya Schweiger, Marc J. Hof, Arnoud W. Hochman, Judith S. James, Stefan K. White, Harvey D. Widimsky, Petr Betriu, Amadeo Bode, Christoph Giugliano, Robert P. Harrington, Robert A. Zeymer, Uwe TI Frequency, clinical and angiographic characteristics, and outcomes of high-risk non-ST-segment elevation acute coronary syndromes patients with left circumflex culprit lesions SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Left circumflex artery; Acute coronary syndromes; Infarct size ID ACUTE MYOCARDIAL-INFARCTION; ARTERY-OCCLUSION; INTERVENTION; EPTIFIBATIDE; INHIBITION; DEPRESSION; MORTALITY; ISCHEMIA; TRIAL AB Background: The relationship between culprit vessel, infarct size, and outcomes in non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unclear. In some reports, the left circumflex artery (LCX) was more often the culprit at angiography than the right coronary artery (RCA) or left anterior descending artery (LAD), and infarcts were larger with LCX culprits. Methods: We determined culprit vessel frequency and initial patency (TIMI flow grade), median fold elevation of peak troponin above the upper limit of normal, and outcomes (30-day death or myocardial infarction [MI] and 1-year mortality) by culprit vessel in high-risk NSTE ACS patients in the EARLY ACS trial. Results: Of 9406 patients, 2066 (22.0%) had angiographic core laboratory data. We evaluated 1774 patients for whom the culprit artery was not the left main, a bypass graft, or branch vessel. The culprit was the LCX in 560 (31.6%), LAD in 653 (36.8%), and RCA in 561 (31.6%) patients. There were fewer women (24.1%) and more prior MI (25.5%) among patients with a culprit LCX compared with those with a culprit LAD or RCA. Patients with LCX (21.2%) and RCA (27.5%) culprits more often had an occluded artery (TIMI 0/1) than did those with LAD (11.3%). Peak troponin elevation was significantly higher for LCX than RCA or LAD culprits. LCX culprit vessels were not associated with worse 30-day or 1-year outcomes in adjusted models. Conclusions: Among patientswith NSTE ACS, the frequencies of LCX, LAD, and RCA culprits were similar. Although LCX lesions were associated with higher peak troponin levels, there was no difference in short-or intermediateterm outcomes by culprit artery. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Halim, Sharif A.; Clare, Robert M.; Newby, L. Kristin; Lokhnygina, Yuliya] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Halim, Sharif A.; Clare, Robert M.; Newby, L. Kristin; Lokhnygina, Yuliya] Duke Clin Res Inst, Durham, NC USA. [Schweiger, Marc J.] Tufts Univ, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA. [Hof, Arnoud W.] Isala Klin, Hosp De Weezenlanden, Div Cardiol, Zwolle, Netherlands. [Hochman, Judith S.] NYU, Sch Med, Dept Med, New York, NY USA. [James, Stefan K.] Univ Uppsala Hosp, Cardiol, Uppsala, Sweden. [White, Harvey D.] Green Lane Cardiovasc Serv, Auckland, New Zealand. [Widimsky, Petr] Charles Univ Prague, Fac Med 3, Prague, Czech Republic. [Betriu, Amadeo] Hosp Clin Barcelona, Dept Cardiol, Barcelona, Spain. [Bode, Christoph] Univ Hosp Freiburg, Freiburg, Germany. [Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Harrington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Ludwigshafen, Germany. RP Newby, LK (reprint author), POB 17969, Durham, NC 27715 USA. EM kristin.newby@duke.edu RI Widimsky, Petr/P-8088-2016; OI Widimsky, Petr/0000-0001-5686-7752; Hochman, Judith/0000-0002-5889-5981 FU Schering-Plough Corporation; Merck and Co., Inc.; National Institutes of Health [HL069749-09] FX The EARLY ACS trial and angiographic substudy were funded by research grants from Schering-Plough Corporation. These analyses were funded by a research grant from Merck and Co., Inc. Dr. Halim was funded by the National Institutes of Health (T-32 training grant HL069749-09). NR 18 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD JAN 15 PY 2016 VL 203 BP 708 EP 713 DI 10.1016/j.ijcard.2015.11.036 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CZ3MC UT WOS:000367007200185 PM 26587725 ER PT J AU Ning, LP Setsompop, K Michailovich, O Makris, N Shenton, ME Westin, CF Rathi, Y AF Ning, Lipeng Setsompop, Kawin Michailovich, Oleg Makris, Nikos Shenton, Martha E. Westin, Carl-Fredrik Rathi, Yogesh TI A joint compressed-sensing and super-resolution approach for very high-resolution diffusion imaging SO NEUROIMAGE LA English DT Article DE Super resolution reconstruction; Diffusion MRI; Spherical ridgelets; Compressed sensing ID HUMAN CONNECTOME PROJECT; WHITE-MATTER; WEIGHTED IMAGES; MRI; RECONSTRUCTION; TENSOR; BRAIN; ACQUISITIONS; TRACTOGRAPHY; MINIMIZATION AB Diffusion MRI (dMRI) can provide invaluable information about the structure of different tissue types in the brain. Standard dMRI acquisitions facilitate a proper analysis (e.g. tracing) of medium-to-large white matter bundles. However, smaller fiber bundles connecting very small cortical or sub-cortical regions cannot be traced accurately in images with large voxel sizes. Yet, the ability to trace such fiber bundles is critical for several applications such as deep brain stimulation and neurosurgery. In this work, we propose a novel acquisition and reconstruction scheme for obtaining high spatial resolution dMRI images using multiple low resolution (LR) images, which is effective in reducing acquisition time while improving the signal-to-noise ratio (SNR). The proposed method called compressed-sensing super resolution reconstruction (CS-SRR), uses multiple overlapping thick-slice dMRI volumes that are under-sampled in q-space to reconstruct diffusion signal with complex orientations. The proposed method combines the twin concepts of compressed sensing and super-resolution to model the diffusion signal (at a given b-value) in a basis of spherical ridgelets with total-variation (TV) regularization to account for signal correlation in neighboring voxels. A computationally efficient algorithm based on the alternating direction method of multipliers (ADMM) is introduced for solving the CS-SRR problem. The performance of the proposed method is quantitatively evaluated on several in-vivo human data sets including a true SRR scenario. Our experimental results demonstrate that the proposed method can be used for reconstructing sub-millimeter super resolution dMRI data with very good data fidelity in clinically feasible acquisition time. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ning, Lipeng; Shenton, Martha E.; Westin, Carl-Fredrik; Rathi, Yogesh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Setsompop, Kawin; Makris, Nikos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Michailovich, Oleg] Univ Waterloo, Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada. RP Ning, LP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. EM lning@bwh.harvard.edu FU Swedish Research Council (VR) [2012-3682]; Swedish Foundation for Strategic Research (SSF) [AM13-0090]; VA Merit; [R01MH099797]; [R00EB012107]; [P41RR14075]; [R01MH074794]; [P41EB015902]; [W81XWH-08-2-0159] FX The authors would like to acknowledge the following grants which supported this work: R01MH099797 (PI: Rathi), R00EB012107 (PI: Setsompop), P41RR14075 (PI: Rosen), R01MH074794 (PI: Westin), P41EB015902 (PI: Kikinis), Swedish Research Council (VR) grant 2012-3682, Swedish Foundation for Strategic Research (SSF) grant AM13-0090, VA Merit (PI: Shenton) and W81XWH-08-2-0159 (Imaging Core PI: Shenton). NR 61 TC 5 Z9 5 U1 6 U2 38 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2016 VL 125 BP 386 EP 400 DI 10.1016/j.neuroimage.2015.10.061 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CY8GT UT WOS:000366647500036 PM 26505296 ER PT J AU Hu, CH Sepulcre, J Johnson, KA Fakhri, GE Lu, YM Li, QZ AF Hu, Chenhui Sepulcre, Jorge Johnson, Keith A. Fakhri, Georges E. Lu, Yue M. Li, Quanzheng TI Matched signal detection on graphs: Theory and application to brain imaging data classification SO NEUROIMAGE LA English DT Article DE Matched signal detection; Graph-structured data; Spectral graph theory; Brain networks; Classification; Alzheimer's disease; PIB-PET; R-fMRI ID NONLINEAR DIMENSIONALITY REDUCTION; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; ANATOMICAL NETWORKS; PET; MRI; CONNECTIVITY; PROGRESSION; FRAMEWORK; DEMENTIA AB Motivated by recent progress in signal processing on graphs, we have developed a matched signal detection (MSD) theory for signals with intrinsic structures described by weighted graphs. First, we regard graph Laplacian eigenvalues as frequencies of graph-signals and assume that the signal is in a subspace spanned by the first few graph Laplacian eigenvectors associated with lower eigenvalues. The conventional matched subspace detector can be applied to this case. Furthermore, we study signals that may not merely live in a subspace. Concretely, we consider signals with bounded variation on graphs and more general signals that are randomly drawn from a prior distribution. For bounded variation signals, the test is a weighted energy detector. For the random signals, the test statistic is the difference of signal variations on associated graphs, if a degenerate Gaussian distribution specified by the graph Laplacian is adopted. We evaluate the effectiveness of the MSD on graphs both with simulated and real data sets. Specifically, we apply MSD to the brain imaging data classification problem of Alzheimer's disease (AD) based on two independent data sets: 1) positron emission tomography data with Pittsburgh compound-B tracer of 30 AD and 40 normal control (NC) subjects, and 2) resting-state functional magnetic resonance imaging (R-fMRI) data of 30 early mild cognitive impairment and 20 NC subjects. Our results demonstrate that the MSD approach is able to outperform the traditional methods and help detect AD at an early stage, probably due to the success of exploiting the manifold structure of the data. (C) 2015 Published by Elsevier Inc. C1 [Hu, Chenhui; Fakhri, Georges E.; Li, Quanzheng] Massachusetts Gen Hosp, NMMI, Ctr Adv Med Imaging Sci, Radiol, Boston, MA 02114 USA. [Hu, Chenhui; Lu, Yue M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Sepulcre, Jorge; Johnson, Keith A.] Massachusetts Gen Hosp, NMMI, Radiol, Boston, MA 02114 USA. RP Li, QZ (reprint author), Massachusetts Gen Hosp, NMMI, Ctr Adv Med Imaging Sci, Radiol, Boston, MA 02114 USA. EM Li.Quanzheng@mgh.harvard.edu FU National Institutes of Health [R01 EB013293, 1 K23 EB19023-01]; National Institute on Aging [P01 AG036694, R01 AG034556, R01 AG037497]; Alzheimers Association Zenith Award FX This research was funded by the National Institutes of Health grants R01 EB013293, 1 K23 EB19023-01, the National Institute on Aging Grants P01 AG036694, R01 AG034556, R01 AG037497, and the Alzheimers Association Zenith Award. NR 62 TC 1 Z9 1 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2016 VL 125 BP 587 EP 600 DI 10.1016/j.neuroimage.2015.10.026 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CY8GT UT WOS:000366647500053 PM 26481679 ER PT J AU Egorova, N Shtyrov, Y Pulvermuller, F AF Egorova, Natalia Shtyrov, Yury Pulvermueller, Friedemann TI Brain basis of communicative actions in language SO NEUROIMAGE LA English DT Article DE Communicative action; Mirror neuron system; Pragmatics; Social interaction; Theory of mind ID SPEECH-ACT COMPREHENSION; SUPERIOR TEMPORAL SULCUS; RIGHT-HEMISPHERE; PARIETAL JUNCTION; SOCIAL COGNITION; SEMANTIC SYSTEM; NEURAL SYSTEMS; BROCAS AREA; MIRROR; MOTOR AB Although language is a key tool for communication in social interaction, most studies in the neuroscience of language have focused on language structures such as words and sentences. Here, the neural correlates of speech acts, that is, the actions performed by using language, were investigated with functional magnetic resonance imaging (fMRI). Participants were shown videos, in which the same critical utterances were used in different communicative contexts, to Name objects, or to Request them from communication partners. Understanding of critical utterances as Requests was accompanied by activation in bilateral premotor, left inferior frontal and temporo-parietal cortical areas known to support action-related and social interactive knowledge. Naming, however, activated the left angular gyrus implicated in linking information about word forms and related reference objects mentioned in critical utterances. These findings show that understanding of utterances as different communicative actions is reflected in distinct brain activation patterns, and thus suggest different neural substrates for different speech act types. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Egorova, Natalia] MRC, Cognit & Brain Sci Unit, Cambridge CB2 7EF, England. [Egorova, Natalia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat Neuroimaging, Charlestown, MA 02129 USA. [Shtyrov, Yury] Aarhus Univ, CFIN, DK-8000 Aarhus C, Denmark. [Shtyrov, Yury] Higher Sch Econ, Ctr Cognit & Decis Making, Moscow 109316, Russia. [Pulvermueller, Friedemann] Free Univ Berlin, Brain Language Lab, D-14195 Berlin, Germany. [Pulvermueller, Friedemann] Humboldt Univ, Berlin Sch Mind & Brain, D-10099 Berlin, Germany. RP Egorova, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 120 2nd Ave, Charlestown, MA 02129 USA. EM negorova2@mgh.harvard.edu; Friedemann.pulvermuller@fu-berlin.de OI Egorova, Natalia/0000-0002-9244-2900 FU UK Medical Research Council [MC_US_A060_0034, MC-A060-5PQ90, U1055.04.003.00001.01]; UK Engineering and Physical Sciences Research Council; Behavioural and Brain Sciences Research Council (BABEL) [EP/J004561/1]; Freie Universitat Berlin; Deutsche Forschungsgemeinschaft (Excellence Cluster Languages of Emotion); Aarhus University; Lundbeck Foundation (Denmark) [2013-12951, 15480]; NRU Higher School of Economics; Gates Cambridge Scholarship FX This work was supported by the UK Medical Research Council (MC_US_A060_0034, MC-A060-5PQ90, U1055.04.003.00001.01), the UK Engineering and Physical Sciences Research Council and Behavioural and Brain Sciences Research Council (BABEL grant, EP/J004561/1), Freie Universitat Berlin, the Deutsche Forschungsgemeinschaft (Excellence Cluster Languages of Emotion), Aarhus University, the Lundbeck Foundation (Denmark; grant 2013-12951 Neolex, project code 15480) and NRU Higher School of Economics (subsidy granted to the HSE by the Government of the Russian Federation for the implementation of the Global Competitiveness Program). N. Egorova was supported by Gates Cambridge Scholarship. We also would like to thank Alejandro Vicente-Grabovetsky, Simon Strangeways, Kevin Symonds, Lucy MacGregor, Lauren Navrady, Charlotte Rae and Philip Gomersall for their help at different stages of the project. NR 88 TC 2 Z9 2 U1 4 U2 25 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2016 VL 125 BP 857 EP 867 DI 10.1016/j.neuroimage.2015.10.055 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CY8GT UT WOS:000366647500077 PM 26505303 ER PT J AU Hazlett, EA AF Hazlett, Erin A. TI Neural Substrates of Emotion-Processing Abnormalities in Borderline Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; HIPPOCAMPAL VOLUME; METAANALYSIS; AMYGDALA C1 [Hazlett, Erin A.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Hazlett, Erin A.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network 3, Bronx, NY 10468 USA. RP Hazlett, EA (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM erin.hazlett@mssm.edu NR 10 TC 0 Z9 0 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2016 VL 79 IS 2 BP 74 EP 75 DI 10.1016/j.biopsych.2015.10.008 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CY7GF UT WOS:000366575900001 PM 26674587 ER PT J AU Hirai, KK Groisser, BN Copen, WA Singhal, AB Schaechter, JD AF Hirai, Kelsi K. Groisser, Benjamin N. Copen, William A. Singhal, Aneesh B. Schaechter, Judith D. TI Comparing prognostic strength of acute corticospinal tract injury measured by a new diffusion tensor imaging based template approach versus common approaches SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article ID ISCHEMIC-STROKE; WHITE-MATTER; WALLERIAN DEGENERATION; MOTOR RECOVERY; RETINAL ISCHEMIA; PYRAMIDAL TRACT; POST-STROKE; TIME-COURSE; INTEGRITY; DAMAGE AB Background: Long-term motor outcome of acute stroke patients with severe motor impairment is difficult to predict. While measure of corticospinal tract (CST) injury based on diffusion tensor imaging (DTI) in subacute stroke patients strongly predicts motor outcome, its predictive value in acute stroke patients is unclear. Using a new DTI-based, density-weighted CST template approach, we demonstrated recently that CST injury measured in acute stroke patients with moderately-severe to severe motor impairment of the upper limb strongly predicts motor outcome of the limb at 6 months. New method: The current study compared the prognostic strength of CST injury measured in 10 acute stroke patients with moderately-severe to severe motor impairment of the upper limb by the new density-weighted CST template approach versus several variants of commonly used DTI-based approaches. Results and comparison with existing methods: Use of the density-weighted CST template approach yielded measurements of acute CST injury that correlated most strongly, in absolute magnitude, with 6-month upper limb strength (r(s) = 0.93), grip (r(s) = 0.94) and dexterity (r(s) = 0.89) compared to all other 11 approaches. Formal statistical comparison of correlation coefficients revealed that acute CST injury measured by the density-weighted CST template approach correlated significantly more strongly with 6-month upper limb strength, grip and dexterity than 9, 10 and 6 of the 11 alternative measurements, respectively. Conclusions: Measurements of CST injury in acute stroke patients with substantial motor impairment by the density-weighted CST template approach may have clinical utility for anticipating healthcare needs and improving clinical trial design. (C) 2015 Elsevier B.V. All rights reserved. C1 [Hirai, Kelsi K.; Groisser, Benjamin N.; Schaechter, Judith D.] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Hirai, Kelsi K.; Groisser, Benjamin N.; Copen, William A.; Schaechter, Judith D.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Singhal, Aneesh B.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schaechter, JD (reprint author), MGH HST Athinoula A Martinos Ctr Biomed Imaging, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. EM judith@nmr.mgh.harvard.edu FU American Heart Association [09GRNT2240036]; MGH Executive Committee on Research; NIH-NINDS [R01NS051412, P50NS051343, R21NS077442, R21-NS085574, U10-NS086729]; NIH [S10RR021110, S10RR023043]; Harvard Catalyst The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award) [UL1 TR001102]; Harvard University FX This study was supported by grants from the Founders Affiliate of the American Heart Association 09GRNT2240036 (to JDS); MGH Executive Committee on Research (to JDS); and NIH-NINDS R01NS051412, P50NS051343, R21NS077442, R21-NS085574 and U10-NS086729 (to ABS). This research was carried out using resources provided by NIH-NIBIB (P41EB015896) and NIH Shared Instrumentation Grants (S10RR021110 and S10RR023043). Statistical consultation was provided with support from Harvard Catalyst The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. NR 52 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 15 PY 2016 VL 257 BP 204 EP 213 DI 10.1016/j.jneumeth.2015.09.005 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CY2FL UT WOS:000366224100021 PM 26386285 ER PT J AU Ren, WM Xu, MM Liang, SH Xiang, HJ Tang, L Zhang, MK Ding, DJ Li, X Zhang, HY Hu, YH AF Ren, Wenming Xu, Mingming Liang, Steven H. Xiang, Huaijiang Tang, Li Zhang, Minkui Ding, Dejun Li, Xin Zhang, Haiyan Hu, Youhong TI Discovery of a novel fluorescent probe for the sensitive detection of beta-amyloid deposits SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE Fluorescent probe; Imaging; A beta plaques; Alzheimer's disease; Photoinduced electron transfer ID IN-VIVO DETECTION; PHOTOINDUCED ELECTRON-TRANSFER; ALZHEIMERS-DISEASE; RECENT PROGRESS; MOUSE-BRAIN; PLAQUES; DESIGN; PROTEIN; DERIVATIVES; HYPOTHESIS AB Here we reported the development of the first photoinduced electron transfer (PeT) probe (1) to directly locate beta-amyloid aggregates (A beta plaques) in the brain without the need of post-washing procedures. The probe showed a high affinity for A beta aggregates with a K-d value of 3.5 nM. It is weakly emissive by itself with its fluorescence quenched by electron transfer from PeT donor to the excited fluorophore. But selective binding to A beta plaques would attenuate the PeT process and restore the fluorescence, therefore facilitating the tracking of A beta plaques. The probe is advantageous in that its fluorescence is environmentless-sensitive and no washing procedure is required to provide high contrast fluorescent signal when applied to stain brain tissues. As a proof of concept, its application has been exemplified by staining A beta plaques in slices of brain tissue from double transgenic (APP/PS1) mice of Alzheimer's disease. (C) 2015 Elsevier B.V. All rights reserved. C1 [Xiang, Huaijiang; Tang, Li; Zhang, Minkui; Li, Xin; Hu, Youhong] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310027, Zhejiang, Peoples R China. [Ren, Wenming; Ding, Dejun; Hu, Youhong] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China. [Xu, Mingming; Zhang, Haiyan] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 200031, Peoples R China. [Liang, Steven H.] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Li, X (reprint author), Zhejiang Univ, Coll Pharmaceut Sci, 866 Yuhangtang Rd, Hangzhou 310027, Zhejiang, Peoples R China. EM lixin81@zju.edu.cn; hzhang@simm.ac.cn; yhhu@zju.edu.cn FU National Natural Science Foundation of China [81225022, 21172232] FX We thank Dr. Chongzhao Ran for helpful discussion. The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (81225022 and 21172232). NR 43 TC 2 Z9 2 U1 10 U2 128 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 EI 1873-4235 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD JAN 15 PY 2016 VL 75 BP 136 EP 141 DI 10.1016/j.bios.2015.08.030 PG 6 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA CT5PI UT WOS:000362862000020 ER PT J AU Volpi, S Santori, E Abernethy, K Mizui, M Dahlberg, CIM Recher, M Capuder, K Csizmadia, E Ryan, D Mathew, D Tsokos, GC Snapper, S Westerberg, LS Thrasher, AJ Candotti, F Notarangelo, LD AF Volpi, Stefano Santori, Elettra Abernethy, Katrina Mizui, Masayuki Dahlberg, Carin I. M. Recher, Mike Capuder, Kelly Csizmadia, Eva Ryan, Douglas Mathew, Divij Tsokos, George C. Snapper, Scott Westerberg, Lisa S. Thrasher, Adrian J. Candotti, Fabio Notarangelo, Luigi D. TI N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome SO BLOOD LA English DT Article ID SYNDROME PROTEIN WASP; ACTIN-DEPOLYMERIZING PROTEIN; REGULATORY T-CELLS; SIGNALS; COMPARTMENT; HOMEOSTASIS; DEFICIENCY; TOLERANCE; COMPLEX AB Mutations of the Wiskott-Aldrich syndrome gene (WAS) are responsible for Wiskott-Aldrich syndrome (WAS), a disease characterized by thrombocytopenia, eczema, immunodeficiency, and autoimmunity. Mice with conditional deficiency of Was in B lymphocytes (B/WcKO) have revealed a critical role for WAS protein (WASP) expression in B lymphocytes in the maintenance of immune homeostasis. Neural WASP (N-WASP) is a broadly expressed homolog of WASP, and regulates B-cell signaling by modulating B-cell receptor (BCR) clustering and internalization. We have generated a double conditional mouse lacking both WASP and N-WASP selectively in B lymphocytes (B/DcKO). Compared with B/WcKO mice, B/DcKO mice showed defective B-lymphocyte proliferation and impaired antibody responses to T-cell dependent antigens, associated with decreased autoantibody production and lack of autoimmune kidney disease. These results demonstrate that N-WASP expression in B lymphocytes is required for the development of autoimmunity of WAS and may represent a novel therapeutic target in WAS. C1 [Volpi, Stefano; Abernethy, Katrina; Recher, Mike; Capuder, Kelly; Ryan, Douglas; Mathew, Divij; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Div Immunol, Boston Childrens Hosp, Boston, MA USA. [Santori, Elettra; Candotti, Fabio] Univ Lausanne Hosp, Div Immunol & Allergy, Lab Ctr Epalinges, Lausanne, Switzerland. [Volpi, Stefano] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy. [Volpi, Stefano] Ist Giannina Gaslini, Unita Operat Pediat 2, I-16148 Genoa, Italy. [Mizui, Masayuki; Tsokos, George C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Rheumatol, Dept Med,Sch Med, Boston, MA 02215 USA. [Dahlberg, Carin I. M.; Westerberg, Lisa S.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Csizmadia, Eva] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplantat Inst,Dept Med, Boston, MA 02215 USA. [Snapper, Scott] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Snapper, Scott] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Snapper, Scott] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Gastroenterol, Boston, MA USA. [Thrasher, Adrian J.] Inst Child Hlth, Ctr Immunodeficiency, Sect Mol & Cellular Immunol, London, England. [Thrasher, Adrian J.] Natl Hlth Serv Fdn Trust, Great Ormond St Hosp Children, London, England. [Notarangelo, Luigi D.] Harvard Stem Cell Inst, Boston, MA USA. RP Notarangelo, LD (reprint author), Boston Childrens Hosp, Div Immunol, Karp Res Bldg,Room 10217,1 Blackfan Circle, Boston, MA 02115 USA. EM luigi.notarangelo@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Westerberg, Lisa/0000-0003-2943-2192 FU NHLBI NIH HHS [5P01HL059561, P01 HL059561]; NIDDK NIH HHS [P30 DK034854]; Wellcome Trust NR 25 TC 4 Z9 4 U1 5 U2 9 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 JAN 14 PY 2016 VL 127 IS 2 BP 216 EP 220 DI 10.1182/blood-2015-05-643817 PG 5 WC Hematology SC Hematology GA DC5UG UT WOS:000369285400011 PM 26468226 ER PT J AU Kollman, C Spellman, SR Zhang, MJ Hassebroek, A Anasetti, C Antin, JH Champlin, RE Confer, DL DiPersio, JF Fernandez-Vina, M Hartzman, RJ Horowitz, MM Hurley, CK Karanes, C Maiers, M Mueller, CR Perales, MA Setterholm, M Woolfrey, AE Yu, N Eapen, M AF Kollman, Craig Spellman, Stephen R. Zhang, Mei-Jie Hassebroek, Anna Anasetti, Claudio Antin, Joseph H. Champlin, Richard E. Confer, Dennis L. DiPersio, John F. Fernandez-Vina, Marcelo Hartzman, Robert J. Horowitz, Mary M. Hurley, Carolyn K. Karanes, Chatchada Maiers, Martin Mueller, Carlheinz R. Perales, Miguel-Angel Setterholm, Michelle Woolfrey, Ann E. Yu, Neng Eapen, Mary TI The effect of donor characteristics on survival after unrelated donor transplantation for hematologic malignancy SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW; RETROSPECTIVE ANALYSIS; RISK-FACTORS; BLOOD; GRAFTS; RECIPIENTS; SELECTION; LEUKEMIA; REGISTRY AB There are >24 million registered adult donors, and the numbers of unrelated donor transplantations are increasing. The optimal strategy for prioritizing among comparably HLA-matched potential donors has not been established. Therefore, the objective of the current analyses was to study the association between donor characteristics (age, sex, parity, cytomegalovirus serostatus, HLA match, and blood group ABO match) and survival after transplantation for hematologic malignancy. The association of donor characteristics with transplantation outcomes was examined using either logistic or Cox regression models, adjusting for patient disease and transplantation characteristics associated with outcomes in 2 independent datasets: 1988 to 2006 (N = 6349; training cohort) and 2007 to 2011 (N = 4690; validation cohort). All donor-recipient pairs had allele-level HLA typing at HLA-A, -B, -C, and -DRB1, which is the current standard for selecting donors. Adjusting for patient disease and transplantation characteristics, survival was better after transplantation of grafts from young donors (aged 18-32 years) who were HLA matched to recipients (P < .001). These findings were validated for transplantations that occurred between 2007 and 2011. For every 10-year increment in donor age, there is a 5.5% increase in the hazard ratio for overall mortality. Increasing HLA disparity was also associated with worsening survival. Donor age and donor-recipient HLA match are important when selecting adult unrelated donors. Other donor characteristics such as sex, parity, and cytomegalovirus serostatus were not associated with survival. The effect of ABO matching on survival is modest and must be studied further before definitive recommendations can be offered. C1 [Kollman, Craig] Jaeb Ctr Hlth Res, Tampa, FL USA. [Spellman, Stephen R.; Hassebroek, Anna; Confer, Dennis L.] Natl Marrow Donor Program Be Match, Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Zhang, Mei-Jie; Horowitz, Mary M.; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Zhang, Mei-Jie] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Anasetti, Claudio] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. [Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Div Canc Med, Houston, TX 77030 USA. [DiPersio, John F.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Fernandez-Vina, Marcelo] Stanford Hosp & Clin, Stanford, CA USA. [Hartzman, Robert J.] Dept Navy, CW Bill Young Marrow Donor Recruitment & Res Prog, Dept Def Marrow Donor Program, Bone Marrow Res Directorate,Naval Med Res Ctr, Washington, DC USA. [Hurley, Carolyn K.] Georgetown Univ, Washington, DC USA. [Karanes, Chatchada] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Maiers, Martin; Setterholm, Michelle] Natl Marrow Donor Program Be Match, Minneapolis, MN USA. [Mueller, Carlheinz R.] ZKRD, Ulm, Germany. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Woolfrey, Ann E.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Yu, Neng] Amer Red Cross Blood Serv East Div, Dedham, MA USA. [Eapen, Mary] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. RP Eapen, M (reprint author), Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. EM meapen@mcw.edu FU NCI NIH HHS [U24 CA076518, U24-CA076518, P30 CA008748]; PHS HHS [HHSH250201200016C] NR 26 TC 15 Z9 15 U1 1 U2 10 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 JAN 14 PY 2016 VL 127 IS 2 BP 260 EP 267 DI 10.1182/blood-2015-08-663823 PG 8 WC Hematology SC Hematology GA DC5UG UT WOS:000369285400016 PM 26527675 ER PT J AU Tonyushkin, A Deelchand, DK Van de Moortele, PF Adriany, G Kiruluta, A AF Tonyushkin, A. Deelchand, D. K. Van de Moortele, P. -F. Adriany, G. Kiruluta, A. TI Direct imaging of radio-frequency modes via traveling wave magnetic resonance imaging SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID DIELECTRIC RESONATORS; GUIDE; FIELD; SPECTROSCOPY; COILS; NMR AB We demonstrate an experimental method for direct 2D and 3D imaging of magnetic radio-frequency (rf) field distribution in metal-dielectric structures based on traveling wave (TW) magnetic resonance imaging (MRI) at ultra-high field (> 7 T). The typical apparatus would include an ultra-high field whole body or small bore MRI scanner, waveguide elements filled with MRI active dielectrics with predefined electric and magnetic properties, and TW rf transmit-receive probes. We validated the technique by obtaining TW MR images of the magnetic field distribution of the rf modes of circular waveguide filled with deionized water in a 16.4 T small-bore MRI scanner and compared the MR images with numerical simulations. Our MRI technique opens up a practical non-perturbed way of imaging of previously inaccessible rf field distribution of modes inside various shapes metal waveguides with inserted dielectric objects, including waveguide mode converters and transformers. (C) 2016 AIP Publishing LLC. C1 [Tonyushkin, A.; Kiruluta, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Deelchand, D. K.; Van de Moortele, P. -F.; Adriany, G.] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN 55406 USA. [Kiruluta, A.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. RP Tonyushkin, A (reprint author), Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. EM alexey.tonyushkin@umb.edu RI Van de Moortele, Pierre-Francois/H-5087-2011; Adriany, Gregor/R-6656-2016; OI Van de Moortele, Pierre-Francois/0000-0002-6941-5947; Tonyushkin, Alexey/0000-0002-0531-715X; Adriany, Gregor/0000-0002-6428-9005 FU [NIH P41 EB015894]; [NIH S10 RR025031] FX We would like to acknowledge help from Dr. M. Garwood from the Center for Magnetic Resonance Research (CMRR). This work was partially supported by Grant Nos. NIH P41 EB015894 and NIH S10 RR025031. NR 25 TC 0 Z9 0 U1 2 U2 5 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-8979 EI 1089-7550 J9 J APPL PHYS JI J. Appl. Phys. PD JAN 14 PY 2016 VL 119 IS 2 AR 024904 DI 10.1063/1.4940019 PG 5 WC Physics, Applied SC Physics GA DC5UA UT WOS:000369284800048 ER PT J AU Marcotte, R Sayad, A Brown, KR Sanchez-Garcia, F Reimand, J Haider, M Virtanen, C Bradner, JE Bader, GD Mills, GB Pe'er, D Moffat, J Neel, BG AF Marcotte, Richard Sayad, Azin Brown, Kevin R. Sanchez-Garcia, Felix Reimand, Jueri Haider, Maliha Virtanen, Carl Bradner, James E. Bader, Gary D. Mills, Gordon B. Pe'er, Dana Moffat, Jason Neel, Benjamin G. TI Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance SO CELL LA English DT Article ID CELL-LINES; MOLECULAR PORTRAITS; DUAL INHIBITION; OVARIAN-CANCER; RNAI SCREENS; STEM-CELLS; SUBTYPES; REVEALS; TUMORS; GROWTH AB Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole-genome small hairpin RNA (shRNA) "dropout screens" on 77 breast cancer cell lines. Using a hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify vulnerabilities in breast cancer, including candidate "drivers," and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, effects of existing anti-cancer drugs, and opportunities for combination therapy. Finally, we demonstrate the utility of this large dataset by identifying BRD4 as a potential target in luminal breast cancer and PIK3CA mutations as a resistance determinant for BET-inhibitors. C1 [Marcotte, Richard; Sayad, Azin; Haider, Maliha; Virtanen, Carl; Neel, Benjamin G.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada. [Brown, Kevin R.; Reimand, Jueri; Bader, Gary D.; Moffat, Jason] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. [Moffat, Jason] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Sanchez-Garcia, Felix; Pe'er, Dana] Columbia Univ, New York, NY 10027 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Sheikh Khalifa Al Nahyan Ben Zayed Inst Personali, Dept Syst Biol, Houston, TX 77030 USA. [Neel, Benjamin G.] NYU Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA. RP Neel, BG (reprint author), NYU Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA. EM benjamin.neel@nyumc.org FU Canadian Foundation for Innovation; Ontario Research Fund; Princess Margaret Cancer Foundation; Canadian Breast Cancer Foundation; NIH [R37 CA49132, P41 GM103504, R01 GM070743, U41 HG006623, PO1 CA099031]; Komen SAC and Promise grant; M.D. Anderson CCSG functional proteomics core [CA16672] FX This work was supported by the Canadian Foundation for Innovation (J.M.) and the Ontario Research Fund (B.G.N. and J.M.). B.G.N. was a Canada Research Chair, Tier 1, and work in his laboratory was supported in part by the Princess Margaret Cancer Foundation. R.M. was partly funded by a postdoctoral fellowship from the Canadian Breast Cancer Foundation. This work was also supported by NIH grants R37 CA49132 (B.G.N.), P41 GM103504, R01 GM070743, U41 HG006623 (G.D.B.), and PO1 CA099031 (G.B.M.), a Komen SAC and Promise grant (G.B.M.), and the M.D. Anderson CCSG functional proteomics core (CA16672). NR 67 TC 26 Z9 27 U1 10 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 14 PY 2016 VL 164 IS 1-2 BP 293 EP 309 DI 10.1016/j.cell.2015.11.062 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DB2LE UT WOS:000368339300028 PM 26771497 ER PT J AU Vo, TV Das, J Meyer, MJ Cordero, NA Akturk, N Wei, XM Fair, BJ Degatano, AG Fragoza, R Liu, LG Matsuyama, A Trickey, M Horibata, S Grimson, A Yamano, H Yoshida, M Roth, FP Pleiss, JA Xia, Y Yu, HY AF Vo, Tommy V. Das, Jishnu Meyer, Michael J. Cordero, Nicolas A. Akturk, Nurten Wei, Xiaomu Fair, Benjamin J. Degatano, Andrew G. Fragoza, Robert Liu, Lisa G. Matsuyama, Akihisa Trickey, Michelle Horibata, Sachi Grimson, Andrew Yamano, Hiroyuki Yoshida, Minoru Roth, Frederick P. Pleiss, Jeffrey A. Xia, Yu Yu, Haiyuan TI A Proteome-wide Fission Yeast Interactome Reveals Network Evolution Principles from Yeasts to Human SO CELL LA English DT Article ID GENOME DUPLICATION; STRESS-RESPONSE; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; GENE DUPLICATION; INTERACTION MAP; COMPLEXES; DROSOPHILA; PATHWAYS; FAMILIES AB Here, we present FissionNet, a proteome-wide binary protein interactome for S. pombe, comprising 2,278 high-quality interactions, of which similar to 50% were previously not reported in any species. Fission-Net unravels previously unreported interactions implicated in processes such as gene silencing and pre-mRNA splicing. We developed a rigorous network comparison framework that accounts for assay sensitivity and specificity, revealing extensive species-specific network rewiring between fission yeast, budding yeast, and human. Surprisingly, although genes are better conserved between the yeasts, S. pombe interactions are significantly better conserved in human than in S. cerevisiae. Our framework also reveals that different modes of gene duplication influence the extent to which paralogous proteins are functionally repurposed. Finally, cross-species interactome mapping demonstrates that coevolution of interacting proteins is remarkably prevalent, a result with important implications for studying human disease in model organisms. Overall, FissionNet is a valuable resource for understanding protein functions and their evolution. C1 [Vo, Tommy V.; Das, Jishnu; Meyer, Michael J.; Fragoza, Robert; Yu, Haiyuan] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. [Vo, Tommy V.; Das, Jishnu; Meyer, Michael J.; Cordero, Nicolas A.; Akturk, Nurten; Wei, Xiaomu; Degatano, Andrew G.; Fragoza, Robert; Liu, Lisa G.; Yu, Haiyuan] Cornell Univ, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA. [Vo, Tommy V.; Fair, Benjamin J.; Fragoza, Robert; Grimson, Andrew; Pleiss, Jeffrey A.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. [Meyer, Michael J.] Triinst Training Program Computat Biol & Med, New York, NY 10065 USA. [Wei, Xiaomu] Weill Cornell Coll Med, Dept Med, New York, NY 10021 USA. [Matsuyama, Akihisa; Yoshida, Minoru] RIKEN, Ctr Sustainable Resource Ctr, Chem Genom Res Grp, Wako, Saitama 3510198, Japan. [Trickey, Michelle; Yamano, Hiroyuki] UCL, Inst Canc, London WC1E 6BT, England. [Horibata, Sachi] Cornell Univ, Baker Inst Anim Hlth, Dept Biomed Sci, Ithaca, NY 14853 USA. [Roth, Frederick P.; Xia, Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Roth, Frederick P.; Xia, Yu] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada. [Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Xia, Yu] McGill Univ, Fac Engn, Dept Bioengn, Montreal, PQ H3A 0C3, Canada. RP Yu, HY (reprint author), Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. EM haiyuan.yu@cornell.edu RI Das, Jishnu/C-6924-2015; Yoshida, Minoru/C-8049-2014; Matsuyama, Akihisa/P-7805-2016; OI Das, Jishnu/0000-0002-5747-064X; Matsuyama, Akihisa/0000-0002-6135-6276; Xia, Yu/0000-0002-5596-5518 FU Marie Curie Cancer Care; Association for International Cancer Research; Cancer Research UK; NHGRI [HG001715, HG004233]; Krembil Foundation; Canada Excellence Research Chairs Program; Canada Research Chairs Program; NSERC [RGPIN-2014-03892]; NSF [CCF-1219007]; CFI [JELF-33732]; NIGMS [GM098634, GM097358, GM104424] FX We thank D. Moazed for S. pombe strains provided for the analyses of centromeric silencing; S. Forsburg, H. Madhani, and J. Nakayama for providing plasmids for protein expression in S. pombe. We are grateful to M. Smolka for experimental advice; D. Barbash, A. Clark, S. Emr, S. Grewal, D. Lin, D. Shalloway, and members of the Yu lab for discussions. The accession number for the DNA microarray data reported in this paper is NCBI GEO: GSE74354. This work was supported by Marie Curie Cancer Care, Association for International Cancer Research, and Cancer Research UK to M.T. and H. Yamano; NHGRI grants HG001715 and HG004233, Krembil Foundation, and Canada Excellence Research Chairs Program to F.P.R.; Canada Research Chairs Program and grants NSERC RGPIN-2014-03892, NSF CCF-1219007, and CFI JELF-33732 to Y.X.; and NIGMS grants GM098634 to J.A.P. and GM097358 and GM104424 to H.Yu. NR 49 TC 6 Z9 6 U1 6 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 14 PY 2016 VL 164 IS 1-2 BP 310 EP 323 DI 10.1016/j.cell.2015.11.037 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DB2LE UT WOS:000368339300029 PM 26771498 ER PT J AU Janakiraman, U Manivasagam, T Thenmozhi, AJ Essa, MM Barathidasan, R SaravanaBabu, C Guillemin, GJ Khan, MAS AF Janakiraman, Udaiyappan Manivasagam, Thamilarasan Thenmozhi, Arokiasamy Justin Essa, Musthafa Mohamed Barathidasan, Rajamani SaravanaBabu, Chidambaram Guillemin, Gilles J. Khan, Mohammed A. S. TI Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice SO PLOS ONE LA English DT Article ID INDUCED PARKINSONS-DISEASE; VENTRAL TEGMENTAL AREA; DORSAL RAPHE NUCLEUS; DOPAMINE RELEASE; MOUSE MODEL; RAT STRIATUM; IN-VIVO; DEPRESSION; DISORDERS; MPTP AB Parkinson's disease (PD) is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic) neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS) such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant/complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS), a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt.) with probenecid (250 mg/kg, s.c.) (MPTP/p) induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks) of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor) impairments, levels and expressions of dopamine (DA), serotonin (5-HT), DAergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporters-2 (VMAT 2) and alpha-synuclein in nigrostriatal (striatum (ST) and substantia nigra (SN)) and extra-nigrostriatal (hippocampus, cortex and cerebellum) tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and a-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD. C1 [Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin] Annamalai Univ, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India. [Essa, Musthafa Mohamed] Sultan Qaboos Univ, CAMS, Dept Food Sci & Nutr, Muscat, Oman. [Essa, Musthafa Mohamed] Sultan Qaboos Univ, Ageing & Dementia Res Grp, Muscat, Oman. [Barathidasan, Rajamani; SaravanaBabu, Chidambaram] Sri Ramachandra Univ, Ctr Toxicol & Dev Res, Madras 600116, Tamil Nadu, India. [Guillemin, Gilles J.] Macquarie Univ, Fac Med & Hlth Sci, Deb Bailey MND Res Lab, Neuropharmacol Grp, N Ryde, NSW 2109, Australia. [Khan, Mohammed A. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children, Boston, MA 02114 USA. RP Manivasagam, T (reprint author), Annamalai Univ, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India. EM mani_pdresearchlab@rediff.com FU Department of Biotechnology, New Delhi [BT/PR4958/MED/30/748/2012] FX Financial assistance in the form of Neuroscience task force project (BT/PR4958/MED/30/748/2012), Department of Biotechnology, New Delhi, is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 5 Z9 6 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 14 PY 2016 VL 11 IS 1 AR e0146671 DI 10.1371/journal.pone.0146671 PG 25 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB4CC UT WOS:000368459300033 PM 26765842 ER PT J AU Vartoukian, SR Adamowska, A Lawlor, M Moazzez, R Dewhirst, FE Wade, WG AF Vartoukian, Sonia R. Adamowska, Aleksandra Lawlor, Megan Moazzez, Rebecca Dewhirst, Floyd E. Wade, William G. TI In Vitro Cultivation of 'Unculturable' Oral Bacteria, Facilitated by Community Culture and Media Supplementation with Siderophores SO PLOS ONE LA English DT Article ID BIOFILM FORMATION; SUBGINGIVAL MICROBIOME; CYSTIC-FIBROSIS; DIVERSITY; DISEASE; GROWTH; PERIODONTITIS; HEALTH; MICROORGANISMS; PATHOGENESIS AB Over a third of oral bacteria are as-yet-uncultivated in-vitro. Siderophores have been previously shown to enable in-vitro growth of previously uncultivated bacteria. The objective of this study was to cultivate novel oral bacteria in siderophore-supplemented culture media. Various compounds with siderophore activity, including pyoverdines-Fe-complex, desferricoprogen and salicylic acid, were found to stimulate the growth of difficult-to-culture strains Prevotella sp. HOT-376 and Fretibacterium fastidiosum. Furthermore, pyrosequencing analysis demonstrated increased proportions of the as-yet-uncultivated phylotypes Dialister sp. HOT-119 and Megasphaera sp. HOT-123 on mixed culture plates supplemented with siderophores. Therefore a culture model was developed, which incorporated 15 mu g siderophore (pyoverdines-Fe-complex or desferricoprogen) or 150 mu l neat subgingival-plaque suspension into a central well on agar plates that were inoculated with heavily-diluted subgingival-plaque samples from subjects with periodontitis. Colonies showing satellitism were passaged onto fresh plates in co-culture with selected helper strains. Five novel strains, representatives of three previously-uncultivated taxa (Anaerolineae bacterium HOT-439, the first oral taxon from the Chloroflexi phylum to have been cultivated; Bacteroidetes bacterium HOT-365; and Peptostreptococcaceae bacterium HOT-091) were successfully isolated. All novel isolates required helper strains for growth, implying dependence on a biofilm lifestyle. Their characterisation will further our understanding of the human oral microbiome. C1 [Vartoukian, Sonia R.; Adamowska, Aleksandra; Lawlor, Megan; Wade, William G.] Queen Mary Univ London, Barts & London Sch Med & Dent, London, England. [Moazzez, Rebecca] Kings Coll London, Inst Dent, London WC2R 2LS, England. [Dewhirst, Floyd E.] Forsyth Inst, Cambridge, MA USA. [Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Wade, WG (reprint author), Queen Mary Univ London, Barts & London Sch Med & Dent, London, England. EM w.wade@qmul.ac.uk FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [R37DE016937, R01DE024468] FX Research reported in this publication was supported by The National Institute of Dental and Craniofacial Research of the National Institutes of Health under awards R37DE016937 and R01DE024468. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Research reported in this publication was supported by The National Institute of Dental and Craniofacial Research of the National Institutes of Health under awards R37DE016937 and R01DE024468. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 40 TC 8 Z9 8 U1 6 U2 15 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 JAN 14 PY 2016 VL 11 IS 1 AR e0146926 DI 10.1371/journal.pone.0146926 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB4CC UT WOS:000368459300051 PM 26764907 ER PT J AU Minshawi, NF Wink, LK Shaffer, R Plawecki, MH Posey, DJ Liu, H Hurwitz, S McDougle, CJ Swiezy, NB Erickson, CA AF Minshawi, Noha F. Wink, Logan K. Shaffer, Rebecca Plawecki, Martin H. Posey, David J. Liu, Hai Hurwitz, Sarah McDougle, Christopher J. Swiezy, Naomi B. Erickson, Craig A. TI A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders SO MOLECULAR AUTISM LA English DT Article DE D-cycloserine; Autism spectrum disorders; Social skills training; Social deficits ID DIAGNOSTIC OBSERVATION SCHEDULE; ADAPTIVE-BEHAVIOR; NEGATIVE SYMPTOMS; EXPOSURE THERAPY; CHILDREN; SCHIZOPHRENIA; ANXIETY; ANTIPSYCHOTICS; INDIVIDUALS; RISPERIDONE AB Background: Researchers have demonstrated that D-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. Methods: A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1: 1 ratio. Results: No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. Conclusions: The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. C1 [Minshawi, Noha F.; Plawecki, Martin H.; Swiezy, Naomi B.] Indiana Univ Sch Med, Riley Hosp Children, Indiana Univ Hlth, Christian Sarkine Autism Treatment Ctr,Dept Psych, Indianapolis, IN 46202 USA. [Wink, Logan K.; Shaffer, Rebecca; Erickson, Craig A.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Posey, David J.] David J Posey MD LLC, Indianapolis, IN USA. [Liu, Hai] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. [Hurwitz, Sarah] Indiana Univ, Sch Educ, Bloomington, IN 47405 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Dept Psychiat, Lurie Ctr Autism,Massachusetts Gen Hosp, Boston, MA 02115 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Dept Pediat, Lurie Ctr Autism,Massachusetts Gen Hosp, Boston, MA 02115 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. RP Erickson, CA (reprint author), Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave MLC 4002, Cincinnati, OH 45229 USA. EM craig.erickson@cchmc.org FU United States Department of Defense [W81XWH-09-1-0091] FX Funding for this study was provided by the United States Department of Defense Award Number W81XWH-09-1-0091. Statistical support was provided by Hai Liu, Ph.D., Indiana University School of Medicine Department of Biostatistics. We would like to acknowledge the contributions of Stacie Pozdol, M.A., Carrie McGinnis, B.S., CCRP, and Lyndsi Moser, B. S., CCRP at Indiana University, and Katherine Friedmann, RN, Lauren Mathieu-Frasier, MA, and Tori Schaefer, PhD at Cincinnati Children's Hospital Medical Center. NR 49 TC 2 Z9 2 U1 8 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2040-2392 J9 MOL AUTISM JI Mol. Autism PD JAN 14 PY 2016 VL 7 AR 2 DI 10.1186/s13229-015-0062-8 PG 10 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA DB1AV UT WOS:000368241300001 PM 26770664 ER PT J AU Perdigao-Henriques, R Petrocca, F Altschuler, G Thomas, MP Le, MTN Tan, SM Hide, W Lieberman, J AF Perdigao-Henriques, R. Petrocca, F. Altschuler, G. Thomas, M. P. Le, M. T. N. Tan, S. M. Hide, W. Lieberman, J. TI miR-200 promotes the mesenchymal to epithelial transition by suppressing multiple members of the Zeb2 and Snail1 transcriptional repressor complexes SO ONCOGENE LA English DT Article ID NEGATIVE BREAST-CANCER; E-CADHERIN; GENE-EXPRESSION; COLORECTAL-CANCER; WIDE IDENTIFICATION; PROGNOSTIC-FACTOR; MICRORNA TARGETS; CELL-MIGRATION; STEM-CELLS; FAMILY AB The miR-200 family promotes the epithelial state by suppressing the Zeb1/Zeb2 epithelial gene transcriptional repressors. To identify other miR-200-regulated genes, we isolated mRNAs bound to transfected biotinylated miR-200c in mouse breast cancer cells. In all, 520 mRNAs were significantly enriched in miR-200c binding at least twofold. Putative miR-200-regulated genes included Zeb2, enriched 3.5-fold in the pull down. However, Zeb2 knockdown does not fully recapitulate miR-200c overexpression, suggesting that regulating other miR-200 targets contributes to miR-200's enhancement of epithelial gene expression. Candidate genes were highly enriched for miR-200c seed pairing in their 3'UTR and coding sequence and for genes that were downregulated by miR-200c overexpression. Epidermal growth factor receptor and downstream MAPK signaling pathways were the most enriched pathways. Genes whose products mediate transforming growth factor (TGF)-beta signaling were also significantly overrepresented, and miR-200 counteracted the suppressive effects of TGF-beta and bone morphogenic protein 2 (BMP-2) on epithelial gene expression. miR-200c regulated the 3'UTRs of 12 of 14 putative miR-200c-binding mRNAs tested. The extent of mRNA binding to miR-200c strongly correlated with gene suppression. Twelve targets of miR-200c (Crtap, Fhod1, Smad2, Map3k1, Tob1, Ywhag/14-3-3 gamma, Ywhab/14-3-3 beta, Smad5, Zfp36, Xbp1, Mapk12, Snail1) were experimentally validated by identifying their 3'UTR miR-200 recognition elements. Smad2 and Smad5 form a complex with Zeb2 and Ywhab/14-3-3 beta and Ywhag/14-3-3 gamma form a complex with Snail1. These complexes that repress transcription assemble on epithelial gene promoters. miR-200 overexpression induced RNA polymerase II localization and reduced Zeb2 and Snail1 binding to epithelial gene promoters. Expression of miR-200-resistant Smad5 modestly, but significantly, reduced epithelial gene induction by miR-200. miR-200 expression and Zeb2 knockdown are known to inhibit cell invasion in in vitro assays. Knockdown of each of three novel miR-200 target genes identified here, Smad5, Ywhag and Crtap, also profoundly suppressed cell invasion. Thus, miR-200 suppresses TGF-beta/BMP signaling, promotes epithelial gene expression and suppresses cell invasion by regulating a network of genes. C1 [Perdigao-Henriques, R.; Petrocca, F.; Thomas, M. P.; Le, M. T. N.; Tan, S. M.; Lieberman, J.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Perdigao-Henriques, R.] Univ Nova Lisboa, ITQB, Anim Cell Technol Unit, P-2780156 Oeiras, Portugal. [Perdigao-Henriques, R.] IBET, Oeiras, Portugal. [Altschuler, G.; Hide, W.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hide, W.] Univ Sheffield, Dept Neurosci, Sheffield Inst Translat Neurosci, Sheffield, S Yorkshire, England. [Lieberman, J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Childrens Hosp Boston, Program Cellular & Mol Med, 200 Longwood Ave,Warren Alpert Bldg 255, Boston, MA 02115 USA. EM judy.lieberman@childrens.harvard.edu OI Hide, Winston/0000-0002-8621-3271; LE, Thi Nguyet Minh/0000-0002-6077-1566 FU Portuguese Ministry of Science and Technology (FCT) [SFRH/BD/37188/2007] FX R Perdigao-Henriques acknowledges the Portuguese Ministry of Science and Technology (FCT) for Ph.D. fellowship SFRH/BD/37188/2007. We thank Alex Amiet and Devin Leake (Dharmacon) for providing the biotinylated miRNAs, Linfeng Huang (Lieberman laboratory) for assistance with ChIP assays and Francisco Navarro (Lieberman laboratory) for helpful suggestions. NR 79 TC 12 Z9 13 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JAN 14 PY 2016 VL 35 IS 2 BP 158 EP 172 DI 10.1038/onc.2015.69 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA DB0JH UT WOS:000368193900003 PM 25798844 ER PT J AU Berliner, N Kurra, C Chou, D AF Berliner, Nancy Kurra, Chandana Chou, David TI Case 1-2016: An 18-Year-Old Man with Fever, Abdominal Pain, and Thrombocytopenia Hemophagocytic lymphohistiocytosis of an unknown cause. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DIAGNOSIS; ADULTS C1 [Berliner, Nancy] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kurra, Chandana] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kurra, Chandana] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Berliner, Nancy] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Kurra, Chandana] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Chou, David] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Berliner, N (reprint author), Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 14 PY 2016 VL 374 IS 2 BP 165 EP 173 DI 10.1056/NEJMcpc1501306 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DA7PQ UT WOS:000367996700012 PM 26760088 ER PT J AU Edelman, EJ Hansen, NB Cutter, CJ Danton, C Fiellin, LE O'Connor, PG Williams, EC Maisto, SA Bryant, KJ Fiellin, DA AF Edelman, E. Jennifer Hansen, Nathan B. Cutter, Christopher J. Danton, Cheryl Fiellin, Lynn E. O'Connor, Patrick G. Williams, Emily C. Maisto, Stephen A. Bryant, Kendall J. Fiellin, David A. TI Implementation of integrated stepped care for unhealthy alcohol use in HIV clinics SO ADDICTION SCIENCE & CLINICAL PRACTICE LA English DT Article DE HIV; Alcohol-related disorders; Qualitative methods; Diffusion of innovation ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBSTANCE-ABUSE TREATMENT; QUALITATIVE CONTENT-ANALYSIS; CENTERED MEDICAL HOME; BRIEF INTERVENTION; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; USE DISORDERS; EMERGENCY-DEPARTMENT; HEPATITIS-C AB Background: Effective counseling and pharmacotherapy for unhealthy alcohol use are rarely provided in HIV treatment settings to patients. Our goal was to describe factors influencing implementation of a stepped care model to address unhealthy alcohol use in HIV clinics from the perspectives of social workers, psychologists and addiction psychiatrists. Methods: We conducted two focus groups with Social Workers (n = 4), Psychologists (n = 2), and Addiction Psychiatrists (n = 4) involved in an ongoing randomized controlled trial evaluating the effectiveness of integrated stepped care for unhealthy alcohol use in HIV-infected patients at five Veterans Health Administration (VA) HIV clinics. Data collection and analyses were guided by the Consolidated Framework for Implementation Research (CFIR) domains, with a focus on the three domains which we considered to be most relevant: intervention characteristics (i.e. motivational interviewing, pharmacotherapy), the inner setting (i.e. HIV clinics), and characteristics of individuals (i.e. the providers). A multidisciplinary team used directed content analysis to identify major themes. Results: From the providers' perspective, the major implementation themes that emerged by CFIR domain included: (1) Intervention characteristics: providers valued tools and processes for facilitating patient motivation for treatment of unhealthy alcohol use given their perceived lack of motivation, but expressed a desire for greater flexibility; (2) Inner setting: treating unhealthy alcohol use in HIV clinics was perceived by providers to be consistent with VA priorities; and (3) Characteristics of individuals: there was high self-efficacy to conduct the intervention, an expressed need for more consistent utilization to maintain skills, and consideration of alternative models for delivering the components of the intervention. Conclusions: Use of the CFIR framework reveals that implementation of integrated stepped care for unhealthy alcohol use in HIV clinics is facilitated by tools to help providers enhance patient motivation or address unhealthy alcohol use among patients perceived to be unmotivated. Implementation may be facilitated by its consistency with organizational values and existing models of care and attention to optimizing provider self-efficacy and roles (i.e. approaches to treatment integration). C1 [Edelman, E. Jennifer; Cutter, Christopher J.; Danton, Cheryl; Fiellin, Lynn E.; O'Connor, Patrick G.; Fiellin, David A.] Yale Univ, Sch Med, ESH A, 367 Cedar St, New Haven, CT 06510 USA. [Edelman, E. Jennifer; Hansen, Nathan B.; Fiellin, Lynn E.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, 135 Coll St, New Haven, CT 06510 USA. [Hansen, Nathan B.] Univ Georgia, Coll Publ Hlth, 131 Wright Hall,Hlth Sci Campus, Athens, GA 30602 USA. [Williams, Emily C.] VA Puget Sound Hlth Care Syst, Ctr Innovat Veteran Ctr & Value Driven Care, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. [Williams, Emily C.] Univ Washington, Dept Hlth Serv, Magnuson Hlth Sci Ctr, 1959 NE Pacific St,Room H-664, Seattle, WA 98195 USA. [Maisto, Stephen A.] Syracuse Univ, 430 Huntington Hall, Syracuse, NY 13244 USA. [Bryant, Kendall J.] NIAAA, HIV AIDS Program, 5635 Fishers Lane, Bethesda, MD 20892 USA. RP Edelman, EJ (reprint author), Yale Univ, Sch Med, ESH A, 367 Cedar St, New Haven, CT 06510 USA. EM ejennifer.edelman@yale.edu RI Hansen, Nathan/F-2074-2016 FU NIAAA NIH HHS [K05 AA016928, 1U01AA020795, 2K05 AA16928, U01 AA020795]; NIDA NIH HHS [K12 DA033312, K12DA033312-02]; NIMH NIH HHS [R25 MH080916, R25 MH080916-01A2] NR 78 TC 3 Z9 3 U1 6 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1940-0640 J9 ADDICT SCI CLIN PRAC JI Addict. Sci. Clin. Pract. PD JAN 13 PY 2016 VL 11 AR 1 DI 10.1186/s13722-015-0048-z PG 14 WC Substance Abuse SC Substance Abuse GA DP0AC UT WOS:000378148900001 PM 26763048 ER PT J AU Meabon, JS Huber, BR Cross, DJ Richards, TL Minoshima, S Pagulayan, KF Li, G Meeker, KD Kraemer, BC Petrie, EC Raskind, MA Peskind, ER Cook, DG AF Meabon, James S. Huber, Bertrand R. Cross, Donna J. Richards, Todd L. Minoshima, Satoshi Pagulayan, Kathleen F. Li, Ge Meeker, Kole D. Kraemer, Brian C. Petrie, Eric C. Raskind, Murray A. Peskind, Elaine R. Cook, David G. TI Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID TRAUMATIC BRAIN-INJURY; AFGHANISTAN WAR VETERANS; CENTRAL-NERVOUS-SYSTEM; VS. BLUNT FORCES; HEAD-INJURY; CEREBROSPINAL-FLUID; INDUCED NEUROTRAUMA; MILITARY PERSONNEL; ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM AB m Blast exposure can cause mild traumatic brain injury (TBI) in mice and other mammals. However, there are important gaps in our understanding of the neuropathology underlying repetitive blast exposure in animal models compared to the neuroimaging abnormalities observed in blast-exposed veterans. Moreover, how an increase in the number of blast exposures affects neuroimaging endpoints in blast-exposed humans is not well understood. We asked whether there is a dose-response relationship between the number of blast-related mild TBIs and uptake of F-18-fluorodeoxyglucose (FDG), a commonly used indicator of neuronal activity, in the brains of blast-exposed veterans with mild TBI. We found that the number of blast exposures correlated with FDG uptake in the cerebellum of veterans. In mice, blast exposure produced microlesions in the blood-brain barrier (BBB) predominantly in the ventral cerebellum. Purkinje cells associated with these BBB microlesions displayed plasma membrane disruptions and aberrant expression of phosphorylated tau protein. Purkinje cell loss was most pronounced in the ventral cerebellar lobules, suggesting that early-stage breakdown of BBB integrity may be an important factor driving long-term brain changes. Blast exposure caused reactive gliosis in mouse cerebellum, particularly in the deep cerebellar nuclei. Diffusion tensor imaging tractography of the cerebellum of blast-exposed veterans revealed that mean diffusivity correlated negatively with the number of blast-related mild TBIs. Together, these results argue that the cerebellum is vulnerable to repetitive mild TBI in both mice and humans. C1 [Meabon, James S.; Pagulayan, Kathleen F.; Li, Ge; Petrie, Eric C.; Raskind, Murray A.; Peskind, Elaine R.] VA Puget Sound Hlth Care Syst VA Puget Sound, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Meabon, James S.; Pagulayan, Kathleen F.; Li, Ge; Petrie, Eric C.; Raskind, Murray A.; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Huber, Bertrand R.] Boston Univ, Sch Med, VA Jama Plain, Dept Neurol, Jamaica Plain, MA 02130 USA. [Cross, Donna J.; Richards, Todd L.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Minoshima, Satoshi] Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA. [Li, Ge; Meeker, Kole D.; Kraemer, Brian C.; Cook, David G.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Kraemer, Brian C.; Cook, David G.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Cook, David G.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Cook, DG (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA.; Cook, DG (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA.; Cook, DG (reprint author), Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. EM dgcook@u.washington.edu FU Department of Veterans Affairs Office of Research and Development Medical Research Service; VA Rehabilitation Research & Development Service; University of Washington Friends of Alzheimer's Research; University of Washington Royalty Research Fund; Northwest Network Mental Illness Research, Education and Clinical Center; Office of Academic Affiliations Advanced Fellowship Program Mental Illness Research and Treatment, Department of Veterans Affairs; VA Clinical Science R&D Career Development Award Program [CX00516] FX This work was supported by the Department of Veterans Affairs Office of Research and Development Medical Research Service (D.G.C. and B.C.K.); VA Rehabilitation Research & Development Service (E.R.P.); University of Washington Friends of Alzheimer's Research (D.G.C. and E.R.P.); University of Washington Royalty Research Fund (D.G.C.); Northwest Network Mental Illness Research, Education and Clinical Center (J.S.M., B.R.H., K.F.P., E.C.P., M.A.R., and E.R.P.); Office of Academic Affiliations Advanced Fellowship Program Mental Illness Research and Treatment, Department of Veterans Affairs (B.R.H.); NIH T32 AG000258 (J.S.M.); and VA Clinical Science R&D Career Development Award Program # CX00516 (K.F.P.). Author contributions: J.S.M. and B.R.H. conducted blast procedures, biochemistry experiments, and microscopy. K.D.M. conducted biochemistry experiments. J.S.M., B.R.H., D.J.C., T.L.R., S.M., G.L., E.C.P., M.A.R., E.R.P., and D.G.C. contributed to study design. J.S.M., D.J.C., E.R.P., G.L., E.R.P., M.A.R., and D.G.C. performed data analysis and data interpretation. J.S.M., D.J.C., T.L.R., K.F.P., G.L., B.C.K., E.C.P., M.A.R., E.R.P., and D.G.C. drafted the manuscript and/or edited it critically for important intellectual content. NR 100 TC 2 Z9 2 U1 6 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 13 PY 2016 VL 8 IS 321 DI 10.1126/scitranslmed.aaa9585 PG 15 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DB4VD UT WOS:000368510800004 ER PT J AU Shaughnessy, T Kantarci, A Kau, CH Skrenes, D Skrenes, S Ma, D AF Shaughnessy, Timothy Kantarci, Alpdogan Kau, Chung How Skrenes, Darya Skrenes, Sanjar Ma, Dennis TI Intraoral photobiomodulation-induced orthodontic tooth alignment: a preliminary study SO BMC ORAL HEALTH LA English DT Article DE Orthodontic tooth movement; Intraoral photobiomodulation; Alignment; Accelerates; Treatment time; Low-level light therapy ID LOW-LEVEL LASER; LITTLES IRREGULARITY INDEX; TREATMENT TIME; MOVEMENT; THERAPY; METAANALYSIS; IRRADIATION; EFFICACY; BRACKETS; MODEL AB Background: Numerous strategies have been proposed to decrease orthodontic treatment time. Photobiomodulation (PBM) has previously been demonstrated to assist in this objective. The aim of this study was to test if intraoral PBM increases the rate of tooth alignment and reduces the time required to resolve anterior dental crowding. Methods: Nineteen orthodontic subjects with Class I or Class II malocclusion and Little's Irregularity Index (LII) >= 3 mm were selected from a pool of applicants, providing 28 total arches. No cases required extraction. The test group (N = 11, 18 arches, 10 upper, 8 lower) received daily PBM treatment with an intraoral LED device (OrthoPulse (TM), Biolux Research Ltd.) during orthodontic treatment, while the control group (N = 8, 10 arches, 3 upper, 7 lower) received only orthodontic treatment. The PBM device exposed the buccal side of the gums to near-infrared light with a continuous 850-nm wavelength, generating an average daily energy density of 9.5 J/cm(2). LII was measured at the start (T0) of orthodontic treatment until alignment was reached (T1, where LII <= 1 mm). The control group was mostly bonded with 0.018-in slot self-ligating SPEED brackets (Hespeler Orthodontics, Cambridge, ON. Canada), while conventionally-ligating Ormco Mini-Diamond twins were used on the PBM group (Ormco, Glendora, Calif. USA). Both groups progressed through alignment with NiTi arch-wires from 0.014-in through to 0.018-in (Ormco), with identical arch-wire changes. The rate of anterior alignment, in LII mm/week, and total treatment time was collected for both groups. Cox proportional hazards models were used to compare groups and while considering age, sex, ethnicity, arch and degree of crowding. Results: The mean alignment rate for the PBM group was significantly higher than that of the control group, with an LII change rate of 1.27 mm/week (SD 0.53, 95 % CI +/- 0.26) versus 0.44 mm/week (SD 0.20, 95 % CI +/- 0.12), respectively (p = 0.0002). The treatment time to alignment was significantly smaller for the PBM group, which achieved alignment in 48 days (SD 39, 95 % CI +/- 39), while the control group took 104 days (SD 55, 95 % CI +/- 19, p = 0.0053) on average. These results demonstrated that intraoral PBM increased the average rate of tooth movement by 2.9-fold, resulting in a 54 % average decrease in alignment duration versus control. The average PBM compliance to daily treatments was 93 % during alignment. Conclusions: Under the limitations of this study, the findings suggest that intraoral PBM could be used to decrease anterior alignment treatment time, which could consequently decrease full orthodontic treatment time. However, due to its limitations, further research in the form of a large, randomized trial is needed. C1 [Shaughnessy, Timothy] Shaughnessy Orthodont, Suwanee, GA 30024 USA. [Kantarci, Alpdogan] Forsyth Inst, Dept Appl Oral Hlth Sci, Cambridge, MA USA. [Kau, Chung How] Univ Alabama Birmingham, Fac Dent, Dept Orthodont, Birmingham, AL USA. [Skrenes, Darya; Skrenes, Sanjar; Ma, Dennis] Biolux Res Ltd, Vancouver, BC, Canada. RP Shaughnessy, T (reprint author), Shaughnessy Orthodont, 4330 Johns Creek Pkwy,Suite 500, Suwanee, GA 30024 USA. EM str8tth@me.com FU Biolux Research Ltd. FX This study was supported by a sponsored research agreement from Biolux Research Ltd. NR 52 TC 1 Z9 1 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6831 J9 BMC ORAL HEALTH JI BMC Oral Health PD JAN 13 PY 2016 VL 16 AR 3 DI 10.1186/s12903-015-0159-7 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DA7JX UT WOS:000367981500001 PM 26762247 ER PT J AU Fields, EC Kuperberg, GR AF Fields, Eric C. Kuperberg, Gina R. TI Dynamic Effects of Self-Relevance and Task on the Neural Processing of Emotional Words in Context SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE emotion; ERP; language; late positive potential (LPP); late positive component (LPC); self-relevance; perspective; task ID EVENT-RELATED POTENTIALS; EVALUATIVE CATEGORIZATION; NARRATIVE COMPREHENSION; FUNCTIONAL MRI; P300; ERP; AROUSAL; PERSPECTIVES; PERCEPTION; DISCOURSE AB We used event-related potentials (ERPs) to examine the interactions between task, emotion, and contextual self-relevance on processing words in social vignettes. Participants read scenarios that were in either third person (other-relevant) or second person (self relevant) and we recorded ERPs to a neutral, pleasant, or unpleasant critical word. In a previously reported study (Fields and Kuperberg, 2012) with these stimuli, participants were tasked with producing a third sentence continuing the scenario. We observed a larger LPC to emotional words than neutral words in both the self-relevant and other relevant scenarios, but this effect was smaller in the self relevant scenarios because the LPC was larger on the neutral words (i.e., a larger LPC to self-relevant than other-relevant neutral words). In the present work, participants simply answered comprehension questions that did not refer to the emotional aspects of the scenario. Here we observed quite a different pattern of interaction between self-relevance and emotion: the LPC was larger to emotional vs. neutral words in the self-relevant scenarios only, and there was no effect of self-relevance on neutral words. Taken together, these findings suggest that the LPC reflects a dynamic interaction between specific task demands, the emotional properties of a stimulus, and contextual self-relevance. We conclude by discussing implications and future directions for a functional theory of the emotional LPC. C1 [Fields, Eric C.; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Fields, Eric C.; Kuperberg, Gina R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Fields, Eric C.; Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Fields, EC (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. EM eric.fields@tufts.edu FU NIMH [R01 MH071635]; Sidney Baer Trust FX This work was supported by NIMH (R01 MH071635) to GK, as well as the Sidney Baer Trust who supported undergraduate students, including Wonja Fairbrother, Sorabh Kothari, Camila Carneiro de Lima, Rohan Natraj, and Erich Tusch, who contributed to data collection and other aspects of the project. NR 60 TC 0 Z9 0 U1 6 U2 8 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD JAN 13 PY 2016 VL 6 AR 2003 DI 10.3389/fpsyg.2015.02003 PG 12 WC Psychology, Multidisciplinary SC Psychology GA DA7TZ UT WOS:000368008400001 ER PT J AU Mekkaoui, C Metellus, P Kostis, WJ Martuzzi, R Pereira, FR Beregi, JP Reese, TG Constable, TR Jackowski, MP AF Mekkaoui, Choukri Metellus, Philippe Kostis, William J. Martuzzi, Roberto Pereira, Fabricio R. Beregi, Jean-Paul Reese, Timothy G. Constable, Todd R. Jackowski, Marcel P. TI Diffusion Tensor Imaging in Patients with Glioblastoma Multiforme Using the Supertoroidal Model SO PLOS ONE LA English DT Article ID WHITE-MATTER; SUPERQUADRIC GLYPHS; WATER DIFFUSION; HUMAN BRAIN; MR-IMAGES; SCHEMES; GLIOMAS; TISSUES; TRACTS AB Purpose Diffusion Tensor Imaging (DTI) is a powerful imaging technique that has led to improvements in the diagnosis and prognosis of cerebral lesions and neurosurgical guidance for tumor resection. Traditional tensor modeling, however, has difficulties in differentiating tumor-infiltrated regions and peritumoral edema. Here, we describe the supertoroidal model, which incorporates an increase in surface genus and a continuum of toroidal shapes to improve upon the characterization of Glioblastoma multiforme (GBM). Materials and Methods DTI brain datasets of 18 individuals with GBM and 18 normal subjects were acquired using a 3T scanner. A supertoroidal model of the diffusion tensor and two new diffusion tensor invariants, one to evaluate diffusivity, the toroidal volume (TV), and one to evaluate anisotropy, the toroidal curvature (TC), were applied and evaluated in the characterization of GBM brain tumors. TV and TC were compared with the mean diffusivity (MD) and fractional anisotropy (FA) indices inside the tumor, surrounding edema, as well as contralateral to the lesions, in the white matter (WM) and gray matter (GM). Results The supertoroidal model enhanced the borders between tumors and surrounding structures, refined the boundaries between WM and GM, and revealed the heterogeneity inherent to tumor-infiltrated tissue. Both MD and TV demonstrated high intensities in the tumor, with lower values in the surrounding edema, which in turn were higher than those of unaffected brain parenchyma. Both TC and FA were effective in revealing the structural degradation of WM tracts. Conclusions Our findings indicate that the supertoroidal model enables effective tensor visualization as well as quantitative scalar maps that improve the understanding of the underlying tissue structure properties. Hence, this approach has the potential to enhance diagnosis, preoperative planning, and intraoperative image guidance during surgical management of brain lesions. C1 [Mekkaoui, Choukri; Kostis, William J.; Reese, Timothy G.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Athinoula Martinos Ctr Bio, Boston, MA 02115 USA. [Metellus, Philippe] Hop Timone Adultes Marseille, Dept Neurosurg, Marseille, Bouches Du Rhon, France. [Kostis, William J.] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Martuzzi, Roberto] Ecole Polytech Fed Lausanne, Sch Life Sci, Brain Mind Inst, Lab Cognit Neurosci, Lausanne, Switzerland. [Pereira, Fabricio R.; Beregi, Jean-Paul] Univ Hosp Ctr Nimes, Dept Radiol, Nimes, Gard, France. [Pereira, Fabricio R.; Beregi, Jean-Paul] Res Team EA 2415, Nimes, Gard, France. [Constable, Todd R.] Yale Univ, Sch Med, Dept Diagnost Radiol, Magnet Resonance Res Ctr, New Haven, CT 06510 USA. [Jackowski, Marcel P.] Univ Sao Paulo, Dept Comp Sci, Inst Math & Stat, Sao Paulo, Brazil. RP Mekkaoui, C (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Athinoula Martinos Ctr Bio, Boston, MA 02115 USA. EM mekkaoui@nmr.mgh.harvard.edu FU Sao Paulo Research Foundation (FAPESP) [2015/01587-0] FX We thank the Sao Paulo Research Foundation (FAPESP grant #2015/01587-0). NR 37 TC 1 Z9 2 U1 0 U2 1 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 JAN 13 PY 2016 VL 11 IS 1 AR e0146693 DI 10.1371/journal.pone.0146693 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA8CX UT WOS:000368033100039 PM 26761637 ER PT J AU El Ouaamari, A Dirice, E Gedeon, N Hu, J Zhou, JY Shirakawa, J Hou, LF Goodman, J Karampelias, C Qiang, GF Boucher, J Martinez, R Gritsenko, MA De Jesus, DF Kahraman, S Bhatt, S Smith, RD Beer, HD Jungtrakoon, P Gong, YP Goldfine, AB Liew, CW Doria, A Andersson, O Qian, WJ Remold-O'Donnell, E Kulkarni, RN AF El Ouaamari, Abdelfattah Dirice, Ercument Gedeon, Nicholas Hu, Jiang Zhou, Jian-Ying Shirakawa, Jun Hou, Lifei Goodman, Jessica Karampelias, Christos Qiang, Guifeng Boucher, Jeremie Martinez, Rachael Gritsenko, Marina A. De Jesus, Dario F. Kahraman, Sevim Bhatt, Shweta Smith, Richard D. Beer, Hans-Dietmar Jungtrakoon, Prapaporn Gong, Yanping Goldfine, Allison B. Liew, Chong Wee Doria, Alessandro Andersson, Olov Qian, Wei-Jun Remold-O'Donnell, Eileen Kulkarni, Rohit N. TI SerpinB1 Promotes Pancreatic beta Cell Proliferation SO CELL METABOLISM LA English DT Article ID INSULIN-RESISTANT STATES; EMBRYONIC STEM-CELLS; IN-VITRO; NEUTROPHIL ELASTASE; GROWTH-FACTOR; INHIBITION; SECRETION; PROTEINS; REPLICATION; DEGRADATION AB Although compensatory islet hyperplasia in response to insulin resistance is a recognized feature in diabetes, the factor(s) that promote beta cell proliferation have been elusive. We previously reported that the liver is a source for such factors in the liver insulin receptor knockout (LIRKO) mouse, an insulin resistance model that manifests islet hyperplasia. Using proteomics we show that serpinB1, a protease inhibitor, which is abundant in the hepatocyte secretome and sera derived from LIRKO mice, is the liver-derived secretory protein that regulates beta cell proliferation in humans, mice, and zebrafish. Small-molecule compounds, that partially mimic serpinB1 effects of inhibiting elastase activity, enhanced proliferation of beta cells, and mice lacking serpinB1 exhibit attenuated beta cell compensation in response to insulin resistance. Finally, SerpinB1 treatment of islets modulated proteins in growth/survival pathways. Together, these data implicate serpinB1 as an endogenous protein that can potentially be harnessed to enhance functional beta cell mass in patients with diabetes. C1 [El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Shirakawa, Jun; Martinez, Rachael; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Harvard Stem Cell Inst,Dept Med,Islet Cell & Rege, Boston, MA 02115 USA. [Zhou, Jian-Ying; Gritsenko, Marina A.; Smith, Richard D.; Qian, Wei-Jun] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Zhou, Jian-Ying; Gritsenko, Marina A.; Smith, Richard D.; Qian, Wei-Jun] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. [Hou, Lifei; Goodman, Jessica; Gong, Yanping; Remold-O'Donnell, Eileen] Boston Childrens Hosp, Program Cellular & Mol Med, 3 Blackfan Circle, Boston, MA 02215 USA. [Hou, Lifei; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. [Karampelias, Christos; Andersson, Olov] Karolinska Inst, Dept Cell & Mol Biol, von Eulers Vag 3, S-17177 Stockholm, Sweden. [Qiang, Guifeng; Liew, Chong Wee] Univ Illinois, Dept Phys & Biophys, Chicago, IL 60612 USA. [Boucher, Jeremie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Beer, Hans-Dietmar] Univ Zurich Hosp, Dept Dermatol, CH-8006 Zurich, Switzerland. [Jungtrakoon, Prapaporn; Doria, Alessandro] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Goldfine, Allison B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Sect Clin Res, Boston, MA 02215 USA. [Goldfine, Allison B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02215 USA. [Remold-O'Donnell, Eileen] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02215 USA. [Boucher, Jeremie] AstraZeneca R&D, Cardiovasc & Metab Dis iMed, S-43183 Molndal, Sweden. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Harvard Stem Cell Inst,Dept Med,Islet Cell & Rege, Boston, MA 02115 USA. EM rohit.kulkarni@joslin.harvard.edu RI Smith, Richard/J-3664-2012; Dirice, Ercument/B-2825-2017; OI Smith, Richard/0000-0002-2381-2349; Kahraman, Sevim/0000-0002-2880-6589; Shirakawa, Jun/0000-0002-0822-8750 FU NIH [RO1 DK67536, RO1 DK103215, RO1 DK55523, RO1 HL066548, R21 AI103407]; Boston Children's Hospital; Societe Francophone du Diabete; Association Francaise des Diabetiques; American Diabetes Association; JDRF [3-APF-2014-182-A-N]; Juvenile Diabetes Research Foundation/Sanofi Aventis Strategic Alliance [17-2011-644, P30 DK036836]; Ragnar Soderbergs Foundation; Swedish Research Council; Department of Energy; DOE [DE-AC05-76RL0 1830]; [R01 DK 074795]; [P41 GM103493]; [UC4 DK104167] FX We thank C. Ronald Kahn, MD for sharing the LIRKO mouse model, Ping Li, MD for assistance with statistical analyses, Dr. Lauge Schaffer (Novo Nordisk) for providing the S961 compound, Drs. Wei-Min Chen and Michele Sale (University of Virginia) for useful discussions, and Sandra Roger for technical assistance. This work was supported by NIH RO1 DK67536 and RO1 DK103215 (to R.N.K.); RO1 DK55523 (to A.D. and R.N.K.); NIH RO1 HL066548, R21 AI103407, and an RRRC award from Boston Children's Hospital (to E.R.O); R01 DK 074795 and P41 GM103493 (to R.D.S.); UC4 DK104167 (to W.-J.Q. and R.N.K.); Societe Francophone du Diabete, Association Francaise des Diabetiques, American Diabetes Association, and JDRF (3-APF-2014-182-A-N) (to A.E.O.); a grant from the Juvenile Diabetes Research Foundation/Sanofi Aventis Strategic Alliance (17-2011-644) (R.N.K.), and P30 DK036836 (DRC). Zebrafish experiments were performed at the Karolinska Institute and supported by the Ragnar Soderbergs Foundation and the Swedish Research Council (O.A.). Proteomics and phosphoproteomics experiments were performed in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by Department of Energy and located at Pacific Northwest National Laboratory, which is operated by Battelle Memorial Institute for the DOE under Contract DE-AC05-76RL0 1830. A.E.O. and R.N.K. are listed as inventors on a patent that is based on these studies. NR 53 TC 22 Z9 22 U1 10 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JAN 12 PY 2016 VL 23 IS 1 BP 194 EP 205 DI 10.1016/j.cmet.2015.12.001 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DI6MO UT WOS:000373613400020 PM 26701651 ER PT J AU Fahiminiya, S Witkowski, L Nadaf, J Carrot-Zhang, J Goudie, C Hasselblatt, M Johann, P Kool, M Lee, RS Gayden, T Roberts, CWM Biegel, JA Jabado, N Majewski, J Foulkes, WD AF Fahiminiya, Somayyeh Witkowski, Leora Nadaf, Javad Carrot-Zhang, Jian Goudie, Catherine Hasselblatt, Martin Johann, Pascal Kool, Marcel Lee, Ryan S. Gayden, Tenzin Roberts, Charles W. M. Biegel, Jaclyn A. Jabado, Nada Majewski, Jacek Foulkes, William D. TI Molecular analyses reveal close similarities between small cell carcinoma of the ovary, hypercalcemic type and atypical teratoid/rhabdoid tumor SO ONCOTARGET LA English DT Article DE SCCOHT; ATRT; exome sequencing; SWI/SNF; methylation ID TERATOID RHABDOID TUMORS; DNA METHYLATION; SEQUENCING DATA; SMARCA4 MUTATIONS; SOMATIC MUTATIONS; CHILDREN; CANCERS; DEFICIENCY; GERMLINE; TARGET AB Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy diagnosed in women under age 40. We and others recently determined that germline and/or somatic deleterious mutations in SMARCA4 characterize SCCOHT. Alterations in this gene, or the related SWI/SNF chromatin remodeling gene SMARCB1, have been previously reported in atypical teratoid/rhabdoid tumors (ATRTs) and malignant rhabdoid tumors (MRTs). To further describe the somatic landscape of SCCOHT, we performed whole exome sequencing on 14 tumors and their matched normal tissues and compared their genomic alterations with those in ATRT and ovarian high grade serous carcinoma (HGSC). We confirmed that SMARCA4 is the only recurrently mutated gene in SCCOHT, and show that recurrent allelic imbalance is observed exclusively on chromosome 19p, where SMARCA4 resides. By comparing genomic alterations between SCCOHT, ATRT and HGSC, we demonstrate that SCCOHTs, like ATRTs, have a remarkably simple genome and harbor significantly fewer somatic protein-coding mutations and chromosomal alterations than HGSC. Furthermore, a comparison of global DNA methylation profiles of 45 SCCOHTs, 65 ATRTs, and 92 HGSCs demonstrates a strong epigenetic correlation between SCCOHT and ATRT. Our results further confirm that the genomic and epigenomic signatures of SCCOHT are more similar to those of ATRT than HGSC, supporting our previous hypothesis that SCCOHT is a rhabdoid tumor and should be renamed MRT of the ovary. Furthermore, we conclude that SMARCA4 inactivation is the main cause of SCCOHT, and that new distinct therapeutic approaches should be developed to specifically target this devastating tumor. C1 [Fahiminiya, Somayyeh; Witkowski, Leora; Nadaf, Javad; Carrot-Zhang, Jian; Jabado, Nada; Majewski, Jacek; Foulkes, William D.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Fahiminiya, Somayyeh; Nadaf, Javad; Carrot-Zhang, Jian; Majewski, Jacek] McGill Univ, Montreal, PQ, Canada. [Fahiminiya, Somayyeh; Nadaf, Javad; Carrot-Zhang, Jian; Majewski, Jacek] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Goudie, Catherine; Jabado, Nada] McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. [Hasselblatt, Martin] Univ Hosp Munster, Inst Neuropathol, Munster, Germany. [Johann, Pascal] Univ Heidelberg Hosp, Pediat Hematol & Oncol, Heidelberg, Germany. [Kool, Marcel] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany. [Kool, Marcel] Core Ctr Heidelberg, German Canc Consortium DKTK, Heidelberg, Germany. [Lee, Ryan S.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Biegel, Jaclyn A.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Foulkes, William D.] McGill Univ, Dept Med Genet, Lady Davis Inst, Montreal, PQ, Canada. [Foulkes, William D.] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada. [Foulkes, William D.] McGill Univ, Ctr Hlth, Res Inst, Dept Med Genet, Montreal, PQ, Canada. [Roberts, Charles W. M.] St Jude Childrens Res Hosp, Ctr Comprehens Canc, 332 N Lauderdale St, Memphis, TN 38105 USA. [Roberts, Charles W. M.] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. RP Foulkes, WD (reprint author), McGill Univ, Dept Human Genet, Montreal, PQ, Canada.; Foulkes, WD (reprint author), McGill Univ, Dept Med Genet, Lady Davis Inst, Montreal, PQ, Canada.; Foulkes, WD (reprint author), McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada.; Foulkes, WD (reprint author), McGill Univ, Ctr Hlth, Res Inst, Dept Med Genet, Montreal, PQ, Canada. EM william.foulkes@mcgill.ca OI Hasselblatt, Martin/0000-0003-2707-8484 FU Network of Applied Medical Genetics; IZKF Munster [Ha3/019/15]; Fonds de recherche du Quebec - Sante; Canadian Cancer Society Research Institute; Small Cell Ovarian Cancer Foundation FX JM is a recipient of a Canada Research Chair. SF received a postdoctoral Fellowship from the Network of Applied Medical Genetics. MH received funding from IZKF Munster (Ha3/019/15). LW received funding from the Fonds de recherche du Quebec - Sante. WDF received funds from the Canadian Cancer Society Research Institute and the Small Cell Ovarian Cancer Foundation. NR 54 TC 3 Z9 3 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 12 PY 2016 VL 7 IS 2 BP 1732 EP 1740 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DD5GP UT WOS:000369951100050 PM 26646792 ER PT J AU Arriga, R Caratelli, S Coppola, A Spagnoli, GC Venditti, A Amadori, S Lanzilli, G Lauro, D Palomba, P Sconocchia, T Del Principe, MI Maurillo, L Buccisano, F Capuani, B Ferrone, S Sconocchia, G AF Arriga, Roberto Caratelli, Sara Coppola, Andrea Spagnoli, Giulio Cesare Venditti, Adriano Amadori, Sergio Lanzilli, Giulia Lauro, Davide Palomba, Patrizia Sconocchia, Tommaso Del Principe, Maria Ilaria Maurillo, Luca Buccisano, Francesco Capuani, Barbara Ferrone, Soldano Sconocchia, Giuseppe TI Enhancement of anti-leukemia activity of NK cells in vitro and in vivo by inhibition of leukemia cell-induced NK cell damage SO ONCOTARGET LA English DT Article DE NK cell; acute myeloid leukemia; CD16; TIMP3; NK cell abnormalities ID ACUTE MYELOID-LEUKEMIA; NATURAL-KILLER-CELLS; EXPRESSION; CD16; TRANSPLANTATION; APOPTOSIS; DEATH; METALLOPROTEASE; ALLOREACTIVITY; INACTIVATION AB Acute myeloid leukemia (AML) cells induce, in vitro, NK cell abnormalities (NKCAs) including apoptosis and activating receptor down-regulation. The potential negative impact of AML cells on the therapeutic efficacy of NK cell-based strategies prompted us to analyze the mechanisms underlying NKCAs and to develop approaches to protect NK cells from NKCAs. NKCA induction by the AML leukemia cells target a subpopulation of peripheral blood NK cells and is interleukin-2 independent but is abrogated by a long-term culture of NK (LTNK) cells at 37 degrees C. LTNK cells displayed a significantly enhanced ability to damage AML cells in vitro and inhibited the subcutaneous growth of ML-2 cells grafted into CB17 SCID mice. Actinomycin D restored the susceptibility of LTNK cells to NKCAs while TAPI-0, a functional analog of the tissue inhibitor of metalloproteinase (TIMP) 3, inhibits ML-2 cell-induced NKCAs suggesting that the generation of NK cell resistance to NKCAs involves RNA transcription and metalloproteinase (MPP) inactivation. This conclusion is supported by the reduced susceptibility to AML cell-induced NKCAs of LTNK cells in which TIMP3 gene and protein are over-expressed. This information may contribute to the rational design of targeted strategies to enhance the efficacy of NK cell-based-immunotherapy of AML with haploidentical NK cells. C1 [Arriga, Roberto; Coppola, Andrea; Lauro, Davide; Capuani, Barbara] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy. [Caratelli, Sara; Lanzilli, Giulia; Sconocchia, Tommaso; Sconocchia, Giuseppe] CNR, Dept Biomed, Inst Translat Pharmacol, Lab Tumor Immunol & Immunotherapy, Rome, Italy. [Spagnoli, Giulio Cesare] Univ Basel, Dept Biomed, Inst Surg Res & Hosp Management, Basel, Switzerland. [Venditti, Adriano; Amadori, Sergio; Palomba, Patrizia; Del Principe, Maria Ilaria; Maurillo, Luca; Buccisano, Francesco] Univ Roma Tor Vergata, Dept Biomed & Prevent, Hematol, Rome, Italy. [Ferrone, Soldano] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ferrone, Soldano] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sconocchia, G (reprint author), CNR, Dept Biomed, Inst Translat Pharmacol, Lab Tumor Immunol & Immunotherapy, Rome, Italy. EM giuseppe.sconocchia@cnr.it FU Ministry of Education, University, and Research (PRIN) [2010AX2JX7_005]; Lazio Regional Agency for Transplantation (ART); Italian Association for Cancer Research (AIRC); Rainbow Association for Research in Pediatric Oncology-Hematology/ the NANDO PERETTI Foundation; PHS - National Cancer Institute [RO1CA138188, P50CA121973]; Swiss National Fund for Scientific Research FX AV, GS, SA were supported by the Ministry of Education, University, and Research (PRIN), grant 2010AX2JX7_005 and Lazio Regional Agency for Transplantation (ART). GS was supported by the Italian Association for Cancer Research (AIRC), the Rainbow Association for Research in Pediatric Oncology-Hematology/ the NANDO PERETTI Foundation. SF was supported in part by PHS grants RO1CA138188, and P50CA121973 awarded by the National Cancer Institute. G.C.S. was supported by a grant awarded by the Swiss National Fund for Scientific Research. NR 25 TC 2 Z9 2 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 12 PY 2016 VL 7 IS 2 BP 2070 EP 2079 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DD5GP UT WOS:000369951100074 PM 26655503 ER PT J AU Keum, N Cao, Y Lee, DH Park, SM Rosner, B Fuchs, CS Wu, K Giovannucci, EL AF Keum, N. Cao, Y. Lee, D. H. Park, S. M. Rosner, B. Fuchs, C. S. Wu, K. Giovannucci, E. L. TI Male pattern baldness and risk of colorectal neoplasia SO BRITISH JOURNAL OF CANCER LA English DT Article DE male pattern baldness; frontal-only baldness; frontal-plus-mild-vertex baldness; frontal-plus-moderate-vertex baldness; frontal-plus-severe-vertex baldness; colorectal cancer; colorectal adenoma; colorectal neoplasia ID FOOD FREQUENCY QUESTIONNAIRE; DOSE-RESPONSE METAANALYSIS; GROWTH-FACTOR 1; CANCER RISK; PROSTATE-CANCER; CALCIUM INTAKE; SEX-HORMONES; INSULIN; MEN; ASSOCIATION AB Background: Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia. Methods: From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mildvertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs. Results: Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03-1.62) and 1.31 (95% CI, 1.01-1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06-1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98-1.33). Conclusions: Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia. C1 [Keum, N.; Cao, Y.; Lee, D. H.; Wu, K.; Giovannucci, E. L.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Bldg 2,3rd Floor,665 Huntington Ave, Boston, MA 02115 USA. [Keum, N.; Cao, Y.; Lee, D. H.; Giovannucci, E. L.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Bldg 2,3rd Floor,665 Huntington Ave, Boston, MA 02115 USA. [Park, S. M.] Seoul Natl Univ, Coll Med, Seoul Natl Univ Hosp, Dept Family Med, Seoul, South Korea. [Rosner, B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Bldg 2,3rd Floor,665 Huntington Ave, Boston, MA 02115 USA. [Fuchs, C. S.] Dana Farber Canc Inst, Dept Oncol, Boston, MA 02215 USA. [Giovannucci, E. L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Giovannucci, E. L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Giovannucci, E. L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Keum, N (reprint author), Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Bldg 2,3rd Floor,665 Huntington Ave, Boston, MA 02115 USA.; Keum, N (reprint author), Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Bldg 2,3rd Floor,665 Huntington Ave, Boston, MA 02115 USA. EM nak212@mail.harvard.edu FU National Institutes of Health [UM1 CA167552] FX NaNa Keum had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We thank the participants and staff of the HSPF for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. This work was supported by the National Institutes of Health (UM1 CA167552). NR 31 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 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 12 PY 2016 VL 114 IS 1 BP 110 EP 117 DI 10.1038/bjc.2015.438 PG 8 WC Oncology SC Oncology GA DB5NU UT WOS:000368561700017 PM 26757425 ER PT J AU Traylor, M Anderson, CD Hurford, R Bevan, S Markus, HS AF Traylor, Matthew Anderson, Christopher D. Hurford, Robert Bevan, Steve Markus, Hugh S. TI Oxidative phosphorylation and lacunar stroke Genome-wide enrichment analysis of common variants SO NEUROLOGY LA English DT Article ID ARGININE SUPPLEMENTATION; ISCHEMIC-STROKE; MITOCHONDRIAL; ASSOCIATION; DYSFUNCTION AB Objective:We investigated whether oxidative phosphorylation (OXPHOS) abnormalities were associated with lacunar stroke, hypothesizing that these would be more strongly associated in patients with multiple lacunar infarcts and leukoaraiosis (LA).Methods:In 1,012 MRI-confirmed lacunar stroke cases and 964 age-matched controls recruited from general practice surgeries, we investigated associations between common genetic variants within the OXPHOS pathway and lacunar stroke using a permutation-based enrichment approach. Cases were phenotyped using MRI into those with multiple infarcts or LA (MLI/LA) and those with isolated lacunar infarcts (ILI) based on the number of subcortical infarcts and degree of LA, using the Fazekas grading. Using gene-level association statistics, we tested for enrichment of genes in the OXPHOS pathway with all lacunar stroke and the 2 subtypes.Results:There was a specific association with strong evidence of enrichment in the top 1% of genes in the MLI/LA (subtype p = 0.0017) but not in the ILI subtype (p = 1). Genes in the top percentile for the all lacunar stroke analysis were not significantly enriched (p = 0.07).Conclusions:Our results implicate the OXPHOS pathway in the pathogenesis of lacunar stroke, and show the association is specific to patients with the MLI/LA subtype. They show that MRI-based subtyping of lacunar stroke can provide insights into disease pathophysiology, and imply that different radiologic subtypes of lacunar stroke subtypes have distinct underlying pathophysiologic processes. C1 [Traylor, Matthew; Hurford, Robert; Markus, Hugh S.] Univ Cambridge, Clin Neurosci, Cambridge CB2 1TN, England. [Bevan, Steve] Lincoln Univ, Sch Life Sci, Lincoln, New Zealand. [Anderson, Christopher D.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. RP Traylor, M (reprint author), Univ Cambridge, Clin Neurosci, Cambridge CB2 1TN, England. EM mt628@medschl.cam.ac.uk OI Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Anderson, Christopher/0000-0002-0053-2002 FU NIHR; NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre; Wellcome Trust; Stroke Association; Stroke Association [TSA 2013/01]; NIH-NINDS [K23 NS086873]; Massachusetts General Hospital Department of Neurology; Biogen Idec, Inc. FX Hugh Markus is supported by an NIHR Senior Investigator award. Hugh Markus and Steve Bevan are supported by the NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre. Collection of the UK Young Lacunar Stroke Resource was primarily supported by a Functional Genomics grant from the Wellcome Trust with additional support from the Stroke Association. Genotyping and MT were supported by a project grant from the Stroke Association (TSA 2013/01). Dr. Anderson is supported by NIH-NINDS K23 NS086873 and a Fellowship in Therapeutic Investigation sponsored by the Massachusetts General Hospital Department of Neurology and Biogen Idec, Inc. NR 20 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 12 PY 2016 VL 86 IS 2 BP 141 EP 145 DI 10.1212/WNL.0000000000002260 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA DB4AJ UT WOS:000368454800007 PM 26674331 ER PT J AU Traylor, M Zhang, CR Adib-Samii, P Devan, WJ Parsons, OE Lanfranconi, S Gregory, S Cloonan, L Falcone, GJ Radmanesh, F Fitzpatrick, K Kanakis, A Barrick, TR Moynihan, B Lewis, CM Boncoraglio, GB Lemmens, R Thijs, V Sudlow, C Wardlaw, J Rothwell, PM Meschia, JF Worrall, BB Levi, C Bevan, S Furie, KL Dichgans, M Rosand, J Markus, HS Rost, N AF Traylor, Matthew Zhang, Cathy R. Adib-Samii, Poneh Devan, William J. Parsons, Owen E. Lanfranconi, Silvia Gregory, Sarah Cloonan, Lisa Falcone, Guido J. Radmanesh, Farid Fitzpatrick, Kaitlin Kanakis, Allison Barrick, Thomas R. Moynihan, Barry Lewis, Cathryn M. Boncoraglio, Giorgio B. Lemmens, Robin Thijs, Vincent Sudlow, Cathie Wardlaw, Joanna Rothwell, Peter M. Meschia, James F. Worrall, Bradford B. Levi, Christopher Bevan, Steve Furie, Karen L. Dichgans, Martin Rosand, Jonathan Markus, Hugh S. Rost, Natalia CA Int Stroke Genetics Consortium TI Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke SO NEUROLOGY LA English DT Article ID SMALL-VESSEL DISEASE; HEMORRHAGIC STROKE; GENETIC-VARIATION; ISCHEMIC-STROKE; ASSOCIATION; VOLUME; LEUKOARAIOSIS; COL4A1; MRI; HERITABILITY AB Objective:For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms.Methods:We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations.Results:There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 x 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 x 10(-8); rs941898 [EVL], p = 4.0 x 10(-8); rs962888 [C1QL1], p = 1.1 x 10(-8); rs9515201 [COL4A2], p = 6.9 x 10(-9)).Conclusions:Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease. C1 [Traylor, Matthew; Markus, Hugh S.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England. [Parsons, Owen E.] Univ Cambridge, Autism Res Ctr, Cambridge CB2 1TN, England. [Zhang, Cathy R.; Devan, William J.; Cloonan, Lisa; Falcone, Guido J.; Fitzpatrick, Kaitlin; Kanakis, Allison; Rost, Natalia] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Devan, William J.; Falcone, Guido J.; Radmanesh, Farid; Rosand, Jonathan; Rost, Natalia] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. [Adib-Samii, Poneh; Gregory, Sarah; Barrick, Thomas R.; Moynihan, Barry] Univ London, St Georges, Neurosci Res Ctr, London WC1E 7HU, England. [Lanfranconi, Silvia; Rosand, Jonathan] IRCCS Ca Granda Osped Maggiore Policlin, Neurol Unit, Milan, Italy. [Radmanesh, Farid] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Lewis, Cathryn M.] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. [Lewis, Cathryn M.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Boncoraglio, Giorgio B.] Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy. [Lemmens, Robin; Thijs, Vincent] Univ Leuven, KU Leuven, Dept Neurosci, Expt Neurol, Leuven, Belgium. [Lemmens, Robin; Thijs, Vincent] Leuven Res Inst Neurosci & Dis, Leuven, Belgium. [Lemmens, Robin; Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium. [Lemmens, Robin; Thijs, Vincent] VIB, Vesalius Res Ctr, Neurobiol Lab, Leuven, Belgium. [Thijs, Vincent] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Austin Hlth, Heidelberg, Vic, Australia. [Thijs, Vincent] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne Brain Ctr, Heidelberg, Vic, Australia. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Neuroimaging Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Wardlaw, Joanna] Univ Edinburgh, Ctr Clin Brain Sci, Neuroimaging Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Rothwell, Peter M.] Univ Oxford, Nuffield Dept Neurosci, Stroke Prevent Res Unit, Oxford OX1 2JD, England. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Levi, Christopher] Univ Newcastle, Hunter Med Res Inst, Ctr Clin Epidemiol & Biostat, Callaghan, NSW 2308, Australia. [Levi, Christopher] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Bevan, Steve] Lincoln Univ, Sch Life Sci, Lincoln, New Zealand. [Furie, Karen L.] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Dept Neurol, Providence, RI 02912 USA. [Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. RP Traylor, M (reprint author), Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England. EM mt628@medschl.cam.ac.uk RI Lee, Chaeyoung/C-7929-2012; Klijn, C.J.M. (Karin)/E-1700-2016; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; JIMENEZ-CONDE, JORDI/C-1941-2012; Falcone, Guido/L-2287-2016; LEYS, Didier/G-2955-2016; Lewis, Cathryn/A-5225-2010; Boncoraglio, Giorgio/B-8647-2011; Bijlenga, Philippe/S-1049-2016; Thijs, Vincent/C-3647-2009; Montaner, Joan/D-3063-2015 OI Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Lebedeva, Elena/0000-0003-2463-7113; Gwinn, Katrina/0000-0002-8277-651X; Olesen, Jes/0000-0002-6712-2702; Lee, Chaeyoung/0000-0002-2940-1778; Falcone, Guido/0000-0002-6407-0302; LEYS, Didier/0000-0003-4408-4392; Lewis, Cathryn/0000-0002-8249-8476; Bijlenga, Philippe/0000-0002-3586-2757; Thijs, Vincent/0000-0002-6614-8417; FU Wellcome Trust; Stroke Association [TSA 2013/01]; Intramural Research Program of National Institute of Ageing (Massachusetts General Hospital [MGH]); Intramural Research Program of National Institute of Ageing (Ischemic Stroke Genetics Study [ISGS]); National Institute of Neurological Disorders and Stroke (Siblings With Ischemic Stroke Study); National Institute of Neurological Disorders and Stroke (ISGS); National Institute of Neurological Disorders and Stroke (MGH); American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (MGH); Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (MGH); National Health and Medical Research Council (Australian Stroke Genetics Collaborative); Italian Ministry of Health (Milan); NIHR; NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre; FWO Flanders; MRC; National Institute for Health Research Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London; BRC for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London FX Funding for collection, genotyping, and analysis of stroke samples was provided by Wellcome Trust Case Control Consortium-2, a functional genomics grant from the Wellcome Trust (DNA-Lacunar), the Stroke Association (DNA-Lacunar), the Intramural Research Program of National Institute of Ageing (Massachusetts General Hospital [MGH] and Ischemic Stroke Genetics Study [ISGS]), National Institute of Neurological Disorders and Stroke (Siblings With Ischemic Stroke Study, ISGS, and MGH), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (MGH), Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (MGH), National Health and Medical Research Council (Australian Stroke Genetics Collaborative), and Italian Ministry of Health (Milan). Additional support for sample collection came from the Medical Research Council, National Institute of Health Research Biomedical Research Centre and Acute Vascular Imaging Centre (Oxford), Wellcome Trust and Binks Trust (Edinburgh), and Vascular Dementia Research Foundation (Munich). M.T. is supported by a project grant from the Stroke Association (TSA 2013/01). H.S.M. is supported by an NIHR Senior Investigator award. H.S.M. and S.B. are supported by the NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre. V.T. and R.L. are supported by grants from FWO Flanders. P.R. holds NIHR and Wellcome Trust Senior Investigator Awards. P.A.S. is supported by an MRC Fellowship. C.M.L.'s research is supported by the National Institute for Health Research Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London, and the BRC for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. NR 30 TC 4 Z9 4 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 12 PY 2016 VL 86 IS 2 BP 146 EP 153 DI 10.1212/WNL.0000000000002263 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DB4AJ UT WOS:000368454800008 PM 26674333 ER PT J AU Mehta, RH Shahian, DM Sheng, SB O'Brien, SM Edwards, FH Jacobs, JP Peterson, ED AF Mehta, Rajendra H. Shahian, David M. Sheng, Shubin O'Brien, Sean M. Edwards, Fred H. Jacobs, Jeffery P. Peterson, Eric D. TI Association of Hospital and Physician Characteristics and Care Processes With Racial Disparities in Procedural Outcomes Among Contemporary Patients Undergoing Coronary Artery Bypass Grafting Surgery SO CIRCULATION LA English DT Article DE coronary artery bypass; race and ethnicity; treatment outcome ID PERFORMANCE; MORTALITY; RACE; RACE/ETHNICITY; SOCIETY; ACCESS; IMPACT; VOLUME AB Background Previous studies have reported that black patients undergoing coronary artery bypass surgery had worse outcomes than white patients, even after accounting for patient factors. The degree to which clinician, hospital, and care factors account for these outcome differences remains unclear. Methods and Results We evaluated procedural outcomes in 11697 blacks and 136362 whites undergoing isolated coronary artery bypass surgery at 663 Society of Thoracic Surgery Database participating sites (January 1, 2010 to June 30, 2011) adjusted for patients' clinical and socioeconomic features, hospital and surgeon effects, and care processes (internal mammary artery graft and perioperative medications use). Relative to whites, blacks undergoing coronary artery bypass surgery were younger, yet had higher comorbidities and more adverse presenting features. Blacks were also more likely to be treated at hospitals with higher risk-adjusted mortality. The use of internal mammary artery was marginally lower in blacks than in whites (93.3% versus 92.2%, P<0.0001). Unadjusted mortality and major morbidity rates were higher in blacks than in whites (1.8% versus 2.5%, P<0.0001) and (13.6% versus 19.4%, P<0.0001), respectively. These racial differences in outcomes narrowed but still persisted after adjusting for surgeon, hospital, and care processes in addition to patient and socioeconomic factors (odds ratio, 1.17; 95% confidence interval, 1.00-1.36 and odds ratio, 1.26; 95% confidence interval, 1.19-1.34, respectively). Conclusions The risks of procedural mortality and morbidity after coronary artery bypass surgery were higher among black patients than among white patients. These differences were in part accounted for by patient comorbidities, socioeconomic status, and surgeon, hospital, and care factors, as well, as suggested by the reduction in the strength of the race-outcomes association. However, black race remained an independent predictor of outcomes even after accounting for these differences. C1 [Mehta, Rajendra H.; Sheng, Shubin; O'Brien, Sean M.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27715 USA. [Mehta, Rajendra H.; Sheng, Shubin; O'Brien, Sean M.; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC USA. [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Edwards, Fred H.] Soc Thorac Surg, Chicago, IL USA. [Jacobs, Jeffery P.] Johns Hopkins Univ, Baltimore, MD USA. RP Mehta, RH (reprint author), Duke Clin Res Inst, Box 17969, Durham, NC 27715 USA. EM raj.mehta@dm.duke.edu NR 28 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 12 PY 2016 VL 133 IS 2 BP 124 EP 130 DI 10.1161/CIRCULATIONAHA.115.015957 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DA6NV UT WOS:000367922700004 PM 26603032 ER PT J AU Dawes, AJ Maggard-Gibbons, M Maher, AR Booth, MJ Miake-Lye, I Beroes, JM Shekelle, PG AF Dawes, Aaron J. Maggard-Gibbons, Melinda Maher, Alicia R. Booth, Marika J. Miake-Lye, Isomi Beroes, Jessica M. Shekelle, Paul G. TI Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery A Meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMORBIDITY SURVEY REPLICATION; GASTRIC BYPASS-SURGERY; BINGE-EATING DISORDER; WEIGHT-LOSS; DEPRESSIVE SYMPTOMS; SYSTEMATIC REVIEWS; CONTROLLED-TRIAL; PREVALENCE; ASSOCIATION; CANDIDATES AB IMPORTANCE Bariatric surgery is associated with sustained weight loss and improved physical health status for severely obese individuals. Mental health conditions may be common among patients seeking bariatric surgery; however, the prevalence of these conditions and whether they are associated with postoperative outcomes remains unknown. OBJECTIVE To determine the prevalence of mental health conditions among bariatric surgery candidates and recipients, to evaluate the association between preoperative mental health conditions and health outcomes following bariatric surgery, and to evaluate the association between surgery and the clinical course of mental health conditions. DATA SOURCES We searched PubMed. MEDLINE on OVID, and PsycINFO for studies published between January 1988 and November 2015. Study quality was assessed using an adapted tool for risk of bias; quality of evidence was rated based on GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. FINDINGS We identified 68 publications meeting inclusion criteria: 59 reporting the prevalence of preoperative mental health conditions (65 363 patients) and 27 reporting associations between preoperative mental health conditions and postoperative outcomes (50182 patients). Among patients seeking and undergoing bariatric surgery, the most common mental health conditions, based on random-effects estimates of prevalence, were depression (19% [95% CI, 14%-25%]) and binge eating disorder (17% [95% CI, 13%-21%]). There was conflicting evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Neither depression nor binge eating disorder was consistently associated with differences in weight outcomes. Bariatric surgery was, however, consistently associated with postoperative decreases in the prevalence of depression (7 studies; 8%-74% decrease) and the severity of depressive symptoms (6 studies; 40%-70% decrease). CONCLUSIONS AND RELEVANCE Mental health conditions are common among bariatric surgery patients in particular, depression and binge eating disorder. There is inconsistent evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Moderate-quality evidence supports an association between bariatric surgery and lower rates of depression postoperatively. C1 [Dawes, Aaron J.; Maggard-Gibbons, Melinda] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Maggard-Gibbons, Melinda; Miake-Lye, Isomi; Beroes, Jessica M.; Shekelle, Paul G.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dawes, Aaron J.] Univ Calif Los Angeles, Vet Affairs RobertWood Johnson Clin Scholars Prog, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Miake-Lye, Isomi] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. [Maggard-Gibbons, Melinda; Maher, Alicia R.; Booth, Marika J.; Shekelle, Paul G.] RAND Corp, Southern Calif Evidence Based Practice Ctr, Santa Monica, CA USA. [Maher, Alicia R.] Akasha Ctr Integrat Med, Santa Monica, CA USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ronald Reagan UCLA Med Ctr, 757Westwood Plaza,B711, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU Department of Veterans Affairs; VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program FX The publication is based on a systematic review conducted by the Evidence-based Synthesis program funded by the Department of Veterans Affairs. Dr Dawes was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. NR 67 TC 13 Z9 14 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 12 PY 2016 VL 315 IS 2 BP 150 EP 163 DI 10.1001/jama.2015.18118 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA DA6XO UT WOS:000367949200017 PM 26757464 ER PT J AU Kunert, C Baish, JW Liao, S Padera, TP Munn, LL AF Kunert, Christian Baish, James W. Liao, Shan Padera, Timothy P. Munn, Lance L. TI REPLY TO DAVIS: Nitric oxide regulates lymphatic contractions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID VESSELS C1 [Kunert, Christian; Liao, Shan; Padera, Timothy P.; Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Kunert, Christian; Liao, Shan; Padera, Timothy P.; Munn, Lance L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Baish, James W.] Bucknell Univ, Biomed Engn & Mech Engn, Lewisburg, PA 17837 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM munn@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Padera, Timothy/0000-0002-3453-9384 FU NCI NIH HHS [P01 CA080124, R01 CA149285]; NHLBI NIH HHS [R01 HL128168]; NIH HHS [DP2 OD008780] NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 12 PY 2016 VL 113 IS 2 BP E106 EP E106 DI 10.1073/pnas.1522233113 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA5ZO UT WOS:000367881500002 PM 26719425 ER PT J AU Rashidian, M Wang, L Edens, JG Jacobsen, JT Hossain, I Wang, QF Victora, GD Vasdev, N Ploegh, H Liang, SH AF Rashidian, Mohammad Wang, Lu Edens, Jerre G. Jacobsen, Johanne T. Hossain, Intekhab Wang, Qifan Victora, Gabriel D. Vasdev, Neil Ploegh, Hidde Liang, Steven H. TI Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE enzymes; isotopic labeling; PEGylation; positron emission tomography; single-domain antibodies ID FRAGMENTS; CANCER; BIODISTRIBUTION; DIABODIES; THERAPY AB Antibodies are currently the fastest-growing class of therapeutics. Although naked antibodies have proven valuable as pharmaceutical agents, they have some limitations, such as low tissue penetration and a long circulatory half-life. They have been conjugated to toxic payloads, PEGs, or radioisotopes to increase and optimize their therapeutic efficacy. Although nonspecific conjugation is suitable for most in vitro applications, it has become evident that site specifically modified antibodies may have advantages for in vivo applications. Herein we describe a novel approach in which the antibody fragment is tagged with two handles: one for the introduction of a fluorophore or F-18 isotope, and the second for further modification of the fragment with a PEG moiety or a second antibody fragment to tune its circulatory half-life or its avidity. Such constructs, which recognize Class II MHC products and CD11b, showed high avidity and specificity. They were used to image cancers and could detect small tumors. C1 [Rashidian, Mohammad; Edens, Jerre G.; Jacobsen, Johanne T.; Hossain, Intekhab; Victora, Gabriel D.; Ploegh, Hidde] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Wang, Lu; Wang, Qifan; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Wang, Lu; Wang, Qifan; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Vasdev, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu; ploegh@wi.mit.edu; liang.steven@mgh.harvard.edu FU Cancer Research Institute; NIH Career Development Award; NIH [R01-AI087879-06, DP1-GM106409-03, R01-GM100518-04]; Lustgarten Foundation FX M.R. is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute. S.H.L. is the recipient of an NIH Career Development Award. This research was funded by NIH R01-AI087879-06 (to H.L.P.), DP1-GM106409-03 (an NIH Pioneer Award to H.L.P.), and R01-GM100518-04 (to H.L.P.), and by the Lustgarten Foundation (H.L.P.). NR 14 TC 3 Z9 3 U1 3 U2 17 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 JAN 11 PY 2016 VL 55 IS 2 BP 528 EP 533 DI 10.1002/anie.201507596 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA DA8PY UT WOS:000368069200008 PM 26630549 ER PT J AU Serresi, M Gargiulo, G Proost, N Siteur, B Cesaroni, M Koppens, M Xie, HF Sutherland, KD Hulsman, D Citterio, E Orkin, S Berns, A van Lohuizen, M AF Serresi, Michela Gargiulo, Gaetano Proost, Natalie Siteur, Bjorn Cesaroni, Matteo Koppens, Martijn Xie, Huafeng Sutherland, Kate D. Hulsman, Danielle Citterio, Elisabetta Orkin, Stuart Berns, Anton van Lohuizen, Maarten TI Polycomb Repressive Complex 2 Is a Barrier to KRAS-Driven Inflammation and Epithelial-Mesenchymal Transition in Non-Small-Cell Lung Cancer SO CANCER CELL LA English DT Article ID GROUP PROTEIN EZH2; K-RAS; METHYLTRANSFERASE EZH2; PANCREATIC-CANCER; SELF-RENEWAL; STEM-CELLS; TGF-BETA; IN-VIVO; ADENOCARCINOMA; SENESCENCE AB Polycomb repressive complexes (PRC) are frequently implicated in human cancer, acting either as oncogenes or tumor suppressors. Here, we show that PRC2 is a critical regulator of KRAS-driven non-small cell lung cancer progression. Modulation of PRC2 by either Ezh2 overexpression or Eed deletion enhances KRAS-driven adenomagenesis and inflammation, respectively. Eed-loss-driven inflammation leads to massive macrophage recruitment and marked decline in tissue function. Additional Trp53 inactivation activates a cell-autonomous epithelial-to-mesenchymal transition program leading to an invasive mucinous adenocarcinoma. A switch between methylated/acetylated chromatin underlies the tumor phenotypic evolution, prominently involving genes controlled by Hippo/Wnt signaling. Our observations in the mouse models were conserved in human cells. Importantly, PRC2 inactivation results in context-dependent phenotypic alterations, with implications for its therapeutic application. C1 [Serresi, Michela; Gargiulo, Gaetano; Proost, Natalie; Koppens, Martijn; Sutherland, Kate D.; Hulsman, Danielle; Citterio, Elisabetta; Berns, Anton; van Lohuizen, Maarten] Netherlands Canc Inst, Ctr Biomed Genet, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. [Siteur, Bjorn] Netherlands Canc Inst, Mouse Clin Intervent Unit, NL-1066 CX Amsterdam, Netherlands. [Cesaroni, Matteo] Temple Univ, Sch Med, Fels Inst, Philadelphia, PA 19140 USA. [Xie, Huafeng; Orkin, Stuart] Harvard Univ, Sch Med, Boston Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. [Xie, Huafeng; Orkin, Stuart] Harvard Univ, Sch Med, Boston Childrens Hosp, Harvard Stem Cell Inst,Div Hematol Oncol, Boston, MA 02115 USA. [van Lohuizen, Maarten] CGC Nl, NL-1066 CX Amsterdam, Netherlands. RP Gargiulo, G (reprint author), Netherlands Canc Inst, Ctr Biomed Genet, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. EM g.gargiulo@nki.nl; m.v.lohuizen@nki.nl OI Sutherland, Kate/0000-0002-7453-3366 FU European Union Marie Curie Actions; Fondazione Lorini; Dutch Cancer Society (KWF) [NKI 2013-61093, NKI 2014-7208]; Netherlands Organization for Scientific Research (NWO) FX We are grateful to M. Melis for Luminex experiments and I. de Rink for help with sequencing data. We thank J.-Y. Song for pathology; E. Tanger, M. Cozijnsen, and NKI Genomics Core, Microscopy, FACS, and Animal Pathology and Animal Facilities for technical assistance; and C. Creasy (GSK) for the GSK126 compound. We also thank F. Scheeren and E. Guccione, for critically reading the manuscript, M. Ogrunc and A. Gruszka for manuscript proofreading, and A. Sparmann for advice. This work was supported by grants from the European Union Marie Curie Actions (G.G.), the Fondazione Lorini (G.G.), the Dutch Cancer Society (KWF; NKI 2013-61093 and NKI 2014-7208; G.G. and M.v.L.) and the Netherlands Organization for Scientific Research (NWO) to Cancer Genomics Netherlands (CGC.nl; M.v.L.). This work is dedicated to the memory of M.S.'s father, Luigi Serresi. NR 55 TC 17 Z9 17 U1 13 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD JAN 11 PY 2016 VL 29 IS 1 BP 17 EP 31 DI 10.1016/j.ccell.2015.12.006 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DA9HB UT WOS:000368118500004 PM 26766588 ER PT J AU Soragni, A Janzen, DM Johnson, LM Lindgren, AG Nguyen, ATQ Tiourin, E Soriaga, AB Lu, J Jiang, L Faull, KF Pellegrini, M Memarzadeh, S Eisenberg, DS AF Soragni, Alice Janzen, Deanna M. Johnson, Lisa M. Lindgren, Anne G. Anh Thai-Quynh Nguyen Tiourin, Ekaterina Soriaga, Angela B. Lu, Jing Jiang, Lin Faull, Kym F. Pellegrini, Matteo Memarzadeh, Sanaz Eisenberg, David S. TI A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas SO CANCER CELL LA English DT Article ID MUTANT P53; CANCER-CELLS; IN-VIVO; SV40-TRANSFORMED CELLS; MEVALONATE PATHWAY; AMYLOID FORMATION; GENE-EXPRESSION; REACTIVATION; APOPTOSIS; PROTEINS AB Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs. C1 [Soragni, Alice; Johnson, Lisa M.; Anh Thai-Quynh Nguyen; Soriaga, Angela B.; Jiang, Lin; Eisenberg, David S.] Univ Calif Los Angeles, DOE Inst, HHMI, Dept Biol Chem, Los Angeles, CA 90095 USA. [Soragni, Alice; Johnson, Lisa M.; Anh Thai-Quynh Nguyen; Soriaga, Angela B.; Jiang, Lin; Eisenberg, David S.] Univ Calif Los Angeles, DOE Inst, HHMI, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Janzen, Deanna M.; Lindgren, Anne G.; Tiourin, Ekaterina; Memarzadeh, Sanaz] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Lu, Jing; Pellegrini, Matteo] Univ Calif Los Angeles, Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. [Faull, Kym F.] Semel Inst, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA. [Memarzadeh, Sanaz] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA. [Memarzadeh, Sanaz] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Eisenberg, DS (reprint author), Univ Calif Los Angeles, DOE Inst, HHMI, Dept Biol Chem, 611 South Charles E Young Dr, Los Angeles, CA 90095 USA. EM smemarzadeh@mednet.ucla.edu; david@mbi.ucla.edu OI Soragni, Alice/0000-0002-6634-2885 FU NIH [1S10RR023718-01A2, AG-029430, R01CA183877]; Pardee Foundation; NIH/National Center for Advancing Translational Science UCLA CTSI Grant [UL1TR000124]; American Cancer Society [RSG-14-217-01-TBG]; National Science Foundation [MCB 0958111]; Jonsson Cancer Center Foundation/UCLA; Lynne Cohen Foundation; Phase One Foundation; Ovarian Cancer Circle; Leath L. and Marcia L. Millen Family Fund; G.O. Discovery Lab Foundation; HHMI; VA CDA-2 award [1 K12 BX 001305-01] FX We thank Dr. Gregory Lawson for assisting with histological examination of tissues and Dr. Jiaoti Huang for sharing the lentiviral GFP/R175H p53 construct; Dr. Stuart Sievers and Jung-Reem Woo for support with the initial p53 structural characterization; Marco Morselli, Arturo Rinaldi and Dr. Ludmilla Rubbi for help with preparation of the libraries; Dr. Hans-Uwe Simon for helpful discussions. We acknowledge the support of Austin Quach and Farbod Fazlollahi with the MRM assay; the Pasarow Mass Spectrometry Laboratory is supported by NIH grant 1S10RR023718-01A2. This work was supported by grants from the Pardee Foundation (to A.S.), the NIH (AG-029430 to D.S.E; R01CA183877 to S.M.), the NIH/National Center for Advancing Translational Science UCLA CTSI Grant UL1TR000124 (to A.S. and D.S.E.), the American Cancer Society (RSG-14-217-01-TBG to S.M.), the National Science Foundation (MCB 0958111, to D.S.E.), the Jonsson Cancer Center Foundation/UCLA (to S.M. and D.S.E.); the Lynne Cohen Foundation, the Phase One Foundation, the Ovarian Cancer Circle Inspired by Robin Babbini, the Leath L. and Marcia L. Millen Family Fund and the G.O. Discovery Lab Foundation (to S.M.), the HHMI (to D.S.E.) and in part by a VA CDA-2 award (1 K12 BX 001305-01 to S.M.). A.S., L.J. and D.S.E. are inventors on a patent application based on ReACp53 (WO2014182961 A1). A.S. is a consultant for ADRx, Inc.; D.S.E. is a founder, head of the scientific advisory board and equity holder of ADRx, Inc. NR 56 TC 28 Z9 28 U1 10 U2 33 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD JAN 11 PY 2016 VL 29 IS 1 BP 90 EP 103 DI 10.1016/j.ccell.2015.12.002 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DA9HB UT WOS:000368118500009 PM 26748848 ER PT J AU Robertson, CE Ratai, EM Kanwisher, N AF Robertson, Caroline E. Ratai, Eva-Maria Kanwisher, Nancy TI Reduced GABAergic Action in the Autistic Brain SO CURRENT BIOLOGY LA English DT Article ID BINOCULAR-RIVALRY; IN-VIVO; SPECTRUM DISORDERS; VISUAL-CORTEX; GABA CONCENTRATION; INHIBITION; PERCEPTION; DYNAMICS; MODEL; EXCITATION/INHIBITION AB An imbalance between excitatory/inhibitory neuro-transmission has been posited as a central characteristic of the neurobiology of autism [1], inspired in part by the striking prevalence of seizures among individuals with the disorder [2]. Evidence supporting this hypothesis has specifically implicated the signaling pathway of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), in this putative imbalance: GABA receptor genes have been associated with autism in linkage and copy number variation studies [3-7], fewer GABA receptor subunits have been observed in the post-mortem tissue of autistic individuals [8, 9], and GABAergic signaling is disrupted across heterogeneous mouse models of autism [10]. Yet, empirical evidence supporting this hypothesis in humans is lacking, leaving a gulf between animal and human studies of the condition. Here, we present a direct link between GABA signaling and autistic perceptual symptomatology. We first demonstrate a robust, replicated autistic deficit in binocular rivalry [11], a basic visual function that is thought to rely on the balance of excitation/inhibition in visual cortex [12-15]. Then, using magnetic resonance spectroscopy, we demonstrate a tight linkage between binocular rivalry dynamics in typical participants and both GABA and glutamate levels in the visual cortex. Finally, we show that the link between GABA and binocular rivalry dynamics is completely and specifically absent in autism. These results suggest a disruption in inhibitory signaling in the autistic brain and forge a translational path between animal and human models of the condition. C1 [Robertson, Caroline E.] Harvard Univ, Harvard Soc Fellows, Cambridge, MA 02138 USA. [Robertson, Caroline E.; Kanwisher, Nancy] MIT, McGovern Inst Brain Res, Cambridge, MA 02138 USA. [Ratai, Eva-Maria] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Robertson, CE (reprint author), Harvard Univ, Harvard Soc Fellows, Cambridge, MA 02138 USA. EM carolinerobertson@fas.harvard.edu FU Harvard Milton Fund award; NARSAD Young Investigator award; MIT-MGH Strategic Partnership grant; Simons Center for the Social Brain FX We thank A.J. Haskins for help with recruitment and project management; S. Raja, A. Mynick, and K. Hermann for help with data collection and analysis; and A. Takahashi, R. Edden, C. Said, D. Heeger, M. Bear, A. Martin, C. Chow, S. Vattikuti, J. Freyberg, S. Baron-Cohen, D. Kravitz, and C.I. Baker for helpful discussion. This work was funded by a Harvard Milton Fund award (C.E.R.), a NARSAD Young Investigator award (C.E.R.), an MIT-MGH Strategic Partnership grant (C.E.R., E.-M.R., N.K.), and a grant from the Simons Center for the Social Brain (C.E.R. and N.K.). NR 48 TC 14 Z9 14 U1 12 U2 30 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD JAN 11 PY 2016 VL 26 IS 1 BP 80 EP 85 DI 10.1016/j.cub.2015.11.019 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DB2EM UT WOS:000368321100025 PM 26711497 ER PT J AU Huang, JL Liu, X Li, D Shao, Z Cao, H Zhang, YY Trompouki, E Bowman, TV Zon, LI Yuan, GC Orkin, SH Xu, J AF Huang, Jialiang Liu, Xin Li, Dan Shao, Zhen Cao, Hui Zhang, Yuannyu Trompouki, Eirini Bowman, Teresa V. Zon, Leonard I. Yuan, Guo-Cheng Orkin, Stuart H. Xu, Jian TI Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis SO DEVELOPMENTAL CELL LA English DT Article ID GENOME-WIDE ANALYSIS; SUPER-ENHANCERS; GENE-EXPRESSION; HISTONE MODIFICATIONS; INTERACTION NETWORKS; ERYTHROID-CELLS; REGULATORS; STEM; BCL11A; ERYTHROPOIESIS AB Enhancers are the primary determinants of cell identity, but the regulatory components controlling enhancer turnover during lineage commitment remain largely unknown. Here we compare the enhancer landscape, transcriptional factor occupancy, and transcriptomic changes in human fetal and adult hematopoietic stem/progenitor cells and committed erythroid progenitors. We find that enhancers are modulated pervasively and direct lineage-and stage-specific transcription. GATA2-to-GATA1 switch is prevalent at dynamic enhancers and drives erythroid enhancer commissioning. Examination of lineage-specific enhancers identifies transcription factors and their combinatorial patterns in enhancer turnover. Importantly, by CRISPR/Cas9-mediated genomic editing, we uncover functional hierarchy of constituent enhancers within the SLC25A37 super-enhancer. Despite indistinguishable chromatin features, we reveal through genomic editing the functional diversity of several GATA switch enhancers in which enhancers with opposing functions cooperate to coordinate transcription. Thus, genome-wide enhancer profiling coupled with in situ enhancer editing provide critical insights into the functional complexity of enhancers during development. C1 [Liu, Xin; Cao, Hui; Zhang, Yuannyu; Xu, Jian] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr, Res Inst, Dept Pediat, Dallas, TX 75390 USA. [Huang, Jialiang; Trompouki, Eirini; Bowman, Teresa V.; Zon, Leonard I.; Orkin, Stuart H.] Harvard Univ, Boston Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. [Huang, Jialiang; Trompouki, Eirini; Bowman, Teresa V.; Zon, Leonard I.; Orkin, Stuart H.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. [Huang, Jialiang; Yuan, Guo-Cheng] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Dan] Harvard Univ, Cambridge, MA 02138 USA. [Shao, Zhen; Zhang, Yuannyu] Chinese Acad Sci, Shanghai Inst Biol Sci, MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai 200031, Peoples R China. [Zon, Leonard I.; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu; jian.xu@utsouthwestern.edu FU NIH/NHLBI [R01HL119099]; NIH/NIDDK [K01DK093543, R03DK101665]; Cancer Prevention and Research Institute of Texas (CPRIT) New Investigator Award [RR140025]; American Cancer Society [IRG-02-196]; Harold C. Simmons Comprehensive Cancer Center at UT Southwestern; American Society of Hematology Scholar Award FX We thank Matthew Canver, Daniel Bauer, Luca Pinello, and members of the Orkin laboratory for assistance and discussion, John Stamatoyannopoulos for assistance with DNase-seq, and Ben van Handel and Hanna Mikkola for providing the fetal CD34+ cells. This work was supported by NIH/NHLBI grant R01HL119099 (to G.C.Y and S.H.O.). L.I.Z and S.H.O. are Investigators of the Howard Hughes Medical Institute (HHMI). This work was also supported by NIH/NIDDK grants K01DK093543 and R03DK101665, by a Cancer Prevention and Research Institute of Texas (CPRIT) New Investigator Award (RR140025), by the American Cancer Society (IRG-02-196) award and the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, and by an American Society of Hematology Scholar Award (to J.X.). NR 56 TC 11 Z9 11 U1 3 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD JAN 11 PY 2016 VL 36 IS 1 BP 9 EP 23 DI 10.1016/j.devcel.2015.12.014 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA DA9ET UT WOS:000368112000005 PM 26766440 ER PT J AU Kim, M Besner, S Ramier, A Kwok, SJJ An, J Scarcelli, G Yun, SH AF Kim, Moonseok Besner, Sebastien Ramier, Antoine Kwok, Sheldon J. J. An, Jeesoo Scarcelli, Giuliano Yun, Seok Hyun TI Shear Brillouin light scattering microscope SO OPTICS EXPRESS LA English DT Article ID OPTICAL MICROSCOPY; HIGH-PRESSURE; FUSED QUARTZ; SPECTROSCOPY; GLASSES; POLYCARBONATE; RESOLUTION; SILICA; WAVES; LENS AB Brillouin spectroscopy has been used to characterize shear acoustic phonons in materials. However, conventional instruments had slow acquisition times over 10 min per 1 mW of input optical power, and they required two objective lenses to form a 90 degrees scattering geometry necessary for polarization coupling by shear phonons. Here, we demonstrate a confocal Brillouin microscope capable of detecting both shear and longitudinal phonons with improved speeds and with a single objective lens. Brillouin scattering spectra were measured from polycarbonate, fused quartz, and borosilicate in 1-10 s at an optical power level of 10 mW. The elastic constants, phonon mean free path and the ratio of the Pockels coefficients were determined at microscopic resolution. (C) 2016 Optical Society of America C1 [Kim, Moonseok; Besner, Sebastien; Ramier, Antoine; Kwok, Sheldon J. J.; An, Jeesoo; Scarcelli, Giuliano; Yun, Seok Hyun] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Kim, Moonseok; Besner, Sebastien; Ramier, Antoine; Kwok, Sheldon J. J.; An, Jeesoo; Scarcelli, Giuliano; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Kim, Moonseok] Korea Univ, Dept Phys, Seoul 136701, South Korea. [Ramier, Antoine; Kwok, Sheldon J. J.; Yun, Seok Hyun] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Scarcelli, Giuliano] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02139 USA. EM syun@mgh.harvard.edu FU U.S. National Institutes of Health [R01-EY025454, P41-EB015903, UL1-RR025758, R21EY023043, K25EB015885]; National Science Foundation [CBET-1264356]; National Research Foundation of Korea [2013R1A1A2062808] FX This research was supported by U.S. National Institutes of Health (R01-EY025454, P41-EB015903, UL1-RR025758, R21EY023043, K25EB015885), National Science Foundation (CBET-1264356), and the National Research Foundation of Korea (2013R1A1A2062808). NR 32 TC 2 Z9 2 U1 8 U2 20 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JAN 11 PY 2016 VL 24 IS 1 BP 319 EP 328 DI 10.1364/OE.24.000319 PG 10 WC Optics SC Optics GA DA7SQ UT WOS:000368004800032 PM 26832263 ER PT J AU Lynch, SM Peek, MK Mitra, N Ravichandran, K Branas, C Spangler, E Zhou, WT Paskett, ED Gehlert, S DeGraffinreid, C Rebbeck, TR Riethman, H AF Lynch, Shannon M. Peek, M. K. Mitra, Nandita Ravichandran, Krithika Branas, Charles Spangler, Elaine Zhou, Wenting Paskett, Electra D. Gehlert, Sarah DeGraffinreid, Cecilia Rebbeck, Timothy R. Riethman, Harold TI Race, Ethnicity, Psychosocial Factors, and Telomere Length in a Multicenter Setting SO PLOS ONE LA English DT Article ID PSYCHOLOGICAL STRESS; POPULATION HEALTH; PERCEIVED STRESS; CANCER; ASSOCIATION; CELLS; WOMEN; DISCRIMINATION; INSTABILITY; VARIANTS AB Background Leukocyte telomere length(LTL) has been associated with age, self-reported race/ethnicity, gender, education, and psychosocial factors, including perceived stress, and depression. However, inconsistencies in associations of LTL with disease and other phenotypes exist across studies. Population characteristics, including race/ethnicity, laboratory methods, and statistical approaches in LTL have not been comprehensively studied and could explain inconsistent LTL associations. Methods LTL was measured using Southern Blot in 1510 participants from a multi-ethnic, multi-center study combining data from 3 centers with different population characteristics and laboratory processing methods. Main associations between LTL and psychosocial factors and LTL and race/ethnicity were evaluated and then compared across generalized estimating equations(GEE) and linear regression models. Statistical models were adjusted for factors typically associated with LTL(age, gender, cancer status) and also accounted for factors related to center differences, including laboratory methods(i.e., DNA extraction). Associations between LTL and psychosocial factors were also evaluated within race/ethnicity subgroups (Non-hispanic Whites, African Americans, and Hispanics). Results Beyond adjustment for age, gender, and cancer status, additional adjustments for DNA extraction and clustering by center were needed given their effects on LTL measurements. In adjusted GEE models, longer LTL was associated with African American race (Beta(beta) (standard error(SE)) = 0.09(0.04), p-value = 0.04) and Hispanic ethnicity (beta(SE) = 0.06 (0.01), p-value = 0.02) compared to Non-Hispanic Whites. Longer LTL was also associated with less than a high school education compared to having greater than a high school education (a(SE) = 0.06(0.02), p-value = 0.04). LTL was inversely related to perceived stress (a (SE) = -0.02(0.003), p < 0.001). In subgroup analyses, there was a negative association with LTL in African Americans with a high school education versus those with greater than a high school education(beta(SE) = -0.11(0.03), p-value < 0.001). Conclusions Laboratory methods and population characteristics that differ by center can influence telomere length associations in multicenter settings, but these effects could be addressed through statistical adjustments. Proper evaluation of potential sources of bias can allow for combined multicenter analyses and may resolve some inconsistencies in reporting of LTL associations. Further, biologic effects on LTL may differ under certain psychosocial and racial/ethnic circumstances and could impact future health disparity studies. C1 [Lynch, Shannon M.; Mitra, Nandita; Branas, Charles; Spangler, Elaine; Zhou, Wenting; Rebbeck, Timothy R.] Univ Penn, Philadelphia, PA 19104 USA. [Lynch, Shannon M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Peek, M. K.; Riethman, Harold] Univ Texas Med Branch, Galveston, TX 77555 USA. [Ravichandran, Krithika] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Paskett, Electra D.; DeGraffinreid, Cecilia] Ohio State Univ, Columbus, OH 43210 USA. [Gehlert, Sarah] Washington Univ, St Louis, MO USA. [Rebbeck, Timothy R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rebbeck, Timothy R.] Harvard Univ, Boston, MA 02115 USA. [Riethman, Harold] Old Dominion Univ, Norfolk, VA USA. RP Lynch, SM (reprint author), Univ Penn, Philadelphia, PA 19104 USA. EM shannon.lynch@fccc.edu FU National Institutes of Health [P50-CA105641, P60-NM006900, R01-CA85074, F31-AG039986] FX This work was supported by the National Institutes of Health [P50-CA105641, P60-NM006900 and R01-CA85074; www.cancer.gov] to TRR and F31-AG039986 to SML[www.nia.nih.gov]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 3 Z9 3 U1 4 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 11 PY 2016 VL 11 IS 1 AR e0146723 DI 10.1371/journal.pone.0146723 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA6CA UT WOS:000367888100140 PM 26752285 ER PT J AU Parikh, RV Ma, YF Scherzer, R Heringer, AS Macgregor, JS Martin, JN Deeks, SG Ganz, P Hsue, PY AF Parikh, Rushi V. Ma, Yifei Scherzer, Rebecca Heringer, Amanda S. Macgregor, John S. Martin, Jeffrey N. Deeks, Steven G. Ganz, Peter Hsue, Priscilla Y. TI Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection SO PLOS ONE LA English DT Article ID ASYMMETRIC DIMETHYLARGININE; DOPPLER-ECHOCARDIOGRAPHY; AMBRISENTAN THERAPY; PROGNOSTIC-FACTORS; PLASMA-LEVELS; BOSENTAN; DISEASE; ERA; PATHOGENESIS; INDIVIDUALS AB Background HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described. Methods We measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP >= 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH. Results Among 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP >= 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses. Conclusions Higher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH. C1 [Parikh, Rushi V.] Stanford Univ, Dept Cardiovasc Med, Stanford, CA 94305 USA. [Ma, Yifei] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Scherzer, Rebecca] San Francisco VA Med Ctr, Div Endocrinol & Metab, San Francisco, CA USA. [Heringer, Amanda S.; Macgregor, John S.; Ganz, Peter; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94117 USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Deeks, Steven G.] Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA USA. RP Hsue, PY (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94117 USA. EM priscilla.hsue@ucsf.edu FU National Institutes of Health [R01HL095130, R01HL095126, K24AI112393] FX The study received National Institutes of Health grant support from R01HL095130 (PYH), R01HL095126 (PYH), K24AI112393 (PYH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 0 Z9 0 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 11 PY 2016 VL 11 IS 1 AR e0146355 DI 10.1371/journal.pone.0146355 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA6CA UT WOS:000367888100069 PM 26752193 ER PT J AU Edlow, BL Copen, WA Izzy, S Bakhadirov, K van der Kouwe, A Glenn, MB Greenberg, SM Greer, DM Wu, O AF Edlow, Brian L. Copen, William A. Izzy, Saef Bakhadirov, Khamid van der Kouwe, Andre Glenn, Mel B. Greenberg, Steven M. Greer, David M. Wu, Ona TI Diffusion tensor imaging in acute-to-subacute traumatic brain injury: a longitudinal analysis SO BMC NEUROLOGY LA English DT Article DE Traumatic axonal injury (TAI); Fractional anisotropy (FA); Corpus callosum; Disability rating scale (DRS) ID WHITE-MATTER INJURY; AXONAL INJURY; HEAD-INJURY; OUTCOME PREDICTION; MRI; BIOMARKERS; ANISOTROPY; COMA; SPECTROSCOPY; TRACTOGRAPHY AB Background: Diffusion tensor imaging (DTI) may have prognostic utility in patients with traumatic brain injury (TBI), but the optimal timing of DTI data acquisition is unknown because of dynamic changes in white matter water diffusion during the acute and subacute stages of TBI. We aimed to characterize the direction and magnitude of early longitudinal changes in white matter fractional anisotropy (FA) and to determine whether acute or subacute FA values correlate more reliably with functional outcomes after TBI. Methods: From a prospective TBI outcomes database, 11 patients who underwent acute (<= 7 days) and subacute (8 days to rehabilitation discharge) DTI were retrospectively analyzed. Longitudinal changes in FA were measured in 11 white matter regions susceptible to traumatic axonal injury. Correlations were assessed between acute FA, subacute FA and the disability rating scale (DRS) score, which was ascertained at discharge from inpatient rehabilitation. Results: FA declined from the acute-to-subacute period in the genu of the corpus callosum (0.70 +/- 0.02 vs. 0.55 +/- 0.11, p < 0.05) and inferior longitudinal fasciculus (0.54+/-0.07 vs. 0.49+/-0.07, p < 0.01). Acute correlations between FA and DRS score were variable: higher FA in the body (R = -0.78, p = 0.02) and splenium (R = -0.83, p = 0.003) of the corpus callosum was associated with better outcomes (i.e. lower DRS scores), whereas higher FA in the genu of the corpus callosum (R = 0.83, p = 0.02) corresponded with worse outcomes (i.e. higher DRS scores). In contrast, in the subacute period higher FA in the splenium correlated with better outcomes (R = -0.63, p < 0.05) and no inverse correlations were observed. Conclusions: White matter FA declined during the acute-to-subacute stages of TBI. Variability in acute FA correlations with outcome suggests that the optimal timing of DTI for TBI prognostication may be in the subacute period. C1 [Edlow, Brian L.; Izzy, Saef; Bakhadirov, Khamid; Greenberg, Steven M.; Greer, David M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Copen, William A.; Wu, Ona] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Edlow, Brian L.; van der Kouwe, Andre; Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Glenn, Mel B.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, Yale New Haven Hosp, New Haven, CT 06510 USA. RP Edlow, BL (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM bedlow@mgh.harvard.edu FU National Institutes of Health [R25NS065743, K23NS094538, R01NS059775, P41EB015896]; American Academy of Neurology/American Brain Foundation; National Institute on Disability and Rehabilitation Research, U.S. Department of Education [H133A020513] FX This study was supported by the National Institutes of Health (R25NS065743, K23NS094538, R01NS059775, and P41EB015896), the American Academy of Neurology/American Brain Foundation, and the National Institute on Disability and Rehabilitation Research, U.S. Department of Education (H133A020513). NR 49 TC 1 Z9 1 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD JAN 11 PY 2016 VL 16 AR 2 DI 10.1186/s12883-015-0525-8 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA DA4SU UT WOS:000367791600001 PM 26754948 ER PT J AU Christopoulos, G Kandzari, DE Yeh, RW Jaffer, FA Karmpaliotis, D Wyman, MR Alaswad, K Lombardi, W Grantham, JA Moses, J Christakopoulos, G Rangan, BV Lembo, N Garcia, S Cipher, D Thompson, CA Banerjee, S Brilakis, ES AF Christopoulos, Georgios Kandzari, David E. Yeh, Robert W. Jaffer, Farouc A. Karmpaliotis, Dimitri Wyman, Michael R. Alaswad, Khaldoon Lombardi, William Grantham, J. Aaron Moses, Jeffrey Christakopoulos, Georgios Rangan, Bavana V. Lembo, Nicholas Garcia, Santiago Cipher, Daisha Thompson, Craig A. Banerjee, Subhash Brilakis, Emmanouil S. TI Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic Total Occlusion Percutaneous Coronary Interventions The PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) Score SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE chronic total occlusion; percutaneous coronary intervention; scoring; technical success ID MULTICENTER US REGISTRY; BYPASS GRAFT-SURGERY; PROCEDURAL OUTCOMES; RETROGRADE APPROACH; ANGIOGRAPHIC SUCCESS; CROSSING CORONARY; HYBRID APPROACH; UNITED-STATES; INSIGHTS; RECANALIZATION AB OBJECTIVES This study sought to develop a novel parsimonious score for predicting technical success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) performed using the hybrid approach. BACKGROUND Predicting technical success of CTO PCI can facilitate clinical decision making and procedural planning. METHODS We analyzed clinical and angiographic parameters from 781 CTO PCIs included in PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) using a derivation and validation cohort (2: 1 sampling ratio). Variables with strong association with technical success in multivariable analysis were assigned 1 point, and a 4-point score was developed from summing all points. The PROGRESS CTO score was subsequently compared with the J-CTO (Multicenter Chronic Total Occlusion Registry in Japan) score in the validation cohort. RESULTS Technical success was 92.9%. On multivariable analysis, factors associated with technical success included proximal cap ambiguity (beta coefficient [b] = 0.88), moderate/severe tortuosity (b = 1.18), circumflex artery CTO (b = 0.99), and absence of "interventional" collaterals (b = 0.88). The resulting score demonstrated good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow chi-square = 2.633; p = 0.268, and receiver-operator characteristic [ROC] area = 0.778) and validation (Hosmer-Lemeshow chi-square = 5.333; p = 0.070, and ROC area = 0.720) subset. In the validation cohort, the PROGRESS CTO and J-CTO scores performed similarly in predicting technical success (ROC area 0.720 vs. 0.746, area under the curve difference = 0.026, 95% confidence interval = -0.093 to 0.144). CONCLUSIONS The PROGRESS CTO score is a novel useful tool for estimating technical success in CTO PCI performed using the hybrid approach. (J Am Coll Cardiol Intv 2016; 9: 1-9) (C) 2016 by the American College of Cardiology Foundation. C1 [Christopoulos, Georgios; Christakopoulos, Georgios; Garcia, Santiago; Cipher, Daisha; Thompson, Craig A.; Banerjee, Subhash] Univ Texas SW Med Ctr Dallas, VA North Texas Hlth Care Syst, Dallas, TX 75390 USA. [Kandzari, David E.; Lembo, Nicholas] Piedmont Heart Inst, Atlanta, GA USA. [Yeh, Robert W.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karmpaliotis, Dimitri; Moses, Jeffrey] Columbia Univ, New York, NY USA. [Wyman, Michael R.] Torrance Mem Med Ctr, Torrance, CA USA. [Alaswad, Khaldoon] Appleton Med Ctr, Appleton, WI USA. [Lombardi, William] Univ Washington, Seattle, WA 98195 USA. [Grantham, J. Aaron] Mid Amer Heart Inst, Kansas City, MO USA. [Garcia, Santiago] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Cipher, Daisha] Univ Texas Arlington, Coll Hlth Innovat, Arlington, TX 76019 USA. [Thompson, Craig A.] Boston Sci, Natick, MA USA. RP Brilakis, ES (reprint author), Dallas VA Med Ctr 111A, 4500 South Lancaster Rd, Dallas, TX 75216 USA. EM esbrilakis@gmail.com FU National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR001105]; Abbott; Boston Scientific; Medtronic Cardiovascular; National Heart, Lung, and Blood Institute [1K23HL118138]; Harvard Clinical Research Institute; Abbott Vascular; National Institutes of Health [HL-R01-108229]; Siemens; Kowa; Asahi; Terumo; Asahi Intecc; Abbott Laboratories; Medtronic; Infraredx; Spectranetics Corporation; Surmodics; Gilead; Medicines Company FX Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Kandzari has received consulting honoraria from Boston Scientific and Medtronic Cardiovascular; and has received research/grant support from Abbott, Boston Scientific, and Medtronic Cardiovascular. Dr. Yeh has received a Career Development Award (1K23HL118138) from the National Heart, Lung, and Blood Institute; has served as a consultant for Abbott Vascular, Gilead Sciences, and Boston Scientific; has served on the advisory board of Abbott Vascular; and receives salary support from Harvard Clinical Research Institute. Dr. Jaffer has served as a consultant to Boston Scientific, Siemens, and Merck; has received nonfinancial research support from Abbott Vascular; and has received research grants from the National Institutes of Health (HL-R01-108229), Siemens, and Kowa. Dr. Karmpaliotis has served on the Speakers Bureau for Abbott Vascular, Boston Scientific, and Medtronic; and has served as a consultant to Bridgepoint Medical. Dr. Wyman has received honoraria/consulting/speaking fees from Boston Scientific, Abbott Vascular, and Asahi. Dr. Alaswad has received consulting fees from Terumo, Asahi Intecc, and Boston Scientific; and has served as a consultant without financial support from Abbott Laboratories. Dr. Lombardi has equity with Bridgepoint Medical; and has served as a consultant to Boston Scientific, Abiomed, and Abbott Vascular. Dr. Grantham has received speaking fees, consulting fees, and honoraria from Boston Scientific, Abbott Vascular, and Asahi Intecc; has received research grants from Boston Scientific, Asahi Intecc, Abbott Vascular, and Medtronic; is a member of the Boston Scientific Executive Physician Leadership Committee; is on the advisory board for BSCI; and is on the CTO advisory board for Abbott Vascular. Dr. Moses has served as a consultant to Boston Scientific and Abbott Vascular. Dr. Rangan has received research grants from Infraredx and The Spectranetics Corporation. Dr. Lembo has served on the Speakers Bureau for Abbott Vascular, Boston Scientific, and Medtronic; and has served on the advisory board for Abbott Vascular and Medtronic. Dr. Garcia has received consulting fees from Medtronic and Surmodics. Dr. Thompson is an employee of Boston Scientific. Dr. Banerjee has received research grants from Gilead and the Medicines Company; has received consultant/speaker honoraria from Covidien, Medtronic, and Merck; has ownership in MDCARE Global and received an educational grant from Boston Scientific (both spouse); and has intellectual property in HygeiaTel. Dr. Brilakis has received consulting/speaker honoraria from Abbott Vascular, Asahi, Boston Scientific, Elsevier, Somahlution, St. Jude Medical, and Terumo; has received research support from Boston Scientific and Infraredx; and his spouse is an employee of Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 33 TC 20 Z9 20 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JAN 11 PY 2016 VL 9 IS 1 BP 1 EP 9 DI 10.1016/j.jcin.2015.09.022 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA3CE UT WOS:000367672700006 PM 26762904 ER PT J AU Albiges, L Mckay, RR Lin, X de Velasco, G Simantov, R Choueiri, TK AF Albiges, Laurence Mckay, Rana R. Lin, Xun de Velasco, Guillermo Simantov, Ronit Choueiri, Toni K. TI The impact of weight change during treatment with targeted therapy in patients with metastatic renal cell carcinoma (mRCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Oncol, La Jolla, CA USA. Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain. Pfizer Oncol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 557 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100550 ER PT J AU Anscher, MS Chang, MG Moghanaki, D Rosu, M Mikkelsen, R Holdford, D Skinner, V Grob, BM Sanyal, AJ Mukhopadhyay, N AF Anscher, Mitchell Steven Chang, Michael G. Moghanaki, Drew Rosu, Mihaela Mikkelsen, Ross Holdford, Diane Skinner, Vicki Grob, B. Mayer Sanyal, Arun J. Mukhopadhyay, Nitai TI Phase II study of lovastatin to prevent rectal injury from radiation therapy for prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. Hunter Holmes McGuire Vet Adm Med Ctr, Richmond, VA USA. US Dept Vet Affairs, Richmond, VA USA. McGuire Vet Affairs Med Ctr, Richmond, VA USA. Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 120 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100120 ER PT J AU Baumann, BC Bosch, W Bahl, A Birtle, AJ Breau, RH Challapalli, A Chang, A Choudhury, A Daneshmand, S Feldman, AS Guzzo, TJ Hilman, S Jani, AB Malkowicz, SB Master, VA Mitra, A Porten, SP Efstathiou, JA Eapen, L Christodouleas, JP AF Baumann, Brian C. Bosch, Walter Bahl, Amit Birtle, Alison J. Breau, Rodney H. Challapalli, Amarnath Chang, Albert Choudhury, Ananya Daneshmand, Siamak Feldman, Adam S. Guzzo, Thomas J. Hilman, Serena Jani, Ashesh B. Malkowicz, S. Bruce Master, Viraj A. Mitra, Anita Porten, Sima P. Efstathiou, Jason A. Eapen, Libni Christodouleas, John Paul TI Development and validation of contouring guidelines for post-cystectomy adjuvant radiation of bladder cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Washington Univ, St Louis, MO USA. Univ Hosp Bristol NHS Fdn Trust, Bristol, Avon, England. Lancashire Teaching Hosp NHS Fdn Trust, Preston, Lancs, England. Ottawa Hosp, Ottawa, ON, Canada. Univ London Imperial Coll Sci Technol & Med, London, England. Univ Calif San Francisco, San Francisco, CA 94143 USA. Christie Hosp NHS Fdn Trust, Manchester, Lancs, England. Univ So Calif, Keck Sch Med, Inst Urol, Los Angeles, CA 90033 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Hosp Univ Penn, Dept Urol, 3400 Spruce St, Philadelphia, PA 19104 USA. Bristol Haematol & Oncol Ctr, Bristol, Avon, England. Emory Univ, Winship Canc Inst, Dept Radiat Oncol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Urol, Winship Canc Inst, Atlanta, GA USA. Univ Coll London Hosp NHS Fdn Trust, Dept Oncol, London, England. Univ Calif San Francisco, Dept Urol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Ottawa Hosp, Ctr Canc, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 409 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100403 ER PT J AU Bergerot, PG Nelson, RA Ye, DW Grivas, P Singh, P Agarwal, N Choueiri, TK Pal, SK AF Bergerot, Paulo Gustavo Nelson, Rebecca A. Ye, Da-Wei Grivas, Petros Singh, Parminder Agarwal, Neeraj Choueiri, Toni K. Pal, Sumanta K. TI Risk of secondary urinary bladder cancer (UBC) in patients receiving radiotherapy for rectal cancer, prostate cancer, and gynecologic malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Fed Univ Sao Paulo UNIFESP, Sao Paulo, Brazil. City Hope Natl Med Ctr, Duarte, CA USA. Tongji Med Coll, Wuhan, Peoples R China. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Univ Arizona, Ctr Canc, Tucson, AZ USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 363 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100361 ER PT J AU Bernard, BD Albiges, L Signoretti, S Novak, J Hirsch, MS Massard, C Loriot, Y Fadel, E Chartier, S de Montpreville, V Fizazi, K Sweeney, C Adam, J AF Bernard, Brandon David Albiges, Laurence Signoretti, Sabina Novak, Jesse Hirsch, Michelle S. Massard, Christophe Loriot, Yohann Fadel, Elie Chartier, Suzanne de Montpreville, Vincent Fizazi, Karim Sweeney, Christopher Adam, Julien TI Programmed death-ligand 1 (PD-L1) expression in cured and not cured testicular and other germ cell tumors (GCT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Paris 11, Inst Gustave Roussy, Villejuif, France. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Inst Gustave Roussy, Villejuif, France. Gustave Roussy, Dept Canc Med, Canc Campus, Villejuif, France. Hop Marie Lannelongue, 133 Ave Resistance, F-92350 Le Plessis Robinson, France. Ctr Chirurg Marie Lannelongue, Le Plessis Robinson, France. Univ Paris 11, Inst Gustave Roussy, Dept Canc Med, Villejuif, France. Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 485 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100479 ER PT J AU Buscariollo, D Drumm, M Claymann, R Rodin, D Galland-Girodet, S Feldman, AS Dahl, DM McGovern, FJ Olumi, AF Eidelman, A Niemierko, A Shipley, WU Zietman, AL Efstathiou, JA AF Buscariollo, Daniela Drumm, Michael Claymann, Rebecca Rodin, Danielle Galland-Girodet, Sigolene Feldman, Adam S. Dahl, Douglas M. McGovern, Francis J. Olumi, Aria F. Eidelman, Alec Niemierko, Andrzej Shipley, William U. Zietman, Anthony L. Efstathiou, Jason A. TI Early salvage versus adjuvant post-prostatectomy radiation therapy: Long-term results of a large institutional experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. CHU Haut Leveque, Radiotherapy, Bordeaux, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 99 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100099 ER PT J AU Davis, ID Xie, WL Pezaro, CJ Donskov, F Wells, C Agarwal, N Srinivas, S Yuasa, T Beuselinck, B Wood, L Ernst, DS Kanesvaran, R Knox, JJ Pantuck, AJ Saleem, S Alva, AS Rini, BI Lee, JL Choueiri, TK Heng, DYC AF Davis, Ian D. Xie, Wanling Pezaro, Carmel Jo Donskov, Frede Wells, Connor Agarwal, Neeraj Srinivas, Sandhya Yuasa, Takeshi Beuselinck, Benoit Wood, Lori Ernst, D. Scott Kanesvaran, Ravindran Knox, Jennifer J. Pantuck, Allan J. Saleem, Sadia Alva, Ajjai Shivaram Rini, Brian I. Lee, Jae-Lyun Choueiri, Toni K. Heng, Daniel Yick Chin TI Change in International mRCC Database Consortium (IMDC) prognostic category and implications for efficacy of second-line targeted therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Monash Univ, Box Hill, Vic, Australia. Eastern Hlth, Box Hill, Vic, Australia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. Tom Baker Canc Clin, Calgary, AB, Canada. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Japanese Fdn Canc Res, Inst Canc, Dept Urol, Tokyo 170, Japan. Katholieke Univ Leuven Hosp, Dept Gen Med Oncol, Leuven, Belgium. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. London Reg Canc Ctr, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. Natl Canc Ctr Singapore, Singapore, Singapore. Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada. Univ Calif Los Angeles, David Geffen Sch Med, Inst Urol Oncol, Los Angeles, CA 90095 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 534 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100527 ER PT J AU de Velasco, G Miao, D Shukla, S Voss, MH Wu, C Murray, B Meyerson, M Signoretti, S Motzer, RJ Van Allen, EM Choueiri, TK AF de Velasco, Guillermo Miao, Diana Shukla, Sachet Voss, Martin Henner Wu, Catherine Murray, Bradley Meyerson, Matthew Signoretti, Sabina Motzer, Robert J. Van Allen, Eliezer Mendel Choueiri, Toni K. TI Integrated genomic correlates of response to PD-1 inhibitor nivolumab in metastatic renal cell carcinoma (mRCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst, Boston, MA USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Broad Inst Harvard,MIT, Massachusetts Gen Hosp,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 545 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100538 ER PT J AU de Velasco, G Xie, WL Donskov, F Albiges, L Beuselinck, B Srinivas, S Agarwal, N Lee, JL Brugarolas, J Wood, L Kollmannsberger, CK Rha, SY North, SA Kanesvaran, R Rini, BI Broom, RJ Yamamoto, H Kaymakcalan, MD Heng, DYC Choueiri, TK AF de Velasco, Guillermo Xie, Wanling Donskov, Frede Albiges, Laurence Beuselinck, Benoit Srinivas, Sandhya Agarwal, Neeraj Lee, Jae-Lyun Brugarolas, James Wood, Lori Kollmannsberger, Christian K. Rha, Sun Young North, Scott A. Kanesvaran, Ravindran Rini, Brian I. Broom, Reuben James Yamamoto, Haru Kaymakcalan, Marina Dusevic Heng, Daniel Yick Chin Choueiri, Toni K. TI Discontinuing VEGF-targeted therapy (VEGF-TT) for progression versus toxicity impacts outcomes of second-line therapies in metastatic renal cell carcinoma (mRCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. Univ Paris 11, Inst Gustave Roussy, Villejuif, France. Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. BC Canc Agcy, Vancouver Canc Ctr, Vancouver, BC, Canada. Yonsei Univ, Coll Med, Seoul, South Korea. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Natl Canc Ctr Singapore, Singapore, Singapore. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Auckland City Hosp, Auckland, New Zealand. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 503 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100496 ER PT J AU Dyer, MA Chen, MH Braccioforte, MH Moran, BJ D'Amico, AV AF Dyer, Michael A. Chen, Ming-Hui Braccioforte, Michelle H. Moran, Brian Joseph D'Amico, Anthony V. TI Comorbidity and androgen deprivation therapy use in men undergoing high-dose radiation for unfavorable intermediate- and high-risk prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Radiat Oncol Program, Boston, MA USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Prostate Canc Fdn Chicago, Westmont, IL USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 41 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100041 ER PT J AU Escudier, BJ Motzer, RJ Powles, T Tannir, NM Davis, ID Donskov, F Grunwald, V Heng, DYC Hutson, T Melichar, B Nosov, D Rini, BI Salman, P Sternberg, CN Szczylik, C Wolter, P Arroyo, AM Mangeshkar, M Agarwal, N Choueiri, TK AF Escudier, Bernard J. Motzer, Robert J. Powles, Thomas Tannir, Nizar M. Davis, Ian D. Donskov, Frede Grunwald, Viktor Heng, Daniel Yick Chin Hutson, Thomas Melichar, Bohuslav Nosov, Dimitry Rini, Brian I. Salman, Pamela Sternberg, Cora N. Szczylik, Cezary Wolter, Pascal Arroyo, Alan M. Mangeshkar, Milan Agarwal, Neeraj Choueiri, Toni K. TI Subgroup analyses of METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients (pts) with advanced renal cell carcinoma (RCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Inst Gustave Roussy, Villejuif, France. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Barts Hlth, Barts Canc Inst, London, England. Royal Free London NHS Fdn Trust, London, England. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Monash Univ, Eastern Hlth Clin Sch, Box Hill, Vic, Australia. Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Texas Oncol Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Univ Palackeho, Lekarska Fak, Onkol Klin, Olomouc, Czech Republic. Fak Nemocnice, Olomouc, Czech Republic. NN Blokhin Oncol Res Ctr, Moscow, Russia. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Fdn Arturo Lopez Perez, Santiago, Chile. San Camillo Forlanini Hosp, Rome, Italy. Mil Inst Med, Dept Oncol, Warsaw, Poland. Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium. Exelixis Inc, San Francisco, CA USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 499 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100492 ER PT J AU Fay, AP de Velasco, G Gray, KP Ho, TH Song, JX Kapur, P Albiges, L McDermott, DF Heng, DYC Brugarolas, J Choueiri, TK Signoretti, S AF Fay, Andre Poisl de Velasco, Guillermo Gray, Kathryn P. Ho, Thai Huu Song, Jiaxi Kapur, Payal Albiges, Laurence McDermott, David F. Heng, Daniel Yick Chin Brugarolas, James Choueiri, Toni K. Signoretti, Sabina TI The impact of PBRM1 and BAP1 expression on outcomes of patients with metastatic renal cell carcinoma (mRCC) treated with VEGF-targeted therapy (TT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Scottsdale, AZ USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 616 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100607 ER PT J AU Ferrari, AC Chen, YH Hudes, GR Carducci, MA Antonarakis, ES Hahn, NM Wong, YN DiPaola, RS AF Ferrari, Anna C. Chen, Yu-Hui Hudes, Gary R. Carducci, Michael Anthony Antonarakis, Emmanuel S. Hahn, Noah M. Wong, Yu-Ning DiPaola, Robert S. TI E2809: Androgen receptor (AR) modulation by bicalutamide (Bic) and MK-2206 (MK) in men with rising PSA at high-risk of progression after local prostate cancer (PC) treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. Dana Farber Canc Inst, Brookline, MA USA. Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Temple Univ Hlth Syst, Fox Chase Canc Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 9 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100009 ER PT J AU Filson, CP Shelton, JB Tan, HJ Kwan, L Skolarus, TA Saigal, C Litwin, MS AF Filson, Christopher Paul Shelton, Jeremy B. Tan, Hung-Jui Kwan, Lorna Skolarus, Ted A. Saigal, Christopher Litwin, Mark S. TI Expectant management of veterans with early-stage prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Emory Univ, Sch Med, Dept Urol, Atlanta VA Med Ctr, Atlanta, GA USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. VA Greater Los Angeles Med Ctr, Los Angeles, CA USA. Ann Arbor VA Med Ctr, VA Ctr Clin Management Res, Ann Arbor, MI USA. Univ Michigan, Dept Urol, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 13 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100013 ER PT J AU Flaig, TW Smith, MR Saad, F Rathkopf, DE Mulders, PFA Small, EJ Shore, ND Fizazi, K De Porre, P Kheoh, T Li, JH Todd, MB Griffin, TW Ryan, CJ De Bono, JS AF Flaig, Thomas W. Smith, Matthew R. Saad, Fred Rathkopf, Dana E. Mulders, Peter F. A. Small, Eric Jay Shore, Neal D. Fizazi, Karim De Porre, Peter Kheoh, Thian Li, Jinhui Todd, Mary Beth Griffin, Thomas W. Ryan, Charles J. De Bono, Johann S. TI Treatment patterns after abiraterone acetate in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post hoc analysis of COU-AA-302. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Colorado, Ctr Canc, Aurora, CO USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Montreal, Montreal, PQ, Canada. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Univ Paris 11, Inst Gustave Roussy, Villejuif, France. Janssen Res & Dev, Beerse, Belgium. Janssen Res & Dev, San Diego, CA USA. Johnson & Johnson Med China, Shanghai, Peoples R China. Janssen Global Serv, Raritan, NJ USA. Janssen Res & Dev, Los Angeles, CA USA. Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 168 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100168 ER PT J AU Gelpi-Hammerschmidt, F Rodriguez, D Tinay, I Allard, CB Blute, M Kibel, AS Chang, SL Trinh, QD Preston, MA AF Gelpi-Hammerschmidt, Francisco Rodriguez, Dayron Tinay, Ilker Allard, Christopher Brian Blute, Michael Kibel, Adam S. Chang, Steven Lee Quoc-Dien Trinh Preston, Mark A. TI The impact of histological variants on bladder cancer survival: A population-based analysis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Fellowship Urol Oncol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. McMaster Univ, Div Urol, Hamilton, ON, Canada. Harvard Univ, Sch Med, Dept Surg, Div Urol,Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 458 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100452 ER PT J AU Giacalone, NJ Clayman, RH Shipley, WU Niemierko, A Heney, NM Michaelson, MD McGovern, FJ Kaufman, DS Zietman, AL Efstathiou, JA AF Giacalone, Nicholas J. Clayman, Rebecca Helen Shipley, William U. Niemierko, Andrzej Heney, Niall M. Michaelson, M. Dror McGovern, Francis J. Kaufman, Donald S. Zietman, Anthony L. Efstathiou, Jason A. TI Long-term outcomes after bladder-preserving combined-modality therapy for patients with muscle-invasive bladder cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Massachusetts Gen Hosp, Harvard Radiat Oncol Program, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 398 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100392 ER PT J AU Haas, NB Manola, J Uzzo, RG Flaherty, K Pins, M Messing, EM DiPaola, RS AF Haas, Naomi B. Manola, Judith Uzzo, Robert G. Flaherty, Keith Pins, Michael Messing, Edward M. DiPaola, Robert S. TI A multivariate analysis of prognostic factors from assure (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Illinois, Coll Med, Chicago, IL USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 618 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100609 ER PT J AU Hamieh, L Mckay, RR Mickey, SS Lin, X Simantov, R Choueiri, TK AF Hamieh, Lana Mckay, Rana R. Mickey, Suzanne S. Lin, Xun Simantov, Ronit Choueiri, Toni K. TI Impact of metformin on outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Oncol, La Jolla, CA USA. Pfizer Oncol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 531 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100524 ER PT J AU Harshman, LC Kaag, M Efstathiou, JA Apolo, AB Hoffman-Censits, JH Stadler, WM Yu, EY Bochner, BH Skinner, EC Downs, T Kiltie, AE Bajorin, DF Guru, K Shipley, WU Steinberg, GD Hahn, NM Sridhar, SS AF Harshman, Lauren Christine Kaag, Matthew Efstathiou, Jason A. Apolo, Andrea B. Hoffman-Censits, Jean H. Stadler, Walter Michael Yu, Evan Y. Bochner, Bernard H. Skinner, Eila C. Downs, Tracy Kiltie, Anne E. Bajorin, Dean F. Guru, Khurshid Shipley, William U. Steinberg, Gary D. Hahn, Noah M. Sridhar, Srikala S. TI Exploring multidisciplinary practice patterns in the management of muscle invasive bladder cancer (MIBC) across the US and Canada in 2015. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Penn State Milton S Hershey Med Ctr, Hershey, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Univ Chicago, Chicago, IL 60637 USA. Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Wisconsin, Madison, WI USA. Gray Inst Radiat Oncol & Biol, Oxford, England. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Chicago, Pritzker Sch Med, Dept Surg, Urol Sect, Chicago, IL 60637 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Princess Margaret Canc Ctr, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 368 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100365 ER PT J AU Harshman, LC Werner, L Nakabayashi, M Tripathi, A Mckay, RR Wang, XD Pomerantz, M Mucci, LA Taplin, ME Sweeney, C Lee, GSM Kantoff, PW AF Harshman, Lauren Christine Werner, Lillian Nakabayashi, Mari Tripathi, Abhishek Mckay, Rana R. Wang, Xiaodong Pomerantz, Mark Mucci, Lorelei A. Taplin, Mary-Ellen Sweeney, Christopher Lee, Gwo-Shu Mary Kantoff, Philip W. TI The impact of statin use on abiraterone acetate (AA) treatment duration in patients with castration-resistant prostate cancer (CRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 196 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100196 ER PT J AU Hoffman-Censits, JH Grivas, P Van der Heijden, MS Dreicer, R Loriot, Y Retz, M Vogelzang, NJ Perez-Gracia, JL Rezazadeh, A Bracarda, S Yu, EY Hoimes, CJ Bellmunt, J Quinn, DI Petrylak, DP Hussain, SA Cui, N Mariathasan, S Abidoye, OO Rosenberg, JE AF Hoffman-Censits, Jean H. Grivas, Petros Van der Heijden, Michiel Simon Dreicer, Robert Loriot, Yohann Retz, Margitta Vogelzang, Nicholas J. Perez-Gracia, Jose Luis Rezazadeh, Arash Bracarda, Sergio Yu, Evan Y. Hoimes, Christopher J. Bellmunt, Joaquim Quinn, David I. Petrylak, Daniel Peter Hussain, Syed A. Cui, Na Mariathasan, Sanjeev Abidoye, Oyewale O. Rosenberg, Jonathan E. TI IMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Gustave Roussy, Dept Canc Med, Canc Campus, Villejuif, France. Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, Munich, Germany. US Oncol Comprehens Canc Ctr Nevada, Las Vegas, NV USA. Univ Navarra Clin, Dept Oncol, Pamplona, Spain. Norton Canc Inst, Louisville, KY USA. Osped San Donato USL8, Ist Toscano Tumori, Med Oncol, Arezzo, Italy. Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. Case Seidman Canc Ctr, Cleveland, OH USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Yale Canc Ctr, New Haven, CT USA. Univ Liverpool, Clatterbridge Canc Ctr, Liverpool L69 3BX, Merseyside, England. Genentech Inc, San Francisco, CA 94080 USA. Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 355 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100353 ER PT J AU Howard, SAH Rosenthal, M Qin, L Bernard, BD Beard, C Sweeney, C AF Howard, Stephanie Anne Holler Rosenthal, Michael Qin, Lei Bernard, Brandon David Beard, Clair Sweeney, Christopher TI Quantifying decreased radiation exposure from modern CT scan surveillance programs of germ cell tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 478 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100472 ER PT J AU Kamran, SC Curreri, SA Muralidhar, V Nguyen, PL Martin, NE Boyajian, R Harshman, LC Efstathiou, JA Beard, C AF Kamran, Sophia C. Curreri, Stephanie A. Muralidhar, Vinayak Nguyen, Paul L. Martin, Neil E. Boyajian, Richard Harshman, Lauren Christine Efstathiou, Jason A. Beard, Clair TI Re-irradiation of the pelvis for a genitourinary second malignant neoplasm or a local recurrence after full-dose pelvic radiotherapy for a pelvic cancer: Experience in a high-volume cancer center. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Radiat Oncol Program, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 494 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100487 ER PT J AU Karnes, J Ashab, HA Trock, BJ Ross, A Tsai, H Tosoian, JJ Erho, N Choeurng, V Yousefi, K Haddad, Z Abdollah, F Klein, EA Nguyen, PL Feng, FYC Dicker, A Den, RB Davicioni, E Jenkins, RB Lotan, TL Schaeffer, EM AF Karnes, Jeffrey Ashab, Hussam Al-Deen Trock, Bruce J. Ross, Ashley Tsai, Harrison Tosoian, Jeffrey J. Erho, Nicholas Choeurng, Voleak Yousefi, Kasra Haddad, Zaid Abdollah, Firas Klein, Eric A. Nguyen, Paul L. Feng, Felix Yi-Chung Dicker, Adam Den, Robert Benjamin Davicioni, Elai Jenkins, Robert B. Lotan, Tamara L. Schaeffer, Edward M. TI Development and validation of an ADT resistance signature to predict adjuvant hormone treatment failure. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Mayo Clin, Rochester, MN USA. GenomeDx Biosci Inc, Vancouver, BC, Canada. Johns Hopkins Univ, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Vattikuti Urol Inst, Detroit, MI USA. Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 106 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100106 ER PT J AU Ko, JJ Bernard, BD Tran, B Li, HC Asif, T Stukalin, I Lee, M Day, D Alimohamed, NS Sweeney, C Bedard, PL Heng, DYC AF Ko, Jenny J. Bernard, Brandon David Ben Tran Li, Haocheng Asif, Tehmina Stukalin, Igor Lee, Margaret Day, Daphne Alimohamed, Nimira S. Sweeney, Christopher Bedard, Philippe L. Heng, Daniel Yick Chin TI Conditional survival of patients with metastatic testicular germ-cell tumors (MT-GCT) treated with first-line curative therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 BC Canc Agcy, Abbotsford Ctr, Abbotsford, BC, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Epworth Freemasons Hosp, East Melbourne, Australia. Univ Calgary, Southern Alberta Canc Res Inst, Dept Oncol, Calgary, AB, Canada. Univ Calgary, Southern Alberta Canc Res Inst, Dept Community Hlth Sci, Calgary, AB, Canada. Saskatoon Canc Ctr, Saskatoon, SK, Canada. Tom Baker Canc Clin, Calgary, AB, Canada. Royal Melbourne Hosp, Melbourne, Vic, Australia. Royal Melbourne Hosp, Surry Hills, Australia. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 472 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100466 ER PT J AU Lee, WR Dignam, JJ Amin, M Bruner, D Low, D Swanson, GP Shah, A D'Souza, D Michalski, JM Dayes, I Seaward, SA Hall, WA Nguyen, PL Pisansky, TM Faria, S Chen, Y Koontz, BF Paulus, R Sandler, HM AF Lee, W. Robert Dignam, James J. Amin, Mahul Bruner, Deborah Low, Daniel Swanson, Gregory P. Shah, Amit D'Souza, David Michalski, Jeff M. Dayes, Ian Seaward, Samantha A. Hall, William Adrian Nguyen, Paul L. Pisansky, Thomas Michael Faria, Sergio Chen, Yuhchyau Koontz, Bridget F. Paulus, Rebecca Sandler, Howard M. TI NRG Oncology RTOG 0415: A randomized phase III non-inferiority study comparing two fractionation schedules in patients with low-risk prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Duke Univ, Sch Med, Durham, NC USA. Univ Chicago, Chicago, IL 60637 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. York Canc Ctr, York, PA USA. London Reg Canc Program, Dept Radiat Oncol, London, ON, Canada. Washington Univ, Sch Med, St Louis, MO USA. McMaster Univ, Hamilton, ON, Canada. Kaiser Permanente, Santa Clara, CA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. McGill Univ, Montreal, PQ, Canada. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Duke Univ, Med Ctr, Durham, NC USA. NRG Oncol, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 1 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100002 ER PT J AU Lerner, SP Kim, J Kwiatkowski, DJ Getz, G Weinstein, JN Cherniack, A Guo, GW Akbani, R Hoadley, KA Kim, WY Robertson, G Mungall, AJ Hinoue, T Laird, PW Al-Ahmadie, H Rosenberg, JE Bellmunt, J Bajorin, DF Hansel, DE Creighton, CJ AF Lerner, Seth P. Kim, Jaegil Kwiatkowski, David J. Getz, Gad Weinstein, John N. Cherniack, Andrew Guo, Guangwu Akbani, Rehan Hoadley, Katherine A. Kim, William Y. Robertson, Gordon Mungall, Andrew J. Hinoue, Toshinori Laird, Peter W. Al-Ahmadie, Hikmot Rosenberg, Jonathan E. Bellmunt, Joaquim Bajorin, Dean F. Hansel, Donna E. Creighton, Chad J. CA TCGA Bladder Canc Working Grp TI Comprehensive characterization of 412 muscle invasive urothelial carcinomas: Final analysis of The Cancer Genome Atlas (TCGA) project SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Broad Inst Harvard & MIT, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ N Carolina, Chapel Hill, NC USA. UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. BC Canc Agcy, Vancouver, BC, Canada. BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada. Van Andel Res Inst, Grand Rapids, MI USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 405 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100399 ER PT J AU Li, H Kroeger, N de Velasco, G Donskov, F Sim, HW Wells, C Stukalin, I Agarwal, N Parekh, HD Rini, BI Knox, JJ Pantuck, AJ Choueiri, TK Heng, DYC AF Li, Haoran Kroeger, Nils de Velasco, Guillermo Donskov, Frede Sim, Hao-Wen Wells, Connor Stukalin, Igor Agarwal, Neeraj Parekh, Hiral D. Rini, Brian I. Knox, Jennifer J. Pantuck, Allan J. Choueiri, Toni K. Heng, Daniel Yick Chin TI The impact of active smoking on survival outcome in metastatic renal cell carcinoma patients treated with targeted therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Tom Baker Canc Clin, Toronto, ON, Canada. Univ Med Greifswald, Tom Baker Canc Ctr, Greifswald, Germany. Univ Med Greifswald, Dept Urol, Greifswald, Germany. Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain. Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Tom Baker Canc Clin, Calgary, AB, Canada. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Cleveland Clin, Cleveland, OH 44106 USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada. Univ Calif Los Angeles, David Geffen Sch Med, Inst Urol Oncol, Los Angeles, CA 90095 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 552 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100545 ER PT J AU Lukka, H Pugh, SL Bruner, D Bahary, JP Lawton, CA Efstathiou, JA Kudchadker, R Ponsky, LE Seaward, SA Dayes, IS Gopaul, D Michalski, JM Delouya, G Kaplan, ID Horwitz, EM Roach, M Pinover, W Beyer, D Sandler, HM Kachnic, LA AF Lukka, Himanshu Pugh, Stephanie L. Bruner, Deborah Bahary, Jean-Paul Lawton, Colleen Anne Efstathiou, Jason A. Kudchadker, Rajat Ponsky, Lee Evan Seaward, Samantha A. Dayes, Ian S. Gopaul, Darindra Michalski, Jeff M. Delouya, Guila Kaplan, Irving D. Horwitz, Eric M. Roach, Mack Pinover, Wayne Beyer, David Sandler, Howard M. Kachnic, Lisa A. TI Patient reported outcomes in NRG Oncology/RTOG 0938, evaluating two ultrahypofractionated regimens (UHR) for prostate cancer (CaP) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 McMaster Univ, Hamilton, ON, Canada. Radiat Therapy Oncol Grp, Ctr Stat, Philadelphia, PA USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ Montreal, Dept Radiat Oncol, Ctr Hosp Univ Montreal, Montreal, PQ, Canada. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Hosp Case Medcl Ctr, Moreland Hill, OH USA. Kaiser Permanente, Santa Clara, CA USA. Juravinski Canc Ctr, Hamilton, ON, Canada. Grand River Hosp, Kitchener, ON, Canada. Washington Univ, Sch Med, St Louis, MO USA. Ctr Hosp Univ Montreal, Montreal, PQ, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Abington Mem Hosp, Philadelphia, PA USA. Arizona Oncol Serv Fdn, Phoenix, AZ USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Boston Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 27 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100027 ER PT J AU Huynh, MA Chen, MH Wu, J Braccioforte, MH Moran, BJ D'Amico, AV AF Mai Anh Huynh Chen, Ming-Hui Wu, Jing Braccioforte, Michelle H. Moran, Brian Joseph D'Amico, Anthony V. TI Comorbidity and the risk of all-cause and prostate cancer-specific mortality in men with unfavorable risk prostate cancer undergoing high dose radiation therapy alone. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Radiat Oncol Program, Boston, MA USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Chicago Prostate Canc Ctr, Westmont, IL USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 207 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100207 ER PT J AU McKay, RR Haider, B Duh, MS Valdarrama, A Nakabayashi, M Fiorillo, M Ristovska, L Wen, LK Kantoff, PW AF McKay, Rana R. Haider, Batool Duh, Mei Sheng Valdarrama, Adriana Nakabayashi, Mari Fiorillo, Matthew Ristovska, Ljubica Wen, Lonnie Kent Kantoff, Philip W. TI Impact of symptomatic skeletal events on healthcare resource utilization, health-related quality of life and pain among patients with castration-resistant prostate cancer and bone metastases. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Anal Grp Inc, Boston, MA USA. Bayer, Whippany, NJ USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 247 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100247 ER PT J AU Meyer, CP Sun, M de Velasco, G Trinh, QD Choueiri, TK AF Meyer, Christian P. Sun, Maxine de Velasco, Guillermo Quoc-Dien Trinh Choueiri, Toni K. TI Trends of metastasectomy for metastatic renal cell carcinoma and their impact on overall survival. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Univ, Brigham & Womens Hosp, Div Urol Surg, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Surg, Div Urol,Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 620 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100611 ER PT J AU Meyer, CP Sun, M de Velasco, G Trinh, QD Choueiri, TK AF Meyer, Christian P. Sun, Maxine de Velasco, Guillermo Quoc-Dien Trinh Choueiri, Toni K. TI Assessment of metastasectomy complications in renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol,Dept Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 619 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100610 ER PT J AU Mihalcik, SA Chen, MH Braccioforte, MH Moran, BJ D'Amico, AV AF Mihalcik, Stephen A. Chen, Ming-Hui Braccioforte, Michelle H. Moran, Brian Joseph D'Amico, Anthony V. TI Comorbidity and the receipt of curative therapy for favorable-risk prostate cancer prior to and following the publication of PIVOT SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Radiat Oncol Program, Boston, MA USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Chicago Prostate Canc Ctr, Westmont, IL USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 17 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100017 ER PT J AU Morales, JMR Wells, JC Donskov, F Bjarnason, GA Lee, JL Knox, JJ Beuselinck, B Vaishampayan, UN Brugarolas, J Broom, RJ Bamias, A Yuasa, T Srinivas, S Ernst, DS Pezaro, CJ Wood, L Kollmannsberger, CK Rini, BI Choueiri, TK Heng, DYC AF Morales, Jose Manuel Ruiz Wells, J. Connor Donskov, Frede Bjarnason, Georg A. Lee, Jae-Lyun Knox, Jennifer J. Beuselinck, Benoit Vaishampayan, Ulka N. Brugarolas, James Broom, Reuben James Bamias, Aristotelis Yuasa, Takeshi Srinivas, Sandhya Ernst, D. Scott Pezaro, Carmel Jo Wood, Lori Kollmannsberger, Christian K. Rini, Brian I. Choueiri, Toni K. Heng, Daniel Yick Chin TI First-line sunitinib versus pazopanib in metastatic renal cell carcinoma (mRCC): Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Tom Baker Canc Clin, Calgary, AB, Canada. Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada. Katholieke Univ Leuven Hosp, Dept Gen Med Oncol, Leuven, Belgium. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Auckland City Hosp, Auckland, New Zealand. Univ Athens, Dept Clin Therapeut, Athens, Greece. Japanese Fdn Canc Res, Canc Inst Hosp, Dept Urol, Tokyo, Japan. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. London Reg Canc Ctr, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. Royal Marsden NHS Fdn Trust, Inst Canc Res, Sutton, Surrey, England. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. BC Canc Agcy, Vancouver Canc Ctr, Vancouver, BC, Canada. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 544 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100537 ER PT J AU Moreira, RB Debiasi, M Maluf, FC Bellmunt, J Fay, AP Choueiri, TK Schutz, FAB AF Moreira, Raphael Brandao Debiasi, Marcio Maluf, Fernando C. Bellmunt, Joaquim Fay, Andre Poisl Choueiri, Toni K. Schutz, Fabio Augusto Barros TI Differential side effects profile in mCRPC patients treated with abiraterone or enzalutamide: A meta-analysis of randomized controlled trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Antonio Ermirio de Moraes Oncol Ctr, Sao Paulo, Brazil. Hosp San Lucas PUC, Porto Alegre, RS, Brazil. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. Pontificia Univ Catolica Rio Grande do Sul, HSL, Oncol Serv, Porto Alegre, RS, Brazil. Pontificia Univ Catolica Rio Grande do Sul, HSL, Oncol Res Unit, Porto Alegre, RS, Brazil. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 73 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100073 ER PT J AU Morgan, TM Mehra, R Wolf, JS Fosso, PG Orr, B Wu, SL Sangale, Z Stone, S Wu, CL Feldman, AS AF Morgan, Todd Matthew Mehra, Rohit Wolf, J. Stuart Fosso, Placede Gangnang Orr, Brian Wu, Shulin Sangale, Zaina Stone, Steven Wu, Chin-Lee Feldman, Adam S. TI Prognostic utility of a multi-gene signature (the cell cycle proliferation score) in patients with renal cell carcinoma (RCC) after radical nephrectomy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Myriad Genet Inc, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 555 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100548 ER PT J AU Mucci, LA Ahearn, T Penney, K Pettersson, A Graff, RE Kantoff, PW Finn, S Loda, M AF Mucci, Lorelei A. Ahearn, Thomas Penney, Kathryn Pettersson, Andreas Graff, Rebecca E. Kantoff, Philip W. Finn, Stephen Loda, Massimo CA Transdisciplinary Prostate Cancer TI Precision prevention of TMPRSS2: ERG prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. Karolinska Inst, Stockholm, Sweden. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St James Hosp, Dublin 8, Ireland. Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 78 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100078 ER PT J AU Mullane, SA de Velasco, G Choueiri, TK Kantoff, PW Bellmunt, J AF Mullane, Stephanie A. de Velasco, Guillermo Choueiri, Toni K. Kantoff, Philip W. Bellmunt, Joaquim TI Genomic alterations in upper tract urothelial carcinoma (UTUC) versus urothelial carcinoma of the bladder (UBC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA USA. Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 431 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100425 ER PT J AU Mullane, SA Meyer, C Choueiri, TK Preston, MA Nguyen, PL Bellmunt, J Trihn, QD AF Mullane, Stephanie A. Meyer, Christian Choueiri, Toni K. Preston, Mark A. Nguyen, Paul L. Bellmunt, Joaquim Quoc-Dien Trihn TI Racial disparities in quality metrics of muscle invasive bladder cancer (MIBC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Div Urol Surg, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA USA. Dana Farber Canc Inst, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 442 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100436 ER PT J AU Muralidhar, V Mahal, BAV Chen, YW Nezolosky, MD Nguyen, PL AF Muralidhar, Vinayak Mahal, Brandon Arvin Virgil Chen, Yu-Wei Nezolosky, Michelle Daniel Nguyen, Paul L. TI Socioeconomic disparities in the receipt of radiation for node-positive prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 53 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100053 ER PT J AU Muralidhar, V Xiang, MH Orio, PF Martin, NE Beard, C Feng, FYC Hoffman, KE Nguyen, PL AF Muralidhar, Vinayak Xiang, MIchael H. Orio, Peter F. Martin, Neil E. Beard, Clair Feng, Felix Yi-Chung Hoffman, Karen E. Nguyen, Paul L. TI Brachytherapy boost and cancer-specific mortality in favorable high-risk and other high-risk prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. Stanford Univ, Dept Radiat Oncol, Palo Alto, CA 94304 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 52 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100052 ER PT J AU Muralidhar, V Mahal, BAV Reznor, G Choueiri, TK Sweeney, C Martin, NE Orio, PF Chen, YW Nezolosky, MD Hoffman, KE Feng, FYC Trinh, QD Nguyen, PL AF Muralidhar, Vinayak Mahal, Brandon Arvin Virgil Reznor, Gally Choueiri, Toni K. Sweeney, Christopher Martin, Neil E. Orio, Peter F. Chen, Yu-Wei Nezolosky, Michelle Daniel Hoffman, Karen E. Feng, Felix Yi-Chung Quoc-Dien Trinh Nguyen, Paul L. TI Variation in national use of long-term ADT by disease aggressiveness among men with unfavorable-risk prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Brookline, MA USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, Dept Urol, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 54 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100054 ER PT J AU Muralidhar, V Regan, MM Werner, L Nakabayashi, M Evan, C Bellmunt, J Choueiri, TK Elfiky, A Harshman, LC Mckay, RR Pomerantz, M Sweeney, C Taplin, ME Kantoff, PW Nguyen, PL AF Muralidhar, Vinayak Regan, Meredith M. Werner, Lillian Nakabayashi, Mari Evan, Carolyn Bellmunt, Joaquim Choueiri, Toni K. Elfiky, Aymen Harshman, Lauren Christine Mckay, Rana R. Pomerantz, Mark Sweeney, Christopher Taplin, Mary-Ellen Kantoff, Philip W. Nguyen, Paul L. TI Duration of androgen deprivation therapy for high-risk prostate cancer: Application of randomized trial data in a tertiary referral cancer center SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 33 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100033 ER PT J AU Olumi, AF Ge, RB Wang, ZW Wu, SL Tabetabaei, S Wu, CL AF Olumi, Aria F. Ge, Rongbin Wang, Zongwei Wu, Shulin Tabetabaei, Shahin Wu, Chin-Lee TI Regulation of steroid-5-alpha-reductase 2 (SRD5A2) in human prostate by epigenetic modifications. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 204 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100204 ER PT J AU Olumi, AF Wang, ZW Ge, RB Wu, SL Tabetabaei, S Wu, CL AF Olumi, Aria F. Wang, Zongwei Ge, Rongbin Wu, Shulin Tabetabaei, Shahin Wu, Chin-Lee TI Epigenetic silencing and variable expression of SRD5A2 in specific compartments of human prostate SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 38 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100038 ER PT J AU Pal, SK Ali, SM Ennis, R Elvin, JA Vergilio, J Suh, J Yelensky, R Ross, JS Miller, VA Joshi, M Choueiri, TK Stephens, PJ Frampton, GM AF Pal, Sumanta K. Ali, Siraj Mahamed Ennis, Riley Elvin, Julia Andrea Vergilio, JoAnn Suh, James Yelensky, Roman Ross, Jeffrey S. Miller, Vincent A. Joshi, Monika Choueiri, Toni K. Stephens, Philip J. Frampton, Garrett Michael TI Characterization of mutational load in patients with advanced urothelial cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 City Hope Natl Med Ctr, Duarte, CA USA. Fdn Med Inc, Cambridge, MA USA. Albany Med Coll, Albany, NY 12208 USA. Penn State Milton S Hershey Med Ctr, Harrisburg, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 460 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100454 ER PT J AU Patrick-Miller, LJ Chen, YH Carducci, MA Cella, D DiPaola, RS Gartrell, BA Jarrard, DF Liu, G Morgans, AK Wong, YN Sweeney, C AF Patrick-Miller, Linda J. Chen, Yu-Hui Carducci, Michael Anthony Cella, David DiPaola, Robert S. Gartrell, Benjamin Adam Jarrard, David Frazier Liu, Glenn Morgans, Alicia Katherine Wong, Yu-Ning Sweeney, Christopher TI Quality of life (QOL) analysis from E3805, chemohormonal androgen ablation randomized trial (CHAARTED) in prostate cancer (PrCa) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Dana Farber Canc Inst, Brookline, MA USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Northwestern Univ, Chicago, IL 60611 USA. Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Temple Univ Hlth Syst, Fox Chase Canc Ctr, Philadelphia, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 2 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 286 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100285 ER PT J AU Preston, MA Zhang, XH Graff, RE Sanchez, A Chang, SL Stampfer, MJ Choueiri, TK Wilson, KM Cho, EY AF Preston, Mark A. Zhang, Xuehong Graff, Rebecca E. Sanchez, Alejandro Chang, Steven L. Stampfer, Meir J. Choueiri, Toni K. Wilson, Kathryn M. Cho, Eunyoung TI Analgesic use and risk of renal cell cancer: Results from two prospective cohort studies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard TH Chan Sch Publ Hlth, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Channing Div Network Med, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 588 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100579 ER PT J AU Ramos, J Wong, YN Crabb, SJ Niegisch, G Bellmunt, J Ladoire, S Hussain, SA Baniel, J Golshayan, AR Powles, T Rosenberg, JE De Giorgi, U Vaishampayan, UN Agarwal, N Pal, SK Harshman, LC Necchi, A Recine, F Galsky, MD Yu, EY AF Ramos, Jorge Wong, Yu-Ning Crabb, Simon J. Niegisch, Guenter Bellmunt, Joaquim Ladoire, Sylvain Hussain, Syed A. Baniel, Jack Golshayan, Ali Reza Powles, Thomas Rosenberg, Jonathan E. De Giorgi, Ugo Vaishampayan, Ulka N. Agarwal, Neeraj Pal, Sumanta K. Harshman, Lauren Christine Necchi, Andrea Recine, Federica Galsky, Matt D. Yu, Evan Y. CA RISC Investigators TI Venous thromboembolism (VTE) risk in patients with localized urinary tract tumors (UTT) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. Temple Univ Hlth Syst, Fox Chase Canc Ctr, Philadelphia, PA USA. Univ Southampton, Southampton, Hants, England. Univ Dusseldorf, Dept Urol, Dusseldorf, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. Georges Francois Leclerc Canc Ctr, Dijon, France. Univ Liverpool, Clatterbridge Canc Ctr, Liverpool L69 3BX, Merseyside, England. Rabin Med Ctr, Petah Tivka, Israel. Carolina Oncol Associates PA, Hickory, NC USA. Barts Hlth, Barts Canc Inst, London, England. Royal Free London NHS Fdn Trust, London, England. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Meldola, Italy. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. City Hope Natl Med Ctr, Duarte, CA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Ist Nazl Tumori, Via Venezian 1, I-20133 Milan, MI, Italy. San Camillo & Forlanini Hosp, Dept Med Oncol, Rome, Italy. Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 422 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100416 ER PT J AU Roberts, HJ Drumm, M Niemierko, A Goldberg, S Clayman, RH Heney, NM Feldman, AS Wszolek, MF Michaelson, MD Lee, RJ Saylor, PJ Zietman, AL Shipley, WU Efstathiou, JA AF Roberts, Hannah J. Drumm, Michael Niemierko, Andrzej Goldberg, Saveli Clayman, Rebecca Helen Heney, Niall M. Feldman, Adam S. Wszolek, Matthew F. Michaelson, M. Dror Lee, Richard J. Saylor, Philip James Zietman, Anthony L. Shipley, William U. Efstathiou, Jason A. TI Renal function in bladder cancer patients after trimodality therapy: Long-term results of a large institutional experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 453 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100447 ER PT J AU Rodin, D Andersen, LW Buscariollo, D Drumm, M Clayman, RH Galland, S Eidelman, A Feldman, AS Lee, RJ Dahl, DM McGovern, FJ Olumi, AF Niemierko, A Shipley, WU Zietman, AL Efstathiou, JA AF Rodin, Danielle Andersen, Lars Wiuff Buscariollo, Daniela Drumm, Michael Clayman, Rebecca Helen Galland, Sigolene Eidelman, Alec Feldman, Adam S. Lee, Richard J. Dahl, Douglas M. McGovern, Francis J. Olumi, Aria F. Niemierko, Andrzej Shipley, William U. Zietman, Anthony L. Efstathiou, Jason A. TI Risk factors for disease progression after post-prostatectomy salvage radiation: Long-term results of a large institutional experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. Aarhus Univ Hosp, Dept Anesthesiol, DK-8000 Aarhus, Denmark. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 110 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100110 ER PT J AU Salari, K Bechis, S Ge, RB Hong, J Otsetov, A Wang, ZW Wu, CL Tabatabaei, S Olumi, AF AF Salari, Keyan Bechis, Seth Ge, Rongbin Hong, Jian Otsetov, Aleksander Wang, Zongwei Wu, Chin-Lee Tabatabaei, Shahin Olumi, Aria F. TI Gene expression profiling of prostate tissue based on variable expression of 5-alpha reductase 2. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 143 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100143 ER PT J AU Serrano, NA Moghanaki, D Asher, D Karlin, J Schutzer, M Chang, MG Hagan, MP AF Serrano, Nicholas A. Moghanaki, Drew Asher, David Karlin, Jeremy Schutzer, Matthew Chang, Michael G. Hagan, Michael Philip TI Comparative study of late rectal toxicity in veterans undergoing low-dose rate prostate brachytherapy treated with or without supplemental external beam radiotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA USA. US Dept Vet Affairs, Richmond, VA USA. Univ Miami, Miami, FL USA. Virginia Commonwealth Univ, Richmond, VA USA. Hunter Holmes McGuire Vet Adm Med Ctr, Richmond, VA USA. Virginia Commonwealth Univ, Mineral, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 112 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100112 ER PT J AU Sevillano, E Werner, L de Velasco, G Mullane, SA Terrasa, J del Alba, AG Bellmunt, J AF Sevillano, Elena Werner, Lillian de Velasco, Guillermo Mullane, Stephanie A. Terrasa, Josefa del Alba, Aranzazu Gonzalez Bellmunt, Joaquim TI Chemotherapy treatment patterns and survival outcomes in patients with visceral metastatic upper tract urothelial cell carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Hosp Univ Son Espases, Palma De Mallorca, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 415 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100409 ER PT J AU Shipley, WU Pugh, SL Lukka, HR Major, P Heney, NM Grignon, DA Sartor, O Patel, M Bahary, JP Zietman, AL Pisanslcy, TM Zeitzer, KL Lawton, CA Feng, FYC Lovett, RD Balogh, AG Souhami, L Rosenthal, SA Kerlin, K Sandler, HM AF Shipley, William U. Pugh, Stephanie L. Lukka, Himu R. Major, Pierre Heney, Niall M. Grignon, David A. Sartor, Oliver Patel, Malti Bahary, Jean -Paul Zietman, Anthony L. Pisanslcy, Thomas Michael Zeitzer, Kenneth Lee Lawton, Colleen Anne Feng, Felix Yi-Chung Lovett, Richard Dana Balogh, Alexander G. Souhami, Luis Rosenthal, Seth A. Kerlin, Kevin Sandler, Howard M. TI NRG Oncology/RTOG 9601, a phase III trial in prostate cancer patients: Anti-androgen therapy (AAT) with bicalutamide during and after salvage radiation therapy (RT) following radical prostatectomy (RP) and an elevated PSA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Radiat Therapy Oncol Grp, Ctr Stat, Philadelphia, PA USA. Juravinski Canc Ctr, Hamilton, ON, Canada. McMaster Univ, Juravinsd Canc Ctr, Hamilton Hlth Sci, Hamilton, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Indiana Univ Sch Med, Indianapolis, IN 46202 USA. Tulane Univ, Sch Med, 1430 Tulane Ave, New Orleans, LA 70112 USA. McMaster Univ, Hamilton, ON, Canada. Univ Montreal, Dept Radiat Oncol, Ctr Hosp Univ Montreal, Montreal, PQ, Canada. Mayo Clin, Rochester, MN USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Rutland Reg Med Ctr, Rutland, VT USA. Tom Baker Canc Clin, Calgary, AB, Canada. McGill Univ, Ctr Hlth, Dept Radiat Oncol, Montreal, PQ, Canada. Sutter Canc Ctr, Sacramento, CA USA. Southeast Canc Control Consortium, Goldsboro, NC USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 3 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100004 ER PT J AU Sonpavde, G Pond, GR di Lorenzo, G Buonerba, C Rozzi, A Lanzetta, G Necchi, A Giannatempo, P Raggi, D Matsumoto, K Choueiri, TK Mullane, SA Niegisch, G Albers, P Lee, JL Kitamura, H Kume, H Bellmunt, J AF Sonpavde, Guru Pond, Gregory Russell di Lorenzo, Giuseppe Buonerba, Carlo Rozzi, Antonio Lanzetta, Gaetano Necchi, Andrea Giannatempo, Patrizia Raggi, Daniele Matsumoto, Kazurrosa Choueiri, Toni K. Mullane, Stephanie A. Niegisch, Guenter Albers, Peter Lee, Jae-Lyun Kitamura, Hiroshi Kume, Haruki Bellmunt, Joaquim TI Impact of prior platinum on patients receiving salvage systemic therapy for advanced urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Univ Naples Federico II, Dept Clin Med, Med Oncol Unit, Naples, Italy. Ist Neurotraumatol Italian Grottaferrata, Clin Oncol Unit, Grottaferrata, Italy. Ist Neurotraumatol Italiano, Grottaferrata, Italy. Ist Nazl Tumori Milan, Milan, MI, Italy. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Kitasato Univ, Sch Med, Dept Urol, Sagamihara, Kanagawa 228, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA USA. Univ Dusseldorf, Dept Urol, Dusseldorf, Germany. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. Sapporo Med Univ, Chuo Ku, Sapporo, Hokkaido, Japan. Univ Tokyo, Fac Med, Dept Urol, Tokyo 113, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. Ontario Clin Oncol Grp, Hamilton, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 386 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100381 ER PT J AU Sonpavde, G Pond, GR Mullane, SA Ramirez, AA Vogelzang, NJ Necchi, A Powles, T Bellmunt, J AF Sonpavde, Guru Pond, Gregory Russell Mullane, Stephanie A. Ramirez, Ana Arlene Vogelzang, Nicholas J. Necchi, Andrea Powles, Thomas Bellmunt, Joaquim TI Outcomes of advanced urothelial carcinoma following discontinuation of programmed death (PD)-1 or PD-ligand (L)-1 inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Ontario Clin Oncol Grp, Hamilton, ON, Canada. Dana Farber Canc Inst, Brigham & Womens Canc Ctr, Bladder Canc Ctr, Boston, MA 02115 USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. US Oncol Network, Carolina Urol Res Ctr, Myrtle Beach, SC USA. Ist Nazl Tumori, Via Venezian 1, I-20133 Milan, MI, Italy. Barts Hlth, Barts Canc Inst, London, England. Royal Free London NHS Fdn Trust, London, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 385 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100380 ER PT J AU Sun, M de Velasco, G Meyer, CP Bellmunt, J Nguyen, PL Trinh, QD Choueiri, TK AF Sun, Maxine de Velasco, Guillermo Meyer, Christian P. Bellmunt, Joaquim Nguyen, Paul L. Quoc-Dien Trinh Choueiri, Toni K. TI Urachal versus nonurachal adenocarcinomas of the bladder: A population-based report. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 450 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100444 ER PT J AU Sun, M Hamnvik, OPR de Velasco, G Jiang, W Loeb, S Nguyen, PL Trinh, QD Choueiri, TK AF Sun, Maxine Hamnvik, Ole-Petter Riksfjord de Velasco, Guillermo Jiang, Wei Loeb, Stacy Nguyen, Paul L. Trinh, Quoc-Dien Choueiri, Toni K. TI The adverse effects of androgen-deprivation therapy: Comparison between gonadotropin-releasing hormone agonists and orchiectomy in the SEER-Medicare population SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain. Johns Hopkins Univ, Baltimore, MD USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol,Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 304 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100302 ER PT J AU Tannir, NM Figlin, RA Gore, ME Michaelson, D Motzer, RJ Porta, C Rini, BI Hoang, CJ Lin, X Escudier, B AF Tannir, Nizar M. Figlin, Robert A. Gore, Martin Eric Michaelson, Dror Motzer, Robert J. Porta, Camillo Rini, Brian I. Hoang, Caroline J. Lin, Xun Escudier, Bernard TI Long-term response to sunitinib treatment in metastatic renal cell carcinoma (mRCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. Royal Marsden Hosp NHS Fdn Trust, London, England. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. IRCCS San Matteo Univ Hosp Fdn, Pavia, Italy. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Pfizer Inc, New York, NY USA. Pfizer Oncol, La Jolla, CA USA. Inst Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 598 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100589 ER PT J AU Ho, TH Choueiri, TK Wang, K Karam, JA Chalmers, ZR Frampton, GM Elvin, JA Johnson, A Liu, XL Lin, YL Joseph, RW Stanton, ML Miller, VA Stephens, PJ Ross, JS Ali, SM Pal, SK AF Thai Huu Ho Choueiri, Toni K. Wang, Kai Karam, Jose A. Chalmers, Zachary Rockow Frampton, Garrett Michael Elvin, Julia Andrea Johnson, Adrienne Liu, Xueli Lin, Yulan Joseph, Richard Wayne Stanton, Melissa L. Miller, Vincent A. Stephens, Philip J. Ross, Jeffrey S. Ali, Siraj Mahamed Pal, Sumanta K. TI Correlation between findings from comprehensive genomic profiling and targeted therapy response in metastatic renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Mayo Clin, Scottsdale, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fdn Med Inc, Cambridge, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. Mayo Clin, Jacksonville, FL 32224 USA. Mayo Clin, Phoenix, AZ USA. Albany Med Coll, Albany, NY 12208 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 570 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100563 ER PT J AU Ho, TH Gagnon, RC Liu, Y Hodi, FS Signoretti, S Choueiri, TK AF Thai Huu Ho Gagnon, Robert Charles Liu, Yuan Hodi, F. Stephen Signoretti, Sabina Choueiri, Toni K. TI T-cell receptor (TCR) repertoire in metastatic renal cell carcinoma (RCC) patients treated with first-line vascular endothelial growth factor receptor blockade. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Mayo Clin, Scottsdale, AZ USA. GlaxoSmithKline, Collegeville, PA USA. Novartis Pharmaceut, Wayne, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 501 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100494 ER PT J AU Voss, MH Hellmann, MD Chen, YB Gold, TM Lambert, CR VanAllen, E Choueiri, TK Charen, AS Motzer, RJ AF Voss, Martin Henner Hellmann, Matthew David Chen, Yingbei Gold, Theresa Margaret Lambert, Courtney Rose VanAllen, Eliezer Choueiri, Toni K. Charen, Alexandra Snyder Motzer, Robert J. TI Mutation burden and tumor neoantigens in RCC patients (pts) treated with nivolumab. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 514 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100507 ER PT J AU Warren, LE Chen, MH Denham, JW Steigler, A Renshaw, AA Loffredo, MJ Kantoff, PW D'Amico, AV AF Warren, Laura Elizabeth Chen, Ming-Hui Denham, James William Steigler, Allison Renshaw, Andrew A. Loffredo, Marian J. Kantoff, Philip W. D'Amico, Anthony V. TI Gleason score and the risk of cause-specific and overall mortality following radiation with or without 6 months of androgen deprivation therapy for men with unfavorable-risk prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Harvard Radiat Oncol Program, Boston, MA USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Univ Newcastle, Callaghan, NSW 2308, Australia. Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. Baptist Hosp Miami, Miami, FL USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 171 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100171 ER PT J AU Wong, SE North, SA Sweeney, C Stockler, MR Sridhar, SS AF Wong, Sarah E. North, Scott A. Sweeney, Christopher Stockler, Martin R. Sridhar, Srikala S. TI Screen failure rates in contemporary phase II/III therapeutic trials in genitourinary malignancies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Princess Margaret Canc Ctr, Toronto, ON, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW 2006, Australia. RI Stockler, Martin/N-3859-2016 OI Stockler, Martin/0000-0003-3793-8724 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 176 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100176 ER PT J AU Zabell, J Sanda, MG Litwin, MS Suarez, JF Regan, MM Saigal, C Kwan, L Gao, TM Rabah, D Klein, EA Kattan, MW Stephenson, AJ AF Zabell, Joseph Sanda, Martin G. Litwin, Mark S. Suarez, Jose Francisco Regan, Meredith M. Saigal, Christopher Kwan, Lorna Gao, Tianming Rabah, Danny Klein, Eric A. Kattan, Michael W. Stephenson, Andrew J. TI Pre-treatment nomogram to predict potency after treatment for localized prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. King Khalid Univ Hosp, Riyadh 11472, Saudi Arabia. Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. Cleveland Clin, Quantitat Hlth Sci, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 32 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100032 ER PT J AU Johung, KL Yeh, N Desai, NB Williams, TM Lautenschlaeger, T Arvold, ND Ning, MS Attia, A Lovly, CM Goldberg, S Beal, K Yu, JB Kavanagh, BD Chiang, VL Camidge, DR Contessa, JN AF Johung, Kimberly L. Yeh, Norman Desai, Neil B. Williams, Terence M. Lautenschlaeger, Tim Arvold, Nils D. Ning, Matthew S. Attia, Albert Lovly, Christine M. Goldberg, Sarah Beal, Kathryn Yu, James B. Kavanagh, Brian D. Chiang, Veronica L. Camidge, D. Ross Contessa, Joseph N. TI Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PARTITIONING ANALYSIS RPA; RADIATION-THERAPY; STEREOTACTIC RADIOSURGERY; OLIGOPROGRESSIVE DISEASE; SURGICAL RESECTION; RANDOMIZED-TRIAL; CRIZOTINIB; CHEMOTHERAPY; RADIOTHERAPY; PROGRESSION AB Purpose We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score >= 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, <.001, and <.001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P=.633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P<.001). Conclusion Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease. (C) 2015 by American Society of Clinical Oncology C1 [Johung, Kimberly L.; Goldberg, Sarah; Yu, James B.; Chiang, Veronica L.; Contessa, Joseph N.] Yale Univ, Sch Med, 15 York St,HRT 139,POB 208040, New Haven, CT 06520 USA. [Yeh, Norman; Kavanagh, Brian D.; Camidge, D. Ross] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA. [Desai, Neil B.; Beal, Kathryn] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Williams, Terence M.; Lautenschlaeger, Tim] Ohio State Univ, Columbus, OH 43210 USA. [Arvold, Nils D.] Dana Farber Brigham & Womens Hosp, Boston, MA USA. [Ning, Matthew S.; Attia, Albert; Lovly, Christine M.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Contessa, JN (reprint author), Yale Univ, Sch Med, 15 York St,HRT 139,POB 208040, New Haven, CT 06520 USA. EM joseph.contessa@yale.edu FU AstraZeneca; Novartis FX AstraZeneca, Novartis NR 29 TC 43 Z9 47 U1 3 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 BP 123 EP + DI 10.1200/JCO.2015.62.0138 PG 9 WC Oncology SC Oncology GA DJ6MH UT WOS:000374327000008 PM 26438117 ER PT J AU Renfro, LA Loupakis, F Adams, RA Seymour, MT Heinemann, V Schmoll, HJ Douillard, JY Hurwitz, H Fuchs, CS Diaz-Rubio, E Porschen, R Tournigand, C Chibaudel, B Falcone, A Tebbutt, NC Punt, CJA Hecht, JR Bokemeyer, C Van Cutsem, E Goldberg, RM Saltz, LB de Gramont, A Sargent, DJ Lenz, HJ AF Renfro, Lindsay A. Loupakis, Fotios Adams, Richard A. Seymour, Matthew T. Heinemann, Volker Schmoll, Hans-Joachim Douillard, Jean-Yves Hurwitz, Herbert Fuchs, Charles S. Diaz-Rubio, Eduardo Porschen, Rainer Tournigand, Christophe Chibaudel, Benoist Falcone, Alfredo Tebbutt, Niall C. Punt, Cornelis J. A. Hecht, J. Randolph Bokemeyer, Carsten Van Cutsem, Eric Goldberg, Richard M. Saltz, Leonard B. de Gramont, Aimery Sargent, Daniel J. Lenz, Heinz-Josef TI Body Mass Index Is Prognostic in Metastatic Colorectal Cancer: Pooled Analysis of Patients From First-Line Clinical Trials in the ARCAD Database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLON-CANCER; ADJUVANT CHEMOTHERAPY; CACHEXIA; SURVIVAL; OBESITY; MORTALITY; PROGRAM; WEIGHT; AGE AB Purpose In recent retrospective analyses of early-stage colorectal cancer (CRC), low and high body mass index (BMI) scores were associated with worsened outcomes. Whether BMI is a prognostic or predictive factor in metastatic CRC (mCRC) is unclear. Patients and Methods Individual data from 21,149 patients enrolled onto 25 first-line mCRC trials during 1997 to 2012 were pooled. We assessed both prognostic and predictive effects of BMI on overall survival and progression-free survival, and we accounted for patient and tumor characteristics and therapy type (targeted v nontargeted). Results BMI was prognostic for overall survival (P < .001) and progression-free survival (P < .001), with an L-shaped pattern. That is, risk of progression and/or death was greatest for low BMI; risk decreased as BMI increased to approximately 28 kg/m(2), and then it plateaued. Relative to obese patients, patients with a BMI of 18.5 kg/m(2) had a 27% increased risk of having a PFS event (95% CI, 20% to 34%) and a 50% increased risk of death (95% CI, 43% to 56%). Low BMI was associated with poorer survival for men than women (interaction P < .001). BMI was not predictive of treatment effect. Conclusion Low BMI is associated with an increased risk of progression and death among the patients enrolled on the mCRC trials, with no increased risk for elevated BMI, in contrast to the adjuvant setting. Possible explanations include negative effects related to cancer cachexia in patients with low BMI, increased drug delivery or selection bias in patients with high BMI, and potential for an interaction between BMI and molecular signaling pathways. (C) 2015 by American Society of Clinical Oncology C1 [Renfro, Lindsay A.; Sargent, Daniel J.] Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. [Loupakis, Fotios; Falcone, Alfredo] Azienda Osped Univ Pisana, Pisa, Italy. [Loupakis, Fotios; Falcone, Alfredo] Univ Pisa, Pisa, Italy. [Adams, Richard A.] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales. [Seymour, Matthew T.] St James Hosp, Leeds, W Yorkshire, England. [Seymour, Matthew T.] Univ Leeds, Leeds, W Yorkshire, England. [Heinemann, Volker] Univ Munich, Munich, Germany. [Schmoll, Hans-Joachim] Univ Clin Halle Saale, Halle, Germany. [Porschen, Rainer] Klinikum Bremen Ost, Klin Innere Med, Bremen, Germany. [Bokemeyer, Carsten] Univ Hamburg Hosp, Univ Hosp Canc Ctr, Hamburg, Germany. [Douillard, Jean-Yves] Ctr Rene Gauducheau, Inst Cancerol, F-44035 Nantes, France. [Tournigand, Christophe] Univ Paris Est Creteil, Henri Mondor Hosp, Creteil, France. [Chibaudel, Benoist; de Gramont, Aimery] Franco British Inst, Levallois Perret, France. [Hurwitz, Herbert] Duke Univ, Med Ctr, Durham, NC USA. [Fuchs, Charles S.] Dana Farber Canc Inst Boston, Boston, MA USA. [Diaz-Rubio, Eduardo] Hosp Clin San Carlos, Inst Invest Sanitaria, Madrid, Spain. [Tebbutt, Niall C.] Austin Hlth, Heidelberg, Vic, Australia. [Punt, Cornelis J. A.] Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Hecht, J. Randolph] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lenz, Heinz-Josef] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Van Cutsem, Eric] Univ Hosp Leuven, Leuven, Belgium. [Goldberg, Richard M.] Ohio State Univ, Columbus, OH 43210 USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. RP Renfro, LA (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM renfro.lindsay@mayo.edu RI Loupakis, Fotios/I-7243-2012; OI Loupakis, Fotios/0000-0001-9651-0395; Saltz, Leonard/0000-0001-8353-4670 FU Foundation ARCAD (Aide et Recherche en Cancerologie Digestive) FX Supported by the Foundation ARCAD (Aide et Recherche en Cancerologie Digestive). NR 24 TC 9 Z9 10 U1 3 U2 11 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 BP 144 EP + DI 10.1200/JCO.2015.61.6441 PG 9 WC Oncology SC Oncology GA DJ6MH UT WOS:000374327000011 PM 26503203 ER PT J AU Clemens, MW Medeiros, LJ Butler, CE Hunt, KK Fanale, MA Horwitz, S Weisenburger, DD Liu, J Morgan, EA Kanagal-Shamanna, R Parkash, V Ning, J Sohani, AR Ferry, JA Mehta-Shah, N Dogan, A Liu, H Thormann, N Di Napoli, A Lade, S Piccolini, J Reyes, R Williams, T McCarthy, CM Hanson, SE Nastoupil, LJ Gaur, R Oki, Y Young, KH Miranda, RN AF Clemens, Mark W. Medeiros, L. Jeffrey Butler, Charles E. Hunt, Kelly K. Fanale, Michelle A. Horwitz, Steven Weisenburger, Dennis D. Liu, Jun Morgan, Elizabeth A. Kanagal-Shamanna, Rashmi Parkash, Vinita Ning, Jing Sohani, Aliyah R. Ferry, Judith A. Mehta-Shah, Neha Dogan, Ahmed Liu, Hui Thormann, Nora Di Napoli, Arianna Lade, Stephen Piccolini, Jorge Reyes, Ruben Williams, Travis McCarthy, Colleen M. Hanson, Summer E. Nastoupil, Loretta J. Gaur, Rakesh Oki, Yasuhiro Young, Ken H. Miranda, Roberto N. TI Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BRENTUXIMAB VEDOTIN SGN-35; OF-THE-LITERATURE; TERM-FOLLOW-UP; CAPSULE; INVOLVEMENT; DIAGNOSIS; DISEASE; ENTITY; TISSUE; WOMEN AB Purpose Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. Patients and Methods In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. Results The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS(P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Conclusion Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. (C) 2015 by American Society of Clinical Oncology C1 [Clemens, Mark W.; Medeiros, L. Jeffrey; Butler, Charles E.; Hunt, Kelly K.; Fanale, Michelle A.; Liu, Jun; Kanagal-Shamanna, Rashmi; Ning, Jing; Hanson, Summer E.; Nastoupil, Loretta J.; Oki, Yasuhiro; Young, Ken H.; Miranda, Roberto N.] Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Horwitz, Steven; Mehta-Shah, Neha; Dogan, Ahmed; McCarthy, Colleen M.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Weisenburger, Dennis D.] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Morgan, Elizabeth A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Morgan, Elizabeth A.; Sohani, Aliyah R.; Ferry, Judith A.] Harvard Univ, Sch Med, Boston, MA USA. [Sohani, Aliyah R.; Ferry, Judith A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parkash, Vinita] Yale Univ, Sch Med, New Haven, CT USA. [Liu, Hui] Xuzhou Med Coll, Xuzhou, Peoples R China. [Thormann, Nora] Fundacao Univ Mario Martins, Porto Alegre, RS, Brazil. [Di Napoli, Arianna] Univ Roma La Sapienza, St Andrea Hosp, Rome, Italy. [Lade, Stephen] Univ Melbourne, Melbourne, Vic, Australia. [Piccolini, Jorge] Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina. [Reyes, Ruben] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Williams, Travis] St Lukes Mt States Tumor Inst, Meridian, ID USA. [Gaur, Rakesh] St Lukes Hosp, Kansas City, MO USA. RP Miranda, RN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Unit 72, 1515 Holcombe Blvd, Houston, TX 77030 USA.; Miranda, RN (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM roberto.miranda@mdanderson.org OI Kanagal-Shamanna, Rashmi/0000-0001-7829-5249; Morgan, Elizabeth/0000-0001-5880-9337 FU Cancer Center Support Grant, National Cancer Institute [P30-CA016672] FX Supported in part by Grant No. P30-CA016672 from the Cancer Center Support Grant, National Cancer Institute. NR 35 TC 15 Z9 16 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 BP 160 EP + DI 10.1200/JCO.2015.63.3412 PG 12 WC Oncology SC Oncology GA DJ6MH UT WOS:000374327000013 PM 26628470 ER PT J AU Bezjak, A Temin, S Azzoli, CG AF Bezjak, Andrea Temin, Sarah Azzoli, Christopher G. TI No Role For Trimodality Therapy and Consolidation Chemotherapy Compared With Concurrent Radiochemotherapy Alone in Stage III Non-Small-Cell Lung Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Bezjak, Andrea] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Temin, Sarah] Amer Soc Clin Oncol, Alexandria, VA USA. [Azzoli, Christopher G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bezjak, A (reprint author), Princess Margaret Canc Ctr, Toronto, ON, Canada. NR 6 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 BP 197 EP + DI 10.1200/JCO.2015.64.1407 PG 2 WC Oncology SC Oncology GA DJ6MH UT WOS:000374327000019 PM 26573071 ER PT J AU Menon, U Kalsi, JK Gentry-Maharaj, A Ryan, A Burnell, M Parmar, M Fallowfield, L Campbell, S McGuire, A Skates, S Jacobs, I AF Menon, Usha Kalsi, Jatinderpal K. Gentry-Maharaj, Aleksandra Ryan, Andy Burnell, Matthew Parmar, Max Fallowfield, Lesley Campbell, Stuart McGuire, Alistair Skates, Steven Jacobs, Ian TI Ovarian Cancer Early Detection Needs Better Imaging, Not Better Algorithms or Biomarkers Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID TRIAL C1 [Menon, Usha; Kalsi, Jatinderpal K.; Gentry-Maharaj, Aleksandra; Ryan, Andy; Burnell, Matthew; Parmar, Max; Jacobs, Ian] UCL, London, England. [Fallowfield, Lesley] Univ Sussex, Falmer, England. [Campbell, Stuart] Create Hlth Clin, London, England. [McGuire, Alistair] London Sch Econ, London WC2A 2AE, England. [Skates, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skates, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Jacobs, Ian] Univ New S Wales, Sydney, NSW, Australia. RP Menon, U (reprint author), UCL, London, England. FU Cancer Research UK; Department of Health; Medical Research Council NR 8 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 BP 201 EP + DI 10.1200/JCO.2015.64.1365 PG 3 WC Oncology SC Oncology GA DJ6MH UT WOS:000374327000023 PM 26573079 ER PT J AU Cai, XM Bhattacharyya, S Plitt, A Raibagkar, P LaBuzetta, JN Schleicher, SM Munshi, NC Klein, JP AF Cai, Xuemei Bhattacharyya, Shamik Plitt, Anna Raibagkar, Pooja LaBuzetta, Jamie N. Schleicher, Stephen M. Munshi, Nikhil C. Klein, Joshua P. TI Management of Posterior Reversible Encephalopathy Syndrome Induced by Carfilzomib in a Patient With Multiple Myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PROTEASOME INHIBITOR CARFILZOMIB; LEUKOENCEPHALOPATHY SYNDROME; SINGLE-AGENT; BORTEZOMIB; PR-171 C1 [Cai, Xuemei; Bhattacharyya, Shamik; Raibagkar, Pooja; LaBuzetta, Jamie N.; Schleicher, Stephen M.; Klein, Joshua P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Cai, Xuemei; Bhattacharyya, Shamik; Raibagkar, Pooja; LaBuzetta, Jamie N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cai, Xuemei; Bhattacharyya, Shamik; Plitt, Anna; Raibagkar, Pooja; LaBuzetta, Jamie N.; Schleicher, Stephen M.; Munshi, Nikhil C.; Klein, Joshua P.] Harvard Univ, Sch Med, Boston, MA USA. [Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cai, XM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.; Cai, XM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Cai, XM (reprint author), Harvard Univ, Sch Med, Boston, MA USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 BP E1 EP E5 DI 10.1200/JCO.2013.49.6166 PG 5 WC Oncology SC Oncology GA DJ6MH UT WOS:000374327000001 PM 24799479 ER PT J AU Fischer, M Quaas, M Steiner, L Engeland, K AF Fischer, Martin Quaas, Marianne Steiner, Lydia Engeland, Kurt TI The p53-p21-DREAM-CDE/CHR pathway regulates G(2)/M cell cycle genes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TOPOISOMERASE-II-ALPHA; TUMOR-SUPPRESSOR P53; HUMAN CANCER-CELLS; DOWN-REGULATION; IONIZING-RADIATION; PROMOTER ELEMENTS; DREAM COMPLEX; B-MYB; TRANSCRIPTIONAL REPRESSION; CYCLIN-B1 TRANSCRIPTION AB The tumor suppressor p53 functions predominantly as a transcription factor by activating and downregulating gene expression, leading to cell cycle arrest or apoptosis. p53 was shown to indirectly repress transcription of the CCNB2, KIF23 and PLK4 cell cycle genes through the recently discovered p53-p21-DREAM-CDE/CHR pathway. However, it remained unclear whether this pathway is commonly used. Here, we identify genes regulated by p53 through this pathway in a genome-wide computational approach. The bioinformatic analysis is based on genome-wide DREAM complex binding data, p53-depedent mRNA expression data and a genome-wide definition of phylogenetically conserved CHR promoter elements. We find 210 target genes that are expected to be regulated by the p53-p21-DREAM-CDE/CHR pathway. The target gene list was verified by detailed analysis of p53-dependent repression of the cell cycle genes B-MYB (MYBL2), BUB1, CCNA2, CCNB1, CHEK2, MELK, POLD1, RAD18 and RAD54L. Most of the 210 target genes are essential regulators of G(2) phase and mitosis. Thus, downregulation of these genes through the p53-p21-DREAM-CDE/CHR pathway appears to be a principal mechanism for G(2)/M cell cycle arrest by p53. C1 [Fischer, Martin; Quaas, Marianne; Engeland, Kurt] Univ Leipzig, Sch Med, Mol Oncol, D-04109 Leipzig, Germany. [Steiner, Lydia] Wisconsin Inst Discovery, Ctr Complex & Collect Computat, Madison, WI USA. [Steiner, Lydia] Univ Leipzig, Computat EvoDevo Grp, D-04109 Leipzig, Germany. [Steiner, Lydia] Univ Leipzig, Dept Comp Sci, Bioinformat Grp, D-04109 Leipzig, Germany. [Steiner, Lydia] Univ Leipzig, Interdisciplinary Ctr Bioinformat, D-04109 Leipzig, Germany. [Fischer, Martin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Fischer, Martin] Harvard Univ, Sch Med, Boston, MA USA. RP Engeland, K (reprint author), Univ Leipzig, Sch Med, Mol Oncol, D-04109 Leipzig, Germany. EM engeland@medizin.uni-leipzig.de RI Fischer, Martin/I-4825-2014; OI Fischer, Martin/0000-0002-3429-1876; Engeland, Kurt/0000-0003-3525-0440 FU Fritz Thyssen Foundation; Freistaat Sachsen; John Templeton Foundation [24332]; German Research Foundation (DFG); University of Leipzig within the program of Open Access Publishing FX Fritz Thyssen Foundation [ to M. F.]; Freistaat Sachsen [ to M. Q.]; John Templeton Foundation [ Grant ID 24332 to L. S.]. Funding for open access charge: German Research Foundation (DFG) and University of Leipzig within the program of Open Access Publishing. NR 65 TC 14 Z9 14 U1 7 U2 19 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 JAN 8 PY 2016 VL 44 IS 1 BP 164 EP 174 DI 10.1093/nar/gkv927 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3RM UT WOS:000371264000021 PM 26384566 ER PT J AU Poggioli, T Vujic, A Yang, PG Macias-Trevino, C Uygur, A Loffredo, FS Pancoast, JR Cho, M Goldstein, J Tandias, RM Gonzalez, E Walker, RG Thompson, TB Wagers, AJ Fong, YW Lee, RT AF Poggioli, Tommaso Vujic, Ana Yang, Peiguo Macias-Trevino, Claudio Uygur, Aysu Loffredo, Francesco S. Pancoast, James R. Cho, Miook Goldstein, Jill Tandias, Rachel M. Gonzalez, Emilia Walker, Ryan G. Thompson, Thomas B. Wagers, Amy J. Fong, Yick W. Lee, Richard T. TI Circulating Growth Differentiation Factor 11/8 Levels Decline With Age SO CIRCULATION RESEARCH LA English DT Article DE aging; Gdf11 protein; mouse; intercellular signaling peptides and proteins; Mstn protein; mouse; transforming growth factor- ID SKELETAL-MUSCLE; GDF11; MYOSTATIN; HYPERTROPHY; MASS AB Rationale: Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor- superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. Objective: Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart. Methods and Results: We validated our previous finding that circulating levels of GDF11/8 decline with age in mice, rats, horses, and sheep. Furthermore, we showed by Western analysis that the apparent age-dependent increase in GDF11 levels, as reported by Egerman et al, is attributable to cross-reactivity of the anti-GDF11 antibody with immunoglobulin, which is known to increase with age. GDF11 administration in mice rapidly activated SMAD2 and SMAD3 signaling in myocardium in vivo and decreased cardiac mass in both young (2-month-old) and old (22-month-old) mice in a dose-dependent manner after only 9 days. Conclusions: Our study confirms an age-dependent decline in serum GDF11/8 levels in multiple mammalian species and that exogenous GDF11 rapidly activates SMAD signaling and reduces cardiomyocyte size. Unraveling the molecular basis for the age-dependent decline in GDF11/8 could yield insight into age-dependent cardiac pathologies. C1 [Poggioli, Tommaso; Vujic, Ana; Yang, Peiguo; Macias-Trevino, Claudio; Uygur, Aysu; Loffredo, Francesco S.; Pancoast, James R.; Cho, Miook; Goldstein, Jill; Tandias, Rachel M.; Gonzalez, Emilia; Wagers, Amy J.; Fong, Yick W.; Lee, Richard T.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Poggioli, Tommaso; Vujic, Ana; Yang, Peiguo; Macias-Trevino, Claudio; Uygur, Aysu; Loffredo, Francesco S.; Pancoast, James R.; Tandias, Rachel M.; Gonzalez, Emilia; Fong, Yick W.; Lee, Richard T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Brigham Regenerat Med Ctr, Boston, MA 02115 USA. [Poggioli, Tommaso; Vujic, Ana; Yang, Peiguo; Macias-Trevino, Claudio; Uygur, Aysu; Loffredo, Francesco S.; Pancoast, James R.; Tandias, Rachel M.; Gonzalez, Emilia; Fong, Yick W.; Lee, Richard T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Walker, Ryan G.; Thompson, Thomas B.] Univ Cincinnati, Coll Med, Dept Mol Genet, Cincinnati, OH 45221 USA. [Cho, Miook; Goldstein, Jill; Wagers, Amy J.] Howard Hughes Med Inst, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Lee, RT (reprint author), Brigham Regenerat Med Ctr, 65 Landsdowne St,Room 280, Cambridge, MA 02139 USA. EM RLee@bwh.harvard.edu RI Loffredo, Francesco/F-6638-2014 OI Loffredo, Francesco/0000-0001-5911-780X FU National Institutes of Health [R01AG032977, R01AG040019, R03AG049657, R56 AG048917]; Leducq Foundation FX This study was supported in part by the National Institutes of Health (RTL R01AG032977, R01AG040019, and R03AG049657; AJW R56 AG048917) and by the Leducq Foundation. NR 19 TC 27 Z9 28 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 8 PY 2016 VL 118 IS 1 BP 29 EP 37 DI 10.1161/CIRCRESAHA.115.307521 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA DB4AN UT WOS:000368455200008 PM 26489925 ER PT J AU Guyette, JP Charest, JM Mills, RW Jank, BJ Moser, PT Gilpin, SE Gershlak, JR Okamoto, T Gonzalez, G Milan, DJ Gaudette, GR Ott, HC AF Guyette, Jacques P. Charest, Jonathan M. Mills, Robert W. Jank, Bernhard J. Moser, Philipp T. Gilpin, Sarah E. Gershlak, Joshua R. Okamoto, Tatsuya Gonzalez, Gabriel Milan, David J. Gaudette, Glenn R. Ott, Harald C. TI Bioengineering Human Myocardium on Native Extracellular Matrix SO CIRCULATION RESEARCH LA English DT Article DE cardiomyocytes; extracellular matrix; induced pluripotent stem cells; regeneration ID PLURIPOTENT STEM-CELLS; ENGINEERED CARDIAC TISSUE; PORCINE HEART; PERFUSION DECELLULARIZATION; ORTHOTOPIC TRANSPLANTATION; MACROPHAGE PHENOTYPE; PASSIVE MYOCARDIUM; CARDIOMYOCYTES; DIFFERENTIATION; REGENERATION AB Rationale: More than 25 million individuals have heart failure worldwide, with approximate to 4000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only approximate to 2500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective: The objective of this study is to translate previous work to human scale and clinically relevant cells for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human induced pluripotent stem cell-derived cardiomyocytes. Methods and Results: To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiomyocytes derived from nontransgenic human induced pluripotent stem cells and generated tissues of increasing 3-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole-heart scaffolds with human induced pluripotent stem cell-derived cardiomyocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue and showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions: Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human induced pluripotent stem cell-derived cardiomyocytes and enable the bioengineering of functional human myocardial-like tissue of multiple complexities. C1 [Guyette, Jacques P.; Charest, Jonathan M.; Jank, Bernhard J.; Moser, Philipp T.; Gilpin, Sarah E.; Okamoto, Tatsuya; Gonzalez, Gabriel; Ott, Harald C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Mills, Robert W.; Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Milan, David J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Guyette, Jacques P.; Jank, Bernhard J.; Moser, Philipp T.; Gilpin, Sarah E.; Gonzalez, Gabriel; Ott, Harald C.] Harvard Univ, Sch Med, Boston, MA USA. [Gershlak, Joshua R.; Gaudette, Glenn R.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. [Ott, Harald C.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Ott, HC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Thorac Surg, Dept Surg,Med Sch, 55 Fruit St,Blake 15, Boston, MA 02114 USA. EM hott@partners.org OI Jank, Bernhard/0000-0003-1420-5034 FU US National Institutes of Health [DP2 OD008749-01]; National Heart Lung and Blood Institute [R21 HL108663-2, R01 HL115282] FX The present study was supported by the US National Institutes of Health Director's New Innovator DP2 OD008749-01, and by the National Heart Lung and Blood Institute R21 HL108663-2 and R01 HL115282. NR 84 TC 18 Z9 18 U1 13 U2 51 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 8 PY 2016 VL 118 IS 1 BP 56 EP 72 DI 10.1161/CIRCRESAHA.115.306874 PG 17 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA DB4AN UT WOS:000368455200011 PM 26503464 ER PT J AU Leong, WY Guo, H Ma, O Huang, H Cantor, AB Friedman, AD AF Leong, Wan Yee Guo, Hong Ma, Ou Huang, Hui Cantor, Alan B. Friedman, Alan D. TI Runx1 Phosphorylation by Src Increases Trans-activation via Augmented Stability, Reduced Histone Deacetylase (HDAC) Binding, and Increased DNA Affinity, and Activated Runx1 Favors Granulopoiesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; CBF-BETA-SMMHC; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; ADULT HEMATOPOIESIS; DIFFERENTIATION; AML1; INHIBITION; PROTEINS AB Src phosphorylates Runx1 on one central and four C-terminal tyrosines. We find that activated Src synergizes with Runx1 to activate a Runx1 luciferase reporter. Mutation of the four Runx1 C-terminal tyrosines to aspartate or glutamate to mimic phosphorylation increases trans-activation of the reporter in 293T cells and allows induction of Cebpa or Pu.1 mRNAs in 32Dcl3 myeloid cells, whereas mutation of these residues to phenylalanine to prevent phosphorylation obviates these effects. Three mechanisms contribute to increased Runx1 activity upon tyrosine modification as follows: increased stability, reduced histone deacetylase (HDAC) interaction, and increased DNA binding. Mutation of the five modified Runx1 tyrosines to aspartate markedly reduced co-immunoprecipitation with HDAC1 and HDAC3, markedly increased stability in cycloheximide or in the presence of co-expressed Cdh1, an E3 ubiquitin ligase coactivator, with reduced ubiquitination, and allowed DNA-binding in gel shift assay similar to wild-type Runx1. In contrast, mutation of these residues to phenylalanine modestly increased HDAC interaction, modestly reduced stability, and markedly reduced DNA binding in gel shift assays and as assessed by chromatin immunoprecipitation with the -14-kb Pu.1 or +37-kb Cebpa enhancers after stable expression in 32Dcl3 cells. Affinity for CBF beta, the Runx1 DNA-binding partner, was not affected by these tyrosine modifications, and in vitro translated CBF beta markedly increased DNA affinity of both the translated phenylalanine and aspartate Runx1 variants. Finally, further supporting a positive role for Runx1 tyrosine phosphorylation during granulopoiesis, mutation of the five Src-modified residues to aspartate but not phenylalanine allows Runx1 to increase Cebpa and granulocyte colony formation by Runx1-deleted murine marrow. C1 [Leong, Wan Yee; Guo, Hong; Ma, Ou; Friedman, Alan D.] Johns Hopkins Univ, Div Pediat Oncol, Baltimore, MD 21231 USA. [Huang, Hui; Cantor, Alan B.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Huang, Hui; Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Friedman, AD (reprint author), Johns Hopkins Univ, CRB 1, Rm 253,1650 Orleans St, Baltimore, MD 21231 USA. EM afriedm2@jhmi.edu FU National Institutes of Health [U01 HL099775, R01 HL082952]; National Institutes of Health Cancer Center [P30 CA006973]; Gabrielle's Angel Foundation; Giant Food Children's Cancer Research Fund FX This work was supported by National Institutes of Health Grants U01 HL099775 (to A. D. F.) and R01 HL082952 (to A. B. C.), National Institutes of Health Cancer Center Core Grant P30 CA006973, a grant from the Gabrielle's Angel Foundation (to A. B. C.), and by the Giant Food Children's Cancer Research Fund. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 40 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 8 PY 2016 VL 291 IS 2 BP 826 EP 836 DI 10.1074/jbc.M115.674234 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA5GF UT WOS:000367830500029 PM 26598521 ER PT J AU Streit, BR Kant, R Tokmina-Lukaszewska, M Celis, AI Machovina, MM Skaar, EP Bothner, B DuBois, JL AF Streit, Bennett R. Kant, Ravi Tokmina-Lukaszewska, Monika Celis, Arianna I. Machovina, Melodie M. Skaar, Eric P. Bothner, Brian DuBois, Jennifer L. TI Time-resolved Studies of IsdG Protein Identify Molecular Signposts along the Non-canonical Heme Oxygenase Pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STAPHYLOCOCCUS-AUREUS ISDG; PSEUDOMONAS-AERUGINOSA HEME; MYCOBACTERIUM-TUBERCULOSIS; DEGRADING ENZYMES; CRYSTAL-STRUCTURE; DEGRADATION; HYDROXYLATION; MACROCYCLE; MONOXIDE; COMPLEX AB IsdGs are heme monooxygenases that break open the tetrapyrrole, releasing the iron, and thereby allowing bacteria expressing this protein to use heme as a nutritional iron source. Little is currently known about the mechanism by which IsdGs degrade heme, although the products differ from those generated by canonical heme oxygenases. A synthesis of time-resolved techniques, including in proteo mass spectrometry and conventional and stopped-flow UV/visible spectroscopy, was used in conjunction with analytical methods to define the reaction steps mediated by IsdG from Staphylococcus aureus and their time scales. An apparent meso-hydroxyheme (forming with k = 0.6 min(-1), pH7.4, 10 mM ascorbate, 10 mu M IsdG-heme, 22 degrees C) was identified as a likely common intermediate with the canonical heme oxygenases. Unlike heme oxygenases, this intermediate does not form with added H2O2 nor does it convert to verdoheme and CO. Rather, the next observable intermediates (k = 0.16 min(-1)) were a set of formyloxobilin isomers, similar to the mycobilin products of the IsdG homolog from Mycobacterium tuberculosis (MhuD). These converted in separate fast and slow phases to beta-/delta-staphylobilin isomers and formaldehyde (CH2O). Controlled release of this unusual C1 product may support IsdG's dual role as both an oxygenase and a sensor of heme availability in S. aureus. C1 [Streit, Bennett R.; Kant, Ravi; Tokmina-Lukaszewska, Monika; Celis, Arianna I.; Machovina, Melodie M.; Bothner, Brian; DuBois, Jennifer L.] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59715 USA. [Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Skaar, Eric P.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37232 USA. RP DuBois, JL (reprint author), Montana State Univ, Dept Chem & Biochem, 221 Chem & Biochem Bldg, Bozeman, MT 59715 USA. EM jdubois@chemistry.montana.edu FU Murdock Charitable Trust; National Institutes of Health of the CoBRE program [5P20RR02437] FX We acknowledge Dr. Jonathan Hilmer for sharing technical expertise in mass spectrometry. We thank Garrett Moraski for helpful discussions. Dr. Sunil Ojha is thanked for contributing to the initiation of this project. The mass spectrometry facility at Montana State University receives funding from the Murdock Charitable Trust and National Institutes of Health Grant 5P20RR02437 of the CoBRE program. NR 31 TC 6 Z9 6 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 8 PY 2016 VL 291 IS 2 BP 862 EP 871 DI 10.1074/jbc.M115.666560 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA5GF UT WOS:000367830500032 PM 26534961 ER PT J AU Ghanem, SS Heinrich, G Lester, SG Pfeiffer, V Bhattacharya, S Patel, PR DeAngelis, AM Dai, T Ramakrishnan, SK Smiley, ZN Jung, DY Lee, Y Kitamura, T Ergun, S Kulkarni, RN Kim, JK Giovannucci, DR Najjar, SM AF Ghanem, Simona S. Heinrich, Garrett Lester, Sumona G. Pfeiffer, Verena Bhattacharya, Sumit Patel, Payal R. DeAngelis, Anthony M. Dai, Tong Ramakrishnan, Sadeesh K. Smiley, Zachary N. Jung, Dae Y. Lee, Yongjin Kitamura, Tadahiro Ergun, Suleyman Kulkarni, Rohit N. Kim, Jason K. Giovannucci, David R. Najjar, Sonia M. TI Increased Glucose-induced Secretion of Glucagon-like Peptide-1 in Mice Lacking the Carcinoembryonic Antigenrelated Cell Adhesion Molecule 2 (CEACAM2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-RECEPTOR; ENERGY-BALANCE; BETA-CELL; KINASE; HOMEOSTASIS; EXPRESSION; RESISTANCE; SUBSTRATE; GLUTAG; BRAIN AB Carcinoembryonic antigen-related cell adhesion molecule 2 (CEACAM2) regulates food intake as demonstrated by hyperphagia in mice with the Ceacam2 null mutation (Cc2(-/-)). This study investigated whether CEACAM2 also regulates insulin secretion. Ceacam2 deletion caused an increase in beta-cell secretory function, as assessed by hyperglycemic clamp analysis, without affecting insulin response. Although CEACAM2 is expressed in pancreatic islets predominantly in non-beta-cells, basal plasma levels of insulin, glucagon and somatostatin, islet areas, and glucose-induced insulin secretion in pooled Cc2(-/-) islets were all normal. Consistent with immunofluorescence analysis showing CEACAM2 expression in distal intestinal villi, Cc2(-/-) mice exhibited a higher release of oral glucose-mediated GLP-1, an incretin that potentiates insulin secretion in response to glucose. Compared with wild type, Cc2(-/-) mice also showed a higher insulin excursion during the oral glucose tolerance test. Pretreating with exendin(9-39), a GLP-1 receptor antagonist, suppressed the effect of Ceacam2 deletion on glucose-induced insulin secretion. Moreover, GLP-1 release into the medium of GLU Tag enteroendocrine cells was increased with siRNA-mediated Ceacam2 down-regulation in parallel to an increase in Ca2+ entry through L-type voltage-dependent Ca2+ channels. Thus, CEACAM2 regulates insulinsecretion, atleastinpart, by a GLP-1-mediated mechanism, independent of confounding metabolic factors. C1 [Ghanem, Simona S.; Heinrich, Garrett; Lester, Sumona G.; Patel, Payal R.; DeAngelis, Anthony M.; Dai, Tong; Ramakrishnan, Sadeesh K.; Smiley, Zachary N.; Najjar, Sonia M.] Univ Toledo, Coll Med & Life Sci, Hlth Sci Campus, Ctr Diabet & Endocrine Res, Toledo, OH 43614 USA. [Ghanem, Simona S.; Heinrich, Garrett; Lester, Sumona G.; Patel, Payal R.; DeAngelis, Anthony M.; Dai, Tong; Ramakrishnan, Sadeesh K.; Smiley, Zachary N.; Najjar, Sonia M.] Univ Toledo, Coll Med & Life Sci, Hlth Sci Campus, Dept Physiol & Pharmacol, Toledo, OH 43614 USA. [Bhattacharya, Sumit; Giovannucci, David R.] Univ Toledo, Coll Med & Life Sci, Hlth Sci Campus, Dept Neurosci, Toledo, OH 43614 USA. [Pfeiffer, Verena] Univ Wurzburg, Inst Anat & Zellbiol, D-97070 Wurzburg, Germany. [Jung, Dae Y.; Lee, Yongjin; Kim, Jason K.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Kitamura, Tadahiro] Gunma Univ, Metab Signal Res Ctr, Inst Mol & Cellular Regulat, Gunma 3718512, Japan. [Kulkarni, Rohit N.] Brigham & Womens Hosp, Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Kulkarni, Rohit N.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Najjar, SM (reprint author), Univ Toledo, Coll Med & Life Sci, Hlth Sci Campus, 3000 Arlington Ave,Mail Stop 1009, Toledo, OH 43614 USA. EM sonia.najjar@utoledo.edu FU National Institutes of Health [R01 DK054254, R01 DK083850, R01 HL112248, R01 DK67536, R01 DK103215, R21 DE023418, U24-DK093000]; United States Department of Agriculture Grant USDA [38903-19826]; Deutsche Forschungsgemeinschaft [ER 276/9-1 TI 690/3-1, SFB 688/3 A19]; Middle-East Diabetes Research Center FX This work was supported in part by National Institutes of Health Grants R01 DK054254, R01 DK083850, and R01 HL112248 (to S. M. N.), Grants R01 DK67536 and R01 DK103215 (to R. N. K.), Grant R21 DE023418 (to D. R. G.), and Grant U24-DK093000 (to the National Mouse Metabolic Phenotyping Center at University of Massachusetts), United States Department of Agriculture Grant USDA 38903-19826 (to S. M. N.), and Deutsche Forschungsgemeinschaft Grants ER 276/9-1 TI 690/3-1 and SFB 688/3 A19 (to S. E.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Supported by a predoctoral fellowship from the Middle-East Diabetes Research Center. NR 36 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 8 PY 2016 VL 291 IS 2 BP 980 EP 988 DI 10.1074/jbc.M115.692582 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA5GF UT WOS:000367830500043 PM 26586918 ER PT J AU Nikiforow, S Ritz, J AF Nikiforow, Sarah Ritz, Jerome TI Dramatic Expansion of HSCs: New Possibilities for HSC Transplants? SO CELL STEM CELL LA English DT Editorial Material ID CORD BLOOD TRANSPLANTATION; PLATELET ENGRAFTMENT; NEUTROPHIL AB The identification of mechanisms that regulate stem cell renewal has led to the development of innovative approaches to expand hematopoietic stem cells ex vivo. One approach reported by Wagner et al. (2016) in this issue of Cell Stem Cell has demonstrated dramatic expansion of umbilical cord blood stem cells that promote rapid engraftment while maintaining capacity for long-term hematopoiesis. C1 [Nikiforow, Sarah; Ritz, Jerome] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [Nikiforow, Sarah; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA.; Ritz, J (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu NR 10 TC 2 Z9 2 U1 1 U2 3 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 JAN 7 PY 2016 VL 18 IS 1 BP 10 EP 12 DI 10.1016/j.stem.2015.12.011 PG 3 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DG8GP UT WOS:000372321300005 PM 26748750 ER PT J AU Hendriks, WT Warren, CR Cowan, CA AF Hendriks, William T. Warren, Curtis R. Cowan, Chad A. TI Genome Editing in Human Pluripotent Stem Cells: Approaches, Pitfalls, and Solutions SO CELL STEM CELL LA English DT Review ID ZINC-FINGER NUCLEASES; RNA-GUIDED ENDONUCLEASES; TAL EFFECTOR NUCLEASES; OFF-TARGET SITES; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; GENE CORRECTION; DISEASE-MODELS; ENGINEERED NUCLEASES; ANALYSIS REVEALS AB Human pluripotent stem cells (hPSCs) with knockout or mutant alleles can be generated using custom-engineered nucleases. Transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nucleases are the most commonly employed technologies for editing hPSC genomes. In this Protocol Review, we provide a brief overview of custom-engineered nucleases in the context of gene editing in hPSCs with a focus on the application of TALENs and CRISPR/Cas9. We will highlight the advantages and disadvantages of each method and discuss theoretical and technical considerations for experimental design. C1 [Hendriks, William T.] Massachusetts Gen Hosp, Collaborat Ctr X Linked Dystonia Parkinsonism, Dept Neurol, Charlestown, MA 02129 USA. [Hendriks, William T.] Harvard Univ, Sch Med, Harvard Brain Sci Initiat, Boston, MA 02114 USA. [Warren, Curtis R.; Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Cowan, CA (reprint author), Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.; Cowan, CA (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM chad_cowan@harvard.edu FU MGH Collaborative Center for X-linked Dystonia-Parkinsonism; NIH [U01HL100408, U01HL107440, R01DK095384, R01DK097768]; Harvard Stem Cell Institute FX The authors would like to thank members of the Bragg, Joung, and C.A.C. labs for helpful discussions during the preparation of this protocol review. The authors also apologize for any references that were left out due to space constraints. Funding for this work was provided by the MGH Collaborative Center for X-linked Dystonia-Parkinsonism (W.T.H.); NIH grants U01HL100408, U01HL107440, R01DK095384, and R01DK097768; and the Harvard Stem Cell Institute (C.A.C.). NR 121 TC 13 Z9 14 U1 15 U2 30 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 JAN 7 PY 2016 VL 18 IS 1 BP 53 EP 65 DI 10.1016/j.stem.2015.12.002 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DG8GP UT WOS:000372321300011 PM 26748756 ER PT J AU Giani, FC Fiorini, C Wakabayashi, A Ludwig, LS Salem, RM Jobaliya, CD Regan, SN Ulirsch, JC Liang, G Steinberg-Shemer, O Guo, MH Esko, T Tong, W Brugnara, C Hirschhorn, JN Weiss, MJ Zon, LI Chou, ST French, DL Musunuru, K Sankaran, VG AF Giani, Felix C. Fiorini, Claudia Wakabayashi, Aoi Ludwig, Leif S. Salem, Rany M. Jobaliya, Chintan D. Regan, Stephanie N. Ulirsch, Jacob C. Liang, Ge Steinberg-Shemer, Orna Guo, Michael H. Esko, Tonu Tong, Wei Brugnara, Carlo Hirschhorn, Joel N. Weiss, Mitchell J. Zon, Leonard I. Chou, Stella T. French, Deborah L. Musunuru, Kiran Sankaran, Vijay G. TI Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells SO CELL STEM CELL LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; IDIOPATHIC ERYTHROCYTOSIS; SELF-RENEWAL; LNK; DIFFERENTIATION; CHALLENGES; MUTATIONS; JAK2; HEMATOPOIESIS; SPECIFICATION AB Multipotent and pluripotent stem cells are potential sources for cell and tissue replacement therapies. For example, stem cell-derived red blood cells (RBCs) are a potential alternative to donated blood, but yield and quality remain a challenge. Here, we show that application of insight from human population genetic studies can enhance RBC production from stem cells. The SH2B3 gene encodes a negative regulator of cytokine signaling and naturally occurring loss-of-function variants in this gene increase RBC counts in vivo. Targeted suppression of SH2B3 in primary human hematopoietic stem and progenitor cells enhanced the maturation and overall yield of in-vitro-derived RBCs. Moreover, inactivation of SH2B3 by CRISPR/Cas9 genome editing in human pluripotent stem cells allowed enhanced erythroid cell expansion with preserved differentiation. Our findings therefore highlight the potential for combining human genome variation studies with genome editing approaches to improve cell and tissue production for regenerative medicine. C1 [Giani, Felix C.; Fiorini, Claudia; Wakabayashi, Aoi; Ludwig, Leif S.; Ulirsch, Jacob C.; Zon, Leonard I.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA 02115 USA. [Giani, Felix C.; Fiorini, Claudia; Wakabayashi, Aoi; Ludwig, Leif S.; Ulirsch, Jacob C.; Zon, Leonard I.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Giani, Felix C.; Fiorini, Claudia; Wakabayashi, Aoi; Ludwig, Leif S.; Salem, Rany M.; Regan, Stephanie N.; Ulirsch, Jacob C.; Guo, Michael H.; Esko, Tonu; Hirschhorn, Joel N.; Zon, Leonard I.; Musunuru, Kiran; Sankaran, Vijay G.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Jobaliya, Chintan D.; Liang, Ge; Steinberg-Shemer, Orna; Tong, Wei; Chou, Stella T.; French, Deborah L.] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Jobaliya, Chintan D.; Liang, Ge; Steinberg-Shemer, Orna; Tong, Wei; Chou, Stella T.; French, Deborah L.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Regan, Stephanie N.; Zon, Leonard I.; Musunuru, Kiran] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Salem, Rany M.; Guo, Michael H.; Esko, Tonu; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Salem, Rany M.; Guo, Michael H.; Esko, Tonu; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Weiss, Mitchell J.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. [Brugnara, Carlo] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Giani, Felix C.; Ludwig, Leif S.] Charite, Dept Neonatol, D-10117 Berlin, Germany. [Ludwig, Leif S.] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany. RP Sankaran, VG (reprint author), Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA 02115 USA.; Sankaran, VG (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.; Sankaran, VG (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM sankaran@broadinstitute.org OI Ludwig, Leif/0000-0002-2916-2164; Fiorini, Claudia/0000-0003-4878-2438 FU National Institutes of Health (NIH) [R21 HL120791, R01 DK103794, K99 HL122515, R01 DK100854, R01 GM104464] FX We thank D. Nathan, S. Orkin, L. Cheng, R. Kapur, D. Wojchowski, J. Flygare, H. Lodish, C. Dame, and members of the Sankaran laboratory for valuable comments on this work. We are grateful to L. Gaffney and T. Dicesare for help with illustrations. This work was supported by National Institutes of Health (NIH) grants R21 HL120791 and R01 DK103794 (V.G.S.), K99 HL122515 (R.M.S.), R01 DK100854 (S.T.C.), and R01 GM104464 (K.M.). NR 35 TC 9 Z9 9 U1 1 U2 9 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 JAN 7 PY 2016 VL 18 IS 1 BP 73 EP 78 DI 10.1016/j.stem.2015.09.015 PG 6 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DG8GP UT WOS:000372321300013 PM 26607381 ER PT J AU van Galen, P Viny, AD Ram, O Ryan, RJH Cotton, MJ Donohue, L Sievers, C Drier, Y Liau, BB Gillespie, SM Carroll, KM Cross, MB Levine, RL Bernstein, BE AF van Galen, Peter Viny, Aaron D. Ram, Oren Ryan, Russell J. H. Cotton, Matthew J. Donohue, Laura Sievers, Cem Drier, Yotam Liau, Brian B. Gillespie, Shawn M. Carroll, Kaitlin M. Cross, Michael B. Levine, Ross L. Bernstein, Bradley E. TI A Multiplexed System for Quantitative Comparisons of Chromatin Landscapes SO MOLECULAR CELL LA English DT Article ID GENOME-WIDE; CHIP-SEQ; HISTONE H3; LYSINE 27; LINEAR AMPLIFICATION; EZH2; DNA; HYPERTRIMETHYLATION; MUTATIONS; LYMPHOMA AB Genome-wide profiling of histone modifications can provide systematic insight into the regulatory elements and programs engaged in a given cell type. However, conventional chromatin immunoprecipitation and sequencing (ChIP-seq) does not capture quantitative information on histone modification levels, requires large amounts of starting material, and involves tedious processing of each individual sample. Here, we address these limitations with a technology that leverages DNA barcoding to profile chromatin quantitatively and in multiplexed format. We concurrently map relative levels of multiple histone modifications across multiple samples, each comprising as few as a thousand cells. We demonstrate the technology by monitoring dynamic changes following inhibition of p300, EZH2, or KDM5, by linking altered epigenetic landscapes to chromatin regulator mutations, and by mapping active and repressive marks in purified human hematopoietic stem cells. Hence, this technology enables quantitative studies of chromatin state dynamics across rare cell types, genotypes, environmental conditions, and drug treatments. C1 [van Galen, Peter; Ram, Oren; Ryan, Russell J. H.; Cotton, Matthew J.; Donohue, Laura; Sievers, Cem; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [van Galen, Peter; Ram, Oren; Ryan, Russell J. H.; Cotton, Matthew J.; Donohue, Laura; Sievers, Cem; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [van Galen, Peter; Ram, Oren; Ryan, Russell J. H.; Cotton, Matthew J.; Donohue, Laura; Sievers, Cem; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [van Galen, Peter; Ram, Oren; Ryan, Russell J. H.; Cotton, Matthew J.; Donohue, Laura; Sievers, Cem; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Viny, Aaron D.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Viny, Aaron D.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA. [Cotton, Matthew J.; Donohue, Laura; Gillespie, Shawn M.; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Carroll, Kaitlin M.; Cross, Michael B.] Hosp Special Surg, Dept Adult Reconstruct & Joint Replacement, 535 E 70th St, New York, NY 10021 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Bernstein, BE (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Bernstein, BE (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Bernstein, BE (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.; Bernstein, BE (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. EM bernstein.bradley@mgh.harvard.edu RI Drier, Yotam/K-5208-2012; OI Drier, Yotam/0000-0003-1725-2995; Viny, Aaron/0000-0001-7039-0110 FU National Human Genome Research Institute [HG006991, HG006193]; National Heart Lung and Blood Institute [U01HL100395]; Howard Hughes Medical Institute; EMBO Fellowships [ALTF 1207-2014, ALTF 654-2014]; Damon Runyon Postdoctoral Fellowship FX We thank D. Flowers and I. Bernstein for providing test samples; R. Nicol, A. Gerard, and A. Kreso for helpful suggestions and comments; and J.D. Jaffe for sharing mass spectrometry data. This research was supported by funds from the National Human Genome Research Institute (HG006991 and HG006193), the National Heart Lung and Blood Institute (U01HL100395), the Howard Hughes Medical Institute, EMBO Fellowships (P.v.G. ALTF 1207-2014 and C.S. ALTF 654-2014), and a Damon Runyon Postdoctoral Fellowship (A.D.V.). B.E.B. is an American Cancer Society Research Professor. NR 32 TC 8 Z9 8 U1 1 U2 6 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 JAN 7 PY 2016 VL 61 IS 1 BP 170 EP 180 DI 10.1016/j.molcel.2015.11.003 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DG8HQ UT WOS:000372324500015 PM 26687680 ER PT J AU Flavahan, WA Drier, Y Liau, BB Gillespie, SM Venteicher, AS Stemmer-Rachamimov, AO Suva, ML Bernstein, BE AF Flavahan, William A. Drier, Yotam Liau, Brian B. Gillespie, Shawn M. Venteicher, Andrew S. Stemmer-Rachamimov, Anat O. Suva, Mario L. Bernstein, Bradley E. TI Insulator dysfunction and oncogene activation in IDH mutant gliomas SO NATURE LA English DT Article ID INTEGRATED GENOMIC ANALYSIS; DNA DEMETHYLATION; STEM-CELLS; GLIOBLASTOMA; METHYLATION; EXPRESSION; GENE; TRANSCRIPTION; PHENOTYPE; 2-HYDROXYGLUTARATE AB Gain-of-function IDH mutations are initiating events that define major clinical and prognostic classes of gliomas(1,2). Mutant IDH protein produces a new onco-metabolite, 2-hydroxyglutarate, which interferes with iron-dependent hydroxylases, including the TET family of 5'-methylcytosine hydroxylases(3-7). TET enzymes catalyse a key step in the removal of DNA methylation(8,9). IDH mutant gliomas thus manifest a CpG island methylator phenotype (G-CIMP)(10,11), although the functional importance of this altered epigenetic state remains unclear. Here we show that human IDH mutant gliomas exhibit hypermethylation at cohesin and CCCTC-binding factor (CTCF)-binding sites, compromising binding of this methylation-sensitive insulator protein. Reduced CTCF binding is associated with loss of insulation between topological domains and aberrant gene activation. We specifically demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to interact aberrantly with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Treatment of IDH mutant gliomaspheres with a demethylating agent partially restores insulator function and downregulates PDGFRA. Conversely, CRISPR-mediated disruption of the CTCF motif in IDH wild-type gliomaspheres upregulates PDGFRA and increases proliferation. Our study suggests that IDH mutations promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression. C1 [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Venteicher, Andrew S.; Stemmer-Rachamimov, Anat O.; Suva, Mario L.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Venteicher, Andrew S.; Stemmer-Rachamimov, Anat O.; Suva, Mario L.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Venteicher, Andrew S.; Stemmer-Rachamimov, Anat O.; Suva, Mario L.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Venteicher, Andrew S.; Suva, Mario L.; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Bernstein, BE (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.; Bernstein, BE (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Bernstein, BE (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Bernstein, BE (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. EM bernstein.bradley@mgh.harvard.edu RI Drier, Yotam/K-5208-2012 OI Drier, Yotam/0000-0003-1725-2995 FU American Brain Tumor Association; Jane Coffin Childs fellowship; Howard Hughes Medical Institute; National Brain Tumor Society; National Human Genome Research Institute FX We thank J. Kim, the MGH Neuro Oncology Tissue Repository, and the MGH Pathology Flow Cytometry Core for assistance with clinical samples and analysis, and E. Lander and W. Kaelin for discussions. W.A.F. is supported by a basic research fellowship from the American Brain Tumor Association. B.B.L. is supported by a Jane Coffin Childs fellowship. B.E.B. is an American Cancer Society Research Professor. This research was supported by funds from Howard Hughes Medical Institute, the National Brain Tumor Society and the National Human Genome Research Institute. NR 44 TC 82 Z9 84 U1 32 U2 59 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 JAN 7 PY 2016 VL 529 IS 7584 BP 110 EP + DI 10.1038/nature16490 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA6VY UT WOS:000367944900037 PM 26700815 ER PT J AU Geng, CR Moteabbed, M Xie, YH Schuemann, J Yock, T Paganetti, H AF Geng, Changran Moteabbed, Maryam Xie, Yunhe Schuemann, Jan Yock, Torunn Paganetti, Harald TI Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: the impact of employing a patient-specific aperture in pencil beam scanning SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE radiation-induced second cancer risk; proton therapy; TOPAS; aperture ID DOSE-RESPONSE RELATIONSHIPS; MONTE-CARLO; SECONDARY NEUTRONS; SOLID CANCER; RADIOTHERAPY; CHILDHOOD; ORGAN; FIELD; MALIGNANCIES; INDUCTION AB The purpose of this study was to compare the radiation-induced second cancer risks for in-field and out-of-field organs and tissues for pencil beam scanning (PBS) and passive scattering proton therapy (PPT) and assess the impact of adding patient-specific apertures to sharpen the penumbra in pencil beam scanning for pediatric brain tumor patients. Five proton therapy plans were created for each of three pediatric patients using PPT as well as PBS with two spot sizes (average sigma of similar to 17 mm and similar to 8 mm at isocenter) and choice of patient-specific apertures. The lifetime attributable second malignancy risks for both in-field and out-of-field tissues and organs were compared among five delivery techniques. The risk for in-field tissues was calculated using the organ equivalent dose, which is determined by the dose volume histogram. For out-of-field organs, the organ-specific dose equivalent from secondary neutrons was calculated using Monte Carlo and anthropomorphic pediatric phantoms. We find that either for small spot size PBS or for large spot size PBS, a patient-specific aperture reduces the in-field cancer risk to values lower than that for PPT. The reduction for large spot sizes (on average 43%) is larger than for small spot sizes (on average 21%). For out-of-field organs, the risk varies only marginally by employing a patient-specific aperture (on average from -2% to 16% with increasing distance from the tumor), but is still one to two orders of magnitude lower than that for PPT. In conclusion, when pencil beam spot sizes are large, the addition of apertures to sharpen the penumbra decreases the in-field radiation-induced secondary cancer risk. There is a slight increase in out-of-field cancer risk as a result of neutron scatter from the aperture, but this risk is by far outweighed by the in-field risk benefit from using an aperture with a large PBS spot size. In general, the risk for developing a second malignancy in out-of-field organs for PBS remains much lower compared to PPT even if apertures are being applied. C1 [Geng, Changran; Moteabbed, Maryam; Xie, Yunhe; Schuemann, Jan; Yock, Torunn; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Moteabbed, Maryam; Schuemann, Jan; Yock, Torunn; Paganetti, Harald] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Geng, Changran] Nanjing Univ Aeronaut & Astronaut, Dept Nucl Sci & Engn, Nanjing 210016, Jiangsu, Peoples R China. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.; Paganetti, H (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. EM HPAGANETTI@mgh.harvard.edu FU China Scholarship Council (CSC); National Natural Science Foundation of China [11475087] FX One of the authors (CG) was funded by the China Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087). We would like to thank the MGH Monte Carlo group for many fruitful discussions and the Partners Research Computing group for maintaining the computer cluster. NR 27 TC 1 Z9 1 U1 2 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 7 PY 2016 VL 61 IS 1 BP 12 EP 22 DI 10.1088/0031-9155/61/1/12 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DC2VG UT WOS:000369075400005 ER PT J AU Clasie, BM Kooy, HM Flanz, JB AF Clasie, Benjamin M. Kooy, Hanne M. Flanz, Jacob B. TI PBS machine interlocks using EWMA SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE pencil beam scanning; EWMA; proton therapy ID MONITOR UNIT CONSTRAINTS; PROTON THERAPY; OPTIMIZATION AB Delivery of pencil beam scanning (PBS) requires the on-line measurement of several beam parameters. If the measurement is outside of specified tolerances and a binary threshold algorithm is used, the beam will be paused. Given instrumentation and statistical noise such a system can lead to many pauses which could increase the treatment time. Statistical quality control methods are typically used on manufacturing lines to monitor a process and give early detection of a gradual problem and stop the process if a deviation is statistically significant. These methods can be used to develop a more intuitive algorithm for (PBS) delivery systems that is robust and safe and leads to decreased treatment times. The Exponentially Weighted Moving Average (EWMA) control scheme monitors deviations in beam properties which are averaged over a specified number of measurements with greater weight applied to the more recent ones. Simulation of an EWMA-style algorithm safely detected shifts in random and systematic delivery errors without false alarms. Binary and EWMA methods can be combined for improved reliability without sacrificing patient safety. In the EWMA method, the mean of a beam property can be related to systematic uncertainties and the standard deviation can be related to random uncertainties. This method allows one to have separate interlock levels for each type of uncertainty and to detect systematic trends. C1 [Clasie, Benjamin M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Clasie, BM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM bclasie@partners.org FU Federal Share of program by Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 10 TC 2 Z9 2 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 7 PY 2016 VL 61 IS 1 BP 400 EP 412 DI 10.1088/0031-9155/61/1/400 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DC2VG UT WOS:000369075400026 PM 26674990 ER PT J AU Hall, DC Makarova, A Paganetti, H Gottschalk, B AF Hall, David C. Makarova, Anastasia Paganetti, Harald Gottschalk, Bernard TI Validation of nuclear models in Geant4 using the dose distribution of a 177 MeV proton pencil beam SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE proton therapy; pencil beam scanning; Monte Carlo; nuclear halo ID MONTE-CARLO; GATE; OPTIMIZATION; SIMULATIONS; SETTINGS; THERAPY; TOOLKIT AB A proton pencil beam is associated with a surrounding low-dose envelope, originating from nuclear interactions. It is important for treatment planning systems to accurately model this envelope when performing dose calculations for pencil beam scanning treatments, and Monte Carlo (MC) codes are commonly used for this purpose. This work aims to validate the nuclear models employed by the Geant4 MC code, by comparing the simulated absolute dose distribution to a recent experiment of a 177 MeV proton pencil beam stopping in water. Striking agreement is observed over five orders of magnitude, with both the shape and normalisation well modelled. The normalisations of two depth dose curves are lower than experiment, though this could be explained by an experimental positioning error. The Geant4 neutron production model is also verified in the distal region. The entrance dose is poorly modelled, suggesting an unaccounted upstream source of low-energy protons. Recommendations are given for a follow-up experiment which could resolve these issues. C1 [Hall, David C.; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hall, David C.; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Makarova, Anastasia] Univ Duisburg Essen, NCTeam, Dept Radiat Oncol, Fac Med, D-45122 North Rhine Westphalia, Germany. [Gottschalk, Bernard] Harvard Univ, Lab Particle Phys & Cosmol, 18 Hammond St, Cambridge, MA 02138 USA. RP Hall, DC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.; Hall, DC (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Makarova, A (reprint author), Univ Duisburg Essen, NCTeam, Dept Radiat Oncol, Fac Med, D-45122 North Rhine Westphalia, Germany. EM dchall@mgh.harvard.edu; anastasia.makarova@uni-due.de FU National Cancer Institute [U19CA21239] FX The authors thank Dr J Daartz and Dr B Clasie for their description of the MGH experimental beam line and Dr J Schumann for comments that greatly improved the manuscript. DH and HP wish to acknowledge support from National Cancer Institute grant U19CA21239. BG thanks the Physics Department of Harvard University for continuing support. AM thanks her PhD supervisor Dr W Sauerwein and the Department of Radiation Oncology at University of Duisburg-Essen. NR 23 TC 0 Z9 0 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 7 PY 2016 VL 61 IS 1 BP N1 EP N10 DI 10.1088/0031-9155/61/1/N1 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DC2VG UT WOS:000369075400002 PM 26611861 ER PT J AU Lee, G Won, HS Lee, YM Choi, JW Oh, TI Jang, JH Choi, DK Lim, BO Kim, YJ Park, JW Puigserver, P Lim, JH AF Lee, Gibok Won, Hyung-Sik Lee, Yoon-Mi Choi, Jae-Wan Oh, Taek-In Jang, Jeong-Hwa Choi, Dong-Kug Lim, Beong-Ou Kim, Young Jun Park, Jong-Wan Puigserver, Pere Lim, Ji-Hong TI Oxidative Dimerization of PHD2 is Responsible for its Inactivation and Contributes to Metabolic Reprogramming via HIF-1 alpha Activation SO SCIENTIFIC REPORTS LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR; DISULFIDE BOND FORMATION; ENDOTHELIAL GROWTH-FACTOR; CANCER-CELL METABOLISM; PROLYL HYDROXYLASE; HIF-ALPHA; TRANSFORMATION; RAS; KINASE; FACTOR-1-ALPHA AB Prolyl hydroxylase domain protein 2 (PHD2) belongs to an evolutionarily conserved superfamily of 2-oxoglutarate and Fe(II)-dependent dioxygenases that mediates homeostatic responses to oxygen deprivation by mediating hypoxia-inducible factor-1 alpha (HIF-1 alpha) hydroxylation and degradation. Although oxidative stress contributes to the inactivation of PHD2, the precise molecular mechanism of PHD2 inactivation independent of the levels of co-factors is not understood. Here, we identified disulfide bond-mediated PHD2 homo-dimer formation in response to oxidative stress caused by oxidizing agents and oncogenic H-ras(V12) signalling. Cysteine residues in the double-stranded beta-helix fold that constitutes the catalytic site of PHD isoforms appeared responsible for the oxidative dimerization. Furthermore, we demonstrated that disulfide bond-mediated PHD2 dimerization is associated with the stabilization and activation of HIF-1 alpha under oxidative stress. Oncogenic H-ras(V12) signalling facilitates the accumulation of HIF-1 alpha in the nucleus and promotes aerobic glycolysis and lactate production. Moreover, oncogenic H-ras(V12) does not trigger aerobic glycolysis in antioxidant-treated or PHD2 knocked-down cells, suggesting the participation of the ROS-mediated PHD2 inactivation in the oncogenic H-ras(V12)-mediated metabolic reprogramming. We provide here a better understanding of the mechanism by which disulfide bond-mediated PHD2 dimerization and inactivation result in the activation of HIF-1 alpha and aerobic glycolysis in response to oxidative stress. C1 [Lee, Gibok; Oh, Taek-In; Lim, Beong-Ou; Kim, Young Jun; Lim, Ji-Hong] Konkuk Univ, Coll Biomed & Hlth Sci, Dept Biomed Chem, Chungju 380701, Chungbuk, South Korea. [Won, Hyung-Sik; Choi, Jae-Wan; Jang, Jeong-Hwa; Choi, Dong-Kug] Konkuk Univ, Dept Biotechnol, Coll Biomed & Hlth Sci, Chungju 380701, Chungbuk, South Korea. [Lee, Yoon-Mi] Konkuk Univ, Dept Food Biosci, Coll Biomed & Hlth Sci, Chungju 380701, Chungbuk, South Korea. [Park, Jong-Wan] Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea. [Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Puigserver, Pere] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA USA. RP Lim, JH (reprint author), Konkuk Univ, Coll Biomed & Hlth Sci, Dept Biomed Chem, Chungju 380701, Chungbuk, South Korea. EM jhlim@kku.ac.kr FU National Research Foundation - Korea government [2014R1A2A2A04007791, 2015R1A2A2A01002483] FX This work was supported by a National Research Foundation grant (2014R1A2A2A04007791 and 2015R1A2A2A01002483) funded by the Korea government. NR 43 TC 5 Z9 5 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 7 PY 2016 VL 6 AR 18928 DI 10.1038/srep18928 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB0IW UT WOS:000368192800002 PM 26740011 ER PT J AU Shaw, AT Friboulet, L Leshchiner, I Gainor, JF Bergqvist, S Brooun, A Burke, BJ Deng, YL Liu, W Dardaei, L Frias, RL Schultz, KR Logan, J James, LP Smeal, T Timofeevski, S Katayama, R Iafrate, AJ Le, L McTigue, M Getz, G Johnson, TW Engelman, JA AF Shaw, Alice T. Friboulet, Luc Leshchiner, Ignaty Gainor, Justin F. Bergqvist, Simon Brooun, Alexei Burke, Benjamin J. Deng, Ya-Li Liu, Wei Dardaei, Leila Frias, Rosa L. Schultz, Kate R. Logan, Jennifer James, Leonard P. Smeal, Tod Timofeevski, Sergei Katayama, Ryohei Iafrate, A. John Le, Long McTigue, Michele Getz, Gad Johnson, Ted W. Engelman, Jeffrey A. TI Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CELL LUNG-CANCER; ANAPLASTIC LYMPHOMA KINASE; INHIBITOR; EFFICACY; SAFETY; PF-06463922; GEFITINIB; CERITINIB; AP26113; GENE AB In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved. C1 [Shaw, Alice T.; Friboulet, Luc; Gainor, Justin F.; Dardaei, Leila; Frias, Rosa L.; Schultz, Kate R.; Logan, Jennifer; Getz, Gad; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Iafrate, A. John; Le, Long; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Leshchiner, Ignaty; Getz, Gad] MIT, Broad Inst, Cambridge, MA 02139 USA. [Leshchiner, Ignaty; Getz, Gad] Harvard, Cambridge, MA USA. [Bergqvist, Simon; Brooun, Alexei; Burke, Benjamin J.; Deng, Ya-Li; Liu, Wei; James, Leonard P.; Smeal, Tod; Timofeevski, Sergei; McTigue, Michele; Johnson, Ted W.] Pfizer Worldwide Res & Dev, La Jolla, CA USA. [Katayama, Ryohei] Japanese Fdn Canc Res, Tokyo, Japan. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org; ted.w.johnson@pfizer.com RI friboulet, luc/N-7276-2015 OI friboulet, luc/0000-0002-1129-4978 FU Pfizer FX Funded by Pfizer and others; ClinicalTrials. gov number, NCT01970865 NR 23 TC 51 Z9 55 U1 3 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 7 PY 2016 VL 374 IS 1 BP 54 EP 61 DI 10.1056/NEJMoa1508887 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DA1UH UT WOS:000367580500008 PM 26698910 ER PT J AU Elman, I Borsook, D AF Elman, Igor Borsook, David TI Common Brain Mechanisms of Chronic Pain and Addiction SO NEURON LA English DT Review ID LOW-BACK-PAIN; REWARD-DEFICIENCY-SYNDROME; OPIOID RECEPTOR AVAILABILITY; MEDIAL PREFRONTAL CORTEX; NEUROPATHIC PAIN; NUCLEUS-ACCUMBENS; FIBROMYALGIA-SYNDROME; DRUG-ADDICTION; PLACEBO ANALGESIA; NEURAL MECHANISMS AB While chronic pain is considered by some to be a CNS disease, little is understood about underlying neurobiological mechanisms. Addiction models have heuristic value in this regard, because both pain and addictive disorders are characterized by impaired hedonic capacity, compulsive drug seeking, and high stress. In drug addiction such symptomatology has been attributed to reward deficiency, impaired inhibitory control, incentive sensitization, aberrant learning, and anti-reward allostatic neuroadaptations. Here we propose that similar neuroadaptations exist in chronic pain patients. C1 [Elman, Igor] Wright State Univ, Boonshoft Sch Med, East Med Plaza,627 South Edwin C Moses Blvd, Dayton, OH 45417 USA. [Elman, Igor] Dayton VA Med Ctr, East Med Plaza,627 South Edwin C Moses Blvd, Dayton, OH 45417 USA. [Borsook, David] Harvard Univ, Sch Med, Ctr Pain & Brain, Boston Childrens Hosp,Massachusetts Gen Hosp, 9 Hope Ave, Waltham, MA 02453 USA. [Borsook, David] McLean Hosp, 9 Hope Ave, Waltham, MA 02453 USA. RP Elman, I (reprint author), Wright State Univ, Boonshoft Sch Med, East Med Plaza,627 South Edwin C Moses Blvd, Dayton, OH 45417 USA.; Elman, I (reprint author), Dayton VA Med Ctr, East Med Plaza,627 South Edwin C Moses Blvd, Dayton, OH 45417 USA. EM igor.elman@wright.edu FU NINDS [NS064050] FX The authors gratefully acknowledge four anonymous reviewers for their enlightening and constructive comments on the manuscript. The authors thank Sarah Steele for her help with the preparation of the manuscript for submission. The work was supported by a K24 grant (NS064050) from NINDS (D.B.). NR 276 TC 16 Z9 16 U1 12 U2 34 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD JAN 6 PY 2016 VL 89 IS 1 BP 11 EP 36 DI 10.1016/j.neuron.2015.11.027 PG 26 WC Neurosciences SC Neurosciences & Neurology GA DI5TV UT WOS:000373564300005 PM 26748087 ER PT J AU Whitley, MJ Cardona, DM Lazarides, AL Spasojevic, I Ferrer, JM Cahill, J Lee, CL Snuderl, M Blazer, DG Hwang, ES Greenup, RA Mosca, PJ Mito, JK Cuneo, KC Larrier, NA O'Reilly, EK Riedel, RF Eward, WC Strasfeld, DB Fukumura, D Jain, RK Lee, WD Griffith, LG Bawendi, MG Kirsch, DG Brigman, BE AF Whitley, Melodi Javid Cardona, Diana M. Lazarides, Alexander L. Spasojevic, Ivan Ferrer, Jorge M. Cahill, Joan Lee, Chang-Lung Snuderl, Matija Blazer, Dan G., III Hwang, E. Shelley Greenup, Rachel A. Mosca, Paul J. Mito, Jeffrey K. Cuneo, Kyle C. Larrier, Nicole A. O'Reilly, Erin K. Riedel, Richard F. Eward, William C. Strasfeld, David B. Fukumura, Dai Jain, Rakesh K. Lee, W. David Griffith, Linda G. Bawendi, Moungi G. Kirsch, David G. Brigman, Brian E. TI A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID SOFT-TISSUE SARCOMAS; BREAST-CANCER; RADIATION-THERAPY; INTRAOPERATIVE DETECTION; CYSTEINE CATHEPSINS; RANDOMIZED TRIAL; OVARIAN-CANCER; TUMORS; PROGRESSION; MODEL AB Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes. C1 [Whitley, Melodi Javid; Mito, Jeffrey K.; Kirsch, David G.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Whitley, Melodi Javid; Mito, Jeffrey K.] Duke Univ, Med Ctr, Med Sci Training Program, Durham, NC 27710 USA. [Cardona, Diana M.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Lazarides, Alexander L.] Duke Univ, Med Ctr, Sch Med, Durham, NC 27710 USA. [Spasojevic, Ivan; Riedel, Richard F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Spasojevic, Ivan] Duke Univ, Med Ctr, PK PD Core Lab, Duke Canc Inst, Durham, NC 27710 USA. [Ferrer, Jorge M.; Strasfeld, David B.; Lee, W. David] Lumicell Inc, Wellesley, MA 02481 USA. [Cahill, Joan; Lee, Chang-Lung; Cuneo, Kyle C.; Larrier, Nicole A.; Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. [Snuderl, Matija; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Snuderl, Matija; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Blazer, Dan G., III; Hwang, E. Shelley; Greenup, Rachel A.; Mosca, Paul J.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [O'Reilly, Erin K.] Duke Univ, Med Ctr, Regulatory Affairs Grp, Duke Translat Med Inst, Durham, NC 27710 USA. [Eward, William C.; Brigman, Brian E.] Duke Univ, Med Ctr, Dept Orthopaed Surg, Durham, NC 27710 USA. [Griffith, Linda G.] MIT, Dept Biol Engn, Cambridge, MA 02142 USA. [Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02142 USA. [Snuderl, Matija] NYU, Langone Med Ctr, Dept Pathol, New York, NY 10016 USA. RP Kirsch, DG (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.; Kirsch, DG (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. EM david.kirsch@duke.edu RI Blazer, Dan/F-7659-2015; OI Lazarides, Alexander/0000-0003-0704-1529; Blazer, Dan/0000-0002-7261-9254; Snuderl, Matija/0000-0003-0752-0917 FU American Society of Clinical Oncology Advanced Clinical Research Award; NIH [T32GM007171]; National Cancer Institute Small Business Innovation Research award [1U43CA165024]; National Center for Advancing Translational Science of the NIH [UL1TR001117]; Duke Comprehensive Cancer Center Support Grant [5P30-CA-014236-38] FX Supported in part by the American Society of Clinical Oncology Advanced Clinical Research Award (D.G.K.), NIH T32 grant #T32GM007171 (M.J.W. and J.K.M.), National Cancer Institute Small Business Innovation Research award #1U43CA165024 (W.D.L.), National Center for Advancing Translational Science of the NIH grant #UL1TR001117 (E.K.O.), and Duke Comprehensive Cancer Center Support Grant 5P30-CA-014236-38. NR 40 TC 11 Z9 11 U1 6 U2 29 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 6 PY 2016 VL 8 IS 320 DI 10.1126/scitranslmed.aad0293 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DB4UT UT WOS:000368509800005 ER PT J AU Walwyn, WM Chen, WL Kim, H Minasyan, A Ennes, HS McRoberts, JA Marvizon, JCG AF Walwyn, Wendy M. Chen, Wenling Kim, Hyeyoung Minasyan, Ani Ennes, Helena S. McRoberts, James A. Marvizon, Juan Carlos G. TI Sustained Suppression of Hyperalgesia during Latent Sensitization by mu-, delta-, and kappa-opioid receptors and alpha(2A) Adrenergic Receptors: Role of Constitutive Activity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adrenergic receptor; constitutive activity; hyperalgesia; kappa-opioid receptor; latent sensitization; mu-opioid receptor ID RAT SPINAL-CORD; TERNARY COMPLEX MODEL; DORSAL-HORN NEURONS; PROTEIN-KINASE-C; NEUROPATHIC PAIN; MICE LACKING; MORPHINE-WITHDRAWAL; INFLAMMATORY PAIN; PRIMARY AFFERENTS; INDUCED ANALGESIA AB Many chronic pain disorders alternate between bouts of pain and periods of remission. The latent sensitization model reproduces this in rodents by showing that the apparent recovery ("remission") from inflammatory or neuropathic pain can be reversed by opioid antagonists. Therefore, this remission represents an opioid receptor-mediated suppression of a sustained hyperalgesic state. To identify the receptors involved, we induced latent sensitization in mice and rats by injecting complete Freund's adjuvant (CFA) in the hindpaw. In WT mice, responses to mechanical stimulation returned to baseline 3 weeks after CFA. In mu-opioid receptor (MOR) knock-out (KO) mice, responses did not return to baseline but partially recovered from peak hyperalgesia. Antagonists of alpha(2A)-adrenergic and delta-opioid receptors reinstated hyperalgesia in WT mice and abolished the partial recovery from hyperalgesia in MOR KO mice. In rats, antagonists of alpha(2A) adrenergic and mu-, delta-, and kappa-opioid receptors reinstated hyperalgesia during remission from CFA-induced hyperalgesia. Therefore, these four receptors suppress hyperalgesia in latent sensitization. We further demonstrated that suppression of hyperalgesia by MORs was due to their constitutive activity because of the following: (1) CFA-induced hyperalgesia was reinstated by the MOR inverse agonist naltrexone (NTX), but not by its neutral antagonist 6 beta-naltrexol; (2) pro-enkephalin, pro-opiomelanocortin, and pro-dynorphin KO mice showed recovery from hyperalgesia and reinstatement by NTX; (3) there was no MOR internalization during remission; (4) MORs immunoprecipitated from the spinal cord during remission had increased Ser(375) phosphorylation; and (5) electrophysiology recordings from dorsal root ganglion neurons collected during remission showed constitutive MOR inhibition of calcium channels. C1 [Walwyn, Wendy M.; Minasyan, Ani] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Chen, Wenling; Kim, Hyeyoung; Ennes, Helena S.; McRoberts, James A.; Marvizon, Juan Carlos G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Marvizon, Juan Carlos G.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Marvizon, JCG (reprint author), VA Greater Los Angeles Healthcare syst, 11301 Wilshire Blvd,Bldg 115, Los Angeles, CA 90073 USA. EM marvizon@g.ucla.edu FU Rehabilitation Research and Development Service, Department of Veterans Affairs [1I01RX000378]; National Institutes of Health-National Institute of Drug Abuse [R01-DA033059, DA005010]; Shirley and Stefas Hatos Center for the Study of Opioid Receptors FX This work was supported by the Rehabilitation Research and Development Service, Department of Veterans Affairs (Grant 1I01RX000378 to J.C.G.M.), the National Institutes of Health-National Institute of Drug Abuse (Grant R01-DA033059 to J.C.G.M. and J.A.M. and Grant DA005010 to W.M.W and A.M.), and by the Shirley and Stefas Hatos Center for the Study of Opioid Receptors. This study was under the venue of the following UCLA institutes: the Brain Research Institute, the Center for the Study of Opioid Receptors and Drugs of Abuse, the CURE: Digestive Diseases Research Center, and the Oppenheimer Family Center for Neurobiology of Stress. We thank Bradley K. Taylor for critical discussion. NR 77 TC 3 Z9 3 U1 1 U2 4 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 JAN 6 PY 2016 VL 36 IS 1 BP 204 EP 221 DI 10.1523/JNEUROSCI.1751-15.2016 PG 18 WC Neurosciences SC Neurosciences & Neurology GA DB2OE UT WOS:000368348100022 PM 26740662 ER PT J AU Ellingsen, DM Leknes, S Loseth, G Wessberg, J Olausson, H AF Ellingsen, Dan-Mikael Leknes, Siri Loseth, Guro Wessberg, Johan Olausson, Hakan TI The Neurobiology Shaping Affective Touch: Expectation, Motivation, and Meaning in the Multisensory Context SO FRONTIERS IN PSYCHOLOGY LA English DT Review DE touch; top-down modulation; hedonics; oxytocin; opioids; social processing; placebo effect ID UNMYELINATED TACTILE AFFERENTS; PITUITARY-ADRENAL AXIS; FEMALE PRAIRIE VOLES; NUCLEUS-ACCUMBENS SHELL; WARM PARTNER CONTACT; PRIMARY TASTE CORTEX; PLACEBO ANALGESIA; MATERNAL-BEHAVIOR; PLEASANT TOUCH; HAIRY SKIN AB Inter individual touch can be a desirable reward that can both relieve negative affect and evoke strong feelings of pleasure. However, if other sensory cues indicate it is undesirable to interact with the toucher, the affective experience of the same touch may be flipped to disgust. While a broad literature has addressed, on one hand the neurophysiological basis of ascending touch pathways, and on the other hand the central neurochemistry involved in touch behaviors, investigations of how external context and internal state shapes the hedonic value of touch have only recently emerged. Here, we review the psychological and neurobiological mechanisms responsible for the integration of tactile "bottom-up" stimuli and "top-down" information into affective touch experiences. We highlight the reciprocal influences between gentle touch and contextual information, and consider how, and at which levels of neural processing, top down influences may modulate ascending touch signals. Finally, we discuss the central neurochemistry, specifically the mu-opioids and oxytocin systems, involved in affective touch processing, and how the functions of these neurotransmitters largely depend on the context and motivational state of the individual. C1 [Ellingsen, Dan-Mikael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HST Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02215 USA. [Ellingsen, Dan-Mikael; Leknes, Siri; Loseth, Guro] Univ Oslo, Dept Psychol, Oslo, Norway. [Wessberg, Johan] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Olausson, Hakan] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden. RP Ellingsen, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HST Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02215 USA. EM d.m.ellingsen@psykologi.uio.no FU Norwegian Research Council (FRIPRO); Marie Sklodowska-Curie Actions, under the COFUND program [240553/F20] FX D-ME is supported by a postdoctoral scholarship from the Norwegian Research Council (FRIPRO) and the Marie Sklodowska-Curie Actions, under the COFUND program (240553/F20). NR 262 TC 4 Z9 4 U1 12 U2 24 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD JAN 6 PY 2016 VL 6 AR 1986 DI 10.3389/fpsyg.2015.01986 PG 16 WC Psychology, Multidisciplinary SC Psychology GA DA3YV UT WOS:000367738200001 ER PT J AU Singh, JA Yu, SH AF Singh, Jasvinder A. Yu, Shaohua TI Utilization due to chronic obstructive pulmonary disease and its predictors: a study using the US National Emergency Department Sample (NEDS) SO RESPIRATORY RESEARCH LA English DT Article ID QUALITY-OF-LIFE; ACUTE EXACERBATION; UNITED-STATES; RISK-FACTORS; HOSPITAL ADMISSION; INPATIENT SAMPLE; ECONOMIC BURDEN; LUNG-FUNCTION; COPD PATIENTS; BODE INDEX AB Background: Previous studies of healthcare utilization for chronic obstructive pulmonary disease (COPD) have focused on time-trends in COPD visits or COPD treatments, or the effect of hospital volume on mortality. Few data are available regarding outcomes after an ED visit (and subsequent hospitalization) for COPD, which are both very common in patients with COPD. Our objective was to assess time-trends and predictors of emergency department and subsequent inpatient health care utilization and charges associated with COPD in the U.S. Method: We used the 2009-12 U.S. Nationwide Emergency Department Sample (NEDS) to study the incidence of ED visits and subsequent hospitalizations with COPD as the primary diagnosis. We used the 2012 NEDS data to study key patient/hospital factors associated with outcomes, including charges, hospitalization and dischage from hospital to home. Results: ED visits for COPD as the primary diagnosis increased from 1.02 million in 2009 to 1.04 in 2010 to 1.10 million in 2012 (0.79-0.82 % of all ED visits); respective charges were $2.13, $2.32, and $3.09 billion. In 2012, mean ED charges/visit were $2,812, hospitalization charges/visit were $29,043 and the length of hospital stay was 4.3 days. 49 % were hospitalized after an ED visit. Older age, higher median income, metropolitan residence and comorbidities (diabetes, hypertension, HF, hyperlipidemia, CHD, renal failure and osteoarthritis) were associated with higher risk whereas male sex, Medicaid or self pay insurance status, hospital location in Midwest, South or West U.S. were associated with lower risk of hospitalization. 65.4 % of all patients hospitalized for COPD from ED were discharged home. Older age, comorbidities (diabetes, HF, CHD, renal failure, osteoarthritis) and metropolitan residence were associated with lower odds of discharge to home, whereas male sex, payer other than Medicare, Midwest, South or West U.S. hospital location were associated with higher odds. Conclusion: Health care utilization and costs in patients with COPD are significant and increasing. COPD constitutes a major public health burden in the U.S. We identified risk factors for hospitalization, costs, and home discharge in patients with COPD that will allow future studies to investigate interventions to potentially reduce COPD-associated utilization. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.; Yu, Shaohua] UAB, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Yu, Shaohua] UAB, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM Jasvinder.md@gmail.com FU National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS) [P50 AR060772]; UAB Division of Rheumatology FX This material is the result of work supported by research funds from UAB Division of Rheumatology and the resources and use of facilities at the Birmingham VA Medical Center. JAS is also supported by grant from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS) P50 AR060772. NR 48 TC 2 Z9 2 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-993X EI 1465-9921 J9 RESP RES JI Respir. Res. PD JAN 6 PY 2016 VL 17 AR 1 DI 10.1186/s12931-015-0319-y PG 12 WC Respiratory System SC Respiratory System GA DA1TN UT WOS:000367578500001 PM 26739476 ER PT J AU Nilsson, RJA Karachaliou, N Berenguer, J Gimenez-Capitan, A Schellen, P Teixido, C Tannous, J Kuiper, JL Drees, E Grabowska, M van Keulen, M Heideman, DAM Thunnissen, E Dingemans, AMC Viteri, S Tannous, BA Drozdowskyj, A Rosell, R Smit, EF Wurdinger, T AF Nilsson, R. Jonas A. Karachaliou, Niki Berenguer, Jordi Gimenez-Capitan, Ana Schellen, Pepijn Teixido, Cristina Tannous, Jihane Kuiper, Justine L. Drees, Esther Grabowska, Magda van Keulen, Marte Heideman, Danielle A. M. Thunnissen, Erik Dingemans, Anne-Marie C. Viteri, Santiago Tannous, Bakhos A. Drozdowskyj, Ana Rosell, Rafael Smit, Egbert F. Wurdinger, Thomas TI Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer SO ONCOTARGET LA English DT Article DE diagnostics; NSCLC; liquid biopsies; platelets; EML4-ALK ID RANDOMIZED PHASE-3 TRIAL; TUMOR-GROWTH; OPEN-LABEL; 1ST-LINE TREATMENT; BIOMARKERS; RNA; ANGIOGENESIS; CHEMOTHERAPY; MUTATIONS; MECHANISM AB Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone. C1 [Nilsson, R. Jonas A.; Berenguer, Jordi; Schellen, Pepijn; Drees, Esther; Grabowska, Magda; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Canc Ctr Amsterdam, Amsterdam, Netherlands. [Nilsson, R. Jonas A.] Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden. [Nilsson, R. Jonas A.; Schellen, Pepijn; Wurdinger, Thomas] ThromboDx BV, Amsterdam, Netherlands. [Karachaliou, Niki; Viteri, Santiago; Rosell, Rafael] Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst, Translat Res Unit, Barcelona, Spain. [Gimenez-Capitan, Ana; Teixido, Cristina; Rosell, Rafael] Pangaea Biotech SL, Barcelona, Spain. [Tannous, Jihane; van Keulen, Marte; Tannous, Bakhos A.; Wurdinger, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Tannous, Jihane; van Keulen, Marte; Tannous, Bakhos A.; Wurdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA USA. [Kuiper, Justine L.; Smit, Egbert F.] Vrije Univ Amsterdam, Med Ctr, Dept Pulm Dis, Canc Ctr Amsterdam, Amsterdam, Netherlands. [Heideman, Danielle A. M.; Thunnissen, Erik] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Canc Ctr Amsterdam, Amsterdam, Netherlands. [Dingemans, Anne-Marie C.] Maastricht Univ, Med Ctr, Dept Pulm Dis, NL-6200 MD Maastricht, Netherlands. [Drozdowskyj, Ana] Pivotal, Madrid, Spain. [Rosell, Rafael] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Barcelona, Spain. [Rosell, Rafael] Mol Oncol Res MORe Fdn, Barcelona, Spain. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Canc Ctr Amsterdam, Amsterdam, Netherlands.; Wurdinger, T (reprint author), ThromboDx BV, Amsterdam, Netherlands.; Wurdinger, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.; Wurdinger, T (reprint author), Harvard Univ, Sch Med, Neurosci Program, Boston, MA USA. EM t.wurdinger@vumc.nl FU European Research Council [E8626, 336540]; Dutch Organisation of Scientific Research [93612003, 91711366]; NIH [2012D006044]; CFF Norrland; Swedish Research Council; "La Caixa" Foundation; Redes Tematicas de Investigacion en Cancer [RD12/0036/0072] FX Financial support was provided by European Research Council E8626 (RJAN, EFS, TW) and 336540 (TW), the Dutch Organisation of Scientific Research 93612003 and 91711366 (TW), the NIH 2012D006044 (BAT), CFF Norrland (RJAN), and the Swedish Research Council (RJAN). Work in Dr Rosell's laboratory is partially supported by a grant from "La Caixa" Foundation and by Redes Tematicas de Investigacion en Cancer (RD12/0036/0072). Employees of thromboDx BV and Pangaea Biotech SL contributed in this study. NR 26 TC 16 Z9 18 U1 2 U2 2 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 5 PY 2016 VL 7 IS 1 BP 1066 EP 1075 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DD5GI UT WOS:000369950300077 PM 26544515 ER PT J AU Castro, VM Kong, SW Clements, CC Brady, R Kaimal, AJ Doyle, AE Robinson, EB Churchill, SE Kohane, IS Perlis, RH AF Castro, V. M. Kong, S. W. Clements, C. C. Brady, R. Kaimal, A. J. Doyle, A. E. Robinson, E. B. Churchill, S. E. Kohane, I. S. Perlis, R. H. TI Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID SPECTRUM DISORDERS; BEHAVIOR; DEPRESSION; ENTERPRISE AB Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1: 3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50 - 1.54 for ASD; 0.97, 95% confidence interval 0.53 - 1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation. C1 [Castro, V. M.; Clements, C. C.; Doyle, A. E.; Robinson, E. B.; Perlis, R. H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, 185 Cambridge St,6th Floor,Simches Res Bldg, Boston, MA 02114 USA. [Castro, V. M.] Partners HealthCare Syst, Constitut Ctr 1, Partners Res Comp, Boston, MA USA. [Kong, S. W.; Kohane, I. S.] Boston Childrens Hosp, Informat Program, Boston, MA USA. [Clements, C. C.; Doyle, A. E.; Perlis, R. H.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Brady, R.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Kaimal, A. J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Robinson, E. B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Analyt & Translat Genom Unit, Boston, MA 02114 USA. [Churchill, S. E.; Kohane, I. S.] Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA USA. [Kohane, I. S.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, 185 Cambridge St,6th Floor,Simches Res Bldg, Boston, MA 02114 USA. EM rperlis@partners.org OI Robinson, Elise/0000-0003-2314-2792 FU National Institute of Mental Health [5R01MH100286-02]; NIMH [R01MH086026, 5 K23 MH100623]; NIMH/NHGRI [1P50MH106933]; NIH/National Library of Medicine [2U54LM008748] FX This work was supported through funding from the National Institute of Mental Health (5R01MH100286-02). RHP is supported by NIMH R01MH086026 and NIMH/NHGRI 1P50MH106933. The i2b2 platform (PI: ISK) is supported by award number 2U54LM008748 from the NIH/National Library of Medicine. RB is supported by NIMH 5 K23 MH100623. The authors express their gratitude to the staff at the Massachusetts Registry of Vital Records and Statistics including Kevin Foster and Dean DiMartino. NR 13 TC 7 Z9 7 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JAN 5 PY 2016 VL 6 AR e708 DI 10.1038/tp.2015.190 PG 6 WC Psychiatry SC Psychiatry GA DB5JD UT WOS:000368549500008 PM 26731445 ER PT J AU Kindy, MS Yu, J Zhu, H Smith, MT Gattoni-Celli, S AF Kindy, Mark S. Yu, Jin Zhu, Hong Smith, Michael T. Gattoni-Celli, Sebastiano TI A therapeutic cancer vaccine against GL261 murine glioma SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Glioblastoma; Immunotherapy; Semi-allogeneic; Cancer; Vaccine ID BRAIN-TUMORS; CELL HYBRIDS; GLIOBLASTOMA; MICROGLIA; MODEL AB Background: Glioblastoma (GBM) is the deadliest of brain tumors. Standard treatment for GBM is surgery, followed by combined radiation therapy and chemotherapy. Current therapy prolongs survival but does not offer a cure. We report on a novel immunotherapy against GBM, tested in an animal model of C57BL/6 mice injected intra-cranially with a lethal dose of murine GL261 glioma cells. Methods: Ten week-old C57BL/6 mice were anesthetized before injection of 2 x 10(4) GL261 cells in the right cerebral hemisphere and after 3 days half of the mice were administered a single subcutaneous (s.c.) injection of irradiated semi-allogeneic vaccine, while mock-vaccinated mice received a s.c. injection of phosphate-buffered saline (PBS). Tumor engraftment was monitored through bioluminescence imaging (BLI). Length of animal survival was measured by Kaplan-Meier graphs and statistics. At time of sacrifice brain tissue was processed for estimation of tumor size and immunohistochemical studies. Results: Overall survival of vaccinated mice was significantly longer compared to mock-vaccinated mice. Five to ten percent of vaccinated mice survived more than 90 days following the engraftment of GL261 cells in the brain and appeared to be free of disease by BLI. Tumor volume in the brain of vaccinated mice was on average five to ten-fold smaller compared to mock-vaccinated mice. In vaccinated mice, conspicuous microglia infiltrates were observed in tumor tissue sections and activated microglia appeared to form a fence along the perimeter of the tumor cells. The results of these animal studies persuaded the Office of Orphan Products Development of the Food and Drug Administration (FDA) to grant Orphan Drug Designation for treatment of GBM with irradiated, semi-allogeneic vaccines. Conclusions: Our preclinical observations suggest that semi-allogeneic vaccines could be tested clinically on subjects with GBM, as an adjuvant to standard treatment. C1 [Kindy, Mark S.; Yu, Jin; Zhu, Hong] Univ S Florida, Dept Pharmaceut Sci, Tampa, FL 33612 USA. [Smith, Michael T.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Gattoni-Celli, Sebastiano] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Gattoni-Celli, S (reprint author), Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. EM gattonis@musc.edu FU Veterans Administration (VA) CSRD Merit Awards [CX000753, RRD RX001450]; National Institutes of Health [NIH R01 ES016774-01, R21AG043718, 1P20GM109091, 2P20GM103444, 5P30GM103342]; National Science Foundation [IIP-0903795] FX We thank Dr. Mark P. Rubinstein (Department of Surgery, MUSC) for helping with the FACS experiments. This research was funded by Veterans Administration (VA) CSR&D Merit Awards CX000753 to SG-C, RR&D RX001450, National Institutes of Health (NIH R01 ES016774-01, R21AG043718, 1P20GM109091, 2P20GM103444, and 5P30GM103342, and a grant from the National Science Foundation (IIP-0903795) to MSK. Mark S. Kindy is a Senior Research Career Scientist in the VA. NR 14 TC 1 Z9 1 U1 3 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JAN 5 PY 2016 VL 14 DI 10.1186/s12967-015-0757-9 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DA8LT UT WOS:000368057000001 ER PT J AU Jehle, J Hoyer, FF Schone, B Pfeifer, P Schild, K Jenniches, I Bindila, L Lutz, B Lutjohann, D Zimmer, A Nickenig, G AF Jehle, Julian Hoyer, Friedrich Felix Schoene, Benedikt Pfeifer, Philipp Schild, Katharina Jenniches, Imke Bindila, Laura Lutz, Beat Luetjohann, Dieter Zimmer, Andreas Nickenig, Georg TI Myeloid-Specific Deletion of Diacylglycerol Lipase a Inhibits Atherogenesis in ApoE-Deficient Mice SO PLOS ONE LA English DT Article ID ACTIVATED ENDOCANNABINOID SYSTEM; CANNABINOID CB2 RECEPTOR; CORONARY-ARTERY-DISEASE; ATHEROSCLEROSIS; CELLS; 2-ARACHIDONOYLGLYCEROL; INFLAMMATION; MACROPHAGES; INVOLVEMENT; BRAIN AB Background The endocannabinoid 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation. Despite its high concentration in vascular tissue, the role of 2-AG in atherogenesis has not yet been examined. Methods ApoE-deficient mice were sublethally irradiated and reconstituted with bone marrow from mice with a myeloid-specific knockout of the 2-AG synthesising enzyme diacylglycerol lipase alpha (Dagla) or control bone marrow with an intact 2-AG biosynthesis. After a cholesterol- rich diet for 8 weeks, plaque size and plaque morphology were examined in chimeric mice. Circulating inflammatory cells were assessed by flow cytometry. Aortic tissue and plasma levels of endocannabinoids were measured using liquid chromatography-multiple reaction monitoring. Results Mice with Dagla-deficient bone marrow and circulating myeloid cells showed a significantly reduced plaque burden compared to controls. The reduction in plaque size was accompanied by a significantly diminished accumulation of both neutrophil granulocytes and macrophages in atherosclerotic lesions of Dagla-deficient mice. Moreover, CB2 expression and the amount of oxidised LDL within atherosclerotic lesions was significantly reduced. FACS analyses revealed that levels of circulating inflammatory cells were unaltered in Dagla-deficient mice. Conclusions Myeloid synthesis of the endocannabinoid 2-AG appears to promote vascular inflammation and atherogenesis. Thus, myeloid-specific disruption of 2-AG synthesis may represent a potential novel therapeutic strategy against atherosclerosis. C1 [Jehle, Julian; Schoene, Benedikt; Pfeifer, Philipp; Schild, Katharina; Nickenig, Georg] Univ Bonn, Klin Innere Med 2, Bonn, Germany. [Hoyer, Friedrich Felix] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Jenniches, Imke; Zimmer, Andreas] Univ Bonn, Inst Mol Psychiat, Bonn, Germany. [Bindila, Laura; Lutz, Beat] Johannes Gutenberg Univ Mainz, Inst Physiol Chem, D-55122 Mainz, Germany. [Luetjohann, Dieter] Univ Bonn, Inst Klin Chem & Klin Pharmakol, Bonn, Germany. RP Jehle, J (reprint author), Univ Bonn, Klin Innere Med 2, Bonn, Germany. EM julian.jehle@ukb.uni-bonn.de FU Deutsche Forschungsgemeinschaft [FOR926 SP6]; Bonfor programm (Gerok scholarship) FX This work was supported by a grant from the Deutsche Forschungsgemeinschaft to AZ (FOR926 SP6) and by the Bonfor programm (Gerok scholarship to JJ). GN and AZ are members of the Excellence Cluster Immunosensation.; We thank Theresa Schmitz, Anna Flender, Kathrin Paul-Krahe Heike Slomka and Anja Kerksiek for excellent technical assistance. We are grateful to Dr. rer. nat. Garbe for the irradiation of the mice. This work was supported by a grant from the Deutsche Forschungsgemeinschaft to AZ (FOR926 SP6) and by the Bonfor programm (Gerok scholarship to JJ). GN and AZ are members of the Excellence Cluster Immunosensation. NR 25 TC 0 Z9 1 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 5 PY 2016 VL 11 IS 1 AR e0146267 DI 10.1371/journal.pone.0146267 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA4VZ UT WOS:000367801400135 PM 26731274 ER PT J AU Li, BT Lou, E Hsu, M Yu, HA Naidoo, J Zauderer, MG Sima, C Johnson, ML Daras, M DeAngelis, LM Fleisher, M Kris, MG Azzoli, CG AF Li, Bob T. Lou, Emil Hsu, Meier Yu, Helena A. Naidoo, Jarushka Zauderer, Marjorie G. Sima, Camelia Johnson, Melissa L. Daras, Mariza DeAngelis, Lisa M. Fleisher, Martin Kris, Mark G. Azzoli, Christopher G. TI Serum Biomarkers Associated with Clinical Outcomes Fail to Predict Brain Metastases in Patients with Stage IV Non-Small Cell Lung Cancers SO PLOS ONE LA English DT Article ID EGFR MUTATION STATUS; TUMOR-MARKERS; CARCINOEMBRYONIC ANTIGEN; PROGNOSTIC-FACTORS; RADIATION-THERAPY; DIAGNOSIS; CYFRA-21-1; CARCINOMA; SURVIVAL; SCC AB Background Lung cancers account for the majority of brain metastases which pose major therapeutic challenges. Biomarkers prognosticating for the development of brain metastases in patients with non-small cell lung cancers (NSCLC) may improve personalized care. Six serum proteomic biomarkers were previously investigated at Memorial Sloan Kettering but their associations with brain metastases were unknown. Methods Serum NSE, CYFRA 21-1, ProGRP, SCC-Ag, TIMP1, and HE4 by ELISA-based proteomic assays were prospectively collected from consecutive patients with stage IV NSCLC. Pretreatment serum biomarker levels as well as age, histology, and epidermal growth factor receptor (EGFR) mutation status were evaluated for association with the baseline presence of brain metastases using logistic regression and multivariable analysis. For patients without brain metastases at baseline, the cumulative incidence of subsequent brain metastases were compared according to baseline biomarkers and clinical factors using Gray's test. Results A total of 118 patients were enrolled, 31 (26%; 95% CI 0.19-0.35) had brain metastases at baseline and a further 26 (22%; 95% CI 0.15-0.30) developed brain metastases subsequently. Pre-treatment serum biomarker levels were available in 104 patients. There was no significant association between the six serum biomarkers and the baseline presence or subsequent development of brain metastases. Age younger than 65 years was the only clinical factor significantly associated with brain metastasis at baseline (OR 3.00; 95% CI 1.22-7.34, P = 0.02) by multivariable analysis. A trend toward increased cumulative incidence of subsequent brain metastases was observed in patients with EGFR mutation (p = 0.2), but this was not statistically significant possibly due to small sample size. Conclusions Serum NSE, CYFRA 21-1, Pro-GRP, SCC-Ag, TIMP1, and HE4 are not significantly associated with brain metastases. Our methods taking into account follow-up time may be applied to independent datasets to identify a patient cohort with a higher biologic propensity for developing brain metastases. Such information may be useful for the study of agents targeting the development of brain metastases. C1 [Li, Bob T.; Yu, Helena A.; Naidoo, Jarushka; Zauderer, Marjorie G.; Johnson, Melissa L.; Kris, Mark G.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, Div Solid Tumor Oncol,Dept Med, New York, NY 10065 USA. [Li, Bob T.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Lou, Emil] Univ Minnesota, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Hsu, Meier; Sima, Camelia] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA. [Daras, Mariza; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. [Fleisher, Martin] Mem Sloan Kettering Canc Ctr, Clin Chem Serv, Dept Lab Med, New York, NY 10065 USA. [Azzoli, Christopher G.] Massachusetts Gen Hosp, Ctr Canc, Thorac Oncol Program, Boston, MA 02114 USA. RP Li, BT (reprint author), Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, Div Solid Tumor Oncol,Dept Med, 300 E 66th St,12th Floor, New York, NY 10065 USA. EM lib1@mskcc.org OI Li, Bob/0000-0001-6661-8733; Zauderer, Marjorie/0000-0002-6109-5790; Kris, Mark/0000-0002-7317-5341 FU Core Grant at Memorial Sloan Kettering Cancer Center from the National Institutes of Health, USA [P30 CA008748] FX Unrestricted philanthropic funding to the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center was used to support the study, as received by MGK. This study was supported by the Core Grant (P30 CA008748) at Memorial Sloan Kettering Cancer Center from the National Institutes of Health, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 3 Z9 3 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 5 PY 2016 VL 11 IS 1 AR e0146063 DI 10.1371/journal.pone.0146063 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA4VZ UT WOS:000367801400086 PM 26730601 ER PT J AU Singhal, PK Sassi, S Lan, L Au, P Halvorsen, SC Fukumura, D Jain, RK Seed, B AF Singhal, Prabhat K. Sassi, Slim Lan, Lan Au, Patrick Halvorsen, Stefan C. Fukumura, Dai Jain, Rakesh K. Seed, Brian TI Mouse embryonic fibroblasts exhibit extensive developmental and phenotypic diversity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryo; fibroblast; lineage; heterogeneity; phenotype ID MESENCHYMAL STEM-CELLS; SIDE POPULATION CELLS; HUMAN BONE-MARROW; GENE-EXPRESSION; TUMOR MICROENVIRONMENT; STROMAL FIBROBLASTS; PROGENITOR CELLS; HETEROGENEITY; PROTEIN; IDENTIFICATION AB Analysis of embryonic fibroblasts from GFP reporter mice indicates that the fibroblast cell type harbors a large collection of developmentally and phenotypically heterogeneous subtypes. Some of these cells exhibit multipotency, whereas others do not. Multiparameter flow cytometry analysis shows that a large number of distinct populations of fibroblast-like cells can be found in cultures initiated from different embryonic organs, and cells sorted according to their surface phenotype typically retain their characteristics on continued propagation in culture. Similarly, surface phenotypes of individual cloned fibroblast-like cells exhibit significant variation. The fibroblast cell class appears to contain a very large number of denumerable subtypes. C1 [Singhal, Prabhat K.; Sassi, Slim; Lan, Lan; Halvorsen, Stefan C.; Seed, Brian] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Singhal, Prabhat K.; Lan, Lan; Seed, Brian] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Sassi, Slim] Harvard Univ, Sch Med, Dept Orthoped, Boston, MA 02115 USA. [Au, Patrick; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. [Au, Patrick; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu; bseed@ccib.mgh.harvard.edu FU National Institutes of Health [P01CA080124, R35CA197743, R01DK103879] FX We thank Sylvie Roberge for assistance with the cranial window preparation, Peigen Huang for management of the mouse colony, and Gino Ferraro for comments on the manuscript. This research was supported by National Institutes of Health Grants P01CA080124, R35CA197743, and R01DK103879. NR 46 TC 4 Z9 4 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 5 PY 2016 VL 113 IS 1 BP 122 EP 127 DI 10.1073/pnas.1522401112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA0XH UT WOS:000367520400043 PM 26699463 ER PT J AU Weinstein, S Toker, IA Emmanuel, R Ramishetti, S Hazan-Halevy, I Rosenblum, D Goldsmith, M Abraham, A Benjamini, O Bairey, O Raanani, P Nagler, A Lieberman, J Peer, D AF Weinstein, Shiri Toker, Itai A. Emmanuel, Rafi Ramishetti, Srinivas Hazan-Halevy, Inbal Rosenblum, Daniel Goldsmith, Meir Abraham, Avigdor Benjamini, Ohad Bairey, Osnat Raanani, Pia Nagler, Arnon Lieberman, Judy Peer, Dan TI Harnessing RNAi-based nanomedicines for therapeutic gene silencing in B-cell malignancies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nanomedicine; siRNA; mantle cell lymphoma; cyclin D1; CD38 ID SIRNA LIPID NANOPARTICLES; CYCLIN D1; IN-VIVO; MULTIPLE-MYELOMA; LYMPHOMA; DELIVERY; IBRUTINIB; LYMPHOCYTES; EXPRESSION; THERAPIES AB Despite progress in systemic small interfering RNA (siRNA) delivery to the liver and to solid tumors, systemic siRNA delivery to leukocytes remains challenging. The ability to silence gene expression in leukocytes has great potential for identifying drug targets and for RNAi-based therapy for leukocyte diseases. However, both normal and malignant leukocytes are among the most difficult targets for siRNA delivery as they are resistant to conventional transfection reagents and are dispersed in the body. We used mantle cell lymphoma (MCL) as a prototypic blood cancer for validating a novel siRNA delivery strategy. MCL is an aggressive B-cell lymphoma that overexpresses cyclin D1 with relatively poor prognosis. Downregulation of cyclin D1 using RNA interference (RNAi) is a potential therapeutic approach to this malignancy. Here, we designed lipid-based nanoparticles (LNPs) coated with anti-CD38 monoclonal antibodies that are specifically taken up by human MCL cells in the bone marrow of xenografted mice. When loaded with siRNAs against cyclin D1, CD38-targeted LNPs induced gene silencing in MCL cells and prolonged survival of tumor-bearing mice with no observed adverse effects. These results highlight the therapeutic potential of cyclin D1 therapy in MCL and present a novel RNAi delivery system that opens new therapeutic opportunities for treating MCL and other B-cell malignancies. C1 [Weinstein, Shiri; Toker, Itai A.; Emmanuel, Rafi; Ramishetti, Srinivas; Hazan-Halevy, Inbal; Rosenblum, Daniel; Goldsmith, Meir; Peer, Dan] Tel Aviv Univ, Dept Cell Res & Immunol, Lab NanoMed, George S Wise Fac Life Sci, IL-6997801 Tel Aviv, Israel. [Weinstein, Shiri; Toker, Itai A.; Emmanuel, Rafi; Ramishetti, Srinivas; Hazan-Halevy, Inbal; Rosenblum, Daniel; Goldsmith, Meir; Peer, Dan] Tel Aviv Univ, Iby & Aladar Fleischman Fac Engn, Dept Mat Sci & Engn, IL-6997801 Tel Aviv, Israel. [Weinstein, Shiri; Toker, Itai A.; Emmanuel, Rafi; Ramishetti, Srinivas; Hazan-Halevy, Inbal; Rosenblum, Daniel; Goldsmith, Meir; Peer, Dan] Tel Aviv Univ, Ctr Nanosci & Nanotechnol, IL-6997801 Tel Aviv, Israel. [Abraham, Avigdor; Benjamini, Ohad; Nagler, Arnon] Chaim Sheba Med Ctr, Div Hematol & Oncol, IL-5262100 Tel Hashomer, Israel. [Bairey, Osnat; Raanani, Pia] Rabin Med Ctr, Inst Hematol, IL-4941492 Petah Tiqwa, Israel. [Lieberman, Judy] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Peer, D (reprint author), Tel Aviv Univ, Dept Cell Res & Immunol, Lab NanoMed, George S Wise Fac Life Sci, IL-6997801 Tel Aviv, Israel. EM peer@tauex.tau.ac.il OI Peer, Dan/0000-0001-8238-0673 FU NIH [5R01CA139444-10]; Dotan Hematology Center at Tel Aviv University; Lewis Family Trust; Israel Science Foundation [181/10, 41/11]; I-CORE Program of the Planning and Budgeting Committee; FTA: Nanomedicines for Personalized Theranostics of the Israeli National Nanotechnology Initiative; Leona M. and Harry B. Helmsley Nanotechnology Research Fund FX We thank Dr. Leonid Mittelman and Dr. Vered Holdengreber for scientific assistance with confocal and electron microscopy and Andrew G. Sprague (Alnylam Pharmaceuticals) for providing siRNA and fluorescently labeled siRNA molecules. This work was supported in part by grants from the NIH (5R01CA139444-10); The Dotan Hematology Center at Tel Aviv University; The Lewis Family Trust; the Israel Science Foundation (Award # 181/10); the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (Grant 41/11) and the FTA: Nanomedicines for Personalized Theranostics of the Israeli National Nanotechnology Initiative; and by The Leona M. and Harry B. Helmsley Nanotechnology Research Fund (D.P.). NR 38 TC 8 Z9 8 U1 3 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 5 PY 2016 VL 113 IS 1 BP E16 EP E22 DI 10.1073/pnas.1519273113 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA0XH UT WOS:000367520400006 PM 26699502 ER PT J AU Jaaskelainen, IP Halme, HL Agam, Y Glerean, E Lahnakoski, JM Sams, M Tapani, K Ahveninen, J Manoach, DS AF Jaaskelainen, Iiro P. Halme, Hanna-Leena Agam, Yigal Glerean, Enrico Lahnakoski, Juha M. Sams, Mikko Tapani, Karoliina Ahveninen, Jyrki Manoach, Dara S. TI Neural mechanisms supporting evaluation of others' errors in real-life like conditions SO SCIENTIFIC REPORTS LA English DT Article ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; FRONTAL-CORTEX; BRAIN; INHIBITION; PERFORMANCE; TASK; CHRONOARCHITECTURE; RESPONSES; CONFLICT AB The ability to evaluate others' errors makes it possible to learn from their mistakes without the need for first-hand trial-and-error experiences. Here, we compared functional magnetic resonance imaging activation to self-committed errors during a computer game to a variety of errors committed by others during movie clips (e.g., figure skaters falling down and persons behaving inappropriately). While viewing errors by others there was activation in lateral and medial temporal lobe structures, posterior cingulate cortex, precuneus, and medial prefrontal cortex possibly reflecting simulation and storing for future use alternative action sequences that could have led to successful behaviors. During both self-and other-committed errors activation was seen in the striatum, temporoparietal junction, and inferior frontal gyrus. These areas may be components of a generic error processing mechanism. The ecological validity of the stimuli seemed to matter, since we largely failed to see activations when subjects observed errors by another player in the computer game, as opposed to observing errors in the rich real-life like human behaviors depicted in the movie clips. C1 [Jaaskelainen, Iiro P.; Halme, Hanna-Leena; Glerean, Enrico; Lahnakoski, Juha M.; Sams, Mikko; Tapani, Karoliina] Aalto Univ, Sch Sci, Dept Neurosci & Biomed Engn, Brain & Mind Lab, FIN-00076 Espoo, Finland. [Agam, Yigal; Manoach, Dara S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Agam, Yigal; Ahveninen, Jyrki; Manoach, Dara S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Sams, Mikko] Aalto Univ, Adv Magnet Imaging Ctr, Aalto Neuroimaging, FIN-00076 Espoo, Finland. RP Jaaskelainen, IP (reprint author), Aalto Univ, Sch Sci, Dept Neurosci & Biomed Engn, Brain & Mind Lab, FIN-00076 Espoo, Finland. EM iiro.jaaskelainen@aalto.fi RI Sams, Mikko/G-7060-2012; Jaaskelainen, Iiro/C-7392-2012; Lahnakoski, Juha/G-2072-2012; OI Jaaskelainen, Iiro/0000-0001-6001-6950; Lahnakoski, Juha/0000-0002-5223-7822; Glerean, Enrico/0000-0003-0624-675X FU Academy of Finland [138145, 276643]; National Institutes of Health [R01HD040712, R21DC014134, R01MH083744, R01NS037462, F32MH088081, R01MH67720, K24MH099421]; Finnish Cultural Foundation [150496]; doctoral program Brain Mind FX The data were collected using Aalto University Neuroimaging Infrastructure. Supported by the Academy of Finland (grant# 138145 and 276643 to IPJ), National Institutes of Health R01HD040712 (JA), R21DC014134 (JA), R01MH083744 (JA), R01NS037462 (JA), F32MH088081 (YA), R01MH67720 (DSM), K24MH099421 (DSM), Finnish Cultural Foundation (#150496 to JML) and doctoral program Brain & Mind. NR 45 TC 0 Z9 0 U1 4 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 5 PY 2016 VL 6 AR 18714 DI 10.1038/srep18714 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB1NU UT WOS:000368275800001 PM 26729348 ER PT J AU Michaut, M Chin, SF Majewski, I Severson, TM Bismeijer, T de Koning, L Peeters, JK Schouten, PC Rueda, OM Bosma, AJ Tarrant, F Fan, Y He, BL Xue, Z Mittempergher, L Kluin, RJC Heijmans, J Snel, M Pereira, B Schlicker, A Provenzano, E Ali, HR Gaber, A O'Hurley, G Lehn, S Muris, JJF Wesseling, J Kay, E Sammut, SJ Bardwell, HA Barbet, AS Bard, F Lecerf, C O'Connor, DP Vis, DJ Benes, CH McDermott, U Garnett, MJ Simon, IM Jirstrom, K Dubois, T Linn, SC Gallagher, WM Wessels, LFA Caldas, C Bernards, R AF Michaut, Magali Chin, Suet-Feung Majewski, Ian Severson, Tesa M. Bismeijer, Tycho de Koning, Leanne Peeters, Justine K. Schouten, Philip C. Rueda, Oscar M. Bosma, Astrid J. Tarrant, Finbarr Fan, Yue He, Beilei Xue, Zheng Mittempergher, Lorenza Kluin, Roelof J. C. Heijmans, Jeroen Snel, Mireille Pereira, Bernard Schlicker, Andreas Provenzano, Elena Ali, Hamid Raza Gaber, Alexander O'Hurley, Gillian Lehn, Sophie Muris, Jettie J. F. Wesseling, Jelle Kay, Elaine Sammut, Stephen John Bardwell, Helen A. Barbet, Aurelie S. Bard, Floriane Lecerf, Caroline O'Connor, Darran P. Vis, Daniel J. Benes, Cyril H. McDermott, Ultan Garnett, Mathew J. Simon, Iris M. Jirstrom, Karin Dubois, Thierry Linn, Sabine C. Gallagher, William M. Wessels, Lodewyk F. A. Caldas, Carlos Bernards, Rene TI Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer SO SCIENTIFIC REPORTS LA English DT Article ID GENE-EXPRESSION; MOLECULAR PORTRAITS; DUCTAL CARCINOMAS; HIGH-FREQUENCY; CHEMOTHERAPY; TUMORS; MUTATIONS; PROFILES; MULTIPLE; PROTEIN AB Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo-and/or immune-therapies. C1 [Michaut, Magali; Majewski, Ian; Bismeijer, Tycho; Bosma, Astrid J.; Xue, Zheng; Mittempergher, Lorenza; Schlicker, Andreas; Vis, Daniel J.; Wessels, Lodewyk F. A.; Bernards, Rene] Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands. [Chin, Suet-Feung; Rueda, Oscar M.; Pereira, Bernard; Ali, Hamid Raza; Sammut, Stephen John; Bardwell, Helen A.; Caldas, Carlos] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England. [Severson, Tesa M.; Schouten, Philip C.; Muris, Jettie J. F.; Wesseling, Jelle; Linn, Sabine C.] Netherlands Canc Inst, Div Mol Pathol, NL-1066 CX Amsterdam, Netherlands. [de Koning, Leanne; He, Beilei; Barbet, Aurelie S.; Bard, Floriane; Lecerf, Caroline; Dubois, Thierry] Inst Curie, Translat Res Dept, F-75248 Paris 05, France. [Peeters, Justine K.; Heijmans, Jeroen; Snel, Mireille; Simon, Iris M.; Bernards, Rene] Agendia NV, NL-1098 XH Amsterdam, Netherlands. [Tarrant, Finbarr; Fan, Yue; O'Connor, Darran P.; Gallagher, William M.] Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Canc Biol & Therapeut Lab, Dublin 4, Ireland. [Tarrant, Finbarr; O'Hurley, Gillian; Gallagher, William M.] OncoMark Ltd, NovaUCD, Dublin 4, Ireland. [Kluin, Roelof J. C.] Netherlands Canc Inst, Genom Core Facil, NL-1066 CX Amsterdam, Netherlands. [Provenzano, Elena; Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Expt Canc Med Ctr ECMR, Cambridge CB2 0QQ, England. [Provenzano, Elena; Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, NIHR Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England. [Provenzano, Elena; Caldas, Carlos] Cambridge Breast Unit, Cambridge CB2 0QQ, England. [Provenzano, Elena; Caldas, Carlos] NHS Fdn Trust, Cambridge Univ Hosp, Cambridge CB2 0QQ, England. [Ali, Hamid Raza] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Gaber, Alexander; Lehn, Sophie; Jirstrom, Karin] Lund Univ, Div Oncol & Pathol, Dept Clin Sci Lund, SE-22185 Lund, Sweden. [Kay, Elaine] Beaumont Hosp, Dept Pathol, RCSI ERC, Dublin 9, Ireland. [Benes, Cyril H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [McDermott, Ultan; Garnett, Mathew J.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Linn, Sabine C.] Netherlands Canc Inst, Div Med Oncol, NL-1066 CX Amsterdam, Netherlands. [Linn, Sabine C.] Univ Med Ctr Utrecht, Dept Pathol, NL-3584 CX Utrecht, Netherlands. [Wessels, Lodewyk F. A.] Delft Univ Technol, Dept EEMCS, Delft, Netherlands. [Caldas, Carlos] Univ Cambridge, Dept Oncol, Addenbrookes Hosp, Cambridge CB2 0QQ, England. [Bernards, Rene] Netherlands Canc Inst, Canc Genom Netherlands, NL-1066 CX Amsterdam, Netherlands. RP Caldas, C (reprint author), Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England. EM l.wessels@nki.nl; carlos.caldas@cruk.cam.ac.uk; r.bernards@nki.nl OI Michaut, Magali/0000-0003-2002-2277; chin, suet-feung/0000-0001-5697-1082; Caldas, Carlos/0000-0003-3547-1489; Bernards, Rene/0000-0001-8677-3423; Bismeijer, Tycho/0000-0001-6514-4767; McDermott, Ultan/0000-0001-9032-4700; Gallagher, William/0000-0002-4307-5999 FU European Union [258967]; NIHR Cambridge Biomedical Research Centre; Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT [CCRC13GAL]; Irish Research Council for Science, Engineering and Technology; Stichting Technologie en Wetenschap (STW) [STW 12725]; National Health and Medical Research Council Australia [575581] FX The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under the RATHER project (Rational Therapy for Breast Cancer; grant agreement no. 258967). We would like to acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB), Annegien Broeks, Koen Van de Vijver and Dennis Peters for supplying NKI-AVL Biobank material and/or lab support and Tony van de Velde for support in obtaining clinical data from the NKI-AVL registries. We also thank the members of the NKI next generation sequencing core facility for help in sequencing and data analysis. We would like to acknowledge the CUH Human Research Tissue Bank (supported by the NIHR Cambridge Biomedical Research Centre) for providing the Addenbrookes Hospital biobank material. We thank Rania El-Botty for her contribution to the RPPA experiments and Celine Baldeyron for temporary supervision. The RPPA platform acknowledges Stephane Liva and Dr Patrick Poullet for crucial bioinformatics support and Dr Philippe Hupe for his statistical expertise. The RNA-sequencing platform acknowledges Dr. Peadar O'Gaora for his invaluable bioinformatics expertise. We thank Wilbert Zwart and Ton Schumacher for insightful discussion. We thank Karen Misstear for providing project communication and dissemination. FT, YF, DPO and WMG were also supported by the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT (CCRC13GAL). FT was supported in part by the Irish Research Council for Science, Engineering and Technology. TB was supported by a grant from Stichting Technologie en Wetenschap (STW), grant STW 12725. IJM was supported by a fellowship from the National Health and Medical Research Council Australia (575581). NR 45 TC 17 Z9 17 U1 6 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 5 PY 2016 VL 6 AR 18517 DI 10.1038/srep18517 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB1FQ UT WOS:000368253900001 PM 26729235 ER PT J AU Paul, S Saxena, A Terrin, N Viveiros, K Balk, EM Wong, JB AF Paul, Sonali Saxena, Akriti Terrin, Norma Viveiros, Kathleen Balk, Ethan M. Wong, John B. TI Hepatitis B Virus Reactivation and Prophylaxis During Solid Tumor Chemotherapy A Systematic Review and Meta-analysis SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BREAST-CANCER PATIENTS; RECEIVING CYTOTOXIC CHEMOTHERAPY; LAMIVUDINE PROPHYLAXIS; HBV REACTIVATION; ADJUVANT CHEMOTHERAPY; RISK-FACTORS; PREEMPTIVE LAMIVUDINE; COST-EFFECTIVENESS; POSITIVE PATIENTS; INFECTION AB Background: Solid tumor chemotherapy regimens pose a risk for hepatitis B virus (HBV) reactivation, but screening and antiviral prophylaxis remains controversial because of insufficient evidence. Purpose: To determine the risk for HBV reactivation with and without antiviral prophylaxis and the effectiveness of prophylaxis in adults with solid tumors and chronic or resolved HBV infection. Data Sources: MEDLINE through 1 July 2015 and Web of Science, Cochrane Central Register of Controlled Trials, TOXNET, and Scopus through 1 March 2015. Study Selection: 26 English-language observational studies and randomized, controlled trials in patients with chronic or resolved HBV receiving chemotherapy for solid tumors. Data Extraction: Study characteristics, quality, and risk of bias were assessed by 1 researcher and verified by another independent researcher. Data Synthesis: Random-effects model meta-analyses were used to estimate the risk and odds ratio (OR) of reactivation with versus without antiviral prophylaxis. Reactivation in chronic HBV without prophylaxis ranged from 4% to 68% (median, 25%) with substantial heterogeneity. Prophylaxis reduced the risk for HBV reactivation (OR, 0.12 [95% CI, 0.06 to 0.22]), HBV-related hepatitis (OR, 0.18 [CI, 0.10 to 0.32]), and chemotherapy interruption (OR, 0.10 [CI, 0.04 to 0.27]). In 3 studies of patients with resolved HBV infection, none received HBV prophylaxis and reactivation risk ranged from 0.3% to 9.0%. Limitations: Significant heterogeneity in underlying study populations and treatment regimens, incomplete baseline data, possibility of publication bias, and limited study quality. Most studies were observational and from Asia. Conclusion: In patients with chronic HBV receiving solid tumor chemotherapy, the risk for HBV reactivation is similar to the risk with other types of immunosuppressive therapy. Results support HBV screening and antiviral prophylaxis before initiation of chemotherapy for solid tumors. C1 Massachusetts Gen Hosp, Tufts Med Ctr, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. RP Paul, S (reprint author), Massachusetts Gen Hosp, Gastroenterol Associates, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM sonali.paul2@gmail.com FU National Center for Advancing Translational Sciences; National Institutes of Health FX National Center for Advancing Translational Sciences and National Institutes of Health. NR 68 TC 11 Z9 11 U1 0 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 5 PY 2016 VL 164 IS 1 BP 30 EP + DI 10.7326/M15-1121 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA DA4WC UT WOS:000367801700008 PM 26595058 ER PT J AU Sgro, G Gladwin, MT Teng, A Moghe, A Zimmer, SM AF Sgro, Gaetan Gladwin, Mark T. Teng, Alexander Moghe, Akshata Zimmer, Shanta M. TI Shining a Light on the Dark Side SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Sgro, Gaetan] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Gladwin, Mark T.; Zimmer, Shanta M.] Univ Pittsburgh, Pittsburgh, PA USA. [Teng, Alexander; Moghe, Akshata] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Sgro, G (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 5 PY 2016 VL 164 IS 1 BP 69 EP 69 DI 10.7326/L16-0013 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DA4WC UT WOS:000367801700018 PM 26747309 ER PT J AU Dudzinski, DM Piazza, G AF Dudzinski, David M. Piazza, Gregory TI Multidisciplinary Pulmonary Embolism Response Teams SO CIRCULATION LA English DT Article DE hospital rapid response team; pulmonary embolism; venous thromboembolism; venous thrombosis ID HEART TEAM; CARE; GUIDELINES; MANAGEMENT; THROMBOSIS C1 Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Echocardiog, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Crit Care, Boston, MA 02114 USA. [Piazza, Gregory] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Piazza, G (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM gpiazza@partners.org NR 15 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 5 PY 2016 VL 133 IS 1 BP 98 EP 103 DI 10.1161/CIRCULATIONAHA.115.015086 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DA1ES UT WOS:000367539700011 PM 26719388 ER PT J AU Joshi, FR Rajani, NK Abt, M Woodward, M Bucerius, J Mani, V Tawakol, A Kallend, D Fayad, ZA Rudd, JHF AF Joshi, Francis R. Rajani, Nikil K. Abt, Markus Woodward, Mark Bucerius, Jan Mani, Venkatesh Tawakol, Ahmed Kallend, David Fayad, Zahi A. Rudd, James H. F. TI Does Vascular Calcification Accelerate Inflammation? A Substudy of the dal-PLAQUE Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atherosclerosis; carotid arteries; cholesterol; dalcetrapib; fluorodeoxyglucose; fluorine-18; positron emission tomography ID CORONARY-ARTERY CALCIUM; ALL-CAUSE MORTALITY; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; THORACIC AORTA CALCIFICATION; RANDOMIZED CLINICAL-TRIAL; RISK-FACTORS; COMPUTED-TOMOGRAPHY; CALCIFIED ATHEROSCLEROSIS; CAROTID ARTERIES; CT ANGIOGRAPHY AB BACKGROUND Atherosclerosis is an inflammatory condition with calcification apparent late in the disease process. The extent and progression of coronary calcification predict cardiovascular events. Relatively little is known about noncoronary vascular calcification. OBJECTIVES This study investigated noncoronary vascular calcification and its influence on changes in vascular inflammation. METHODS A total of 130 participants in the dal-PLAQUE (Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging) study underwent fluorodeoxyglucose positron emission tomography/computed tomography at entry and at 6 months. Calcification of the ascending aorta, arch, carotid, and coronary arteries was quantified. Cardiovascular risk factors were related to arterial calcification. The influences of baseline calcification and drug therapy (dalcetrapib vs. placebo) on progression of calcification were determined. Finally, baseline calcification was related to changes in vascular inflammation. RESULTS Age >65 years old was consistently associated with higher baseline calcium scores. Arch calcification trended to progress more in those with calcification at baseline (p = 0.055). There were no significant differences between progression of vascular calcification with dalcetrapib compared to that with placebo. Average carotid target-to-background ratio indexes declined over 6 months if carotid calcium was absent (single hottest slice [p = 0.037], mean of maximum target-to-background ratio [p = 0.010], and mean most diseased segment [p < 0.001]), but did not significantly change if calcification was present at baseline. CONCLUSIONS Across multiple arterial regions, higher age is consistently associated with higher calcium scores. The presence of vascular calcification at baseline is associated with progressive calcification; in the carotid arteries, calcification appears to influence vascular inflammation. Dalcetrapib therapy did not affect vascular calcification. (C) 2016 by the American College of Cardiology Foundation. C1 [Joshi, Francis R.; Rajani, Nikil K.; Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge CB2 0QQ, England. [Abt, Markus; Kallend, David] F Hoffmann La Roche & Cie AG, Pharma Dev, Basel, Switzerland. [Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Woodward, Mark] Univ Oxford, Oxford, England. [Bucerius, Jan; Mani, Venkatesh; Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Bucerius, Jan] Maastricht Univ, Med Ctr, Dept Nucl Med, NL-6200 MD Maastricht, Netherlands. [Bucerius, Jan] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, NL-6200 MD Maastricht, Netherlands. [Bucerius, Jan] Univ Hosp RWTH Aachen, Dept Nucl Med, Aachen, Germany. [Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. RP Rudd, JHF (reprint author), Univ Cambridge, Div Cardiovasc Med, Addenbrookes Hosp, Box 110,ACCI Level 6,Hills Rd, Cambridge CB2 0QQ, England. EM jhfr2@cam.ac.uk RI Woodward, Mark/D-8492-2015; OI Mani, Venkatesh/0000-0002-0432-2918 FU F. Hoffmann-La Roche AG; U.S. National Institutes of Health/National Heart, Lung, and Blood Institute [R01 HL071021]; British Heart Foundation [FS/12/29/29463]; Raymond and Beverly Sackler PhD studentship; National Institute for Health Research Cambridge Biomedical Research Centre; Takeda; Actelion; F. Hoffmann-La Roche AG/Genentech; Merck; Bristol-Myers Squibb; GlaxoSmithKline; VBL Therapeutics; Novartis; Via Pharmaceuticals FX This study was supported by F. Hoffmann-La Roche AG and U.S. National Institutes of Health/National Heart, Lung, and Blood Institute grant R01 HL071021 (Dr. Fayad), and some editorial assistance was provided by Prime Healthcare. Dr. Joshi is supported by British Heart Foundation Research Fellowship award FS/12/29/29463 and a Raymond and Beverly Sackler PhD studentship. Dr. Rudd is supported in part by the National Institute for Health Research Cambridge Biomedical Research Centre. Dr. Abt is an employee of and holds stock options in F. Hoffmann-La Roche AG. Prof. Woodward has received honoraria and research funding from F. Hoffmann-La Roche AG and honoraria from Novartis. Dr. Tawakol has received honoraria from F. Hoffmann-La Roche AG, Bristol-Myers Squibb, and Novartis; research grants from Takeda, Actelion, F. Hoffmann-La Roche AG/Genentech, Merck, Bristol-Myers Squibb, GlaxoSmithKline, and VBL Therapeutics; and has consulted for Roche, Takeda, AstraZeneca, Amgen, and Actelion. Dr. Kallend is a former employee of F. Hoffmann-La Roche AG and holds stock options in The Medicines Company. Prof. Fayad has received research grants from F. Hoffmann-La Roche AG, GlaxoSmithKline, Merck, VBL Therapeutics, Novartis, Bristol-Myers Squibb, and Via Pharmaceuticals; and honoraria from F. Hoffmann-La Roche AG. Dr. Rudd has received honoraria from F. Hoffmann-La Roche AG. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 39 TC 6 Z9 6 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 5 PY 2016 VL 67 IS 1 BP 69 EP 78 DI 10.1016/j.jacc.2015.10.050 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DA0XI UT WOS:000367520500011 PM 26764069 ER PT J AU Mucci, LA Hjelmborg, JB Harris, JR Czene, K Havelick, DJ Scheike, T Graff, RE Holst, K Moller, S Unger, RH McIntosh, C Nuttall, E Brandt, I Penney, KL Hartman, M Kraft, P Parmigiani, G Christensen, K Koskenvuo, M Holm, NV Heikkila, K Pukkala, E Skytthe, A Adami, HO Kaprio, J AF Mucci, Lorelei A. Hjelmborg, Jacob B. Harris, Jennifer R. Czene, Kamila Havelick, David J. Scheike, Thomas Graff, Rebecca E. Holst, Klaus Moeller, Soeren Unger, Robert H. McIntosh, Christina Nuttall, Elizabeth Brandt, Ingunn Penney, Kathryn L. Hartman, Mikael Kraft, Peter Parmigiani, Giovanni Christensen, Kaare Koskenvuo, Markku Holm, Niels V. Heikkila, Kauko Pukkala, Eero Skytthe, Axel Adami, Hans-Olov Kaprio, Jaakko CA Nordic Twin Study Canc NorTwinCan TI Familial Risk and Heritability of Cancer Among Twins in Nordic Countries SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BREAST-CANCER; MISSING HERITABILITY; ASSOCIATION ANALYSIS; SUSCEPTIBILITY LOCI; PROSTATE-CANCER; POOLED ANALYSIS; REGISTRY; COMPLETENESS; INDIVIDUALS; DISEASE AB IMPORTANCE Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. OBJECTIVE To estimate familial risk and heritability of cancer types in a large twin cohort. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 80 309 monozygotic and 123 382 same-sex dizygotic twin individuals (N = 203 691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50 990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. EXPOSURES Shared environmental and heritable risk factors among pairs of twins. MAIN OUTCOMES AND MEASURES The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS A total of 27 156 incident cancers were diagnosed in 23 980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5%(95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14%(95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33%(95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). CONCLUSIONS AND RELEVANCE In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling. C1 [Mucci, Lorelei A.; Havelick, David J.; Graff, Rebecca E.; Unger, Robert H.; Nuttall, Elizabeth; Kraft, Peter; Adami, Hans-Olov] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mucci, Lorelei A.] Univ Iceland, Div Publ Hlth Sci, Reykjavik, Iceland. [Mucci, Lorelei A.; Penney, Kathryn L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Hjelmborg, Jacob B.; Czene, Kamila; Moeller, Soeren; Christensen, Kaare; Skytthe, Axel] Univ Southern Denmark, Dept Biostat & Epidemiol, Odense, Denmark. [Hjelmborg, Jacob B.; Czene, Kamila; Moeller, Soeren; Holm, Niels V.; Skytthe, Axel] Univ Southern Denmark, Danish Twin Registry, Odense, Denmark. [Harris, Jennifer R.; Brandt, Ingunn] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. [Czene, Kamila; Hartman, Mikael; Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Scheike, Thomas; Holst, Klaus] Univ Copenhagen, Dept Biostat, Copenhagen, Denmark. [Graff, Rebecca E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [McIntosh, Christina; Kraft, Peter; Parmigiani, Giovanni] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hartman, Mikael] Natl Univ Singapore Hosp, Dept Surg, Singapore 117548, Singapore. [Hartman, Mikael] NUHS, Singapore, Singapore. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Computat Biol & Biostat, Boston, MA 02115 USA. [Koskenvuo, Markku; Heikkila, Kauko; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Holm, Niels V.] Odense Univ Hosp, Dept Oncol, DK-5000 Odense, Denmark. [Pukkala, Eero] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland. [Pukkala, Eero] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland. [Kaprio, Jaakko] Univ Helsinki, Inst Mol Med, Helsinki, Finland. RP Mucci, LA (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,920E, Boston, MA 02115 USA. EM lmucci@hsph.harvard.edu RI Christensen, Kaare/C-2360-2009; OI Christensen, Kaare/0000-0002-5429-5292; Scheike, Thomas/0000-0002-2148-4740; Kaprio, Jaakko/0000-0002-3716-2455; Moller, Soren/0000-0003-0858-4269 FU Ellison Foundation; Nordic Cancer Union; Academy of Finland [213506, 129680, 265240, 263278]; US BioSHaRE-EU [HEALTH-F4-2010-261433]; Ministry for Higher Education; Odense University Hospital AgeCare program of the Academy of Geriatric Cancer Research; Karolinska Institutet [2368/10-221]; National Cancer Institute [R25 CA098566, R25 CA112355] FX This work was supported by funding from the Ellison Foundation (awarded to Drs Mucci and Adami at the Harvard School of Public Health) and the Nordic Cancer Union (awarded to Dr Kaprio). The Finnish Twin Cohort was supported by grants 213506, 129680, 265240, and 263278 from the Academy of Finland and grant agreement HEALTH-F4-2010-261433 from US BioSHaRE-EU. The Swedish Twin Registry was supported by the Ministry for Higher Education. The Danish Twin Cohort was supported by the Odense University Hospital AgeCare program of the Academy of Geriatric Cancer Research. Data collection and research stemming from the Norwegian Twin Registry is supported, in part, from the European Union's Seventh Framework Programme and grant agreement HEALTH-F4-2010-261433 from US BioSHaRE-EU. Dr Mucci is a Prostate Cancer Foundation young investigator. Dr Adami received distinguished professor award 2368/10-221 from the Karolinska Institutet. Dr Graff is supported by National Cancer Institute training grants R25 CA098566 and R25 CA112355. NR 39 TC 23 Z9 23 U1 7 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 5 PY 2016 VL 315 IS 1 BP 68 EP 76 DI 10.1001/jama.2015.17703 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DA0YH UT WOS:000367523000016 PM 26746459 ER PT J AU Chandler, P Kochupurakkal, BS Alam, S Richardson, AL Soybel, DI Kelleher, SL AF Chandler, Paige Kochupurakkal, Bose S. Alam, Samina Richardson, Andrea L. Soybel, David I. Kelleher, Shannon L. TI Subtype-specific accumulation of intracellular zinc pools is associated with the malignant phenotype in breast cancer SO MOLECULAR CANCER LA English DT Article DE Breast cancer; Basal/Luminal; Metallothionein; Zinc; Zinc importer; Zinc transporter ID TRANS-GOLGI NETWORK; SIGNALING PATHWAYS; OXIDATIVE STRESS; CELL-LINES; TRANSPORTERS ZIP4; EPITHELIAL-CELLS; GENE-EXPRESSION; MAMMARY-GLAND; DIETARY ZINC; PROTEIN AB Background: Zinc (Zn) hyper-accumulates in breast tumors and malignant cell lines compared to normal mammary epithelium. The mechanisms responsible for Zn accumulation and the consequence of Zn dysregulation are poorly understood. Methods: Microarrays were performed to assess differences in the expression of Zn transporters and metallothioneins (MTs) in human breast tumors and breast cancer cell lines. Real-time PCR and immunoblotting were employed to profile Zn transporter expression in representative luminal (T47D), basal (MDA-MB-231), and non-malignant (MCF10A) cell lines. Zn distribution in human tumors was assessed by X-ray fluorescence imaging. Zn distribution and content in cell lines was measured using FluoZin-3 imaging, and quantification and atomic absorption spectroscopy. Functional consequences of ZnT2 over-expression in MDA-MB-231 cells including invasion, proliferation, and cell cycle were measured using Boyden chambers, MTT assays, and flow cytometry, respectively. Results: Gene expression profiling of human breast tumors and breast cancer cell lines identified subtype-specific dysregulation in the Zn transporting network. X-ray fluorescence imaging of breast tumor tissues revealed Zn hyper-accumulation at the margins of Luminal breast tumors while Zn was more evenly distributed within Basal tumors. While both T47D and MDA-MB-231 cells hyper-accumulated Zn relative to MCF10A cells, T47D cells accumulated 2.5-fold more Zn compared to MDA-MB-231 cells. FluoZin-3 imaging indicated that Zn was sequestered into numerous large vesicles in T47D cells, but was retained in the cytoplasm and found in fewer and larger, amorphous sub-cellular compartments in MDA-MB-231 cells. The differences in Zn localization mirrored the relative abundance of the Zn transporter ZnT2; T47D cells over-expressed ZnT2, whereas MDA-MB-231 cells did not express ZnT2 protein due to proteasomal degradation. To determine the functional relevance of the lack of ZnT2 in MDA-MB-231cells, cells were transfected to express ZnT2. ZnT2 over-expression led to Zn vesicularization, shifts in cell cycle, enhanced apoptosis, and reduced proliferation and invasion. Conclusions: This comprehensive analysis of the Zn transporting network in malignant breast tumors and cell lines illustrates that distinct subtype-specific dysregulation of Zn management may underlie phenotypic characteristics of breast cancers such as grade, invasiveness, metastatic potential, and response to therapy. C1 [Chandler, Paige; Kelleher, Shannon L.] Penn State Hershey Coll Med, Interdisciplinary Grad Program Physiol, Hershey, PA 17033 USA. [Chandler, Paige; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.] Penn State Hershey Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. [Kelleher, Shannon L.] Penn State Hershey Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. [Alam, Samina; Soybel, David I.; Kelleher, Shannon L.] Penn State Hershey Coll Med, Dept Surg, Hershey, PA 17033 USA. [Kochupurakkal, Bose S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kochupurakkal, Bose S.; Richardson, Andrea L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Kelleher, SL (reprint author), Penn State Hershey Coll Med, Interdisciplinary Grad Program Physiol, Hershey, PA 17033 USA. EM slk39@psu.edu FU Hale and Terri Brodeur Breast Cancer Foundation; Breast Cancer Research Foundation; Department of Surgery Intramural Funds FX Intramural funds to SLK; Hale and Terri Brodeur Breast Cancer Foundation fellowships to BSK; Breast Cancer Research Foundation to ALR; and Department of Surgery Intramural Funds to DIS and SLK. NR 86 TC 3 Z9 3 U1 4 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD JAN 5 PY 2016 VL 15 AR 2 DI 10.1186/s12943-015-0486-y PG 19 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA DA1CZ UT WOS:000367535200001 PM 26728511 ER PT J AU Calvo, SE Clauser, KR Mootha, VK AF Calvo, Sarah E. Clauser, Karl R. Mootha, Vamsi K. TI MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-CENTERED INFORMATION; INTEGRATIVE GENOMICS; PROTEOME DATABASE; HIGH-THROUGHPUT; MITOP2; SEQUENCE; DISEASE; NCBI; EXPRESSION; DISORDERS AB Mitochondria are complex organelles that house essential pathways involved in energy metabolism, ion homeostasis, signalling and apoptosis. To understand mitochondrial pathways in health and disease, it is crucial to have an accurate inventory of the organelle's protein components. In 2008, we made substantial progress toward this goal by performing in-depth mass spectrometry of mitochondria from 14 organs, epitope tagging/microscopy and Bayesian integration to assemble MitoCarta (www.broadinstitute.org/pubs/MitoCarta): an inventory of genes encoding mitochondrial-localized proteins and their expression across 14 mouse tissues. Using the same strategy we have now reconstructed this inventory separately for human and for mouse based on (i) improved gene transcript models, (ii) updated literature curation, including results from proteomic analyses of mitochondrial subcompartments, (iii) improved homology mapping and (iv) updated versions of all seven original data sets. The updated human MitoCarta2.0 consists of 1158 human genes, including 918 genes in the original inventory as well as 240 additional genes. The updated mouse MitoCarta2.0 consists of 1158 genes, including 967 genes in the original inventory plus 191 additional genes. The improved MitoCarta 2.0 inventory provides a molecular framework for system-level analysis of mammalian mitochondria. C1 [Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Calvo, Sarah E.; Clauser, Karl R.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02141 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Calvo, SE; Mootha, VK (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.; Calvo, SE; Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Calvo, SE; Mootha, VK (reprint author), Broad Inst, Cambridge, MA 02141 USA.; Calvo, SE; Mootha, VK (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM scalvo@broadinstitute.org; vamsi@hms.harvard.edu FU National Institutes of Health [GM0077465] FX National Institutes of Health [GM0077465 to V.K.M.]. V.K.M. is an investigator of the Howard Hughes Medical Institute. Funding for open access charge: National Institutes of Health [GM0077465 to V.K.M.]. NR 45 TC 55 Z9 56 U1 2 U2 2 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 JAN 4 PY 2016 VL 44 IS D1 BP D1251 EP D1257 DI 10.1093/nar/gkv1003 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700176 PM 26450961 ER PT J AU Savova, V Patsenker, J Vigneau, S Gimelbrant, AA AF Savova, Virginia Patsenker, Jon Vigneau, Sebastien Gimelbrant, Alexander A. TI dbMAE: the database of autosomal monoallelic expression SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; STEM-CELLS; INACTIVATION; DISEASE AB Recently, data on 'random' autosomal monoallelic expression has become available for the entire genome in multiple human and mouse tissues and cell types, creating a need for better access and dissemination. The database of autosomal monoallelic expression (dbMAE; https://mae.hms.harvard.edu) incorporates data from multiple recent reports of genome-wide analyses. These include transcriptome-wide analyses of allelic imbalance in clonal cell populations based on sequence polymorphisms, as well as indirect identification, based on a specific chromatin signature present in MAE gene bodies. Currently, dbMAE contains transcriptome-wide chromatin identification calls for 8 human and 21 mouse tissues, and describes over 16 000 murine and similar to 700 human cases of directly measured biased expression, compiled from allele-specific RNA-seq and genotyping array data. All data are manually cu-rated. To ensure cross-publication uniformity, we performed re-analysis of transcriptome-wide RNA-seq data using the same pipeline. Data are accessed through an interface that allows for basic and advanced searches; all source references, including raw data, are clearly described and hyperlinked. This ensures the utility of the resource as an initial screening tool for those interested in investigating the role of monoallelic expression in their specific genes and tissues of interest. C1 [Savova, Virginia; Patsenker, Jon; Vigneau, Sebastien; Gimelbrant, Alexander A.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Savova, Virginia; Patsenker, Jon; Vigneau, Sebastien; Gimelbrant, Alexander A.] Harvard Univ, Sch Med, Dept Genet, 450 Brookline Ave, Boston, MA 02215 USA. [Savova, Virginia] Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02215 USA. RP Savova, V; Gimelbrant, AA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.; Savova, V; Gimelbrant, AA (reprint author), Harvard Univ, Sch Med, Dept Genet, 450 Brookline Ave, Boston, MA 02215 USA.; Savova, V (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02215 USA. EM Vireinia_Savova@hms.harvard.edu; gimelbrant@mail.dfci.harvard.edu FU Pew scholar award; NIH [R01GM114864]; NIH through NCRR [1S10RR028832-01] FX Pew scholar award [to A.A.G. in part]; NIH [R01GM114864 to V.S., S.V. A.A.G in part]. This NIH supported shared facility is partially provided through NCRR 1S10RR028832-01. Funding for open access charge: NIH. NR 19 TC 3 Z9 3 U1 0 U2 0 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 JAN 4 PY 2016 VL 44 IS D1 BP D753 EP D756 DI 10.1093/nar/gkv1106 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700106 PM 26503248 ER PT J AU Sgroi, DC Chapman, JAW Badovinac-Crnjevic, T Zarella, E Binns, S Zhang, Y Schnabel, CA Erlander, MG Pritchard, KI Han, L Shepherd, LE Goss, PE Pollak, M AF Sgroi, Dennis C. Chapman, Judy-Anne W. Badovinac-Crnjevic, T. Zarella, Elizabeth Binns, Shemeica Zhang, Yi Schnabel, Catherine A. Erlander, Mark G. Pritchard, Kathleen I. Han, Lei Shepherd, Lois E. Goss, Paul E. Pollak, Michael TI Assessment of the prognostic and predictive utility of the Breast Cancer Index (BCI): an NCIC CTG MA.14 study SO BREAST CANCER RESEARCH LA English DT Article DE Breast Cancer Index; HOXB13: IL17BR; Molecular grade index; MA. 14 ID MOLECULAR GRADE INDEX; 21-GENE RECURRENCE SCORE; LATE-DISTANT RECURRENCE; GENE-EXPRESSION; RANDOMIZED-TRIAL; TAMOXIFEN; SURVIVAL; RISK; CHEMOTHERAPY; THERAPY AB Background: Biomarkers that can be used to accurately assess the residual risk of disease recurrence in women with hormone receptor-positive breast cancer are clinically valuable. We evaluated the prognostic value of the Breast Cancer Index (BCI), a continuous risk index based on a combination of HOXB13: IL17BR and molecular grade index, in women with early breast cancer treated with either tamoxifen alone or tamoxifen plus octreotide in the NCIC MA. 14 phase III clinical trial (ClinicalTrials.gov Identifier NCT00002864; registered 1 November 1999). Methods: Gene expression analysis of BCI by real-time polymerase chain reaction was performed blinded to outcome on RNA extracted from archived formalin-fixed, paraffin-embedded tumor samples of 299 patients with both lymph node-negative (LN-) and lymph node-positive (LN+) disease enrolled in the MA. 14 trial. Our primary objective was to determine the prognostic performance of BCI based on relapse-free survival (RFS). MA. 14 patients experienced similar RFS on both treatment arms. Association of gene expression data with RFS was evaluated in univariate analysis with a stratified log-rank test statistic, depicted with a Kaplan-Meier plot and an adjusted Cox survivor plot. In the multivariate assessment, we used stratified Cox regression. The prognostic performance of an emerging, optimized linear BCI model was also assessed in a post hoc analysis. Results: Of 299 samples, 292 were assessed successfully for BCI for 146 patients accrued in each MA. 14 treatment arm. BCI risk groups had a significant univariate association with RFS (stratified log-rank p = 0.005, unstratified log-rank p = 0.007). Adjusted 10-year RFS in BCI low-, intermediate-, and high-risk groups was 87.5 %, 83.9 %, and 74.7 %, respectively. BCI had a significant prognostic effect [ hazard ratio (HR) 2.34, 95 % confidence interval (CI) 1.33-4.11; p = 0.004], although not a predictive effect, on RFS in stratified multivariate analysis, adjusted for pathological tumor stage (HR 2.22, 95 % CI 1.22-4.07; p = 0.01). In the post hoc multivariate analysis, higher linear BCI was associated with shorter RFS (p = 0.002). Conclusions: BCI had a strong prognostic effect on RFS in patients with early-stage breast cancer treated with tamoxifen alone or with tamoxifen and octreotide. BCI was prognostic in both LN- and LN+ patients. This retrospective study is an independent validation of the prognostic performance of BCI in a prospective trial. C1 [Sgroi, Dennis C.; Zarella, Elizabeth; Binns, Shemeica] Massachusetts Gen Hosp, Mol Pathol Unit, MGH East, Mol Pathol,Res, Charlestown, MA 02129 USA. [Sgroi, Dennis C.; Badovinac-Crnjevic, T.; Zarella, Elizabeth; Binns, Shemeica; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Sgroi, Dennis C.; Zarella, Elizabeth; Binns, Shemeica] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chapman, Judy-Anne W.; Han, Lei; Shepherd, Lois E.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. [Zhang, Yi; Schnabel, Catherine A.] bioTheranost Inc, San Diego, CA USA. [Erlander, Mark G.] Trovagene Inc, San Diego, CA USA. [Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Pritchard, Kathleen I.] Univ Toronto, Toronto, ON, Canada. [Pollak, Michael] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, MGH East, Mol Pathol,Res, 149 13th St, Charlestown, MA 02129 USA. EM dsgroi@partners.org NR 25 TC 2 Z9 2 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PD JAN 4 PY 2016 VL 18 AR 1 DI 10.1186/s13058-015-0660-6 PG 7 WC Oncology SC Oncology GA DA3QH UT WOS:000367712300001 PM 26728744 ER PT J AU Lambertini, M Del Mastro, L Pescio, MC Andersen, CY Azim, HA Peccatori, FA Costa, M Revelli, A Salvagno, F Gennari, A Ubaldi, FM La Sala, GB De Stefano, C Wallace, WH Partridge, AH Anserini, P AF Lambertini, Matteo Del Mastro, Lucia Pescio, Maria C. Andersen, Claus Y. Azim, Hatem A., Jr. Peccatori, Fedro A. Costa, Mauro Revelli, Alberto Salvagno, Francesca Gennari, Alessandra Ubaldi, Filippo M. La Sala, Giovanni B. De Stefano, Cristofaro Wallace, W. Hamish Partridge, Ann H. Anserini, Paola TI Cancer and fertility preservation: international recommendations from an expert meeting SO BMC MEDICINE LA English DT Article DE Fertility preservation; cancer patients; survivorship issues; sperm cryopreservation; embryo cryopreservation; oocyte cryopreservation; ovarian tissue cryopreservation; luteinizing hormone-releasing hormone analogs ID CRYOPRESERVED OVARIAN TISSUE; IN-VITRO FERTILIZATION; OF-THE-LITERATURE; HUMAN OOCYTE CRYOPRESERVATION; HODGKIN STUDY-GROUP; BREAST-CANCER; YOUNG-WOMEN; RANDOMIZED-TRIAL; HORMONE AGONISTS; LIVE BIRTH AB In the last years, thanks to the improvement in the prognosis of cancer patients, a growing attention has been given to the fertility issues. International guidelines on fertility preservation in cancer patients recommend that physicians discuss, as early as possible, with all patients of reproductive age their risk of infertility from the disease and/or treatment and their interest in having children after cancer, and help with informed fertility preservation decisions. As recommended by the American Society of Clinical Oncology and the European Society for Medical Oncology, sperm cryopreservation and embryo/oocyte cryopreservation are standard strategies for fertility preservations in male and female patients, respectively; other strategies (e.g. pharmacological protection of the gonads and gonadal tissue cryopreservation) are considered experimental techniques. However, since then, new data have become available, and several issues in this field are still controversial and should be addressed by both patients and their treating physicians. In April 2015, physicians with expertise in the field of fertility preservation in cancer patients from several European countries were invited in Genova (Italy) to participate in a workshop on the topic of "cancer and fertility preservation". A total of ten controversial issues were discussed at the conference. Experts were asked to present an up-to-date review of the literature published on these topics and the presentation of own unpublished data was encouraged. On the basis of the data presented, as well as the expertise of the invited speakers, a total of ten recommendations were discussed and prepared with the aim to help physicians in counseling their young patients interested in fertility preservation. Although there is a great interest in this field, due to the lack of large prospective cohort studies and randomized trials on these topics, the level of evidence is not higher than 3 for most of the recommendations highlighting the need of further research efforts in many areas of this field. The participation to the ongoing registries and prospective studies is crucial to acquire more robust information in order to provide evidence-based recommendations. C1 [Lambertini, Matteo] IRCCS AOU San Martino IST, UO Oncol Med 2, Dept Med Oncol, Genoa, Italy. [Del Mastro, Lucia] IRCCS AOU San Martino IST, UO Sviluppo Terapie Innovat, Dept Med Oncol, Genoa, Italy. [Pescio, Maria C.; Anserini, Paola] IRCCS AOU San Martino IST, Physiopathol Human Reprod, Genoa, Italy. [Andersen, Claus Y.] Univ Copenhagen Hosp, Juliane Marie Ctr Women Children & Reprod, Sect 5712, Lab Reprod Biol, DK-2100 Copenhagen, Denmark. [Azim, Hatem A., Jr.] Univ Libre Bruxelles, Inst Jules Bordet, Dept Med, BrEAST Data Ctr, Brussels, Belgium. [Peccatori, Fedro A.] European Inst Oncol, Dept Gynecol Oncol, Fertil & Procreat Unit, Milan, Italy. [Costa, Mauro] Int Evangel Hosp, Reprod Med Dept, Genoa, Italy. [Revelli, Alberto; Salvagno, Francesca] Univ Turin, S Anna Hosp, Physiopathol Reprod & In Vitro Fertilizat Unit, Turin, Italy. [Gennari, Alessandra] EO Galliera, Dept Med Oncol, Genoa, Italy. [Ubaldi, Filippo M.] Clin Valle Giulia, GENERA Ctr Reprod Med, Rome, Italy. [La Sala, Giovanni B.] Univ Modena & Reggio Emilia, Azienda Osped Arcispedale S Maria Nuova IRCCS, Obstet & Gynecol Dept, Reggio Emilia, Italy. [De Stefano, Cristofaro] San Giuseppe Moscati Hosp, Physiopathol Human Reprod Unit, Children & Women Hlth Dept, Avellino, Italy. [Wallace, W. Hamish] Univ Edinburgh, Royal Hosp Sick Children, Dept Haematol Oncol, Edinburgh, Midlothian, Scotland. [Wallace, W. Hamish] Univ Edinburgh, Dept Child Life & Hlth, Edinburgh, Midlothian, Scotland. [Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Lambertini, M (reprint author), IRCCS AOU San Martino IST, UO Oncol Med 2, Dept Med Oncol, Genoa, Italy. EM matteo.lambertini85@gmail.com OI wallace, william, hamish/0000-0001-8080-5674; pescio, maria c/0000-0002-5101-5822; anserini, paola/0000-0003-2546-2626; Lambertini, Matteo/0000-0003-1797-5296; Del Mastro, Lucia/0000-0002-9546-5841 FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [2013-14272]; Italian Ministry of Health (Centro Nazionale per la Prevenzione e il Controllo delle Malattie, CCM project) FX This work was partially supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC; investigator grant number: 2013-14272) and by a grant from the Italian Ministry of Health (Centro Nazionale per la Prevenzione e il Controllo delle Malattie, CCM project, approved by D.M. 05/03/2012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 151 TC 23 Z9 23 U1 8 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD JAN 4 PY 2016 VL 14 AR 1 DI 10.1186/s12916-015-0545-7 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA CZ9TA UT WOS:000367438700001 PM 26728489 ER PT J AU Katnani, HA Patel, SR Kwon, CS Abdel-Aziz, S Gale, JT Eskandar, EN AF Katnani, Husam A. Patel, Shaun R. Kwon, Churl-Su Abdel-Aziz, Samer Gale, John T. Eskandar, Emad N. TI Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning SO SCIENTIFIC REPORTS LA English DT Article ID LONG-TERM POTENTIATION; NUCLEUS-ACCUMBENS; ELECTRICAL-STIMULATION; NEURONAL-ACTIVITY; TEGMENTAL AREA; REWARD; DOPAMINE; ORGANIZATION; EXPECTATION; PREDICTION AB The primate brain has the remarkable ability of mapping sensory stimuli into motor behaviors that can lead to positive outcomes. We have previously shown that during the reinforcement of visual-motor behavior, activity in the caudate nucleus is correlated with the rate of learning. Moreover, phasic microstimulation in the caudate during the reinforcement period was shown to enhance associative learning, demonstrating the importance of temporal specificity to manipulate learning related changes. Here we present evidence that extends upon our previous finding by demonstrating that temporally coordinated phasic deep brain stimulation across both the nucleus accumbens and caudate can further enhance associative learning. Monkeys performed a visual-motor associative learning task and received stimulation at time points critical to learning related changes. Resulting performance revealed an enhancement in the rate, ceiling, and reaction times of learning. Stimulation of each brain region alone or at different time points did not generate the same effect. C1 [Katnani, Husam A.; Patel, Shaun R.; Kwon, Churl-Su; Abdel-Aziz, Samer; Eskandar, Emad N.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Gale, John T.] Cleveland Clin, Dept Neurosci, Cleveland, OH 44106 USA. RP Katnani, HA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. EM hkatnani@mgh.harvard.edu FU National Institute of Neurological Disorders and Stroke [R01 NS086422]; National Eye Institute [R01EY017658]; DARPA Subnets award FX The work done in this investigation was supported by the National Institute of Neurological Disorders and Stroke (R01 NS086422) and the National Eye Institute (R01EY017658). We thank M. Thombs, Angelique Paulk, and E. McDonald for general assistance. E.E was also supported by the DARPA Subnets award. NR 32 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 4 PY 2016 VL 6 AR 18806 DI 10.1038/srep18806 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EH7SH UT WOS:000391972400001 PM 26725509 ER PT J AU Stroud, CB Hershenberg, R Cardenas, S Greiter, E Richmond, M AF Stroud, Catherine B. Hershenberg, Rachel Cardenas, Stephanie Greiter, Elizabeth Richmond, Margaret TI U.S. College Students' Sexual Activity: The Unique and Interactive Effects of Emotion Regulation Difficulties and Attachment Style SO INTERNATIONAL JOURNAL OF SEXUAL HEALTH LA English DT Article DE gender differences; Emotion regulation difficulties; sexual activity; attachment anxiety; attachment avoidance ID ADULT ATTACHMENT; INDIVIDUAL-DIFFERENCES; ROMANTIC RELATIONSHIPS; EXPERIENCES; BEHAVIOR; DYSREGULATION; CONSEQUENCES; MOTIVATIONS; HOOKING; MODEL AB ABSTACT Objectives: This study explored the association between emotion regulation difficulties and sexual activity, and whether emotion regulation difficulties moderated the link between attachment and sexual activity. Methods: U.S. college students (N = 373) from two institutions completed self-report measures of sexual activity, emotion regulation difficulties and attachment. Results: Findings indicated that greater emotion regulation difficulties were associated with less frequent exclusive sexual activity. Moreover, emotion regulation difficulties moderated links between attachment avoidance and sexual activity, and associations varied according to relational context and gender. Conclusions: Implications for promoting sexual health and relationship intimacy are discussed. C1 [Stroud, Catherine B.; Cardenas, Stephanie; Greiter, Elizabeth; Richmond, Margaret] Williams Coll, Dept Psychol, Williamstown, MA 01267 USA. [Hershenberg, Rachel] Univ Penn, Educ & Clin Ctr, VISN Mental Illness Res 4, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Hershenberg, Rachel] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Stroud, CB (reprint author), Williams Coll, Dept Psychol, Bronfman Sci Ctr, 18 Hoxsey St, Williamstown, MA 01267 USA. EM Catherine.B.Stroud@williams.edu FU Williams College; the VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA FX This research was supported by institutional funds from Williams College. Catherine B. Stroud was supported by institutional funds from Williams College. This article was prepared with the support of the VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA. NR 56 TC 0 Z9 0 U1 3 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1931-7611 EI 1931-762X J9 INT J SEX HEALTH JI Int. J. Sex. Health PD JAN 2 PY 2016 VL 28 IS 1 BP 37 EP 49 DI 10.1080/19317611.2015.1073824 PG 13 WC Psychology, Clinical; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Psychology; Public, Environmental & Occupational Health; Social Sciences - Other Topics GA DJ0SC UT WOS:000373913700005 ER PT J AU Lewis, RC Hauser, R Maynard, AD Neitzel, RL Wang, L Kavet, R Meeker, JD AF Lewis, Ryan C. Hauser, Russ Maynard, Andrew D. Neitzel, Richard L. Wang, Lu Kavet, Robert Meeker, John D. TI Exposure to Power-Frequency Magnetic Fields and the Risk of Infertility and Adverse Pregnancy Outcomes: Update on the Human Evidence and Recommendations for Future Study Designs SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS LA English DT Review ID VIDEO-DISPLAY TERMINALS; URINARY BISPHENOL-A; SPERM DNA-DAMAGE; SPONTANEOUS-ABORTION; BIRTH-DEFECTS; SEMEN QUALITY; DEVELOPMENTAL TOXICITY; ELECTROMAGNETIC-FIELDS; RESIDENTIAL PROXIMITY; CHILDHOOD LEUKEMIA AB Infertility and adverse pregnancy outcomes are significant public health concerns with global prevalence. Over the past 35years, research has addressed whether exposure to power-frequency magnetic fields is one of the etiologic factors attributed to these conditions. However, no apparent authoritative reviews on this topic have been published in the peer-reviewed literature for nearly 15years. This review provides an overview and critical analysis of human studies that were published in the peer-reviewed literature between 2002 and July 2015. Using PubMed, 13 epidemiology studies published during this time frame that concern exposure to magnetic fields and adverse prenatal (e.g., miscarriage), neonatal (e.g., preterm birth or birth defects), and male fertility (e.g., poor semen quality) outcomes were identified. Some of these studies reported associations whereas others did not, and study design limitations may explain these inconsistencies. Future investigations need to be designed with these limitations in mind to address existing research gaps. In particular, the following issues are discussed: (1) importance of selecting the appropriate study population, (2) need for addressing confounding due to unmeasured physical activity, (3) importance of minimizing information bias from exposure measurement error, (4) consideration of alternative magnetic field exposure metrics, and (5) implications and applications of personal exposure data that are correlated within female-male couples. Further epidemiologic research is needed, given the near ubiquitous exposures to power-frequency magnetic fields in the general population. C1 [Lewis, Ryan C.; Maynard, Andrew D.; Neitzel, Richard L.; Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 1415 Washington Hts, Ann Arbor, MI 48109 USA. [Lewis, Ryan C.] Exponent Inc, Ctr Occupat & Environm Hlth Risk Assessment, Oakland, CA USA. [Hauser, Russ] Harvard Univ, Dept Environm Hlth, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Wang, Lu] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Kavet, Robert] Elect Power Res Inst, Palo Alto, CA USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu FU Electric Power Research Institute FX Ryan Lewis began this research while he was a PhD student at University of Michigan. However, he has since graduated from the University of Michigan and now works for Exponent, Inc., a firm that provides consultation on the potential human health risks posed by exposure to environmental agents, including power-frequency magnetic fields. Robert Kavet is employed by the Electric Power Research Institute, which partially funded this research. All others authors declare no conflict of interest. NR 87 TC 1 Z9 1 U1 7 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1093-7404 EI 1521-6950 J9 J TOXICOL ENV HEAL B JI J. Toxicol. Env. Health-Pt b-Crit. Rev. PD JAN 2 PY 2016 VL 19 IS 1 BP 29 EP 45 DI 10.1080/10937404.2015.1134370 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DI8WF UT WOS:000373782300002 PM 27030583 ER PT J AU Binswanger, IA Gordon, AJ AF Binswanger, Ingrid A. Gordon, Adam J. TI From risk reduction to implementation: Addressing the opioid epidemic and continued challenges to our field SO SUBSTANCE ABUSE LA English DT Editorial Material C1 [Binswanger, Ingrid A.] Kaiser Permanente Colorado, Inst Hlth Res, POB 378066, Denver, CO USA. [Binswanger, Ingrid A.] Univ Colorado, Sch Med, Aurora, CO USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Binswanger, IA (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, POB 378066, Denver, CO USA. EM Ingrid.A.Binswanger@kp.org FU Substance Abuse Mental Health Services Administration (SAMHSA) [5H79TI025595] FX Funding for this initiative was made possible (in part) by Providers' Clinical Support System for Opioid Therapies (grant no. 5H79TI025595) from the Substance Abuse Mental Health Services Administration (SAMHSA). 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 US government. NR 17 TC 3 Z9 3 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 2 PY 2016 VL 37 IS 1 BP 1 EP 3 DI 10.1080/08897077.2015.1134152 PG 3 WC Substance Abuse SC Substance Abuse GA DH4GQ UT WOS:000372743900001 PM 26820257 ER PT J AU Hinrichs, KLM Sharma, S Thurston, J Sivashanker, K Chang, GH AF Hinrichs, Kate L. M. Sharma, Samata Thurston, Joe Sivashanker, Karthik Chang, Grace H. TI Management of opioid use disorders among veterans in subacute rehab: Use of an interdisciplinary task force to address an emerging concern SO SUBSTANCE ABUSE LA English DT Letter DE opioid, rehabilitation; intervention; Interdisciplinary ID SUBSTANCE USE AB There is both rapidly growing need, and limited evidence-based guidelines, for the management of opioid use disorders in subacute rehab and other nonaddiction medical settings. Following 2 unintentional opioid overdoses within the Community Living Center (CLC), a VA (Veterans Administration) subacute rehab setting, an interdisciplinary CLC Addictions Task Force was created to address a critical issue: how to best meet the combined neuropsychiatric and medical needs of the opiate use disorder patient through a multifaceted treatment approach. The goals of the task force were to develop and institute educational initiatives for providers; create patient care guidelines; increase safety on the unit; improve provider confidence when caring for this high-risk population; and mitigate the risk of unintentional overdose. The task force divided into 4 working groups to meet these aims. Process and outcomes are discussed. We found that in-services by addiction specialists improved clinician comfort in caring for this high-risk patient group. Specific areas that yielded the greatest clinician satisfaction ratings included didactics on how to identify at-risk patients and techniques on how to manage the patient in a general rehab setting. Utilizing an interdisciplinary approach, and an iterative process, at all stages was critical to the success of the CLC Addictions Task Force, as it improved buy-in and motivation from all disciplines. Improvements have been made to enhance patient safety, improve communication amongst providers, and provide a foundation to improve patient outcomes. Our preliminary work to enhance the identification and management of opioid use disorders at our CLC is an important first step towards a standardized curriculum that could be applied to other VA and non-VA subacute rehab settings. C1 [Hinrichs, Kate L. M.; Sharma, Samata; Thurston, Joe; Sivashanker, Karthik; Chang, Grace H.] VA Boston Healthcare Syst, Boston, MA USA. RP Hinrichs, KLM (reprint author), VA Boston Healthcare Syst, 940 Belmont St,GEC 181, Brockton, MA 02301 USA. EM kate.hinrichs@va.gov FU VA [VA999999] NR 4 TC 0 Z9 0 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 2 PY 2016 VL 37 IS 1 BP 4 EP 6 DI 10.1080/08897077.2015.1127871 PG 3 WC Substance Abuse SC Substance Abuse GA DH4GQ UT WOS:000372743900002 PM 26672391 ER PT J AU Burns, RM Pacula, RL Bauhoff, S Gordon, AJ Hendrikson, H Leslie, DL Stein, BD AF Burns, Rachel M. Pacula, Rosalie L. Bauhoff, Sebastian Gordon, Adam J. Hendrikson, Hollie Leslie, Douglas L. Stein, Bradley D. TI Policies related to opioid agonist therapy for opioid use disorders: The evolution of state policies from 2004 to 2013 SO SUBSTANCE ABUSE LA English DT Article DE policy; Buprenorphine; opioid use disorder ID SUBSTANCE-ABUSE TREATMENT; METHADONE-MAINTENANCE TREATMENT; OFFICE-BASED TREATMENT; COST-EFFECTIVENESS; UNITED-STATES; MEDICAID POPULATION; ADDICTION TREATMENT; PRIOR AUTHORIZATION; OPIATE ADDICTION; HEROIN-ADDICTION AB Background: State Medicaid policies play an important role in Medicaid enrollees' access to and use of opioid agonists, such as methadone and buprenorphine, in the treatment of opioid use disorders. Little information is available, however, regarding the evolution of state policies facilitating or hindering access to opioid agonists among Medicaid enrollees. Methods: During 2013-2014, we surveyed state Medicaid officials and other designated state substance abuse treatment specialists about their state's recent history of Medicaid coverage and policies pertaining to methadone and buprenorphine. We describe the evolution of such coverage and policies and present an overview of the Medicaid policy environment with respect to opioid agonist therapy from 2004 to 2013. Results: Among our sample of 45 states with information on buprenorphine and methadone coverage, we found a gradual trend toward adoption of coverage for opioid agonist therapies in state Medicaid agencies. In 2013, only 11% of states in our sample (n = 5) had Medicaid policies that excluded coverage for methadone and buprenorphine, whereas 71% (n = 32) had adopted or maintained policies to cover both buprenorphine and methadone among Medicaid enrollees. We also noted an increase in policies over the time period that may have hindered access to buprenorphine and/or methadone. Conclusions: There appears to be a trend for states to enact policies increasing Medicaid coverage of opioid agonist therapies, while in recent years also enacting policies, such as prior authorization requirements, that potentially serve as barriers to opioid agonist therapy utilization. Greater empirical information about the potential benefits and potential unintended consequences of such policies can provide policymakers and others with a more informed understanding of their policy decisions. C1 [Burns, Rachel M.; Pacula, Rosalie L.; Bauhoff, Sebastian; Stein, Bradley D.] RAND Corp, 4570 Fifth Ave, Pittsburgh, PA USA. [Gordon, Adam J.; Stein, Bradley D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hendrikson, Hollie] Natl Conf State Legislatures, Denver, CO USA. [Leslie, Douglas L.] Penn State Coll Med, Hershey, PA USA. RP Burns, RM (reprint author), RAND Corp, 4570 Fifth Ave, Pittsburgh, PA USA. EM rachel@rand.org FU National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) [1R01DA032881-01A1] FX The National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) provided support (award 1R01DA032881-01A1) for this study. The study's results and interpretation are those of the authors and do not represent those of NIDA or the NIH. The authors declare that they have no conflicts of interest. NR 61 TC 4 Z9 4 U1 4 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 2 PY 2016 VL 37 IS 1 BP 63 EP 69 DI 10.1080/08897077.2015.1080208 PG 7 WC Substance Abuse SC Substance Abuse GA DH4GQ UT WOS:000372743900013 PM 26566761 ER PT J AU Mitchell, MA Poyrazli, S Broyles, LM AF Mitchell, Michael A. Poyrazli, Senel Broyles, Lauren Matukaitis TI Hazardous alcohol use and cultural adjustment among U.S. college students abroad in Italy: Findings and recommendations for study abroad staff and researchers SO SUBSTANCE ABUSE LA English DT Article DE alcohol drinking; students; binge drinking; Italy; young adults; Acculturation ID DISORDERS IDENTIFICATION TEST; BINGE DRINKING; UNIVERSITY-STUDENTS AB Background: Italy is a top destination for U.S. college students studying abroad. Both international and local Italian media outlets, such as city newspapers, have cited the discordance between Italian cultural norms and U.S. college students' drinking behaviors. Hazardous alcohol consumption abroad, such as binge drinking, can result in individual- (e.g., physical injury) and social- (e.g., promotion of negative stereotypes) level adverse consequences. Methods: We assessed the prevalence of hazardous alcohol use and recent binge drinking in a sample of U.S. college students studying abroad in Italy (n = 111). We evaluated associations among drinking and cultural adjustment and determined which sociocultural factors predicted binge drinking for students abroad. Results: Forty-six percent of students were classified as hazardous drinkers and 63% reported recent binge drinking. Socializing with American peers was a significant predictor for binge drinking abroad. Conclusions: Binge drinking was quite prevalent in our sample of students studying abroad in Italy. Study abroad advisors, instructors, and staff should consider diverse strategies to screen, educate, prevent, and/or intervene on alcohol misuse with their students. These strategies should be personalized to both the student as well as the host culture's norms. C1 [Mitchell, Michael A.] VA Pittsburgh Healthcare Syst, VA Pittsburgh Healthcare Syst Interdisciplinary A, Univ Dr C,151C, Pittsburgh, PA 15240 USA. [Poyrazli, Senel] Penn State Univ Harrisburg, Behav Sci & Educ, Middletown, PA USA. [Broyles, Lauren Matukaitis] VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA 15240 USA. [Broyles, Lauren Matukaitis] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15240 USA. [Broyles, Lauren Matukaitis] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Mitchell, MA (reprint author), VA Pittsburgh Healthcare Syst, VA Pittsburgh Healthcare Syst Interdisciplinary A, Univ Dr C,151C, Pittsburgh, PA 15240 USA. EM Mitchellm59@gmail.com FU Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Addiction Treatment; Career Development Award from the Health Services Research & Development service (CDA) [10-014] FX This work was partially supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Addiction Treatment (M. Mitchell), a Career Development Award from the Health Services Research & Development service (CDA 10-014, Principal Investigator [PI]: L. Broyles), and with resources and facilities at the VA Pittsburgh Healthcare System, Pittsburgh, PA. The views expressed in this article are those of the authors and do not necessarily reflect the position of the Department of Veterans Affairs or the United States government. NR 39 TC 1 Z9 1 U1 1 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 2 PY 2016 VL 37 IS 1 BP 215 EP 221 DI 10.1080/08897077.2015.1019663 PG 7 WC Substance Abuse SC Substance Abuse GA DH4GQ UT WOS:000372743900036 PM 26848514 ER PT J AU Casaletto, KB Moore, DJ Woods, SP Umlauf, A Scott, JC Heaton, RK AF Casaletto, Kaitlin B. Moore, David J. Woods, Steven Paul Umlauf, Anya Scott, J. C. Heaton, Robert K. TI Abbreviated Goal Management Training Shows Preliminary Evidence as a Neurorehabilitation Tool for HIV-associated Neurocognitive Disorders among Substance Users SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Activities of daily living; Executive functions; Compensatory strategies.; Awareness ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRAUMATIC BRAIN-INJURY; FRONTAL-LOBE DAMAGE; METHAMPHETAMINE DEPENDENCE; NEUROPSYCHOLOGICAL IMPAIRMENT; ANTIRETROVIRAL THERAPY; SELF-AWARENESS; MEDICATION ADHERENCE; EXECUTIVE FUNCTIONS; METAMEMORY DEFICIT AB Objective: Substance use disorders are highly comorbid with and contribute to the increased prevalence of neurocognitive dysfunction observed in HIV infection. Despite their adverse impact on everyday functioning, there are currently no compensatory-based neurorehabilitation interventions validated for use among HIV+ substance users (HIV/SUD). This study examined the effectiveness of goal management training (GMT) alone or GMT as part of a metacognitive training among HIV/SUD individuals with executive dysfunction. Methods: Ninety HIV/SUD individuals were randomized to a single 15-min session: (1) GMT (n=30); (2) GMT plus metacognitive training (neurocognitive awareness; GMT+Meta; n=30); or (3) active control (n=30). Following a brief neurocognitive battery and study condition, participants performed a complex laboratory-based function task, Everyday Multitasking Test (Everyday MT), during which metacognition (awareness) was evaluated. Results: There was an increasing, but non-significant tendency for better Everyday MT performances across study conditions (Control <= GMT <= GMT+Meta; ps<.08). Post hoc analyses showed that GMT and GMT+Meta groups demonstrated small benefits (d=.20-.27) compared to the control arm but did not differ from one another (ds<.10). When GMT groups were combined, there were significant medium effect size benefits in Everyday MT performance and metacognitive task appraisals as compared to the control condition. Among participants who underwent GMT, benefits were most prominent in persons with poorer pre-training dual-tasking ability, depression, and methamphetamine use disorders (ds=.35-1.04). Conclusions: A brief compensatory strategy has benefits for everyday multitasking and metacognition among HIV+ substance users with executive dysfunction. Future work exploring more intensive trainings, potentially complimentary to other restorative approaches and/or pharmacological treatments, is warranted. C1 [Casaletto, Kaitlin B.] SDSU UCSD Joint Doctoral Program Clin Psychol, San Diego, CA USA. [Moore, David J.; Umlauf, Anya; Heaton, Robert K.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Woods, Steven Paul] Univ Houston, Dept Psychol, Houston, TX USA. [Scott, J. C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Scott, J. C.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA USA. RP Casaletto, KB (reprint author), Univ Calif San Diego, Dept Psychiat, HIV Neurobehav Res Program, 220 Dickinson St,Suite B, San Diego, CA 92103 USA. EM kablackstone@ucsd.edu FU CSRD VA [IK2 CX000772]; NIDA NIH HHS [F31 DA035708, F31-DA035708, P50 DA026306]; NIMH NIH HHS [P30 MH062512] NR 66 TC 0 Z9 0 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD JAN 2 PY 2016 VL 30 IS 1 BP 107 EP 130 DI 10.1080/13854046.2015.1129437 PG 24 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA DH4CM UT WOS:000372733100008 PM 26753986 ER PT J AU Chang, G Martin, KB Tang, M Fleming, JA AF Chang, Grace Martin, Katherine Brooke Tang, Michael Fleming, Jerry A. TI Inpatient hospitalization for substance use disorders one year after residential rehabilitation: predictors among US veterans SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Residential rehabilitation; inpatient admission; clinical predictors ID ABUSE TREATMENT; REDUCE DEMAND; OUTCOMES; CARE; DETOXIFICATION; DEPENDENCE AB Background: The Veterans Health Administration (VHA) is among the principal providers of the full range of substance use disorders (SUD) treatment in the US. Relatively little, however, is known about patient outcomes after residential rehabilitation. Objective: To identify predictors of SUD inpatient hospitalization (primarily medically managed detoxification) in the year after SUD residential rehabilitation among US veterans. Methods: Medical records of 64 veterans admitted to one of two residential rehabilitation programs in the Northeast during the first quarter of FY 2012 were abstracted. Data included demographic, clinical, and treatment (inpatient and outpatient) information for the year before and after residential rehabilitation. Annual rates of treatment utilization were compared. Results: The veterans (mean age, 48.2 years) used substances for a mean of 27.6 years. Alcohol was the primary drug of choice (69%). More than half had SUD inpatient hospitalizations in the year before (79%) and after (53%) residential rehabilitation; SUD inpatient admission occurred an average of 64 days after discharge. According to the multivariate Cox regression model, the estimated risk of SUD inpatient hospitalization increased by 25% for each past year SUD inpatient hospitalization, decreased by 74% if there was no opiate use disorder diagnosis, and decreased by 2% for each day increase in residential rehabilitation length of stay when extent of service connected disability, marital status, and days since last SUD inpatient admission are taken into account. Conclusions: Risk factors for SUD inpatient hospitalization after residential rehabilitation have been identified and, if confirmed, may represent opportunities for targeted program change. C1 [Chang, Grace; Tang, Michael; Fleming, Jerry A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. [Martin, Katherine Brooke] LVPG Consult Liaison Psychiat, Psychiat, Allentown, PA USA. RP Chang, G (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM grace.chang2@va.gov NR 28 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JAN 2 PY 2016 VL 42 IS 1 BP 56 EP 62 DI 10.3109/00952990.2015.1088863 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA DG1CP UT WOS:000371803200008 PM 26485005 ER PT J AU Henley, SS Kashner, TM Golden, RM Westover, AN AF Henley, Steven S. Kashner, T. Michael Golden, Richard M. Westover, Arthur N. TI Response to letter regarding "A systematic approach to subgroup analyses in a smoking cessation trial" SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Letter C1 [Henley, Steven S.] Martingale Res Corp, Plano, TX USA. [Henley, Steven S.; Kashner, T. Michael] Loma Linda Univ, Sch Med, Dept Med, Loma Linda, CA 92354 USA. [Golden, Richard M.] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA. [Westover, Arthur N.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. [Westover, Arthur N.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. [Kashner, T. Michael] US Dept Vet Affairs, Off Acad Affiliat, Washington, DC USA. RP Westover, AN (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.; Westover, AN (reprint author), Univ Texas SW Med Ctr Dallas, Dept Clin Sci, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM arthur.westover@utsouthwestern.edu FU NCI NIH HHS [R44 CA139607]; NIAAA NIH HHS [R43 AA013670, R43 AA013351, R43 AA014302, R44 AA011607, R44 AA013351]; NIGMS NIH HHS [R43 GM106465] NR 14 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JAN 2 PY 2016 VL 42 IS 1 BP 112 EP 113 DI 10.3109/00952990.2015.1117482 PG 2 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA DG1CP UT WOS:000371803200014 PM 26717302 ER PT J AU Lewis, A Wahlster, S Karinja, S Czeisler, BM Kimberly, WT Lord, AS AF Lewis, Ariane Wahlster, Sarah Karinja, Sarah Czeisler, Barry M. Kimberly, W. Taylor Lord, Aaron S. TI Ventriculostomy-related infections: The performance of different definitions for diagnosing infection SO BRITISH JOURNAL OF NEUROSURGERY LA English DT Article DE ventriculitis; CSF shunt; surgical-site infection; cerebrospinal fluid; infection ID CEREBROSPINAL-FLUID; ANTIMICROBIAL PROPHYLAXIS; SUBARACHNOID HEMORRHAGE; NEUROSURGICAL PATIENTS; DRAINS; EFFICACY; INTERLEUKIN-6; VENTRICULITIS; MENINGITIS; EXPERIENCE AB Introduction. Comparison of rates of ventriculostomy-related infections (VRIs) across institutions is difficult due to the lack of a standard definition. We sought to review published definitions of VRI and apply them to a test cohort to determine the degree of variability in VRI diagnosis. Materials and methods. We conducted a PubMed search for definitions of VRI using the search strings "ventriculostomy-related infection" and "ventriculostomy-associated infection." We applied these definitions to a test cohort of 18 positive cerebrospinal fluid (CSF) cultures taken from ventriculostomies at two institutions to compare the frequency of infection using each definition. Results. We found 16 unique definitions of VRI. When the definitions were applied to the test cohort, the frequency of infection ranged from 22 to 94% (median 61% with interquartile range (IQR) 56-74%). The concordance between VRI diagnosis and treatment with VRI-directed antibiotics for at least seven days ranged from 56 to 89% (median: 72%, IQR: 71-78%). Conclusions. The myriad of definitions in the literature produce widely different frequencies of infection. In order to compare rates of VRI between institutions for the purposes of qualitative metrics and research, a consistent definition of VRI is needed. C1 [Lewis, Ariane; Karinja, Sarah; Czeisler, Barry M.; Lord, Aaron S.] NYU, Langone Med Ctr, Dept Neurol, Div Neurocrit Care, 530 First Ave,HCC 522F, New York, NY 10016 USA. [Wahlster, Sarah; Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Wahlster, Sarah] Univ Washington, Harborview Med Ctr, Dept Neurol, Div Neurocrit Care, 325 9Th Ave, Seattle, WA 98104 USA. [Karinja, Sarah] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. RP Lewis, A (reprint author), NYU, Langone Med Ctr, Dept Neurol, Div Neurocrit Care, 530 First Ave,HCC 522F, New York, NY 10016 USA. EM ariane.kansas.lewis@gmail.com OI Lewis, Ariane/0000-0002-0756-7320; Lord, Aaron/0000-0001-8755-7773; Czeisler, Barry/0000-0002-7888-0373 FU NYU-HHC Clinical and Translational Science Institute from National Center for Advancing Translational Sciences of the National Institutes of Health [UL1 TR000038]; Andrew David Heitman Neurovascular Research Foundation FX Ariane Lewis, Sarah Wahlster, Sarah Karinja, and Barry Czeisler do not have any financial conflicts of interest. Aaron Lord received support from the NYU-HHC Clinical and Translational Science Institute via grant UL1 TR000038 from the National Center for Advancing Translational Sciences of the National Institutes of Health. W. Taylor Kimberly receives support from the Andrew David Heitman Neurovascular Research Foundation. The Foundation had no role in study design, collection, analysis, interpretation of data, writing of the manuscript, or decision to submit the manuscript for publication. NR 37 TC 2 Z9 2 U1 2 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0268-8697 EI 1360-046X J9 BRIT J NEUROSURG JI Br. J. Neurosurg. PD JAN 2 PY 2016 VL 30 IS 1 BP 49 EP 56 DI 10.3109/02688697.2015.1080222 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DG6LM UT WOS:000372195900012 PM 26372297 ER PT J AU Elahi, D Ruff, DA Carlson, OD Meneilly, GS Habener, JF Egan, JM AF Elahi, Dariush Ruff, Dennis A. Carlson, Olga D. Meneilly, Graydon S. Habener, Joel F. Egan, Josephine M. TI Does GLP-1 suppress its own basal secretion? SO ENDOCRINE RESEARCH LA English DT Article DE GLP-1; glucose clamp; insulin; negative feedback ID GLUCAGON-LIKE PEPTIDE-1; INSULIN-SECRETION; INHIBITION; HUMANS; SOMATOSTATIN; SPECIFICITY; RELEASE; OBESITY; AMIDE; STATE AB Purpose/Aim: Negative feedback controls in endocrine regulatory systems are well recognized. The incretins and their role in glucose regulation have been of major interest recently. Whether the same negative control system applies to the regulation of incretin secretion is not clear. We sought to examine the hypothesis that exogenous administration of glucagon like peptide-1, GLP-1(7-36) amide or its metabolite GLP-1(9-36) amide, reduces the endogenous basal release of this incretin. Materials and Methods: We evaluated the endogenous basal release of GLP-1 using two separate study designs. In protocol A we examined the GLP-1(7-36) amide levels during the infusion of GLP-1(9-36) amide. In protocol B, we used PYY and GLP-2 as biomarkers for the endogenous basal release of GLP-1(7-36) amide and assessed the endogenous basal release of these two hormones during the GLP-1(7-36) infusion. Twelve lean and 12 obese subjects were enrolled in protocol A and 10 obese volunteers in protocol B. Results: The plasma levels of GLP-1(7-36) amide in protocol A and PYY and GLP-2 in protocol B remained unchanged during the exogenous infusion of GLP-1(9-36) and GLP-1(7-36) amide, respectively. Conclusions: The negative feedback control system as described by inhibition of the release of endogenous hormone while infusing it exogenously was not observed for the basal secretion of GLP-1(7-36) amide. C1 [Elahi, Dariush; Ruff, Dennis A.] ICON Early Phase Serv LLC, 8307 Gault Lane, San Antonio, TX 78209 USA. [Carlson, Olga D.; Egan, Josephine M.] NIA, Diabet Sect, Baltimore, MD 21224 USA. [Meneilly, Graydon S.] Univ British Columbia, Dept Med, Sch Med, Vancouver, BC, Canada. [Habener, Joel F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Habener, Joel F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Elahi, D (reprint author), ICON Early Phase Serv LLC, 8307 Gault Lane, San Antonio, TX 78209 USA. EM dariush.elahi@iconplc.com FU National Institutes of Health (NIH) [AG 00599, AG 623175, DK 30834]; Intramural Research Program of NIA; Alan McGavin Geriatric Medicine Endowment of University of British Columbia FX Authors have nothing to declare. This work has been supported in part by the National Institutes of Health (NIH) Grants: AG 00599, AG 623175, DK 30834 and by the Intramural Research Program of NIA. We gratefully acknowledge the support of the Alan McGavin Geriatric Medicine Endowment of the University of British Columbia. NR 27 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0743-5800 EI 1532-4206 J9 ENDOCR RES JI Endocr. Res. PD JAN 2 PY 2016 VL 41 IS 1 BP 16 EP 20 DI 10.3109/07435800.2015.1038353 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DG4AT UT WOS:000372013000003 PM 26186406 ER PT J AU Manchikanti, L Hirsch, JA Kaye, AD Boswell, MV AF Manchikanti, Laxmaiah Hirsch, Joshua A. Kaye, Alan D. Boswell, Mark V. TI Cervical zygapophysial (facet) joint pain: effectiveness of interventional management strategies SO POSTGRADUATE MEDICINE LA English DT Review DE Cervical intra-articular injections; Cervical facet joint pain; Cervical facet joint; Cervical facet joint radiofrequency neurotomy; Controlled diagnostic blocks; Cervical facet joint nerve blocks ID MEDIAL BRANCH BLOCKS; CHRONIC SPINAL PAIN; NONSPECIFIC NECK PAIN; RE MANCHIKANTI L; PERCUTANEOUS RADIOFREQUENCY NEUROTOMY; WHIPLASH-ASSOCIATED DISORDERS; CLINICAL-PREDICTION RULE; PLACEBO-CONTROLLED TRIAL; LUMBAR RADICULAR PAIN; LOW-BACK-PAIN AB Diagnostic facet joint nerve blocks have been utilized in the diagnosis of cervical facet joint pain in patients without disk herniation or radicular pain due to a lack of reliable noninvasive diagnostic measures. Therapeutic interventions include intra-articular injections, facet joint nerve blocks and radiofrequency neurotomy. The diagnostic accuracy and effectiveness of facet joint interventions have been assessed in multiple diagnostic accuracy studies, randomized controlled trials (RCTs), and systematic reviews in managing chronic neck pain. This assessment shows there is Level II evidence based on a total of 11 controlled diagnostic accuracy studies for diagnosing cervical facet joint pain in patients without disk herniation or radicular pain utilizing controlled diagnostic blocks. Due to significant variability and internal inconsistency regarding prevalence in a heterogenous population; despite 11 studies, evidence is determined as Level II. Prevalence ranged from 36% to 67% with at least 80% pain relief as the criterion standard with a false-positive rate ranging from 27% to 63%. The evidence is Level II for the long-term effectiveness of radiofrequency neurotomy and facet joint nerve blocks in managing cervical facet joint pain. There is Level III evidence for cervical intra-articular injections. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah; Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, Dept Anesthesia, New Orleans, LA USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 109 TC 6 Z9 6 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0032-5481 EI 1941-9260 J9 POSTGRAD MED JI Postgrad. Med. PD JAN 2 PY 2016 VL 128 IS 1 BP 54 EP 68 DI 10.1080/00325481.2016.1105092 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA DF3OO UT WOS:000371254400008 PM 26653406 ER PT J AU Serrao, E Engelman, AN AF Serrao, Erik Engelman, Alan N. TI Sites of retroviral DNA integration: From basic research to clinical applications SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Gene therapy; HIV-1; illumina; intasome; integrase; integration sites; next-generation sequencing; retrovirus ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; MAMMARY-TUMOR VIRUS; POLYMERASE-CHAIN-REACTION; AVIAN-SARCOMA VIRUS; T-CELL LEUKEMIA; HEMATOPOIETIC STEM-CELLS; TYPE-1 PREINTEGRATION COMPLEXES; COMPLEMENTARY ASSAYS REVEAL; TRANSCRIPTION START SITES AB One of the most crucial steps in the life cycle of a retrovirus is the integration of the viral DNA (vDNA) copy of the RNA genome into the genome of an infected host cell. Integration provides for efficient viral gene expression as well as for the segregation of viral genomes to daughter cells upon cell division. Some integrated viruses are not well expressed, and cells latently infected with human immunodeficiency virus type 1 (HIV-1) can resist the action of potent antiretroviral drugs and remain dormant for decades. Intensive research has been dedicated to understanding the catalytic mechanism of integration, as well as the viral and cellular determinants that influence integration site distribution throughout the host genome. In this review, we summarize the evolution of techniques that have been used to recover and map retroviral integration sites, from the early days that first indicated that integration could occur in multiple cellular DNA locations, to current technologies that map upwards of millions of unique integration sites from single in vitro integration reactions or cell culture infections. We further review important insights gained from the use of such mapping techniques, including the monitoring of cell clonal expansion in patients treated with retrovirus-based gene therapy vectors, or patients with acquired immune deficiency syndrome (AIDS) on suppressive antiretroviral therapy (ART). These insights span from integrase (IN) enzyme sequence preferences within target DNA (tDNA) at the sites of integration, to the roles of host cellular proteins in mediating global integration distribution, to the potential relationship between genomic location of vDNA integration site and retroviral latency. C1 [Serrao, Erik; Engelman, Alan N.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. RP Engelman, AN (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU US National Institutes of Health [AI052014, AI039394]; [AI007386] FX The authors declare no conflict of financial interest. This study was supported by US National Institutes of Health grants AI052014 and AI039394 (to A.N.E.) as well as AI007386 (to E.S.). NR 275 TC 5 Z9 5 U1 4 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1040-9238 EI 1549-7798 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD JAN 2 PY 2016 VL 51 IS 1 BP 26 EP 42 DI 10.3109/10409238.2015.1102859 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DD2RG UT WOS:000369769300004 PM 26508664 ER PT J AU Nishi, A Milner, DA Giovannucci, EL Nishihara, R Tan, AS Kawachi, I Ogino, S AF Nishi, Akihiro Milner, Danny A., Jr. Giovannucci, Edward L. Nishihara, Reiko Tan, Andy S. Kawachi, Ichiro Ogino, Shuji TI Integration of molecular pathology, epidemiology and social science for global precision medicine SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE clinical outcome; disparity; epigenetics; interdisciplinary; molecular pathologic epidemiology; network analysis; personalized medicine; social medicine ID ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER RISK; BODY-MASS INDEX; DISEASE CLASSIFICATION DATA; BETA-CATENIN ALTERATIONS; INVASIVE BREAST-CANCER; ASPIRIN USE; MICROSATELLITE-INSTABILITY; MENDELIAN RANDOMIZATION; ETIOLOGIC HETEROGENEITY AB The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. C1 [Nishi, Akihiro] Yale Univ, Inst Network Sci, New Haven, CT USA. [Nishi, Akihiro] Yale Univ, Dept Sociol, New Haven, CT USA. [Milner, Danny A., Jr.; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Milner, Danny A., Jr.; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Milner, Danny A., Jr.] Harvard Univ, Dept Immunol & Infect Dis, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Giovannucci, Edward L.; Nishihara, Reiko; Ogino, Shuji] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Giovannucci, Edward L.; Nishihara, Reiko] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Nishihara, Reiko] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Nishihara, Reiko; Tan, Andy S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tan, Andy S.; Kawachi, Ichiro] Harvard Univ, Dept Social & Behav Sci, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU USA National Institute of Health [K07 CA190673, R35 CA197735, R01 CA151993]; Konosuke Matsushita Memorial Foundation; Japan Society for the Promotion of Science FX This work was supported in part by grants from the USA National Institute of Health (grants K07 CA190673 to R Nishihara, R35 CA197735 to S Ogino and R01 CA151993 to S Ogino) and the Konosuke Matsushita Memorial Foundation and the Japan Society for the Promotion of Science, both to A Nishi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 222 TC 9 Z9 10 U1 10 U2 37 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1473-7159 EI 1744-8352 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD JAN 2 PY 2016 VL 16 IS 1 BP 11 EP 23 DI 10.1586/14737159.2016.1115346 PG 13 WC Pathology SC Pathology GA DB3WV UT WOS:000368445000001 PM 26636627 ER PT J AU Kalapatapu, RK Delucchi, KL Wang, S Harbison, JD Nelson, EE Kramer, JH AF Kalapatapu, Raj K. Delucchi, Kevin L. Wang, Sophia Harbison, John D. Nelson, Emily E. Kramer, Joel H. TI Substance use history in behavioral-variant frontotemporal dementia versus primary progressive aphasia SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE Frontotemporal; dementia; cigarette smoking; alcohol; substance use; drug ID UNIFORM DATA SET; ALCOHOL-USE DISORDERS; OLDER-ADULTS; DISEASE CENTERS; ABUSE; ADDICTIONS; REWARD; METHAMPHETAMINE; EPIDEMIOLOGY; POPULATION AB As older adults are prone to cognitive disorders, the interaction of the fields of substance use and misuse and cognitive neuroscience is an emerging area of research. Substance use has been reported in some subtypes of frontotemporal dementia, such as behavioral variant frontotemporal dementia. However, characterization of substance use in other subtypes of frontotemporal dementia, such as primary progressive aphasia, is unknown. The objective of this baseline analysis was to explore whether any measures of substance use history differed significantly among behavioral variant frontotemporal dementia (n = 842) and primary progressive aphasia (n = 526) in a large national dataset. The National Alzheimer's Coordinating Center's Uniform Data Set study is a national dataset that collects data on patients with various cognitive disorders and includes some questions on substance use. Each substance use variable was used as the outcome and the frontotemporal dementia subtype as the predictor. Total years smoked cigarettes, age when last smoked cigarettes, average number of packs/day smoked when participants smoked, and any recent, remote, or combined recent/remote history of alcohol abuse or drug abuse did not significantly differ between the behavioral variant frontotemporal dementia and primary progressive aphasia subtypes (all p-values > .001). A significantly greater percentage of participants smoked in the last 30 days in the behavioral variant frontotemporal dementia subtype (10.4%, n = 834) compared to the primary progressive aphasia subtype (3.3%, n = 517; p < .001). Clinical providers in both the dementia and substance use fields are encouraged to screen for and monitor substance use in all frontotemporal dementia subtypes. C1 [Kalapatapu, Raj K.; Delucchi, Kevin L.; Harbison, John D.; Nelson, Emily E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Kalapatapu, Raj K.; Nelson, Emily E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Kalapatapu, Raj K.; Harbison, John D.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Wang, Sophia] Indiana Univ, Ctr Hlth Innovat & Implementat Sci, Dept Psychiat, Indianapolis, IN 46204 USA. [Kramer, Joel H.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. RP Kalapatapu, RK (reprint author), San Francisco VA Med Ctr, Opioid Treatment Program, Bldg 1,Ground Floor,Room 24,Mailstop 116F,4150 Cl, San Francisco, CA 94121 USA. EM kalapatapu.raj.k@gmail.com FU National Institute on Aging [UO1 AG016976]; [K23DA034883]; [P50DA009253]; [P50AG023501]; [R01AG022983]; [R01AG032289] FX The NACC is funded by the National Institute on Aging (UO1 AG016976) and located in the Department of Epidemiology at the University of Washington School of Public Health. Dr. Kalapatapu is currently funded by K23DA034883. Dr. Delucchi is currently funded by P50DA009253. Dr. Kramer is currently funded by P50AG023501, R01AG022983, and R01AG032289. NR 49 TC 1 Z9 1 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0887 EI 1545-0848 J9 J ADDICT DIS JI J. Addict. Dis. PD JAN 2 PY 2016 VL 35 IS 1 BP 36 EP 41 DI 10.1080/10550887.2015.1102026 PG 6 WC Substance Abuse SC Substance Abuse GA DB7TW UT WOS:000368720200006 PM 26485480 ER PT J AU Cornford, EM Hyman, S Cornford, ME Chytrova, G Rhee, J Suzuki, T Yamagata, T Yamakawa, K Penichet, ML Pardridge, WM AF Cornford, Eain M. Hyman, Shigeyo Cornford, Marcia E. Chytrova, Gabriela Rhee, Jennifer Suzuki, Toshimitsu Yamagata, Tetsushi Yamakawa, Kazuhiro Penichet, Manuel L. Pardridge, William M. TI Non-invasive gene targeting to the fetal brain after intravenous administration and transplacental transfer of plasmid DNA using PEGylated immunoliposomes SO JOURNAL OF DRUG TARGETING LA English DT Article DE Adult and fetal blood-brain barrier; EPM2a null mutant mice; Lafora's disease; non-invasive gene delivery; PEGylated immunoliposome; transferrin receptor-mediated endocytosis; transplacental gene transfer ID RECEPTOR EXPRESSION; EXOGENOUS GENE; EPM2A GENE; IN-VIVO; DELIVERY; BARRIER; MOUSE; TRIAL; MICE; IRON AB Research was undertaken to establish transplacental delivery of active genes to fetal brain by a non-viral vector, antibody-specific targeted therapeutic procedure. PEGylated immunoliposomes (PILs) containing firefly luciferase DNA under the influence of the SV40 promoter injected intravenously into near-term pregnant mice produced luminometric evidence of CNS tissue luciferase activity at 48-h post-injection in all newborn pups. In utero delivery of this pGL3 DNA was shown after a single i.v. injection in maternal and neonatal brains, spleen and lesser amounts in lungs, with only negligible background levels in negative controls exposed to unencapsulated pDNA. In addition to studies of normal wild-type mice, we similarly injected pregnant Lafora Knockout (EPM2a null-mutant) and demonstrated luciferase activity days later in the maternal and newborn pup brains of both types. Delivery of PILs containing a second reporter gene (the pSV40 beta-galactosidase transgene) transplacentally by the same procedure was also successful. Histochemical and biochemical demonstration of beta-galactosidase was documented for all mutant and non-mutant neonates. Brain areas of highest Lafora body development (such as the hippocampus and pontine nuclei) showed intraneuronal beta-glucosidase activity. We conclude that receptor-mediated transport of PIL-borne gene therapeutics across both the placental barrier as well as the fetal BBB in utero is feasible. C1 [Cornford, Eain M.; Hyman, Shigeyo; Chytrova, Gabriela; Rhee, Jennifer] West Los Angeles Med Ctr, VA Greater Los Angeles Healthcare Syst, Neurol & Res Serv, Los Angeles, CA 90073 USA. [Cornford, Eain M.; Hyman, Shigeyo; Chytrova, Gabriela] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Cornford, Marcia E.] Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA. [Cornford, Marcia E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Suzuki, Toshimitsu; Yamagata, Tetsushi; Yamakawa, Kazuhiro] RIKEN, Brain Sci Inst, Saitama, Japan. [Penichet, Manuel L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Surg Oncol, Los Angeles, CA 90095 USA. [Penichet, Manuel L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Penichet, Manuel L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Penichet, Manuel L.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. [Pardridge, William M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Cornford, EM (reprint author), West Los Angeles Med Ctr, VA Greater Los Angeles Healthcare Syst, Neurol & Res Serv, Bldg 114 Room 217B, Los Angeles, CA 90073 USA. EM cornford@ucla.edu FU National Institutes of Health [1RO1 NS 052456]; France Lafora; Lysosomal Storage Diseases Research Consortium FX Supported by grants from the National Institutes of Health [1RO1 NS 052456], France Lafora, and the Lysosomal Storage Diseases Research Consortium. The authors report no declarations of interest. NR 33 TC 0 Z9 0 U1 1 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1061-186X EI 1029-2330 J9 J DRUG TARGET JI J. Drug Target. PD JAN 2 PY 2016 VL 24 IS 1 BP 58 EP 67 DI 10.3109/1061186X.2015.1055569 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB3ZZ UT WOS:000368453800006 PM 26133964 ER PT J AU Kondo, KK Rossi, JS Schwartz, SJ Zamboanga, BL Scalf, CD AF Kondo, Karli K. Rossi, Joseph S. Schwartz, Seth J. Zamboanga, Byron L. Scalf, Carissa D. TI Acculturation and cigarette smoking in Hispanic women: A meta-analysis SO JOURNAL OF ETHNICITY IN SUBSTANCE ABUSE LA English DT Article DE Acculturation; Hispanic; meta-analysis; smoking ID HEALTH-RISK BEHAVIORS; SUBSTANCE USE; ALCOHOL-CONSUMPTION; MEXICAN-AMERICANS; UNITED-STATES; ADOLESCENTS; EDUCATION; LANGUAGE; GENDER; MODEL AB The present study was a random-effects model meta-analysis of 26 studies published between 1990 and 2010 (k=32; n=39,777) that (a) examined the association between acculturation and cigarette smoking in Hispanic women and (b) evaluated age, national origin, and measure and dimensionality (unidimensional vs. bidimensional) of acculturation as moderating variables. Results indicate a strong positive relationship and suggest larger effects of acculturation on cigarette smoking in women of Mexican descent as compared with women originating from other Latin American countries for current and lifetime smoking, as well as smoking overall. The effect of acculturation on cigarette smoking was larger in adults as compared with adolescents for current smoking and smoking overall. Few differences in effect size by measure or dimensionality of acculturation emerged. Results are discussed with regard to implications for future research and the measurement of acculturation. C1 [Kondo, Karli K.] Portland VA Med Ctr, Portland, OR 97239 USA. [Kondo, Karli K.; Scalf, Carissa D.] Univ Pacific, Hillsboro, OR USA. [Rossi, Joseph S.] Univ Rhode Isl, Kingston, RI 02881 USA. [Schwartz, Seth J.] Univ Miami, Miami, FL USA. [Zamboanga, Byron L.] Smith Coll, Northampton, MA 01063 USA. RP Kondo, KK (reprint author), Portland VA Med Ctr, Mailcode RD71,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM karli.kondo@va.gov FU National Center for Research Resources of the National Institutes of Health [G20RR030883] FX This research was supported in part by the National Center for Research Resources of the National Institutes of Health under Award Number G20RR030883. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 68 TC 2 Z9 2 U1 5 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1533-2640 EI 1533-2659 J9 J ETHN SUBST ABUSE JI J. Ethn. Subst. Abuse PD JAN 2 PY 2016 VL 15 IS 1 BP 46 EP 72 DI 10.1080/15332640.2014.1002878 PG 27 WC Substance Abuse SC Substance Abuse GA DB4YF UT WOS:000368518800004 PM 26114872 ER PT J AU Liu, LCY Dorhout, B van der Meer, P Teerlink, JR Voors, AA AF Liu, Licette C. Y. Dorhout, Bernard van der Meer, Peter Teerlink, John R. Voors, Adriaan A. TI Omecamtiv mecarbil: a new cardiac myosin activator for the treatment of heart failure SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE cardiac myosin activator; CK-1827452; heart failure with reduced ejection fraction; omecamtiv mecarbil ID DOUBLE-BLIND; DOBUTAMINE; TRIAL; CARDIOMYOPATHY; MILRINONE; 1ST; LEVOSIMENDAN; MYOFILAMENTS; ASSOCIATION; SAFETY AB Introduction: Current available inotropic agents increase cardiac contractility, but are associated with myocardial ischemia, arrhythmias, and mortality. A novel selective cardiac myosin activator, omecamtiv mecarbil (CK-1827452/ AMG-423) is a small molecule that activates the sarcomere proteins directly, resulting in prolonged systolic ejection time and increased cardiac contractility. Areas covered: This paper discusses the chemistry, pharmacokinetics, clinical efficacy and safety of omecamtiv mecarbil. Omecamtiv mecarbil represents a novel therapeutic approach to directly improve cardiac function and is therefore proposed as a potential new treatment of patients with systolic heart failure. The authors review results of previous studies investigating the effect of omecamtiv mecarbil in heart failure animal models, healthy volunteers, and patients with acute and chronic systolic heart failure. Expert opinion: Results of phase I and phase II studies demonstrate that omecamtiv mecarbil is safe and well tolerated both as an intravenous and oral formulation. In healthy volunteers and chronic systolic heart failure patients, administration of omecamtiv mecarbil resulted in a concentration-dependent increase of left ventricular ejection time, ejection fraction, fractional shortening, and stroke volume. The first results of a double-blind, randomized, placebo-controlled phase IIb dose-finding study with the oral formulation of omecamtiv mecarbil demonstrated beneficial effects on cardiac function and N-terminal pro-brain natriuretic peptide levels. This study will provide essential dosing information for the requisite phase III trials which will investigate whether the beneficial effects of omecamtiv mecarbil translate into improved clinical outcomes. C1 [Liu, Licette C. Y.; Dorhout, Bernard; van der Meer, Peter; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Sect Cardiol, San Francisco, CA 94143 USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Voors, AA (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl FU Amgen Inc; Bayer Healthcare; Novartis; Servier; Stealth Peptides; Trevena Inc; Vifor Pharma; ZS Pharma; Cytokinetics; Theravance FX AA Voors has received consultancy fees and or research grants from Amgen Inc, Bayer Healthcare, Novartis, Servier, Stealth Peptides, Trevena Inc, Vifor Pharma and ZS Pharma. JR Teerlink has received consultancy fees and/or research grants from Amgen Inc, Bayer Healthcare, Cytokinetics, Novartis, Servier, Stealth Peptides, Theravance, Trevena Inc and ZS Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 31 TC 2 Z9 2 U1 2 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JAN 2 PY 2016 VL 25 IS 1 BP 117 EP 127 DI 10.1517/13543784.2016.1123248 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DA7ZI UT WOS:000368023700001 PM 26587768 ER PT J AU Steensma, DP AF Steensma, David P. TI Graphical representation of clinical outcomes for patients with myelodysplastic syndromes SO LEUKEMIA & LYMPHOMA LA English DT Review DE Patient outcomes; myelodysplastic syndromes; infographic; stem cell transplantation; causes of death ID STEM-CELL TRANSPLANTATION; IRON CHELATION-THERAPY; OLDER PATIENTS; SCORING SYSTEM; EPIDEMIOLOGY; DEATH; MDS AB The causes of death in patients with myelodysplastic syndromes (MDS) are diverse: infections, hemorrhage, complications of chronic anemia and repeated blood transfusions, and complications of progression to acute myeloid leukemia. Since most patients with MDS are diagnosed late in life, some individuals with MDS will succumb to an unrelated condition, such as one of the disorders that are common in geriatric populations. Currently, only a small proportion of patients with MDS - less than 5% - undergo allogeneic stem cell transplantation, a procedure that offers the only possibility of cure. This brief review summarizes outcomes for patients diagnosed with MDS using a pictographical format that illustrates both the challenges patients face and the pressing need for development of novel therapies, as well as highlighting the potential for increased use of allogeneic stem cell transplant. This informational graphic may be useful for teaching or in counseling certain patients. C1 [Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Steensma, DP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,D2037, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu NR 33 TC 4 Z9 4 U1 2 U2 7 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 JAN 2 PY 2016 VL 57 IS 1 BP 17 EP 20 DI 10.3109/10428194.2015.1061191 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA DA8AC UT WOS:000368025700006 PM 26098015 ER PT J AU Beltran, BE Aguilar, C Quinones, P Morales, D Chavez, JC Sotomayor, EM Castillo, JJ AF Beltran, Brady E. Aguilar, Christian Quinones, Pilar Morales, Domingo Chavez, Julio C. Sotomayor, Eduardo M. Castillo, Jorge J. TI The neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with peripheral T-cell lymphoma, unspecified SO LEUKEMIA & LYMPHOMA LA English DT Article DE lymphopenia; neutrophil; neutrophil-to-lymphocyte ratio; peripheral T-cell lymphoma; unspecified; PTCL; prognostic factor ID HEPATOCELLULAR-CARCINOMA; MONOCYTE COUNT; SURVIVAL; CANCER; LYMPHOPENIA; IMPACT; NEUTROPHIL/LYMPHOCYTE; CLASSIFICATION; INFLAMMATION; RITUXIMAB AB Peripheral T-cell lymphoma (PTCL) encompasses a group of rare and aggressive lymphomas. PTCL, unspecified (PTCLU) is the most common subtype of PTCL, and carries a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCLU (PIT) scoring systems are powerful risk-stratification tools in patients with PTCL. The aim of this study was to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in PTCLU. We retrospectively studied 83 patients with diagnosis of PTCLU. In the univariate analysis, NLR 4 was associated with worse overall survival (HR 3.96, 95% CI 1.92-8.17; p < 0.001). In the multivariate analysis, NLR 4 was independently associated with worse overall survival after adjustment for the PIT score (HR 4.30, 95% CI 1.90-9.69; p < 0.001), and for the IPI score (HR 2.60, 95% CI 1. 12-6.04; p = 0.03). Our study suggests the NLR could be helpful in refining the survival prognostication in patients with PTCLU. C1 [Beltran, Brady E.; Aguilar, Christian] Hosp Nacl Edgardo Rebagliati Martins, Dept Radiotherapy & Oncol, Lima, Peru. [Quinones, Pilar; Morales, Domingo] Hosp Nacl Edgardo Rebagliati Martins, Dept Pathol, Lima, Peru. [Chavez, Julio C.; Sotomayor, Eduardo M.] Univ S Florida, Moffitt Canc & Res Inst, Div Malignant Hematol, Tampa, FL USA. [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Beltran, Brady/0000-0003-4469-3817; Castillo, Jorge/0000-0001-9490-7532 NR 39 TC 4 Z9 4 U1 0 U2 1 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 JAN 2 PY 2016 VL 57 IS 1 BP 58 EP 62 DI 10.3109/10428194.2015.1045897 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA DA8AC UT WOS:000368025700013 PM 25926063 ER PT J AU Kelly, JF Saitz, R Wakeman, S AF Kelly, John F. Saitz, Richard Wakeman, Sarah TI Language, Substance Use Disorders, and Policy: The Need to Reach Consensus on an "Addiction-ary" SO ALCOHOLISM TREATMENT QUARTERLY LA English DT Article DE Language; stigma; terminology; policy; addiction; substance abuse; substance use disorders ID STIGMA; CARE AB The language used to describe health conditions reflects and influences our attitudes and approaches to addressing them, even to the extent of suggesting that a health condition is a moral, social, or criminal issue. The language and terminology we use is particularly important when it comes to highly stigmatized and life-threatening conditions, such as those relating to alcohol and other drugs. Scientific research has demonstrated that, whether we are aware of it, the use of certain terms implicitly generates biases that can influence the formation and effectiveness of our social and public health policies in addressing them. Such research has made it difficult to trivialize or dismiss the terminology debate as merely semantics or a linguistic preference for political correctness. Furthermore, given that alcohol and other drug-related conditions are among the top public health concerns in the United States and in most English speaking countries globally (e.g., United Kingdom, Australia, Ireland), this is no trivial matter. In this article, the authors detail the conceptual and empirical basis for the need to avoid using certain terms and to reach consensus on an addiction-ary. The authors conclude that consistent use of agreed-upon terminology will aid precise and unambiguous clinical and scientific communication and help reduce stigmatizing and discriminatory public health and social policies. C1 [Kelly, John F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kelly, John F.; Wakeman, Sarah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saitz, Richard] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kelly, JF (reprint author), Ctr Addict Med, Dept Psychiat, 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@mgh.harvard.edu NR 18 TC 1 Z9 1 U1 3 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7324 EI 1544-4538 J9 ALCOHOL TREAT Q JI Alcohol. Treat. Q. PD JAN 2 PY 2016 VL 34 IS 1 BP 116 EP 123 DI 10.1080/07347324.2016.1113103 PG 8 WC Substance Abuse SC Substance Abuse GA DA5FQ UT WOS:000367829000009 ER PT J AU Haggerty, G Bornstein, RF Khalid, M Sharma, V Riaz, U Blanchard, M Siefert, CJ Sinclair, SJ AF Haggerty, Greg Bornstein, Robert F. Khalid, Mohammad Sharma, Vishal Riaz, Usman Blanchard, Mark Siefert, Caleb J. Sinclair, Samuel J. TI Construct Validity of the Relationship Profile Test: Links With Measures of Psychopathology and Adult Attachment SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID INTERPERSONAL DEPENDENCY; DEPATHOLOGIZING DEPENDENCY; PERSONALITY-DISORDERS; INTERACTIONIST MODEL; PSYCHOLOGICAL HEALTH; URBAN WOMEN; SELF; CONNECTEDNESS; DETACHMENT; SCALES AB This study assessed the construct validity of the Relationship Profile Test (RPT; Bornstein & Languirand, 2003) with a substance abuse sample. One hundred-eight substance abuse patients completed the RPT, Experiences in Close Relationships Scale-Short Form (Wei, Russell, Mallinckrodt, & Vogel, 2007), Personality Assessment Inventory (Morey, 1991), and Symptom Checklist-90-Revised (Derogatis, 1983). Results suggest that the RPT has good construct validity when compared against theoretically related broadband measures of personality, psychopathology, and adult attachment. Overall, health dependency was negatively related to measures of psychopathology and insecure attachment, and overdependence was positively related to measures of psychopathology and attachment anxiety. Many of the predictions regarding RPT detachment and the criterion measures were not supported. Implications of these findings are discussed. C1 [Haggerty, Greg; Khalid, Mohammad; Sharma, Vishal; Riaz, Usman] Nassau Univ Med Ctr, Von Tauber Inst Global Psychiat, E Meadow, NY 11554 USA. [Bornstein, Robert F.; Blanchard, Mark] Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY USA. [Siefert, Caleb J.] Univ Michigan Dearborn, Dept Behav Sci, Dearborn, MI USA. [Sinclair, Samuel J.] Harvard Univ, Massachusetts Gen Hosp, Psychol Evaluat & Res Lab PEaRL, Sch Med, Cambridge, MA 02138 USA. RP Haggerty, G (reprint author), Nassau Univ Med Ctr, Von Tauber Inst Global Psychiat, 2201 Hempstead Turnpike,Box 48, E Meadow, NY 11554 USA. EM ghag541@aol.com FU National Institute of Mental Health (NIMH) [1R21MH097781-01A1] FX The preparation of this article was funded in part by National Institute of Mental Health (NIMH) Grant No. 1R21MH097781-01A1 awarded to Greg Haggerty and Robert F. Bornstein. NR 65 TC 0 Z9 0 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 EI 1532-7752 J9 J PERS ASSESS JI J. Pers. Assess. PD JAN 2 PY 2016 VL 98 IS 1 BP 82 EP 87 DI 10.1080/00223891.2015.1110824 PG 6 WC Psychology, Clinical; Psychology, Social SC Psychology GA DA2JM UT WOS:000367621100010 PM 26620463 ER PT J AU Pino, RM AF Pino, Richard M. TI Why is residual neuromuscular blockade a universal issue? SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Editorial Material DE Complications of general anesthesia; Neuromuscular blocking drugs; Residual neuromuscular blockade; Train of four ID RECOVERY C1 [Pino, Richard M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pino, Richard M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Pino, RM (reprint author), Massachusetts Gen Hosp, Jackson 4,55 Fruit St, Boston, MA 02114 USA. EM rpino@mgh.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-7995 EI 1473-4877 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JAN 2 PY 2016 VL 32 IS 1 BP 11 EP 12 DI 10.1185/03007995.2015.1108911 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CZ3LQ UT WOS:000367006000001 PM 26471243 ER PT J AU Garcia-Borreguero, D Allen, R Hudson, J Dohin, E Grieger, F Moran, K Schollmayer, E Smit, R Winkelman, J AF Garcia-Borreguero, Diego Allen, Richard Hudson, John Dohin, Elisabeth Grieger, Frank Moran, Kimberly Schollmayer, Erwin Smit, Rene Winkelman, John TI Effects of rotigotine on daytime symptoms in patients with primary restless legs syndrome: a randomized, placebo-controlled study SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Dopamine receptor agonist; Periodic limb movements; Restless legs syndrome; Rotigotine ID DOUBLE-BLIND; TRANSDERMAL ROTIGOTINE; CONTROLLED TRIAL; OPEN-LABEL; SLEEP; MOVEMENTS; DIAGNOSIS; EFFICACY; IMMOBILITY; DOPAMINE AB Objective: This 12 week double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01569464) was conducted to evaluate the effects of rotigotine transdermal patch on daytime symptoms in patients with idiopathic restless legs syndrome (RLS). Methods: Adult patients with moderate-to-severe RLS were randomized to rotigotine (optimal dose: 1-3mg/24h) or placebo. A modified four-assessment version (4:00pm, 6:00pm, 8:00pm, and 10:00pm) of the Multiple Suggested Immobilization Test (m-SIT) was performed at baseline and end of 4 week maintenance (EoM). Primary study outcomes were change from baseline to EoM in International Restless Legs Syndrome Rating Scale (IRLS) and in average of means for the m-SIT Discomfort Scale (m-SIT-DS) (combined average of mean values from each of the individual assessments). Secondary outcomes included average of means of Periodic Limb Movement during Wakefulness Index (PLMWI; PLM/hour) for the combination of m-SIT. Results: A total of 150 patients were randomized and 137 (rotigotine: 92/101 [91.1%]; placebo: 45/49 [91.8%]) completed maintenance. All 150 randomized patients were assessed for efficacy. At EoM, mean change in IRLS was -14.99.3 with rotigotine vs. -12.77.6 with placebo (ANCOVA, LS mean treatment difference [95% CI]: -0.27 [-2.96, 2.42]; p=0.8451). Changes in average of means of m-SIT-DS values of each individual SIT were comparable with rotigotine (-2.68 +/- 2.31) vs. placebo (-2.62 +/- 2.61) (ANCOVA, LS mean treatment difference [95% CI]: 0.07 [-0.61, 0.75]; p=0.8336) and comparable reductions in PLMWI were observed in both treatment groups (8.34 [-8.50, 25.17]; p=0.3290). Rotigotine was generally well tolerated. Application site reactions (rotigotine: 20 patients [19.8%]; placebo: 4 [8.2%]) and nausea (16 [15.8%]; 3 [6.1%]) were the most common AEs. Conclusions: Rotigotine was beneficial in improving overall RLS symptom severity (assessed by IRLS) and RLS symptom severity at various times of the day (m-SIT-DS); however, superiority to placebo was not established. C1 [Garcia-Borreguero, Diego] Sleep Res Inst, Madrid 28036, Spain. [Allen, Richard] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. [Hudson, John] FutureSearch Trials Neurol, Austin, TX USA. [Dohin, Elisabeth] UCB Pharma, Brussels, Belgium. [Grieger, Frank; Schollmayer, Erwin] UCB Pharma, Monheim, Germany. [Moran, Kimberly] UCB Pharma, Smyrna, GA USA. [Smit, Rene] UCB Pharma, Raleigh, NC USA. [Winkelman, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Garcia-Borreguero, D (reprint author), Sleep Res Inst, Alberto Alcocer 19, Madrid 28036, Spain. EM dgb@iis.es FU UCB Pharma, Monheim am Rhein, Germany FX This study was supported by UCB Pharma, Monheim am Rhein, Germany. All costs associated with manuscript development and publication were met by the sponsor. NR 25 TC 2 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-7995 EI 1473-4877 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JAN 2 PY 2016 VL 32 IS 1 BP 77 EP 85 DI 10.1185/03007995.2015.1103216 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CZ3LR UT WOS:000367006100003 PM 26569149 ER PT J AU Banks, HT Hu, SH Link, K Rosenberg, ES Mitsuma, S Rosario, L AF Banks, H. T. Hu, Shuhua Link, Kathryn Rosenberg, Eric S. Mitsuma, Sheila Rosario, Lauren TI Modelling immune response to BK virus infection and donor kidney in renal transplant recipients SO INVERSE PROBLEMS IN SCIENCE AND ENGINEERING LA English DT Article DE renal transplant; human polyomavirus type 1 (BKV); mathematical model; inverse problem; sensitivity analysis; 62F12; 65L09; 92B05 ID POLYOMAVIRUS BK; EXPERIMENTAL-DESIGN; VIRAL LOAD; VALIDATION; PREDICTION; DYNAMICS; PLASMA AB In this paper, we develop and validate with bootstrapping techniques a mechanistic mathematical model of immune response to both BK virus infection and a donor kidney based on known and hypothesized mechanisms in the literature. The model presented does not capture all the details of the immune response but possesses key features that describe a very complex immunological process. We then estimate model parameters using a least squares approach with a typical set of available clinical data. Sensitivity analysis combined with asymptotic theory is used to determine the number of parameters that can be reliably estimated given the limited number of observations. C1 [Banks, H. T.; Hu, Shuhua; Link, Kathryn] N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. [Rosenberg, Eric S.; Mitsuma, Sheila; Rosario, Lauren] Massachusetts Gen Hosp, Partners Human Res Comm, Boston, MA 02114 USA. RP Banks, HT (reprint author), N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. EM htbanks@ncsu.edu FU National Institute of Allergy and Infectious Diseases [NIAID R01AI071915-10]; Air Force Office of Scientific Research [AFOSR FA9550-12-1-0188]; National Science Foundation under Research Training Grant (RTG) [DMS-1246991] FX This research was supported in part by [grant number NIAID R01AI071915-10] from the National Institute of Allergy and Infectious Diseases, in part by the Air Force Office of Scientific Research under [grant number AFOSR FA9550-12-1-0188], and in part by the National Science Foundation under Research Training Grant (RTG) [DMS-1246991]. NR 38 TC 0 Z9 0 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1741-5977 EI 1741-5985 J9 INVERSE PROBL SCI EN JI Inverse Probl. Sci. Eng. PD JAN 2 PY 2016 VL 24 IS 1 BP 127 EP 152 DI 10.1080/17415977.2015.1017484 PG 26 WC Engineering, Multidisciplinary; Mathematics, Interdisciplinary Applications SC Engineering; Mathematics GA CZ5OK UT WOS:000367151700008 PM 26925154 ER PT J AU Byrne, T Treglia, D Culhane, DP Kuhn, J Kane, V AF Byrne, Thomas Treglia, Dan Culhane, Dennis P. Kuhn, John Kane, Vincent TI Predictors of Homelessness Among Families and Single Adults After Exit From Homelessness Prevention and Rapid Re-Housing Programs: Evidence From the Department of Veterans Affairs Supportive Services for Veteran Families Program SO HOUSING POLICY DEBATE LA English DT Article DE homelessness; veterans; rapid re-housing; homelessness prevention; housing assistance programs ID NEW-YORK-CITY; SHELTER; RISK AB This article assesses the extent and predictors of homelessness among veterans (both veterans in families with children and single adults veterans) exiting the Supportive Services for Veteran Families (SSVF) program, which is a nationwide homelessness prevention and rapid re-housing program geared primarily toward those experiencing crisis homelessness. Among rapid re-housing participants, 16% and 26% of single adult veterans experienced an episode of homelessness at 1 and 2 years post-SSVF exit; the comparable figures at those follow-up times for veterans in families were 9.4% and 15.5%, respectively. Relatively fewer single adult veterans and veterans in families receiving homelessness prevention services experienced an episode of homelessness at 1 and 2 years post-SSVF exit. veteran-level characteristics, including age, gender, prior history of homelessness, and recent engagement with U.S. Department of Veterans Affairs (VA) health care, were generally more salient predictors of homelessness following SSVF exit than variables measuring SSVF program factors or community-level housing market conditions. C1 [Byrne, Thomas; Treglia, Dan; Culhane, Dennis P.; Kuhn, John; Kane, Vincent] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA 19144 USA. [Byrne, Thomas] Boston Univ, Sch Social Work, Boston, MA 02215 USA. [Treglia, Dan; Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Byrne, T (reprint author), US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA 19144 USA. EM tbyrne@bu.edu FU U.S. Department of Veterans Affairs (VA), National Center on Homelessness Among Veterans FX This study was funded by the U.S. Department of Veterans Affairs (VA), National Center on Homelessness Among Veterans. The contents of this article do not necessarily represent the views of the VA or the United States Government. NR 52 TC 0 Z9 0 U1 5 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1051-1482 EI 2152-050X J9 HOUS POLICY DEBATE JI Hous. Policy Debate PD JAN 2 PY 2016 VL 26 IS 1 BP 252 EP 275 DI 10.1080/10511482.2015.1060249 PG 24 WC Planning & Development; Urban Studies SC Public Administration; Urban Studies GA CY7UK UT WOS:000366614600001 ER PT J AU Fan, KH Li, HQ Wang, ZR Du, WJ Yin, W Sun, YG Jiang, JB AF Fan, Kuohai Li, Hongquan Wang, Zhirui Du, Wenjuan Yin, Wei Sun, Yaogui Jiang, Junbing TI Expression and purification of the recombinant porcine NK-lysin in Pichia pastoris and observation of anticancer activity in vitro SO PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY LA English DT Article DE Antitumor; expression; fascin 1; Pichia pastoris; porcine NK-lysin; purification ID ANTIMICROBIAL PEPTIDES; ANTITUMOR-ACTIVITY; CANCER-CELLS; CYTOTOXICITY; METASTASIS; MODULATION; FASCIN-1; TUMOR AB Natural killer (NK)-lysin, a broad-spectrum antimicrobial peptide, has antitumor and antibactericidal activities against both gram-positive and gram-negative bacteria. In this study the recombinant porcine NK-lysin was expressed and purified in the Pichia pastoris system, and then 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to assess its anticancer activity in vitro. The results showed that the recombinant porcine NK-lysin possesses potent antitumor activity against the human hepatocellular carcinoma cell line SMMC-7721 in a time- and dose-dependent manner, but has negligible hemolysis activity against human erythrocytes. Scanning electronic microscopy was used to directly observe the ultrastructure of SMMC-7721 cells treated with NK-lysin; untreated cells showed lamellipodia and filopodia scattered with the cell surface, with good cell-cell contacts among neighboring cells. In contrast, treated tumor cells exhibited marked alterations in cell morphology, and cell-cell contacts disappeared among neighboring cells. Compared with the untreated tumor cells, the tumor cells treated with NK-lysin for 12 and 24hr were suppressed for the expression of fascin 1. Thus, the recombinant porcine NK-lysin potentially could be developed as a therapeutic agent for inhibiting tumor growth. C1 [Fan, Kuohai; Li, Hongquan; Du, Wenjuan; Yin, Wei; Sun, Yaogui; Jiang, Junbing] Shanxi Agr Univ, Coll Anim Sci & Vet Med, Taigu 030801, Shanxi, Peoples R China. [Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Zhirui] MGH DF HCC Recombinant Prot Express & Purificat C, Boston, MA USA. RP Jiang, JB (reprint author), Shanxi Agr Univ, Coll Anim Sci & Vet Med, 1 Mingxian Rd, Taigu 030801, Shanxi, Peoples R China. EM sxndjeffrey@126.com FU Shanxi Province Key Scientific and Techological Project [20100312016] FX This work was supported in part by the Shanxi Province Key Scientific and Techological Project (20100312016). NR 23 TC 0 Z9 0 U1 1 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6068 EI 1532-2297 J9 PREP BIOCHEM BIOTECH JI Prep. Biochem. Biotechnol. PD JAN 2 PY 2016 VL 46 IS 1 BP 65 EP 70 DI 10.1080/10826068.2014.979206 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA CY9PY UT WOS:000366740000010 PM 25357101 ER PT J AU Chernikova, DA Koestler, DC Hoen, AG Housman, ML Hibberd, PL Moore, JH Morrison, HG Sogin, ML Zain-ul-abideen, M Madan, JC AF Chernikova, Diana A. Koestler, Devin C. Hoen, Anne Gatewood Housman, Molly L. Hibberd, Patricia L. Moore, Jason H. Morrison, Hilary G. Sogin, Mitchell L. Zain-ul-abideen, Muhammad Madan, Juliette C. TI Fetal exposures and perinatal influences on the stool microbiota of premature infants SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Antibiotics; chorioamnionitis; microbiome; obstetrical complications; obstetrical interventions; PPPROM; prematurity ID HUMAN GUT MICROBIOME; INTESTINAL MICROBIOTA; DISEASE; HEALTH; ESTABLISHMENT; COLONIZATION; DIVERSITY; AGE AB Objective: To test the hypothesis that maternal complications significantly affect gut colonization patterns in very low birth weight infants.Methods: Forty-nine serial stool samples were obtained weekly from nine extremely premature infants enrolled in a prospective longitudinal study. Sequencing of the bacterial 16S rRNA gene from stool samples was performed to approximate the intestinal microbiome. Linear mixed effects models were used to evaluate relationships between perinatal complications and intestinal microbiome development.Results: Subjects with prenatal exposure to a non-sterile intrauterine environment, i.e. prolonged preterm premature rupture of membranes (PPPROM) and chorioamnionitis exposure, were found to have a relatively higher abundance of potentially pathogenic bacteria in the stool across all time points compared to subjects without those exposures, irrespective of exposure to postnatal antibiotics. Compared with those delivered by Caesarean section, vaginally delivered subjects were found to have significantly lower diversity of stool microbiota across all time points, with lower abundance of many genera, most in the family Enterobacteriaceae.Conclusions: We identified persistently increased potential pathogen abundance in the developing stool microbiota of subjects exposed to a non-sterile uterine environment. Maternal complications appear to significantly influence the diversity and bacterial composition of the stool microbiota of premature infants, with findings persisting over time. C1 [Chernikova, Diana A.; Moore, Jason H.] Dartmouth Coll, Inst Quantitat Biomed Sci, Dept Genet, Geisel Sch Med, Hanover, NH 03755 USA. [Koestler, Devin C.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA. [Hoen, Anne Gatewood; Zain-ul-abideen, Muhammad] Dartmouth Coll, Dept Epidemiol, Geisel Sch Med, Hanover, NH 03755 USA. [Housman, Molly L.] Dartmouth Coll, Dept Microbiol & Immunol, Geisel Sch Med, Hanover, NH 03755 USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. [Morrison, Hilary G.; Sogin, Mitchell L.] Marine Biol Lab, Josephine Bay Paul Ctr, Woods Hole, MA 02543 USA. [Madan, Juliette C.] Dartmouth Hitchcock Med Ctr, Div Neonatol, Dept Pediat, Lebanon, NH 03756 USA. RP Madan, JC (reprint author), Dartmouth Hitchcock Med Ctr, Div Neonatol, Dept Pediat, Lebanon, NH 03756 USA. EM Juliette.C.Madan@Hitchcock.Org OI Morrison, Hilary/0000-0003-0281-326X FU Hearst Foundation; Joshua Burnett Career Development Award through the Hitchcock Foundation (Dartmouth); CF Foundation Harry Shwachman Clinical Investigator Award; CTSA grant from NCATS [KL2TR000119]; Neukom Institute; NIH [K01LM011985, R01AI59694, GM103534, GM103506, 5T32DK007301-35, 4UH3DK 083993, K24AT003683] FX JCM is a member of the Children's Environmental Health and Disease Prevention Research Center at Dartmouth (P01ES022832 from NIEHS and RD83544201 from the EPA) as well as the Molecular Epidemiology Center at Dartmouth COBRE (NIGMS P20 GM104416). JCM also received funds from the Hearst Foundation, the Joshua Burnett Career Development Award through the Hitchcock Foundation (Dartmouth), the CF Foundation Harry Shwachman Clinical Investigator Award. DCK was supported by a CTSA grant from NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research # KL2TR000119. Additionally, this work was supported by: the Neukom Institute (JHM); NIH grants K01LM011985 (AGH); R01AI59694, GM103534, GM103506 (JHM); 5T32DK007301-35 (DAC); 4UH3DK 083993 (MLS and HGM); K24AT003683 (PLH). NR 30 TC 2 Z9 2 U1 0 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JAN 2 PY 2016 VL 29 IS 1 BP 99 EP 105 DI 10.3109/14767058.2014.987748 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CX3VP UT WOS:000365627900019 PM 25394613 ER PT J AU Kuperberg, GR Jaeger, TF AF Kuperberg, Gina R. Jaeger, T. Florian TI What do we mean by prediction in language comprehension? SO LANGUAGE COGNITION AND NEUROSCIENCE LA English DT Article DE Language comprehension; prediction error; generative model; probabilistic; surprisal ID SPOKEN WORD-RECOGNITION; SYNTACTIC AMBIGUITY RESOLUTION; THEMATIC ROLE-ASSIGNMENT; ONLINE SENTENCE COMPREHENSION; PARAFOVEAL VISUAL INFORMATION; CONTINUOUS SPEECH RECOGNITION; INTERACTIVE ACTIVATION MODEL; LATENT SEMANTIC ANALYSIS; EVENT-RELATED POTENTIALS; EYE-MOVEMENTS AB We consider several key aspects of prediction in language comprehension: its computational nature, the representational level(s) at which we predict, whether we use higher-level representations to predictively pre-activate lower level representations, and whether we commit in any way to our predictions, beyond pre-activation. We argue that the bulk of behavioural and neural evidence suggests that we predict probabilistically and at multiple levels and grains of representation. We also argue that we can, in principle, use higher-level inferences to predictively pre-activate information at multiple lower representational levels. We suggest that the degree and level of predictive pre-activation might be a function of its expected utility, which, in turn, may depend on comprehenders' goals and their estimates of the relative reliability of their prior knowledge and the bottom-up input. Finally, we argue that all these properties of language understanding can be naturally explained and productively explored within a multi-representational hierarchical actively generative architecture whose goal is to infer the message intended by the producer, and in which predictions play a crucial role in explaining the bottom-up input. C1 [Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Kuperberg, Gina R.] Tufts Univ, Ctr Cognit Sci, Medford, MA 02155 USA. [Kuperberg, Gina R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Kuperberg, Gina R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA USA. [Jaeger, T. Florian] Univ Rochester, Dept Brain & Cognit Sci, Rochester, MA USA. [Jaeger, T. Florian] Univ Rochester, Dept Comp Sci, Rochester, MA USA. [Jaeger, T. Florian] Univ Rochester, Dept Linguist, Rochester, MA USA. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. EM kuperber@nmr.mgh.harvard.edu FU NIMH [R01 MH071635]; NICHD [R01 HD082527, R01 HD075797]; NSF CAREER grant [IIS 1150028] FX This work was partially funded by NIMH [R01 MH071635] and NICHD [R01 HD082527] grants to G. R. K., as well as by NICHD [R01 HD075797] and an NSF CAREER grant [IIS 1150028] to T. F. J. NR 281 TC 23 Z9 23 U1 14 U2 45 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 2327-3798 EI 2327-3801 J9 LANG COGN NEUROSCI JI Lang. Cogn. Neurosci. PD JAN 2 PY 2016 VL 31 IS 1 SI SI BP 32 EP 59 DI 10.1080/23273798.2015.1102299 PG 28 WC Audiology & Speech-Language Pathology; Behavioral Sciences; Linguistics; Psychology, Experimental SC Audiology & Speech-Language Pathology; Behavioral Sciences; Linguistics; Psychology GA CX3VJ UT WOS:000365627300004 PM 27135040 ER PT J AU Richardson, PG Harvey, RD Laubach, JP Moreau, P Lonial, S San-Miguel, JF AF Richardson, Paul G. Harvey, R. Donald Laubach, Jacob P. Moreau, Philippe Lonial, Sagar San-Miguel, Jesus F. TI Panobinostat for the treatment of relapsed or relapsed/refractory multiple myeloma: pharmacology and clinical outcomes SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY LA English DT Article DE bortezomib; deacetylase inhibitors; multiple myeloma; panobinostat; relapsed and refractory multiple myeloma ID HISTONE DEACETYLASE INHIBITOR; LENALIDOMIDE PLUS DEXAMETHASONE; ADVANCED SOLID TUMORS; PHASE-I; ORAL PANOBINOSTAT; ADVANCED CANCER; OPEN-LABEL; HEMATOLOGIC MALIGNANCIES; DOSE-ESCALATION; HYDROXAMIC ACID AB Recently, outcomes for patients with multiple myeloma have improved dramatically due to improved and innovative therapies. However, most patients will either relapse or become refractory to current therapy. Thus, a significant unmet need remains for novel agents to treat this patient population. Panobinostat, a potent pan-deacetylase inhibitor with a unique mechanism of action targeting both epigenetic regulation of gene expression and protein metabolism, has preclinical synergy with a number of agents, including the proteasome inhibitor bortezomib. In a phase 3 trial of panobinostat with bortezomib and dexamethasone, addition of panobinostat significantly prolonged the median progression-free survival of patients with relapsed or relapsed and refractory multiple myeloma. This review focuses on clinical development of panobinostat, with particular emphasis on pharmacokinetics and adverse event management. C1 [Richardson, Paul G.; Laubach, Jacob P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Harvey, R. Donald; Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Moreau, Philippe] Univ Hosp, Dept Hematol, Nantes, France. [San-Miguel, Jesus F.] Univ Navarra Clin, CIMA, IDISNA, Pamplona, Spain. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu RI richard, chrystelle/K-8595-2015 FU Novartis; Celgene; Millennium; Onyx; Novartis Pharmaceuticals FX P Richardson is on advisory committees for Novartis, Takeda and Johnson and Johnson. R Harvey is on advisory committees for Onyx and Millennium. J Laubach has received research funding from Novartis, Celgene, Millennium and Onyx. P Moreau is on advisory committees for Novartis, Takeda, Janssen, Millennium and Onyx. S Lonial has provided consultancy for Millennium, Celgene, Novartis, Bristol-Myers Squibb, Onyx and Sanofi. J San-Miguel is on advisory committees for Janssen, Bristol-Myers Squibb, Merck Sharpe & Dohme, Millennium, Celgene, Novartis and Onyx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript and performed by Michael Demars of Articulate Science and funded by Novartis Pharmaceuticals. NR 49 TC 7 Z9 7 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1751-2433 EI 1751-2441 J9 EXPERT REV CLIN PHAR JI Expert Rev. Clin. Pharmacol. PD JAN 2 PY 2016 VL 9 IS 1 BP 35 EP 48 DI 10.1586/17512433.2016.1096773 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CW9WI UT WOS:000365348500005 PM 26503877 ER PT J AU Fossett, TRD McNeil, MR Pratt, SR Tompkins, CA Shuster, LI AF Fossett, Tepanta R. D. McNeil, Malcolm R. Pratt, Sheila R. Tompkins, Connie A. Shuster, Linda I. TI The effect of speaking rate on serial-order sound-level errors in normal healthy controls and persons with aphasia SO APHASIOLOGY LA English DT Article DE phonologic encoding; speech production; aphasia; serial-order errors; speech rate ID SPEECH PRODUCTION; LANGUAGE PRODUCTION; REACTION-TIME; NORMAL SPEAKERS; MOTOR ERRORS; APRAXIA; TONGUE; MODEL; RETRIEVAL; PATTERNS AB Background: Although many speech errors can be generated at either a linguistic or motoric level of production, phonetically well-formed sound-level serial-order errors are generally assumed to result from disruption of phonologic encoding (PE) processes. An influential model of PE predicts that speaking rate should affect the relative proportion of these serial-order sound errors (anticipations, perseverations, exchanges). These predictions have been extended to, and have special relevance for persons with aphasia (PWA) because of the increased frequency with which speech errors occur and because their localisation within the functional linguistic architecture may help in diagnosis and treatment. Supporting evidence regarding the effect of speaking rate on phonological encoding has been provided by studies using young normal language (NL) speakers and computer simulations. Limited data exist for older NL users and no group data exist for PWA.Aims: This study tested the phonologic encoding properties of Dell's model of speech production, which predicts that increasing speaking rate affects the relative proportion of serial-order sound errors (i.e., anticipations, perseverations and exchanges).Methods & Procedures: The effects of speech rate on the error ratios of anticipation/exchange (AE), anticipation/perseveration (AP) and vocal reaction time (VRT) were examined in 16 normal healthy controls (NHC) and 16 PWA without concomitant motor speech disorders. The participants were recorded performing a phonologically challenging (tongue twister) speech production task at their typical and two faster speaking rates.Outcomes & Results: A significant effect of increased rate was obtained for the AP but not the AE ratio. Significant effects of group and rate were obtained for VRT.Conclusion: Although the significant effect of rate for the AP ratio provided evidence that changes in speaking rate did affect PE, the results failed to support the model-derived predictions regarding the direction of change for error-type proportions. The current findings argued for an alternative concept of the role of activation and decay in influencing types of serial-order sound errors. Rather than a slow activation decay rate, the results of the current study were more compatible with an alternative explanation of rapid activation decay or slow build-up of residual activation. C1 [Fossett, Tepanta R. D.; McNeil, Malcolm R.; Pratt, Sheila R.; Tompkins, Connie A.] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [McNeil, Malcolm R.; Pratt, Sheila R.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Tompkins, Connie A.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA USA. [Tompkins, Connie A.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Shuster, Linda I.] W Virginia Univ, Dept Speech Pathol & Audiol, Morgantown, WV 26506 USA. RP Fossett, TRD (reprint author), Loyola Univ Maryland, Dept Speech & Language Pathol, Baltimore, MD 21210 USA. EM trfossett@loyola.edu FU National Institutes of Health (NIH) F31 Pre-doctoral Fellowship [1 F31 DC005940-01]; Provost's Development and Faculty of Arts and Sciences (FAS) African American Summer Graduate Research Awards from the University of Pittsburgh FX This research was supported by a National Institutes of Health (NIH) F31 Pre-doctoral Fellowship award [grant number 1 F31 DC005940-01] and by the Provost's Development and Faculty of Arts and Sciences (FAS) African American Summer Graduate Research Awards from the University of Pittsburgh. NR 67 TC 0 Z9 0 U1 3 U2 23 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0268-7038 EI 1464-5041 J9 APHASIOLOGY JI Aphasiology PD JAN 2 PY 2016 VL 30 IS 1 BP 74 EP 95 DI 10.1080/02687038.2015.1063581 PG 22 WC Clinical Neurology SC Neurosciences & Neurology GA CU1TI UT WOS:000363303800004 PM 26973373 ER PT J AU Yehuda, R Spiegel, D Southwick, S Davis, LL Neylan, TC Krystal, JH AF Yehuda, Rachel Spiegel, David Southwick, Steven Davis, Lori L. Neylan, Thomas C. Krystal, John H. TI What I have changed my mind about and why SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Article DE PTSD; resilience; evidenced based treatments; fear extinction; alternative treatments; neurobiology; pharmacotherapy; novel approaches; mindfulness; randomized clinical trials ID POSTTRAUMATIC-STRESS-DISORDER; VETERANS; TRIAL AB This paper is based upon a panel discussion "What I Have Changed My Mind About and Why'' held on 5 November in New Orleans, Louisiana (USA), as part of the ISTSS 2015 annual meeting "Back to Basics: Integrating Clinical and Scientific Knowledge to Advance the Field of Trauma.'' The panel was chaired by Professor Dr. Rachel Yehuda of the Icahn School of Medicine at Mount Sinai and the James J. Peters Veterans Affairs, and included five clinician-scholars who exchanged thoughts about what they have changed their minds about over the years: Dr. David Spiegel, Dr. Steven Southwick, Dr. Lori Davis, Dr. Thomas Neylan, and Dr. John Krystal. This paper provides a summary of the salient points made by each expert and the questions and discussion that ensured. Major issues raised included the increasingly clear limitations to the fear-based model that has advanced the field. While treatments for PTSD have improved, there are some aspects of trauma exposure that cannot be entirely repaired. Research providing an evidence base to treatment has led to overly specific treatment guidelines that may obscure more general principles of effective treatment. Treatment might be viewed as a way to increase the plasticity of the brain in the context of processing social cues. A variety of novel and integrative therapies include comprehensive holistic care, exercise, returning to competitive work, logotherapy, mindfulness, enhancing wellbeing and resilience, and medications with novel mechanisms, such as ketamine. C1 [Yehuda, Rachel] James J Peters Vet Affairs, New York, NY USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Spiegel, David] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA USA. [Southwick, Steven; Krystal, John H.] Yale Univ, Sch Med, New Haven, CT USA. [Southwick, Steven; Krystal, John H.] Vet Adm, Natl Ctr PTSD, Clin Neurosci Div, West Haven, CT USA. [Davis, Lori L.] Univ Alabama Hlth Syst, Dept Psychiat & Behav Neurobiol, Birmingham, AL USA. [Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Neylan, Thomas C.] San Francisco VA, San Francisco, CA USA. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, 526 OOMH PTSD 116-A,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.yehuda@va.gov NR 24 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2016 VL 7 AR 33768 DI 10.3402/ejpt.v7.33768 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA EN7GL UT WOS:000396170000001 PM 27837585 ER PT J AU Oltrabella, F Pietka, G Ramirez, IBR Mironov, A Starborg, T Drummond, IA Lowe, M AF Oltrabella, F. Pietka, G. Ramirez, I. Barinaga-Rementeria Mironov, A. Starborg, T. Drummond, I. A. Lowe, M. TI The Lowe Syndrome Protein OCRL1 is Required for Endocytosis in the Zebrafish Pronephric Tubule SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Oltrabella, F.] Univ Calif San Francisco, Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Pietka, G.] Royal Marsden NHS Fdn Trust, Mol, London, England. [Ramirez, I. Barinaga-Rementeria; Mironov, A.; Starborg, T.; Lowe, M.] Univ Manchester, Life Sci, Manchester, Lancs, England. [Drummond, I. A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1265 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100267 ER PT J AU Schmider, AB Godin, M Elliott, HD Soberman, RJ AF Schmider, A. B. Godin, M. Elliott, H. D. Soberman, R. J. TI Organization of the Leukotriene Synthetic Complex in Neutrophils as an Indicator of Disease State. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Schmider, A. B.; Godin, M.; Soberman, R. J.] Massachusetts Gen Hosp, Nephrol, Charlestown, MA USA. [Elliott, H. D.] Harvard Med Sch, Cell Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1363 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100364 ER PT J AU Shen, H Mootha, VK AF Shen, H. Mootha, V. K. TI De-orphaning human metabolic enzymes of unknown function SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Shen, H.; Mootha, V. K.] Massachusetts Gen Hosp, Department Mol Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1346 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100704 ER PT J AU Simon, MT Eftekharian, S Stover, A Steeves, MA Sahai, I Tang, S Wang, R Abdenur, J Rafelski, SM AF Simon, M. T. Eftekharian, S. Stover, A. Steeves, M. A. Sahai, I. Tang, S. Wang, R. Abdenur, J. Rafelski, S. M. TI Novel mutations in the substrate binding domain of the mitochondrial matrix protease LonP1 are a cause of mitochondrial disease. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Simon, M. T.; Eftekharian, S.; Stover, A.; Wang, R.; Abdenur, J.] CHOC Childrens, Metab, Orange, CA USA. [Simon, M. T.; Rafelski, S. M.] Univ Calif Irvine, Dev & Cellular Biol, Irvine, CA USA. [Steeves, M. A.; Sahai, I.] Massachusetts Gen Hosp, Genet, Boston, MA 02114 USA. [Tang, S.] Ambry Genet, Aliso Viejo, CA USA. [Wang, R.; Abdenur, J.] Univ Calif Irvine, Pediat, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1336 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100338 ER PT J AU Sharma, A Hoover, DR Shi, QH Holman, S Plankey, MW Wheeler, AL Weber, K Floris-Moore, M Bolivar, HH Vance, DE Mack, WJ Golub, ET Holstad, MM Yin, MT AF Sharma, Anjali Hoover, Donald R. Shi, Qiuhu Holman, Susan Plankey, Michael W. Wheeler, Amber L. Weber, Kathleen Floris-Moore, Michelle Bolivar, Hector H. Vance, David E. Mack, Wendy J. Golub, Elizabeth T. Holstad, Marcia McDonnell Yin, Michael T. TI Falls among middle-aged women in the Women's Interagency HIV Study SO ANTIVIRAL THERAPY LA English DT Article ID RISK-FACTORS; ANTIRETROVIRAL THERAPY; INFECTED PERSONS; ELDERLY PERSONS; OLDER-ADULTS; GERIATRIC SYNDROMES; GENERAL-POPULATION; FRACTURES; COHORT; POLYPHARMACY AB Background: To determine the frequency and risk factors for falls among middle-aged HIV+ and HIV-women in the Women's Interagency HIV Study (WIHS). Methods: We quantified self-report of any and multiple (>= 2) falls in the prior 6 months among 1,412 HIV+ and 650 HIV-women with mean age 48 years. Logistic regression was used to evaluate associations of demographics, behavioural factors, comorbid conditions and medications with odds of any fall (versus none) and multiple falls (versus <= 1 fall). Results: At least one fall was reported in 263 HIV+ (19%) versus 119 HIV-(18%) women, and >= 2 falls reported in 133 HIV+ (9%) versus 65 HIV-(10%) women. HIV infection was not associated with falls in multivariate analyses. Factors independently associated with any fall included age (adjusted odds ratio [aOR] 1.71, 95% CI 1.17, 2.49 age 50-59 versus < 39 years; aOR 2.26, 95% CI 1.38, 3.71 age >= 60 versus < 39), current marijuana use (aOR 2.19, 95% CI 1.53, 3.13) depressive symptoms (aOR 1.57, 95% CI 1.21, 2.05 for Center for Epidemiology Studies Depression score >= 16), subjective cognitive complaints (aOR 2.19, 95% CI 1.56, 3.08), neuropathy (aOR 1.59, 95% CI 1.19, 2.13), obesity (aOR 1.39, 95% CI 1.08, 1.80), number of central nervous system active agents (aOR 2.98, 95% CI 1.90, 4.68 for >= 3 agents versus 0) and WIHS site. Factors associated with >= 2 falls included age, marijuana use, number of central nervous system active agents, subjective cognitive complaints, depressive symptoms, neuropathy and study site. Conclusions: Falls were associated with factors affecting cognition, but not HIV status in this large cohort of women. Longitudinal studies are needed to determine the incidence and consequences of falls by HIV status as women age. C1 [Sharma, Anjali] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA. [Shi, Qiuhu] New York Med Coll, Dept Epidemiol & Community Hlth, Valhalla, NY 10595 USA. [Holman, Susan] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. [Plankey, Michael W.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Wheeler, Amber L.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Weber, Kathleen] John H Stroger Jr Hosp Cook Cty, Dept Med, Chicago, IL USA. [Floris-Moore, Michelle] Univ N Carolina, Dept Med, Sch Med, Chapel Hill, NC USA. [Bolivar, Hector H.] Univ Miami Hlth Syst, Dept Med, Miami, FL USA. [Vance, David E.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Mack, Wendy J.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Golub, Elizabeth T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Holstad, Marcia McDonnell] Emory Sch Nursing, Off Acad Adv, Atlanta, GA USA. [Yin, Michael T.] Columbia Univ, Dept Med, Med Ctr, New York, NY USA. RP Sharma, A (reprint author), Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. EM anjali.sharma@einstein.yu.edu FU National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Cancer Institute (NCI); National Institute on Drug Abuse (NIDA); National Institute on Mental Health (NIMH); National Institute of Dental and Craniofacial Research (NIDCR); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Deafness and other Communication Disorders (NIDCD); NIH Office of Research on Women's Health; National Institutes of Health [K23AR06199301] FX Data in this manuscript were collected by the WIHS. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA) and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD) and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA). This research was also supported by National Institutes of Health K23AR06199301 (AS). NR 49 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2016 VL 21 IS 8 BP 697 EP 706 DI 10.3851/IMP3070 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA EN6BP UT WOS:000396089800007 PM 27427794 ER PT S AU Ghani, MU Ren, LQ Yang, K Chen, WR Wu, XZ Liu, H AF Ghani, Muhammad. U. Ren, Liqiang Yang, Kai Chen, Wei R. Wu, Xizeng Liu, Hong BE Chen, WR TI Characterization of operating parameters of an in-vivo micro CT system SO BIOPHOTONICS AND IMMUNE RESPONSES XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses XI CY FEB 15, 2016 CL San Francisco, CA SP SPIE ID BEAM BREAST CT; SPATIAL-RESOLUTION CHARACTERISTICS; PERFORMANCE EVALUATION; COMPUTED-TOMOGRAPHY; VASCULATURE AB The objective of this study was to characterize the operating parameters of an in-vivo micro CT system. In-plane spatial resolution, noise, geometric accuracy, CT number uniformity and linearity, and phase effects were evaluated using various phantoms. The system employs a flat panel detector with a 127 mu m pixel pitch, and a micro focus x-ray tube with a focal spot size ranging from 5-30 mu m. The system accommodates three magnification sets of 1.72, 2.54 and 5.10. The in-plane cutoff frequencies (10% MTF) ranged from 2.31 lp/mm (60 mm FOV, M=1.72, 2x2 binning) to 13 lp/mm (10 mm FOV, M=5.10, 1x1 binning). The results were qualitatively validated by a resolution bar pattern phantom and the smallest visible lines were in 30-40 mu m range. Noise power spectrum (NPS) curves revealed that the noise peaks exponentially increased as the geometric magnification (M) increased. True in-plane pixel spacing and slice thickness were within 2% of the system's specifications. The CT numbers in cone beam modality are greatly affected by scattering and thus they do not remain the same in the three magnifications. A high linear relationship (R-2 > 0.999) was found between the measured CT numbers and Hydroxyapatite (HA) loadings of the rods of a water filled mouse phantom. Projection images of a laser cut acrylic edge acquired at a small focal spot size of 5 mu m with 1.5 fps revealed that noticeable phase effects occur at M=5.10 in the form of overshooting at the boundary of air and acrylic. In order to make the CT numbers consistent across all the scan settings, scatter correction methods may be a valuable improvement for this system. C1 [Ghani, Muhammad. U.; Ren, Liqiang; Liu, Hong] Univ Oklahoma, Ctr Biomed Engn, Norman, OK 73019 USA. [Ghani, Muhammad. U.; Ren, Liqiang; Liu, Hong] Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA. [Yang, Kai] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. [Chen, Wei R.] Univ Cent Oklahoma, Dept Engn & Phys, Edmond, OK 73034 USA. [Wu, Xizeng] Univ Alabama Birmingham, Dept Radiol, 619 19th St S 331, Birmingham, AL 35249 USA. RP Liu, H (reprint author), Univ Oklahoma, Ctr Biomed Engn, Norman, OK 73019 USA.; Liu, H (reprint author), Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA. EM liu@ou.edu FU NIH [R01 CA193378]; University of Oklahoma Charles and Peggy Stephenson Cancer Center - Oklahoma Tobacco Settlement Endowment Trust; Charles and Jean Smith Chair endowment fund FX This research was supported in part by the NIH under grant R01 CA193378, and supported in part by a grant from the University of Oklahoma Charles and Peggy Stephenson Cancer Center funded by the Oklahoma Tobacco Settlement Endowment Trust. We would like to acknowledge the support of Charles and Jean Smith Chair endowment fund as well. NR 26 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-943-6 J9 PROC SPIE PY 2016 VL 9709 AR UNSP 97090M DI 10.1117/12.2209626 PG 7 WC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BH0AY UT WOS:000394523700008 ER PT J AU Fadil, S Smith, K Lord, W Beshay, M Bawazir, N Myre, M Janetopoulos, CJ AF Fadil, S. Smith, K. Lord, W. Beshay, M. Bawazir, N. Myre, M. Janetopoulos, C. J. TI The Contractile Vacuole Polarizes to the Rear of Migrating Dictyostelium SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Fadil, S.; Smith, K.; Lord, W.; Beshay, M.; Bawazir, N.; Janetopoulos, C. J.] Univ Sci, Cell Biol & Biotechnol, Philadelphia, PA USA. [Myre, M.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2087 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200388 ER PT J AU Kim, J Zelter, A Umbreit, NT Bollozos, A Johnson, R MacCoss, M Asbury, CL Davis, TN AF Kim, J. Zelter, A. Umbreit, N. T. Bollozos, A. Johnson, R. MacCoss, M. Asbury, C. L. Davis, T. N. TI The Ndc80 complex bridges two Dam1 complex rings. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Kim, J.; Zelter, A.; Umbreit, N. T.; Bollozos, A.; Davis, T. N.] Univ Washington, Biochem, Seattle, WA 98195 USA. [Umbreit, N. T.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Johnson, R.; MacCoss, M.] Univ Washington, Genome Sci, Seattle, WA 98195 USA. [Asbury, C. L.] Univ Washington, Physiol & Biophys, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1897 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200199 ER PT J AU Liu, Y Lee, I Sun, M Lower, CA Ma, J Wu, J AF Liu, Y. Lee, I. Sun, M. Lower, C. A. Ma, J. Wu, J. TI Roles of the novel coiled-coil protein Rng10 in septum formation during fission yeast cytokinesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Liu, Y.; Lee, I.; Lower, C. A.; Wu, J.] Ohio State Univ, Mol Genet, Columbus, OH 43210 USA. [Lee, I.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sun, M.; Ma, J.] Davis Heart & Lung Res Inst, Surg, Columbus, OH USA. [Wu, J.] Ohio State Univ, Biol Chem & Pharmacol, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P189 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900189 ER PT J AU Swaminathan, V Mathew, JK Mehta, S Nordenfelt, P Moore, TI Nobuyasu, K Baker, D Oldenbourg, R Tani, T Mayor, S Springer, TA Waterman, CM AF Swaminathan, V. Mathew, J. K. Mehta, S. Nordenfelt, P. Moore, T. I. Nobuyasu, K. Baker, D. Oldenbourg, R. Tani, T. Mayor, S. Springer, T. A. Waterman, C. M. TI Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, Bangalore, Karnataka, India. [Mehta, S.; Oldenbourg, R.; Tani, T.] Marine Biol Sci, Woods Hole, MA USA. [Nordenfelt, P.] Lund Univ, Div Infect Med, Lund, MD, Sweden. [Moore, T. I.; Springer, T. A.] Harvard Univ, Program Cellular & Mol Med, Boston, MA 02115 USA. [Nobuyasu, K.; Baker, D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P646 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900645 ER PT J AU Thiam, HR Wong, SL Wagner, DD Waterman, CM AF Thiam, H. R. Wong, S. L. Wagner, D. D. Waterman, C. M. TI Cellular events mediating extracellular trap formation in neutrophil-like granulocytes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Thiam, H. R.; Waterman, C. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Wong, S. L.; Wagner, D. D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Wong, S. L.; Wagner, D. D.] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Wagner, D. D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1746 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200047 ER PT J AU Wong, VC Chavali, AK Lee, RE Mothes, W Gaudet, S Miller-Jensen, K AF Wong, V. C. Chavali, A. K. Lee, R. E. Mothes, W. Gaudet, S. Miller-Jensen, K. TI Chromatin modifies the decoding of NF-kappa B signals to regulate transcription SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Wong, V. C.; Miller-Jensen, K.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. [Chavali, A. K.; Miller-Jensen, K.] Yale Univ, Dept Biomed Engn, New Haven, CT USA. [Lee, R. E.] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA USA. [Mothes, W.] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT USA. [Gaudet, S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Gaudet, S.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Gaudet, S.] Harvard Med Sch, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P558 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900557 ER PT J AU Mallidi, S Anbil, S Bulin, AL Obaid, G Ichikawa, M Hasan, T AF Mallidi, Srivalleesha Anbil, Sriram Bulin, Anne-Laure Obaid, Girgis Ichikawa, Megumi Hasan, Tayyaba TI Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy SO THERANOSTICS LA English DT Review DE photodynamic therapy; light penetration ID GROWTH-FACTOR RECEPTOR; RESONANCE ENERGY-TRANSFER; SINGLET OXYGEN GENERATION; OVARIAN-CANCER CELLS; IN-VIVO; 2-PHOTON ABSORPTION; MONOCLONAL-ANTIBODIES; IONIZING-RADIATION; PANCREATIC-CANCER; PROTOPORPHYRIN-IX AB Photodynamic therapy (PDT) is a photochemistry based treatment modality that involves the generation of cytotoxic species through the interactions of a photosensitizer molecule with light irradiation of an appropriate wavelength. PDT is an approved therapeutic modality for several cancers globally and in several cases has proved to be effective where traditional treatments have failed. The key parameters that determine PDT efficacy are 1. the photosensitizer (nature of the molecules, selectivity, and macroscopic and microscopic localization etc.), 2. light application (wavelength, fluence, fluence rate, irradiation regimes etc.) and 3. the microenvironment (vascularity, hypoxic regions, stromal tissue density, molecular heterogeneity etc.). Over the years, several groups aimed to monitor and manipulate the components of these critical parameters to improve the effectiveness of PDT treatments. However, PDT is still misconstrued to be a surface treatment primarily due to the limited depths of light penetration. In this review, we present the recent advances, strategies and perspectives in PDT approaches, particularly in cancer treatment, that focus on increasing the `damage zone' beyond the reach of light in the body. This is enabled by a spectrum of approaches that range from innovative photosensitizer excitation strategies, increased specificity of phototoxicity, and biomodulatory approaches that amplify the biotherapeutic effects induced by photodynamic action. Along with the increasing depth of understanding of the underlying physical, chemical and physiological mechanisms, it is anticipated that with the convergence of these strategies, the clinical utility of PDT will be expanded to a powerful modality in the armamentarium for the management of cancer. C1 [Mallidi, Srivalleesha; Anbil, Sriram; Bulin, Anne-Laure; Obaid, Girgis; Ichikawa, Megumi; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Anbil, Sriram] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Anbil, Sriram] Univ Texas Sch Med San Antonio, San Antonio, TX 78229 USA. RP Hasan, T (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu FU NIH [F32CA165881, 5R01CA156177, R01 CA158415, R01-CA160998, S10 ODO1232601]; Canon USA Inc.; Bullock-Wellman Postdoctoral Fellowship (Obaid); Howard Hughes Medical Institute Medical Research Fellows Program (Anbil) FX This work was supported by NIH grants F32CA165881 (Mallidi), 5R01CA156177, R01 CA158415, R01-CA160998 (Hasan) and S10 ODO1232601 (Hasan) and funds from Canon USA Inc. Financial support by the Bullock-Wellman Postdoctoral Fellowship (Obaid) and Howard Hughes Medical Institute Medical Research Fellows Program (Anbil) is gratefully acknowledged. The authors would like to acknowledge Mr. Brian Battersby, Director of Computational Core, Wellman Center for Photomedicine for the help with cover art. NR 199 TC 1 Z9 1 U1 4 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2016 VL 6 IS 13 BP 2458 EP 2487 DI 10.7150/thno.16183 PG 30 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EO2UN UT WOS:000396551600014 PM 27877247 ER PT S AU MacRae, CA Boss, G Brenner, M Gerszten, RE Mahon, S Peterson, RT AF MacRae, Calum A. Boss, Gerry Brenner, Matthew Gerszten, Robert E. Mahon, Sari Peterson, Randall T. BE Laskin, JD Braaten, D TI A countermeasure development pipeline SO COUNTERMEASURES AGAINST CHEMICAL THREATS II SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE cyanide; countermeasure; drug discovery; animal models; metabolomics ID ACUTE CYANIDE INTOXICATION; ZINC-FINGER NUCLEASES; CHEMICAL GENETICS; SMALL MOLECULES; SODIUM-NITROPRUSSIDE; LIPID-PEROXIDATION; TRIAZINE LIBRARY; DRUG DISCOVERY; SULFUR DONORS; ZEBRAFISH AB We have developed an integrated pipeline for countermeasure discovery that, under the auspices of the National Institutes of Health Countermeasures Against Chemical Threats network, is one of the few efforts within academia that by design spans the spectrum from discovery to phase I. The successful implementation of this approach for cyanide would enable efficient proof-of-concept studies that would lay the foundation for a generalizable strategy for parallel mechanistic studies and accelerated countermeasure development in the face of new and emerging chemical threats. C1 [MacRae, Calum A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [MacRae, Calum A.; Gerszten, Robert E.; Peterson, Randall T.] Harvard Med Sch, Boston, MA USA. [Boss, Gerry; Mahon, Sari] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Brenner, Matthew] Univ Calif Irvine, Irvine, CA USA. [Gerszten, Robert E.; Peterson, Randall T.] Massachusetts Gen Hosp, Charlestown, MA USA. RP MacRae, CA (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM camacrae@bics.bwh.harvard.edu NR 91 TC 0 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1378 BP 58 EP 67 DI 10.1111/nyas.13224 PG 10 WC Chemistry, Applied; Public, Environmental & Occupational Health; Toxicology SC Chemistry; Public, Environmental & Occupational Health; Toxicology GA BG9XR UT WOS:000394087800007 PM 27737495 ER PT S AU Niquet, J Baldwin, R Suchomelova, L Lumley, L Naylor, D Eavey, R Wasterlain, CG AF Niquet, Jerome Baldwin, Roger Suchomelova, Lucie Lumley, Lucille Naylor, David Eavey, Roland Wasterlain, Claude G. BE Laskin, JD Braaten, D TI Benzodiazepine-refractory status epilepticus: pathophysiology and principles of treatment SO COUNTERMEASURES AGAINST CHEMICAL THREATS II SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE refractory status epilepticus; cholinergic seizures; pharmacoresistance; polytherapy; nerve agent ID SUSTAINING STATUS EPILEPTICUS; LIMBIC STATUS EPILEPTICUS; CONVULSIVE STATUS EPILEPTICUS; RECEPTOR ANTAGONISTS; GABA(A) RECEPTORS; PERFORANT-PATH; RECTAL GEL; STIMULATION; SEIZURES; RATS AB Cholinergic status epilepticus (CSE) quickly becomes self-sustaining, independent of its initial trigger, and resistant to benzodiazepines and other antiepileptic drugs. We review a few of the many physiological changes associated with CSE, with an emphasis on receptor trafficking. Time-dependent internalization of synaptic gamma-aminobutyric acid (GABA)(A) receptors explains, in part, the loss of inhibition and the loss of response to benzodiazepines in the early stages of CSE. The increase in N-methyl-D-aspartate receptors may contribute to the runaway excitation and excitotoxicity of CSE. These changes have therapeutic implications. The time-dependent increase in maladaptive changes points to the importance of early treatment. The involvement of both inhibitory and excitatory systems challenges current therapeutic guidelines, which recommend treating only one system, and questions the rationale for monotherapy. It suggests that polytherapy may be needed, especially when treatment is delayed, so that drugs can only reach amuch reduced number of GABA(A) receptors. Finally, it raises the possibility that the current practice of waiting for one treatment to fail before starting the next drug may need to be reevaluated. C1 [Niquet, Jerome; Naylor, David; Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Niquet, Jerome; Baldwin, Roger; Suchomelova, Lucie; Eavey, Roland; Wasterlain, Claude G.] Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, 11301 Wilshire Blvd,Bldg 114,Room 139, West Los Angeles, CA 90073 USA. [Lumley, Lucille] USAMRICD, Aberdeen, MD USA. [Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Niquet, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, 11301 Wilshire Blvd,Bldg 114,Room 139, West Los Angeles, CA 90073 USA. EM jniquet@ucla.edu FU BLRD VA [I01 BX000273]; NINDS NIH HHS [U01 NS074926] NR 37 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1378 BP 166 EP 173 DI 10.1111/nyas.13147 PG 8 WC Chemistry, Applied; Public, Environmental & Occupational Health; Toxicology SC Chemistry; Public, Environmental & Occupational Health; Toxicology GA BG9XR UT WOS:000394087800018 PM 27392038 ER PT J AU Streba, CT Giltan, AM Gheonea, IA Demetrian, A Soimu, AV Saftoiu, A Gruionu, G Gruionu, LG AF Streba, Costin Teodor Giltan, Ana Maria Gheonea, Ioana Andreea Demetrian, Alin Soimu, Andreea-Valentina Saftoiu, Adrian Gruionu, Gabriel Gruionu, Lucian Gheorghe TI Utility of confocal laser endomicroscopy in pulmonology and lung cancer SO ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY LA English DT Review DE optical biopsy; probe-based confocal laser endomicroscopy; lung cancer; diagnosis; therapy ID OPTICAL COHERENCE TOMOGRAPHY; GROWTH-FACTOR RECEPTOR; WHITE-LIGHT BRONCHOSCOPY; IN-VIVO; AUTOFLUORESCENCE BRONCHOSCOPY; FLUORESCENCE MICROSCOPY; PRECANCEROUS LESIONS; RESPIRATORY-TRACT; COLORECTAL-CANCER; DIAGNOSIS AB Primary lung cancer is an increasing health issue worldwide, with an ever-growing incidence due to various risk factors dispersed in all settings of modern society. Late discovery and poor survival rates for patients that do not qualify for surgical treatments greatly decrease overall mortality. Imaging methods remain powerful tools for early detection; however, molecular profiling is currently required for better understanding treatment options and for developing novel agents. Most procedures that are associated with tissue collection are invasive and, if performed in suboptimal conditions, may lead to morbidity and mortality. The need for better optical biopsy tools has thus arisen, directing further tissue collection and minimizing the chance of misdiagnosis. A series of methods have been proposed, including optical coherence tomography, narrow band imaging or autofluorescence. Lately, a novel in vivo tool for rapid and non-invasive microscopy gained traction probe based confocal laser endomicroscopy became available in an increased number of referral centers worldwide. Miniaturization and the use of optical fibers allowed for the development of a dedicated device for pulmonary applications; lung cancer diagnosis and characterization are key issues targeted by this novel technology. We present here recent advancements in the field of optical biopsy of lung tissue, with a focus on emerging technologies and their involvement in cancer diagnostics and future therapeutic options. C1 [Streba, Costin Teodor] Univ Med & Pharm Craiova, Dept Pulmonol, Craiova, Romania. [Streba, Costin Teodor; Saftoiu, Adrian] Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol, Dept Gastroenterol, Craiova, Romania. [Giltan, Ana Maria] Emergency Cty Hosp, Dept Pulmonol, Craiova, Romania. [Gheonea, Ioana Andreea] Univ Med & Pharm Craiova, Dept Med Imaging, 2 Petru Rares St, Craiova 200349, Romania. [Demetrian, Alin] Copenhagen Univ Hosp Herlev, Gastrointestinal Unit, Dept Endoscopy, Herlev, Denmark. [Soimu, Andreea-Valentina] Natl Inst Res Dev & Testing Elect Engn, High Voltage Div, Craiova, Romania. [Saftoiu, Adrian] Univ Med & Pharm Craiova, Dept Thorac Surg, Craiova, Romania. [Gruionu, Gabriel] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Gruionu, Gabriel] Harvard Med Sch, Boston, MA USA. [Gruionu, Lucian Gheorghe] Univ Craiova, Fac Mech, Dept Automot Transports & Ind Engn, Craiova, Romania. RP Gheonea, IA (reprint author), Univ Med & Pharm Craiova, Dept Med Imaging, 2 Petru Rares St, Craiova 200349, Romania. EM iagheonea@gmail.com FU EEA [EEA-JRP-RO-NO-2013-1-0123, 3SEE/30.06.2014] FX This study was funded by the EEA Financial Mechanism 2009-2014 under the project EEA-JRP-RO-NO-2013-1-0123 - Navigation System for Confocal Laser Endomicroscopy to Improve Optical Biopsy of Peripheral Lesions in the Lungs (NAVICAD), Contract No. 3SEE/30.06.2014. NR 43 TC 0 Z9 0 U1 0 U2 0 PU EDITURA ACAD ROMANE PI BUCURESTI PA CALEA 13 SEPTEMBRIE NR 13, SECTOR 5, BUCURESTI 050711, ROMANIA SN 1220-0522 J9 ROM J MORPHOL EMBRYO JI Rom. J. Morphol. Embryol. PY 2016 VL 57 IS 4 BP 1221 EP 1227 PG 7 WC Developmental Biology SC Developmental Biology GA EK8UY UT WOS:000394201300005 PM 28174787 ER PT S AU Hodes, RJ Sierra, F Austad, SN Epel, E Neigh, GN Erlandson, KM Schafer, MJ LeBrasseur, NK Wiley, C Campisi, J Sehl, ME Scalia, R Eguchi, S Kasinath, BS Halter, JB Cohen, HJ Demark-Wahnefried, W Ahles, TA Barzilai, N Hurria, A Hunt, PW AF Hodes, Richard J. Sierra, Felipe Austad, Steven N. Epel, Elissa Neigh, Gretchen N. Erlandson, Kristine M. Schafer, Marissa J. LeBrasseur, Nathan K. Wiley, Christopher Campisi, Judith Sehl, Mary E. Scalia, Rosario Eguchi, Satoru Kasinath, Balakuntalam S. Halter, Jeffrey B. Cohen, Harvey Jay Demark-Wahnefried, Wendy Ahles, Tim A. Barzilai, Nir Hurria, Arti Hunt, Peter W. GP NY Acad Sci BE Braaten, D TI Disease drivers of aging SO ANNALS REPORTS, VOL 1386 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE disease; aging; pathology; chronic; prevention; age-related; HIV; diabetes; cancer ID QUALITY-OF-LIFE; BETA-CELL PROLIFERATION; TERM CANCER SURVIVORS; CHRONIC HIV-INFECTION; INSULIN-RESISTANCE; NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION; ISCHEMIA-REPERFUSION; HYDROGEN-SULFIDE; OXIDATIVE-STRESS AB It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. C1 [Hodes, Richard J.; Sierra, Felipe] NIA, Bethesda, MD 20892 USA. [Austad, Steven N.] Univ Alabama Birmingham, Dept Biol, Birmingham, AL 35294 USA. [Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Neigh, Gretchen N.] Virginia Commonwealth Univ, Richmond, VA USA. [Erlandson, Kristine M.] Univ Colorado, Anschutz Med Ctr, Aurora, CO USA. [Schafer, Marissa J.; LeBrasseur, Nathan K.] Mayo Clin, Coll Med, Robert & Arlene Kogod Ctr Aging, Rochester, MN USA. [Schafer, Marissa J.; LeBrasseur, Nathan K.] Mayo Clin, Coll Med, Dept Phys Med & Rehabil, Rochester, MN USA. [Wiley, Christopher; Campisi, Judith] Buck Inst Res Aging, Novato, CA USA. [Sehl, Mary E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Scalia, Rosario; Eguchi, Satoru] Temple Univ, Lewis Katz Sch Med, Dept Physiol, Philadelphia, PA 19122 USA. [Scalia, Rosario; Eguchi, Satoru] Temple Univ, Lewis Katz Sch Med, Cardiovasc Res Ctr, Philadelphia, PA 19122 USA. [Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Halter, Jeffrey B.] Univ Michigan, Div Geriatr & Palliat Med, Ann Arbor, MI 48109 USA. [Cohen, Harvey Jay] Duke Univ, Sch Med, Durham, NC USA. [Demark-Wahnefried, Wendy] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Ahles, Tim A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Barzilai, Nir] Albert Einstein Coll Med, Inst Aging Res, New York, NY USA. [Hurria, Arti] City Hope Natl Med Ctr, Natl Med Ctr, Duarte, CA USA. [Hunt, Peter W.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Hodes, RJ (reprint author), NIA, Bethesda, MD 20892 USA. EM annals@nyas.org FU NIA NIH HHS [K23 AG050260]; NIDDK NIH HHS [P30 DK079626] NR 160 TC 1 Z9 1 U1 2 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1386 BP 45 EP 68 DI 10.1111/nyas.13299 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BG9XT UT WOS:000394090800004 PM 27943360 ER PT J AU Moin, T Damschroder, LJ Youles, B Makki, F Billington, C Yancy, W Maciejewski, ML Kinsinger, LS Weinreb, JE Steinle, N Richardson, CR AF Moin, Tannaz Damschroder, Laura J. Youles, Bradley Makki, Fatima Billington, Charles Yancy, William Maciejewski, Matthew L. Kinsinger, Linda S. Weinreb, Jane E. Steinle, Nanette Richardson, Caroline R. TI Implementation of a prediabetes identification algorithm for overweight and obese Veterans SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE diabetes; diabetes prevention; guidelines; health services research; implementation research; obesity; prediabetes; screening; Veterans; weight management ID FINNISH DIABETES PREVENTION; WEIGHT-MANAGEMENT PROGRAM; LIFE-STYLE INTERVENTIONS; FOLLOW-UP; TYPE-2; REDUCTION; ADULTS; RISK; HEMOGLOBIN; CRITERIA AB Type 2 diabetes prevention is an important national goal for the Veterans Health Administration (VHA): one in four Veterans has diabetes. We implemented a prediabetes identification algorithm to estimate prediabetes prevalence among overweight and obese Veterans at Department of Veterans Affairs (VA) medical centers (VAMCs) in preparation for the launch of a pragmatic study of Diabetes Prevention Program (DPP) delivery to Veterans with prediabetes. This project was embedded within the VA DPP Clinical Demonstration Project conducted from 2012 to 2015. Veterans who attended orientation sessions for an established VHA weight-loss program (MOVE!) were recruited from VAMCs with geographically and racially diverse populations using existing referral processes. Each site implemented and adapted the prediabetes identification algorithm to best fit its local clinical context. Sites relied on an existing referral process in which a prediabetes identification algorithm was implemented in parallel with existing clinical flow; this approach limited the number of overweight and obese Veterans who were assessed and screened. We evaluated 1,830 patients through chart reviews, interviews, and/or laboratory tests. In this cohort, our estimated prevalence rates for normal glycemic status, prediabetes, and diabetes were 29% (n = 530), 28% (n = 504), and 43% (n = 796), respectively. Implementation of targeted prediabetes identification programs requires careful consideration of how prediabetes assessment and screening will occur. C1 [Moin, Tannaz; Weinreb, Jane E.] Dept Vet Affairs VA Greater Los Angeles Healthcar, Los Angeles, CA USA. [Moin, Tannaz; Weinreb, Jane E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moin, Tannaz] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Damschroder, Laura J.; Youles, Bradley; Makki, Fatima; Richardson, Caroline R.] VA Ctr Clin Management Res, Ann Arbor, MI USA. [Billington, Charles] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Billington, Charles] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Yancy, William; Maciejewski, Matthew L.] Durham VA Med Ctr VAMC, Durham, NC USA. [Yancy, William; Maciejewski, Matthew L.] Duke Univ, Sch Med, Durham, NC USA. [Kinsinger, Linda S.] Vet Hlth Adm, Natl Ctr Hlth Promot & Dis Prevent, Durham, NC USA. [Steinle, Nanette] Baltimore VAMC, Baltimore, MD USA. [Steinle, Nanette] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Richardson, Caroline R.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. [Richardson, Caroline R.] VA Diabet Qual Enhancement Res Initiat, Ann Arbor, MI USA. RP Moin, T (reprint author), VA Greater Los Angeles Healthcare Syst, Mail Code 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Tannaz.moin@va.gov FU VA [XVA 41-048, RRP 12-440, SDP 12-549]; VA Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program, VA Greater Los Angeles [TPM65-010] FX This material was based on work supported by the VA (awards XVA 41-048, RRP 12-440, and SDP 12-549). Dr. Moin received support from the VA Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program (award TPM65-010), VA Greater Los Angeles, from 2011 to 2014. NR 31 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2016 VL 53 IS 6 BP 853 EP 862 DI 10.1682/JRRD.2015.06.0104 PG 10 WC Rehabilitation SC Rehabilitation GA EK5SC UT WOS:000393985100017 PM 28273326 ER PT J AU Glimcher, LH AF Glimcher, L. H. TI Stressed Out: A Novel Approach to Cancer Immunotherapy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Glimcher, L. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA S9 PG 2 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500137 ER PT J AU Mootha, VK AF Mootha, V. K. TI Mitochondrial parts, pathways, and pathogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Mootha, V. K.] Massachusetts Gen Hosp, Mol Biol, Boston, MA 02114 USA. [Mootha, V. K.] Harvard Med Sch, Syst Biol, Boston, MA USA. [Mootha, V. K.] Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA S7 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500135 ER PT J AU Schmider, AB Godin, M Elliott, HD Soberman, RJ AF Schmider, A. B. Godin, M. Elliott, H. D. Soberman, R. J. TI Organization of the Leukotriene Synthetic Complex in Neutrophils as an Indicator of Disease State. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Schmider, A. B.; Godin, M.; Soberman, R. J.] Massachusetts Gen Hosp, Nephrol, Charlestown, MA USA. [Elliott, H. D.] Harvard Med Sch, Cell Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E105 PG 2 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500248 ER PT J AU Spektor, A Zhang, C Umbreit, N Feldman, M Ahsan, A Zhang, Y Pellman, DS AF Spektor, A. Zhang, C. Umbreit, N. Feldman, M. Ahsan, A. Zhang, Y. Pellman, D. S. TI ORC is not essential for DNA replication in human cell lines, but important for repressing Rb-E2F and Polycomb group regulated genes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Spektor, A.] Dana Farber Canc Inst, Radiat Oncol, Boston, MA 02115 USA. [Spektor, A.; Umbreit, N.; Feldman, M.; Ahsan, A.; Pellman, D. S.] Harvard Med Sch, Cell Biol, Boston, MA USA. [Zhang, C.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Zhang, C.] Harvard Med Sch, Biomed Informat, Boston, MA USA. [Umbreit, N.; Feldman, M.; Ahsan, A.; Pellman, D. S.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Zhang, Y.] Dana Farber Canc Inst, Single Cell Sequencing Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M172 PG 2 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500307 ER PT J AU Swaminathan, V Mathew, JK Mehta, S Nordenfelt, P Moore, TI Nobuyasu, K Baker, D Oldenbourg, R Tani, T Mayor, S Springer, TA Waterman, CM AF Swaminathan, V. Mathew, J. K. Mehta, S. Nordenfelt, P. Moore, T. I. Nobuyasu, K. Baker, D. Oldenbourg, R. Tani, T. Mayor, S. Springer, T. A. Waterman, C. M. TI Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, Bangalore, Karnataka, India. [Mehta, S.; Oldenbourg, R.; Tani, T.] Marine Biol Sci, Woods Hole, MA USA. [Nordenfelt, P.] Lund Univ, Div Infect Med, Lund, MD USA. [Moore, T. I.; Springer, T. A.] Harvard Univ, Program Cellular & Mol Med, Boston, MA 02115 USA. [Nobuyasu, K.; Baker, D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E58 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500202 ER PT J AU Weinstein, SR Meehan, KB Cain, NM Ripoll, LH Boussi, AR Papouchis, N Siever, LJ New, AS AF Weinstein, Shauna R. Meehan, Kevin B. Cain, Nicole M. Ripoll, Luis H. Boussi, Ayelet R. Papouchis, Nicholas Siever, Larry J. New, Antonia S. TI Mental State Identification, Borderline Pathology, and the Neglected Role of Childhood Trauma SO PERSONALITY DISORDERS-THEORY RESEARCH AND TREATMENT LA English DT Article DE borderline personality disorder; childhood trauma; mental state identification; mentalization; RMET ID POSTTRAUMATIC-STRESS-DISORDER; PERSONALITY-DISORDER; ASPERGER-SYNDROME; NORMAL ADULTS; EYES TEST; EMOTION; MIND; RECOGNITION; AUTISM; WOMEN AB Research evaluating mental state identification in individuals with borderline pathology has yielded inconsistent results; contradictory findings were hypothesized to be driven by moderating effects of childhood trauma. Participants were 105 ethnically diverse men and women who exhibited a range of borderline pathology measured by Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for borderline personality disorder. Mental state identification accuracy was measured using the Reading the Mind in the Eyes Test (RMET). Greater childhood abuse, but not childhood neglect, was associated with enhanced mental state identification accuracy on negative stimuli, when controlling for dissociation (ps < .05); these findings could not be explained by reaction time (RT) or response bias. Childhood abuse and childhood neglect were not related to mental state identification accuracy on neutral or positive stimuli, and they did not moderate the relationship between borderline pathology and mental state identification accuracy on negative, neutral, or positive stimuli. Borderline pathology was not independently related to mental state identification accuracy on negative, neutral, or positive stimuli. Greater childhood neglect, but not childhood abuse, was related to slower RTs on negative, neutral, and positive stimuli (ps < .05). Results underline the importance of separately assessing childhood abuse and childhood neglect and of controlling for dissociation, and they suggest borderline pathology may not universally hinder complex mental state identification. C1 [Weinstein, Shauna R.; Meehan, Kevin B.; Cain, Nicole M.; Boussi, Ayelet R.; Papouchis, Nicholas] Long Isl Univ, Dept Psychol, Brooklyn Campus, Brookville, NY USA. [Ripoll, Luis H.; Siever, Larry J.; New, Antonia S.] James J Peters VA Med Ctr, MIRECC, Bronx, NY USA. [Ripoll, Luis H.; Boussi, Ayelet R.; Siever, Larry J.; New, Antonia S.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Weinstein, Shauna R.] Elmhurst Hosp Ctr, Queens, NY USA. [Ripoll, Luis H.] New York Psychoanalyt Inst, New York, NY USA. RP Weinstein, SR (reprint author), Long Isl Univ, Dept Psychol, 1 Univ Plaza, Brooklyn, NY 11201 USA. EM shaunaweinstein3@gmail.com NR 34 TC 0 Z9 0 U1 1 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1949-2715 EI 1949-2723 J9 PERSONAL DISORD JI Personal. Disord. PD JAN PY 2016 VL 7 IS 1 BP 61 EP 71 DI 10.1037/per0000139 PG 11 WC Psychology, Clinical SC Psychology GA EL3GH UT WOS:000394507100008 PM 26461046 ER PT J AU Kim, NH Chin, KM Muros-Le Rouzic, E Brand, M Selej, M Channick, RN McLaughlin, VV AF Kim, N. H. Chin, K. M. Muros-Le Rouzic, E. Brand, M. Selej, M. Channick, R. N. McLaughlin, V. V. TI Opsumit (R) Users Registry (opus): Insights Into The Safety And Tolerability Of Opsumit (R) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kim, N. H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Chin, K. M.] UT Southwestern, Dallas, TX USA. [Muros-Le Rouzic, E.; Brand, M.] Actel Pharmaceut LTD, Allschwille, Switzerland. [Selej, M.] Actel Pharmaceut, San Francisco, CA USA. [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McLaughlin, V. V.] Univ Michigan Cardiol, Ann Arbor, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7396 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607332 ER PT J AU Gorcsan, J Sogaard, P Bax, JJ Singh, JP Abrahams, WT Borer, JS Dickstein, K Gras, D Krum, H Brugada, J Robertson, M Ford, I Holzmeister, J Ruschitzka, F AF Gorcsan, John, III Sogaard, Peter Bax, Jeroen J. Singh, Jagmeet P. Abrahams, William T. Borer, Jeffrey S. Dickstein, Kenneth Gras, Daniel Krum, Henry Brugada, Josep Robertson, Michele Ford, Ian Holzmeister, Johannes Ruschitzka, Frank TI Association of persistent or worsened echocardiographic dyssynchrony with unfavourable clinical outcomes in heart failure patients with narrow QRS width: a subgroup analysis of the EchoCRT trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Heart failure; Echocardiography; Cardiac resynchronization therapy ID CARDIAC-RESYNCHRONIZATION THERAPY; LEFT-VENTRICULAR DYSSYNCHRONY; LONG-TERM SURVIVAL; MECHANICAL DYSSYNCHRONY; STRAIN; ARRHYTHMIAS; PERFORMANCE; ASYNCHRONY; COMPLEXES; RISK AB Aims EchoCRTwas a randomized trial of cardiac resynchronization therapy (CRT) in severely symptomatic heart failure (HF) patients with narrow QRS width <130 ms, ejection fraction <= 35%, and echocardiographic dyssynchrony. All received CRT implants which were then randomized to CRT-On or CRT-Off. While the trial showed no benefit of CRT to these patients, the aim of this subgroup analysis was to test the hypothesis that persistent or worsening dyssynchrony is associated with unfavourable clinical outcomes. Methods and results We studied 614 EchoCRT patients with baseline and 6-month echocardiograms. Baseline dyssynchrony required for study inclusion was either tissue Doppler imaging longitudinal velocity delay >= 80 ms or speckle-tracking radial strain delay >= 130 ms. Persistent dyssynchrony at 6 months was observed similarly in both groups (77% in CRT-On; 76% in CRT-Off). Persistent dyssynchrony was associated with a significantly higher primary end point of death or HF hospitalization (HR = 1.54, 95% CI 1.03-2.30, P = 0.03), and in particular secondary endpoint of HF hospitalization (HR = 1.66, 95% CI 1.07-2.57, P = 0.02). HF hospitalizations were also associated with worsening longitudinal dyssynchrony (HR = 1.45, 95% CI 1.02-2.05, P = 0.037), and worsening radial dyssynchrony (HR = 1.81, 95% CI 1.16-2.81, P = 0.008). Associations of persistent or worsening dyssynchrony with outcomes were similar in CRT-Off and CRTOn groups. Conclusions Persistent or worsening echocardiographic dyssynchrony in HF patients with narrow QRS width was a marker for unfavourable clinical outcomes unaffected by CRT. In particular, echocardiographic dyssynchrony on follow-up was strongly associated with HF hospitalizations and appears to be a prognostic marker of disease severity. C1 [Gorcsan, John, III] Univ Pittsburgh, Scaife 564,200 Lothrop St, Pittsburgh, PA 15213 USA. [Sogaard, Peter] Aalborg Univ, Aalborg, Denmark. [Bax, Jeroen J.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Abrahams, William T.] Ohio State Univ, Davis Heart & Lung Res Inst, Div Cardiovasc Med, Columbus, OH 43210 USA. [Borer, Jeffrey S.] SUNY Downstate Coll Med, Dept Cardiol, Div Cardiovasc Med, Brooklyn, NY USA. [Borer, Jeffrey S.] SUNY Downstate Coll Med, Howard Gilmanand Ron Inst, Brooklyn, NY USA. [Borer, Jeffrey S.] SUNY Downstate Coll Med, Jean Schiavone Inst, Brooklyn, NY USA. [Dickstein, Kenneth] Univ Bergen, Stavanger Univ Hosp, Stavanger, Norway. [Gras, Daniel] Nouvelles Clin Nantaises, Nantes, France. [Krum, Henry] Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic, Australia. [Brugada, Josep] Univ Barcelona, Dept Cardiol, Thorax Inst, Hosp Clin, Barcelona, Spain. [Robertson, Michele; Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Holzmeister, Johannes; Ruschitzka, Frank] Univ Heart Ctr Zurich, Dept Cardiol, Zurich, Switzerland. RP Gorcsan, J (reprint author), Univ Pittsburgh, Scaife 564,200 Lothrop St, Pittsburgh, PA 15213 USA.; Abrahams, WT (reprint author), Ohio State Univ, Davis Heart & Lung Res Inst, Div Cardiovasc Med, Columbus, OH 43210 USA.; Ruschitzka, F (reprint author), Univ Heart Ctr Zurich, Dept Cardiol, Zurich, Switzerland. EM gorcsanj@upmc.cdu FU Biotronik, Inc.; Biotronik; GE; Medtronic; St. Jude; GE HealthCare; Bayer; EBR systems; Boston Scientific; Lantheus; Servier; Edwards Lifesciences; Sorin Group; St. Jude Medical; CardioInsight Inc; Servier Laboratoires; Amgen; Takeda USA; Pfizer; Cardiorentis; Novartis; ARMGO; Celladon; Sorin; RESMED FX The EchoCRT trial was sponsored by Biotronik, Inc. with an equipment grant from G.E. J.G. reports grants and personal fees from Biotronik, grants from GE, during the conduct of the study; grants from Medtronic, grants from St. Jude, outside the submitted work. P.S. has received consultant fees from Biotronik, speaker fees from GE HealthCare, and research grants from Biotronik, GE Health Care, Bayer, and EBR systems. J.J.B. reports grant support from GE Healthcare, Biotronik, Boston Scientific, Medtronic, Lantheus, Servier, and Edwards Lifesciences. J.P.S. reports grants and personal fees from Biotronik, grants and personal fees from Boston Scientific, grants and personal fees from Sorin Group, grants and personal fees from Medtronic, grants and personal fees from St. Jude Medical, personal fees from CardioInsight Inc, outside the submitted work. W.T.A. reports grant support and personal fees from Biotronik during the conduct of the study; and grant support and personal fees from Medtronic and St. Jude Medical. J.S.B. reports personal fees from BioTRONIK, during the conduct of the study; personal fees from Servier Laboratoires, personal fees from Amgen, personal fees from Takeda USA, personal fees from Pfizer, personal fees from Cardiorentis, personal fees from Novartis, personal fees from ARMGO, personal fees from Celladon, outside the submitted work. K.D. reports personal fees from Biotronik; and personal fees from Medtronic, Sorin, and Boston Scientific. D.G. reports personal fees from Medtronic, St. Jude Medical, Boston Scientific, and Biotronik. H.K. reports personal fees from Biotronik. J.B. reports personal fees and other from BIOTRONIK, during the conduct of the study; M.R. has nothing to declare. I.F. reports grant support from Biotronik; grant support and personal fees from Servier, and Medtronic, and personal fees from RESMED. J.H. reports grant support from St. Jude Medical and grant support and personal fees from Biotronik; and other support from Cardiorentis. F.R. reports personal fees from Biotronik; and personal fees from Servier, Cardiorentis, and St. Jude Medical. NR 33 TC 13 Z9 13 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JAN 1 PY 2016 VL 37 IS 1 SI SI BP 49 EP 59 DI 10.1093/eurheartj/ehv418 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE9QW UT WOS:000370974000007 PM 26321238 ER PT J AU Balter, ML Chen, AI Colinco, CA Gorshkov, A Bixon, B Martin, V Fromholtz, A Maguire, TJ Yarmush, ML AF Balter, Max L. Chen, Alvin I. Colinco, C. Amara Gorshkov, Alexander Bixon, Brian Martin, Vincent Fromholtz, Alexander Maguire, Timothy J. Yarmush, Martin L. TI Differential leukocyte counting via fluorescent detection and image processing on a centrifugal microfluidic platform SO ANALYTICAL METHODS LA English DT Article ID WHOLE-BLOOD; LAB; DISK; SEPARATION AB Centrifugal microfluidics has received much attention in the last decade for the automation of blood testing at the point-of-care, specifically for the detection of chemistries, proteins, and nucleic acids. However, the detection of common blood cells on-disc, particularly leukocytes, remains a challenge. In this paper, we present two methods for enumerating leukocytes on a centrifugal platform using a custom-built fluorescent microscope, nuclear staining, and image processing. In the first method, cell analysis is performed in glass capillary tubes; in the second, acrylic chips are used. A bulk-cell analysis approach is implemented in both cases where the pixel areas of fractionated lymphocyte/monocyte and granulocyte layers are correlated with cell counts. Generating standard curves using porcine blood sample controls, we observed strong linear fits to measured cell counts using both methods. Analyzing the pixel intensities of the fluorescing white cell region, we are able to differentiate lymphocytes from monocytes via pixel clustering, demonstrating the capacity to perform a 3-part differential. Finally, a discussion of pros and cons of the bulk-cell analysis approach concludes the paper. C1 [Balter, Max L.; Chen, Alvin I.; Colinco, C. Amara; Gorshkov, Alexander; Bixon, Brian; Martin, Vincent; Fromholtz, Alexander; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Maguire, Timothy J.] VascuLogic LLC, Piscataway, NJ 08854 USA. [Yarmush, Martin L.] Massachusetts Gen Hosp, Boston, MA 02108 USA. RP Balter, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. EM balterm53@gmail.com FU NIH [R01EB020036, EB018191]; NSF [DGE-0937373] FX This research was supported by a grant from the NIH (R01EB020036). The work of M. Balter was supported by an NSF Graduate Fellowship (DGE-0937373). The work of A. Chen was supported by an NIH F31 Predoctoral Fellowship (EB018191). NR 40 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 EI 1759-9679 J9 ANAL METHODS-UK JI Anal. Methods PY 2016 VL 8 IS 47 BP 8272 EP 8279 DI 10.1039/c6ay02614a PG 8 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA EJ3GN UT WOS:000393100700004 ER PT J AU Ruella, M Maus, MV AF Ruella, Marco Maus, Marcela V. TI Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies SO COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL LA English DT Article DE Chimeric antigen receptor T cells; Blinatumomab; Bispecific antibodies; Adoptive cell therapy; dualCART; tanCAR; biCAR; CART19; CTL019; Leukemia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHIMERIC ANTIGEN RECEPTOR; SINGLE-CHAIN ANTIBODY; B-LINEAGE; ENGAGING ANTIBODY; FREE SURVIVAL; CD19; BLINATUMOMAB; PRECURSOR; CANCER AB Immunotherapy is the revolution in cancer treatment of this last decade. Among multiple approaches able to harness the power of the immune system against cancer, T cell based immunotherapies represent one of the most successful examples. In particular, biotechnological engineering of protein structures, like the T cell receptor or the immunoglobulins, allowed the generation of synthetic peptides like chimeric antigen receptors and bispecific antibodies that are able to redirect non-tumor specific T cells to recognize and kill leukemic cells. The anti-CD19/CD3 bispecific antibody blinatumomab and anti-CD19 chimeric antigen receptor T cells (CART19) have produced deep responses in patients with relapsed and refractory B-cell acute leukemias. However, although the majority of these patients responds to anti-CD19 immunotherapy, a subset of them still relapses. Interestingly, a novel family of leukemia escape mechanisms has been described, all characterized by the apparent loss of CD19 on the surface of leukemic blasts. This extraordinary finding demonstrates the potent selective pressure of CART19/blinatumomab that drives extreme and specific escape strategies by leukemic blasts. Patients with CD19-negative relapsed leukemia have very poor prognosis and novel approaches to treat and ideally prevent antigen-loss are direly needed. In this review we discuss the incidence, mechanisms and therapeutic approaches for CD19-negative leukemia relapses occuring after CD19-directed T cell immunotherapies and present our future perspective. (C) 2016 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. C1 [Ruella, Marco] Univ Penn, Ctr Cellular Immunotherapies, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ruella, Marco] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Ruella, Marco] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Maus, Marcela V.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RP Ruella, M (reprint author), Smilow Ctr Transl Res, 8-196 C,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM marco.ruella@uphs.upenn.edu FU SITC (EMD-Serono Cancer Immunotherapy Clinical Fellowship); AACR (Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research); Gabrielle's Angel Foundation; SIES-AIL; NCI [K08CA166039] FX This work was supported by grants from the SITC (EMD-Serono Cancer Immunotherapy Clinical Fellowship, PI: M.R.), the AACR (Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research, PI: M.R.), the Gabrielle's Angel Foundation (PI: M.R., PI, M.V.M), the SIES-AIL (PI: M.R.) and the NCI (K08CA166039, PI: MVM) NR 58 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2001-0370 J9 COMPUT STRUCT BIOTEC JI Comp. Struct. Biotechnol. J.. PY 2016 VL 14 BP 357 EP 362 DI 10.1016/j.csbj.2016.09.003 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA EI6TO UT WOS:000392630000043 PM 27761200 ER PT J AU Allahabadi, S Haroun, KB Musher, DM Lipsky, BA Barshes, NR AF Allahabadi, Sachin Haroun, Kareem B. Musher, Daniel M. Lipsky, Benjamin A. Barshes, Neal R. TI Consensus on surgical aspects of managing osteomyelitis in the diabetic foot SO DIABETIC FOOT & ANKLE LA English DT Article DE osteomyelitis; foot infection; foot ulcer; forefoot; diabetic foot; diabetes; consensus; Delphi methodology; consensus ID RANDOMIZED CONTROLLED-TRIAL; CONSERVATIVE SURGERY; CLINICAL-TRIAL; AMPUTATION; THERAPY; ULCERS; TRANSMETATARSAL; ANTIBIOTICS; MULTICENTER; MANAGEMENT AB Background: The aim of this study was to develop consensus statements that may help share or even establish 'best practices' in the surgical aspects of managing diabetic foot osteomyelitis (DFO) that can be applied in appropriate clinical situations pending the publication of more high-quality data. Methods: We asked 14 panelists with expertise in DFO management to participate. Delphi methodology was used to develop consensus statements. First, a questionnaire elicited practices and beliefs concerning various aspects of the surgical management of DFO. Thereafter, we constructed 63 statements for analysis and, using a nine-point Likert scale, asked the panelists to indicate the extent to which they agreed or disagreed with the statements. We defined consensus as a mean score of greater than 7.0. Results: The panelists reached consensus on 38 items after three rounds. Among these, seven provide guidance on initial diagnosis of DFO and selection of patients for surgical management. Another 15 statements provide guidance on specific aspects of operative management, including the timing of operations and the type of specimens to be obtained. Ten statements provide guidance on postoperative management, including wound closure and offloading, and six statements summarize the panelists' agreement on general principles for surgical management of DFO. Conclusions: Consensus statement on the perioperative management of DFO were formed with an expert panel comprised of a variety of surgical specialties. We believe these statements may serve as 'best practice' guidelines until properly performed studies provide more robust evidence to support or refute specific surgical management steps in DFO. C1 [Allahabadi, Sachin; Haroun, Kareem B.] Baylor Coll Med, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Med, Div Infect Dis, Houston, TX 77030 USA. [Lipsky, Benjamin A.] Univ Washington, Dept Med, Seattle, WA USA. [Lipsky, Benjamin A.] Univ Geneva, Dept Med Infect Dis, Geneva, Switzerland. [Lipsky, Benjamin A.] Univ Oxford, Dept Med, Green Templeton Coll, Oxford, England. [Barshes, Neal R.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA. RP Barshes, NR (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA. EM nbarshes@bcm.tmc.edu NR 28 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2000-625X J9 DIABET FOOT ANKLE JI Diabet. Foot Ankle PY 2016 VL 7 AR 30079 DI 10.3402/dfa.v7.30079 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EJ3QB UT WOS:000393125600003 PM 27414481 ER PT J AU Brown, GK Karlin, BE Trockel, M Gordienko, M Yesavage, J Taylor, CB AF Brown, Gregory K. Karlin, Bradley E. Trockel, Mickey Gordienko, Maria Yesavage, Jerry Taylor, C. Barr TI Effectiveness of Cognitive Behavioral Therapy for Veterans with Depression and Suicidal Ideation SO ARCHIVES OF SUICIDE RESEARCH LA English DT Article DE cognitive behavioral therapy; depression; suicide; suicidal ideation; veterans ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE-SYSTEM; NATIONAL-DISSEMINATION AB The current study examined suicidal ideation (SI) and depression outcomes among Veterans receiving Cognitive Behavioral Therapy for depression (CBT-D) throughout the Department of Veterans Affairs health care system. Patient outcomes included Beck Depression Inventory-II total score and SI item. Of 902 patients, 427 (47%) had no SI, 405 (45%) had SI but no suicidal intent, 26 (3%) indicated suicidal desire, 8 (1%) indicated suicide intent if they had the chance, and 36 (4%) did not answer this question at session one. The odds of SI decreased by 64% from 1.03 at session one to 0.37 at final assessment (OR = 0.36; 95% CI: 0.31, 0.43). Findings reveal that CBT-D was associated with significant decreases in SI and depression among Veterans. C1 [Brown, Gregory K.] US Dept Vet Affairs, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Brown, Gregory K.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Karlin, Bradley E.] US Dept Vet Affairs, Mental Hlth Serv, Cent Off, Washington, DC USA. [Karlin, Bradley E.] Educ Dev Ctr Inc, Waltham, MA USA. [Karlin, Bradley E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Trockel, Mickey; Gordienko, Maria; Yesavage, Jerry; Taylor, C. Barr] Stanford Univ, Med Ctr, Dept Psychiat, Palo Alto, CA 94304 USA. [Trockel, Mickey; Gordienko, Maria; Yesavage, Jerry; Taylor, C. Barr] US Dept Vet Affairs, VISN Mental Illness Res Educ & Clin Ctr 21, Palo Alto, CA USA. [Karlin, Bradley E.] Johns Hopkins Univ, Educ Dev Ctr, Baltimore, MD 21218 USA. [Karlin, Bradley E.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. RP Karlin, BE (reprint author), Educ Dev Ctr Inc, 96 Morton St,7th Floor, New York, NY 10014 USA. EM bkarlin@edc.org FU Mental Health Services, U. S. Department of Veterans Affairs Central Office FX This project was supported by Mental Health Services, U. S. Department of Veterans Affairs Central Office. NR 16 TC 0 Z9 0 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1381-1118 EI 1543-6136 J9 ARCH SUICIDE RES JI Arch. Suicide Res. PY 2016 VL 20 IS 4 BP 677 EP 682 DI 10.1080/13811118.2016.1162238 PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA EJ1PH UT WOS:000392982200014 PM 26983897 ER PT J AU Hackel, LM Larson, GM Bowen, JD Ehrlich, GA Mann, TC Middlewood, B Roberts, ID Eyink, J Fetterolf, JC Gonzalez, F Garrido, CO Kim, J O'Brien, TC O'Malley, EE Mesquita, B Barrett, LF AF Hackel, Leor M. Larson, Grace M. Bowen, Jeffrey D. Ehrlich, Gaven A. Mann, Thomas C. Middlewood, Brianna Roberts, Ian D. Eyink, Julie Fetterolf, Janell C. Gonzalez, Fausto Garrido, Carlos O. Kim, Jinhyung O'Brien, Thomas C. O'Malley, Ellen E. Mesquita, Batja Barrett, Lisa Feldman TI On the neural implausibility of the modular mind: Evidence for distributed construction dissolves boundaries between perception, cognition, and emotion SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material C1 [Hackel, Leor M.] New York Univ, Dept Psychol, New York, NY 10003 USA. [Larson, Grace M.] Northwestern Univ, Dept Psychol, Evanston, IL 60208 USA. [Bowen, Jeffrey D.] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA. [Ehrlich, Gaven A.] Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. [Mann, Thomas C.] Cornell Univ, Dept Psychol, Ithaca, NY 14853 USA. [Middlewood, Brianna; Garrido, Carlos O.] Penn State Univ, Dept Psychol, University Pk, PA 16801 USA. [Roberts, Ian D.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Eyink, Julie] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Fetterolf, Janell C.] Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA. [Gonzalez, Fausto] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Kim, Jinhyung] Texas A&M Univ, Dept Psychol, College Stn, TX 77840 USA. [O'Brien, Thomas C.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [O'Malley, Ellen E.] SUNY Albany, Dept Psychol, Albany, NY 12222 USA. [Mesquita, Batja] Univ Leuven, Ctr Social & Cultural Psychol, B-3000 Leuven, Belgium. [Barrett, Lisa Feldman] Northwestern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Biomed Imaging, Dept Psychiat & Martinos, Boston, MA 02114 USA. RP Hackel, LM (reprint author), New York Univ, Dept Psychol, New York, NY 10003 USA. EM leor.hackel@nyu.edu; gracelarson2017@u.northwestern.edu; bowen@psych.ucsb.edu; gaehrlic@syr.edu; tcm79@cornell.edu; blm266@psu.edu; roberts.1134@osu.edu; jeyink@indiana.edu; j.fetterolf@gmail.com; fjgonzal@berkeley.edu; carlosgarrido@psu.edu; jhkim82@tamu.edu; tcobrien@psych.umass.edu; ellen.e.omalley@gmail.com; mesquita@psy.kuleuven.be; l.barrett@neu.edu FU US National Institute on Aging [R01AG030311]; US National Institute of Child Health and Human Development [R21 HD076164]; US Army Research Institute for the Behavioral and Social Sciences [W5J9CQ12C0049, W5J9CQ11C0046] FX This manuscript was supported by a US National Institute on Aging grant (R01AG030311), a US National Institute of Child Health and Human Development grant (R21 HD076164), and contracts from the US Army Research Institute for the Behavioral and Social Sciences (contracts W5J9CQ12C0049 and W5J9CQ11C0046) to Barrett. The views, opinions, and findings contained in this article are those of the authors and should not be construed as an official position, policy, or decision of the US National Institutes of Health or Department of the Army unless so designated by other documents. 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 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PY 2016 VL 39 AR e246 DI 10.1017/S0140525X15002770 PG 3 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA EJ0UE UT WOS:000392925200018 PM 28355867 ER PT J AU O'Callaghan, C Kveraga, K Shine, JM Adams, RB Bar, M AF O'Callaghan, Claire Kveraga, Kestutis Shine, James M. Adams, Reginald B., Jr. Bar, Moshe TI Convergent evidence for top-down effects from the "predictive brain" SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material C1 [O'Callaghan, Claire] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. [Kveraga, Kestutis] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Harvard Med Sch, Boston, MA 02129 USA. [Shine, James M.] Stanford Univ, Sch Psychol, Stanford, CA 94305 USA. [Adams, Reginald B., Jr.] Penn State Univ, Dept Psychol, University Pk, PA 16801 USA. [Bar, Moshe] Bar Ilan Univ, Gonda Ctr Brain Res, IL-5290002 Ramat Gan, Israel. RP O'Callaghan, C (reprint author), Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. EM co365@cam.ac.uk; kestas@nmr.mgh.harvard.edu; macshine@stanford.edu; radams@psu.edu; moshe.bar@biu.ac.il 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 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PY 2016 VL 39 AR e254 DI 10.1017/S0140525X15002599 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA EJ0UE UT WOS:000392925200026 PM 28355846 ER PT J AU Lin, WC Francis, JM Li, H Gao, XP Pedamallu, CS Ernst, P Meyerson, M AF Lin, Wenchu Francis, Joshua M. Li, Hong Gao, Xiaoping Pedamallu, Chandra Sekhar Ernst, Patricia Meyerson, Matthew TI Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets SO CANCER BIOLOGY & THERAPY LA English DT Article DE Kmt2a; Men1; methyltransferase; PanNETs; tumorigenesis ID HEMATOPOIETIC STEM-CELLS; MIXED-LINEAGE LEUKEMIA; NEUROENDOCRINE TUMORS; MLL; EPIDEMIOLOGY; MICE AB The reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlying this disease. The Men1 knockout mouse model recapitulates the early stage of human PanNET development and can serve as a foundation for the development of advanced mouse models that are necessary for preclinical testing. Menin, the product of the MEN1 gene, has been shown to physically interact with the KMT2A and KMT2B histone methyltransferases. Both the KMT2A and MEN1 genes are located on chromosome 11q, which frequently undergoes loss of heterozygosity (LOH) in PanNETs. We report herein that inactivation of Kmt2a in Men1-deficient mice accelerated pancreatic islet tumorigenesis and shortened the average life span. Increases in cell proliferation were observed in mouse pancreatic islet tumors upon inactivation of both Kmt2a and Men1. The Kmt2a/Men1 double knockout mouse model can be used as a mouse model to study advanced PanNETs. C1 [Lin, Wenchu; Li, Hong; Gao, Xiaoping] Chinese Acad Sci, High Magnet Field Lab, 350 Shushanhu Rd,Rm 410,Bldg 2, Hefei 230031, Anhui, Peoples R China. [Lin, Wenchu; Francis, Joshua M.; Pedamallu, Chandra Sekhar; Meyerson, Matthew] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Lin, Wenchu; Francis, Joshua M.; Pedamallu, Chandra Sekhar; Meyerson, Matthew] Harvard Med Sch, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA USA. [Francis, Joshua M.; Pedamallu, Chandra Sekhar; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Ernst, Patricia] Univ Colorado, Dept Pediat, Anschutz Med Campus, Aurora, CO USA. RP Lin, WC (reprint author), Chinese Acad Sci, High Magnet Field Lab, 350 Shushanhu Rd,Rm 410,Bldg 2, Hefei 230031, Anhui, Peoples R China. EM wenchu@hmfl.ac.cn FU NHLBI NIH HHS [R01 HL090036] NR 24 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2016 VL 17 IS 12 BP 1274 EP 1281 DI 10.1080/15384047.2016.1250986 PG 8 WC Oncology SC Oncology GA EI9KR UT WOS:000392827300006 PM 27801610 ER PT J AU Groner, AC Brown, M Theurillat, JP AF Groner, Anna C. Brown, Myles Theurillat, Jean-Philippe TI Targeting transcriptional co-activators in advanced prostate cancer SO CELL CYCLE LA English DT Editorial Material DE Bromodomain; LXXLL motif; prostate cancer progression; targeting androgen receptor-mediated transcription; TRIM24 C1 [Groner, Anna C.; Brown, Myles] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Groner, Anna C.; Brown, Myles] Harvard Med Sch, Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA USA. [Theurillat, Jean-Philippe] Oncol Inst Southern Switzerland, Inst Oncol Res, Bellinzona, Switzerland. [Theurillat, Jean-Philippe] Univ Lausanne, Univ Vaudois, Ctr Hosp, Fac Biol & Med, Lausanne, Switzerland. RP Theurillat, JP (reprint author), Oncol Res Inst, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. EM JeanP_Theurillat@ior.iosi.ch NR 7 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2016 VL 15 IS 24 BP 3333 EP 3334 DI 10.1080/15384101.2016.1229019 PG 2 WC Cell Biology SC Cell Biology GA EI9MR UT WOS:000392832700008 PM 27610751 ER PT J AU Ng, MY Eckshtain, D Weisz, JR AF Ng, Mei Yi Eckshtain, Dikla Weisz, John R. TI Assessing Fit Between Evidence-Based Psychotherapies for Youth Depression and Real-Life Coping in Early Adolescence SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID RELAXATION AB The modest efficacy of psychological interventions for youth depression, including evidence-based psychotherapies (EBPs), suggests a question: Do the therapy components match the coping strategies youths find helpful when dealing with depressed mood? Answering this question may help strengthen treatments. We asked 105 middle schoolers across a range of depression symptom levels to identify the coping strategies they used when they felt sad (habitual responses) and those that made them feel better (perceived-effective responses). Habitual and perceived-effective responses were coded for resemblance to EBPs, and each youth's habitual responses were coded for their match to the youth's perceived-effective responses. Most perceived-effective responses (92.6%) matched EBP components (most frequent: Behavioral Activation); however, 65.0% of the EBP components did not match any youth's habitual or perceived-effective responses. Youths at higher depression symptom levels were significantly more likely than low-symptom youths to report (a) habitual responses that did not match EBP components, (b) habitual responses that did not match their own perceived-effective responses, and (c) perceiving no effective response. The higher their depression symptom level, the less likely youths were to use strategies identified by researchers and perceived by themselves as effective, and the less likely they were to identify any perceived-effective coping strategy. The findings suggest a need to (a) determine which EBP components do in fact enhance youth coping, (b) design the most effective ways to help youths master those effective components, and (c) facilitate more frequent use of those strategies the youths already find effective. C1 [Ng, Mei Yi; Weisz, John R.] Harvard Univ, Dept Psychol, William James Hall 902,33 Kirkland St, Cambridge, MA 02138 USA. [Eckshtain, Dikla] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Eckshtain, Dikla] Harvard Med Sch, Boston, MA USA. RP Ng, MY (reprint author), Harvard Univ, Dept Psychol, William James Hall 902,33 Kirkland St, Cambridge, MA 02138 USA. EM myng@fas.harvard.edu FU NIMH NIH HHS [K23 MH093491, R01 MH068806] NR 13 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1537-4416 EI 1537-4424 J9 J CLIN CHILD ADOLESC JI J. Clin. Child Adolesc. Psychol. PY 2016 VL 45 IS 6 BP 732 EP 748 DI 10.1080/15374416.2015.1041591 PG 17 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA EJ1JD UT WOS:000392965500004 PM 26043230 ER PT J AU Solinsky, R Svircev, JN James, JJ Burns, SP Bunnell, AE AF Solinsky, Ryan Svircev, Jelena N. James, Jennifer J. Burns, Stephen P. Bunnell, Aaron E. TI A retrospective review of safety using a nursing driven protocol for autonomic dysreflexia in patients with spinal cord injuries SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Review DE Autonomic dysreflexia; Spinal cord injuries; Hydralazine; Nitroglycerin ID AMBULATORY BLOOD-PRESSURE; MANAGEMENT; COMPLICATIONS; HYPERTENSION; BLADDER; BLOCKER; AGE AB Objective/Background: Autonomic dysreflexia is a potentially life-threatening condition which afflicts a significant proportion of individuals with spinal cord injuries (SCI). To date, the safety and efficacy of several commonly used interventions for this condition have not been studied. Design: A retrospective chart review of the safety of a previously implemented nursing driven inpatient autonomic dysreflexia protocol. Methods: Seventy-eight male patients with SCI who experienced autonomic dysreflexia while inpatient at our Veterans Affairs SCI unit over a 3-1/2-year period were included. The safety of a nursing driven protocol utilizing conservative measures, nitroglycerin paste, and oral hydralazine was evaluated. Outcome Measures: Occurrence of adverse events and relative hypotensive events during all episodes treated with the protocol, and efficacy of attaining target blood pressure for all episodes with protocol adherence and for initial episode experienced by each patient. Results: Four hundred forty-five episodes of autonomic dysreflexia were recorded in the study period, with 92% adherence to the protocol. When the protocol was followed, target blood pressure was achieved for 97.6% of all episodes. Twenty-three total adverse events occurred (5.2% of all episodes). All adverse events were due to hypotension and only 0.9% required interventions beyond clinical monitoring. Of each patient's initial autonomic dysreflexia episode, 97.3% resolved using the protocol without need for further escalation of care. Conclusion: This inpatient nursing driven-protocol for treating autonomic dysreflexia utilizing conservative measures, nitroglycerin paste and oral hydralazine achieved target blood pressure with a high success rate and a low incidence of adverse events. C1 [Solinsky, Ryan; Svircev, Jelena N.; Burns, Stephen P.; Bunnell, Aaron E.] Univ Washington, Dept Rehabil Med, 1959 NE Pacific St, Seattle, WA 98195 USA. [Svircev, Jelena N.; Burns, Stephen P.] Vet Affairs Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. [James, Jennifer J.] Northwest Phys Med, Seattle, WA USA. [Bunnell, Aaron E.] Harborview Med Ctr, Seattle, WA USA. RP Solinsky, R (reprint author), Univ Washington, Dept Rehabil Med, 1959 NE Pacific St, Seattle, WA 98195 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PY 2016 VL 39 IS 6 BP 713 EP 719 DI 10.1080/10790268.2015.1118186 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA EJ0RI UT WOS:000392917600014 PM 26838482 ER PT J AU Menon, BB Zhou, XH Spurr-Michaud, S Rajaiya, J Chodosh, J Gipsona, IK AF Menon, Balaraj B. Zhou, Xiaohong Spurr-Michaud, Sandra Rajaiya, Jaya Chodosh, James Gipsona, Ilene K. TI Epidemic Keratoconjunctivitis-Causing Adenoviruses Induce MUC16 Ectodomain Release To Infect Ocular Surface Epithelial Cells SO MSPHERE LA English DT Article DE adenoviruses; keratoconjunctivitis; mucin ID MEDIATED GENE-TRANSFER; HUMAN CORNEAL-LIMBAL; USES SIALIC-ACID; CELLULAR RECEPTOR; TETHERED MUCINS; OVARIAN-CANCER; SEA DOMAIN; IN-VIVO; BARRIER; GLYCOCALYX AB Human adenoviruses (HAdV), species D in particular (HAdV-D), are frequently associated with epidemic keratoconjunctivitis (EKC). Although the infection originates at the ocular surface epithelium, the mechanisms by which HAdV-Ds bypass the membrane-associated mucin (MAM)-rich glycocalyx of the ocular surface epithelium to trigger infection and inflammation remain unknown. Here, we report that an EKC-causing adenovirus (HAdV-D37), but not a non-EKC-causing one (HAdVD19p), induces ectodomain release of MUC16-a MAM with barrier functions at the ocular surface-from cultured human corneal and conjunctival epithelial cells. HAdVD37, but not HAdV-D19p, is also found to decrease the glycocalyx barrier function of corneal epithelial cells, as determined by rose bengal dye penetrance assays. Furthermore, results from quantitative PCR (qPCR) amplification of viral genomic DNA using primers specific to a conserved region of the E1B gene show that, in comparison to infection by HAdV-D19p, infection by HAdV-D37 is significantly increased in corneal epithelial cells. Collectively, these results point to a MUC16 ectodomain release-dependent mechanism utilized by the EKC-causing HAdV-D37 to initiate infection at the ocular surface. These findings are important in terms of understanding the pathogenesis of adenoviral keratoconjunctivitis. Similar MAM ectodomain release mechanisms may be prevalent across other mucosal epithelia in the body (e.g., the airway epithelium) that are prone to adenoviral infection. IMPORTANCE Human adenoviruses (HAdVs) are double-stranded DNA viruses that cause infections across all mucosal tissues in the body. At the ocular surface, HAdVs cause keratoconjunctivitis (E. Ford, K. E. Nelson, and D. Warren, Epidemiol Rev 9: 244-261, 1987, and C. M. Robinson, D. Seto, M. S. Jones, D. W. Dyer, and J. Chodosh, Infect Genet Evol 11: 1208-1217, 2011, doi: 10.1016/j.meegid.2011.04.031)-a highly contagious infection that accounts for nearly 60% of conjunctivitis cases in the United States (R. P. Sambursky, N. Fram, and E. J. Cohen, Optometry 78: 236-239, 2007, doi: 10.1016/j.optm.2006.11.012, and A. M. Pihos, J Optom 6: 69-74, 2013, doi: 10.1016/j.optom.2012.08.003). The infection begins with HAdV entry within ocular surface epithelial cells; however, the mechanisms used by HAdVs to transit the otherwise protective mucosal barrier of ocular surface epithelial cells prior to entry remain unknown. Here, we report that the highly virulent keratoconjunctivitis-causing HAdV-D37 induces release of the extracellular domain (ectodomain) of MUC16, a major component of the mucosal barrier of ocular surface epithelial cells, prior to infecting underlying cells. Currently, there is no specific treatment for controlling this infection. Understanding the early steps involved in the pathogenesis of keratoconjunctivitis and using this information to intercept adenoviral entry within cells may guide the development of novel strategies for controlling the infection. C1 [Menon, Balaraj B.; Spurr-Michaud, Sandra; Gipsona, Ilene K.] Harvard Med Sch, Schepens Eye Res Inst, Boston, MA 02115 USA. [Zhou, Xiaohong; Rajaiya, Jaya; Chodosh, James] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Menon, Balaraj B.; Zhou, Xiaohong; Spurr-Michaud, Sandra; Rajaiya, Jaya; Chodosh, James; Gipsona, Ilene K.] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA. EM raj_menon@meei.harvard.edu FU Research to Prevent Blindness (RPB); HHS \ NIH \ National Eye Institute (NEI) [EY018850, EY013124, EY021558]; Falk Foundation; Massachusetts Lions Eye Research Fund (MLERF) FX Research to Prevent Blindness (RPB) provided funding to James Chodosh. HHS vertical bar NIH vertical bar National Eye Institute (NEI) provided funding to Ilene K. Gipson under grant number EY018850. HHS vertical bar NIH vertical bar National Eye Institute (NEI) provided funding to James Chodosh under grant number EY013124. HHS vertical bar NIH vertical bar National Eye Institute (NEI) provided funding to Jaya Rajaiya under grant number EY021558. Falk Foundation provided funding to James Chodosh. Massachusetts Lions Eye Research Fund (MLERF) provided funding to James Chodosh. NR 45 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2379-5042 J9 MSPHERE JI mSphere PD JAN-FEB PY 2016 VL 1 IS 1 AR e00112-15 DI 10.1128/mSphere.00112-15 PG 8 WC Microbiology SC Microbiology GA EI6CX UT WOS:000392583700039 ER PT S AU Ibrahim, A Kirouac-Turmel, M Sharma, G Singh, K Ferachou, D Ozaki, T AF Ibrahim, A. Kirouac-Turmel, M. Sharma, G. Singh, K. Ferachou, D. Ozaki, T. GP IEEE TI Advanced techniques for terahertz detection using spectral-domain interferometry SO 2016 41ST INTERNATIONAL CONFERENCE ON INFRARED, MILLIMETER, AND TERAHERTZ WAVES (IRMMW-THZ) SE International Conference on Infrared Millimeter and Terahertz Waves LA English DT Proceedings Paper CT 41st International Conference on Infrared, Millimeter, and Terahertz Waves (IRMMW-THz) CY SEP 25-30, 2016 CL Copenhagen, DENMARK SP DTU, IEEE, QMC Instruments, Danish Ctr Laser Infrastructure, DTU Fotonik, Dept Photon Engn, ARL, CARLSBERG FDN, AF OFF SCI RES, Tech Univ Denmark, IEEE Microwave Theory & Tech Soc, Azpect Photon, Ekspla, Hubner HF Syst Engn, I2S, Laser Quantum, Menlo Syst, Neaspec, Springer, TeraView, Virginia Diodes ID RADIATION AB We demonstrate and compare the use of Mach-Zehnder and the fiber based interferometer schemes in improving the performance of terahertz electric field measurements based on spectral-domain interferometry. The new schemes enable unlimited temporal scanning window without significant loss in the signal-to-noise ratio, thus overcoming a major limitation in conventional spectral-domain interferometry techniques for terahertz electric field detection. Moreover, both detection techniques offer significantly higher dynamic range compared to the conventional electro-optic sampling technique. C1 [Ibrahim, A.; Kirouac-Turmel, M.; Ferachou, D.; Ozaki, T.] Univ Quebec, INRS EMT, Adv Laser Light Source, 1650 Blvd Lionel Boulet, Varennes, PQ J3X 1S2, Canada. [Sharma, G.] Univ Massachusetts Lowell, 1 Univ Ave, Lowell, MA 01854 USA. [Singh, K.] Harvard Med Sch, Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA. RP Ibrahim, A (reprint author), Univ Quebec, INRS EMT, Adv Laser Light Source, 1650 Blvd Lionel Boulet, Varennes, PQ J3X 1S2, Canada. NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2162-2027 BN 978-1-4673-8485-8 J9 INT CONF INFRA MILLI PY 2016 PG 2 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BG7KC UT WOS:000391406200671 ER PT J AU Suh, CH Tirumani, SH Keraliya, A Kim, KW Ramaiya, NH Shinagare, AB AF Suh, Chong Hyun Tirumani, Sree H. Keraliya, Abhishek Kim, Kyung Won Ramaiya, Nikhil H. Shinagare, Atul B. TI Molecular targeted therapy in gynaecologic malignancies: primer for radiologists SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID RENAL-CELL CARCINOMA; RECURRENT ENDOMETRIAL CARCINOMA; GROWTH-FACTOR RECEPTOR; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CHEMOTHERAPY PLUS RITUXIMAB; GUIDELINE VERSION 1.1; OF-THE-LITERATURE; PHASE-III TRIAL; OVARIAN-CANCER; ONCOLOGY-GROUP AB The identification of characteristic genetic alteration in gynaecological malignancies has opened the door for molecular targeted therapy. The purpose of this review is to provide a primer for the radiologist on these agents with emphasis on the role of imaging in treatment response assessment and drug toxicities. The use of targeted therapy in gynaecological malignancies will likely increase in the future and make the role of the radiologist critical in response assessment and detection of toxicities. C1 [Suh, Chong Hyun; Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul, South Korea. [Suh, Chong Hyun; Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul, South Korea. [Suh, Chong Hyun] Namwon Med Ctr, Dept Radiol, Namwon Si, Jeollabuk Do, South Korea. [Tirumani, Sree H.; Keraliya, Abhishek; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Med Sch, Dana Farber Canc Inst, Dept Imaging, Boston, MA USA. [Tirumani, Sree H.; Keraliya, Abhishek; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. RP Suh, CH (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul, South Korea.; Suh, CH (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul, South Korea.; Suh, CH (reprint author), Namwon Med Ctr, Dept Radiol, Namwon Si, Jeollabuk Do, South Korea. EM jhsuh04@gmail.com NR 98 TC 0 Z9 0 U1 1 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PY 2016 VL 89 IS 1066 AR 20160086 DI 10.1259/bjr.20160086 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI4XO UT WOS:000392497400007 PM 27331884 ER PT J AU Sturgeon, C Fasano, A AF Sturgeon, Craig Fasano, Alessio TI Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases SO TISSUE BARRIERS LA English DT Review DE autoimmune disease; barrier function; intestinal permeability; tight junctions; zonulin ID INCREASED INTESTINAL PERMEABILITY; EXPERIMENTAL NECROTIZING ENTEROCOLITIS; PROTEASE-ACTIVATED RECEPTOR-2; CELIAC GLUTEN SENSITIVITY; IRRITABLE-BOWEL-SYNDROME; TIGHT JUNCTIONS; CROHNS-DISEASE; OCCLUDENS TOXIN; LARAZOTIDE ACETATE; HAPTOGLOBIN POLYMORPHISM AB Beside digesting nutrients and absorbing solutes and electrolytes, the intestinal epithelium with its barrier function is in charge of a tightly controlled antigen trafficking from the intestinal lumen to the submucosa. This trafficking dictates the delicate balance between tolerance and immune response causing inflammation. Loss of barrier function secondary to upregulation of zonulin, the only known physiological modulator of intercellular tight junctions, leads to uncontrolled influx of dietary and microbial antigens. Additional insights on zonulin mechanism of action and the recent appreciation of the role that altered intestinal permeability can play in the development and progression of chronic inflammatory disorders has increased interest of both basic scientists and clinicians on the potential role of zonulin in the pathogenesis of these diseases. This review focuses on the recent research implicating zonulin as a master regulator of intestinal permeability linked to the development of several chronic inflammatory disorders. C1 [Sturgeon, Craig; Fasano, Alessio] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Ctr Celiac Res & Treatment, Boston, MA 02114 USA. [Sturgeon, Craig; Fasano, Alessio] Div Pediat Gastroenterol & Nutr, Boston, MA USA. [Sturgeon, Craig] Univ Maryland, Sch Med, Grad Program Life Sci, Baltimore, MD 21201 USA. [Fasano, Alessio] EBRIS, Salerno, Italy. RP Fasano, A (reprint author), Massachusetts Gen Hosp Children, 175 Cambridge St, Boston, MA 02114 USA. EM afasano@mgh.harvard.edu FU NIH [DK048373] FX This work was supported by NIH grant DK048373. NR 153 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 2168-8370 J9 TISSUE BARRIERS JI Tissue Barriers PY 2016 VL 4 IS 4 AR e1251384 DI 10.1080/21688370.2016.1251384 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EI4XE UT WOS:000392496300004 PM 28123927 ER PT S AU Charan, K Heberle, D Lin, CP Xu, C AF Charan, Kriti Heberle, Dylan Lin, Charles P. Xu, Chris GP IEEE TI High pulse energy, tunable repetition rate source for two-photon microscopy SO 2016 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 05-10, 2016 CL San Jose, CA AB Multiphoton microscopy requires balancing high peak powers for depth penetration with low average powers to prevent thermal damage. We demonstrate a wavelength-tunable source with 27 to 48 nJ pulse energy and an adjustable repetition rate. C1 [Charan, Kriti; Heberle, Dylan; Xu, Chris] Cornell Univ, Sch Appl Engn & Phys, Ithaca, NY 14853 USA. [Lin, Charles P.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Lin, Charles P.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA. RP Charan, K (reprint author), Cornell Univ, Sch Appl Engn & Phys, Ithaca, NY 14853 USA. EM kc636@cornell.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-9435-8011-8 J9 CONF LASER ELECTR PY 2016 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BG7HE UT WOS:000391286402113 ER PT S AU Cho, S Humar, M Yun, SH AF Cho, Sangyeon Humar, Matjaz Yun, Seok-Hyun GP IEEE TI Laser-particle stimulated emission (LASE) microscopy with super resolution SO 2016 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 05-10, 2016 CL San Jose, CA ID FLUORESCENCE AB We introduce a novel microscopy technique that utilizes optically pumped, nano-lasers as imaging probes. The lasing threshold and narrow spectrum of laser particles enables optical sectioning, sub-diffraction, and low-background imaging. Using nanowire lasers, we demonstrate similar to 180 nm resolution with large beam sizes of a few microns (>10-fold enhancement). C1 [Cho, Sangyeon; Humar, Matjaz; Yun, Seok-Hyun] Harvard Med Sch, Dept Dermatol, Wellman Ctr Photomed, 65 Landsdowne St Up 5, Cambridge, MA 02139 USA. [Cho, Sangyeon; Humar, Matjaz; Yun, Seok-Hyun] Massachusetts Gen Hosp, 65 Landsdowne St Up 5, Cambridge, MA 02139 USA. [Cho, Sangyeon; Yun, Seok-Hyun] MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Humar, Matjaz] J Stefan Inst, Condensed Matter Dept, Jamova 39, Ljubljana 1000, Slovenia. RP Cho, S (reprint author), Harvard Med Sch, Dept Dermatol, Wellman Ctr Photomed, 65 Landsdowne St Up 5, Cambridge, MA 02139 USA.; Cho, S (reprint author), Massachusetts Gen Hosp, 65 Landsdowne St Up 5, Cambridge, MA 02139 USA.; Cho, S (reprint author), MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM sycho@mit.edu NR 3 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-9435-8011-8 J9 CONF LASER ELECTR PY 2016 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BG7HE UT WOS:000391286400056 ER PT S AU Villiger, M Karanasos, A Ren, J Lippok, N Shishkov, M van Soest, G Nadkarni, S Regar, E Bouma, BE AF Villiger, Martin Karanasos, Antonios Ren, Jian Lippok, Norman Shishkov, Milen van Soest, Gijs Nadkarni, Seemantini Regar, Evelyn Bouma, Brett E. GP IEEE TI Intravascular polarization sensitive optical coherence tomography in human patients SO 2016 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 05-10, 2016 CL San Jose, CA ID MODE DISPERSION; ARTIFACTS AB Polarization sensitive optical coherence tomography (PS-OCT) provides measures of tissue birefringence and depolarization. Here, we demonstrate catheter-based PS-OCT in the coronary arteries of human patients to obtain valuable insight into the morphology of atherosclerotic plaques. C1 [Villiger, Martin; Ren, Jian; Lippok, Norman; Shishkov, Milen; Nadkarni, Seemantini; Bouma, Brett E.] Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA. [Villiger, Martin; Ren, Jian; Lippok, Norman; Shishkov, Milen; Nadkarni, Seemantini; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. [Karanasos, Antonios; van Soest, Gijs; Regar, Evelyn] Erasmus MC, Thorax Ctr, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands. RP Villiger, M (reprint author), Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA.; Villiger, M (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM mvilliger@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 3 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-9435-8011-8 J9 CONF LASER ELECTR PY 2016 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BG7HE UT WOS:000391286400161 ER PT J AU Melton, BL Zillich, AJ Saleem, JJ Russ, AL Tisdale, JE Overholser, BR AF Melton, Brittany L. Zillich, Alan J. Saleem, Jason J. Russ, Alissa L. Tisdale, James E. Overholser, Brian R. TI Iterative Development and Evaluation of a Pharmacogenomic-Guided Clinical Decision Support System for Warfarin Dosing SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Clinical decision support systems; pharmacogenetics; CPOE; computer-assisted drug therapy; warfarin ID PERSONALIZED MEDICINE; RANDOMIZED-TRIAL; IMPLEMENTATION; PROGRAM; ANTICOAGULATION; INFORMATICS; UNIVERSITY; PROJECT; SERVICE; DESIGN AB Objective: Pharmacogenomic-guided dosing has the potential to improve patient outcomes but its implementation has been met with clinical challenges. Our objective was to develop and evaluate a clinical decision support system (CDSS) for pharmacogenomic-guided warfarin dosing designed for physicians and pharmacists. Methods: Twelve physicians and pharmacists completed 6 prescribing tasks using simulated patient scenarios in two iterations (development and validation phases) of a newly developed pharmacogenomic-driven CDSS prototype. For each scenario, usability was measured via efficiency, recorded as time to task completion, and participants' perceived satisfaction which were compared using Kruskal-Wallis and Mann Whitney U tests, respectively. Debrief interviews were conducted and qualitatively analyzed. Usability findings from the first (i.e. development) iteration were incorporated into the CDSS design for the second (i.e. validation) iteration. Results: During the CDSS validation iteration, participants took more time to complete tasks with a median (IQR) of 183 (124-247) seconds versus 101 (73.5-197) seconds in the development iteration (p=0.01). This increase in time on task was due to the increase in time spent in the CDSS corresponding to several design changes. Efficiency differences that were observed between pharmacists and physicians in the development iteration were eliminated in the validation iteration. The increased use of the CDSS corresponded to a greater acceptance of CDSS recommended doses in the validation iteration (4% in the first iteration vs. 37.5% in the second iteration, p<0.001). Overall satisfaction did not change statistically between the iterations but the qualitative analysis revealed greater trust in the second prototype. Conclusions: A pharmacogenomic-guided CDSS has been developed using warfarin as the test drug. The final CDSS prototype was trusted by prescribers and significantly increased the time using the tool and acceptance of the recommended doses. This study is an important step toward incorporating pharmacogenomics into CDSS design for clinical testing. C1 [Melton, Brittany L.] Univ Kansas, Sch Pharm, Lawrence, KS 66045 USA. [Zillich, Alan J.; Russ, Alissa L.; Tisdale, James E.; Overholser, Brian R.] Purdue Univ, Coll Pharm, Res Inst 2,Room 402,950 W Walnut St, Indianapolis, IN 46202 USA. [Zillich, Alan J.; Russ, Alissa L.] US Dept Vet Affairs, Ctr Hlth Informat & Commun, Vet Hlth Adm, Hlth Serv Res & Dev, Washington, DC USA. [Zillich, Alan J.; Russ, Alissa L.] Regenstrief Inst Inc, Indianapolis, IN USA. [Zillich, Alan J.; Russ, Alissa L.] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Bloomington, IN 47405 USA. [Saleem, Jason J.] Univ Louisville, Dept Ind Engn, Louisville, KY 40292 USA. [Tisdale, James E.; Overholser, Brian R.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Overholser, BR (reprint author), Purdue Univ, Coll Pharm, Res Inst 2,Room 402,950 W Walnut St, Indianapolis, IN 46202 USA. EM boverhol@purdue.edu FU Lilly seed grant; VA HSR&D Research Career Development Award [CDA 11-214]; National Heart, Lung, and Blood Institute, National Institutes of Health (Bethesda, MD) [K08HL095655] FX This work was supported by a Lilly seed grant to the Purdue University College of Pharmacy. Drs. Russ was supported in part by a VA HSR&D Research Career Development Award (CDA 11-214) and Dr. Overholser was supported in part by K08HL095655 (BRO) from the National Heart, Lung, and Blood Institute, National Institutes of Health (Bethesda, MD). Views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the U.S. government. NR 45 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2016 VL 7 IS 4 BP 1088 EP 1106 DI 10.4338/ACI-2016-05-RA-0081 PG 19 WC Medical Informatics SC Medical Informatics GA EH7MZ UT WOS:000391958400012 PM 27878205 ER PT J AU Brinker, TJ Holzapfel, J Baudson, TG Sies, K Jakob, L Baumert, HM Heckl, M Cirac, A Suhre, JL Mathes, V Fries, FN Spielmann, H Rigotti, N Seeger, W Herth, F Groneberg, DA Raupach, T Gall, H Bauer, C Marek, P Batra, A Harrison, CH Taha, L Owczarek, A Hofmann, FJ Thomas, R Mons, U Kreuter, M AF Brinker, Titus J. Holzapfel, Julia Baudson, Tanja G. Sies, Katharina Jakob, Lena Baumert, Hannah Maria Heckl, Marlene Cirac, Ana Suhre, Janina L. Mathes, Verena Fries, Fabian N. Spielmann, Hannah Rigotti, Nancy Seeger, Werner Herth, Felix Groneberg, David A. Raupach, Tobias Gall, Henning Bauer, Claudia Marek, Pat Batra, Anil Harrison, Chase H. Taha, Lava Owczarek, Andreas Hofmann, Felix J. Thomas, Roger Mons, Ute Kreuter, Michael TI Photoaging smartphone app promoting poster campaign to reduce smoking prevalence in secondary schools: the Smokerface Randomized Trial: design and baseline characteristics SO BMJ OPEN LA English DT Article ID HEALTH-EDUCATION; MOBILE APPS; HAIR LOSS; ADOLESCENTS; CESSATION; OPPORTUNITY; PREVENTION; GERMANY; ACNE; LONG AB Introduction: Smoking is the largest cause of preventable death globally. Most smokers smoke their first cigarette in early adolescence. We took advantage of the widespread availability of mobile phones and adolescents' interest in appearance to develop a free photoaging app which is promoted via a poster campaign in secondary schools. This study aims to evaluate its effectiveness regarding smoking prevalence and students' attitudes towards smoking. Methods and analysis: A randomised controlled trial is conducted with 9851 students of both genders with an average age of 12 years in grades 6 and 7 of 126 secondary schools in Germany. At present, cigarette smoking prevalence in our sample is 4.7%, with 4.6% of the students currently using e-cigarettes (1.6% use both). The prospective experimental study design includes measurements at baseline and at 6, 12 and 24 months postintervention via a questionnaire plus a random cotinine saliva sample at 24 months postintervention. The study groups consist of randomised schools receiving the Smokerface poster campaign and control schools with comparable baseline data (no intervention). The primary end point is the difference of change in smoking prevalence in the intervention group versus the difference in the control group at 24 months follow-up. Longitudinal changes in smoking-related attitudes, the number of new smokers and quitters and the change in the number of never-smokers will be compared between the two groups as secondary outcomes. Ethics and dissemination: Ethical approval was obtained from the ethics committee of the University of Giessen and the ministries of cultural affairs, both in Germany. Results will be disseminated at conferences, in peer-reviewed journals, on our websites and throughout the multinational Education Against Tobacco network. C1 [Brinker, Titus J.; Holzapfel, Julia; Mathes, Verena; Seeger, Werner; Gall, Henning; Owczarek, Andreas; Hofmann, Felix J.] Justus Liebig Univ Giessen, UGMLC, Giessen, Germany. [Brinker, Titus J.; Holzapfel, Julia; Mathes, Verena; Seeger, Werner; Gall, Henning; Owczarek, Andreas; Hofmann, Felix J.] Justus Liebig Univ Giessen, German Ctr Lung Res DZL, Giessen, Germany. [Baudson, Tanja G.] Univ Duisburg Essen, Essen, Germany. [Sies, Katharina; Jakob, Lena; Baumert, Hannah Maria] Univ Freiburg, Freiburg, Germany. [Heckl, Marlene; Cirac, Ana] Tech Univ Munich, Munich, Germany. [Suhre, Janina L.] Univ Bonn, Bonn, Germany. [Fries, Fabian N.; Spielmann, Hannah] Saarland Univ, Med Ctr, Homburg, Germany. [Fries, Fabian N.; Spielmann, Hannah] Saarland Univ, Fac Med, Homburg, Germany. [Rigotti, Nancy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herth, Felix; Bauer, Claudia; Kreuter, Michael] Heidelberg Univ, Pulm & Resp Crit Care Med, TLRCH, Heidelberg, Germany. [Herth, Felix; Bauer, Claudia; Kreuter, Michael] Heidelberg Univ, German Ctr Lung Res DZL, Heidelberg, Germany. [Groneberg, David A.] Goethe Univ, Inst Occupat Med Social Med & Environm Med, Frankfurt, Germany. [Raupach, Tobias] Univ Med Ctr, Dept Cardiol & Pneumol, Gottingen, Germany. [Marek, Pat] Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Batra, Anil] Univ Hosp Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany. [Harrison, Chase H.] Harvard Univ, Fac Arts & Sci, Dept Govt, Cambridge, MA 02138 USA. [Taha, Lava] Univ Erlangen Nurnberg, Erlangen, Germany. [Thomas, Roger] Univ Calgary, Hlth Sci Ctr, Calgary, AB, Canada. [Mons, Ute] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. RP Brinker, TJ (reprint author), Justus Liebig Univ Giessen, UGMLC, Giessen, Germany.; Brinker, TJ (reprint author), Justus Liebig Univ Giessen, German Ctr Lung Res DZL, Giessen, Germany. EM titus.brinker@gmail.com OI Brinker, Titus Josef/0000-0002-3620-5919; Groneberg, David/0000-0001-8551-6556; Fries, Fabian N./0000-0002-8526-4712 FU German Heart Foundation [94-96, 60323] FX The Smokerface Randomized Trial was funded by the German Heart Foundation (Bockenheimer Landstrasse 94-96, 60323 Frankfurt am Main, Germany). The German Heart Foundation had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review, or approval of the manuscript. NR 31 TC 0 Z9 0 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 11 AR e014288 DI 10.1136/bmjopen-2016-014288 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JQ UT WOS:000391303400019 PM 27821601 ER PT J AU Manchikanti, L Pampati, V Hirsch, JA AF Manchikanti, Laxmaiah Pampati, Vidyasagar Hirsch, Joshua A. TI Retrospective cohort study of usage patterns of epidural injections for spinal pain in the US fee-for-service Medicare population from 2000 to 2014 SO BMJ OPEN LA English DT Article ID LOW-BACK-PAIN; PREVENT NEUROLOGIC COMPLICATIONS; LUMBAR DISC HERNIATION; LONG-TERM RELIEF; CORTICOSTEROID INJECTIONS; INTERVENTIONAL TECHNIQUES; GLOBAL BURDEN; UNITED-STATES; STENOSIS; METAANALYSIS AB Objective: To assess the usage patterns of epidural injections for chronic spinal pain in the fee-for-service (FFS) Medicare population from 2000 to 2014 in the USA. Design: A retrospective cohort. Methods: The descriptive analysis of the administrative database from Centers for Medicare and Medicaid Services (CMS) Physician/Supplier Procedure Summary (PSPS) master data from 2000 to 2014 was performed. The guidance from Strengthening the Reporting of Observational studies in Epidemiology (STROBE) was applied. Analysis included multiple variables based on the procedures, specialties and geography. Results: Overall epidural injections increased 99% per 100 000 Medicare beneficiaries with an annual increase of 5% from 2000 to 2014. Lumbar interlaminar and caudal epidural injections constituted 36.2% of all epidural injections, with an overall decrease of 2% and an annual decrease of 0.2% per 100 000 Medicare beneficiaries. However, lumbosacral transforaminal epidural injections increased 609% with an annual increase of 15% from 2000 to 2014 per 100 000 Medicare population. Conclusions: Usage of epidural injections increased from 2000 to 2014, with a decline thereafter. However, an escalating growth has been seen for lumbosacral transforaminal epidural injections despite numerous reports of complications and regulations to curb the usage of transforaminal epidural injections. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Med Sch, Boston, MA USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, Paducah, KY USA.; Manchikanti, L (reprint author), Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. EM drlm@thepainmd.com NR 57 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 12 AR e013042 DI 10.1136/bmjopen-2016-013042 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JS UT WOS:000391303600092 PM 27965254 ER PT J AU Morillon, MB Stamp, L Taylor, W Fransen, J Dalbeth, N Singh, JA Christensen, R Lassere, M AF Morillon, Melanie B. Stamp, Lisa Taylor, William Fransen, Jaap Dalbeth, Nicola Singh, Jasvinder A. Christensen, Robin Lassere, Marissa TI Using serum urate as a validated surrogate end point for flares in patients with gout: protocol for a systematic review and meta-regression analysis SO BMJ OPEN LA English DT Review ID THRESHOLD EFFECT STE; HIERARCHICAL LEVELS; EVALUATION SCHEMA; MANAGEMENT; SURVIVAL; TRIALS; METAANALYSIS; CRITERIA; CANCER; HYPERURICEMIA AB Introduction: Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate. Our objective is to investigate the strength of the relationship between changes in serum urate in randomised controlled trials and changes in clinically relevant outcomes according to the 'Biomarker-Surrogacy Evaluation Schema version 3' (BSES3), documenting the validity of selected instruments by applying the 'OMERACT Filter 2.0'. Methods and analysis: A systematic review described in terms of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will identify all relevant studies. Standardised data elements will be extracted from each study by 2 independent reviewers and disagreements are resolved by discussion. The data will be analysed by meta-regression of the between-arm differences in the change in serum urate level (independent variable) from baseline to 3 months (or 6 and 12 months if 3-month values are not available) against flare rate, tophus size and number and pain at the final study visit (dependent variables). Ethics and dissemination: This study will not require specific ethics approval since it is based on analysis of published (aggregated) data. The intended audience will include healthcare researchers, policymakers and clinicians. Results of the study will be disseminated by peer-reviewed publications. C1 [Morillon, Melanie B.; Christensen, Robin] Copenhagen Univ Hosp, Parker Inst, Dept Rheumatol, Musculoskeletal Stat Unit, Frederiksberg, Denmark. [Morillon, Melanie B.] Odense Univ Hosp, Dept Rheumatol, Svendborg, Denmark. [Stamp, Lisa] Univ Otago, Dept Med, Christchurch, New Zealand. [Taylor, William] Univ Otago, Dept Med, Wellington, New Zealand. [Fransen, Jaap] Radboud Univ Nijmegen, Med Ctr, JF Dept Rheumatol, Nijmegen, Netherlands. [Dalbeth, Nicola] Univ Auckland, Dept Med, Auckland, New Zealand. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Lassere, Marissa] Univ NSW, St George Hosp, Dept Rheumatol, Sydney, NSW, Australia. RP Morillon, MB (reprint author), Copenhagen Univ Hosp, Parker Inst, Dept Rheumatol, Musculoskeletal Stat Unit, Frederiksberg, Denmark.; Morillon, MB (reprint author), Odense Univ Hosp, Dept Rheumatol, Svendborg, Denmark. EM melanie.birger.morillon@rsyd.dk OI Christensen, Robin/0000-0002-6600-0631 FU Oak Foundation FX Musculoskeletal Statistics Unit at the Parker Institute is supported by grants from the Oak Foundation. NR 26 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 9 AR e012026 DI 10.1136/bmjopen-2016-012026 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JL UT WOS:000391302900134 ER PT J AU Nieboer, D Douw, L van Dijk, BW Heymans, MW Stam, CJ Twisk, JWR AF Nieboer, Dagmar Douw, Linda van Dijk, Bob W. Heymans, Martijn W. Stam, Cornelis J. Twisk, Jos W. R. TI Relation between carotid stiffness, cognitive performance and brain connectivity in a healthy middle-aged population: an observational neurophysiological cohort study with magnetoencephalography SO BMJ OPEN LA English DT Article ID ARTERIAL STIFFNESS; FUNCTIONAL CONNECTIVITY; INDEPENDENT PREDICTOR; LONGITUDINAL CHANGES; MULTIPLE-SCLEROSIS; AMSTERDAM GROWTH; DISEASE; RISK; MEG; IMPAIRMENT AB Objective: Impaired blood flow of the carotid artery can result in cognitive impairment, but how these vascular impairments lead to global cognitive disturbances is largely unknown. Problems in functional connectivity between brain areas may be responsible for these widespread effects. Therefore, the aim of this study was to examine the association between carotid stiffness, functional connectivity and cognitive performance in relatively young and healthy adults before clinical vascular pathology occurs. Design: The Amsterdam Growth and Health Longitudinal Study: an observational study. Setting: Participants were included by attending 1 of the 2 selected secondary schools in The Netherlands. Participants: Men (n=110) and women (n=120) aged 41-44 years (42 +/- 0.7). Primary and secondary outcome measures: Data were obtained with regard to local carotid stiffness captured measured with the Young's elastic modulus (YEM). All participants underwent a commonly used Dutch intelligence test and resting-state eyes-closed magnetoencephalography (MEG). Five artefact-free epochs were analysed. The phase lag index (PLI) was used as a measure of functional connectivity between all sensors and was assessed in six frequency bands (delta-gamma). Results: Carotid stiffness was significantly associated with increased functional connectivity in the alpha 2 band in men (beta: 0.287; p=0.008). The same results were found for women in the beta band (beta: 0.216; p=0.040). Furthermore, carotid stiffness was associated with superior cognitive function in men (beta: 0.238; p=0.007). In addition, there was neither a significant association nor a consistent pattern between cognitive function and functional connectivity. Conclusions: The increased connectivity might be a maladaptive phenomenon caused by disinhibition of neurons which may explain the direction of the results. This study suggests that detection of increased (local) carotid stiffness may be promising to identify a disturbance in the organisation of the functional brain network, even before clinical vascular pathology occurs. C1 [Nieboer, Dagmar; Heymans, Martijn W.] Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Methodol & Appl Biostat, Amsterdam, Netherlands. [Douw, Linda] Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands. [Douw, Linda] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [van Dijk, Bob W.; Stam, Cornelis J.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Neurophysiol, Amsterdam, Netherlands. [van Dijk, Bob W.; Stam, Cornelis J.] Vrije Univ Amsterdam, Med Ctr, MEG Ctr, Amsterdam, Netherlands. [van Dijk, Bob W.] Vrije Univ Amsterdam, Med Ctr, Dept Phys & Med Technol, Amsterdam, Netherlands. [Heymans, Martijn W.; Twisk, Jos W. R.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. RP Nieboer, D (reprint author), Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Methodol & Appl Biostat, Amsterdam, Netherlands. EM d.nieboer@vu.nl FU Dairy Foundation; Netherlands Heart Foundation; Dutch Prevention Fund; Heineken BV; Ministry of Public Health, Well-being and Sport (VWS); Scientific Board of Smoking and Health; VU University; VU University Medical Centre FX This work was supported by grants from the Dairy Foundation, the Netherlands Heart Foundation, the Dutch Prevention Fund, Heineken BV, the Ministry of Public Health, Well-being and Sport (VWS), the Scientific Board of Smoking and Health, the VU University and the VU University Medical Centre since the start of the study in 1976. NR 54 TC 0 Z9 0 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 12 AR e013441 DI 10.1136/bmjopen-2016-013441 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JS UT WOS:000391303600113 PM 27979838 ER PT J AU Niles, BL Mori, DL Polizzi, CP Kaiser, AP Ledoux, AM Wang, CC AF Niles, Barbara L. Mori, DeAnna L. Polizzi, Craig P. Kaiser, Anica Pless Ledoux, Annie M. Wang, Chenchen TI Feasibility, qualitative findings and satisfaction of a brief Tai Chi mind-body programme for veterans with post-traumatic stress symptoms SO BMJ OPEN LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; ALTERNATIVE MEDICINE; PTSD SYMPTOMS; DISORDER; SAMPLE; COMORBIDITY; COMPLEMENTARY; PSYCHOTHERAPY; MINDFULNESS; PREVALENCE AB Objective: To examine feasibility, qualitative feedback and satisfaction associated with a 4-session introduction to Tai Chi for veterans with post-traumatic stress symptoms. Design: We observed and reported recruitment and retention rates, participant characteristics, adherence, and satisfaction across 2 cohorts. We also examined qualitative feedback provided by questionnaires, focus groups and individual interviews. Main outcome measures: Rates of recruitment and retention, focus group and individual feedback interviews, self-reported satisfaction. Participants: 17 veterans with post-traumatic stress symptoms. Results: Almost 90% (17/19) of those eligible following the telephone screen enrolled in the programme. Three-quarters (76.4%) of the participants attended at least 3 of the 4 Tai Chi sessions. Qualitative data analysis revealed themes indicating favourable impressions of the Tai Chi sessions. In addition, participants reported feeling very engaged during the sessions, and found Tai Chi to be helpful for managing distressing symptoms (ie, intrusive thoughts, concentration difficulties, physiological arousal). Participants also reported high satisfaction: 93.8% endorsed being very or mostly satisfied with the programme. All participants (100%) indicated that they would like to participate in future Tai Chi programmes and would recommend it to a friend. Conclusions: Tai Chi appears to be feasible and safe for veterans with symptoms of post-traumatic stress disorder (PTSD), is perceived to be beneficial and is associated with high rates of satisfaction. This study highlights the need for future investigation of Tai Chi as a novel intervention to address symptoms of PTSD. C1 [Niles, Barbara L.; Kaiser, Anica Pless] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Niles, Barbara L.; Mori, DeAnna L.; Kaiser, Anica Pless] Boston Univ, Sch Med, Boston, MA 02118 USA. [Mori, DeAnna L.; Polizzi, Craig P.; Ledoux, Annie M.] VA Boston Healthcare Syst, Boston, MA USA. [Polizzi, Craig P.; Ledoux, Annie M.] Natl Ctr PTSD, Boston, MA USA. [Wang, Chenchen] Tufts Univ, Sch Med, Tufts Med Ctr, Div Rheumatol,Ctr Integrat Med, Boston, MA 02111 USA. RP Niles, BL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA.; Niles, BL (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA. EM Barbara.Niles@va.gov FU National Center for Complementary and Integrative Health (NCCIH) [R01AT006367-01A1, K24AT007323]; National Center for PTSD FX This study was supported by the National Center for Complementary and Integrative Health (NCCIH; R01AT006367-01A1 and K24AT007323) and funds from the National Center for PTSD. NR 42 TC 0 Z9 0 U1 3 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 11 AR e012464 DI 10.1136/bmjopen-2016-012464 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JQ UT WOS:000391303400140 PM 27899398 ER PT J AU Zheng, JS Niu, KJ Jacobs, S Dashti, H Huang, T AF Zheng, Ju-Sheng Niu, Kaijun Jacobs, Simone Dashti, Hassan Huang, Tao TI Nutritional Biomarkers, Gene-Diet Interaction, and Risk Factors for Type 2 Diabetes SO JOURNAL OF DIABETES RESEARCH LA English DT Editorial Material ID IMPAIRED GLUCOSE-TOLERANCE; PREVENTION; HUMANS C1 [Zheng, Ju-Sheng] Univ Cambridge, Epidemiol Unit, MRC, Cambridge, England. [Niu, Kaijun] Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China. [Jacobs, Simone] Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany. [Dashti, Hassan] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. [Huang, Tao] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore. RP Zheng, JS (reprint author), Univ Cambridge, Epidemiol Unit, MRC, Cambridge, England. EM jusheng.zheng@mrc-epid.cam.ac.uk NR 10 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-6745 EI 2314-6753 J9 J DIABETES RES JI J. Diabetes Res. PY 2016 AR 8610501 DI 10.1155/2016/8610501 PG 2 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA EH8AI UT WOS:000391993600001 ER PT J AU Shu, YL Tao, Y Li, WY Shen, J Wang, ZM Chen, ZY AF Shu, Yilai Tao, Yong Li, Wenyan Shen, Jun Wang, Zhengmin Chen, Zheng-Yi TI Adenovirus Vectors Target Several Cell Subtypes of Mammalian Inner Ear In Vivo SO NEURAL PLASTICITY LA English DT Article ID HAIR-CELLS; GENE-TRANSFER; ADENOASSOCIATED VIRUS; SUPPORTING CELLS; ACOUSTIC TRAUMA; COCHLEAR FUNCTION; SCALA MEDIA; REGENERATION; EXPRESSION; DELIVERY AB Mammalian inner ear harbors diverse cell types that are essential for hearing and balance. Adenovirus is one of the major vectors to deliver genes into the inner ear for functional studies and hair cell regeneration. To identify adenovirus vectors that target specific cell subtypes in the inner ear, we studied three adenovirus vectors, carrying a reporter gene encoding green fluorescent protein (GFP) from two vendors or with a genome editing gene Cre recombinase (Cre), by injection into postnatal days 0 (P0) and 4 (P4) mouse cochlea through scala media by cochleostomy in vivo. We found three adenovirus vectors transduced mouse inner ear cells with different specificities and expression levels, depending on the type of adenoviral vectors and the age of mice. The most frequently targeted region was the cochlear sensory epithelium, including auditory hair cells and supporting cells. Adenovirus with GFP transduced utricular supporting cells as well. This study shows that adenovirus vectors are capable of efficiently and specifically transducing different cell types in the mammalian inner ear and provides useful tools to study inner ear gene function and to evaluate gene therapy to treat hearing loss and vestibular dysfunction. C1 [Shu, Yilai; Tao, Yong; Li, Wenyan; Chen, Zheng-Yi] Harvard Med Sch, Dept Otolaryngol, Boston, MA 02114 USA. [Shu, Yilai; Tao, Yong; Li, Wenyan; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Shu, Yilai; Li, Wenyan; Wang, Zhengmin] Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Otolaryngol Head & Neck Surg, Shanghai, Peoples R China. [Shu, Yilai; Li, Wenyan; Wang, Zhengmin] Natl Hlth & Family Planning Commiss, Key Lab Hearing Med, Shanghai, Peoples R China. [Shen, Jun] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Shen, Jun] Partners Personalized Med, Lab Mol Med, Cambridge, MA 02139 USA. RP Chen, ZY (reprint author), Harvard Med Sch, Dept Otolaryngol, Boston, MA 02114 USA.; Chen, ZY (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA.; Wang, ZM (reprint author), Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Otolaryngol Head & Neck Surg, Shanghai, Peoples R China.; Wang, ZM (reprint author), Natl Hlth & Family Planning Commiss, Key Lab Hearing Med, Shanghai, Peoples R China. EM fjswzm2015@126.com; zheng-yi_chen@meei.harvard.edu FU US National Institutes of Health [R01 DC006908]; Frederick and Ines Yeatts Hair Cell Regeneration Grant; National Nature Science Foundation of China [NSFC81300824]; Science and Technology Commission of Shanghai Municipality [15pj1401000] FX Zheng-Yi Chen was supported by US National Institutes of Health (R01 DC006908). Yilai Shu, Yong Tao, and Wenyan Li were supported by the Frederick and Ines Yeatts Hair Cell Regeneration Grant and Yilai Shu by the National Nature Science Foundation of China (NSFC81300824) and Science and Technology Commission of Shanghai Municipality (15pj1401000). NR 26 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2016 AR 9409846 DI 10.1155/2016/9409846 PG 8 WC Neurosciences SC Neurosciences & Neurology GA EH8CV UT WOS:000392000100001 ER PT S AU Zhang, YZ Aganj, I van der Kouwe, AJW Tisdall, MD AF Zhang, Yingzhuo Aganj, Iman van der Kouwe, Andre J. W. Tisdall, M. Dylan GP IEEE TI Effects of Resolution and Registration Algorithm on the Accuracy of EPI vNavs for Real Time Head Motion Correction in MRI SO PROCEEDINGS OF 29TH IEEE CONFERENCE ON COMPUTER VISION AND PATTERN RECOGNITION WORKSHOPS, (CVPRW 2016) SE IEEE Computer Society Conference on Computer Vision and Pattern Recognition Workshops LA English DT Proceedings Paper CT 29th IEEE Conference on Computer Vision and Pattern Recognition Workshops (CVPRW) CY JUN 26-JUL 01, 2016 CL Las Vegas, NV SP IEEE, IEEE Comp Soc AB Low-resolution, EPI-based Volumetric Navigators (vNavs) have been used as a prospective motion-correction system in a variety of MRI neuroimaging pulse sequences. The use of low-resolution volumes represents a trade-off between motion tracking accuracy and acquisition time. However, this means that registration must be accurate on the order of 0.2 voxels or less to be effective for motion correction. While vNavs have shown promising results in clinical and research use, the choice of navigator and registration algorithm have not previously been systematically evaluated. In this work we experimentally evaluate the accuracy of vNavs, and possible design choices for future improvements to the system, using real human data. We acquired navigator volumes at three isotropic resolutions (6.4 mm, 8 mm, and 10 mm) with known rotations and translations. The vNavs were then rigidly registered using trilinear, tricubic, and cubic B-spline interpolation. We demonstrate a novel refactoring of the cubic B-spline algorithm that stores pre-computed coefficients to reduce the per-interpolation time to be identical to tricubic interpolation. Our results show that increasing vNav resolution improves registration accuracy, and that cubic B-splines provide the highest registration accuracy at all vNav resolutions. Our results also suggest that the time required by vNavs may be reduced by imaging at 10 mm resolution, without substantial cost in registration accuracy. C1 [Zhang, Yingzhuo] Harvard John A Paulson Sch Engn & Appl Sci, Inst Appl Computat Sci & Engn, Cambridge, MA 02138 USA. [Aganj, Iman; van der Kouwe, Andre J. W.; Tisdall, M. Dylan] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Aganj, Iman; van der Kouwe, Andre J. W.; Tisdall, M. Dylan] Harvard Med Sch, Dept Radiol, Boston, MA USA. RP Zhang, YZ (reprint author), Harvard John A Paulson Sch Engn & Appl Sci, Inst Appl Computat Sci & Engn, Cambridge, MA 02138 USA. EM yingzhuozhang@g.harvard.edu; iman@nmr.mgh.harvard.edu; andre@nmr.mgh.harvard.edu; tisdall@nmr.mgh.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-7508 BN 978-1-5090-1437-8 J9 IEEE COMPUT SOC CONF PY 2016 BP 583 EP 591 DI 10.1109/CVPRW.2016.79 PG 9 WC Computer Science, Artificial Intelligence SC Computer Science GA BG7PP UT WOS:000391572100072 ER PT S AU Alegro, M Amaro, E Loring, B Heinsen, H Alho, E Zollei, L Ushizima, D Grinberg, LT AF Alegro, Maryana Amaro-, Edson, Jr. Loring, Burlen Heinsen, Helmut Alho, Eduardo Zollei, Lilla Ushizima, Daniela Grinberg, Lea T. GP IEEE TI Multimodal Whole Brain Registration: MRI and High Resolution Histology SO PROCEEDINGS OF 29TH IEEE CONFERENCE ON COMPUTER VISION AND PATTERN RECOGNITION WORKSHOPS, (CVPRW 2016) SE IEEE Computer Society Conference on Computer Vision and Pattern Recognition Workshops LA English DT Proceedings Paper CT 29th IEEE Conference on Computer Vision and Pattern Recognition Workshops (CVPRW) CY JUN 26-JUL 01, 2016 CL Las Vegas, NV SP IEEE, IEEE Comp Soc AB Three-dimensional brain imaging through cutting-edge MRI technology allows assessment of physical and chemical tissue properties at sub-millimeter resolution. In order to improve brain understanding as part of diagnostic tasks using MRI images, other imaging modalities to obtain deep cerebral structures and cytoarchitectural boundaries have been investigated. Under availability of postmortem samples, the fusion of MRI to brain histology supports more accurate description of neuroanatomical structures since it preserves microscopic entities and reveal fine anatomical details, unavailable otherwise. Nonetheless, histological processing causes severe tissue deformation and loss of the brain original 3D conformation, preventing direct comparisons between MRI and histology. This paper proposes an interactive computational pipeline designed to register multimodal brain data and enable direct histology-MRI correlation. Our main contribution is to develop schemes for brain data fusion, distortion corrections, using appropriate diffeomorphic mappings to align the 3D histological and MRI volumes. We describe our pipeline and preliminary developments of scalable processing schemes for high-resolution images. Tests consider a postmortem human brain, and include qualitatively and quantitatively results, such as 3D visualizations and the Dice coefficient (DC) between brain structures. Preliminary results show promising DC values when comparing our scheme results to manually labeled neuroanatomical regions defined by a neurosurgeon on MRI and histology data sets. DC was computed for the left caudade gyrus (LC), right hippocampus (RH) and lateral ventricles (LV). C1 [Alegro, Maryana; Grinberg, Lea T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Amaro-, Edson, Jr.; Heinsen, Helmut; Alho, Eduardo; Grinberg, Lea T.] Univ Sao Paulo, Sao Paulo, Brazil. [Loring, Burlen; Ushizima, Daniela] Lawrence Berkeley Natl Lab, Berkeley, CA USA. [Loring, Burlen] Natl Energy Res Sci Comp, Berkeley, CA USA. [Heinsen, Helmut] Univ Wurzburg, Wurzburg, Germany. [Zollei, Lilla] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ushizima, Daniela] Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Alegro, M (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM maryana.alegro@ucsf.edu; eamaro@usp.br; bloring@lbl.gov; heinsen@uni-wuerzburg.de; eduardoalho@hotmail.com; lzollei@nmr.mgh.harvard.edu; dushizima@lbl.gov; lea.grinberg@ucsf.edu OI Amaro Jr, Edson/0000-0002-5889-1382 NR 36 TC 0 Z9 0 U1 3 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-7508 BN 978-1-5090-1437-8 J9 IEEE COMPUT SOC CONF PY 2016 BP 634 EP 642 DI 10.1109/CVPRW.2016.85 PG 9 WC Computer Science, Artificial Intelligence SC Computer Science GA BG7PP UT WOS:000391572100078 ER PT S AU Brattain, LJ Landman, R Johnson, KA Chwalek, P Hyman, J Sharma, J Jennings, C Desimone, R Feng, GP Quatieri, TF AF Brattain, Laura J. Landman, Rogier Johnson, Kerry A. Chwalek, Patrick Hyman, Julia Sharma, Jitendra Jennings, Charles Desimone, Robert Feng, Guoping Quatieri, Thomas F. GP IEEE TI A Multimodal Sensor System for Automated Marmoset Behavioral Analysis SO 2016 IEEE 13TH INTERNATIONAL CONFERENCE ON WEARABLE AND IMPLANTABLE BODY SENSOR NETWORKS (BSN) SE International Conference on Wearable and Implantable Body Sensor Networks LA English DT Proceedings Paper CT 13th IEEE International Conference on Wearable and Implantable Body Sensor Networks (BSN) CY JUN 14-17, 2016 CL San Francisco, CA SP IEEE, EMB ID COMMON MARMOSET; NEUROSCIENCE RESEARCH; MODEL SYSTEM; MONKEYS; TRACKING; SCALE AB The common marmoset is emerging as an important transgenic model for improving the understanding of the underlying neurological basis of many brain disorders. Automated systems for quantitative monitoring of marmoset behaviors in naturalist settings over long period of time are needed to facilitate this process. This paper presents the preliminary work toward building a novel multimodal acquisition system for the automated marmoset behavior analysis in home cage. In addition to integrating commercial available devices such as Microsoft Kinect sensors and microphones of different characteristics, we also developed a wireless flexible neck collar with acoustic and non-acoustic sensors onboard for marmoset vocalization recording and caller identification. Our initial effort has been focused on the real-time synchronization of multiple sensor outputs, the engineering design of the wireless collar, and algorithms for global 3D position and local head movement from a Microsoft Kinect sensor. With limited preliminary data, we are able to estimate 3D trajectories of two marmosets with a RMSE of similar to 3.2 mm and track colored ear tufts with an accuracy of RMSE similar to 1.8 mm. A larger dataset is needed for a complete assessment and validation. Our system architecture is modular and flexible, and can he extended to include more sensors and devices if needed. C1 [Brattain, Laura J.; Johnson, Kerry A.; Chwalek, Patrick; Quatieri, Thomas F.] MIT, Lincoln Lab, Lexington, MA 02420 USA. [Landman, Rogier; Feng, Guoping] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Hyman, Julia; Jennings, Charles; Desimone, Robert; Feng, Guoping] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Sharma, Jitendra] MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Sharma, Jitendra] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sharma, Jitendra] Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA. RP Brattain, LJ (reprint author), MIT, Lincoln Lab, Lexington, MA 02420 USA. EM brattainl@mit.edu NR 30 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2376-8886 BN 978-1-5090-3087-3 J9 INT CONF WEARAB IMPL PY 2016 BP 254 EP 259 PG 6 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BG7EY UT WOS:000391251700047 ER PT J AU Fletcher, RR Chamberlain, D Richman, D Oreskovic, N Taveras, E AF Fletcher, R. R. Chamberlain, D. Richman, D. Oreskovic, N. Taveras, E. GP IEEE TI Wearable Sensor and Algorithm for Automated Measurement of Screen Time SO 2016 IEEE WIRELESS HEALTH (WH) LA English DT Proceedings Paper CT IEEE Wireless Health Conference (WH) CY OCT 25-27, 2016 CL Bethesda, MD SP IEEE DE Screen time; automated measurement; television; computer; behavior; clinical study; obesity; sedentary; cardiometabolic; circadian; wearable; sensor ID SEDENTARY BEHAVIOR; CARDIOVASCULAR-DISEASE; ADOLESCENTS; CHILDREN; ASSOCIATIONS; RELIABILITY; VALIDITY; ADULTS; MEDIA AB The human use of electronic displays (television or computers), also known as "screen time," is currently a topic of great interest within behavior medicine and general clinical research. This behavior has been linked with a wide variety of pathologies, including obesity, circadian disruption, sleeping disorders, cardiometabolic disease, and socio-emotional behavior disorders in children. As an alternative to conventional data collection methods, such as self-reported questionnaires or interviews, we present an automated objective method for estimating screen time that makes use of a wearable wrist band containing an optical color sensor. By applying a machine learning model, and using data collected from a custom designed sensor band, we present results from a small study to demonstrate that it is possible to measure screen time exposure using the color sensor alone without the use of an accelerometer. Using data from two users in two different homes under a variety of activities and lighting conditions, we achieved a classification score of AUC=0.90 for television alone, 0.89 for computer alone, and 0.83 for the combination of both devices. As an additional test, we also present sample results from an experiment in a natural environment. These preliminary results are encouraging and are comparable to the accuracy of conventional self-reported methods. Limitations of this method and potential improvements are also discussed. C1 [Fletcher, R. R.; Chamberlain, D.; Richman, D.] MIT, Cambridge, MA 02139 USA. [Fletcher, R. R.] UMass Med Sch, Worcester, MA 01655 USA. [Oreskovic, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Oreskovic, N.] Harvard Med Sch, Boston, MA USA. [Taveras, E.] Massachusetts Gen Hosp Children, Div, Boston, MA USA. [Taveras, E.] Massachusetts Gen Hosp Children, Gen Acad Pediat, Boston, MA USA. [Taveras, E.] Harvard Sch Publ Hlth, Boston, MA USA. RP Fletcher, RR (reprint author), MIT, Cambridge, MA 02139 USA.; Fletcher, RR (reprint author), UMass Med Sch, Worcester, MA 01655 USA. EM fletcher@media.mit.edu NR 28 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-5090-3090-3 PY 2016 BP 109 EP 116 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Electrical & Electronic; Medical Informatics; Telecommunications SC Computer Science; Engineering; Medical Informatics; Telecommunications GA BG7HG UT WOS:000391291200016 ER PT J AU Webner, D Iverson, GL AF Webner, David Iverson, Grant L. TI Suicide in professional American football players in the past 95 years SO BRAIN INJURY LA English DT Article DE Suicide; athletes; chronic traumatic encephalopathy; depression; football ID CHRONIC TRAUMATIC ENCEPHALOPATHY; STRESSFUL LIFE EVENTS; MAJOR DEPRESSION; CHRONIC PAIN; PSYCHIATRIC-DISORDERS; MENTAL-HEALTH; BRAIN TRAUMA; METAANALYSIS; RISK; ASSOCIATION AB Objective: To examine publicly-available information on all identified cases of suicide in active or former American professional football players between 1920 and the spring of 2015. Design: Retrospective cohort study. Setting: Professional American Football in the US. Participants: A cohort of 26 702 athletes who had died, retired or were currently playing in the NFL from nfl.com since 1920 was identified. Main outcome measures: Internet queries identifying 26 professional football players who completed suicide. Obituaries and news reports were reviewed. The primary outcome measures included mortality, demographic characteristics and life circumstances in professional American football players completing suicide. Results: From 1920-2015, the median age of the 26 men who completed suicide was 39.5 years (range = 23-85). The median number of years after retirement was 6.5 (range = 0-63). Most of the deaths since 1920 have occurred in the past 15 years (58.7%) and a large percentage have occurred since 2009 (42.3%). Most of the men suffered from multiple life stressors prior to their deaths, such as retirement from sport, loss of steady income, divorce, failed business ventures, estrangement from family members and medical, psychiatric and/or substance abuse problems. Conclusions: A disproportionate number of completed suicides in current and former professional football players have occurred since 2009 (42.3%). It is well established in the literature that the causes of depression and suicidality are diverse, often multifactorial and treatable. Providing at-risk retired athletes with mental health treatment will likely reduce their suffering and improve their quality-of-life. C1 [Webner, David] Crozer Keystone Hlth Syst, Dept Family Med, Philadelphia, PA USA. [Iverson, Grant L.] Harvard Med Sch, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] Mass Gen Hosp Children Sport Concuss Program, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Webner, D (reprint author), Crozer Keystone Hlth Syst, Dept Family Med, Philadelphia, PA USA. EM david.webner@crozer.org NR 60 TC 0 Z9 0 U1 4 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2016 VL 30 IS 13-14 BP 1718 EP 1721 DI 10.1080/02699052.2016.1202451 PG 4 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA EG8YO UT WOS:000391343800027 PM 27996330 ER PT S AU Johnston, N Ondrey, F Rosen, R Hurley, BP Gould, J Allen, J DelGaudio, J Altman, KW AF Johnston, Nikki Ondrey, Frank Rosen, Rachel Hurley, Bryan P. Gould, Jon Allen, Jacquie DelGaudio, John Altman, Kenneth W. BE Giuli, R Gregersen, H TI Airway reflux SO 13TH OESO WORLD CONFERENCE: THE ESOPHAGIOME II SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 13th OESO World Conference CY AUG 31-SEP 03, 2015 CL MONACO SP OESO, United Nat Educ Sci & Cultural Org DE reflux; airway; laryngopharyngeal reflux (LPR); extraesophageal reflux (EER); pepsin; surgical approaches; therapeutic approaches ID COUGH HYPERSENSITIVITY SYNDROME; ATPASE PROTON PUMP; LARYNGOPHARYNGEAL REFLUX; EXTRAESOPHAGEAL REFLUX; CHRONIC RHINOSINUSITIS; SUBMANDIBULAR-GLAND; N-METHYLNITROSOUREA; BARRETTS-ESOPHAGUS; POSTNASAL DRIP; BILE-ACIDS AB An ever-increasing number of adult and pediatric disorders have been shown to be influenced or caused by airway reflux. This has become a controversial and complicated aspect of medicine that requires a multidisciplinary approach. Evidence indicates that it is not only the acidic components of gastric refluxate that injure extraesophageal tissues but also the nonacidic components, such as pepsin and bile. There is a realization that proton pump inhibitors will not be effective when nonacidic components of refluxate are causing the problem. New in vitro and in vivo models for the study of airway reflux and new therapeutic and surgical approaches are discussed in this review article. C1 [Johnston, Nikki] Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI 53226 USA. [Johnston, Nikki] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. [Ondrey, Frank] Univ Minnesota, Sch Med, Dept Otolaryngol, Duluth, MN 55812 USA. [Ondrey, Frank] Univ Minnesota, Sch Med, Masonic Canc Ctr, Duluth, MN 55812 USA. [Rosen, Rachel] Harvard Med Sch, Bostons Childrens Hosp, Dept Gastroenterol & Nutr, Boston, MA USA. [Hurley, Bryan P.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA. [Gould, Jon] Med Coll Wisconsin, Dept Surg, 8700 W Wisconsin Ave, Milwaukee, WI 53226 USA. [Allen, Jacquie] Univ Auckland, Dept Surg, Auckland, New Zealand. [DelGaudio, John] Emory Univ, Dept Otolaryngol, Atlanta, GA 30322 USA. [Altman, Kenneth W.] Baylor Coll Med, Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. RP Johnston, N (reprint author), Med Coll Wisconsin Otolaryngol, Dept Otolaryngol & Commun Sci, 9200 West Wisconsin Ave, Milwaukee, WI 53226 USA.; Johnston, N (reprint author), Med Coll Wisconsin Otolaryngol, Dept Microbiol & Mol Genet, 9200 West Wisconsin Ave, Milwaukee, WI 53226 USA. EM njohnsto@mcw.edu NR 56 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1381 BP 5 EP 13 DI 10.1111/nyas.13080 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BG7AK UT WOS:000391122800001 PM 27310222 ER PT S AU Hu, CH Ju, RH Shen, YS Zhou, P Li, QZ AF Hu, Chenhui Ju, Ronghui Shen, Yusong Zhou, Pan Li, Quanzheng GP IEEE TI Clinical Decision Support for Alzheimer's Disease Based on Deep Learning and Brain Network SO 2016 IEEE INTERNATIONAL CONFERENCE ON COMMUNICATIONS (ICC) SE IEEE International Conference on Communications LA English DT Proceedings Paper CT IEEE International Conference on Communications (ICC) CY MAY 22-27, 2016 CL Kuala Lumpur, MALAYSIA SP IEEE AB Modern e-health systems have undergone rapid development thanks to the advances in communications, computing and machine learning technology. Especially, deep learning has great superiority in image analysis and disease prediction. In this paper, we use Alzheimer's Disease (AD) as an example to show advantages of deep learning in diagnosing brain diseases and providing clinical decision support. Firstly, we convert raw functional magnetic resonance imaging (fMRI) to a matrix to represent activity of 90 brain regions. Secondly, to represent the functional connectivity between different brain regions, a correlation matrix is obtained by calculating the correlation between each pair of brain regions. In the next, a targeted autoencoder network is built to classify the correlation matrix, which is sensitive to AD. Finally, the experiment results show that our proposed method for AD prediction achieves much better effects than traditional means. It finds the correlations between different brain regions efficiently, provides strong reference for AD prediction. Compared to Support Vector Machine (SVM), about 25% improvement is gained in prediction accuracy. The e-health field becomes more complete and effective owing to that. Our work helps predict AD at an early stage and take measures to slow down or even prevent the onset of it. C1 [Hu, Chenhui] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Ju, Ronghui; Zhou, Pan] Huazhong Univ Sci & Technol, Sch Elect Informat & Commun, Wuhan, Peoples R China. [Shen, Yusong] Rice Univ, Sch Engn, Houston, TX 77251 USA. [Li, Quanzheng] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, Quanzheng] Harvard Med Sch, Boston, MA USA. RP Hu, CH (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM hu4@seas.harvard.edu; juronghui@hust.edu.cn; Yusong.Shen@rice.edu; panzhou@hust.edu.cn; li.quanzheng@mgh.harvard.edu NR 15 TC 0 Z9 0 U1 2 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1550-3607 BN 978-1-4799-6664-6 J9 IEEE ICC PY 2016 PG 6 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA BG6YK UT WOS:000390993201027 ER PT J AU Akgun, KM Gruenewald, D Wertheimer, D Gabriel, M Rizzo, D Zuccaro, M Luhrs, C AF Akgun, K. M. Gruenewald, D. Wertheimer, D. Gabriel, M. Rizzo, D. Zuccaro, M. Luhrs, C. TI A National Va Palliative Care Quality Improvement Project For Improving Intensive Care Unit Family Meetings (icu-Fms) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Akgun, K. M.] VA Connecticut, West Haven, CT USA. [Akgun, K. M.] Yale Univ, Sch Med, West Haven, CT 06516 USA. [Gruenewald, D.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Wertheimer, D.] VA Maryland Hlth Care Syst, Baltimore, MD USA. [Gabriel, M.; Zuccaro, M.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Rizzo, D.] Salem Vet Affairs Med Ctr, Salem, VA USA. [Luhrs, C.] Vet Affairs New York Harbor Healthcare Syst, Brooklyn, NY USA. EM kathleen.akgun@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7925 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749608014 ER PT J AU Alba, GA Truong, QA Gaggin, HK Gandhi, PU De Berardinis, B Magrini, L Bajwa, EK Di Somma, S Januzzi, JL AF Alba, G. A. Truong, Q. A. Gaggin, H. K. Gandhi, P. U. De Berardinis, B. Magrini, L. Bajwa, E. K. Di Somma, S. Januzzi, J. L. TI Diagnostic And Prognostic Utility Of Procalcitonin In Patients Presenting To The Emergency Department With Dyspnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Alba, G. A.; Gaggin, H. K.; Gandhi, P. U.; Bajwa, E. K.; Januzzi, J. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Truong, Q. A.] New York Presbyterian Hosp, New York, NY USA. [Truong, Q. A.] Weill Cornell Med Coll, New York, NY USA. [De Berardinis, B.; Magrini, L.; Di Somma, S.] Univ Roma La Sapienza, St Andrea Hosp, Rome, Italy. EM galba@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2108 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601248 ER PT J AU Aziz, R Kingery, JR Moschovis, P AF Aziz, R. Kingery, J. R. Moschovis, P. TI Implementation Of A Tetanus Treatment Protocol In A Sub-Saharan African Intensive Care Unit Improves Patient Mortality And Increases Length Of Stay SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Aziz, R.] Bugando Med Ctr, Bugando, Tanzania. [Kingery, J. R.] Weill Cornell Med Coll, New York, NY USA. [Moschovis, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM azizriaz@googlemail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7822 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607755 ER PT J AU Bajwa, EK Bhan, I Quraishi, S Matthay, M Thompson, BT AF Bajwa, E. K. Bhan, I. Quraishi, S. Matthay, M. Thompson, B. T. TI Low Vitamin D Status Occurs In 90% Of Patients With Ards And Is Associated With Longer Duration Of Mechanical Ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Bajwa, E. K.; Bhan, I.; Quraishi, S.; Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Matthay, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1846 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600845 ER PT J AU Becerra, MB Becerra, BJ Teodorescu, M AF Becerra, M. B. Becerra, B. J. Teodorescu, M. TI Health Resource Utilization Of Asthma Hospitalizations With Comorbid Sleep Apnea And Obesity: Results From The Nationwide Inpatient Sample SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Becerra, M. B.] Calif State Univ San Bernardino, San Bernardino, CA 92407 USA. [Becerra, B. J.] Loma Linda Univ, Loma Linda, CA 92350 USA. [Teodorescu, M.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. EM mbecerra@csusb.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3111 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602359 ER PT J AU Berra, L Rodriguez-Lopez, J Yu, B Rezoagli, E Strelow, S Fisher, D Channick, RN Zapol, W AF Berra, L. Rodriguez-Lopez, J. Yu, B. Rezoagli, E. Strelow, S. Fisher, D. Channick, R. N. Zapol, W. TI A Proof Of Concept Study Of Human Volunteers And Pulmonary Hypertension Patients Breathing Nitric Oxide Produced By Electrical Pulsed Discharge SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Berra, L.; Rodriguez-Lopez, J.; Yu, B.; Rezoagli, E.; Strelow, S.; Fisher, D.; Channick, R. N.; Zapol, W.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. EM erezoagli@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7382 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607318 ER PT J AU Bhatraju, P Mukherjee, P Robinson-Cohen, C Christie, JD Meyer, NJ Matthay, M Calfee, CS O'Keefe, G Christiani, DC Himmelfarb, J Wurfel, MM AF Bhatraju, P. Mukherjee, P. Robinson-Cohen, C. Christie, J. D. Meyer, N. J. Matthay, M. Calfee, C. S. O'Keefe, G. Christiani, D. C. Himmelfarb, J. Wurfel, M. M. TI Acute Kidney Injury Sub-Phenotypes Based On Creatinine Trajectory Identifies Critically Ill Patients At Increased Risk Of Death SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Bhatraju, P.; Mukherjee, P.; Robinson-Cohen, C.; O'Keefe, G.] Univ Washington, Seattle, WA 98195 USA. [Christie, J. D.; Meyer, N. J.] Univ Penn, Philadelphia, PA 19104 USA. [Matthay, M.; Calfee, C. S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Himmelfarb, J.; Wurfel, M. M.] Harborview Med Ctr, Seattle, WA USA. EM bhatraju@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3645 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603029 ER PT J AU Bigatello, L Linde-Zwirble, W Crowell, J Hansell, D Sahatjian, J AF Bigatello, L. Linde-Zwirble, W. Crowell, J. Hansell, D. Sahatjian, J. TI Effects Of Fluids Administration In Patients With Septic Shock With Or Without Heart Failure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Bigatello, L.] St Elizabeths Med Ctr, Brighton, MA USA. [Linde-Zwirble, W.; Crowell, J.] Trexin, Chicago, IL USA. [Hansell, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sahatjian, J.] Cheetah Med, Newton, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7047 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606817 ER PT J AU Billatos, E Muse, M Jiwani, A Maple, E Mahon, I Apgar, C Atwood, CW Battaile, JT Browning, R Garshick, E Goldstein, RH Keith, RL More, K Morris, M Parrish, JS Reid, M Gatsonis, C Elashoff, D Duan, F Dubinett, SM Lenburg, M Massion, PP Remick, D Wistuba, II Schnall, M Vachani, A Spira, A AF Billatos, E. Muse, M. Jiwani, A. Maple, E. Mahon, I. Apgar, C. Atwood, C. W. Battaile, J. T. Browning, R. Garshick, E. Goldstein, R. H. Keith, R. L. More, K. Morris, M. Parrish, J. S. Reid, M. Gatsonis, C. Elashoff, D. Duan, F. Dubinett, S. M. Lenburg, M. Massion, P. P. Remick, D. Wistuba, I. I. Schnall, M. Vachani, A. Spira, A. TI Diagnostic Evaluation Of The Indeterminate Pulmonary Nodule Among Military And Veteran Personnel With Suspect Lung Cancer: The Decamp Consortium SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Billatos, E.; Muse, M.; Maple, E.; Remick, D.] Boston Univ, Boston, MA 02215 USA. [Jiwani, A.; Vachani, A.] Univ Penn, Philadelphia, PA 19104 USA. [Mahon, I.; Apgar, C.; Schnall, M.] Amer Coll Radiol, Imaging Network, Philadelphia, PA USA. [Atwood, C. W.] Univ Pittsburgh, Pittsburgh, PA USA. [Battaile, J. T.] Univ Texas Southwestern, Dallas, TX USA. [Browning, R.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Garshick, E.; Goldstein, R. H.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Keith, R. L.] UC Denver, DVAMC, Denver, CO USA. [More, K.] Portsmouth Naval Med Ctr, Virginia Beach, VA USA. [Morris, M.] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. [Parrish, J. S.] Naval Med Ctr, San Diego, CA USA. [Reid, M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Gatsonis, C.] Brown Univ, Providence, RI 02912 USA. [Elashoff, D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Duan, F.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Dubinett, S. M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lenburg, M.; Spira, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Massion, P. P.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Wistuba, I. I.] MD Anderson Canc Ctr, Houston, TX USA. EM ehab.billatos@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6183 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605843 ER PT J AU Black, KE Pace, VA Tager, AM AF Black, K. E. Pace, V. A. Tager, A. M. TI Alveolar Epithelial Cells Release Pro-Fibrotic Mediators In Response To Endoplasmic Reticulum Stress SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Black, K. E.; Pace, V. A.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kblack1@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4159 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603542 ER PT J AU Bose, S Moskowitz, A Jalilian, L Celi, LA Johnson, AEW AF Bose, S. Moskowitz, A. Jalilian, L. Celi, L. A. Johnson, A. E. W. TI Impact Of Intensive Care Unit Discharge Delays SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Bose, S.; Moskowitz, A.; Celi, L. A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jalilian, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Johnson, A. E. W.] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM somnathbose@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4695 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604211 ER PT J AU Cade, BE Chen, H Stilp, AM Gleason, KJ Sofer, T Arens, R Bell, GI Below, JE Bjonnes, AC Chun, SG Conomos, MP Johnson, WC Frazier-Wood, AC Lane, JM Larkin, EK Loredo, JS Post, WS Ramos, AR Rice, K Rotter, JI Shah, NA Taylor, KD Thornton, TA Wang, C Zee, PC Hanis, CL Sunyaev, SR Patel, SR Laurie, CC Zhu, X Saxena, R Lin, X Redline, S AF Cade, B. E. Chen, H. Stilp, A. M. Gleason, K. J. Sofer, T. Arens, R. Bell, G. I. Below, J. E. Bjonnes, A. C. Chun, S. G. Conomos, M. P. Johnson, W. C. Frazier-Wood, A. C. Lane, J. M. Larkin, E. K. Loredo, J. S. Post, W. S. Ramos, A. R. Rice, K. Rotter, J. I. Shah, N. A. Taylor, K. D. Thornton, T. A. Wang, C. Zee, P. C. Hanis, C. L. Sunyaev, S. R. Patel, S. R. Laurie, C. C. Zhu, X. Saxena, R. Lin, X. Redline, S. TI Genetic Associations With Obstructive Sleep Apnea Traits In Hispanic/latino Americans SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Cade, B. E.; Chun, S. G.; Lane, J. M.; Sunyaev, S. R.; Patel, S. R.; Saxena, R.; Redline, S.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Chen, H.; Wang, C.; Lin, X.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Stilp, A. M.; Sofer, T.; Conomos, M. P.; Johnson, W. C.; Rice, K.; Thornton, T. A.; Laurie, C. C.] Univ Washington, Seattle, WA 98195 USA. [Gleason, K. J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Arens, R.] Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY USA. [Bell, G. I.] Univ Chicago, Chicago, IL 60637 USA. [Below, J. E.; Hanis, C. L.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Bjonnes, A. C.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. [Frazier-Wood, A. C.] Baylor Coll Med, Houston, TX 77030 USA. [Larkin, E. K.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Loredo, J. S.] UC San Diego Sch Med, La Jolla, CA USA. [Post, W. S.] Johns Hopkins Univ, Baltimore, MD USA. [Ramos, A. R.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Rotter, J. I.; Taylor, K. D.] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Los Angeles, CA USA. [Shah, N. A.] Icahn Sch Med, New York, NY USA. [Zee, P. C.] Northwestern Univ, Chicago, IL 60611 USA. [Zhu, X.] Case Western Reserve Univ, Cleveland, OH 44106 USA. EM bcade@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4324 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603707 ER PT J AU Carson, SS Cox, CE Wallenstein, S Hanson, L Danis, M Tulsky, JA Chai, E Nelson, J AF Carson, S. S. Cox, C. E. Wallenstein, S. Hanson, L. Danis, M. Tulsky, J. A. Chai, E. Nelson, J. TI A Multicenter Randomized Controlled Trial Of Palliative Care-Led Informational/emotional Support Meetings For Family Decision Makers Of Patients With Chronic Critical Illness SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Carson, S. S.; Hanson, L.] Univ N Carolina, Chapel Hill, NC USA. [Cox, C. E.] Duke Univ, Med Ctr, Durham, NC USA. [Wallenstein, S.; Chai, E.] Mt Sinai Sch Med, New York, NY USA. [Danis, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Tulsky, J. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nelson, J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4296 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603679 ER PT J AU Causton, B Jones, K Cho, JL Medoff, BD AF Causton, B. Jones, K. Cho, J. L. Medoff, B. D. TI Carma3 Mediates The Pulmonary Immune Response To Alternaria Alternata SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Causton, B.; Jones, K.; Cho, J. L.; Medoff, B. D.] Massachusetts Gen Hosp, Charlestown, MA USA. EM bcauston@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7545 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607480 ER PT J AU Chan, ED Bai, A Bai, X AF Chan, E. D. Bai, A. Bai, X. TI Aat Reduces Burden Of Mycobacterium Intracellulare In Human Macrophages By Inducing Phagosome-Lysosome Fusion SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Chan, E. D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Bai, A.; Bai, X.] Natl Jewish Hlth, Denver, CO USA. EM chane@njhealth.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3747 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603131 ER PT J AU Chan, ED Stitzel, J Bai, A Phillips, M Bai, X AF Chan, E. D. Stitzel, J. Bai, A. Phillips, M. Bai, X. TI Nicotine Impairs Macrophage Control Of Mycobacterium Tuberculosis By Binding To Nicotinic Acetylcholine Receptor, Activating Nfkappab And Inhibiting Autophagy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Chan, E. D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Stitzel, J.] Univ Colorado, Boulder, CO 80309 USA. [Bai, A.; Phillips, M.; Bai, X.] Natl Jewish Hlth, Denver, CO USA. EM ChanE@njhealth.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2892 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602140 ER PT J AU Charnin, J Arsenault, C Mark, L Muse, S Eromo, E AF Charnin, J. Arsenault, C. Mark, L. Muse, S. Eromo, E. TI Overcoming Time And Room Limitations During In-Situ Simulations In The Intensive Care Unit SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Charnin, J.; Arsenault, C.; Mark, L.; Muse, S.; Eromo, E.] Massachusetts Gen Hosptial, Boston, MA USA. EM jcharnin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3205 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602453 ER PT J AU Cho, JL Ling, MF Faustino, L Islam, S Afshar, R Griffith, JW Harris, RS Ng, A Ford, AA Xavier, R Boucher, RC Kwok, WW Hamilos, DL Kesimer, M Moon, JJ Luster, AD Medoff, BD AF Cho, J. L. Ling, M. F. Faustino, L. Islam, S. Afshar, R. Griffith, J. W. Harris, R. S. Ng, A. Ford, A. A. Xavier, R. Boucher, R. C. Kwok, W. W. Hamilos, D. L. Kesimer, M. Moon, J. J. Luster, A. D. Medoff, B. D. TI Innate Type 2 Receptor Expression On Airway Allergen-Specific Cd4+T Cells Distinguishes Allergic Asthmatics From Allergic Non-Asthmatics SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Cho, J. L.; Ling, M. F.; Faustino, L.; Islam, S.; Afshar, R.; Griffith, J. W.; Harris, R. S.; Ng, A.; Xavier, R.; Hamilos, D. L.; Moon, J. J.; Luster, A. D.; Medoff, B. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ford, A. A.; Boucher, R. C.; Kesimer, M.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Kwok, W. W.] Benaroya Res Inst, Seattle, WA USA. EM jlcho@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2600 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601740 ER PT J AU Cloonan, SM Glass, K Laucho-Contreras, M Bhashyam, AR Cervo, M Pabon, M Konrad, C Polverino, F Siempos, II Perez, E Mizumura, K Ghosh, M Parameswaran, H Williams, N Rooney, KT Chen, ZH Goldklang, MP Yuan, GC Moore, S DeMeo, DL Rouault, TA D'Armiento, JM Schon, E Manfredi, G Quackenbush, J Mahmood, A Silverman, EK Owen, CA Choi, AMK AF Cloonan, S. M. Glass, K. Laucho-Contreras, M. Bhashyam, A. R. Cervo, M. Pabon, M. Konrad, C. Polverino, F. Siempos, I. I. Perez, E. Mizumura, K. Ghosh, M. Parameswaran, H. Williams, N. Rooney, K. T. Chen, Z-H. Goldklang, M. P. Yuan, G-C. Moore, S. DeMeo, D. L. Rouault, T. A. D'Armiento, J. M. Schon, E. Manfredi, G. Quackenbush, J. Mahmood, A. Silverman, E. K. Owen, C. A. Choi, A. M. K. TI Linking The COPD Susceptibility Gene Iron-Responsive Element Binding Protein 2 (irp2) With Pathological Outcomes In Experimental COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Cloonan, S. M.; Pabon, M.; Konrad, C.; Siempos, I. I.; Perez, E.; Mizumura, K.; Williams, N.; Rooney, K. T.; Manfredi, G.; Choi, A. M. K.] Weill Cornell Med Coll, New York, NY USA. [Glass, K.; Laucho-Contreras, M.; Bhashyam, A. R.; Chen, Z-H.; Silverman, E. K.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Laucho-Contreras, M.; Bhashyam, A. R.; Chen, Z-H.] Harvard Med Sch, Boston, MA USA. [Cervo, M.; Polverino, F.; Moore, S.; Mahmood, A.; Owen, C. A.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Ghosh, M.; Rouault, T. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Parameswaran, H.] Boston Univ, Boston, MA 02215 USA. [Goldklang, M. P.] Columbia Univ, New York, NY USA. [Yuan, G-C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [DeMeo, D. L.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [D'Armiento, J. M.] Columbia Univ, Dept Anesthesiol, New York, NY USA. [D'Armiento, J. M.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY USA. [D'Armiento, J. M.] Columbia Univ, Dept Med, New York, NY USA. [Schon, E.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. [Schon, E.] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY USA. [Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4083 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603466 ER PT J AU Crothers, KA Kross, EK Shahrir, SF Reisch, LM Slatore, CG Zeliadt, SB Triplette, M Meza, R Elmore, JG AF Crothers, K. A. Kross, E. K. Shahrir, S. F. Reisch, L. M. Slatore, C. G. Zeliadt, S. B. Triplette, M. Meza, R. Elmore, J. G. TI Attitudes Regarding Lung Cancer Screening And Decision Aids: A Survey And Focus Group Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Crothers, K. A.; Kross, E. K.; Shahrir, S. F.; Reisch, L. M.; Triplette, M.; Elmore, J. G.] Univ Washington, Seattle, WA 98195 USA. [Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. [Zeliadt, S. B.] Seattle VA, Seattle, WA USA. [Zeliadt, S. B.] Univ Washington, Seattle, WA 98195 USA. [Meza, R.] Univ Michigan, Ann Arbor, MI 48109 USA. EM KCrothers@medicine.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1274 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600274 ER PT J AU Dada, LA Tokhtaeva, E Soni, PN Ridge, KM Sachs, G Sznajder, JI Vagin, O AF Dada, L. A. Tokhtaeva, E. Soni, P. N. Ridge, K. M. Sachs, G. Sznajder, J. I. Vagin, O. TI The O-Glycosylated Ectodomain Of Fxyd5 Impairs Alveolar Epithelial Integrity By Inhibiting The Intercellular Trans-Dimerization Of The Na,k-Atpase SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Dada, L. A.; Soni, P. N.; Ridge, K. M.; Sznajder, J. I.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Tokhtaeva, E.; Sachs, G.; Vagin, O.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Tokhtaeva, E.; Sachs, G.; Vagin, O.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM lauradada@northwestern.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5763 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605425 ER PT J AU Dahl, R Anzueto, A Metzdorf, N Mueller, A Calverley, PM AF Dahl, R. Anzueto, A. Metzdorf, N. Mueller, A. Calverley, P. M. TI Using Different Sets Of Patient-Relevant Outcomes In Chronic Obstructive Pulmonary Disease To Evaluate Efficacy Of Tiotropium Respimat (R) - A Post-Hoc Analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Dahl, R.] Odense Univ Hosp, Odense C, Denmark. [Anzueto, A.] Univ Texas San Antonio, San Antonio, TX USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Metzdorf, N.] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. [Mueller, A.] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany. [Calverley, P. M.] Univ Liverpool, Inst Ageing & Chron Dis, Liverpool, Merseyside, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6803 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606574 ER PT J AU De Haro, C Montanya, J Lopez-Aguilar, J Fernandez, R Albaiceta, G Fernandez-Gonzalo, S Turon, M Goma, G Chacon, E Estruga, A Subira, C Murias, G Lucangelo, U Villar, J Skrobik, Y Kacmarek, R Oliva, J Blanch, L AF De Haro, C. Montanya, J. Lopez-Aguilar, J. Fernandez, R. Albaiceta, G. Fernandez-Gonzalo, S. Turon, M. Goma, G. Chacon, E. Estruga, A. Subira, C. Murias, G. Lucangelo, U. Villar, J. Skrobik, Y. Kacmarek, R. Oliva, J. Blanch, L. TI Asynchronies Evaluation During The First 72 Hours Of Mechanical Ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [De Haro, C.; Chacon, E.; Estruga, A.; Blanch, L.] Corporacio Sanitaria & Univ Parc Tauli, Hosp Sabadell, Sabadell, Spain. [Montanya, J.; Turon, M.; Villar, J.] CIBERES, Madrid, Spain. [Lopez-Aguilar, J.; Fernandez-Gonzalo, S.; Goma, G.; Oliva, J.] Fundacio Parc Tauli, Sabadell, Spain. [Fernandez, R.; Subira, C.] UIC, Fundacio Althaia, Manresa, Spain. [Albaiceta, G.] Hosp Cent Asturias, Oviedo, Spain. [Murias, G.] Clin Bazterr, Buenos Aires, DF, Argentina. [Lucangelo, U.] Cattinara Hosp, Trieste, Italy. [Skrobik, Y.] Hosp Maisonneuve Rosemont, Montreal, PQ, Spain. [Kacmarek, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM candelariadeharo@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5279 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604793 ER PT J AU Deshane, JS Trevor, J Wang, Y Zhi, D Curtiss, M Wang, F Eipers, PG William, V Morrow, C Dransfield, MT AF Deshane, J. S. Trevor, J. Wang, Y. Zhi, D. Curtiss, M. Wang, F. Eipers, P. G. William, V. Morrow, C. Dransfield, M. T. TI Longitudinal Changes In Airway Microbiome Signatures And Immunoregulatory Cell Dynamics Following Bronchial Thermoplasty SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Deshane, J. S.; Trevor, J.; Wang, Y.; Zhi, D.; Curtiss, M.; Wang, F.; Eipers, P. G.; William, V.; Morrow, C.; Dransfield, M. T.] Univ Alabama Birmingham, Birmingham, AL USA. [Trevor, J.; Wang, Y.; Dransfield, M. T.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. EM treena@uab.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1057 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600057 ER PT J AU DuBrock, HM Krowka, MJ Forde, K Krok, K Patel, M Sharkoski, TE Batra, S Lin, G Oh, J Mottram, CD Scanlon, PD Fallon, M Kawut, SM AF DuBrock, H. M. Krowka, M. J. Forde, K. Krok, K. Patel, M. Sharkoski, T. E. Batra, S. Lin, G. Oh, J. Mottram, C. D. Scanlon, P. D. Fallon, M. Kawut, S. M. TI The Clinical Impact Of Intrapulmonary Vascular Dilation In Liver Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [DuBrock, H. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Krowka, M. J.; Lin, G.; Oh, J.; Mottram, C. D.; Scanlon, P. D.] Mayo Clin, Rochester, MN USA. [Forde, K.; Patel, M.; Sharkoski, T. E.; Kawut, S. M.] Perelman Sch Med, Philadelphia, PA USA. [Krok, K.] Penn State, Hershey, PA USA. [Batra, S.; Fallon, M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. EM hdubrock@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6305 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606077 ER PT J AU DuBrock, HM Rodriguez-Lopez, J LeVarge, BL Curry, MP Preston, IR Channick, RN Karumanchi, S AF DuBrock, H. M. Rodriguez-Lopez, J. LeVarge, B. L. Curry, M. P. Preston, I. R. Channick, R. N. Karumanchi, S. TI Macrophage Migration Inhibitory Factor (mif): A Novel Biomarker Of Portopulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [DuBrock, H. M.; LeVarge, B. L.; Curry, M. P.; Karumanchi, S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rodriguez-Lopez, J.; Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Preston, I. R.] Tufts Med Ctr, Boston, MA USA. EM hdubrock@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6306 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606078 ER PT J AU Dudley, K Lobato, R Wong, J Maxwell, B Rhoads, K Zamanian, RT AF Dudley, K. Lobato, R. Wong, J. Maxwell, B. Rhoads, K. Zamanian, R. T. TI Perioperative Morbidity And Mortality In Patients With Pulmonary Hypertension Undergoing Non-Cardiac Surgery: An Analysis Of Admission Records From The Nationwide Inpatient Sample From 2005-2009 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Dudley, K.; Wong, J.; Rhoads, K.; Zamanian, R. T.] Stanford Univ, Stanford, CA 94305 USA. [Lobato, R.] VA Greater Los Angeles, Los Angeles, CA USA. [Maxwell, B.] Legacy Emanuel Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6310 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606082 ER PT J AU Dumas, O Wiley, AS Henneberger, PK Speizer, FE Zock, JP Varraso, R Le Moual, N Boggs, K Camargo, CA AF Dumas, O. Wiley, A. S. Henneberger, P. K. Speizer, F. E. Zock, J. -P. Varraso, R. Le Moual, N. Boggs, K. Camargo, C. A. TI Variations In Disinfectants Used By Nurses In Us Healthcare Facilities SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Dumas, O.; Varraso, R.; Le Moual, N.] INSERM, U1168, VIMA Aging & Chron Dis Epidemiol & Publ Hlth Appr, Villejuif, France. [Wiley, A. S.; Speizer, F. E.; Boggs, K.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Wiley, A. S.; Speizer, F. E.; Boggs, K.] Harvard Med Sch, Boston, MA USA. [Henneberger, P. K.] NIOSH, CDC, Morgantown, WV USA. [Zock, J. -P.] Netherlands Inst Hlth Serv Res NIVEL, Utrecht, Netherlands. [Camargo, C. A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM orianne.dumas@inserm.fr RI LeMoual, Nicole/R-8976-2016 OI LeMoual, Nicole/0000-0002-2723-5569 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7671 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607606 ER PT J AU Dumas, O Varraso, R Speizer, FE Camargo, CA AF Dumas, O. Varraso, R. Speizer, F. E. Camargo, C. A. TI Longitudinal Asthma Patterns In A Large Cohort Of Us Women With 22-Year Follow-Up SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Dumas, O.; Varraso, R.] INSERM, U1168, VIMA Aging & Chron Dis Epidemiol & Publ Hlth Appr, Villejuif, France. [Speizer, F. E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Camargo, C. A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM orianne.dumas@inserm.fr NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2784 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602033 ER PT J AU Emery, MJ Anderson, J Swenson, ER AF Emery, M. J. Anderson, J. Swenson, E. R. TI Ventilation Heterogeneity Is Substantially Decreased When Breathing 5% Carbon Dioxide SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Emery, M. J.; Anderson, J.; Swenson, E. R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Swenson, E. R.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5960 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605620 ER PT J AU Famous, KR Delucchi, K Ware, LB Parsons, PE Thompson, BT Matthay, MA Calfee, CS AF Famous, K. R. Delucchi, K. Ware, L. B. Parsons, P. E. Thompson, B. T. Matthay, M. A. Calfee, C. S. TI Latent Class Analysis Demonstrates The Stability Of Acute Respiratory Distress Syndrome (ards) Endotypes Over Time SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Famous, K. R.; Delucchi, K.; Matthay, M. A.; Calfee, C. S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ware, L. B.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Parsons, P. E.] Univ Vermont, Burlington, VT USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7791 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607724 ER PT J AU Famous, KR Delucchi, K Ware, LB Liu, K Kangelaris, KN Thompson, BT Matthay, M Calfee, CS AF Famous, K. R. Delucchi, K. Ware, L. B. Liu, K. Kangelaris, K. N. Thompson, B. T. Matthay, M. Calfee, C. S. TI Is A Fluid-Conservative Strategy Optimal For All Patients With Acute Respiratory Distress Syndrome (ards)? Latent Class Analysis Indicates That Ards Endotypes Have A Differential Response To Fluid-Management Strategy In The Nhlbi Ards Network Fluid And Catheter Treatment Trial (factt) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Famous, K. R.; Delucchi, K.; Liu, K.; Kangelaris, K. N.; Matthay, M.; Calfee, C. S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ware, L. B.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6445 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606216 ER PT J AU Farmer, MS Preston, I Channick, RN AF Farmer, M. S. Preston, I. Channick, R. N. TI Atypical Hemolytic Uremic Syndrome (hus) And Pulmonary Veno-Occlusive Disease (pvod) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Farmer, M. S.] Baystate Hlth, Springfield, MA USA. [Preston, I.] Tufts Med Ctr, Boston, MA USA. [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3934 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603318 ER PT J AU Fumagalli, J Zhang, C Torsani, V Pirrone, M Gomez, S De Santis, S Tucci, M Ramos, O Lima, C Bento, G Berra, L Kacmarek, R Amato, MBP AF Fumagalli, J. Zhang, C. Torsani, V. Pirrone, M. Gomez, S. De Santis, S. Tucci, M. Ramos, O. Lima, C. Bento, G. Berra, L. Kacmarek, R. Amato, M. B. P. TI Transpulmonary Pressure Based On Absolute Esophageal Pressure Measurement Predicts Morphological Changes Of Lung Parenchyma In An Experimental Animal Model SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Fumagalli, J.; Zhang, C.; Berra, L.; Kacmarek, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Torsani, V.; Gomez, S.; De Santis, S.; Tucci, M.; Ramos, O.; Lima, C.; Bento, G.; Amato, M. B. P.] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Pirrone, M.] Univ Milan, Milan, Italy. EM jfumagalli@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4421 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603803 ER PT J AU Gaffney, A Hang, JQ Lee, MS Su, L Zhang, FY Christiani, DC AF Gaffney, A. Hang, J. -Q. Lee, M. -S. Su, L. Zhang, F. -Y. Christiani, D. C. TI Commuting Mode And Cardiovascular Risk Factors In A Shanghai, China SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gaffney, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hang, J. -Q.; Zhang, F. -Y.] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Lee, M. -S.; Su, L.; Christiani, D. C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. EM agaffney@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5418 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605081 ER PT J AU Gaffney, A Hang, JQ Lee, MS Su, L Zhang, FY Christiani, DC AF Gaffney, A. Hang, J. -Q. Lee, M. -S. Su, L. Zhang, F. -Y. Christiani, D. C. TI Socioeconomic Status And Cardiovascular Health In Shanghai, China SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gaffney, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hang, J. -Q.; Zhang, F. -Y.] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Lee, M. -S.; Su, L.; Christiani, D. C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5419 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605082 ER PT J AU Gaine, SP Channick, RN Di Scala, L Galie, N Ghofrani, HA Hoeper, MM Lang, I McLaughlin, V Preiss, R Rubin, LJ Simonneau, G Sitbon, O Tapson, V Chin, KM AF Gaine, S. P. Channick, R. N. Di Scala, L. Galie, N. Ghofrani, H. -A. Hoeper, M. M. Lang, I. McLaughlin, V. Preiss, R. Rubin, L. J. Simonneau, G. Sitbon, O. Tapson, V. Chin, K. M. TI Targeting The Prostacyclin Pathway In The Treatment Of Connective Tissue Disease Associated Pulmonary Arterial Hypertension (pah): Insights From The Randomized Controlled Griphon Trial With Selexipag SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gaine, S. P.] Mater Misericordiae Univ Hosp, Natl Pulm Hypertens Unit, Dublin, Ireland. [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Di Scala, L.; Preiss, R.] Actel Pharmaceut ltd, Allschwil, Switzerland. [Galie, N.] Univ Bologna, Ist Malattie Apparato Cardiovasc, Bologna, Italy. [Ghofrani, H. -A.] Univ Giessen & Marburg, Lung Ctr, Giessen, Germany. [Hoeper, M. M.] Hannover Med Sch, Dept Resp Med, Hannover, Germany. [Hoeper, M. M.] German Ctr Lung Res, Hannover, Germany. [Lang, I.] Med Univ Vienna, Dept Internal Med 2, Div Cardiol, Allgemeines Krankenhaus, Vienna, Austria. [McLaughlin, V.] Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA. [Rubin, L. J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Simonneau, G.; Sitbon, O.] Univ Paris Sud, Hop Univ Bicetre, Le Kremlin Bicetre, France. [Tapson, V.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Chin, K. M.] UT Southwestern Med Ctr, Dallas, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6466 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606237 ER PT J AU Garshick, E Grady, S Hart, JE Moy, ML Coull, B Schwartz, J Laden, F Koutrakis, P AF Garshick, E. Grady, S. Hart, J. E. Moy, M. L. Coull, B. Schwartz, J. Laden, F. Koutrakis, P. TI Traffic Related Particulate Matter And Elevated Crp In COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Garshick, E.; Grady, S.; Moy, M. L.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Hart, J. E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Coull, B.; Schwartz, J.; Laden, F.; Koutrakis, P.] Harvard Sch Publ Hlth, Boston, MA USA. EM eric.garshick@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4442 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603824 ER PT J AU Gesthalter, YB Koppelman, E Slatore, CG Kinsinger, L Yoon, S Cain, H Tanner, NT Au, DH Clark, J Wiener, RS AF Gesthalter, Y. B. Koppelman, E. Slatore, C. G. Kinsinger, L. Yoon, S. Cain, H. Tanner, N. T. Au, D. H. Clark, J. Wiener, R. S. TI Lessons Learned From Early-Adopting Lung Cancer Screening Programs: Staff Perspectives On Implementation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gesthalter, Y. B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Koppelman, E.; Clark, J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. [Kinsinger, L.] Vet Hlth Adm, Durham, NC USA. [Yoon, S.] VA Boston HealthCare Syst, West Roxbury, MA USA. [Cain, H.] VA CT Healthcare Syst, West Haven, CT USA. [Tanner, N. T.] Med Univ South Carolina, Charleston, SC USA. [Au, D. H.] Univ Washington, Seattle, WA 98195 USA. [Au, D. H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Wiener, R. S.] ENRM VA Hosp, Bedford, MA USA. EM ygesty@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1279 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600279 ER PT J AU Gilpin, SE Charest, JM Tapias, LF Ren, X Wu, T Mathisen, DJ Ott, HC AF Gilpin, S. E. Charest, J. M. Tapias, L. F. Ren, X. Wu, T. Mathisen, D. J. Ott, H. C. TI Patient-Derived Airway Stem Cells In Human Lung Bio-Engineering SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gilpin, S. E.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Charest, J. M.; Tapias, L. F.; Ren, X.; Wu, T.; Mathisen, D. J.; Ott, H. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3078 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602326 ER PT J AU Goto, T Camargo, CA Hasegawa, K AF Goto, T. Camargo, C. A. Hasegawa, K. TI Fractional Exhaled Nitric Oxide Levels In Asthma-COPD Overlap Syndrome: Analysis Of The Nhanes, 2007-2012 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Goto, T.; Camargo, C. A.; Hasegawa, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6238 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606010 ER PT J AU Goto, T Camargo, CA Hasegawa, K AF Goto, T. Camargo, C. A. Hasegawa, K. TI Absence Of Wheezing Is Associated With Underdiagnosis Of Chronic Obstructive Pulmonary Disease: Analysis Of The Nhanes, 2007-2012 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Goto, T.; Camargo, C. A.; Hasegawa, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1703 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600702 ER PT J AU Guo, L Freeman, CM Budoff, MJ Dransfield, MT Han, MK Hokanson, JE Kinney, GL Regan, EA Wells, JM Curtis, JL Martinez, CH AF Guo, L. Freeman, C. M. Budoff, M. J. Dransfield, M. T. Han, M. K. Hokanson, J. E. Kinney, G. L. Regan, E. A. Wells, J. M. Curtis, J. L. Martinez, C. H. CA COPDGene Investigators TI Greater Walking Distance Is Associated With Lower Levels Of Growth Differentiation Factor-15 in COPD: An Analysis Of The COPDgene Cohort SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Guo, L.] Univ Hosp Elect Sci & Technol China, Sichuan Provincal Peoples Hosp, Sichuan Acad Med Sci, Chengdu, Peoples R China. [Freeman, C. M.; Curtis, J. L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Freeman, C. M.; Curtis, J. L.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Budoff, M. J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Dransfield, M. T.; Wells, J. M.] Univ Alabama Birmingham, Birmingham, AL USA. [Dransfield, M. T.; Wells, J. M.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Martinez, C. H.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Kinney, G. L.] Univ Colorado, Aurora, CO USA. [Regan, E. A.] Natl Jewish Hlth & Res Ctr, Denver, CO USA. [Regan, E. A.] Univ Colorado, Denver, CO 80202 USA. EM 18981838226@163.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3483 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602730 ER PT J AU Hariri, LP Adams, DC Lanuti, M Wain, JC Tager, AM Suter, MJ AF Hariri, L. P. Adams, D. C. Lanuti, M. Wain, J. C. Tager, A. M. Suter, M. J. TI Bronchoscopic Optical Coherence Tomography As A Low Risk Method For Microscopic Diagnosis Of Idiopathic Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Hariri, L. P.; Adams, D. C.; Lanuti, M.; Wain, J. C.; Tager, A. M.; Suter, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2608 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601748 ER PT J AU Hashimoto, S Paula, L Winkler, T Oviedo, A Le, L Brandao, J Musch, G Baron, R Melo, MFV AF Hashimoto, S. Paula, L. Winkler, T. Oviedo, A. Le, L. Brandao, J. Musch, G. Baron, R. Melo, M. F. Vidal TI Heterogeneity In Regional Gene Expression In A 24-Hour Sheep Model Of Mild Septic Ards SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Hashimoto, S.; Paula, L.; Winkler, T.; Oviedo, A.; Le, L.; Brandao, J.; Musch, G.; Melo, M. F. Vidal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baron, R.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM soshi@koto.kpu-m.ac.jp NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4402 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603784 ER PT J AU Hibbert, KA Winkler, T Cruz, L Kelly, VJ Holland, CA Brait, KL Venegas, JG Vidal-Melo, M Harris, RS Bajwa, EK AF Hibbert, K. A. Winkler, T. Cruz, L. Kelly, V. J. Holland, C. A. Brait, K. L. Venegas, J. G. Vidal-Melo, M. Harris, R. S. Bajwa, E. K. TI Lung Inflammation In Ards And Heart Failure Is Not Related To The Degree Of Regional Strain SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Hibbert, K. A.; Winkler, T.; Kelly, V. J.; Holland, C. A.; Brait, K. L.; Venegas, J. G.; Vidal-Melo, M.; Harris, R. S.; Bajwa, E. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Cruz, L.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. EM kahibbert@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4423 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603805 ER PT J AU Holland, DP Sheehan, D Wright, A Scott, NA Belknap, RW Borisov, AS AF Holland, D. P. Sheehan, D. Wright, A. Scott, N. A. Belknap, R. W. Borisov, A. S. CA TB Trials Consortium TI Iadhere Study: Cost-Effectiveness Of Self-Administered Isoniazid/rifapentine For Treatment Of Latent Tuberculosis Infection In The United States SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Holland, D. P.] Emory Univ, Atlanta, GA 30322 USA. [Sheehan, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wright, A.] Nashville Metro Publ Hlth Dept, Nashville, TN USA. [Scott, N. A.] CDC Fdn Res Collaborat, Atlanta, GA USA. [Belknap, R. W.] Denver Hlth & Hosp, Denver, CO USA. [Borisov, A. S.] Ctr Dis Control & Prevent, Atlanta, GA USA. EM david.holland@emory.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7888 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607821 ER PT J AU Honda, JR Hasan, NA Zhou, Y Chan, ED AF Honda, J. R. Hasan, N. A. Zhou, Y. Chan, E. D. TI Clinical And Environmental Nontuberculous Mycobacteria From Hawai'i Demonstrate Varying Degrees Of Virulence SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Honda, J. R.] Univ Colorado, Anschutz Med Campus, Aurora, CO USA. [Hasan, N. A.; Zhou, Y.] Natl Jewish Hlth, Denver, CO USA. [Chan, E. D.] Denver Vet Affairs Med Ctr, Denver, CO USA. EM Jennifer.Honda@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7501 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607436 ER PT J AU Huhle, R D'Antini, D Herrmann, J Herzog, M Bluth, T Vidal-Melo, M Cinnella, G Abreu, MGD AF Huhle, R. D'Antini, D. Herrmann, J. Herzog, M. Bluth, T. Vidal-Melo, M. Cinnella, G. Abreu, M. G. D. TI End-Expiratory Airway Pressure Effects On Respiratory System Mechanics And Incidence Of Tidal Hyper-Inflation During Open Abdominal Surgery SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Huhle, R.; Herzog, M.; Bluth, T.; Abreu, M. G. D.] Univ Hosp Carl Gustav Carus, Dresden, Germany. [D'Antini, D.; Cinnella, G.] Univ Foggia, Foggia, Italy. [Herrmann, J.] Univ Iowa, Iowa City, IA USA. [Vidal-Melo, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM robert.huhle@tu-dresden.de NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7928 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749608017 ER PT J AU Iaccarino, J Simmons, J Slatore, CG Gould, MK Wiener, RS AF Iaccarino, J. Simmons, J. Slatore, C. G. Gould, M. K. Wiener, R. S. TI Availability Of Resources And Processes Of Care For Pulmonary Nodule Evaluation: A National Survey Of American Thoracic Society Clinicians SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Iaccarino, J.; Simmons, J.] Boston Univ, Med Ctr, Boston, MA USA. [Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. [Gould, M. K.] Kaiser Permanente Southern Calif, Pasadena, CA USA. [Wiener, R. S.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM jmi@bu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1294 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600294 ER PT J AU Jensen, ME Camargo, CA Gibson, PG Mattes, J Murphy, VE AF Jensen, M. E. Camargo, C. A. Gibson, P. G. Mattes, J. Murphy, V. E. TI Maternal Serum Ditamin D Levels >= 75nmol/l During Pregnancy Are Associated With Fewer Adverse Respiratory Outcomes In Infants At 12 Months Of Age SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Jensen, M. E.; Gibson, P. G.; Murphy, V. E.] Hunter Med Res Inst, New Lambton Hts, NSW, Australia. [Camargo, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mattes, J.] Univ Newcastle, Callaghan, NSW, Australia. EM megan.jensen@newcastle.edu.au NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2172 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601312 ER PT J AU Jones, BE Brown, KA Jones, MM Huttner, B Greene, T Sauer, B Madaras-Kelly, K Rubin, M Goetz, MB Samore, M AF Jones, B. E. Brown, K. A. Jones, M. M. Huttner, B. Greene, T. Sauer, B. Madaras-Kelly, K. Rubin, M. Goetz, M. B. Samore, M. TI Variation In Detection And Coverage Of Resistant Pathogens In Hospitalized Veterans With Pneumonia At 128 Medical Centers SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Jones, B. E.; Brown, K. A.; Huttner, B.; Greene, T.; Sauer, B.] Univ Utah, Salt Lake City, UT USA. [Jones, M. M.; Rubin, M.; Samore, M.] Div Epidemiol, Salt Lake City, UT USA. [Madaras-Kelly, K.] Coll Pharm, Boise, ID USA. [Goetz, M. B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM barbara.jones@hsc.utah.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2104 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601244 ER PT J AU Kadri, SS Spaulding, AB Lai, Y Adjemian, J Prevots, DR Palmore, T Masur, H Rhee, C Klompas, M Dekker, J Suffredini, A Hooper, DC Fridkin, S Danner, RL AF Kadri, S. S. Spaulding, A. B. Lai, Y. Adjemian, J. Prevots, D. R. Palmore, T. Masur, H. Rhee, C. Klompas, M. Dekker, J. Suffredini, A. Hooper, D. C. Fridkin, S. Danner, R. L. CA NIH Antimicrobial Resistance TI Five-Year Trends In Difficult To Treat Antimicrobial-Resistant Gram-Negative Bloodstream Infections Among Inpatients At 180 Us Hospitals SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kadri, S. S.; Palmore, T.; Masur, H.; Dekker, J.; Suffredini, A.; Danner, R. L.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Spaulding, A. B.; Lai, Y.; Adjemian, J.; Prevots, D. R.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Rhee, C.; Klompas, M.] Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Hooper, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fridkin, S.] US Ctr Dis Control & Prevent, Atlanta, GA USA. EM sameer.kadri@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6911 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606682 ER PT J AU Kelly, VJ Winkler, T Kone, M Hamilos, DL Afshar, R Cho, JL Liang, LL Griffith, JW Venegas, JG Luster, AD Medoff, BD Harris, RS AF Kelly, V. J. Winkler, T. Kone, M. Hamilos, D. L. Afshar, R. Cho, J. L. Liang, L. L. Griffith, J. W. Venegas, J. G. Luster, A. D. Medoff, B. D. Harris, R. S. TI Pulmonary Physiologic Response To Segmental Allergen Challenge Differs In Allergic Adults With And Without Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kelly, V. J.; Winkler, T.; Kone, M.; Cho, J. L.; Griffith, J. W.; Venegas, J. G.; Medoff, B. D.; Harris, R. S.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Hamilos, D. L.; Afshar, R.; Liang, L. L.; Luster, A. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM vjkelly@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6634 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606405 ER PT J AU Kelly, VJ Kohli, P Winkler, T Kehl, E Rodriguez-Lopez, J Hibbert, KA Kone, M Venegas, JG Channick, RN Harris, RS AF Kelly, V. J. Kohli, P. Winkler, T. Kehl, E. Rodriguez-Lopez, J. Hibbert, K. A. Kone, M. Venegas, J. G. Channick, R. N. Harris, R. S. TI Novel Pet Vascular Biomarkers In Pulmonary Arterial Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kelly, V. J.; Kohli, P.; Winkler, T.; Rodriguez-Lopez, J.; Hibbert, K. A.; Kone, M.; Venegas, J. G.; Channick, R. N.; Harris, R. S.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Kehl, E.] Baylor Coll Med, Houston, TX 77030 USA. EM vjkelly@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3980 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603364 ER PT J AU Kerr, KM Auger, WR Benza, RL Channick, RN Chin, KM Davis, RD Elliott, CG LaCroix, AZ Madani, MM McLaughlin, V Park, MH AF Kerr, K. M. Auger, W. R. Benza, R. L. Channick, R. N. Chin, K. M. Davis, R. D. Elliott, C. G. LaCroix, A. Z. Madani, M. M. McLaughlin, V. Park, M. H. CA US CTEPH Registry Steering Comm TI Development Of The United States Chronic Thromboembolic Pulmonary Hypertension (cteph) Registry SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kerr, K. M.; Auger, W. R.; LaCroix, A. Z.; Madani, M. M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Benza, R. L.] Allegheny Hlth Network, Pittsburgh, PA USA. [Channick, R. N.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Chin, K. M.] UT Southwestern Med Ctr, Dallas, TX USA. [Davis, R. D.] Duke Univ, Durham, NC USA. [Elliott, C. G.] Intermt Med Ctr, Murray, UT USA. [McLaughlin, V.] Univ Michigan, Hlth Syst Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Park, M. H.] Houston Methodist, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7398 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607334 ER PT J AU Kiss, T Bluth, T Gueldner, A Braune, A Huhle, R Ball, L Simonassi, F Rentzsch, I Wittenstein, J Rocco, PRM Oehme, L Andreeff, M Winkler, T Vidal-Melo, M Pelosi, P Kotzerke, J De Abreu, MG AF Kiss, T. Bluth, T. Gueldner, A. Braune, A. Huhle, R. Ball, L. Simonassi, F. Rentzsch, I. Wittenstein, J. Rocco, P. R. M. Oehme, L. Andreeff, M. Winkler, T. Vidal-Melo, M. Pelosi, P. Kotzerke, J. De Abreu, M. G. TI Effects Of 24h Variable Ventilation On Lung Function And Inflammation In Experimental Severe Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kiss, T.; Bluth, T.; Gueldner, A.; Braune, A.; Huhle, R.; Rentzsch, I.; Wittenstein, J.; Oehme, L.; Andreeff, M.; Winkler, T.; Kotzerke, J.; De Abreu, M. G.] Univ Hosp Carl Gustav Carus, Dresden, Germany. [Ball, L.; Simonassi, F.; Pelosi, P.] Univ Genoa, Genoa, Italy. [Rocco, P. R. M.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Vidal-Melo, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5222 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604736 ER PT J AU Knipe, RS Probst, CK Griffith, JW Shea, BS Liao, JK Tager, AM AF Knipe, R. S. Probst, C. K. Griffith, J. W. Shea, B. S. Liao, J. K. Tager, A. M. TI Critical Importance Of The Rock Isoforms Rock1 And Rock2 For Vascular Leak And Dendritic Cell Recruitment In Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Knipe, R. S.; Probst, C. K.; Griffith, J. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shea, B. S.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Liao, J. K.] Univ Chicago, Chicago, IL 60637 USA. [Tager, A. M.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4546 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604062 ER PT J AU Ko, S Greif, S Lee, JS Liu, A Desai, SA Harrington, A Lee, SM Moy, ML Fan, VS Gould, MK Nguyen, HQ AF Ko, S. Greif, S. Lee, J. S. Liu, A. Desai, S. A. Harrington, A. Lee, S. M. Moy, M. L. Fan, V. S. Gould, M. K. Nguyen, H. Q. TI Validating An Automated Algorithm To Identify Outpatient Treated COPD Exacerbations Using Electronic Medical Records Data SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Ko, S.; Lee, S. M.] Kaiser Permanente Southern Calif, Fontana, CA USA. [Greif, S.] Los Angeles Med Ctr, Los Angeles, CA USA. [Lee, J. S.; Liu, A.; Gould, M. K.; Nguyen, H. Q.] Kaiser Permanente Southern Calif, Pasadena, CA USA. [Desai, S. A.] Kaiser Permanente, San Diego, CA USA. [Harrington, A.] Anaheim Med Ctr, Anaheim, CA USA. [Moy, M. L.] Harvard Med Sch, VA Boston Healthcare Syst, Boston, MA USA. [Fan, V. S.] Seattle VA Med Ctr, Seattle, WA USA. EM Huong.Q2.Nguyen@kp.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1087 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600087 ER PT J AU Kohli, P Staziaki, P Janjua, S Hallett, T Hennessy, O Takx, R Addison, D Lu, M Fintelmann, F Hoffmann, U Celli, B Harris, RS Neilan, T AF Kohli, P. Staziaki, P. Janjua, S. Hallett, T. Hennessy, O. Takx, R. Addison, D. Lu, M. Fintelmann, F. Hoffmann, U. Celli, B. Harris, R. S. Neilan, T. TI Effect Of Emphysema On Re-Admission Rates And Survival In Individuals With Heart Failure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kohli, P.; Staziaki, P.; Janjua, S.; Hallett, T.; Hennessy, O.; Takx, R.; Addison, D.; Lu, M.; Fintelmann, F.; Hoffmann, U.; Harris, R. S.; Neilan, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Celli, B.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3563 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602810 ER PT J AU Kohli, P Staziaki, P Addison, D Hennessy, O Takx, R Janjua, S Hallett, T Lu, M Fintelmann, F Hoffmann, U Celli, B Harris, RS Neilan, T AF Kohli, P. Staziaki, P. Addison, D. Hennessy, O. Takx, R. Janjua, S. Hallett, T. Lu, M. Fintelmann, F. Hoffmann, U. Celli, B. Harris, R. S. Neilan, T. TI Effect Of Unrecognized Emphysema On Re-Admission And Survival In Patients With Congestive Heart Failure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kohli, P.; Staziaki, P.; Addison, D.; Hennessy, O.; Takx, R.; Janjua, S.; Hallett, T.; Lu, M.; Fintelmann, F.; Hoffmann, U.; Harris, R. S.; Neilan, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Celli, B.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3562 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602809 ER PT J AU Kor, DJ Carter, RE Park, PK Festic, E Banner-Goodspeed, V Hinds, RF Talmor, DS Gajic, O Gong, MN AF Kor, D. J. Carter, R. E. Park, P. K. Festic, E. Banner-Goodspeed, V. Hinds, R. F. Talmor, D. S. Gajic, O. Gong, M. N. CA US Critical Illness & Injury TI Lung Injury Prevention Study With Aspirin (lips-A): A Multicenter Randomized Clinical Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kor, D. J.; Carter, R. E.; Hinds, R. F.; Gajic, O.] Mayo Clin, Rochester, MN USA. [Park, P. K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Festic, E.] Mayo Clin, Jacksonville, FL 32224 USA. [Banner-Goodspeed, V.; Talmor, D. S.] Beth Israel Deaconness Med Ctr, Boston, MA USA. [Gong, M. N.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. EM festic.emir@mayo.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2864 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602112 ER PT J AU Lagares, D Grasberger, P Probst, C Engler, A Tager, AM AF Lagares, D. Grasberger, P. Probst, C. Engler, A. Tager, A. M. TI Therapeutic Targeting Of Fibroblast Durotaxis: A Novel Class Of Anti-Fibrotic Therapies For Ipf SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Lagares, D.; Grasberger, P.; Probst, C.; Tager, A. M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Engler, A.] Univ Calif San Diego, La Jolla, CA USA. EM dlagares@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4582 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604098 ER PT J AU Lai, PS Allen, JG Winters, T North, CM Hug, C Vallarino, J Christiani, DC AF Lai, P. S. Allen, J. G. Winters, T. North, C. M. Hug, C. Vallarino, J. Christiani, D. C. TI Occupational Microbial Exposures Of Animal Care Workers Measured By 16s Rdna Sequencing SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Lai, P. S.; Allen, J. G.; Winters, T.; Vallarino, J.; Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. [North, C. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hug, C.] Boston Childrens Hosp, Boston, MA USA. EM pslai@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3004 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602252 ER PT J AU Lasky-Su, JSA Virkud, Y Kelly, RS McGeachie, M Croteau-Chonka, DC Weiss, ST AF Lasky-Su, J. -S. A. Virkud, Y. Kelly, R. S. McGeachie, M. Croteau-Chonka, D. C. Weiss, S. T. TI Gene Expression Networks Of Allergic Asthma As Characterized By Ige Levels Among Costa Rican Children SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Lasky-Su, J. -S. A.; Kelly, R. S.; McGeachie, M.; Croteau-Chonka, D. C.; Weiss, S. T.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Virkud, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2932 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602180 ER PT J AU Lessa, MA Wellman, T De Prost, N Tucci, M Winkler, T Musch, G Chung, JH Baron, R Raby, BA Vidal-Melo, M AF Lessa, M. A. Wellman, T. De Prost, N. Tucci, M. Winkler, T. Musch, G. Chung, J. H. Baron, R. Raby, B. A. Vidal-Melo, M. TI Functional Analysis Of Regionally Differentially Expressed Genes In A Sheep Model Of Lung Injury Due To Endotoxemia And Mechanical Ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Lessa, M. A.; Musch, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wellman, T.; De Prost, N.; Winkler, T.; Vidal-Melo, M.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Tucci, M.] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Chung, J. H.] Univ Chicago, Chicago, IL 60637 USA. [Baron, R.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Raby, B. A.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. EM mlessa@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4403 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603785 ER PT J AU Levy, SD Bajwa, E O'Donnell, W AF Levy, S. D. Bajwa, E. O'Donnell, W. TI Chyloptysis, Hemoptysis, And Chylothorax In A Fifty Year Old Woman SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Levy, S. D.; Bajwa, E.; O'Donnell, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sdlevy@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6043 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605703 ER PT J AU Li, Z Kesse-Guyot, E Dumas, O Garcia-Aymerich, J Leynaert, B Pison, C Le Moual, N Romieu, I Siroux, V Camargo, CA Nadif, R Varraso, R AF Li, Z. Kesse-Guyot, E. Dumas, O. Garcia-Aymerich, J. Leynaert, B. Pison, C. Le Moual, N. Romieu, I. Siroux, V. Camargo, C. A. Nadif, R. Varraso, R. TI Prospective Study Of Alternate Health Eating Index 2010 And Asthma Symptom Score: Mediation Through Body Mass Index And Effect Modification By Smoking SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Li, Z.; Dumas, O.; Le Moual, N.; Nadif, R.; Varraso, R.] INSERM, Villejuif, France. [Kesse-Guyot, E.] INSERM, Bobigny, France. [Garcia-Aymerich, J.] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Leynaert, B.] Univ Paris Diderot, Paris, France. [Pison, C.] CHU Grenoble, La Tronche, France. [Romieu, I.] Int Agcy Res Canc, Lyon, France. [Siroux, V.] Albert Bonniot Inst, La Tronche, France. [Camargo, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM zhen.li@inserm.fr NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1031 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600031 ER PT J AU Lindenauer, PK Stefan, MS Feemster, LC Shieh, MS Carson, SS Au, DH Krishnan, JA AF Lindenauer, P. K. Stefan, M. S. Feemster, L. C. Shieh, M. -S. Carson, S. S. Au, D. H. Krishnan, J. A. TI Overuse Of Antibiotics Among Patients Hospitalized For Exacerbations Of Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Lindenauer, P. K.; Shieh, M. -S.] Univ Massachusetts, Med Sch Baystate, Springfield, MA USA. [Stefan, M. S.] Baystate Med Ctr, Springfield, MA USA. [Feemster, L. C.] Puget Sound VA, Seattle, WA USA. [Feemster, L. C.] Univ Washington, Seattle, WA 98195 USA. [Carson, S. S.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Krishnan, J. A.] Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7878 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607811 ER PT J AU Lynch, Y Clark, B Taylor, H Treviso, L Macht, M White, SD Wimbish, T Moss, M AF Lynch, Y. Clark, B. Taylor, H. Treviso, L. Macht, M. White, S. D. Wimbish, T. Moss, M. TI Accuracy Of The Bedside Swallowing Evaluation And 3-Ounce Water Swallow Test For Diagnosing Aspiration In Survivors Of Acute Respiratory Failure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Lynch, Y.] Denver VA Med Ctr, Denver, CO USA. [Clark, B.; Moss, M.] Univ Colorado, Sch Med, Aurora, CO USA. [Taylor, H.; Treviso, L.; White, S. D.; Wimbish, T.] Univ Colorado Hosp, Aurora, CO USA. [Macht, M.] Crit Care Pulm & Sleep Associates Prof LLP, Lakewood, CO USA. EM ylinne.lynch@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1157 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600157 ER PT J AU Maddock, L Rippberger, E Wang, J Lee, JS Coleman, KJ Desai, SA Fan, VS Gould, MK Moy, ML Towner, WJ Xiang, A Nguyen, HQ AF Maddock, L. Rippberger, E. Wang, J. Lee, J. S. Coleman, K. J. Desai, S. A. Fan, V. S. Gould, M. K. Moy, M. L. Towner, W. J. Xiang, A. Nguyen, H. Q. TI Characteristics Of COPD Patients Who Agree To Participate In A Pragmatic Trial Of Physical Activity Coaching Compared To Non-Participants SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Maddock, L.; Rippberger, E.; Wang, J.; Lee, J. S.; Coleman, K. J.; Gould, M. K.; Towner, W. J.; Xiang, A.; Nguyen, H. Q.] Kaiser Permanente Southern Calif, Pasadena, CA USA. [Desai, S. A.] Kaiser Permanente, San Diego, CA USA. [Fan, V. S.] Seattle VA Med Ctr, Seattle, WA USA. [Moy, M. L.] VA Boston Healthcare Syst, West Roxbury, MA USA. EM Huong.Q2.Nguyen@kp.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2674 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601814 ER PT J AU McKown, AC Semler, MW Thompson, BT Calfee, CS Rice, TW AF McKown, A. C. Semler, M. W. Thompson, B. T. Calfee, C. S. Rice, T. W. TI Driving Pressure And Inflammation In Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [McKown, A. C.; Semler, M. W.; Rice, T. W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Calfee, C. S.] UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5243 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604757 ER PT J AU McNeill, JN Channick, R AF McNeill, J. N. Channick, R. TI A Case Report Of Pulmonary Tumor Emboli Leading To The Diagnosis Of Underlying Squamous Cell Cancer: The Role Of Thromboendartectomy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [McNeill, J. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Channick, R.] MGH, Boston, MA USA. EM jmcneill2@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2255 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601395 ER PT J AU Melzer, AC Feemster, LC Crothers, KA Gillespie, SE Henderson, AG Krishnan, JA Lindenauer, PK McBurnie, M Mularski, RA Naureckas, ET Pickard, S Au, DH AF Melzer, A. C. Feemster, L. C. Crothers, K. A. Gillespie, S. E. Henderson, A. G. Krishnan, J. A. Lindenauer, P. K. McBurnie, M. Mularski, R. A. Naureckas, E. T. Pickard, S. Au, D. H. CA CONCERT TI Respiratory Symptoms Predict Motivation To Quit Smoking Among Smokers With And Without COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Melzer, A. C.; Au, D. H.] VA Puget Sound, Seattle, WA USA. [Feemster, L. C.; Crothers, K. A.] Univ Washington, Seattle, WA 98195 USA. [Gillespie, S. E.; McBurnie, M.; Mularski, R. A.] Kaiser Permanente Northwest, Portland, OR USA. [Henderson, A. G.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Krishnan, J. A.; Naureckas, E. T.] Univ Illinois, Chicago, IL USA. [Lindenauer, P. K.] Bay State Med Ctr, Springfield, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6515 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606286 ER PT J AU Minhas, JK Rahaghi, FN Vegas-Sanchez-Ferrero, G Bowler, RP Wells, JM Come, CE De la Bruere, I Fenster, B Gonzalez, G Diaz, AA Kohli, P Bhatt, SP Lynch, DA Dransfield, MT Estepar, RS Washko, G AF Minhas, J. K. Rahaghi, F. N. Vegas-Sanchez-Ferrero, G. Bowler, R. P. Wells, J. M. Come, C. E. De la Bruere, I. Fenster, B. Gonzalez, G. Diaz, A. A. Kohli, P. Bhatt, S. P. Lynch, D. A. Dransfield, M. T. Estepar, R. San Jose Washko, G. TI The Geometry Of The Right Ventricle From CT Scans As A Predictor Of Pulmonary Vascular Disease In Smokers In The COPDgene Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Minhas, J. K.; Rahaghi, F. N.; Vegas-Sanchez-Ferrero, G.; Come, C. E.; De la Bruere, I.; Gonzalez, G.; Diaz, A. A.; Estepar, R. San Jose; Washko, G.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Bowler, R. P.; Fenster, B.; Lynch, D. A.] Natl Jewish Hlth, Denver, CO USA. [Wells, J. M.; Bhatt, S. P.; Dransfield, M. T.] Univ Alabama Birmingham, Birmingham, AL USA. [Kohli, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM frahaghi@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7342 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607278 ER PT J AU Montesantos, S Katz, IM Pichelin, M Harris, RS Venegas, JG Caillibotte, G AF Montesantos, S. Katz, I. M. Pichelin, M. Harris, R. S. Venegas, J. G. Caillibotte, G. TI Statistical Comparison Of Segmented High Resolution Computed Tomography (hrct) Images Taken At Mean Lung Volume Versus Total Lung Capacity In Subjects With Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc ID MODELS C1 [Montesantos, S.; Katz, I. M.; Pichelin, M.; Caillibotte, G.] Air Liquide Sante Int, Jouy En Josas, France. [Harris, R. S.; Venegas, J. G.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. EM spyridon.montesantos@airliquide.com NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2489 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601629 ER PT J AU Montesi, SB Namude, M Pardo, A Selman, M Tager, AM Lagares, D AF Montesi, S. B. Namude, M. Pardo, A. Selman, M. Tager, A. M. Lagares, D. TI Soluble Ephrin-B2 Is A Novel Biomarker Of Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Montesi, S. B.; Namude, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pardo, A.] Univ Nacl Autonoma Mexico, Mexico City, DF, Mexico. [Selman, M.] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Tager, A. M.; Lagares, D.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7217 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607154 ER PT J AU Moon, HG Lee, J Choi, H Jin, Y AF Moon, H. -G. Lee, J. Choi, H. Jin, Y. TI Pro-Inflammatory Function Of Circulating Exosome After Hyperoxia Induced Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Moon, H. -G.; Jin, Y.] Boston Univ, Boston, MA 02215 USA. [Lee, J.; Choi, H.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5921 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605582 ER PT J AU Moraco, A Bozkurtlar, E Hironori, U Akalin, A Mark, E Kopec, S AF Moraco, A. Bozkurtlar, E. Hironori, U. Akalin, A. Mark, E. Kopec, S. TI Acute Fibrinous And Organizing Pneumonia: A Newly Recognized, But Poorly Understood Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Moraco, A.; Akalin, A.; Kopec, S.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Bozkurtlar, E.] Marmara Univ, Sch Med, Istanbul, Turkey. [Hironori, U.] Toanomon Hosp, Tokyo, Japan. [Mark, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM andrewmoraco@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1149 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600149 ER PT J AU Morrow, JD Hersh, CP Pinto-Plata, V Celli, BR Marchetti, N Criner, GJ Bueno, R Washko, G Glass, K Quackenbush, J Silverman, EK DeMeo, DL AF Morrow, J. D. Hersh, C. P. Pinto-Plata, V. Celli, B. R. Marchetti, N. Criner, G. J. Bueno, R. Washko, G. Glass, K. Quackenbush, J. Silverman, E. K. DeMeo, D. L. TI Dna Methylation Sites In Human Lung Tissue Are Associated With COPD Status SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Morrow, J. D.; Hersh, C. P.; Celli, B. R.; Glass, K.; Silverman, E. K.; DeMeo, D. L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Pinto-Plata, V.] Baystate Med Ctr, Springfield, MA USA. [Marchetti, N.; Criner, G. J.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Bueno, R.; Washko, G.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2352 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601492 ER PT J AU Mortensen, EM Metersky, ML Frei, CR Attridge, RT Anzueto, A AF Mortensen, E. M. Metersky, M. L. Frei, C. R. Attridge, R. T. Anzueto, A. TI Azithromycin Is Associated With Improved Survival In Patients With Healthcare-Associated Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Mortensen, E. M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Metersky, M. L.] Univ Connecticut, Sch Med, Farmington, CT USA. [Frei, C. R.] UTHSCSA, San Antonio, TX USA. [Attridge, R. T.] Univ Incarnate Word, San Antonio, TX USA. [Anzueto, A.] Univ Texas San Antonio, San Antonio, TX USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2139 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601279 ER PT J AU Moschovis, PP Wiens, MO Kiwanuka, JP Kumbakumba, E Ndamira, A Keneema, O Hayden, D Hess, DR Ansermino, JM Hibberd, PL AF Moschovis, P. P. Wiens, M. O. Kiwanuka, J. P. Kumbakumba, E. Ndamira, A. Keneema, O. Hayden, D. Hess, D. R. Ansermino, J. M. Hibberd, P. L. TI Predictors Of Unreliable Pulse Oximetry Among Young Children With Sepsis In Uganda SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Moschovis, P. P.; Hayden, D.; Hess, D. R.; Hibberd, P. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wiens, M. O.; Ansermino, J. M.] Univ British Columbia, Vancouver, BC, Canada. [Kiwanuka, J. P.; Kumbakumba, E.; Keneema, O.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Ndamira, A.] Holy Innocents Childrens Hosp, Mbarara, Uganda. EM pmoschovis@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4763 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604279 ER PT J AU Moskowitz, A Astor, T Selig, M Cheng, G Kradin, RL AF Moskowitz, A. Astor, T. Selig, M. Cheng, G. Kradin, R. L. TI The Relationship Between Alveolar Wall Thickness And Lung Function In Orthotopic Lung Grafts SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Moskowitz, A.; Astor, T.; Selig, M.; Cheng, G.; Kradin, R. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3459 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602706 ER PT J AU Ribeiro, GCM Hashimoto, S Winkler, T Grogg, K Paula, L Oviedo, A Brandao, J Vidal-Melo, M AF Motta Ribeiro, G. C. Hashimoto, S. Winkler, T. Grogg, K. Paula, L. Oviedo, A. Brandao, J. Vidal-Melo, M. TI Regional Pulmonary Metabolic Activation In The First 24h Of Lung Injury Due To Mild Endotoxemia And Mechanical Ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Motta Ribeiro, G. C.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Hashimoto, S.] Kyoto Prefectural Univ Med, Kyoto 8566, Japan. [Winkler, T.; Vidal-Melo, M.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Grogg, K.; Paula, L.; Oviedo, A.; Brandao, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM gabrielcasulari@poli.ufrj.br NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4408 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603790 ER PT J AU Muyanja, D Vallarino, J Allen, JG Kakuhikire, B Christiani, DC Tsai, AC Lai, PS AF Muyanja, D. Vallarino, J. Allen, J. G. Kakuhikire, B. Christiani, D. C. Tsai, A. C. Lai, P. S. TI Fine Particulate Matter Exposure From Biomass Fuel Use In Rural Uganda SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Muyanja, D.; Kakuhikire, B.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Vallarino, J.; Allen, J. G.; Lai, P. S.] Harvard Sch Publ Hlth, Boston, MA USA. [Christiani, D. C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Tsai, A. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mdmuyanja@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7883 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607816 ER PT J AU Ngo, D Latourelle, J Dupuis, J Clish, C Wang, TJ O'Connor, GT Gerszten, RE AF Ngo, D. Latourelle, J. Dupuis, J. Clish, C. Wang, T. J. O'Connor, G. T. Gerszten, R. E. TI Metabolite Profiles Of COPD And Pulmonary Function In The Framingham Heart Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Ngo, D.; Gerszten, R. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Latourelle, J.; Dupuis, J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Clish, C.] Broad Inst, Cambridge, MA USA. [Wang, T. J.] Vanderbuilt Univ, Nashville, TN USA. [O'Connor, G. T.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM dngo1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3505 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602752 ER PT J AU North, CM Kakuhikire, B Vorechovska, D Kigozi, SH McDonough, AQ Christiani, DC Bangsberg, DR Tsai, AC Siedner, MJ AF North, C. M. Kakuhikire, B. Vorechovska, D. Kigozi, S. H. McDonough, A. Q. Christiani, D. C. Bangsberg, D. R. Tsai, A. C. Siedner, M. J. TI Prevalence And Correlates Of Obstructive Lung Disease In Rural Uganda: A Population-Based, Cross-Sectional Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [North, C. M.; Vorechovska, D.; McDonough, A. Q.; Bangsberg, D. R.; Tsai, A. C.; Siedner, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kakuhikire, B.; Kigozi, S. H.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Christiani, D. C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. EM cnorth@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2003 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601144 ER PT J AU Osorio-Valencia, JS Kelly, VJ Harris, RS Winkler, T Venegas, JG AF Osorio-Valencia, J. S. Kelly, V. J. Harris, R. S. Winkler, T. Venegas, J. G. TI Peri-Bronchial Parenchyma Expands Less Than Segmental After Bronchoconstriction, A Difference That Increases With Lung Volume SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Osorio-Valencia, J. S.; Kelly, V. J.; Harris, R. S.; Winkler, T.; Venegas, J. G.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. EM josorio-valencia@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6624 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606395 ER PT J AU Patino, CM Au, DH Lane, CJ Buist, AS Vollmer, WM AF Patino, C. M. Au, D. H. Lane, C. J. Buist, A. S. Vollmer, W. M. TI Building Research Capacity In Middle And Low-Income Countries Through Research Methodology And Career Development Education SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Patino, C. M.; Lane, C. J.] Univ Southern Calif, Los Angeles, CA 90032 USA. [Au, D. H.] VA Puget Sound, Seattle, WA USA. [Buist, A. S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Vollmer, W. M.] Kaiser Permanente, Portland, OR USA. EM patinosu@usc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7567 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607502 ER PT J AU Pickerodt, PA Kronfeldt, S Russ, M Vorbrodt, K Lother, P Busch, T Boemke, W Swenson, ER Francis, RCE AF Pickerodt, P. A. Kronfeldt, S. Russ, M. Vorbrodt, K. Lother, P. Busch, T. Boemke, W. Swenson, E. R. Francis, R. C. E. TI Carbonic Anhydrase Is Not A Relevant Nitrite Reductase In The Lung SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Pickerodt, P. A.; Kronfeldt, S.; Russ, M.; Vorbrodt, K.; Lother, P.; Boemke, W.; Francis, R. C. E.] Charite Univ Med Berlin, Berlin, Germany. [Busch, T.] Univ Leipzig, Leipzig, Germany. [Swenson, E. R.] Univ Washington, Seattle, WA 98195 USA. [Swenson, E. R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. EM philipp.pickerodt@charite.de NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3891 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603275 ER PT J AU Putcha, N Dusser, D Anzueto, A Metzdorf, N Mueller, A Wise, RA AF Putcha, N. Dusser, D. Anzueto, A. Metzdorf, N. Mueller, A. Wise, R. A. TI Mortality And Exacerbation Risk By Body Mass Index In The (tiospir (R)) Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Putcha, N.; Wise, R. A.] Johns Hopkins Univ, Baltimore, MD USA. [Dusser, D.] Hop Cochin, Serv Pneumol, Paris, France. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Metzdorf, N.] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. [Mueller, A.] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3530 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602777 ER PT J AU Putman, RK Hatabu, H Araki, T Gudmundsson, G Gao, W Nishino, M Okajima, Y Dupuis, J Latourelle, J Cho, MH El-Chemaly, S Coxson, H Celli, BR Fernandez, IE Zazueta, OE Ross, JC Harmouche, R Estepar, RS Diaz, AA Sigurdsson, S Gudmundsson, E Eiriksdottir, G Aspelund, T Budoff, MJ Kinney, GL Hokanson, J Williams, MC Murchison, JT MacNee, W Hoffmann, U O'Donnell, CJ Launer, LJ Harris, TB Gudnason, V Silverman, EK O'Connor, GT Washko, G Rosas, IO Hunninghake, GM AF Putman, R. K. Hatabu, H. Araki, T. Gudmundsson, G. Gao, W. Nishino, M. Okajima, Y. Dupuis, J. Latourelle, J. Cho, M. H. El-Chemaly, S. Coxson, H. Celli, B. R. Fernandez, I. E. Zazueta, O. E. Ross, J. C. Harmouche, R. Estepar, R. San Jose Diaz, A. A. Sigurdsson, S. Gudmundsson, E. Eiriksdottir, G. Aspelund, T. Budoff, M. J. Kinney, G. L. Hokanson, J. Williams, M. C. Murchison, J. T. MacNee, W. Hoffmann, U. O'Donnell, C. J. Launer, L. J. Harris, T. B. Gudnason, V. Silverman, E. K. O'Connor, G. T. Washko, G. Rosas, I. O. Hunninghake, G. M. CA COPDGene ECLIPSE TI Mortality And Undiagnosed Interstitial Lung Abnormalities SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Putman, R. K.; Hatabu, H.; Araki, T.; Nishino, M.; Okajima, Y.; Cho, M. H.; El-Chemaly, S.; Celli, B. R.; Fernandez, I. E.; Zazueta, O. E.; Ross, J. C.; Harmouche, R.; Estepar, R. San Jose; Diaz, A. A.; Silverman, E. K.; Washko, G.; Rosas, I. O.; Hunninghake, G. M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Gudmundsson, G.] Landspital Univ Hosp, Reykjavik, Iceland. [Gao, W.; Dupuis, J.; Latourelle, J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Coxson, H.] Univ British Columbia, Vancouver, BC, Canada. [Sigurdsson, S.; Gudmundsson, E.; Eiriksdottir, G.; Aspelund, T.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Budoff, M. J.] Harbor UCLA, Los Angeles Biomed Res Inst, Torrance, CA USA. [Kinney, G. L.; Hokanson, J.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO USA. [Williams, M. C.] Univ Edinburgh, British Heart Fdn, Edinburgh, Midlothian, Scotland. [Murchison, J. T.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [MacNee, W.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Hoffmann, U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Donnell, C. J.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Launer, L. J.; Harris, T. B.] NIA, NIH, Baltimore, MD 21224 USA. [O'Connor, G. T.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM rputman@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4284 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603667 ER PT J AU Reddy, KP Parker, RA Losina, E Baggett, TP Paltiel, AD Rigotti, NA Weinstein, MC Freedberg, KA Walensky, RP AF Reddy, K. P. Parker, R. A. Losina, E. Baggett, T. P. Paltiel, A. D. Rigotti, N. A. Weinstein, M. C. Freedberg, K. A. Walensky, R. P. TI Projected Burden Of Lung Cancer Among People With Hiv In The United States SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Reddy, K. P.; Parker, R. A.; Baggett, T. P.; Rigotti, N. A.; Freedberg, K. A.; Walensky, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Losina, E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Paltiel, A. D.] Yale Sch Publ Hlth, New Haven, CT USA. [Weinstein, M. C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4721 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604237 ER PT J AU Reynolds, IR Chan, ED AF Reynolds, I. R. Chan, E. D. TI An Update On The Trends And Treatment In Multidrug-Resistant Tuberculosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Reynolds, I. R.] Univ Colorado, Denver, CO USA. [Chan, E. D.] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5533 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605196 ER PT J AU Rinne, S Bastian, LA Lindenauer, PK Kaboli, P Cook, MA Wong, ES Liu, CF AF Rinne, S. Bastian, L. A. Lindenauer, P. K. Kaboli, P. Cook, M. A. Wong, E. S. Liu, C. -F. TI Organizational Factors Associated With Length Of Stay For Veterans With Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Rinne, S.] Yale Univ, New Haven, CT USA. [Bastian, L. A.] VA Connecticut Healthcare Syst, Newington, CT USA. [Lindenauer, P. K.] Baystate Med Ctr, Springfield, MA USA. [Kaboli, P.] Iowa City Va Hlth Care Syst, Iowa City, IA USA. [Cook, M. A.; Wong, E. S.; Liu, C. -F.] VA Puget Sound Healthcare Syst, Seattle, WA USA. EM seppo.rinne@yale.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6154 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605814 ER PT J AU Rinne, S Gerity, AH Thayer, LM Liu, CF Cook, MA Bastian, LA AF Rinne, S. Gerity, A. H. Thayer, L. M. Liu, C. -F. Cook, M. A. Bastian, L. A. TI Gender Differences In Appropriate Treatment For Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Rinne, S.] Yale Univ, New Haven, CT USA. [Gerity, A. H.; Thayer, L. M.; Bastian, L. A.] VA Connecticut Healthcare Syst, Newington, CT USA. [Liu, C. -F.; Cook, M. A.] VA Puget Sound Healthcare Syst, Seattle, WA USA. EM seppo.rinne@yale.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4560 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604076 ER PT J AU Russell, DW Payne, GA Xing, D Wu, Y Viera, L Szul, T Gautney, J McNicholas-Bevensee, CM Gaggar, A Yang, Q Xu, X Jackson, PL Dransfield, MT Blalock, JE Wells, JM AF Russell, D. W. Payne, G. A. Xing, D. Wu, Y. Viera, L. Szul, T. Gautney, J. McNicholas-Bevensee, C. M. Gaggar, A. Yang, Q. Xu, X. Jackson, P. L. Dransfield, M. T. Blalock, J. E. Wells, J. M. TI The Extracellular Matrix Collagen Fragment Acpgp Facilitates Pulmonary Vascular Remodeling Through Rho Kinase Signaling SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Payne, G. A.; Xing, D.; Wu, Y.; Viera, L.; McNicholas-Bevensee, C. M.; Yang, Q.; Blalock, J. E.] Univ Alabama Birmingham, Birmingham, AL USA. [Dransfield, M. T.; Wells, J. M.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2798 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602047 ER PT J AU Sanchez-Ferrero, GV Gonzalez, G Rahaghi, FN Minhas, J Bowler, RP Wells, JM Come, CE De La Bruere, I Fenster, B Diaz, AA Kohli, P Bhatt, SP Lynch, DA Dransfield, MT Washko, G Estepar, RS AF Sanchez-Ferrero, G. Vegas Gonzalez, G. Rahaghi, F. N. Minhas, J. Bowler, R. P. Wells, J. M. Come, C. E. De La Bruere, I. Fenster, B. Diaz, A. A. Kohli, P. Bhatt, S. P. Lynch, D. A. Dransfield, M. T. Washko, G. Estepar, R. San Jose TI Automatic Segmentation Of The Heart With A Statistical Shape Model And Tissue Characteristics In CT Scans From The COPDgene Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Sanchez-Ferrero, G. Vegas; Gonzalez, G.; Rahaghi, F. N.; Minhas, J.; Come, C. E.; De La Bruere, I.; Diaz, A. A.; Estepar, R. San Jose] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Bowler, R. P.; Fenster, B.; Lynch, D. A.] Natl Jewish Hlth, Denver, CO USA. [Wells, J. M.] Univ Alabama Birmingham UAB, Birmingham, AL USA. [Kohli, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhatt, S. P.; Dransfield, M. T.] Univ Alabama Birmingham, Birmingham, AL USA. [Washko, G.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2291 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601431 ER PT J AU Santos, A Rivas, E Rodriguez-Roisin, R Sanchez, M Ruiz-Cabello, J Arismendi, E Venegas, JG AF Santos, A. Rivas, E. Rodriguez-Roisin, R. Sanchez, M. Ruiz-Cabello, J. Arismendi, E. Venegas, J. G. TI Is The Lung In Obesity Also Obese?: lung Tissue Volume is Elevated In Obesity And Reduced By Bariatric Surgery SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Santos, A.; Venegas, J. G.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Rivas, E.; Rodriguez-Roisin, R.; Sanchez, M.; Arismendi, E.] Univ Barcelona, Hosp Clin, Barcelona, Spain. [Ruiz-Cabello, J.] Ctr Nacl Invest Cardiovasc Carlos III CNIC, Madrid, Spain. EM asantosoviedo@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6623 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606394 ER PT J AU Sicard, D Tan, Q Choi, KM Mehra, D Lagares, D Probst, C Tager, AM Tschumperlin, DJ AF Sicard, D. Tan, Q. Choi, K. M. Mehra, D. Lagares, D. Probst, C. Tager, A. M. Tschumperlin, D. J. TI Taz Activation Promotes Fibroblast- Mediated Matrix Stiffening In The Lung SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Sicard, D.; Tan, Q.; Choi, K. M.; Mehra, D.; Tschumperlin, D. J.] Mayo Clin, Rochester, MN USA. [Lagares, D.; Probst, C.; Tager, A. M.] Massachusetts Gen Hosp, Charlestown, MA USA. EM sicard.delphine@mayo.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4580 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604096 ER PT J AU Sullivan, DR Golden, SE Ganzini, L Wiener, RS Slatore, CG AF Sullivan, D. R. Golden, S. E. Ganzini, L. Wiener, R. S. Slatore, C. G. TI Association Of Actual And Preferred Decision-Making Roles With Patient-Reported Satisfaction And Quality Of Medical Care Among Patients With Pulmonary Nodules SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Sullivan, D. R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Golden, S. E.; Ganzini, L.; Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. [Wiener, R. S.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM sullivad@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2684 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601824 ER PT J AU Suryadevara, V Huang, L Berdyshev, EV Tager, AM Royston, T Natarajan, V AF Suryadevara, V. Huang, L. Berdyshev, E. V. Tager, A. M. Royston, T. Natarajan, V. TI Differential Role Of Phospholipase D In Regulating Emt And Fibroblast Differentiation In Bleomycin-Induced Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Suryadevara, V.; Huang, L.; Royston, T.; Natarajan, V.] Univ Illinois, Chicago, IL USA. [Berdyshev, E. V.] Natl Jewish Hlth, Denver, CO USA. [Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM vsurya2@uic.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2415 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601555 ER PT J AU Suter, MJ Adams, DC Hariri, LP Miller, AJ Holz, JA Szabari, MV Harris, RS Cho, JL Griffith, JW Hamilos, DL Luster, AD Medoff, BD AF Suter, M. J. Adams, D. C. Hariri, L. P. Miller, A. J. Holz, J. A. Szabari, M. V. Harris, R. S. Cho, J. L. Griffith, J. W. Hamilos, D. L. Luster, A. D. Medoff, B. D. TI Quantitative Assessment Of Airway Remodeling With Birefringence Microscopy: Phenotyping Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Suter, M. J.; Adams, D. C.; Hariri, L. P.; Miller, A. J.; Holz, J. A.; Szabari, M. V.; Cho, J. L.; Griffith, J. W.; Hamilos, D. L.; Luster, A. D.; Medoff, B. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R. S.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. EM MSUTER@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6171 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605831 ER PT J AU Taylor, MS Myers, LC Selig, MK Rajagopal, J Chivukula, RR O'Donnell, WJ Medoff, BD Kradin, RL AF Taylor, M. S. Myers, L. C. Selig, M. K. Rajagopal, J. Chivukula, R. R. O'Donnell, W. J. Medoff, B. D. Kradin, R. L. TI Defective Alveolar Epithelial Cell Regeneration In A 27 Year-Old Man With Acute Respiratory Distress Syndrome (ards) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Taylor, M. S.; Myers, L. C.; Selig, M. K.; Rajagopal, J.; Chivukula, R. R.; O'Donnell, W. J.; Medoff, B. D.; Kradin, R. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1889 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601030 ER PT J AU Teshome, M Denman, T Teodorescu, M AF Teshome, M. Denman, T. Teodorescu, M. TI Obstructive Sleep Apnea Features, Lower Airway Obstruction And Inflammation In Patients With Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Teshome, M.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Denman, T.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Teodorescu, M.] Univ Wisconsin, Sch Med, Madison, WI USA. EM mteshome@uwhealth.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6639 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606410 ER PT J AU Teylan, M Homsy, D Okunbur, O Gao, J Garshick, E Moy, ML AF Teylan, M. Homsy, D. Okunbur, O. Gao, J. Garshick, E. Moy, M. L. TI The Minimal Clinically Important Difference For Daily Step Counts In Persons With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Teylan, M.; Homsy, D.; Okunbur, O.; Gao, J.; Garshick, E.; Moy, M. L.] VA Boston Healthcare Syst, Boston, MA USA. EM marilyn.moy@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5742 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605404 ER PT J AU Teylan, M Homsy, D Okunbur, O Gao, J Garshick, E Moy, ML AF Teylan, M. Homsy, D. Okunbur, O. Gao, J. Garshick, E. Moy, M. L. TI Concordance Between Self-Reported And Chart-Based Assessment Of Comorbidities In Veterans With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Teylan, M.; Homsy, D.; Okunbur, O.; Gao, J.; Garshick, E.; Moy, M. L.] VA Boston Healthcare Syst, Boston, MA USA. EM marilyn.moy@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3580 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602827 ER PT J AU Tham, A AF Tham, A. TI Modeling Vascular Inflammation And Atherogenicity After Inhalation Of Ambient Levels Of Ozone: Exploratory Lessons From Transcriptomics SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Tham, A.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1183 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600183 ER PT J AU Trevor, J Zhi, D Wang, F Dransfield, MT Curtiss, M Deshane, J AF Trevor, J. Zhi, D. Wang, F. Dransfield, M. T. Curtiss, M. Deshane, J. TI Longitudinal Changes In Proportions Of Regulatory T Cell And Myeloid Cell Populations Following Bronchial Thermoplasty SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Trevor, J.; Zhi, D.; Wang, F.; Dransfield, M. T.; Curtiss, M.] Univ Alabama Birmingham, Birmingham, AL USA. [Trevor, J.; Dransfield, M. T.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Deshane, J.] UAB, Birmingham, AL USA. EM jtrevor@uab.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1335 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600335 ER PT J AU Triplette, M Sigel, K Morris, AM Petraglia, A Wisnivesky, JP Kong, CY Diaz, P Crothers, KA AF Triplette, M. Sigel, K. Morris, A. M. Petraglia, A. Wisnivesky, J. P. Kong, C. Y. Diaz, P. Crothers, K. A. TI The Association Between Emphysema And Non-Calcified Lung Nodules In Hiv-Infected And Uninfected Individuals And Implications For Lung Cancer Screening SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Triplette, M.; Crothers, K. A.] Univ Washington, Seattle, WA 98195 USA. [Sigel, K.] Mt Sinai Sch Med, New York, NY USA. [Morris, A. M.; Petraglia, A.] Univ Pittsburgh, Pittsburgh, PA USA. [Wisnivesky, J. P.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Kong, C. Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Diaz, P.] Ohio Univ, Columbus, OH USA. EM mtrip@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4719 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604235 ER PT J AU Tukey, MH Clark, J Bolton, R Slatore, CG Au, DH Wiener, RS AF Tukey, M. H. Clark, J. Bolton, R. Slatore, C. G. Au, D. H. Wiener, R. S. TI Readiness For Implementation Of CT Lung Cancer Screening Within A National Healthcare System SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Tukey, M. H.] Rhode Isl Hosp, Providence, RI USA. [Clark, J.; Bolton, R.] ENRM VA Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. [Au, D. H.] VA Puget Sound, Seattle, WA USA. [Wiener, R. S.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM mtukey@lifespan.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1280 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600280 ER PT J AU Varraso, R Dumas, O Boogs, KM Willett, WC Speizer, FE Camargo, CA AF Varraso, R. Dumas, O. Boogs, K. M. Willett, W. C. Speizer, F. E. Camargo, C. A. TI Prospective Study Of Processed Meat Intake And The Risk Of Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Varraso, R.; Dumas, O.] INSERM, Villejuif, France. [Boogs, K. M.; Speizer, F. E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Boogs, K. M.; Speizer, F. E.] Harvard Med Sch, Boston, MA USA. [Willett, W. C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Camargo, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM raphaelle.varraso@inserm.fr NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2995 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602243 ER PT J AU Wan, ES Kantorowski, A Teylan, M Homsy, D Garshick, E Moy, ML AF Wan, E. S. Kantorowski, A. Teylan, M. Homsy, D. Garshick, E. Moy, M. L. TI Self-Reported Daily Physical Activity Complements Objectively Measured Physical Activity In Veterans With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Wan, E. S.; Kantorowski, A.; Teylan, M.; Homsy, D.; Garshick, E.; Moy, M. L.] VA Boston Healthcare Syst, West Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4523 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604039 ER PT J AU Wang, Z Wei, Y Zhang, R Su, L Khetani, R Sui, SH Lin, X Bajwa, EK Thompson, BT Wurfel, MM Christiani, DC AF Wang, Z. Wei, Y. Zhang, R. Su, L. Khetani, R. Sui, S. Ho Lin, X. Bajwa, E. K. Thompson, B. T. Wurfel, M. M. Christiani, D. C. TI Targeted Sequencing Of Top Loci Identified By Genome-Wide Association Study (gwas) Associated With Acute Respiratory Distress Syndrome (ards) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Wang, Z.; Wei, Y.; Zhang, R.; Khetani, R.; Sui, S. Ho; Lin, X.; Christiani, D. C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Su, L.] Harvard Sch Publ Hlth, Boston, MA USA. [Bajwa, E. K.; Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wurfel, M. M.] Harborview Med Ctr, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7792 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607725 ER PT J AU Wang, Z Wei, Y Tejera, P Su, L Bajwa, EK Christiani, DC AF Wang, Z. Wei, Y. Tejera, P. Su, L. Bajwa, E. K. Christiani, D. C. TI A Functional Missense Snp In Lrrc16a Contributes To An Improved Prognosis Of Ards Patients Mediated Through Attenuated Platelet Count Decline In Icu SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Wang, Z.; Wei, Y.; Tejera, P.; Su, L.; Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. [Bajwa, E. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7489 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607424 ER PT J AU Wepler, M Beloiartsev, A Panigrahy, D Bloch, DB Ichinose, F Zapol, WM AF Wepler, M. Beloiartsev, A. Panigrahy, D. Bloch, D. B. Ichinose, F. Zapol, W. M. TI Soluble Epoxide Hydrolase Deficiency Or Inhibition Enhances Murine Hypoxic Pulmonary Vasoconstriction After Lipopolysaccharide Challenge SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Wepler, M.; Beloiartsev, A.; Bloch, D. B.; Ichinose, F.; Zapol, W. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wepler, M.; Beloiartsev, A.; Panigrahy, D.; Bloch, D. B.; Ichinose, F.; Zapol, W. M.] Harvard Med Sch, Boston, MA USA. [Panigrahy, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4785 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604300 ER PT J AU Winkler, T Thamrin, C Farah, CS King, GG AF Winkler, T. Thamrin, C. Farah, C. S. King, G. G. TI Regional Increase In Airway Wall Thickness Could Explain Increase In Ventilation Defects (vdefs) And Heterogeneity In Ventilation In Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Winkler, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winkler, T.] Harvard Med Sch, Boston, MA USA. [Thamrin, C.; King, G. G.] Univ Sydney, Glebe, NSW, Australia. [Farah, C. S.] Univ Sydney, Woolcock Inst Med Res, Glebe, NSW, Australia. [Farah, C. S.] Univ Sydney, Sydney Med Sch, Glebe, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7524 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607459 ER PT J AU Winkler, T Braune, A Kelly, VJ Harris, RS Musch, G Rashid, A Venegas, JG AF Winkler, T. Braune, A. Kelly, V. J. Harris, R. S. Musch, G. Rashid, A. Venegas, J. G. TI Unstable Size Of Ventilation Defects (vdefs) In An Animal Model Of Bronchoconstriction Using Continuous Methacholine (mch) Infusion SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Winkler, T.; Kelly, V. J.; Harris, R. S.; Musch, G.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winkler, T.; Kelly, V. J.; Harris, R. S.; Musch, G.; Venegas, J. G.] Harvard Med Sch, Boston, MA USA. [Braune, A.] Univ Hosp Carl Gustav Carus, Dresden, Germany. [Rashid, A.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6635 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606406 ER PT J AU Witkin, AS Rodriguez-Lopez, J Chang, Y Huang, F Jaff, M Parry, BA Rosenfield, K Rosovsky, R Channick, RN Kabrhel, C AF Witkin, A. S. Rodriguez-Lopez, J. Chang, Y. Huang, F. Jaff, M. Parry, B. A. Rosenfield, K. Rosovsky, R. Channick, R. N. Kabrhel, C. TI Chronic Right Ventricular Pressure Overload May Be Protective In Patients With Large Acute Pulmonary Emboli SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Witkin, A. S.; Rodriguez-Lopez, J.; Chang, Y.; Huang, F.; Jaff, M.; Parry, B. A.; Rosenfield, K.; Rosovsky, R.; Channick, R. N.; Kabrhel, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM aswitkin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3896 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603280 ER PT J AU Zhang, R Wang, Z Wei, Y Alvarez, PT Zhu, Z Su, L Bajwa, EK Thompson, BT Christiani, DC AF Zhang, R. Wang, Z. Wei, Y. Alvarez, P. T. Zhu, Z. Su, L. Bajwa, E. K. Thompson, B. T. Christiani, D. C. TI A Two-Stage Association Study Identifies A High Risk Window Of Acute Respiratory Distress Syndrome Onset Time Correlated With Poor 28 Day Overall Survival SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Zhang, R.; Wang, Z.; Alvarez, P. T.; Zhu, Z.; Su, L.; Christiani, D. C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Wei, Y.] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China. [Bajwa, E. K.; Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ruzhang@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7794 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607727 ER PT J AU Kwong, KK Chan, ST AF Kwong, K. K. Chan, S. -T. TI Oxytocin, a missing link of the gut-brain axis between probiotics and chronic migraine? Comment on 'The effects of the multispecies probiotic mixture Ecologic (R) Barrier on migraine: results of an open-label pilot study' SO BENEFICIAL MICROBES LA English DT Letter ID RECEPTOR EXPRESSION; PLASMA-LEVELS; PROLACTIN; SYSTEM; NERVE; RATS C1 [Kwong, K. K.; Chan, S. -T.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. RP Kwong, KK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM kwong@nmr.mgh.harvard.edu NR 13 TC 0 Z9 0 U1 4 U2 4 PU WAGENINGEN ACADEMIC PUBLISHERS PI WAGENINGEN PA PO BOX 220, WAGENINGEN, 6700 AE, NETHERLANDS SN 1876-2883 EI 1876-2891 J9 BENEF MICROBES JI Benef. Mirbobes PY 2016 VL 7 IS 5 BP 623 EP 624 DI 10.3920/BM2016.x003 PG 2 WC Microbiology; Nutrition & Dietetics SC Microbiology; Nutrition & Dietetics GA EG4WM UT WOS:000391044600002 PM 27892710 ER PT J AU Huang, JS Huang, FW Johnson, FE Huang, SS AF Huang, J. S. Huang, F. W. Johnson, F. E. Huang, S. S. BE Lewis, BS Borer, JS Halon, DA TI Molecular Basis of Diet, Exercise and Lifestyle Interventions in Atherosclerotic Cardiovascular Disease SO CORONARY ARTERY DISEASE 2015 LA English DT Proceedings Paper CT 11th International Congress on Coronary Artery Disease (ICCAD) CY NOV 29-DEC 02, 2015 CL Florence, ITALY SP Assoc Nazl Med Cardiologi Ospedalieri, Int Acad Cardiovascular Sci DE ASCVD prevention and treatment; TGF-beta enhancers; diet; exercise; moderate ingestion of red wine ID TGF-BETA AB Aims: Circulating TGF-beta is a cytokine that inhibits atherosclerotic cardiovascular disease (ASCVD). Hypercholesterolemia and high levels of dietary trans fats cause ASCVD, at least in part, by suppressing TGF-beta activity in arterial endothelium. Dynasore, a TGF-beta enhancer, retards ASCVD without altering high plasma cholesterol levels in ApoE-null mice. Interventions (prudent diet, exercise and lifestyle) decrease the risk of ASCVD but the molecular basis is unclear. We tested the hypothesis that TGF-beta activity enhancers inhibit ASCVD. Method: Moderate ingestion of ethanol, high plasma HDL levels and low-dose aspirin are known to decrease the risk of ASCVD in humans. Evidence from observational studies indicates that regular consumption of foods containing antioxidants may reduce the risk of ASCVD. We determined the TGF-beta enhancer activity of ethanol and antioxidants by measuring their effects on TGF-beta-stimulated expression of luciferase reporter genes, P-Smad2 and PAI-1 mRNA, and examining their ability to recruit TGF-beta receptors from lipid rafts/caveolae to non-lipid raft microdomains using cell-surface I-125-TGF-beta affinity labeling, sucrose density gradient ultracentrifugation and indirect immunofluorescence staining in Mv1Lu cells: a model system for studying TGF-beta-stimulated signaling and responses. Results: Ethanol enhances TGF-beta-stimulated luciferase activity in Mv1Lu cells stably expressing a luciferase reporter gene driven by the canonical TGF-beta signaling-dependent PAI-1 promoter. Ethanol at 0.5% (v/v) enhances TGF-beta activity by recruiting the type II TGF-beta receptor (T beta R-II) from its cytoplasmic vesicle pool to the plasma membrane by inducing vesicle-membrane fusion. At 0.5-1% (v/v), ethanol recruits T beta R-I and T beta R-II from lipid rafts/caveolae to non-lipid raft microdomains where canonical signaling occurs. Antioxidants (e.g., betulinic acid, resveratrol and cyanidin) enhance TGF-beta activity in these cells, which express the luciferase reporter gene. These agents, HMG-CoA reductase inhibitors, and HDL enhance TGF-beta activity by recruiting T beta R-I and T beta R-II from cytoplasmic vesicles (intracellular pool) and lipid rafts/caveolae to non-lipid raft microdomains. Conclusion: Diets containing natural TGF-beta enhancers (fruits/vegetables/nuts rich in triterpenoids, polyphenols and antioxidants), synthetic TGF-beta enhancers (such as HMG-CoA reductase inhibitors, resveratrol and cyanidin), moderate ingestion of red wine, and exercise (which increases plasma HDL levels) are now known to prevent and treat ASCVD. C1 [Huang, J. S.] St Louis Univ, Sch Med, Dept Biochem & Mol Biol, St Louis, MO 63104 USA. [Huang, F. W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huang, F. W.] Harvard Med Sch, Boston, MA 02115 USA. [Johnson, F. E.] St Louis Univ, Sch Med, Dept Surg, St Louis, MO 63104 USA. [Huang, S. S.] Auxagen Inc, St Louis, MO 63132 USA. RP Huang, JS (reprint author), St Louis Univ, Sch Med, Dept Biochem & Mol Biol, St Louis, MO 63104 USA. EM huangjs@slu.edu NR 5 TC 0 Z9 0 U1 2 U2 2 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-729-3 PY 2016 BP 49 EP 52 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BG7DH UT WOS:000391237200012 ER PT J AU Tolis, G Sundt, TM AF Tolis, George, Jr. Sundt, Thoralf M., III TI Contemporary insights into the management of type A aortic dissection SO EXPERT REVIEW OF CARDIOVASCULAR THERAPY LA English DT Review DE Aortic dissection; aortic aneurysm; ascending aortic replacement; aortic root replacement; aortic arch replacement; malperfusion ID ANTEGRADE CEREBRAL PERFUSION; TOTAL ARCH REPLACEMENT; TRUE LUMEN CANNULATION; ELEPHANT TRUNK; INTRAMURAL HEMATOMA; ASCENDING AORTA; AXILLARY ARTERY; REPAIR; STRATEGY; SURGERY AB Introduction: Acute Type A Dissection remains a surgical emergency with a relatively high operative mortality despite advances in cardiac surgical techniques and medical management over the past thirty years. Areas covered: In this presentation we will discuss the issues surrounding diagnosis, triage, surgical treatment and perioperative medical management as well as long term surveillance of patients suffering from Acute Type A Dissection and present the literature that supports our management strategies. Expert commentary: The ultimate goal of surgical intervention for patients with Type A Acute Aortic Dissection is an alive patient. A more complicated operation which addresses the root and arch and potentially reduces late complications should be approached with caution since it may increase the operative mortality of the procedure itself. With the recent evolution in endovascular techniques, there is hope that later complications can be reduced without increasing the risk of the primary operation. It remains to be seen whether the improved distal aortic remodeling afforded by a combined open/endovascular approach to Acute Type A Dissection will lead to decreased need for aortic reinterventions and overall long term complications of a residual descending thoracic chronic dissection. C1 [Tolis, George, Jr.; Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. EM TSUNDT@mgh.harvard.edu NR 38 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1477-9072 EI 1744-8344 J9 EXPERT REV CARDIOVAS JI Expert Rev. Cardiovasc. Ther. PY 2016 VL 14 IS 10 BP 1189 EP 1196 DI 10.1080/14779072.2016.1216315 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EG3EH UT WOS:000390926100011 PM 27454184 ER PT J AU Aghi, M Nagler, EM Lando, H Pednekar, M Gupta, PC Sorensen, G AF Aghi, Mira Nagler, Eve M. Lando, Harry Pednekar, Mangesh Gupta, Prakash C. Sorensen, Glorian TI Training lay interventionists to support tobacco cessation among teachers in India SO INTERNATIONAL JOURNAL OF HEALTH PROMOTION AND EDUCATION LA English DT Article DE tobacco; cessation; lay interventionists; India ID SMOKING; BEHAVIOR; PROGRAM; BIHAR; MODEL AB Despite the rapidly increasing burden of tobacco-related morbidity and mortality in low-and middle-income countries, tobacco control initiatives - especially cessation receive little emphasis. This is true despite low-cost methods that have potential for widespread dissemination. The purpose of this paper is to provide a case study example of how lay interventionists may be trained and supported to facilitate tobacco use cessation, based on the successful Tobacco-Free Teachers-Tobacco-Free Society program (TFT-TFS) implemented in Bihar, India. This school-based program included multiple components, with lay interventionists having a crucial role. The lay interventionists included health educators and lead teachers, both of whom were selected based on formative research, underwent extensive training and received continuing support. We emphasized encouraging and supporting teachers to quit tobacco use and engaging both tobacco users and nonusers to create a supportive environment for cessation. We also stressed that neither the health educators nor lead teachers were being trained as counselors or as cessation experts. We focused on the importance of respecting teachers as individuals and identifying locally relevant methods of cessation. Although we cannot isolate the precise contribution of the lay interventionists to the successful TFT-TFS intervention, the abstinence findings in favor of the intervention at follow-up are highly encouraging. Teachers have been neglected as lay interventionists for tobacco cessation despite the fact that they tend to be highly respected and credible. The approach used for TFT-TFS could be disseminable in multiple low-and middle-income country contexts through train-the-trainer programs targeted to teachers. C1 [Aghi, Mira; Pednekar, Mangesh; Gupta, Prakash C.] Healis Sekhsaria Inst Publ Hlth, 501 Technocity,Plot X-4-5 TTC Ind Area, Mahape 400701, Navi Mumbai, India. [Nagler, Eve M.; Sorensen, Glorian] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Nagler, Eve M.; Sorensen, Glorian] Harvard TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. [Lando, Harry] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 S 2nd St, Minneapolis, MN 55454 USA. RP Nagler, EM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.; Nagler, EM (reprint author), Harvard TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM eve_nagler@dfci.harvard.edu FU National Cancer Institute [K05 CA108663, R01 CA120958] FX This work was supported by National Cancer Institute [grant number K05 CA108663], [grant number R01 CA120958]. NR 27 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1463-5240 EI 2164-9545 J9 INT J HEALTH PROMOT JI Int. J. Health Promot. Educ. PY 2016 VL 54 IS 6 BP 304 EP 317 DI 10.1080/14635240.2016.1193761 PG 14 WC Education, Scientific Disciplines SC Education & Educational Research GA EG4HL UT WOS:000391004400005 ER PT J AU Chopra, V Quinti, L Khanna, P Paganetti, P Kuhn, R Young, AB Kazantsev, AG Hersch, S AF Chopra, Vanita Quinti, Luisa Khanna, Prarthana Paganetti, Paolo Kuhn, Rainer Young, Anne B. Kazantsev, Aleksey G. Hersch, Steven TI LBH589, A Hydroxamic Acid-Derived HDAC Inhibitor, is Neuroprotective in Mouse Models of Huntington's Disease SO JOURNAL OF HUNTINGTONS DISEASE LA English DT Article DE HDAC inhibitor; huntington; neuroprotection; panobinostat ID HISTONE DEACETYLASE INHIBITOR; TRANSGENIC MICE; NEURONAL DEATH; CAG REPEATS; PHASE-II; PANOBINOSTAT; PHENOTYPE; LYMPHOMA; TARGETS; POTENT AB Background: Modulation of gene transcription by HDAC inhibitors has been shown repeatedly to be neuroprotective in cellular, invertebrate, and rodent models of Huntington's disease (HD). It has been difficult to translate these treatments to the clinic, however, because existing compounds have limited potency or brain bioavailability. Objective: In the present study, we assessed the therapeutic potential of LBH589, an orally bioavailable hydroxamic acid-derived nonselective HDAC inhibitor in mouse models of HD. Method: The efficacy of LBH589 is tested in two HD mouse models using various biochemical, behavioral and neuropathological outcome measures. Results: We show that LBH589 crosses the blood brain barrier; induces histone hyperacetylation and prevents striatal neuronal shrinkage in R6/2 HD mice. In full-length knock-in HD mice LBH589-treatment improves motor performance and reduces neuronal atrophy. Conclusions: Our efficacious results of LBH589 in fragment and full-length mouse models of HD suggest that LBH589 is a promising candidate for clinical assessment in HD patients and provides confirmation that non-selective HDAC inhibitors can be viable clinical candidates. C1 [Chopra, Vanita; Quinti, Luisa; Khanna, Prarthana; Young, Anne B.; Kazantsev, Aleksey G.; Hersch, Steven] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, East Bldg 114,Room 2005, Charlestown, MA 02129 USA. [Paganetti, Paolo; Kuhn, Rainer] Novartis Inst Biomed Res, Basel, Switzerland. [Khanna, Prarthana] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Paganetti, Paolo] Neuroctr Svizzera Italiana EOC, Lab Biomed Neurosci, Via Soi 24, CH-6807 Torricella Taverne, Switzerland. [Kuhn, Rainer] Evotec AG, Essener Bogen 7, Hamburg, Germany. RP Hersch, S (reprint author), Harvard Med Sch, Neurol, East Bldg 114,Room 2005, Charlestown, MA 02129 USA.; Hersch, S (reprint author), Harvard Med Sch, New England Ctr Excellence Huntingtons Dis, East Bldg 114,Room 2005, Charlestown, MA 02129 USA.; Hersch, S (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Lab Neurodegenerat & Neurotherapeut, East Bldg 114,Room 2005, Charlestown, MA 02129 USA. EM hersch@helix.mgh.harvard.edu FU Beat HD Collaborative grant from the Novartis Institutes for BioMedical Research (NIBR) FX We thank Lorraine Vollor and Teal Connor for maintaining mouse colonies and help in behavioral and neuropathological studies. We also thank Dr. Jonathan Fox for his help in statistical analysis. This work was supported by the Beat HD Collaborative grant from the Novartis Institutes for BioMedical Research (NIBR). NR 34 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1879-6397 EI 1879-6400 J9 J HUNTINGTONS DIS JI J. Huntingtons Dis. PY 2016 VL 5 IS 4 BP 347 EP 355 DI 10.3233/JHD-160226 PG 9 WC Neurosciences SC Neurosciences & Neurology GA EG4QN UT WOS:000391028900004 PM 27983565 ER PT J AU Braisch, U Martinez-Horta, S MacDonald, M Orth, M AF Braisch, Ulrike Martinez-Horta, Saul MacDonald, Marcy Orth, Michael TI Important but not Enough - Information about HD Related Topics and Peer and Professional Support for Young Adults from HD Families SO JOURNAL OF HUNTINGTONS DISEASE LA English DT Article DE Genetic counselling; life-style; legal advice; research participation; care ID HUNTINGTONS-DISEASE; EXPERIENCE; IMPACT; ONSET; LIFE AB Background: The number of people affected by Huntington's disease (HD) is far greater than those with manifest HD because it also includes those at risk, both HD gene mutation carriers and family members not carrying the HD mutation. Many relevant needs of young adults from HD families may not be met at present. This includes advice on important life decisions e.g. family planning and having children, psychological support and treatment of medical conditions. Objective: To survey the opinion of young adults from HD families about relevance and availability of information and support regarding several aspects of HD. Methods: An online anonymous questionnaire translated into ten languages contained questions regarding the importance and availability of information and support about HD related topics, and attitudes towards research. Answers were captured in categories or on Likert scales. Results: Information about HD related topics and the availability of peer and professional support are very important for young adults from HD families. In addition, with the exception of general information about HD, or predictive testing, the vast majority of respondents stated that they did not receive enough information on other important topics, for instance regarding legal advice and they did not feel supported enough by healthcare professionals. HD research was considered to be of high value, though most did not participate in HD research. Conclusion: The results of this survey can help devise a strategy to address these unmet needs and also to facilitate research participation of more young adults from HD families. C1 [Braisch, Ulrike] Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany. [Martinez-Horta, Saul] Hosp Santa Creu & Sant Pau, Movement Disorders Grp, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain. [MacDonald, Marcy] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Orth, Michael] Univ Ulm, Dept Neurol, Ulm, Germany. RP Orth, M (reprint author), Ulm Univ Hosp, Dept Neurol, Oberer Eselsberg 45-1, D-89081 Ulm, Germany. EM michael.orth@uni-ulm.de NR 17 TC 0 Z9 0 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1879-6397 EI 1879-6400 J9 J HUNTINGTONS DIS JI J. Huntingtons Dis. PY 2016 VL 5 IS 4 BP 379 EP 387 DI 10.3233/JHD-160218 PG 9 WC Neurosciences SC Neurosciences & Neurology GA EG4QN UT WOS:000391028900007 PM 27983563 ER PT J AU Anderson, KE Eberly, S Groves, M Kayson, E Marder, K Young, AB Shoulson, I AF Anderson, Karen E. Eberly, Shirley Groves, Mark Kayson, Elise Marder, Karen Young, Anne B. Shoulson, Ira CA PHAROS Investigators TI Risk Factors for Suicidal Ideation in People at Risk for Huntington's Disease SO JOURNAL OF HUNTINGTONS DISEASE LA English DT Article DE Huntington's disease; suicidal ideation; suicide; suicide attempt ID HOPELESSNESS SCALE; COMPLETED SUICIDE; COMORBIDITY; POPULATION; PREVALENCE; DISORDERS AB Background: Suicidal ideation (SI) and attempts are increased in Huntington's disease (HD), making risk factor assessment a priority. Objective: To determine whether, hopelessness, irritability, aggression, anxiety, CAG expansion status, depression, and motor signs/symptoms were associated with Suicidal Ideation (SI) in those at risk for HD. Methods: Behavioral and neurological data were collected from subjects in an observational study. Subject characteristics were calculated by CAG status and SI. Logistic regression models were adjusted for demographics. Separate logistic regressions were used to compare SI and non-SI subjects. A combined logistic regression model, including 4 pre-specified predictors, (hopelessness, irritability, aggression, anxiety) was used to assess the relationship of SI to these predictors. Results: 801 subjects were assessed, 40 were classified as having SI, 6.3% of CAG mutation expansion carriers had SI, compared with 4.3% of non-CAGmutation expansion carriers (p = 0.2275). SI subjects had significantly increased depression (p < 0.0001), hopelessness (p < 0.0001), irritability (p < 0.0001), aggression (p = 0.0089), and anxiety (p < 0.0001), and an elevated motor score (p = 0.0098). Impulsivity, assessed in a subgroup of subjects, was also associated with SI (p = 0.0267). Hopelessness and anxiety remained significant in combined model (p < 0.001; p < 0.0198, respectively) even when motor score was included. Conclusions: Behavioral symptoms were significantly higher in those reporting SI. Hopelessness and anxiety showed a particularly strong association with SI. Risk identification could assist in assessment of suicidality in this group. C1 [Anderson, Karen E.] Georgetown Univ, Dept Psychiat, Div Res, Washington, DC USA. [Anderson, Karen E.; Shoulson, Ira] Georgetown Univ, Dept Neurol, Washington, DC USA. [Eberly, Shirley] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA. [Groves, Mark] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Groves, Mark] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Kayson, Elise] Univ Rochester, Clin Trials Coordinat Ctr, Ctr Human Expt Therapeut, Rochester, NY USA. [Marder, Karen] Columbia Univ, Med Ctr, Dept Neurol, Psychiat, New York, NY USA. [Marder, Karen] Columbia Univ, Med Ctr, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA. [Young, Anne B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Anderson, KE (reprint author), Georgetown Univ, Washington, DC 20057 USA. EM kea45@georgetown.edu FU National Human Genome Research Institute; National Institute of Neurological Disorders and Stroke of the National Institutes of Health [5RO1-HG-02449]; Griffin Foundation FX This research was supported by grants and awards from the National Human Genome Research Institute and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (5RO1-HG-02449).; We thank the Griffin Foundation for support of this study. NR 33 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1879-6397 EI 1879-6400 J9 J HUNTINGTONS DIS JI J. Huntingtons Dis. PY 2016 VL 5 IS 4 BP 389 EP 394 DI 10.3233/JHD-160206 PG 6 WC Neurosciences SC Neurosciences & Neurology GA EG4QN UT WOS:000391028900008 PM 27983561 ER PT J AU Giladi, N Nicholas, AP Asgharnejad, M Dohin, E Woltering, F Bauer, L Poewe, W AF Giladi, Nir Nicholas, Anthony P. Asgharnejad, Mahnaz Dohin, Elisabeth Woltering, Franz Bauer, Lars Poewe, Werner TI Efficacy of Rotigotine at Different Stages of Parkinson's Disease Symptom Severity and Disability: A Post Hoc Analysis According to Baseline Hoehn and Yahr Stage SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Dopamine receptor agonist; Parkinson's disease; disease progression; treatment efficacy; clinical trial ID TRANSDERMAL ROTIGOTINE; DOUBLE-BLIND; INITIATION; PROGRESSION; RECOMMENDATIONS; IMPAIRMENTS; PLACEBO; PROFILE; SCALE; GAIT AB Background: The efficacy of rotigotine has been demonstrated in studies of patients with early (i.e. not receiving levodopa) and advanced (i.e. not adequately controlled on levodopa; average 2.5 h/day in 'off' state) Parkinson's disease (PD). Objective: To further investigate the efficacy of rotigotine transdermal patch across different stages of PD symptom severity and functional disability, according to baseline Hoehn and Yahr (HY) staging. Methods: Post hoc analysis of six placebo-controlled studies of rotigotine in patients with early PD (SP506, SP512, SP513; rotigotine <= 8 mg/24 h) or advanced-PD (CLEOPATRA-PD, PREFER, SP921; rotigotine <= 16 mg/24 h). Data were pooled and analyzed according to baseline HY stage (1, 2, 3 or 4) for change from baseline to end of maintenance in Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living), UPDRS III (motor) and UPDRS II+III; statistical tests are exploratory. Results: Data were available for 2057 patients (HY 1 : 262; HY 2 : 1230; HY 3 : 524; HY 4 : 41). Patients at higher HY stages were older, had a longer time since PD diagnosis and higher baseline UPDRS II+III scores vs patients at lower HY stages. Rotigotine improved UPDRS II+III versus placebo for each individual HY stage (p < 0.05 for each HY stage), with treatment differences increasing with increasing HY stages. Similar results were observed for UPDRS II and UPDRS III. Conclusions: This post hoc analysis suggests that rotigotine may be efficacious across a broad range of progressive stages of PD symptom severity and functional disability (HY stages 1-4). C1 [Giladi, Nir] Tel Aviv Univ, Tel Aviv Med Ctr, Neurol Inst, Tel Aviv, Israel. [Giladi, Nir] Tel Aviv Univ, Dept Neurol & Neurosurg, Sackler Sch Med, Sagol Sch Neurosci, Tel Aviv, Israel. [Nicholas, Anthony P.] Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA. [Nicholas, Anthony P.] Birmingham VA Med Ctr, Birmingham, AL USA. [Asgharnejad, Mahnaz] UCB Pharma, Raleigh, NC USA. [Dohin, Elisabeth] UCB Pharma, Brussels, Belgium. [Woltering, Franz; Bauer, Lars] UCB Pharma, Monheim, Germany. [Poewe, Werner] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria. RP Giladi, N (reprint author), Tel Aviv Med Ctr & Sch Med, Neurol Inst, 6 Weizmann St, IL-64239 Tel Aviv, Israel. EM nirg@tlvmc.gov.il FU UCB Pharma; UCB Pharma, Brussels, Belgium FX This post hoc analysis was supported by UCB Pharma, Monheim am Rhein, Germany. The analysis and manuscript development was a full partnership between the sponsor (UCB Pharma) and academic experts in the field of PD, who were investigators/principal investigators for the original double-blind studies included. The final data reported in this manuscript are the outcome of scientific discussions between all authors. Specifically, the original analysis was initially designed by the study sponsor, and subsequently modified upon review by the academic authors. All authors contributed significantly to the design/specifics of the analyses included in the manuscript, reviewed the data, were involved in the interpretation of the results, and reviewed and critiqued the manuscript. The sponsor statistician author was involved in running the data analysis. The authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to the studies included in these analyses. The authors also acknowledge Karolina Rzeniewicz, PhD (Evidence Scientific Solutions, London, UK) for writing assistance, which was funded by UCB Pharma, Brussels, Belgium, and Cedric Laloyaux (Strategic Publication Lead Neurology, UCB Pharma, Brussels, Belgium) for publication coordination. The authors also acknowledge Marc Derycke, MSc (UCB Pharma, Monheim am Rhein, Germany) for his contributions to the specifications and programming of the post hoc analyses. NR 30 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2016 VL 6 IS 4 BP 741 EP 749 DI 10.3233/JPD-160847 PG 9 WC Neurosciences SC Neurosciences & Neurology GA EH0CO UT WOS:000391430300010 PM 27567886 ER PT J AU Matias, WR Bourque, DL Niwano, T Onderdonk, AB Katz, JT AF Matias, Wilfredo R. Bourque, Daniel L. Niwano, Tomoko Onderdonk, Andrew B. Katz, Joel T. TI Subacute Bacterial Endocarditis with Leptotrichia goodfellowii in a Patient with a Valvular Allograft: A Case Report and Review of the Literature SO CASE REPORTS IN INFECTIOUS DISEASES LA English DT Review ID BUCCALIS; BACTEREMIA; INFECTION; DIVERSITY AB Leptotrichia species are normal constituents of the oral cavity and the genitourinary tract microbiota that are known to provoke disease in immunocompromised patients and rarely in immunocompetent individuals. Following the description of Leptotrichia goodfellowii sp. nov., two cases of endocarditis by this species have been reported. Here, we report a case of Leptotrichia goodfellowii endocarditis in an immunocompetent patient with a valvular allograft. The isolation and identification of Leptotrichia can be challenging, and it is likely that infection with this pathogen is significantly underdiagnosed. A definitive identification, as in this case, most often requires 16S rRNA gene sequencing, highlighting the increasingly important role of this diagnostic modality among immunocompetent patients with undetermined anaerobic bacteremia. C1 [Matias, Wilfredo R.; Bourque, Daniel L.; Onderdonk, Andrew B.; Katz, Joel T.] Harvard Med Sch, Boston, MA 02115 USA. [Bourque, Daniel L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Niwano, Tomoko] Tokyo Med & Dent Univ, Tokyo, Japan. [Onderdonk, Andrew B.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Katz, Joel T.] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. RP Matias, WR (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM wilfredo_matias@hms.harvard.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [T32 AI007061]; Paul and Daisy Soros Foundation FX Daniel L. Bourque received funding support from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (T32 AI007061). Wilfredo R. Matias was supported in part by the Paul and Daisy Soros Foundation through their Fellowship for New Americans Program. NR 17 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-6625 EI 2090-6633 J9 CASE REP INFECT DIS JI Case Rep. Infect. Dis. PY 2016 AR 3051212 DI 10.1155/2016/3051212 PG 5 WC Infectious Diseases SC Infectious Diseases GA EG1KL UT WOS:000390791000001 ER PT J AU Wei, W Ramos, PS Hunt, KJ Wolf, BJ Hardiman, G Chung, DJ AF Wei, Wei Ramos, Paula S. Hunt, Kelly J. Wolf, Bethany J. Hardiman, Gary Chung, Dongjun TI GPA-MDS: A Visualization Approach to Investigate Genetic Architecture among Phenotypes Using GWAS Results SO INTERNATIONAL JOURNAL OF GENOMICS LA English DT Article ID DISEASE AB Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. Recently, there has been accumulating evidence suggesting that different complex traits share a common risk basis, namely, pleiotropy. Previously, a statistical method, namely, GPA (Genetic analysis incorporating Pleiotropy and Annotation), was developed to improve identification of risk variants and to investigate pleiotropic structure through a joint analysis of multiple GWAS datasets. While GPA provides a statistically rigorous framework to evaluate pleiotropy between phenotypes, it is still not trivial to investigate genetic relationships among a large number of phenotypes using the GPA framework. In order to address this challenge, in this paper, we propose a novel approach, GPA-MDS, to visualize genetic relationships among phenotypes using the GPA algorithm and multidimensional scaling (MDS). This tool will help researchers to investigate common etiology among diseases, which can potentially lead to development of common treatments across diseases. We evaluate the proposed GPA-MDS framework using a simulation study and apply it to jointly analyze GWAS datasets examining 18 unique phenotypes, which helps reveal the shared genetic architecture of these phenotypes. C1 [Wei, Wei; Ramos, Paula S.; Hunt, Kelly J.; Wolf, Bethany J.; Hardiman, Gary; Chung, Dongjun] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Ramos, Paula S.; Hardiman, Gary] Med Univ South Carolina, Dept Med, Charleston, SC USA. [Hunt, Kelly J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Hardiman, Gary] Med Univ South Carolina, Ctr Genom Med, Charleston, SC USA. RP Chung, DJ (reprint author), Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. EM chungd@musc.edu OI Ramos, Paula/0000-0002-9433-6634 FU US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [K01 AR067280, P60 AR062755]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK088778]; National Institute of General Medical Sciences (NIGMS) [R01 GM122078]; National Cancer Institute (NCI) from the National Institutes of Health (NIH) [R21 CA209848] FX This work was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants K01 AR067280 (Paula S. Ramos) and P60 AR062755 (Paula S. Ramos and Bethany J. Wolf), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01 DK088778 (Kelly J. Hunt), National Institute of General Medical Sciences (NIGMS) grant R01 GM122078, and National Cancer Institute (NCI) grant R21 CA209848 (Dongjun Chung and Gary Hardiman) from the National Institutes of Health (NIH). NR 14 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-436X EI 2314-4378 J9 INT J GENOMICS JI Int. J. Genomics PY 2016 AR 6589843 DI 10.1155/2016/6589843 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA EF8JA UT WOS:000390573900001 ER PT J AU Zhang, YC Corapi, KM Luongo, M Thadhani, R Nigwekar, SU AF Zhang, Yanchen Corapi, Kristin M. Luongo, Maria Thadhani, Ravi Nigwekar, Sagar U. TI Calciphylaxis in peritoneal dialysis patients: a single center cohort study SO INTERNATIONAL JOURNAL OF NEPHROLOGY AND RENOVASCULAR DISEASE LA English DT Article DE calcific uremic arteriolopathy; dialysis; hypotension; warfarin ID CALCIFIC UREMIC ARTERIOLOPATHY; INTRAPERITONEAL SODIUM THIOSULFATE; STAGE RENAL-DISEASE; RISK-FACTORS; END; DIAGNOSIS; PROTEINS; THERAPY AB Background: Calciphylaxis is a rare but devastating condition in end-stage renal disease (ESRD) patients. Most research in the field of calciphylaxis is focused on hemodialysis (HD) patients; however, data on calciphylaxis incidence, risk factors, and mortality in peritoneal dialysis (PD) patients are limited. Methods: In this cohort study, we examined data from adult patients who initiated PD for ESRD management at our institute's PD unit from January 2001 to December 2015. Associations with the development of calciphylaxis were examined for clinical, laboratory, and medication exposures. Incidence of calciphylaxis and mortality in PD patients who developed calciphylaxis were analyzed. Treatments administered to treat calciphylaxis in PD patients were summarized. Results: In this cohort of 63 patients, 7 patients developed calciphylaxis (incidence rate: 9.0 per 1,000 patient-years). Median age of PD patients who developed calciphylaxis was 50 years, 57% were white, 71% females, and 71% were previously on HD. Female sex, obesity, HD as a prior dialysis modality, recurrent hypotension, elevated time-averaged serum phosphorous levels, reduced time-averaged serum albumin levels, and warfarin therapy were associated with increased calciphylaxis risk in univariate logistic regression analyses. Intravenous sodium thiosulfate was administered in 57% of PD patients who developed calciphylaxis. One-year mortality in PD patients who developed calciphylaxis was 71% despite multimodal treatment including sodium thiosulfate, hyperbaric oxygen, cinacalcet, and wound debridement. Conclusion: Calciphylaxis is a rare but frequently fatal condition in PD patients. Our study provides critical early insights into calciphylaxis incidence, risk factors, and prognosis in PD patients. Sample size and characteristics of patients included in our study limit generalizability to overall PD population and warrant examination in larger independent studies. C1 [Zhang, Yanchen] Harvard Summer Res Program Kidney Med, Boston, MA USA. [Corapi, Kristin M.; Luongo, Maria; Thadhani, Ravi; Nigwekar, Sagar U.] Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. RP Nigwekar, SU (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM snigwekar@mgh.harvard.edu FU American Heart Association's NCRP Winter Fellow-to-Faculty Transition Award [15FTF25980003]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health) [KL2 TR001100]; National Kidney Foundation; Massachusetts General Hospital's Executive Committee on Research [R00000000007190]; American Heart Association's NCRP Summer Mentored Clinical and Population Research Award [15CRP22900008]; National Institute of Health [DK094872, DK094486] FX Sagar U Nigwekar is supported by American Heart Association's NCRP Winter 2015 Fellow-to-Faculty Transition Award (15FTF25980003) and by KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award) from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR001100). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic healthcare centers, or the National Institutes of Health. This work also received support from National Kidney Foundation's Young Investigator Award, Fund for Medical Discovery Award from Massachusetts General Hospital's Executive Committee on Research (R00000000007190), American Heart Association's NCRP Summer 2014 Mentored Clinical and Population Research Award (15CRP22900008) to Sagar U Nigwekar. Ravi I Thadhani is supported by National Institute of Health grants DK094872 and DK094486. NR 32 TC 0 Z9 0 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-7058 J9 INT J NEPHROL RENOV JI Int. J. Nephrol. Renov. Dis. PY 2016 VL 9 BP 235 EP 241 DI 10.2147/IJNRD.S115701 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA EF8WE UT WOS:000390610100002 PM 27698566 ER PT J AU D'Elia, JA Gleason, RE Monaco, AP Weinrauch, LA AF D'Elia, John A. Gleason, Ray E. Monaco, Anthony P. Weinrauch, Larry A. TI Does calcium channel blockade have a role in prevention of expression of sepsis in renal transplant recipients? SO INTERNATIONAL JOURNAL OF NEPHROLOGY AND RENOVASCULAR DISEASE LA English DT Review DE renal transplant; transplantation sepsis; calcium channel blockade ID RESPIRATORY-TRACT INFECTION; RENIN-ANGIOTENSIN SYSTEM; IMPROVES SURVIVAL; VITAMIN-D; RAT; CYCLOSPORINE; SHOCK; MICE; LIPOPOLYSACCHARIDE; RESUSCITATION AB Many antihypertensive agents have been demonstrated to assist in preservation of kidney function, among them those that modulate calcium channels. Calcium channel blockers may also be of value in protecting hemodialysis patients from complications of sepsis. In diabetic recipients of kidney transplant allografts treated with cyclosporine, calcium channel blockade has been retrospectively linked to improved graft preservation and to fewer episodes of sepsis. This brief review outlines clinical and experimental publications on potential protection from sepsis by addition of calcium channel blockers to standard antibiotic therapy in individuals who may or may not have normal kidney function, or in the presence or absence of immunosuppression. Such mechanisms include blockade of antibiotic cytosolic extrusion in the cases of Pneumococci, Mycobacterium tuberculosis, Plasmodium falciparum malaria, or Schistosoma mansoni; blockade of the calcineurin/calmodulin pathway (in immunosuppressed patients allowing for lower dosage of cyclosporine); stabilization of calcium movement at the level of sarcoplasmic reticulum by which shock (vasopressor instability) is prevented; or of cytosolic calcium influx and cell death (in the case of allograft acute tubular necrosis). Given the high cost of development of new antibiotics, a role for generic calcium channel blockade in sepsis prevention should be pursued by additional studies to investigate potential links between blockade of calcium channels and expression of sepsis in at-risk populations. C1 [D'Elia, John A.; Weinrauch, Larry A.] Joslin Diabet Ctr, Kidney & Hypertens Sect, Boston, MA 02215 USA. [D'Elia, John A.; Monaco, Anthony P.; Weinrauch, Larry A.] Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA. [D'Elia, John A.; Monaco, Anthony P.; Weinrauch, Larry A.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [D'Elia, John A.; Gleason, Ray E.; Monaco, Anthony P.; Weinrauch, Larry A.] Harvard Med Sch, Boston, MA USA. [Weinrauch, Larry A.] Mt Auburn Hosp, Dept Med, Cambridge, MA USA. RP Weinrauch, LA (reprint author), 521 Mt Auburn St, Watertown, MA 02472 USA. EM lweinrauch@hms.harvard.edu NR 41 TC 0 Z9 0 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-7058 J9 INT J NEPHROL RENOV JI Int. J. Nephrol. Renov. Dis. PY 2016 VL 9 BP 291 EP 295 DI 10.2147/IJNRD.S121492 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA EF8WN UT WOS:000390611100006 PM 27920569 ER PT J AU Harrison, KL Taylor, HA AF Harrison, Krista Lyn Taylor, Holly A. TI Healthcare resource allocation decisions affecting uninsured services SO JOURNAL OF HEALTH ORGANIZATION AND MANAGEMENT LA English DT Article DE Organizational culture; Decision making; Values; Policy; Healthcare; Uninsured ID POPULATION HEALTH AB Purpose - Using the example of community access programs (CAPs), the purpose of this paper is to describe resource allocation and policy decisions related to providing health services for the uninsured in the USA and the organizational values affecting these decisions. Design/methodology/approach - The study used comparative case study methodology at two geographically diverse sites. Researchers collected data from program documents, meeting observations, and interviews with program stakeholders. Findings - Five resource allocation or policy decisions relevant to providing healthcare services were described at each site across three categories: designing the health plan, reacting to funding changes, and revising policies. Organizational values of access to care and stewardship most frequently affected resource allocation and policy decisions, while economic and political pressures affect the relative prioritization of values. Research limitations/implications - Small sample size, the potential for social desirability or recall bias, and the exclusion of provider, member or community perspectives beyond those represented among participating board members. Practical implications - Program directors or researchers can use this study to assess the extent to which resource allocation and policy decisions align with organizational values and mission statements. Social implications - The description of how healthcare decisions are actually made can be matched with literature that describes how healthcare resource decisions ought to be made, in order to provide a normative grounding for future decisions. Originality/value - This study addresses a gap in literature regarding how CAPs actually make resource allocation decisions that affect access to healthcare services. C1 [Harrison, Krista Lyn] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Harrison, Krista Lyn] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Taylor, Holly A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Taylor, Holly A.] Johns Hopkins Univ, Berman Inst Bioeth, Baltimore, MD USA. RP Harrison, KL (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.; Harrison, KL (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. FU AHRQ NRSA Health Services Research and Policy Traineeship [T32-HS00029]; Victor P. Raymond Memorial Fund Health Policy and Management Endowment Award; National Institute of Aging [T32-AG000212] FX The authors would like to thank the study participants and the hard work of people who run Community Access Programs and other safety net programs to provide people with access to healthcare. The authors would also like to thank Drs Anne Riley, Shannon Frattaroli, Maria Merritt, Ruth Faden, David Holtgrave, Bradley Herring, Carlton Haywood Jr, and Jessica Holzer for their feedback on earlier versions of this work. Dr Harrison was supported by the AHRQ NRSA Health Services Research and Policy Traineeship (No. T32-HS00029) and the Victor P. Raymond Memorial Fund Health Policy and Management Endowment Award when conducting this work, and is currently supported by the National Institute of Aging (No. T32-AG000212). NR 44 TC 0 Z9 0 U1 1 U2 1 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 1477-7266 EI 1758-7247 J9 J HEALTH ORGAN MANAG JI J. Health Organ. Manag. PY 2016 VL 30 IS 8 BP 1162 EP 1182 DI 10.1108/JHOM-01-2016-0003 PG 21 WC Health Policy & Services SC Health Care Sciences & Services GA EG0JG UT WOS:000390717700001 PM 27934550 ER PT J AU Shiferaw, N Brooks, MI Salvador-Davila, G Lonsako, S Kassahun, K Ansel, J Osakwe, C Weldegebreal, T Ahmed, I Asnake, M Blumenthal, PD AF Shiferaw, Netsanet Brooks, Mohamad I. Salvador-Davila, Graciela Lonsako, Shumet Kassahun, Konjit Ansel, Jodi Osakwe, Chidude Weldegebreal, Teklu Ahmed, Ismael Asnake, Mengistu Blumenthal, Paul D. TI Knowledge and Awareness of Cervical Cancer among HIV-Infected Women in Ethiopia SO JOURNAL OF OBESITY LA English DT Article ID SQUAMOUS INTRAEPITHELIAL LESIONS; ATTITUDES; RISK AB Introduction. Cervical cancer is one of the leading causes of cancer death among Ethiopian women. Low awareness of cervical cancer, in combination with low health care seeking behavior, is a key challenge for cervical cancer prevention. This study assessed the knowledge of cervical cancer among HIV-infected women in Ethiopia. Methods. A facility-based cross-sectional survey was conducted from August to September 2012 among HIV-infected women between 21 and 49 years of age. Basic descriptive statistics were performed using SPSS. Results. A total of 432 HIV-infected women participated in this study. About 71% of participants had ever heard of cervical cancer. Among women who had ever heard of cervical cancer, 49% did not know the cause while 74% were able to identify at least one risk factor for cervical cancer. Only 33% of women were able to correctly address when women should seek care and 33% identified at least one treatment option for cervical cancer. Conclusion. This study revealed that knowledge about cervical cancer was generally low, in particular for health care seeking behavior and treatment of cervical cancer. Health awareness programs should be strengthened at both community and health facility levels with emphasis highlighting the causes, risk factors, care seeking behaviors, and treatment options for cervical cancer. C1 [Shiferaw, Netsanet; Kassahun, Konjit; Asnake, Mengistu] Pathfinder Int, Addis Ababa, Ethiopia. [Brooks, Mohamad I.; Osakwe, Chidude] Pathfinder Int, Watertown, MA USA. [Brooks, Mohamad I.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Salvador-Davila, Graciela] UMCOR, New York, NY USA. [Lonsako, Shumet] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Ansel, Jodi] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Weldegebreal, Teklu; Ahmed, Ismael] United States Ctr Dis Control & Prevent CDC, Addis Ababa, Ethiopia. [Blumenthal, Paul D.] Stanford Univ, Sch Med, SPIRES, Stanford, CA 94305 USA. RP Shiferaw, N (reprint author), Pathfinder Int, Addis Ababa, Ethiopia. EM neshihana@gmail.com FU President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC) FX The "Addis Tesfa" project was a collaboration between Pathfinder International and the Ethiopian Federal Ministry of Health with support from President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC). The authors also thank the Regional Health Bureaus, the health facilities, service providers, Addis Tesfa project regional coordinators, and data collectors for their support during this study. The authors further extend their gratitude and eternal thanks to all the women who voluntarily agreed to participate in this study and offer their responses. NR 24 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-0708 EI 2090-0716 J9 J OBES JI J. Obes. PY 2016 AR 1274734 DI 10.1155/2016/1274734 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG1PT UT WOS:000390805400001 ER PT J AU Wang, P Petrella, F Nicosia, L Bellomi, M Rizzo, S AF Wang, Ping Petrella, Francesco Nicosia, Luca Bellomi, Massimo Rizzo, Stefania TI Molecular Imaging of Stem Cell Transplantation for Liver Diseases: Monitoring, Clinical Translation, and Theranostics SO STEM CELLS INTERNATIONAL LA English DT Review ID HEPATOCYTE-LIKE CELLS; MARROW STROMAL CELLS; IN-VIVO TRACKING; AUTOLOGOUS TRANSPLANTATION; FAILURE PATIENTS; DRUG-DELIVERY; RAT-LIVER; GD-DTPA; CIRRHOSIS; NANOPARTICLES AB Stem cell transplantation has been investigated to rescue experimental liver failure and is promising to offer an alternative therapy to liver transplantation for liver diseases treatment. Several clinical studies in this field have been carried out, but the therapeutic benefit of this treatment is still controversial. A major obstacle to developing stem cell therapies in clinic is being able to visualize the cells in vivo. Imaging modalities allow optimization of delivery, detecting cell survival and functionality by in vivo monitoring these transplanted graft cells. Moreover, theranostic imaging is a brand new field that utilizes nanometer-scale materials to glean diagnostic insight for simultaneous treatment, which is very promising to improve stem cell-based therapy for treatment of liver diseases. The aim of this review was to summarize the various imaging tools that have been explored with advanced molecular imaging probes. We also outline some recent progress of preclinical and clinical studies of liver stem cells transplantation. Finally, we discuss theranostic imaging for stem cells transplantation for liver dysfunction and future opportunities afforded by theranostic imaging. C1 [Wang, Ping] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Mol Imaging Lab,MGH MIT HMS Athinoula A Martinos, Boston, MA 02129 USA. [Petrella, Francesco] European Inst Oncol, Dept Thorac Surg, Via Ripamonti 435, I-20141 Milan, Italy. [Nicosia, Luca] Univ Milan, Postgrad Sch Radiodiagnost, Via Festa del Perdono 7, I-20122 Milan, Italy. [Bellomi, Massimo; Rizzo, Stefania] European Inst Oncol, Dept Radiol, Via Ripamonti 435, I-20141 Milan, Italy. [Bellomi, Massimo] Univ Milan, Dept Oncol, Via Festa del Perdono 7, I-20142 Milan, Italy. RP Rizzo, S (reprint author), European Inst Oncol, Dept Radiol, Via Ripamonti 435, I-20141 Milan, Italy. EM stefania.rizzo@ieo.it OI Bellomi, Massimo/0000-0001-7798-1175; Wang, Ping/0000-0001-6712-8939 NR 74 TC 0 Z9 0 U1 2 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2016 AR 4058656 DI 10.1155/2016/4058656 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA EF8BF UT WOS:000390552400001 ER PT S AU Zhao, WB Babi, M Yang, W Luo, X Zhu, YQ Yang, J Luo, CM Yang, M AF Zhao, Wenbing Babi, Mamdouh Yang, William Luo, Xiong Zhu, Yueqin Yang, Jack Luo, Chaomin Yang, Mary GP IEEE TI Byzantine Fault Tolerance for Collaborative Editing with Commutative Operations SO 2016 IEEE INTERNATIONAL CONFERENCE ON ELECTRO INFORMATION TECHNOLOGY (EIT) SE International Conference on Electro Information Technology LA English DT Proceedings Paper CT IEEE International Conference on Electro Information Technology (EIT) CY MAY 19-21, 2016 CL Univ N Dakota, Grand Forks, ND SP IEEE HO Univ N Dakota DE Byzantine Fault Tolerance; Optimistic Replication; Conflict-free Replicated Data Types; Distributed Consensus AB In this paper, we present a study on how to achieve Byzantine fault tolerance for collaborative editing systems with commutative operations. Recent research suggests that Conflict-free Replicated Data Types (CRDTs) can be used to construct collaborative editing systems where concurrent update operations are commutative. This new approach is shown to avoid the complex issue of conflict resolution for concurrent updates to a shared document. The shared document is often modeled as a linear text buffer where each basic element is assigned a globally unique and totally ordered identifier. The linear text buffer constructed this way would constitute as a CRDT, which would make concurrent update operations issued by different users commutative. State convergence at all users can be achieved automatically as long as the users could receive the same set of operations irrespective of their relative ordering. However, it is not straightforward to guarantee state convergence in the presence of malicious users and external adversaries. In this paper, we carefully analyze the threats towards this type of systems, and propose a lightweight solution to achieve Byzantine fault tolerance with low runtime overhead. We define a set of correctness properties for such systems and prove that the proposed Byzantine fault tolerance mechanisms guarantee these properties. C1 [Zhao, Wenbing; Babi, Mamdouh] Cleveland State Univ, Dept Elect Engn & Comp Sci, Cleveland, OH 44115 USA. [Yang, William] Univ Texas Austin, Texas Adv Comp Ctr, 10100 Burnet Rd, Austin, TX 78758 USA. [Luo, Xiong] Univ Sci & Technol Beijing, Sch Comp & Commun Engn, Beijing 100083, Peoples R China. [Zhu, Yueqin] Minist Land & Resources, Dev Res Ctr China Geol Survey, Beijing 100037, Peoples R China. [Zhu, Yueqin] Minist Land & Resources, Key Lab Geol Informat Technol, Beijing 100037, Peoples R China. [Yang, Jack] Massachusetts Gen Hosp, Div Biostat & Biomath, Boston, MA 02114 USA. [Yang, Jack] Harvard Med Sch, Boston, MA 02114 USA. [Luo, Chaomin] Univ Detroit Mercy, Dept Elect & Comp Engn, Detroit, MI 48221 USA. [Yang, Mary] Univ Arkansas, George Washington Donaghey Coll Engn & Informat T, Dept Informat Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA. [Yang, Mary] Univ Arkansas, Joint Bioinformat Program, 2801 S Univ Ave, Little Rock, AR 72204 USA. [Yang, Mary] Univ Arkansas Med Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA. RP Zhao, WB (reprint author), Cleveland State Univ, Dept Elect Engn & Comp Sci, Cleveland, OH 44115 USA. EM wenbing@ieee.org OI Zhao, Wenbing/0000-0002-3202-1127 NR 21 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2154-0357 BN 978-1-4673-9985-2 J9 INT CONF ELECTRO INF PY 2016 BP 246 EP 251 PG 6 WC Computer Science, Interdisciplinary Applications; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BG6HW UT WOS:000390300900027 ER PT J AU Moura, LMVR Schwamm, EL Moura, V Seitz, MP Hoch, DB Hsu, J Schwamm, LH AF Moura, Lidia M. V. R. Schwamm, Eli L. Moura, Valdery, Jr. Seitz, Michael P. Hoch, Daniel B. Hsu, John Schwamm, Lee H. TI Patient-reported financial barriers to adherence to treatment in neurology SO CLINICOECONOMICS AND OUTCOMES RESEARCH LA English DT Article DE outcomes; adherence; cost ID COST-RELATED NONADHERENCE; MEDICARE PART D; ANTIEPILEPTIC DRUG ADHERENCE; QUALITY-OF-LIFE; ADMINISTRATIVE DATA; CASE-DEFINITION; HEALTH DATA; EPILEPSY; BENEFICIARIES; VALIDATION AB Objective: Many effective medical therapies are available for treating neurological diseases, but these therapies tend to be expensive and adherence is critical to their effectiveness. We used patient-reported data to examine the frequency and determinants of financial barriers to medication adherence among individuals treated for neurological disorders. Patients and methods: Patients completed cross-sectional surveys on iPads as part of routine outpatient care in a neurology clinic. Survey responses from a 3-month period were collected and merged with administrative sources of demographic and clinical information (eg, insurance type). We explored the association between patient characteristics and patient-reported failure to refill prescription medication due to cost in the previous 12 months, termed here as "nonadherence". Results: The population studied comprised 6075 adults who were presented between July and September 2015 for outpatient neurology appointments. The mean age of participants was 56 (standard deviation: 18) years, and 1613 (54%) were females. The patients who participated in the surveys (2992, 49%) were comparable to nonparticipants with respect to gender and ethnicity but more often identified English as their preferred language (94% vs 6%, p<0.01). Among respondents, 9.8% (n=265) reported nonadherence that varied by condition. These patients were more frequently Hispanic (16.7% vs 9.8% white, p=0.01), living alone (13.9% vs 8.9% cohabitating, p<0.01), and preferred a language other than English (15.3% vs 9.4%, p=0.02). Conclusion: Overall, the magnitude of financial barriers to medication adherence appears to vary across neurological conditions and demographic characteristics. C1 [Moura, Lidia M. V. R.; Schwamm, Eli L.; Moura, Valdery, Jr.; Seitz, Michael P.; Hoch, Daniel B.; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Wang 720 Neurol,55 Fruit St, Boston, MA 02114 USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Hsu, John] Harvard Med Sch, Dept Med, Boston, MA USA. [Hsu, John] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. RP Moura, LMVR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang 720 Neurol,55 Fruit St, Boston, MA 02114 USA. EM lidia.moura@mgh.harvard.edu FU American Brain Foundation; NIH; AHRQ [1R01 CA164023, 2P01AG032952, R01 HD075121, R01 MH104560, R01HS023128]; NINDS [5U01NS077179-02, U10 NS086729]; PCORI [CE-1304-7073, CDRN-1306-04608, IHS-1310-07420, P50 NS051343] FX LMVRM is the recipient of a 2015-2016 Clinical Research Fellowship sponsored by the American Brain Foundation. LMVRM is a neurologist and health services researcher married to co-author VMJ who is a database analyst and PhD candidate in health care analytics. ELS is a former research student at the MGH Neurovalue laboratory. LHS is a senior health services researcher, mentor of LMVRM, and father of ELS. JH is supported by grants from NIH and AHRQ (1R01 CA164023, 2P01AG032952, R01 HD075121, R01 MH104560, and R01HS023128). LS is supported by grants from NINDS (5U01NS077179-02 and U10 NS086729) and PCORI (CE-1304-7073, CDRN-1306-04608, IHS-1310-07420, and P50 NS051343). There is no study funding. NR 63 TC 0 Z9 0 U1 3 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-6981 J9 CLINICOECONOMIC OUTC JI CLINICOECONOMICS OUTCOMES RES. PY 2016 VL 8 BP 685 EP 694 DI 10.2147/CEOR.S119971 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EF7CN UT WOS:000390487800001 PM 27895506 ER PT J AU Gokduman, K AF Gokduman, Kurtulus TI Strategies Targeting DNA Topoisomerase I in Cancer Chemotherapy: Camptothecins, Nanocarriers for Camptothecins, Organic Non-Camptothecin Compounds and Metal Complexes SO CURRENT DRUG TARGETS LA English DT Review DE Cancer chemotherapy; topoisomerase I; camptothecin topoisomerase I inhibitors; nano drug delivery systems; organic non-camptothecin topoisomerase I inhibitors; metal complexes ID POTENTIAL ANTICANCER AGENTS; IRON-OXIDE NANOPARTICLES; DRUG-DELIVERY SYSTEM; MESOPOROUS SILICA NANOPARTICLES; PLANT ANTITUMOR AGENTS; BIOLOGICAL EVALUATION; BIOMEDICAL APPLICATIONS; GOLD NANOPARTICLES; PLATINUM COMPLEXES; POLYMERIC MICELLES AB Topoisomerase I (Topo I) is a nuclear enzyme engaged in adjustment of DNA topological structure during cell cycle by cleaving and reannealing one of the two strands of the DNA double helix. Inhibition of this enzyme results in DNA strand breaks, ultimately leads to apoptosis and cell death; additionally it is in raised level in solid tumors contrasted with healthy tissues. Consequently, Topo I has a great potential as a target for the treatment of tumors. Although significant anti-tumor activity of first Topo I inhibitor, camptothecin (CPT), was observed on colon, lung, ovarian, breast, liver, pancreas and stomach cancers, CPT and its clinical derivatives (topotecan and irinotecan) have several restrictions. In addition to their low water solubility and cell resistance to CPTs, lactone ring opening causes a reduction in cytotoxic activity and severe side effects in physiological conditions (pH: 7.4, 37 degrees C). Although numerous efficient nano drug delivery systems were developed for CPT and its derivatives to compensate the handicaps of these compounds, none of them has been approved so far. On the other hand, organic non-CPT compounds have been searched; indolocarbazoles, indenoiso-quinolines and dibenzonaphthyridines have been applied to clinical development. Especially, indenoiso-quinolines and dibenzonaphthyridines have favorable characteristics compared to CPTs: They are chemically stable; they have the ability to overcome cell resistance; they stabilize enzyme-DNA cleavage complexes more persistently. In addition to the approaches based on organic compounds, recently some metal complexes (e.g., platinum, gold, copper, cobalt, zinc, vanadium, ruthenium) have also been reported as inhibitors of Topo I. This review will discuss the whole aspects of strategies targeting Topo I in cancer chemotherapy from past to the recent progresses. C1 [Gokduman, Kurtulus] Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, Harvard Med Sch, Boston, MA 02114 USA. RP Gokduman, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, Harvard Med Sch, Boston, MA 02114 USA. EM k.gokduman@gmail.com FU Scientific and Technological Research Council of Turkey (TUBITAK) FX Studies of the author are supported by The Scientific and Technological Research Council of Turkey (TUBITAK). My apologies in advance to the authors of primary articles whom I have failed to cite owing to space restrictions. NR 123 TC 0 Z9 0 U1 10 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 EI 1873-5592 J9 CURR DRUG TARGETS JI Curr. Drug Targets PY 2016 VL 17 IS 16 BP 1928 EP 1939 DI 10.2174/1389450117666160502151707 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EF5BJ UT WOS:000390345400011 PM 27138759 ER PT J AU Karimi, M Basri, SMM Vossoughi, M Pakchin, PS Mirshekari, H Hamblin, MR AF Karimi, Mahdi Basri, Seyed M. Moosavi Vossoughi, Manouchehr Pakchin, Parvin S. Mirshekari, Hamed Hamblin, Michael R. TI Redox-Sensitive Smart Nanosystems for Drug and Gene Delivery SO CURRENT ORGANIC CHEMISTRY LA English DT Review DE Redox-Sensitive; glutathione; drug delivery; micelle; nanogel; polymersome; nanocapsule ID CROSS-LINKED MICELLES; MESOPOROUS SILICA NANOPARTICLES; IN-VITRO; POLYMERIC MICELLES; NANOMEDICINE APPLICATIONS; RESPONSIVE NANOCAPSULES; POLY(ETHYLENE GLYCOL); TRIBLOCK COPOLYMERS; INTRACELLULAR DRUG; ANTICANCER DRUGS AB Background: Smart stimulus-responsive nanocarriers represent a rapidly growing class of drug-delivery systems for cancer and other diseases. Objective: The alterations of redox potential between the intracellular environment and the extracellular space have been widely utilized as a trigger for delivery of therapeutic agents by smart stimulus-responsive nanocarriers. We set out to review the scientific literature. Method: Published papers between 1980 and the present day were surveyed. Results: The advantages of redox-activated smart delivery of drugs, genes, and imaging agents include: the amplitude of the redox-responsive signal; the simple chemical features needed to trigger the activation process; and the relative simplicity of preparing these nanocarriers with an integrated redox-sensitive triggering element. Redox-sensitive nanovehicles are often sensitive to glutathione (GSH) as a regulator of cellular redox potential, which is a very important redox couple in mammalian cells. Other nanostructures can be designed to respond to oxidation, which may be useful for drug-delivery to sites with oxidative stress. Conclusion: Redox-responsive nanocarriers are a prominent member of the class of smart nanocarriers, and are expected to grow importance in coming years. C1 [Karimi, Mahdi] Iran Univ Med Sci, Fac Adv Technol Med, Dept Med Nanotechnol, Tehran, Iran. [Karimi, Mahdi] Iran Univ Med Sci, Cellular & Mol Res Ctr, Tehran, Iran. [Basri, Seyed M. Moosavi] Shahid Beheshti Univ, Civil & Environm Engn Dept, Tehran, Iran. [Basri, Seyed M. Moosavi; Mirshekari, Hamed] Iran Univ Med Sci, Adv Nanobiotechnol & Nanomed Res Grp ANNRG, Tehran, Iran. [Vossoughi, Manouchehr] Sharif Univ Technol, Dept Chem & Petr Engn, Biochem, Tehran, Iran. [Vossoughi, Manouchehr] Sharif Univ Technol, Bioenvironm Res Ctr, Tehran, Iran. [Pakchin, Parvin S.] Tabriz Univ Med Sci TUOMS, Res Ctr Pharmaceut Nanotechnol RCPN, Tabriz, Iran. [Pakchin, Parvin S.] Univ Tehran Med Sci, Fac Adv Med Technol, Dept Med Nanotechnol, Tehran, Iran. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, 414 Bartlett Bldg,40 Blossom St, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 414 Bartlett Bldg,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu FU US NIH [R01AI050875] FX MRH was supported by US NIH grant R01AI050875. NR 125 TC 0 Z9 0 U1 15 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1385-2728 EI 1875-5348 J9 CURR ORG CHEM JI Curr. Org. Chem. PY 2016 VL 20 IS 28 BP 2949 EP 2959 DI 10.2174/1385272820666160510154557 PG 11 WC Chemistry, Organic SC Chemistry GA EF5CK UT WOS:000390348100003 ER PT J AU Pope, C Davis, BH North-Lee, B Egede, L AF Pope, Charlene Davis, Boyd H. North-Lee, Bertha Egede, Leonard TI Searching for Empathy in the Talk of Veterans With Diabetes and Their Primary Care Providers: A Mixed-Methods Study SO INTERNATIONAL JOURNAL OF QUALITATIVE METHODS LA English DT Meeting Abstract C1 [Pope, Charlene] Ralph H Johnson Vet Affairs VA Med Ctr, Charleston, SC USA. [Davis, Boyd H.] Univ N Carolina, Charlotte, NC USA. [North-Lee, Bertha; Egede, Leonard] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1609-4069 J9 INT J QUAL METH JI Int. J. Qual. Meth. PD JAN-DEC PY 2016 VL 15 IS 1 PG 1 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA EE9BW UT WOS:000389921700386 ER PT J AU Arentsen, TJ Panos, S Thames, AD Arbid, JN Castellon, SA Hinkin, CH AF Arentsen, Timothy J. Panos, Stella Thames, April D. Arbid, J. Natalie Castellon, Steven A. Hinkin, Charles H. TI Psychosocial correlates of medication adherence among HIV-positive, cognitively impaired individuals SO JOURNAL OF HIV-AIDS & SOCIAL SERVICES LA English DT Article DE cognitively impaired; HIV; medication adherence; stimulant use; stress ID ACTIVE ANTIRETROVIRAL THERAPY; SELF-REPORTED ADHERENCE; DRUG-USE; NEUROPSYCHOLOGICAL IMPAIRMENT; NEUROCOGNITIVE IMPAIRMENT; PROSPECTIVE MEMORY; IMPROVE ADHERENCE; INFECTED ADULTS; VIRAL LOAD; NONADHERENCE AB Although cognitive impairment has been shown to adversely affect antiviral medication adherence, a subset of cognitively impaired adults nonetheless are able to adequately adhere to their medication regimen. However, little is known about factors that serve as buffers against suboptimal adherence among the cognitively impaired. This study consisted of 160 HIV-positive, cognitively impaired adults (Global Deficit Score >= 0.50) whose medication adherence was monitored over 6 months using an electronic monitoring device (MEMS caps). Logistic regressions were run to determine psychosocial variables associated with medication adherence. Higher self-efficacy, greater perception of treatment-related support, a stable medication regimen, stable stress levels, and absence of current stimulant use were predictive of optimal adherence. A distinct array of psychosocial factors was found that buffer against the adverse effects of cognitive impairment on medication adherence. Assessment and interventions targeting these factors may improve adherence rates among cognitively impaired adults. C1 [Arentsen, Timothy J.] Memphis Vet Affairs Med Ctr, 1030 Jefferson Ave, Memphis, TN 38104 USA. [Panos, Stella; Castellon, Steven A.; Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Panos, Stella; Thames, April D.; Castellon, Steven A.; Hinkin, Charles H.] Univ Calif Los Angeles, Psychiat & Biobehav Sci, Los Angeles, CA USA. [Arbid, J. Natalie] Univ Massachusetts, Boston, MA 02125 USA. RP Arentsen, TJ (reprint author), Memphis Vet Affairs Med Ctr, 1030 Jefferson Ave, Memphis, TN 38104 USA. EM Timothy.Arentsen2@va.gov NR 47 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1538-1501 EI 1538-151X J9 J HIV-AIDS SOC SERV JI J. HIV-AIDS Soc. Serv. PY 2016 VL 15 IS 4 BP 404 EP 416 DI 10.1080/15381501.2016.1228309 PG 13 WC Social Work SC Social Work GA EF2RT UT WOS:000390172700005 ER PT J AU Yi, RL Chen, BX Duan, P Zheng, CJ Shen, HY Liu, Q Yuan, C Ou, WL Zhou, ZH AF Yi, Renliang Chen, Baoxin Duan, Peng Zheng, Chanjiao Shen, Huanyu Liu, Qun Yuan, Chen Ou, Weilin Zhou, Zhiheng TI Sipuleucel-T and Androgen Receptor-Directed Therapy for Castration-Resistant Prostate Cancer: A Meta-Analysis SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Review ID ABIRATERONE ACETATE; ENZALUTAMIDE MDV3100; SURVIVAL ANALYSIS; CLINICAL ACTIVITY; DOUBLE-BLIND; IMMUNOTHERAPY; CHEMOTHERAPY; DOCETAXEL; TRIAL; PREDNISONE AB New treatments, such as sipuleucel-T and androgen receptor-(AR-) directed therapies (enzalutamide (Enz) and abiraterone acetate (AA)), have emerged and been approved for the management of castration-resistant prostate cancer (CRPC). There are still debates over their efficacy and clinical benefits. This meta-analysis aimed to investigate the efficacy and safety of sipuleucel-T and AR-directed therapies in patients with CRPC. RevMan 5.1 was used for pooled analysis and analysis of publication bias. Seven studies were included in the meta-analysis, with three studies in sipuleucel-T (totally 737 patients, 488 patients in treatment group, and 249 patients in placebo group) and four in AR- directed therapies (totally 5,199 patients, 3,015 patients in treatment group, and 2,184 patients in placebo group). Treatment with sipuleucel-T significantly improved overall survival in patients with CRPC and was not associated with increased risk of adverse event of grade >= 3 (p > 0.05). However, treatment with sipuleucel-T did not improve time-to-progression and reduction of prostate-specific antigen (PSA) level >= 50% was not significantly different from that with placebo. AR- directed therapies significantly improved overall survival in patients with CRPC and improved time-to-progression and reduction of PSA level >= 50%. AR-directed therapies did not increase risk of adverse event of grade >= 3 (p > 0.05). C1 [Yi, Renliang] Guangzhou Hosp Guangzhou Mil Reg, Guangzhou, Guangdong, Peoples R China. [Chen, Baoxin; Duan, Peng; Zheng, Chanjiao; Shen, Huanyu; Liu, Qun; Yuan, Chen; Ou, Weilin] Guangzhou Med Univ, Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China. [Zhou, Zhiheng] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Zhou, ZH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. EM zhihengz@163.com FU Healthcare Project of the Health Department of the General Logistics Department of the Chinese People's Liberation Army [14BJZ34]; National Natural Science Foundation of China [81473001]; Training Project of Outstanding Young College Teachers in Guangdong Province, China [Yq2013138] FX The authors thank Dr. Zining Lei for her helpful suggestions and advice on this paper. This work was supported byThe Healthcare Project of the Health Department of the General Logistics Department of the Chinese People's Liberation Army (Renliang Yi: 14BJZ34), the National Natural Science Foundation of China (Zhiheng Zhou: 81473001), and the Training Project of Outstanding Young College Teachers in Guangdong Province, China (Zhiheng Zhou: Yq2013138). NR 47 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-8861 EI 2314-7156 J9 J IMMUNOL RES JI J Immunol. Res. PY 2016 AR 4543861 DI 10.1155/2016/4543861 PG 10 WC Immunology SC Immunology GA EF7CZ UT WOS:000390489000001 ER PT J AU Al-Hebshi, NN Abdulhaq, A Albarrag, A Basode, VK Chen, T AF Al-hebshi, Nezar Noor Abdulhaq, Ahmed Albarrag, Ahmed Basode, Vinod Kumar Chen, Tsute TI Species-level core oral bacteriome identified by 16S rRNA pyrosequencing in a healthy young Arab population SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE core; human; high-throughput nucleotide sequencing; microbiome; mouth; pyrosequencing ID MICROBIOME; DIVERSITY; CAVITY; COMMUNITIES; ASSIGNMENT; SEQUENCES; TAXONOMY; ADULTS AB Background: Reports on the composition of oral bacteriome in Arabs are lacking. In addition, the majority of previous studies on other ethnic groups have been limited by low-resolution taxonomic assignment of next-generation sequencing reads. Furthermore, there has been a conflict about the existence of a 'core' bacteriome. Objective: The objective of this study was to characterize the healthy core oral bacteriome in a young Arab population at the species level. Methods: Oral rinse DNA samples obtained from 12 stringently selected healthy young subjects of Arab origin were pyrosequenced (454's FLX chemistry) for the bacterial 16S V1-V3 hypervariable region at an average depth of 11,500 reads. High-quality, non-chimeric reads >= 380 bp were classified to the species level using the recently described, prioritized, multistage assignment algorithm. A core bacteriome was defined as taxa present in at least 11 samples. The Chao2, abundance-based coverage estimator (ACE), and Shannon indices were computed to assess species richness and diversity. Results: Overall, 557 species-level taxa (211942 per subject) were identified, representing 122 genera and 13 phyla. The core bacteriome comprised 55 species-level taxa belonging to 30 genera and 7 phyla, namely Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, Fusobacteria, Saccharibacteria, and SR1. The core species constituted between 67 and 87% of the individual bacteriomes. However, the abundances differed by up to three orders of magnitude among the study subjects. On average, Streptococcus mitis, Rothia mucilaginosa, Haemophilus parainfluenzae, Neisseria flavescence/subflava group, Prevotella melaninogenica, and Veillonella parvula group were the most abundant. Streptococcus sp. C300, a taxon never reported in the oral cavity, was identified as a core species. Species richness was estimated at 586 (Chao2) and 614 (ACE) species, whereas diversity (Shannon index) averaged at 3.99. Conclusions: A species-level core oral bacteriome representing the majority of reads was identified, which can serve as a reference for comparison with oral bacteriomes of other populations as well as those associated with disease. C1 [Al-hebshi, Nezar Noor] Jazan Univ, Coll Dent, Dept Prevent Dent, POB 114, Jazan, Saudi Arabia. [Abdulhaq, Ahmed; Basode, Vinod Kumar] Jazan Univ, Coll Appl Med Sci, Dept Med Lab Technol, Unit Med Microbiol, Jazan, Saudi Arabia. [Albarrag, Ahmed] King Saud Univ, Coll Med, Dept Pathol, Riyadh, Saudi Arabia. [Chen, Tsute] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. RP Al-Hebshi, NN (reprint author), Jazan Univ, Coll Dent, Dept Prevent Dent, POB 114, Jazan, Saudi Arabia. EM nazhebshi@yahoo.com RI Al-hebshi, Nezar/J-9180-2013 OI Al-hebshi, Nezar/0000-0003-1841-9304 FU SABIC through the Deanship of Scientific Research at Jazan University, Saudi Arabia [33/4/35] FX The study was funded by SABIC through the Deanship of Scientific Research at Jazan University, Saudi Arabia (grant #33/4/35). We thank Dr. Mohammed Muzaffer Ali Khan, Dr. Ahmed Alqahtani, and Dr. Yousef Al-shamrani for their kind help with collection of the samples. NR 34 TC 1 Z9 1 U1 1 U2 1 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2016 VL 8 AR 31444 DI 10.3402/jom.v8.31444 PG 9 WC Microbiology SC Microbiology GA EE9WF UT WOS:000389976300001 PM 27193835 ER PT J AU Belstrom, D Holmstrup, P Bardow, A Kokaras, A Fiehn, NE Paster, BJ AF Belstrom, Daniel Holmstrup, Palle Bardow, Allan Kokaras, Alexis Fiehn, Nils-Erik Paster, Bruce J. TI Comparative analysis of bacterial profiles in unstimulated and stimulated saliva samples SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE saliva; HOMINGS; bacteria ID ORAL MICROBIOME; HEALTH; DISEASE; PERIODONTITIS; BIOMARKERS; LESIONS; CAVITY; COHORT AB Background and objective: The microbial profiles of stimulated saliva samples have been shown to differentiate between patients with periodontitis, patients with dental caries, and orally healthy individuals. Saliva was stimulated to allow for easy and rapid collection; however, microbial composition may not reflect the more natural, unstimulated state. The purpose of this study was to validate whether stimulated saliva is an adequate surrogate for unstimulated saliva in determining salivary microbiomes. Design: Unstimulated (n = 20) and stimulated (n = 20) saliva samples were collected from 20 orally and systemically healthy, non-smoking participants. Salivary bacterial profiles were analyzed by means of the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS), and statistical analysis was performed using Mann-Whitney test with Benjamini-Hochberg's correction for multiple comparison, cluster analysis, principal component analysis, and correspondence analysis. Results: From a total of 40 saliva samples, 496 probe targets were identified with a mean number of targets per sample of 203 (range: 146 = 303), and a mean number of probe targets of 206 and 200 in unstimulated and stimulated saliva samples, respectively (p = 0.62). Based on all statistical methods used for this study, the microbial profiles of unstimulated and stimulated saliva samples collected from the same person were not statistically significantly different. Conclusions: Analysis of bacterial salivary profiles in unstimulated and stimulated saliva samples collected from the same individual showed comparable results. Thus, the results verify that stimulated saliva is an adequate surrogate of unstimulated saliva for microbiome-related studies. C1 [Belstrom, Daniel; Holmstrup, Palle] Univ Copenhagen, Fac Hlth & Med Sci, Sect Periodontol & Microbiol, Dept Odontol, Norre Alle 20, DK-2200 Copenhagen, Denmark. [Bardow, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Sect Oral Med, Copenhagen, Denmark. [Kokaras, Alexis; Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Fiehn, Nils-Erik] Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen, Denmark. [Paster, Bruce J.] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. RP Belstrom, D (reprint author), Univ Copenhagen, Fac Hlth & Med Sci, Sect Periodontol & Microbiol, Dept Odontol, Norre Alle 20, DK-2200 Copenhagen, Denmark. EM dbel@sund.ku.dk FU Danish Dental Association; Danish Foundation of Mutual Efforts in Dental Care; Trygfonden; Simon Spies Foundation; NIH [DE021565] FX The authors declare no conflict of interest. This study was supported by external financial support from the Danish Dental Association, the Danish Foundation of Mutual Efforts in Dental Care, Trygfonden, and the Simon Spies Foundation. Funded in part from NIH grant, DE021565 (BJP). NR 30 TC 4 Z9 4 U1 2 U2 5 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2016 VL 8 AR 30112 DI 10.3402/jom.v8.30112 PG 7 WC Microbiology SC Microbiology GA EE9VP UT WOS:000389974700001 PM 26987356 ER PT J AU Mougeot, JLC Stevens, CB Cotton, SL Morton, DS Krishnan, K Brennan, MT Lockhart, PB Paster, BJ Mougeot, FKB AF Mougeot, Jean-Luc C. Stevens, Craig B. Cotton, Sean L. Morton, Darla S. Krishnan, Keerthana Brennan, Michael T. Lockhart, Peter B. Paster, Bruce J. Mougeot, Farah K. Bahrani TI Concordance of HOMIM and HOMINGS technologies in the microbiome analysis of clinical samples SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE HOMINGS; HOMIM; MiSeq; ProbeSeq; dental plaque; oral microbiome ID IDENTIFICATION MICROARRAY; REFRACTORY PERIODONTITIS; BACTEREMIA; EXTRACTION; PROFILES AB Background: Over 700 bacterial species reside in human oral cavity, many of which are associated with local or distant site infections. Extensive characterization of the oral microbiome depends on the technologies used to determine the presence and proportions of specific bacterial species in various oral sites. Objective: The objective of this study was to compare the microbial composition of dental plaque at baseline using Human Oral Microbe Identification Microarray (HOMIM) and Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) technologies, which are based on 16S rRNA. Methods: Dental plaque samples were collected from 96 patients at baseline prior to a dental procedure involving manipulation of gingival tissues. The samples were surveyed for 293 and 597 oral bacterial species via HOMIM and HOMINGS, respectively, based on 16S rRNA gene sequences. We determined the concordance between the two technologies for common species. Genus level analysis was performed using HOMINGS-specific genus identification capabilities. Results: HOMINGS detected twice the number of species in the same dental plaque samples compared to HOMIM. For the species detected by both HOMIM and HOMINGS, there was no difference in relative proportions of overall bacterial composition at the species, genus or phylum levels. Additionally, there was no difference in relative proportion for total species per patient between the two technologies. Conclusion: HOMINGS significantly expanded oral bacterial species identification compared to HOMIM. The genus and species probes, combined in HOMINGS, provided a more comprehensive representation of oral bacterial community, critical for future characterization of oral microbes in distant site infections. C1 [Mougeot, Jean-Luc C.; Stevens, Craig B.; Morton, Darla S.; Brennan, Michael T.; Lockhart, Peter B.; Mougeot, Farah K. Bahrani] Carolinas Hlth Care Syst, Dept Oral Med, Cannon Res Ctr, POB 32861, Charlotte, NC 28232 USA. [Cotton, Sean L.; Krishnan, Keerthana; Paster, Bruce J.] Forsyth Inst, Cambridge, MA USA. RP Mougeot, JLC; Mougeot, FKB (reprint author), Carolinas Hlth Care Syst, Dept Oral Med, Cannon Res Ctr, POB 32861, Charlotte, NC 28232 USA. EM jean-luc.mougeot@carolinashealthcare.org; farah.mougeot@carolinashealthcare.org FU National Institute of Dental and Craniofacial Research/National Institute of Health [R01 DE13559-01, R01 DE021565]; Carolinas HealthCare System (CHS) Research Fund FX This study was supported by National Institute of Dental and Craniofacial Research/National Institute of Health grants # R01 DE13559-01, R01 DE021565, and Carolinas HealthCare System (CHS) Research Fund. We thank the residents and clinical coordinators at CMC Dental Clinic for sample collection, Megan Templin for her help in statistical analysis, and P. Hanjra for her help with the database. NR 14 TC 3 Z9 3 U1 1 U2 1 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2016 VL 8 AR 30379 DI 10.3402/jom.v8.30379 PG 9 WC Microbiology SC Microbiology GA EE9VU UT WOS:000389975200001 PM 27065347 ER PT J AU Siddiqui, H Chen, T Aliko, A Mydel, PM Jonsson, R Olsen, I AF Siddiqui, Huma Chen, Tsute Aliko, Ardita Mydel, Piotr M. Jonsson, Roland Olsen, Ingar TI Microbiological and bioinformatics analysis of primary Sjogren's syndrome patients with normal salivation SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE primary Sjogren's syndrome; whole saliva; normal salivary flow rate; bacteria; high throughput sequencing; pyrosequencing ID BACTERIA; MICROBIOTA; ARTHRITIS; DISEASE; SEARCH; BLAST; GUT AB Background: Reduced salivation is considered a major clinical feature of most but not all cases of primary Sjogren's syndrome (pSS). Reduced saliva flow may lead to changes in the salivary microbiota. These changes have mainly been studied with culture that typically recovers only 65% of the bacteria present. Objective: This study was to use high throughput sequencing, covering both cultivated and not-yet-cultivated bacteria, to assess the bacterial microbiota of whole saliva in pSS patients with normal salivation. Methods: Bacteria of whole unstimulated saliva from nine pSS patients with normal salivation flow and from nine healthy controls were examined by high throughput sequencing of the hypervariable region V1V2 of 16S rRNA using the 454 GS Junior system. Raw sequence reads were subjected to a species-level, reference-based taxonomy assignment pipeline specially designed for studying the human oral microbial community. Each of the sequence reads was BLASTN-searched against a database consisting of reference sequences representing 1,156 oral and 12,013 non-oral species. Unassigned reads were then screened for high-quality non-chimeras and subjected to de novo species-level operational taxonomy unit (OTU) calling for potential novel species. Down-stream analyses, including alpha and beta diversities, were analyzed using the Quantitative Insights into Microbial Ecology (QIIME) pipeline. To reveal significant differences between the microbiota of control saliva and Sjogren's saliva, a statistical method introduced in Metastats www.metastats.cbcb.umd.edu was used. Results: Saliva of pSS patients with normal salivation had a significantly higher frequency of Firmicutes compared with controls (p = 0.004). Two other major phyla, Synergistetes and Spirochaetes, were significantly depleted in pSS (p = 0.001 for both). In addition, we saw a nearly 17% decrease in the number of genera in pSS (25 vs. 30). While Prevotella was almost equally abundant in both groups (25% in pSS and 22% in controls), about a twofold increase in pSS of Streptococcus (28% vs. 17%) and Veillonella (26% vs. 12%) was detected. Prevotella melaninogenica was the major species in controls (13%) while Veillonella atypica and the Veillonella parvula groups dominated in patient samples (14 and 14%). The scarcity in bacterial species in pSS compared with controls was also demonstrated by alpha and beta diversity analyses, as well as read abundance depicted in a phylogenetic tree. Conclusions: While Firmicutes was significantly higher in pSS patients than in controls, Synergistetes and Spirochaetes were significantly lower. The number of bacterial genera and species was also lower. These data showed that microbial dysbiosis is another key characteristic of pSS whole saliva which can occur independent of hyposalivation. C1 [Siddiqui, Huma; Olsen, Ingar] Univ Oslo, Dept Oral Biol, Fac Dent, Oslo, Norway. [Chen, Tsute] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Aliko, Ardita; Mydel, Piotr M.; Jonsson, Roland] Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway. [Mydel, Piotr M.] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Microbiol, Krakow, Poland. [Mydel, Piotr M.] Jagiellonian Univ, Malopolska Ctr Biotechnol, Krakow, Poland. [Jonsson, Roland] Haukeland Hosp, Dept Rheumatol, Bergen, Norway. RP Olsen, I (reprint author), Univ Oslo, Fac Dent, Dept Oral Microbiol, POB 1052 Blindern, NO-0316 Oslo, Norway. EM ingar.olsen@odont.uio.no FU European Commission [FP7-HEALTH-306029 'TRIGGER']; National Science Center (Poland) [2014/14/E/NZ6/00162]; Broegelmann Foundation FX PMM was also supported by a grant from the National Science Center (2014/14/E/NZ6/00162, Poland) and by the Broegelmann Foundation. NR 25 TC 0 Z9 0 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2016 VL 8 AR 31119 DI 10.3402/jom.v8.31119 PG 10 WC Microbiology SC Microbiology GA EE9WA UT WOS:000389975800001 PM 27770517 ER PT J AU Virtej, A Papadakou, P Sasaki, H Bletsa, A Berggreen, E AF Virtej, Anca Papadakou, Panagiota Sasaki, Hajime Bletsa, Athanasia Berggreen, Ellen TI VEGFR-2 reduces while combined VEGFR-2 and-3 signaling increases inflammation in apical periodontitis SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE bone resorption; osteoclasts; angiogenesis and lymphangiogenesis; immune cells; cytokines ID COLONY-STIMULATING FACTOR; ENDOTHELIAL GROWTH-FACTORS; PERIAPICAL LESIONS; BLOCKADE INCREASES; LYMPHATIC DRAINAGE; INTERFERON-GAMMA; BONE LOSS; LYMPHANGIOGENESIS; RECEPTORS; CELLS AB Background: In apical periodontitis, oral pathogens provoke an inflammatory response in the apical area that induces bone resorptive lesions. In inflammation, angio-and lymphangiogenesis take place. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key players in these processes and are expressed in immune cells and endothelial cells in the lesions. Objective: We aimed at testing the role of VEGFR-2 and -3 in periapical lesion development and investigated their role in lymphangiogenesis in the draining lymph nodes. Design: We induced lesions by pulp exposure in the lower first molars of C57BL/6 mice. The mice received IgG injections or blocking antibodies against VEGFR-2 (anti-R2), VEGFR-3 (anti-R3), or combined VEGFR-2 and -3, starting on day 0 until day 10 or 21 post-exposure. Results: Lesions developed faster in the anti-R2 and anti-R3 group than in the control and anti-R2/R3 groups. In the anti-R2 group, a strong inflammatory response was found expressed as increased number of neutrophils and osteoclasts. A decreased level of pro-inflammatory cytokines was found in the anti-R2/R3 group. Lymphangiogenesis in the draining lymph nodes was inhibited after blocking of VEGFR-2 and/or -3, while the largest lymph node size was seen after anti-R2 treatment. Conclusions: We demonstrate an anti-inflammatory effect of VEGFR-2 signaling in periapical lesions which seems to involve neutrophil regulation and is independent of angiogenesis. Combined signaling of VEGFR-2 and -3 has a pro-inflammatory effect. Lymph node lymphangiogenesis is promoted through activation of VEGFR-2 and/or VEGFR-3. C1 [Virtej, Anca; Papadakou, Panagiota; Berggreen, Ellen] Univ Bergen, Dept Biomed, Jonas Lies Vei 91, NO-5009 Bergen, Norway. [Sasaki, Hajime] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. [Bletsa, Athanasia] Univ Bergen, Dept Clin Dent, Bergen, Norway. RP Virtej, A (reprint author), Univ Bergen, Dept Biomed, Jonas Lies Vei 91, NO-5009 Bergen, Norway. EM anca.virtej@uib.no FU Helse Vest, Norway [911684]; University of Bergen FX Financial support received from Helse Vest, Norway, project number 911684 and from the University of Bergen. There is no conflict of interest in the present study for any of the authors. NR 37 TC 0 Z9 0 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2016 VL 8 AR 32433 DI 10.3402/jom.v8.32433 PG 11 WC Microbiology SC Microbiology GA EE9WQ UT WOS:000389977400001 PM 27650043 ER PT S AU Bagheri, E Jin, J Dauwels, J Cash, S Westover, MB AF Bagheri, Elham Jin, Jing Dauwels, Justin Cash, Sydney Westover, M. Brandon GP IEEE TI FAST AND EFFICIENT REJECTION OF BACKGROUND WAVEFORMS IN INTERICTAL EEG SO 2016 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING PROCEEDINGS SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech, and Signal Processing CY MAR 20-25, 2016 CL Shanghai, PEOPLES R CHINA SP Inst Elect & Elect Engineers, Inst Elect & Elect Engineers Signal Proc Soc DE Spike Detection; Electroencephalogram; Interictal Discharges; Epileptiform Transients; Epilepsy ID SPIKE DETECTION AB Automated annotation of electroencephalograms (EEG) of epileptic patients is important in diagnosis and management of epilepsy. Epilepsy is often associated with the presence of epileptiform transients (ET) in the EEG. To develop an efficient ET detector, a vast amount of data is required to train and evaluate the performance of the detector. Interictal EEG data contains mostly background waveforms, since ETs only occur occasionally in most patients. In order to detect ETs in an automated fashion, it is meaningful to first try to eliminate most background waveforms by means of simple, fast classifiers. The remaining waveforms can in a following step be processed by more sophisticated and computationally demanding classification algorithms, such as deep learning systems. In this study, we design a cascade of simple thresholding steps to reject most background waveforms in interictal EEG, while maintaining most ETs. Several simple and quick-to-compute EEG features are chosen. By thresholding these features in consecutive steps, background waveforms are rejected sequentially. In our numerical experiments, a cascade of 10 steps is able to reject 98.65% of all background segments in the dataset, while preserving 90.6% of the ETs. C1 [Bagheri, Elham; Jin, Jing; Dauwels, Justin] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. [Cash, Sydney; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney; Westover, M. Brandon] Harvard Med Sch, Cambridge, MA USA. RP Bagheri, E (reprint author), Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4799-9988-0 J9 INT CONF ACOUST SPEE PY 2016 BP 744 EP 748 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BG3XQ UT WOS:000388373400150 ER PT S AU Thomas, J Jin, J Dauwels, J Cash, SS Westover, MB AF Thomas, John Jin, Jing Dauwels, Justin Cash, Sydney S. Westover, M. Brandon GP IEEE TI CLUSTERING OF INTERICTAL SPIKES BY DYNAMIC TIME WARPING AND AFFINITY PROPAGATION SO 2016 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING PROCEEDINGS SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech, and Signal Processing CY MAR 20-25, 2016 CL Shanghai, PEOPLES R CHINA SP Inst Elect & Elect Engineers, Inst Elect & Elect Engineers Signal Proc Soc DE Epilepsy; Electroencephalogram; Affinity propagation; K-means; Dynamic time warping; Euclidean distance AB Epilepsy is often associated with the presence of spikes in electroencephalograms (EEGs). The spike waveforms vary vastly among epilepsy patients, and also for the same patient across time. In order to develop semi-automated and automated methods for detecting spikes, it is crucial to obtain a better understanding of the various spike shapes. In this paper, we develop several approaches to extract exemplars of spikes. We generate spike exemplars by applying clustering algorithms to a database of spikes from 12 patients. As similarity measures for clustering, we consider the Euclidean distance and Dynamic Time Warping (DTW). We assess two clustering algorithms, namely, K-means clustering and affinity propagation. The clustering methods are compared based on the mean squared error, and the similarity measures are assessed based on the number of generated spike clusters. Affinity propagation with DTW is shown to be the best combination for clustering epileptic spikes, since it generates fewer spike templates and does not require to pre-specify the number of spike templates. C1 [Thomas, John; Jin, Jing; Dauwels, Justin] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. [Cash, Sydney S.; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney S.; Westover, M. Brandon] Harvard Med Sch, Boston, MA USA. RP Thomas, J (reprint author), Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. NR 17 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4799-9988-0 J9 INT CONF ACOUST SPEE PY 2016 BP 749 EP 753 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BG3XQ UT WOS:000388373400151 ER PT S AU Johansen, AR Jin, J Maszczyk, T Dauwels, J Cash, SS Westover, MB AF Johansen, Alexander Rosenberg Jin, Jing Maszczyk, Tomasz Dauwels, Justin Cash, Sydney S. Westover, M. Brandon GP IEEE TI EPILEPTIFORM SPIKE DETECTION VIA CONVOLUTIONAL NEURAL NETWORKS SO 2016 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING PROCEEDINGS SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech, and Signal Processing CY MAR 20-25, 2016 CL Shanghai, PEOPLES R CHINA SP Inst Elect & Elect Engineers, Inst Elect & Elect Engineers Signal Proc Soc DE Epilepsy; Spike detection; EEG; Deep learning; Convolutional neural network ID EEG; RECOGNITION AB The EEG of epileptic patients often contains sharp waveforms called "spikes", occurring between seizures. Detecting such spikes is crucial for diagnosing epilepsy. In this paper, we develop a convolutional neural network (CNN) for detecting spikes in EEG of epileptic patients in an automated fashion. The CNN has a convolutional architecture with filters of various sizes applied to the input layer, leaky ReLUs as activation functions, and a sigmoid output layer. Balanced mini-batches were applied to handle the imbalance in the data set. Leave-one-patient-out cross-validation was carried out to test the CNN and benchmark models on EEG data of five epilepsy patients. We achieved 0.947 AUC for the CNN, while the best performing benchmark model, Support Vector Machines with Gaussian kernel, achieved an AUC of 0.912. C1 [Johansen, Alexander Rosenberg] Tech Univ Denmark, DTU Compute, Lyngby, Denmark. [Johansen, Alexander Rosenberg; Jin, Jing; Maszczyk, Tomasz; Dauwels, Justin] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore, Singapore. [Cash, Sydney S.; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney S.; Westover, M. Brandon] Harvard Med Sch, Boston, MA USA. RP Johansen, AR (reprint author), Tech Univ Denmark, DTU Compute, Lyngby, Denmark.; Johansen, AR (reprint author), Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore, Singapore. NR 29 TC 0 Z9 0 U1 2 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4799-9988-0 J9 INT CONF ACOUST SPEE PY 2016 BP 754 EP 758 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BG3XQ UT WOS:000388373400152 ER PT S AU Ying, J Dutta, J Guo, N Xia, L Sitek, A Li, QZ AF Ying, Jun Dutta, Joyita Guo, Ning Xia, Lei Sitek, Arkadiusz Li, Quanzheng GP IEEE TI GOLD CLASSIFICATION OF COPDGENE COHORT BASED ON DEEP LEARNING SO 2016 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING PROCEEDINGS SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech, and Signal Processing CY MAR 20-25, 2016 CL Shanghai, PEOPLES R CHINA SP Inst Elect & Elect Engineers, Inst Elect & Elect Engineers Signal Proc Soc DE Chronic Obstructive Pulmonary Disease (COPD); Global Initiative for Chronic Obstructive Lung Disease (GOLD); deep learning; Deep Belief Networks (DBNs); classification ID OBSTRUCTIVE PULMONARY-DISEASE; SEVERITY AB This study aims to employ deep learning for the development of an automatic classifier for the severity of chronic obstructive pulmonary disease (COPD) in patients. A three-layer deep belief network (DBN) with two hidden layers and one visible layer was employed to generate a model for classification, and the model's robustness against exacerbation was analyzed. Subjects from the COPDGene cohort were staged using the GOLD 2011 guidelines. 10,300 subjects with 361 features each were included in the analysis. After feature selection and parameter optimization, the proposed classification method achieved an accuracy of 97.2% by using a 10-fold cross validation experiment. The most sensitive features as revealed by the DBN weights were consistent with the clinical consensus as per previous studies and clinical diagnosis rules. In summary, we demonstrate that the DBN is a competitive tool for exacerbation risk assessment for patients suffering from COPD. C1 [Ying, Jun; Dutta, Joyita; Guo, Ning; Sitek, Arkadiusz; Li, Quanzheng] Massachusetts Gen Hosp, Nucl Med & Mol Imaging Radiol Dept, Boston, MA 02114 USA. [Ying, Jun; Xia, Lei] 301 Hosp, Med Support Ctr, Beijing, Peoples R China. RP Ying, J (reprint author), Massachusetts Gen Hosp, Nucl Med & Mol Imaging Radiol Dept, Boston, MA 02114 USA.; Ying, J (reprint author), 301 Hosp, Med Support Ctr, Beijing, Peoples R China. NR 19 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4799-9988-0 J9 INT CONF ACOUST SPEE PY 2016 BP 2474 EP 2478 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BG3XQ UT WOS:000388373402123 ER PT S AU Palmer, LD Skaar, EP AF Palmer, Lauren D. Skaar, Eric P. BE Bonini, NM TI Transition Metals and Virulence in Bacteria SO ANNUAL REVIEW OF GENETICS, VOL 50 SE Annual Review of Genetics LA English DT Review; Book Chapter DE host-pathogen interface; metal acquisition; metal homeostasis; nutritional immunity; transition metal ID STAPHYLOCOCCUS-AUREUS INFECTION; LACTOFERRIN-BINDING PROTEIN; INNATE IMMUNE-RESPONSE; HELICOBACTER-PYLORI; PSEUDOMONAS-AERUGINOSA; MYCOBACTERIUM-TUBERCULOSIS; STREPTOCOCCUS-PNEUMONIAE; NUTRITIONAL IMMUNITY; PATHOGENIC BACTERIA; ESCHERICHIA-COLI AB Transition metals are required trace elements for all forms of life. Due to their unique inorganic and redox properties, transition metals serve as cofactors for enzymes and other proteins. In bacterial pathogenesis, the vertebrate host represents a rich source of nutrient metals, and bacteria have evolved diverse metal acquisition strategies. Host metal homeostasis changes dramatically in response to bacterial infections, including production of metal sequestering proteins and the bombardment of bacteria with toxic levels of metals. In response, bacteria have evolved systems to subvert metal sequestration and toxicity. The coevolution of hosts and their bacterial pathogens in the battle for metals has uncovered emerging paradigms in social microbiology, rapid evolution, host specificity, and metal homeostasis across domains. This review focuses on recent advances and open questions in our understanding of the complex role of transition metals at the host-pathogen interface. C1 [Palmer, Lauren D.; Skaar, Eric P.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Skaar, Eric P.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA. RP Skaar, EP (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA.; Skaar, EP (reprint author), Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA. EM eric.skaar@vanderbilt.edu FU BLRD VA [I01 BX002482]; NIAID NIH HHS [R01 AI069233, F32 AI122516, R01 AI101171, R21 AI107233] NR 152 TC 0 Z9 0 U1 7 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4197 BN 978-0-8243-1250-3 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2016 VL 50 BP 67 EP 91 DI 10.1146/annurev-genet-120215-035146 PG 25 WC Genetics & Heredity SC Genetics & Heredity GA BG5NP UT WOS:000389584800004 PM 27617971 ER PT S AU Yazinski, SA Zou, L AF Yazinski, Stephanie A. Zou, Lee BE Bonini, NM TI Functions, Regulation, and Therapeutic Implications of the ATR Checkpoint Pathway SO ANNUAL REVIEW OF GENETICS, VOL 50 SE Annual Review of Genetics LA English DT Review; Book Chapter DE checkpoint; ATR; Chk1; DNA damage; DNA repair; replication stress; genomic instability; cancer therapy ID DNA-DAMAGE RESPONSE; STALLED REPLICATION FORKS; HOMOLOGOUS RECOMBINATION REPAIR; TOPBP1 ACTIVATES ATR; DOUBLE-STRAND BREAKS; PROTEIN-A RPA; S-PHASE; END RESECTION; CANCER-CELLS; MEDIATED PHOSPHORYLATION AB The ATR (ATM and rad3-related) pathway is crucial for proliferation, responding to DNA replication stress and DNA damage. This critical signaling pathway is carefully orchestrated through a multistep process requiring initial priming of ATR prior to damage, recruitment of ATR to DNA damage lesions, activation of ATR signaling, and, finally, modulation of ATR activity through a variety of post-translational modifications. Following activation, ATR functions in several vital cellular processes, including suppression of replication origin firing, promotion of deoxynucleotide synthesis and replication fork restart, prevention of double-stranded DNA break formation, and avoidance of replication catastrophe and mitotic catastrophe. In many cancers, tumor cells have increased dependence on ATR signaling for survival, making ATR a promising target for cancer therapy. Tumor cells compromised in DNA repair pathways or DNA damage checkpoints, cells reliant on homologous recombination, and cells with increased replication stress are particularly sensitive to ATR inhibition. Understanding ATR signaling and modulation is essential to unraveling which tumors have increased dependence on ATR signaling as well as how the ATR pathway can best be exploited for targeted cancer therapy. C1 [Yazinski, Stephanie A.; Zou, Lee] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zou, L (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.; Zou, L (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. EM zou.lee@mgh.harvard.edu NR 124 TC 3 Z9 3 U1 7 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4197 BN 978-0-8243-1250-3 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2016 VL 50 BP 155 EP 173 DI 10.1146/annurev-genet-121415-121658 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA BG5NP UT WOS:000389584800008 PM 27617969 ER PT S AU Smirnakis, SM AF Smirnakis, Stelios M. BE Movshon, JA Wandell, BA TI Probing Human Visual Deficits with Functional Magnetic Resonance Imaging SO ANNUAL REVIEW OF VISION SCIENCE, VOL 2 SE Annual Review of Vision Science LA English DT Article; Book Chapter DE V1 lesion; fMRI; scotoma; visual perception; visual field perimetry; rehabilitation ID PERCEPTION FOLLOWING LESIONS; VISION RESTORATION THERAPY; LATERAL GENICULATE-NUCLEUS; STRIATE CORTEX V1; FIELD DEFECTS; MACULAR DEGENERATION; MOTION PERCEPTION; MACAQUE MONKEY; AREA MT; HOMONYMOUS HEMIANOPIA AB Much remains to be understood about visual system malfunction following injury. The resulting deficits range from dense, visual field scotomas to mild dysfunction of visual perception. Despite the predictive value of anatomical localization studies, much patient-to-patient variability remains regarding (a) perceptual abilities following injury and (b) the capacity of individual patients for visual rehabilitation. Visual field perimetry is used to characterize the visual field deficits that result from visual system injury. However, standard perimetry mapping does not always precisely correspond to underlying anatomical or functional deficits. Functional magnetic resonance imaging can be used to probe the function of surviving visual circuits, allowing us to classify better how the pattern of injury relates to residual visual perception. Identifying pathways that are potentially modifiable by training may guide the development of improved strategies for visual rehabilitation. This review discusses primary visual cortex lesions, which cause dense contralateral scotomas. C1 [Smirnakis, Stelios M.] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Smirnakis, Stelios M.] Boston Healthcare Syst, Vet Adm, Dept Neurol, Jamaica Plain Campus, Boston, MA 02130 USA. [Smirnakis, Stelios M.] Harvard Med Sch, Boston, MA 02115 USA. RP Smirnakis, SM (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.; Smirnakis, SM (reprint author), Boston Healthcare Syst, Vet Adm, Dept Neurol, Jamaica Plain Campus, Boston, MA 02130 USA.; Smirnakis, SM (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM smsmirnakis@partners.org NR 146 TC 0 Z9 0 U1 1 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2374-4642 BN 978-0-8243-5102-1 J9 ANNU REV VIS SCI PY 2016 VL 2 BP 171 EP 195 DI 10.1146/annurev-vision-111815-114535 PG 25 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA BG5OA UT WOS:000389589000009 ER PT J AU Simon, TG Kim, AY Stamm, LM Liu, L Mo, HM Doehle, B Pang, PS Brainard, DM McHutchison, JG Gustafson, J Lauer, GM Chung, RT AF Simon, Tracey G. Kim, Arthur Y. Stamm, Luisa M. Liu, Lin Mo, Hongmei Doehle, Brian Pang, Phillip S. Brainard, Diana M. McHutchison, John G. Gustafson, Jenna Lauer, Georg M. Chung, Raymond T. TI The safety and efficacy of ledipasvir/sofosbuvir for the treatment of a nosocomial outbreak of HCV in patients with significant cardiovascular disease SO ANTIVIRAL THERAPY LA English DT Article ID HEPATITIS-C VIRUS; SUSTAINED VIROLOGICAL RESPONSE; GENOTYPE 1 INFECTION; ALL-CAUSE MORTALITY; PEGYLATED INTERFERON; TREATMENT-NAIVE; PLUS RIBAVIRIN; PHASE-2 TRIAL; OPEN-LABEL; SOFOSBUVIR AB Background: There is an unmet need for interferon-and ribavirin-free treatment for chronic HCV infection in patients with comorbidities including cardiovascular disease (CVD). The aim of this study was to evaluate the rates of sustained virological response (SVR) and adverse events in a cohort of patients with nosocomially acquired HCV genotype-1b following 12 weeks of therapy with fixed-dose combination (FDC) ledipasvir/sofosbuvir (LDV/SOF). Methods: This is a prospective, single-centre, open-label study of five non-cirrhotic patients with HCV genotype-1b and significant comorbid CVD, conducted at the Massachusetts General Hospital. All patients were prescribed an FDC tablet (LDV 90 mg/SOF 400 mg) once daily for 12 weeks. Serial measurements of safety parameters, virology, host immune correlates and adherence were performed. The primary outcome was the proportion of patients with SVR (plasma HCV RNA level <25 IU/ml), 12 weeks after treatment completion (SVR12). Results: All five patients (100%) achieved SVR12, with no episodes of on- or post-treatment relapse. The most commonly reported adverse events were gastrointestinal illness and upper respiratory viral-type illness. There were no serious adverse events or discontinuations of medication attributable to the study drug. Deep sequencing analysis revealed no baseline NS3, NS5A or NS5B resistance-associated variants. Conclusions: In this open-label, uncontrolled, pilot study enrolling patients with HCV genotype-1b and significant CVD, administration of a fixed-dose, oral combination of LDV and SOF for 12 weeks was associated with high rates of SVR and minimal adverse events. Larger prospective studies that also include patients with cirrhosis and prior treatment non-responders are necessary. C1 [Simon, Tracey G.; Kim, Arthur Y.; Gustafson, Jenna; Lauer, Georg M.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Div, Liver Ctr, Boston, MA 02114 USA. [Simon, Tracey G.; Kim, Arthur Y.; Lauer, Georg M.; Chung, Raymond T.] Harvard Med Sch, Boston, MA 02115 USA. [Stamm, Luisa M.; Liu, Lin; Mo, Hongmei; Doehle, Brian; Pang, Phillip S.; Brainard, Diana M.; McHutchison, John G.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Div, Liver Ctr, Boston, MA 02114 USA.; Chung, RT (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM rtchung@partners.org FU [K24 DK078772] FX Grant support for this study: K24 DK078772 (RTC). NR 35 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2016 VL 21 IS 3 BP 185 EP 194 DI 10.3851/IMP2997 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA EE6TN UT WOS:000389745600001 PM 26440471 ER EF